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Phospholamban, through modulation of sarcoplasmic reticulum calcium-ATPase activity, is a key regulator of cardiac diastolic function. Alterations in phospholamban expression may define parameters of muscle relaxation. In experimental animals, phospholamban is differentially expressed in various striated and smooth muscles, and within the four chambers of the heart. Decreased phospholamban expression within the heart during heart failure has also been observed. Furthermore, regulatory elements of mammalian phospholamban genes remain poorly defined. To extend these studies to humans, we (1) characterized phospholamban expression in various human organs, (2) isolated genomic clones encoding the human phospholamban gene, and (3) prepared human phospholamban promoter/luciferase reporter constructs and performed transient transfection assays to begin identification of regulatory elements. We observed that human ventricle and quadriceps displayed high levels of phospholamban transcripts and proteins, with markedly lower expression observed in smooth muscles, while the right atria also expressed low levels of phospholamban. The human phospholamban gene structure closely resembles that reported for chicken, rabbit, rat, and mouse. Comparison of the human to other mammalian phospholamban genes indicates a marked conservation of sequence for at least 217 bp upstream of the transcription start site, which contains conserved motifs for GATA, CP1/NFY, M-CAT-like, and E-box elements. Transient transfection assays with a series of plasmids containing deleted 5' flanking regions (between -2530 and -66 through +85) showed that sequences between -169 and the CP1-box at -93 were required for maximal promoter activity in neonatal rat cardiomyocytes. Activity of these reporters in HeLa cells was markedly lower than that observed in rat cardiomyocytes, suggesting at least a partial tissue selectivity of these reporter constructs.

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UNLABELLED: Isolated, heated limb perfusion is used for the treatment of locally recurrent melanoma, intransit metastases, and acral lentiginous melanomas. Tissue warming during this procedure requires adequate perfusion within the isolated extremity. At our institution, spinal or epidural anesthesia was used to produce sympathetic blockade and vasodilation for lower extremity procedures. More recently, we began using mild systemic hyperthermia to produce active thermoregulatory vasodilation. In the presence of heat stress, sympathetic blockade may actually decrease skin blood flow because active cutaneous vasodilation, which is associated with sweating, is dependent on intact sympathetic innervation. We therefore investigated whether the continued use of neuraxial blockade was justified. Twenty patients undergoing lower extremity perfusions were alternately assigned to receive either combined general and spinal anesthesia or general anesthesia alone. All were aggressively warmed using forced air and circulating water. There were no significant differences in tissue temperatures (measured at four sites in the isolated limb) between groups at any time before or after the start of perfusion. Similarly, pump flow (715 +/- 211 mL/min versus 965 +/- 514 mL/min) and the time required to achieve an average tissue temperature of 39 degrees C (43 +/- 16 vs 34 +/- 13 min) were not different between groups (spinal versus no spinal). Sweating was observed in all but three patients at esophageal temperatures of 37.9 +/- 0.6 degrees C. We conclude that sympathetic blockade confers no added benefit for tissue warming during isolated limb perfusions in the presence of induced mild systemic hyperthermia. IMPLICATIONS: Sympathetic blockade prevents adrenergic vasoconstriction, but also inhibits active, neurally mediated cutaneous vasodilation (a normal thermoregulatory response to heat). In slightly hyperthermic patients, we demonstrated that spinal anesthesia does not improve convective tissue warming during isolated, heated limb perfusion. Mild systemic hyperthermia may promote greater vasodilation than sympathetic blockade.

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The mechanism of BLV-induced tumorigenesis has not been clear up to now. Changes of viral protein expression in infected cells may be involved in the molecular events leading to BLV-induced leukaemogenesis. In this study Western blot investigations of cells transfected with plasmid DNA containing the complete Japanese BLV tumour clone provirus demonstrate that this provirus is unable to express gag and env proteins. Following this an attempt was made to express the genes from this provirus in eukaryotic and prokaryotic cells using the phagemid pBK-RSV (Stratagene), but not as fusion proteins. The protein patterns expressed from the 5' and the 3' region of the BLV genome were compared with those of FLK/BLV cells. The results indicate that there is a defect in this provirus located in the genome region between the gag and env gene.

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Reports of intracranial self-mutilation by psychotic individuals are associated with severe mental disorders, criminality, or both. We describe a psychotically depressed male who drove a ballpoint pen through his right medial canthus and into his intracranial compartment. The patient developed a cavernous sinus syndrome and a traumatic dissection of the cavernous portion of the carotid artery. The pen was removed intraoperatively. Postoperatively, the patient was placed on a course of broad-spectrum antibiotics, antidepressants, and antipsychotic medications, and he has received long-term psychiatric follow-up. The literature related to these unusual cases is reviewed, and relevant surgical, medical, and psychiatric aspects of treatment are discussed.

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This study reports quantitative and qualitative differences in intestinal bile acids and cholesterol in miniature pigs following dietary casein or soy protein isolate. The total amount of bile acids in the small intestine was significantly higher when soy protein isolate was fed in comparison to casein. The values were (mean +/- SEM) 4.51 +/- 0.39 mmol and 2.43 +/- 0.08 mmol, respectively, when the proteins were given as the sole component of the diet. When the proteins were given as part of a semi-purified diet, these values were 6.44 +/- 1.04 mmol and 3.95 +/- 0.39 mmol, respectively. Hyocholic acid amounted to 39.6%, hyodeoxycholic acid to 31%, and chenodeoxycholic acid to 27.6% of total bile acids in the small intestine when casein was fed. The soy-fed animals tended to have more secondary bile acids. The total small bowel chymus content, on a wet weight basis, was 63% higher in the soy group. In all experimental conditions studied, there was a close correlation between small bowel chyme content and bile acid content. The distribution of bile acids in the small intestine showed that the soy fed animals tended to have more bile acids in the distal parts of the jejunum. The intestinal cholesterol contents were not significantly different between dietary groups.

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