Relation of growth hormone and myocardial collagen accumulation in experimental diabetes

A pathogenic role of growth hormone in the tissue complications of diabetes has been postulated. Because collagen has been found to accumulate in myocardial interstitium in diabetes, we have undertaken a study of the relationship of plasma growth hormone levels to collagen accumulation in a canine model of chronic diabetes. Sedentary normal animals and diabetic animals were compared respectively with physically conditioned animals in which the collagen increment associated with diabetes was minimized. Basal growth hormone levels as well as increments induced by hormone release after clonidine have been related to the myocardial alteration. Myocardial collagen concentration was increased to 2.94 +/- 0.11 micrograms/mg dry weight in the sedentary diabetic animals vs. 1.97 +/- 0.07 micrograms/mg dry weight in sedentary normals (P less than 0.01), but was normal in the exercised diabetic animals after 1 year. However, levels of growth hormone in the basal state were similar in all four groups. After provocative stimulation with clonidine in the normals there was a progressive rise of growth hormone levels that was similar in the sedentary and physically conditioned animals. The diabetic groups exhibited a rise of plasma growth hormone that was not significantly higher in the nonexercised animals. Moreover the peak levels of growth hormone after clonidine were comparable. The data suggest that collagen accumulation in diabetic myocardium does not appear to be dependent on increased plasma levels of growth hormone, but a role for enhanced sensitivity to hormonal action is not excluded.     

Obsessive-compulsive disorder, depression, and the dexamethasone suppression test

Five of 29 obsessive-compulsive disorder patients were dexamethasone suppression test (DST) nonsuppressors, all of whom met standard Hamilton Depression Rating scale criteria for at least mild depression. None of 24 nondepressed obsessive-compulsive disorder patients had an abnormal DST. The relationship of the DST to specificity of psychiatric diagnoses is discussed.     

Cysteine Conjugate beta-Lyase-Dependent Metabolism of Compound A (2-[fluoromethoxy]-1,1,3,3,3-pentafluoro-1-propene) in Human Subjects Anesthetized with Sevoflurane and in Rats Given Compound A

Background: Sevoflurane undergoes Baralyme- or soda lime-catalyzed degradation in the anesthesia circuit to yield compound A (2-[fluoromethoxy]-1,1,3,3,3-pentafluoro-1-propene), which is nephrotoxic in rats and undergoes metabolism via the cysteine conjugate beta-lyase pathway in those animals. The objective of these experiments was to test the hypothesis that compound A undergoes beta-lyase-dependent metabolism in humans.

Methods: Human volunteers were anesthetized with sevoflurane (1.25 minimum alveolar concentration, 3%, 2 l/min, 8 h) and thereby exposed to compound A. Urine was collected at 24-h intervals for 72 h after anesthesia. Rats, which served as a positive control, were given compound A intraperitoneally, and urine was collected for 24 h afterward. Human and rat urine samples were analyzed by19 F nuclear magnetic resonance spectroscopy and gas chromatography-mass spectrometry for the presence of compound A metabolites.

Results: Analysis of human and rat urine showed the presence of the compound A metabolites [S-[2-(fluoromethoxy)-1,1,3,3,3-pentafluoropropyl]-N-acetyl-L-cysteine, (E)- and (Z)-S-[2-(fluoromethoxy)-1,3,3,3-tetrafluoro-1-propenyl]-N-acetyl-L-cyst eine, 2-(fluoromethoxy)-3,3,3-trifluoropropanoic acid, 3,3,3-trifluorolactic acid, and inorganic fluoride. The presence of 2-(fluoromethoxy)-3,3,3-trifluoropropanoic acid and 3,3,3-trifluorolactic acid in human urine was confirmed by gas chromatography-mass spectrometry.     

Mutations in the retinal guanylate cyclase (RETGC-1) gene in dominant cone-rod dystrophy

The dominant cone-rod dystrophy gene CORD6 has previously been mapped to within an 8 cM interval on chromosome 17p12-p13. The retinal- specific guanylate cyclase gene (RETGC-1), which maps to within this genetic interval and previously was implicated in Leber's congenital amaurosis, was screened for mutations within this family and in a panel of small families and individuals with various cone and cone- rod dystrophy phenotypes. A missense mutation (E837D) was identified in affected members of the CORD6 family, as well as a second missense mutation (R838C) in three other families with dominant cone-rod dystrophy. RETGC-1 is only the fourth gene to be implicated in cone-rod dystrophy and this is the first report of dominant mutations in this gene.      

Soft tissue infection with Absidia corymbifera in a patient with idiopathic aplastic anemia

We describe a case of primary cutaneous mucormycosis (zygomycosis) in a patient with idiopathic aplastic anemia which responded to surgical debridement and therapy with liposomal amphotericin B. The tissue removed at surgery showed dense infiltration with fungal hyphae on histopathological examination. Primary cultures of tissue on solid media were negative, but Absidia corymbifera was isolated from unprocessed tissue placed in brain heart infusion broth.     

Isolation and characterization of human and rabbit sperm tail fibrous sheath

Using mechanical and chemical dissection methods, fibrous sheath was isolated both from normal ejaculated human spermatozoa and from rabbit cauda epididymal spermatozoa. The same techniques did not produce a pure preparation of fibrous sheath from ejaculated rabbit spermatozoa, suggesting that further cross-linking and stabilization of sperm structures occurs in response to components of the seminal plasma. The isolation procedures were monitored by phase contrast microscopy and the purity of the fibrous sheath was verified by electron microscopy. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) of isolated human fibrous sheath revealed at least 14 protein bands of which the most intensely stained were of molecular weight 84, 72, 66.2, 57, 32 and 28.5 kDa. The rabbit fibrous sheath revealed at least 10 protein bands, of which the most intensely stained were 35.2, 32.7 and 28.5 kDa. The amino acid composition of the purified fibrous sheath from human and rabbit spermatozoa was similar, being high in aspartic acid and/or asparagine and glutamic acid and/or glutamine, serine, alanine, leucine, lysine and glycine, but low in histidine, tyrosine and isoleucine. This composition is similar to that reported for the rat and suggests that mammalian sperm tail fibrous sheaths are composed of similar types of proteins, although there are apparent differences in protein components between species.