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We propose a photonic crystal slab-based 1 × 3 power splitter with high output transmission and equal power distribution. It is designed by cascading an asymmetric 1 × 2 power splitter and a symmetric 1 × 2 power splitter. Desired equal power splitting is achieved by introducing and optimizing the splitting region of the 1 × 2 power splitters with flexible structural defects. Simulations were carried out by using 3-D Finite Difference Time Domain method showing equal normalized power distributions of 29.6%, 28.9% and 30.5% at 1550 nm optical wavelength. In addition, equal power splitting also takes place at 1561 nm.

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This work examined how quinine, a drug that induces both hearing loss and tinnitus, interfered with the excitability of spiral ganglion (SG) neurons in cultures. The membrane potential changes and the modification of the action-potential waveform induced by quinine were studied in SG neurons under current clamp. The effects of the drug on voltage-dependent currents in SG neurons were also investigated by the voltage-clamp method. Quinine did not appreciably affect either resting membrane potentials or input resistance at rest. However, action potentials fired by SG neurons were significantly broadened by the presence of quinine. With higher concentrations of quinine (>20 microM), the amplitude of action potentials was also reduced. Voltage-clamp results demonstrated that quinine primarily blocked the whole cell potassium currents (IK) in a voltage-dependent manner. Up to 100 microM of quinine did not appreciably block IK evoked by a test pulse to -35 mV. In contrast, IK was significantly reduced with more positive test pulses, e.g., the concentration needed to obtain 50% inhibition (IC50) was 8 microM for a test pulse to 65 mV. At higher concentrations (>20 microM), quinine also reduced the size of sodium currents (INa) in a use-dependent manner, while leaving calcium currents (ICa) relatively unaffected. Compared with the potency of quinine's effects on other targets in the inner ear, the relatively low IC50 and the voltage-dependent nature of quinine inhibition on IK suggested that its modulation of the waveform and threshold of action potentials of SG neurons probably was primarily responsible for its ototoxic effects. From the point of view of how neural signaling process is affected by the drug, quinine-induced tinnitus may be explained by its broadening of action potentials while the drug's inhibition on INa may result in hearing loss by making the conversion from excitatory postsynaptic potentials to the generation of action potentials more difficult.

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A simple method permitting the flow cytometric examination of cervical specimens has been developed and an assessment made of the feasibility of relying on this method to screen women for cervical neoplasia. Examination of four flow cytometric parameters showed differences between morphologically normal and abnormal specimens and allowed identification of a proportion of the normal specimens. The system had a false negative rate of 8%. Our experience with cervical specimens has revealed a number of problems associated with their examination by flow cytometry and these are discussed.

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In vitro studies implicate classical and alternative complement pathway activation in the pathogenesis of human immunodeficiency virus (HIV) infection. To ascertain their importance in vivo, activation fragments of the classical (C4d), alternative (Ba), and common (C3d) pathways were measured and fragment to parent molecule ratios derived in 74 HIV-infected individuals and related to circulating immune complex (CIC) levels, Centers for Disease Control (CDC) stage, and beta 2-microglobulin, neopterin, and CD4-positive (CD4+) lymphocyte levels. All fragments and ratios were significantly higher in patients (P less than .01) than controls. C4 conversion indices (C4d and C4d to C4) increased linearly with increasing CDC stage (P less than .001), while CD4+ lymphocytes decreased linearly (P less than .001). C4d, C3d, C4d to C4, and C3d to C3 correlated with increasing CIC and beta 2-microglobulin, and C4d and C4d to C4 correlated with decreasing CD4+ lymphocytes (P less than .05). The relationship of classical complement pathway activation to disease progression and CD4+ lymphocytes suggests its involvement in the pathogenesis of HIV infection.

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Using a commercial source of peroxidase-labelled anti-C3d antibody (Dakopatts), an enzyme-linked immunosorbent assay (ELISA) has been developed to quantify the complement fragment C3d. The technique enables the detection of C3d in plasma, urine and cerebrospinal fluid (CSF). The C3d-ELISA therefore provides a very sensitive technique for the evaluation of complement activation in biological fluids. In both plasma and urine the technique is able to discriminate between samples from normal controls and patients with rheumatoid arthritis in whom complement activation is known to occur. A good correlation was found between results obtained by ELISA and those by laser nephelometry (r = 0.91, P less than 0.0001). Microtitre plates pre-coated with anti-C3d antibody and subsequently stored at -70 degrees C retained the ability to perform in this assay. The sensitivity, short assay time and use of commercial reagents and pre-coated plates give this technique numerous potential applications in the evaluation of complement activation.

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A new laser nephelometric technique for the measurement of the alternative complement pathway fragment Ba has been developed. Activation of the alternative complement pathway was assessed in 16 patients with Gram negative bacteraemia, six with Gram positive bacteraemia, 20 with rheumatoid arthritis, and 18 healthy subjects. Patients with Gram negative bacteraemia had significantly higher values of Ba (median 14.8%) than controls (9.3%) (p less than 0.01), while patients with Gram positive bacteraemia and rheumatoid arthritis had values similar to those of controls (10.1% and 9.5%). The technique proved sensitive and precise, and is suitable for the routine laboratory evaluation of complement activation through the alternative pathway.

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Eighteen patients with solid tumours were treated with human recombinant interferon-gamma at escalating dose levels starting at 1 X 10(6) units/m2 per infusion and rising through 3 X 10(6), 6 X 10(6), 9 X 10(6) and 22 X 10(6) to a maximum of 110 X 10(6) units/m2 per infusion. The IV infusions were given three times a week over a 4-week period. Side effects were seen in all patients, but were mild except at the highest dose. Acute dose-related effects included pyrexia, tiredness, thirst, chills and rigors. Chronic dose-related effects included anorexia, lethargy, weakness, disorientation, a trace of proteinuria and minimal rises in liver enzymes. In addition, effects were observed which were not related to dose. These included headache, nausea and vomiting, backache, myalgia, flatulence and a mild, transient reduction in neutrophils and erythrocytes. At the highest dose level dose-limiting toxicity was observed, consisting in severe tiredness and anorexia, hypotension, disorientation and changes on the electrocardiograph. Overall, toxicity was similar to that seen with preparations of interferon-alpha, except that no tolerance to the effects of interferon-gamma was noted. We observed less hepatic and haematological toxicity, but also recorded flatulence, handcramps and electrocardiograph changes, which have not been reported with interferon-alpha. When given according to this regimen, doses of 22 X 10(6) units/m2 per infusion of recombinant interferon-gamma were generally well tolerated by the patients.

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Expression of HLA DR antigens on T lymphocytes indicates that these cells are actively involved in an immune response. Raised levels of activated T lymphocytes were found in 14 of 15 recently diagnosed but in only 7 of 28 long-standing insulin-dependent diabetics. 9 of the recently diagnosed patients retested 6 months later still had high levels of activated T lymphocytes. Even long-standing insulin-dependent diabetics had significantly higher levels of activated T lymphocytes than non-insulin-dependent diabetics and healthy controls. 5 of 7 unaffected co-twins of recently diagnosed insulin-dependent diabetics had high levels of activated T cells; this increase persisted in 2 retested 6 months later, when mildly impaired glucose tolerance had developed. These results confirm that there is an active cellular immune reaction in newly diagnosed insulin-dependent diabetics which may precede the disease and persist for at least 6 months after its appearance.

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The distribution of an epitope of the transferrin receptor in the human uterine cervical epithelium has been investigated. Immunohistochemical staining, both immunofluorescent and immunoperoxidase, was performed on biopsy specimens and cytological samples from normal, dysplastic, and neoplastic cervical epithelia using the monoclonal OKT9 antibody. The results of staining 145 cervical biopsy specimens with OKT9 showed widespread staining in all malignant epithelia and most severely dysplastic epithelia. No such staining was seen in either normal epithelia or in mildly dysplastic epithelia apart from the staining of the basal cell layer in some normal epithelia. The incidence of staining in the 50 cervical cytocentrifuge preparations was not as high as that in the 145 tissue sections. The potential role of the OKT9 antibody in both the screening of cervical cytocentrifuge preparations and the prediction of malignancy is discussed. The antibody is considered to be of more value in the examination of biopsy material than of cytocentrifuge preparations.

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Immunohistochemical staining was performed on biopsies and cytological samples from normal, dysplastic and neoplastic squamous epithelia using the monoclonal Ca 1 antibody. The results of staining 92 biopsies and 20 cytological samples are described and it is reported that positive staining with Ca 1 antibody was detected in normal, dysplastic and neoplastic epithelia. The role of the Ca 1 antibody in the study of cervical cancer is discussed.

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Recombinant interferon-gamma was given to patients with tumours by a six-hour intravenous infusion using a portable mini-pump, to assess the side-effects of the drug. At present, 11 patients have been treated; 2 adenocarcinoma of the ovary, 3 squamous carcinoma of the bronchus, 1 adenocarcinoma of the breast, 1 adenocarcinoma of the stomach, 1 Hodgkin's lymphoma, 1 case of two primaries, adenocarcinoma of the breast and ovary, and 1 adenocarcinoma of unknown origin. Two patients received 1 X 10(6) units/m2/infusion, four received 3 X 10(6) U/m2/inf., three received 6 X 10(6) U/m2/inf. and two received 9 X 10(6) U/m2/inf. Two further dose levels will be used in the future; 27 and 51 X 10(6) U/m2/inf. Three 6-hour infusions a week were given for a four week period. The major side-effects of gamma-interferon were dose-related pyrexia with rigors to which there was no tachyphylaxis, acute and chronic tiredness, nausea with or without vomiting, headache, backache and myalgia. There was also a dose-dependent immediate but mild and transient decrease in the total white cell count. All effects have been transient, and none have been severe. We have also noticed that intravenous infusions by mini-pumps are tolerated far better by the patients than conventional drip systems, and we feel mini-pumps are the ideal way to give intravenous infusions.

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Using monoclonal antibodies OKT3, OKT4 and OKT8, T lymphocyte subpopulations were determined in eight normal male volunteers. One month later, the T cell populations were again measured before and during an insulin stress test. Compared to the month before, there was a statistically significant reduction in the numbers of OKT4 cells (P less than 0.01) in the basal sample. Administration of insulin produced a statistically significant rise in the numbers of total lymphocytes and in each of the T cell subpopulations at 30 and/or 60 min (P less than 0.01) when compared with the basal values. It was also noted that in some of the subjects, the sum of OKT4 and OKT8 cells was greater than the number of OKT3 cells after insulin administration. This suggests that under certain circumstances T cells in circulation may express both the helper and suppressor cell antigen. Insulin stress test is associated with increased production of stress hormones in response to the hypoglycaemia, and the observed lymphocyte changes may be mediated via these hormonal alterations.

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A new nephelometric technique to measure C3d as an indicator of complement activation, is described. C3d is isolated at high concentration of polyethyleneglycol (PEG), incubated with commercially available anti-C3d antiserum at a final concentration of 2.5% PEG and then measured in a Behring Laser Nephelometer. In contrast to previously available techniques our assay detects the low concentrations of C3d present in all normal subjects, which result from the continuous C3 catabolism occurring in vivo. We have also measured C3d blood concentrations in a large number of patients with diseases associated with complement activation. Raised C3d concentrations were found in 68% of rheumatoid arthritis, 57% of primary biliary cirrhosis, 38% of chronic active hepatitis, 100% of Gram-negative bacteraemia and 100% of malaria. The nephelometric technique has proved to be sensitive, economical and fast, and could be adapted for routine determination of C3d blood concentrations to monitor disease activity and response to treatment.

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The concentrations of C3d in the plasma and of C-reactive protein (CRP), immune complexes and rheumatoid factor in the serum were measured in 99 patients with rheumatoid arthritis. Most patients had raised levels, the values of which correlated with disease activity assessed according to a newly described index based on multivariate analysis of subjective, semi-objective and objective features of the disease. There were also significant correlations between the values for plasma C3d and circulating immune complexes, immune complexes and rheumatoid factor, serum CRP and immune complexes, and serum CRP and plasma C3d. Measurement of plasma C3d provides a useful means of detecting in vivo complement activation, which may be involved in the pathogenesis of rheumatoid arthritis, but neither C3d levels nor any of the other variables correlated as closely with disease activity as did the serum CRP concentration.

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A high percentage of patients with acute leukaemia in established remission develop chronic liver disease: how important hepatitis-B-virus (HBV) infection is as an aetiological factor is not clear. The presence of HBV markers in liver and serum of 23 leukaemic children with liver disease was investigated at the time of a diagnostic biopsy just before treatment withdrawal. Although, at this time, none had HBV antigens or antibodies in the serum by radioimmunoassay, HBsAg was detected by direct immunofluorescence in the cytoplasm of hepatocytes in 13 children, 7 of whom also had hepatitis-B core or e antigens in hepatocyte nuclei. This pattern of both cytoplasmic and nuclear fluorescence was present in 4 of 6 patients with the histological features of chronic active hepatitis on liver biopsy. The failure of release of viral antigens into serum and the absence of an adequate immune response were probably due to the intense chemotherapy used to induce and maintain remission, since HBV markers appeared in the serum within 15 months of stopping treatment in 8 of the children in whom viral antigens had been detected in liver tissue but in none of those whose biopsy specimens were negative by immunofluorescence. These results suggest that HBV infection may be an important cause of chronic liver disease in children with leukaemia and show that during treatment serological tests may fail to detect the presence of the virus.

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