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Tachykinins (tachykinin-related peptides, TRPs) are multifunctional neuropeptides that have widespread distribution in the central nervous system (CNS) and in the gastrointestinal tract of many insects, and most have been shown to stimulate contractions of visceral muscles. Invertebrate TRPs carry a characteristic conserved C-terminal pentapeptide (FXGXR-amide) and most of them share some amino acid sequence similarities (approx. 45%) with the vertebrate and mammalian tachykinin family. We have functionally characterized the tachykinins in R. prolixus (Rhopr-TKs) and partially cloned the transcript that encodes for the peptide precursor. The transcript encodes 8 Rhopr-TKs, 7 of which are unique with Rhopr-TK 5 having 2 copies. The spatial distribution analysis of the Rhopr-TK transcript indicates that the highest expression levels are in the CNS, but transcript expression is also associated with salivary glands, fat body, dorsal vessel, and the various gut compartments. Rhopr-TK 1, 2 and 5 significantly increase the frequency and amplitude of peristaltic contractions of the salivary glands. Hindgut muscle also displayed a dose-dependent increase in basal tonus in response to Rhopr-TK1, 2 and 5. TK-like immunoreactivity was seen in a small group of processes that are situated on the lateral margins of the hindgut. Interestingly, kinin-like immunoreactivity is seen in immunoreactive processes on the lateral margin of the hindgut as well as fine processes covering the entire hindgut. Co-localization studies show that TK-like staining is always co-localized with kinin-like immunoreactivity, whereas kinin-like staining is seen in the fine processes that are devoid of TK-like immunoreactivity indicating that TKs are most likely released together with kinins to act on the hindgut. Rhopr-Kinin 2 is a potent stimulator of hindgut muscle contraction in R. prolixus. Addition of Rhopr-Kinin 2 and Rhopr-TK 2 to the hindgut leads to a contraction that was additive of the effects of Rhopr-Kinin 2 and Rhopr-TK 2 alone.

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An extended family with three individuals affected by two different forms of double heterozygosity for beta-thalassemia and Hb New York is reported. Double heterozygosity of Hb New York [beta 113 GTG-->GAG; VAL-->GLU] and beta degrees codon 17 was detected in a fetus following prenatal screening for thalassemia. The father and a paternal aunt were also found to be heterozygous for Hb New York and beta degrees IVSII-654. Both adults had clinical and hematological features consistent with beta-thalassemia trait. The affected child was followed up after birth and manifested the typical course of a thalassemia trait, with no signs of organomegaly or overt hemolysis. Observations strongly suggest that double heterozygosity of Hb New York and beta degrees thalassemia has mild, if any, clinical symptoms, and is not an indication of therapeutic abortion when detected antenatally.

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BACKGROUND: Tacrine is one of the first drugs to be widely marketed for the loss of memory and intellectual decline in Alzheimer's disease, often accompanied by abnormal behaviour and physical decline. The alleged success of tacrine in the treatment of these symptoms has been heralded as confirmation of the cholinergic theory of Alzheimer's disease. The efficacy of tacrine for symptoms of dementia remains controversial. This is reflected by the low rate of prescription of tacrine in countries where it is approved and the lack of approval by several regulatory authorities in Europe and elsewhere. The uncertainty about the efficacy of tacrine is due to the difficulties in interpretation of the results from the clinical trials. The reasons for this are the small effects of tacrine compared to placebo for all outcomes; the high incidence of adverse events; the lack of benefit observed in several trials; the use of cross-over designs and their associated methodological problems in a disease like dementia; the use of different measurement scales to assess outcome in different trials; and the problem of high dropout rates. OBJECTIVES: To determine the clinical efficacy of tacrine for the symptoms of Alzheimer's disease. SEARCH STRATEGY: The Cochrane Dementia Group Register of Clinical Trials was searched using the terms 'tacrine', 'tetrahydroaminoacridine' and 'THA' (see the Group's search strategy for full details). SELECTION CRITERIA: All unconfounded, double-blind, randomized trials in which treatment with tacrine was administered for more than a day and compared to placebo in patients with dementia of the Alzheimer's type. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two reviewers, pooled if appropriate and possible, and the pooled odds ratios (95%CI) or the average differences (95%CI) were estimated. Where possible, intention-to-treat data were used. MAIN RESULTS: This review produced no clear results. The results were compatible with tacrine producing improvement, no change or even harm for those with Alzheimer's disease. It was not possible to use many of the published results in a combined analysis. For measures of overall clinical improvement, the intention-to-treat analyses failed to detect any difference between tacrine and placebo (OR 0.87; 95%CI 0.61 - 1.23). Behavioural disturbance, as measured by the Alzheimer's Disease Assessment Scale-noncognitive, failed to detect any difference between tacrine and placebo (SMD -0.04; 95%CI -0.52 - 0.43). For cognition function, the effect of tacrine was not statistically significantly different from placebo for the MiniMental State Examination score (0-30; high =good) (SMD 0.14; 95%CI -0.02 - 0.30) and was barely statistically significantly in favour of treatment for the Alzheimer's Disease Assessment Scale-cognitive scale (SMD -0.22; 95%CI -0.32 - -0.13). Adverse events were not reported in a systematic way in the different trials, making formal comparison difficult. Raised serum liver enzymes was the major reason for withdrawal. The odds ratio for withdrawal due to an adverse event was significantly different from one, the control group experienced fewer events (OR 5.7; 95%CI 4.1-7.9). Gastrointestinal side effects (diarrhoea, anorexia, dyspepsia and abdominal pain) were the other major cause of adverse events and for withdrawal, and the odds ratio for withdrawal was also significantly different from one in favour of the control group (OR 3.8; 95%CI 2.8-5.1). No deaths were reported in any of the studies during the trial period, up to six months. AUTHORS' CONCLUSIONS: This review provides no convincing evidence that tacrine is a useful treatment for the symptoms of Alzheimer's disease. However, as so few trials presented data in a format suitable for pooling, the results of this review may be modified when further data from all relevant trials are included. There is an urgent need for the independent evaluation of the data already existing in the trials but not accessible through published or grouped data. An independent meta-analysis of the individual-patient data is required. The results and conclusions of this update are unaltered by further searching as the additional studies do not add any further valid/eligible data.

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OBJECTIVE: To determine the incidence of venous thromboembolic disease in children of Chinese origin, and associated predisposing factors. DESIGN. Retrospective case series. SETTING: A general, public hospital serving a population of approximately 181,000 children in Hong Kong. PATIENTS AND METHODS: Hong Kong Chinese children under the age of 15 years who were diagnosed with a symptomatic venous thromboembolic event between 1995 and 2000 were included. Data on clinical features, predisposing factors, treatment, and outcome were obtained from review of hospital medical records. RESULTS: Eight children (five girls and three boys) of mean age 11.5 years (range, 0-14.7 years) were included in the study. They presented with deep vein thrombosis (n=4, with pulmonary embolism in one), superior vena cava thrombosis (n=1), and cerebral venous sinus thrombosis (n=3). Predisposing factors included hereditary protein C deficiency (n=3), protein S deficiency (n=2), anticardiolipin antibodies (n=1), malignancy (n=3), recent neurosurgery (n=2), infection (n=1), with multiple predisposing factors seen in three patients. Anticoagulant therapy was prescribed in five patients, and long-term warfarin therapy was required in two cases. Venous thromboembolic disease resolved in all children, but one patient had a recurrence after cessation of warfarin therapy, and one patient had post-thrombotic syndrome. CONCLUSION: The rate of venous thromboembolic disease in Hong Kong Chinese children was comparable to that seen in Caucasian children, with an annual incidence of 0.74 per 100,000 children. Predisposing factors, including hereditary prothrombotic conditions, were common.

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Apolipoprotein E (apoE) is a 299 amino acid, anti-atherogenic protein that plays a key role in regulating plasma lipoprotein metabolism. It is composed of an N-terminal (NT) domain (residues 1-191) that is responsible for binding to members of the low density lipoprotein receptor family and a C-terminal (CT) domain (residues 216-299) that anchors the protein to lipoprotein particles by virtue of its high-affinity lipid binding characteristics. Isoform-specific differences in the NT domain that modulate the lipoprotein binding preference elicited by the CT domain suggest the existence and importance of domain interactions in this protein. Employing steady state fluorescence quenching and resonance energy transfer techniques, spatial proximity relationships between the N- and C-terminal domains were investigated in recombinant human apoE3. ApoE3 containing a single Trp at position 264 and an N-iodoacetyl-N'-(5-sulfo-1-napthyl) ethylenediamine (AEDANS) moiety covalently attached to the lone Cys residue at position 112 was used (AEDANS-apoE3/W@264). Fluorescence quenching studies revealed a solvent-exposed location for Trp-264. In the lipid-free state, fluorescence resonance energy transfer (FRET) was noted between Trp-264 and AEDANS, with a calculated distance of 27 A between the two fluorophores. Control experiments established that FRET observed in this system is intramolecular. FRET was abolished upon proteolysis in the linker region connecting the NT and CT domains. Lowering the solution pH to 4 induced an increase in the efficiency of intramolecular energy transfer, with the two domains reorienting about 5 A closer to one another. Interdomain FRET was retained in the presence of 0.6-1.0 m guanidine hydrochloride but was lost at higher concentrations, a manifestation of unfolding of the domains and increased distance between the donor-acceptor pair. Interaction of AEDANS-apoE3/W@264 with lipid induced a loss of FRET, attributed to spatial repositioning of the domains by >80 A. The data provide biophysical evidence that, in addition to reported conformational changes in the four-helix bundle configuration induced by lipid association, lipid binding of apoE is accompanied by reorientation of the tertiary disposition of the NT and CT domains.

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OBJECTIVE: To assess patient satisfaction with and preference for naratriptan hydrochloride therapy over previous "nontriptan" therapy for migraines. DESIGN AND SETTING: Open-label study conducted at 15 primary care clinics. PATIENTS: One hundred forty-three adults meeting International Headache Society diagnostic criteria for migraine who were not using triptans as first-line therapy for migraines were enrolled; 115 completed the study. INTERVENTION AND OUTCOME ASSESSMENTS: At baseline, satisfaction with current migraine therapy was assessed. Patients were provided with naratriptan hydrochloride, 2.5 mg, to treat 3 migraines and diaries to record headache symptoms and response to treatment. After treating 3 migraines, satisfaction with naratriptan therapy and preference for either previous or naratriptan therapy were assessed. RESULTS: Eighty-nine (62%) of 143 patients had previous exposure to triptans, with lack of prescribing (55%) as the primary reason for not continuing their use as first-line therapy. Medications used for first-line therapy included simple analgesics (59%), combination products (46%), and narcotics (13%). After treating 3 migraines with naratriptan, satisfaction with migraine therapy increased from 47% to 75%. Sixty-three percent of patients preferred naratriptan therapy over their previous nontriptan therapy, 27% preferred their previous therapy, and 10% had no preference. The main reasons for preference for naratriptan therapy were "relieves pain effectively" (86%) and "restores ability to function/perform task" (81%). CONCLUSION: Naratriptan for first-line migraine therapy was preferred by most patients over previous nontriptan therapy.

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OBJECTIVES: To determine the clinical efficacy of tacrine for the symptoms of Alzheimer's disease. SEARCH STRATEGY: The Cochrane Dementia Group Register of Clinical Trials was searched using the terms 'tacrine', 'tetrahydroaminoacridine' and 'THA' (see the Group's search strategy for full details). SELECTION CRITERIA: All unconfounded, double-blind, randomized trials in which treatment with tacrine was administered for more than a day and compared to placebo in patients with dementia of the Alzheimer's type. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two reviewers, pooled if appropriate and possible, and the pooled odds ratios (95%CI) or the average differences (95%CI) were estimated. Where possible, intention-to-treat data were used. MAIN RESULTS: This review produced no clear results. The results were compatible with tacrine producing improvement, no change or even harm for those with Alzheimer's disease. It was not possible to use many of the published results in a combined analysis. For measures of overall clinical improvement, the intention-to-treat analyses failed to detect any difference between tacrine and placebo (OR 0.87; 95%CI 0. 61 - 1.23). Behavioural disturbance, as measured by the Alzheimer's Disease Assessment Scale-noncognitive, failed to detect any difference between tacrine and placebo (SMD -0.04; 95%CI -0.52 - 0. 43). For cognition function, the effect of tacrine was not statistically significantly different from placebo for the MiniMental State Examination score (0-30; high =good) (SMD 0.14; 95%CI -0.02 - 0.30) and was barely statistically significantly in favour of treatment for the Alzheimer's Disease Assessment Scale-cognitive scale (SMD -0.22; 95%CI -0.32 - -0.13). Adverse events were not reported in a systematic way in the different trials, making formal comparison difficult. Raised serum liver enzymes was the major reason for withdrawal. The odds ratio for withdrawal due to an adverse event was significantly different from one, the control group experienced fewer events (OR 5.7; 95%CI 4.1-7.9). Gastrointestinal side effects (diarrhoea, anorexia, dyspepsia and abdominal pain) were the other major cause of adverse events and for withdrawal, and the odds ratio for withdrawal was also significantly different from one in favour of the control group (OR 3.8; 95%CI 2. 8-5.1). No deaths were reported in any of the studies during the trial period, up to six months. REVIEWER'S CONCLUSIONS: This review provides no convincing evidence that tacrine is a useful treatment for the symptoms of Alzheimer's disease. However, as so few trials presented data in a format suitable for pooling, the results of this review may be modified when further data from all relevant trials are included. There is an urgent need for the independent evaluation of the data already existing in the trials but not accessible through published or grouped data. An independent meta-analysis of the individual-patient data is required. The results and conclusions of this update are unaltered by further searching as the additional studies do not add any further valid/eligible data.

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BACKGROUND: Tacrine is one of the first drugs to be widely marketed for the loss of memory and intellectual decline in Alzheimer's disease. The alleged success of tacrine in the treatment of these symptoms has been heralded as confirmation of the cholinergic theory of Alzheimer's disease. However, the efficacy of tacrine for symptoms of dementia remains controversial. This is reflected by the low rate of prescription of tacrine in countries where it is approved and the lack of approval by several regulatory authorities in Europe and elsewhere. The uncertainty about the efficacy of tacrine is due to the difficulties in interpretation of the results from the clinical trials. The reasons for this are the small effects of tacrine compared to placebo for all outcomes; the high incidence of adverse events; the lack of benefit observed in several trials; the use of cross-over designs and their associated methodological problems in a disease like dementia; the use of different measurement scales to assess outcome in different trials; and the problem of high dropout rates. OBJECTIVES: To determine the clinical efficacy of tacrine for the symptoms of Alzheimer's disease. SEARCH STRATEGY: The Cochrane Dementia Group Register of Clinical Trials was searched using the terms 'tacrine', 'tetrahydroaminoacridine' and 'THA' (see the Group's search strategy for full details). SELECTION CRITERIA: All unconfounded, double-blind, randomized trials in which treatment with tacrine was administered for more than a day and compared to placebo in patients with dementia of the Alzheimer's type. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two reviewers, pooled if appropriate and possible, and the pooled odds ratios (95%CI) or the average differences (95%CI) were estimated. Where possible, intention-to-treat data were used. MAIN RESULTS: This review produced no clear results. The results were compatible with tacrine producing improvement, no change or even harm for those with Alzheimer's disease. It was not possible to use many of the published results in a combined analysis. For measures of overall clinical improvement, the intention-to-treat analyses failed to detect any difference between tacrine and placebo (OR 0.87; 95%CI 0.61 - 1.23). Behavioural disturbance, as measured by the Alzheimer's Disease Assessment Scale-noncognitive, failed to detect any difference between tacrine and placebo (SMD -0.04; 95%CI -0.52 - 0.43). For cognition function, the effect of tacrine was not statistically significantly different from placebo for the MiniMental State Examination score (0-30; high =good) (SMD 0.14; 95%CI -0.02 - 0.30) and was barely statistically significantly in favour of treatment for the Alzheimer's Disease Assessment Scale-cognitive scale (SMD -0.22; 95%CI -0.32 - -0.13). Adverse events were not reported in a systematic way in the different trials, making formal comparison difficult. Raised serum liver enzymes was the major reason for withdrawal. The odds ratio for withdrawal due to an adverse event was significantly different from one, the control group experienced fewer events (OR 5.7; 95%CI 4.1-7.9). Gastrointestinal side effects (diarrhoea, anorexia, dyspepsia and abdominal pain) were the other major cause of adverse events and for withdrawal, and the odds ratio for withdrawal was also significantly different from one in favour of the control group (OR 3.8; 95%CI 2.8-5.1). No deaths were reported in any of the studies during the trial period, up to six months. REVIEWER'S CONCLUSIONS: This review provides no convincing evidence that tacrine is a useful treatment for the symptoms of Alzheimer's disease. However, as so few trials presented data in a format suitable for pooling, the results of this review may be modified when further data from all relevant trials are included. There is an urgent need for the independent evaluation of the data already existing in the trials but not accessible through published or grouped data. A

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Photodynamic therapy (PDT) is a new approach to cancer treatment for a variety of malignant tumors. In this study, two clinical photosensitizers, Temoporfin (meta-tetra-hydroxyl-phenyl-chlorin; mTHPC) and merocyanine 540 (MC540), were selected to explore for their photocytotoxic and genotoxic effects on nasopharyngeal carcinoma cells (NPC/HK1 and CNE2). Results of tetrazolium reduction assay showed that 80% cell killing were achieved for both cell lines at 0.4 microg/ml mTHPC for 24 h incubation and then with 40 kJ/m2 light irradiation, whereas 40 microg/ml MC540 with 50 kJ/m2 light dosage was required to attain the same level of phototoxicity for NPC/HK1. On the contrary, NPC/CNE2 was quite resistant to MC540. Hence, mTHPC-mediated PDT exerted a more potent effect than MC540-mediated PDT, even though the molar extinction coefficient of the main absorption peak for MC540 is much higher than that of mTHPC. Dark cytotoxicity remained negligible for both sensitizers. Comet assay was used to evaluate the DNA strand break and potential genotoxic effect induced by mTHPC and MC540 on the NPC cells. No DNA strand break was detected in the absence of light, and under sublethal treatment (LD25) for either sensitizer-loaded cells. Confocal laser scanning microscopy showed that mTHPC and MC540 localized in the cytoplasm but not in the nucleus of the tumor cells, which provided evidence for undetectable DNA damage under dark and low photodynamic dose.

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Two cases of anti-Dib, a rarely encountered antibody, were identified in serum samples referred by hospital blood banks during the past 13 months. Case 1 is a 41-year-old female who required blood for elective surgery. Case 2 is a premature infant suffering from mild neonatal jaundice on day 2 after birth. The anti-Dib in both cases exhibited marked dosage effect. The titer/score against Di(a+b+) and Di(a-b+) red blood cells (RBCs) in case 1 was 8/10 and 32/32, respectively, and in case 2, 4/18 and 32/46. The monocyte monolayer assay (MMA) also gave a similar pattern of results, being l5 percent and 100 percent reactive when tested with Di(a+b+) and Di(a-b+) RBCs in case 1, and 0.4 percent (within normal range) and l4.4 percent in case 2. The patient in case 1 underwent her operation without blood transfusion. The infant in case 2 was treated by phototherapy and subsequently recovered without the need for exchange transfusion.

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The fifth child of a Hong Kong Chinese mother developed moderate jaundice, attributable to antibodies (anti-Mi) against antigenic determinants in GP.Mur (Miltenberger, class III) red cells. Both the father and the eldest sister were of the phenotype GP.Mur. Testing of maternal serum against a red cell panel including cells known to carry the antigenic determinants of some Miltenberger phenotypes revealed the presence of anti-Mur. This report documents the first case of haemolytic disease of the newborn (HDN) due to anti-Mur in Hong Kong.

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We collected 103 clinical Enterococcus faecium isolates from across Canada, performed standard broth microdilution susceptibility testing, and compared these results with results from the MicroScan Pos MIC Type 6 panel (Baxter Health Care Corp., West Sacramento, Calif.) and the AMS-Vitek Gram-Positive Susceptibility card (Vitek Inc., St. Louis, Mo.). High-level aminoglycoside resistance to gentamicin and streptomycin was detected by a single-concentration agar method with 1,000 micrograms of each aminoglycoside per ml. In addition, we tested the effect of the lower calcium content in broth media as recommended in National Committee for Clinical Laboratory Standards (NCCLS) guideline M7-A2 on the activity of the highly calcium-dependent agent daptomycin. Of the 103 E. faecium isolates, there were 4 and 30 isolates with high-level gentamicin resistance (HLGR) and high-level streptomycin resistance (HLSR), respectively. An additional 39 (37 with HLGR and 36 with HLSR) E. faecium isolates were tested by both the MicroScan and the AMS-Vitek systems. The AMS-Vitek card demonstrated sensitivities of 95 and 82% for detecting HLGR strains and HLSR strains, respectively. The MicroScan panel demonstrated improved sensitivities for detecting HLGR (42 to 97%) and HLSR (64 to 84%) when readings were performed manually instead of being generated automatically. Ampicillin resistance (MIC, greater than or equal to 16 micrograms/ml) was detected in 23 of the 103 E. faecium isolates. Only 14 and 20 of these were detected by the MicroScan panels and AMS-Vitek cards, respectively. beta-Lactamase activity was not detected in any isolates. The lower calcium content in broth media recommended by NCCLS guideline M7-A2 markedly reduced the in vitro activity of daptomycin against Enterococcus spp.

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We compared the MicroScan Pos MIC Type 6 panel and AMS-Vitek Gram Positive Susceptibility Card (GPS-TA) to agar dilution screen plates for the detection of high-level aminoglycoside resistance in 182 enterococcal isolates. The specificity of the two commercial systems was 100%, with the exception of one susceptible isolate found to be streptomycin resistant by the Vitek system. The MicroScan and Vitek systems had comparable sensitivities for the detection of gentamicin resistance (90 and 95% respectively) and streptomycin resistance (85 and 78%, respectively). These results suggest that screening tests such as agar dilution screen plates, broth dilution, or disk diffusion should continue to be used to detect high-level gentamicin and streptomycin resistance.

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Three cases of juvenile chronic myeloid leukemia (JCML) are reported. The patients were aged 3-4.5 years and presented with generalized lymphadenopathy, hepatosplenomegaly, anemia, thrombocytopenia, elevated white blood cell count with monocytosis, and high fetal hemoglobin level. Philadelphia chromosome was absent in two cases studied. The bone marrow showed myeloid hyperplasia with increased monocytoid cells and blasts. Biopsy or postmortem material available in two cases revealed malignant infiltration of lymph nodes, liver, spleen, lungs, intestines, and skin. The neoplastic cells ranged from cells with irregular nuclei possessing nuclear grooves to large blastic cells with round to lobulated nuclei and prominent nucleoli. They showed weak staining for acid phosphatase and nonspecific esterase and exhibited the immunophenotype EBM11+KiM1+KiM6+KiM8+CD4+HLADR+ S-100 protein+. The neoplastic cells of JCML therefore share features of dendritic cells and mononuclear phagocytes. The authors' findings show that JCML is a unique histiocytic malignancy in which S-100 protein is a useful marker.

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A patient with immunohistochemically confirmed nasal T-cell lymphoma is reported. He developed systemic histiocytosis with marked hemophagocytosis, simulating malignant histiocytosis. The differential diagnosis from the latter is discussed.

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Class I human alcohol dehydrogenase (ADH; alcohol:NAD+ oxidoreductase, EC 1.1.1.1) consists of several homo- and heterodimers of alpha, beta, and gamma subunits that are governed by the ADH1, ADH2, and ADH3 loci. We previously cloned a full length of cDNA for the beta subunit, and the complete sequence of 374 amino acid residues was established. cDNAs for the alpha and gamma subunits were cloned and characterized. A human liver cDNA library, constructed in phage lambda gt11, was screened by using a synthetic oligonucleotide probe that was matched to the gamma but not to the beta sequence. Clone pUCADH gamma 21 and clone pUCADH alpha 15L differed from beta cDNA with respect to restriction sites and hybridization with the nucleotide probe. Clone pUCADH gamma 21 contained an insertion of 1.5 kilobase pairs (kbp) and encodes 374 amino acid residues compatible with the reported amino acid sequence of the gamma subunit. Clone pUCADH alpha 15L contained an insertion of 2.4 kbp and included nucleotide sequences that encode 374 amino acid residues for another subunit, the alpha subunit. In addition, this clone contained the sequences that encode the COOH-terminal part of the beta subunit at its extended 5' region. The amino acid sequences and coding regions of the cDNAs of the three subunits are very similar (approximately 93-95% identity). A high degree of resemblance is observed also in their 3' noncoding regions. However, distinctive differences exist in the vicinity of the Zn-binding cysteine residue at position 46--i.e., Cys-Gly-Thr in the alpha, Cys-Arg-Thr in the wild-type beta 1, Cys-His-Thr in the Oriental-type beta 2, and Cys-Arg-Ser in the gamma, reflecting the differences in their kinetic properties. Based on the cDNA sequences and the deduced amino acid sequences of the three subunits, their structural and evolutionary relationships are discussed.

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A 38 yr-old man has chronic non-spherocytic hemolytic anemia which was attributed to glucose-6-phosphate dehydrogenase (G-6PD) deficiency for the past 20 yr. A diagnosis of congenital dyserythropoietic anemia Type II (CDA) was made because of the bone marrow findings and electron microscopic appearance of the peripheral erythrocytes. Congenital dyserythropoietic anemia, though well recognized in Caucasians, has not hitherto been described in Chinese. Erythrocyte G-6PD deficiency has been found to have an incidence of 5.5% in Southern Chinese. The coexistence of CDA Type II and G-6PD deficiency in this patient may be a chance finding or there may be an interaction between the 2 abnormalities in the clinical manifestations of CDA Type II and G-6PD deficiency.

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In-vitro inhibitions of brain AChE in brook trout, Salvelinus fontinalis (Mitchill), by aminocarb (4-dimethylamino-m-tolyl N-methylcarbamate) and its toxic metabolites, MAA (4-methylamino-m-tolyl N-methylcarbamate), AA(4-amino-m-tolyl N-methylcarbamate), MFA (4-methylformamido-m-tolyl N-methylcarbamate) and FA (4-formamido-m-tolyl N-methylcarbamate) were investigated. The molar concentrations of inhibitors causing 50% inhibition (I50s) were AA (3.62 X 10(-6] less than MAA (7.92 X 10(-6] less than aminocarb (1.01 X 10(-5] less than MFA (4.29 X 10(-5] less than FA (7.11 X 10(-5]. After exposure of fish to various concentrations of aminocarb (25, 250 and 2500 ppb) and MAA (25, 250, 500 and 2500 ppb) at 9 degrees C in dechlorinated tap water for 96 h, inhibitions of brain AChE ranged from 13 to 77%. Mortality occurred only in fish exposed to 500 ppb (22%) and 2500 ppb (100%) of MAA. Enzyme activities recovered to the control levels 12 to 96 h after the fish had been transferred to clean water for clearing; in survivors of the 500-ppb MAA exposure, however, AChE activities decreased again thereafter.

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