Characterization of type I 5 alpha-reductase activity in DU145 human prostatic adenocarcinoma cells

Each amino acid is represented by a vector of numerical measurements for the attributes of volume, area, hydrophilicity, polarity, hydrogen bonding, shape, and charge. Inter-residue distances are then calculated according to common metrics, and we introduce a new clustering objective function derived from information-theoretic considerations. The arguments of the function are the inter-object distances of the things to be clustered: in this case the amino acids. By means of approximating the solution of an integer programming problem, then, the residues are partitioned into clusters. The clusters obtained are compared with groups obtained in substitution/mutation studies and found to be similar. Thus, probably the strongest and most objective evidence to date is supplied for believing that physico-chemical properties account for the viability of substitutions and that the important similarities/differences are explained by a relatively small and simple set of properties.     

(1-Benzylindole-3-yl)alkanoic acids; novel nonsteroidal inhibitors of steroid 5 alpha-reductase (I)

A novel series of indole-3-alkanoic acids with varied N-benzyl substituents were synthesized as nonsteroidal inhibitors of steroid 5 alpha-reductase. The structure-activity relationships in this series were studied and the optimum carboxylic acid side chain was butyric acid. Furthermore, compounds with a diaryl substituent at the 1-position of the indole ring displayed strong inhibitory activities in vitro. Amongst these derivatives, 4-[1-(6,6-dimethyl-6H-dibenzo[b,d]pyran-3-yl)methylindol-3-yl]b uty ric acid (FR119680) displayed very high inhibitory activity in vitro against rat prostatic 5 alpha-reductase (IC50 = 5.0 nM) and good in vivo activity in the castrated young rat model.     

Human T cell leukemia virus type I expression in salivary glands of infected patients

Human T cell leukemia virus type I (HTLV-I) sequences were sought in labial salivary glands of patients with HTLV-I-associated myelopathy or tropical spastic paraparesis and of seropositive neurologically healthy carriers. HTLV-I proviral DNA was found by polymerase chain reaction amplification in DNA extracted from lip biopsies of every patient. Viral RNA was found by in situ hybridization in the acini epithelium, as well as in lymphocytic infiltrates. This observation suggests that HTLV-I expression in labial salivary glands could participate in the inflammatory lesions observed in these patients. Some seronegative patients with Sj?gren's syndrome or dryness syndrome were also positive for viral transactivator tax DNA (41% in Martinique and 16% in non-HTLV-I-endemic region). Despite histologic signs of lymphocytic infiltration, no viral expression was found in the labial salivary glands of these patients.     

Demonstration of anionic sites in human eccrine and apocrine sweat glands in post-embedded ultra-thin sections with cationic colloidal gold: effect of enzyme digestion on these anionic sites

We localized anionic sites ultrastructurally in human eccrine and apocrine sweat glands with a poly-L-lysine-gold complex (cationic colloidal gold). Anionic sites were labeled by incubating Lowicryl K4M-embedded sections on droplets of cationic colloidal gold. In eccrine sweat glands, colloidal gold particles were restricted to the basolateral membrane of the secretory cells at low pH, whereas the luminal membrane did not react with the gold particles. Chondroitinase ABC digested these anionic sites. This indicates that chondroitin sulfate and/or dermatan sulfate constitutes anionic sites in the basal labyrinth of eccrine sweat glands. In apocrine sweat glands, the luminal membrane of the secretory cells showed strong reaction at low pH, whereas the contraluminal membrane did not show any reaction. Neuraminidase completely digested these anionic sites, which indicated that the anionic charge of the apocrine lumen was due to sialic acid. Differences in distribution and susceptibility to enzymes of anionic sites in cell membranes between eccrine and apocrine sweat glands may reflect functional differences between these glands. Dark cell granules in eccrine secretory cells were negative for the anionic sites when sections were labeled without any pre-treatment. However, pre-incubation of the grids on EGTA or deionized water unmasked the anionic sites on the dark cell granules. The positive staining after EGTA treatment was greatly decreased by reincubation with CaCl2. These results suggested that Ca blocked anionic sites in dark cell granules. Exposed anionic sites were digested with chondroitinase ABC. This indicated that chondroitinase ABC and/or dermatan sulfate composed the anionic sites in dark cell granules.     

Increased risk for type I (insulin-dependent) diabetes in relatives of patients with alopecia areata (AA)

The prevalence of various chronic diseases was compared in 517 individuals with alopecia areata, and 2,969 of their first degree relatives. As previous reports have suggested an increased incidence of diabetes in relatives of patients with alopecia areata, special attention was given to the prevalence of Type 1 and Type 2 diabetes in the patients and in their relatives. Several immunologic diseases were increased in alopecia probands and relatives. Thyroid disease, vitiligo, Addison disease, and pernicious anemia were more prevalent in probands and in their relatives than in the general population. Specifically, a high rate of thyroid disease was found in probands (14.7%) and in their first degree relatives (4.2%). Only one proband had Type 1 diabetes, yet there were 14 sibs with Type 1 diabetes. Thus, Type 1 diabetes was significantly more prevalent in the sibs (1.2%) than in either the probands with alopecia (0.2%), or the general population (0.12-0.25%) (P < 0.05)). In contrast, Type 2 diabetes was not more common in probands or in sibs than in the general population. These data suggest that alopecia areata protects against Type 1 diabetes in predisposed individuals. The high rate of thyroid disease suggests that screening probands and first degree relatives for thyroid disease should be considered.     

Defective human T-cell lymphotropic virus type I (HTLV-I) provirus in 10 Chilean seronegative patients with tropical spastic paraparesis or HTLV-I-associated myelopathy

We studied the presence of tax and ltr genes from human T-cell lymphotropic virus type I (HTLV-I) provirus in the peripheral blood mononuclear cells from 15 seronegative patients with tropical spastic paraparesis or HTLV-I-associated myelopathy by PCR. Only a region of the tax gene from 10 patients was amplified. The nucleotide homologies of six Chilean isolates to the ATK-1 clone ranged between 98.7 and 99.4%.     

High prevalence of celiac disease among patients with insulin-dependent (type I) diabetes mellitus

OBJECTIVES: Diagnosis of unrecognized celiac disease is potentially important. The prevalence of celiac disease in patients with insulin-dependent diabetes mellitus is uncertain. We report the prevalence of celiac disease in a stratified random sample (n = 101) of adult insulin-dependent diabetic patients (age, 18-59 yr) attending our clinic, and in an age- and sex-matched control group (n = 51). METHODS: Screening was by anti-endomysial antibody, measured by indirect immunofluorescence using sections of human umbilical cord. RESULTS: Celiac disease had not been suspected in any patient at the time of screening. Eight patients tested positive for anti-endomysial antibody, all of whom had a distal duodenal biopsy performed. Five patients had histologic evidence of celiac disease. One patient with negative histology was receiving immunosuppressive therapy for a renal-pancreas transplant. Of the five patients with abnormal histology, two improved on gluten restriction, one was unable to comply, one refused treatment, and one was lost to follow-up. No control subject tested positive for endomysial antibody. CONCLUSIONS: Patients with insulin-dependent diabetes have an increased prevalence of celiac disease. Because most cases are clinically unrecognized, consideration should be given to screening all insulin-dependent diabetes mellitus patients with endomysial antibodies.     

Combined use of 5 alpha-reductase inhibitors and alpha-l adrenergic receptor blockers in patients with benign prostatic hyperplasia

Historically, the ethics of a professional were the ethics of a gentleman. The social changes in the 1960s, where citizens asked for a greater voice in all affairs that affected them gave rise to formal approaches to ethics in the health fields. Principle-based and case-based reasoning have been dominant. Neither codes nor approaches based on virtue (the character of the professional) are perfect solutions in all cases, but professions are strengthened through the development and discussion of statements about ethical conduct.     

Purification and characterization of gonadotropin I and II from pituitary glands of tuna (Thunnus obesus)

The duality of teleost pituitary gonadotropins was established in an advanced marine fish, the tuna (Thunnus obesus). Two different molecular forms of gonadotropins, designated tGTH I and tGTH II, were isolated from an alcoholic extract of pituitary glands following ion-exchange chromatography and reversed-phase HPLC. Both tGTH I and tGTH II stimulated estradiol-17 beta and testosterone production in tuna ovarian follicles in vitro, although responses to tGTH II were significantly greater than those to tGTH I. Each gonadotropin consisted of alpha- and beta-subunits. tGTH I was stable in acidic conditions, whereas tGTH II dissociated into two subunits after acid treatment. Alpha subunits of tGTH I and tGTH II had identical amino acid sequences of 94 amino acid residues. The tGTH I beta and tGTH II beta consisted of 102 and 115 amino acid residues, respectively, and showed 35% sequence identity. tGTH I beta is structurally more similar to salmon GTH I beta than to salmon GTH II beta, whereas tGTH II beta is more similar to salmon GTH II beta. Thus it is evident that the tuna pituitary gland produces two chemically distinct gonadotropins.     

Prevention of type I diabetes in the non-obese diabetic (NOD) mouse with 15-deoxyspergualin (15-DS) or 15-DS + cyclosporin A (CyA)

By selectively inbreeding diabetic individuals, we have been able to establish an NOD mouse population with a genetic predisposition towards insulin-dependent diabetes mellitus (IDDM) in approximately 100% of cases. We examined the preventive effect of 15-DS or 15DS + CyA on developing IDDM in these animals. Whereas 15-DS has been proved to be effective in preventing diabetes (significant decrease of the diabetic risk ratio to 0.368 and a reduction of the incidence of the disease to 46.7%), combined treatment with CyA did not produce any additional benefit.     

Effects of opiate receptor blockade with naloxone on prolactin (PRL) secretion in patients with diabetes type I (IDDM) with chronic renal failure treated with hemodialysis (HD)

Minute dissection was performed on the ventral primary rami of the first thoracic to first lumbar nerves in two halves of an adult male cadaver in order to determine points of origins of muscular branches from the intercostal nerves. Generally, the muscular branches originated independently, but the branches supplying the intercostalis intimus and internus tended to originate as a common trunk. The muscular branching patterns were compiled in an illustration, and based on these patterns the serial homology of the thoracic and abdominal muscles was proposed. Although the obliquus externus abdominis has been thought to correspond to the intercostales externi, from these innervation findings it appears to correspond to the intercostales interni. Further, the quadratus lumborum seems homologous to the intercostales externi.     

Apolipoprotein(a) concentrations in type 2 (non-insulin dependent) diabetic patients from Romania

Several studies suggested that lipoprotein (a)-Lp(a) is an independent atherogenic risk factor. Since non-insulin-dependent diabetes mellitus (NIDDM) is characterized by an increased risk of coronary heart disease (CHD) as related to the general population, the main purpose of our study was to compare the plasma levels of apolipoprotein (a)-(apo) (a) in 30 NIDDM patients hospitalized in our department, and in 20 non-diabetic controls from Timi?oara. Apo (a) values were similar in the two groups (medians, 95% confidence intervals 57 (50-107) in NIDDM versus 58 (51-106) U/l in controls; p = 0.9097). We found weak correlations between apo (a) and hemoglobin A1 (HbA1) (r = 0.42). A significant association was noticed between apo (a) and apo B, both in NIDDM (r = 0.71) and in control subjects (r = 0.81) p < < 0.001. The diabetic patients were screened for microalbuminaria with the MICRAL-test and we compared apo (a) levels in those having albumin excretion values above and under the cut-off point (20 mg/l). Apo (a) concentrations were similar in both samples. We found no association between apo (a) and plasma lipid values. NIDDM patients on fair glycemic control have similar apo (a) concentrations to non-diabetic subjects and they do not seem to be influenced by diabetes duration, HbA1, microalbuminuria and plasma lipid values Apo (a) and apo B are significantly correlated, both in diabetic and non-diabetic subjects.     

Human T lymphotropic virus type I (HTLV-I)-specific T helper cell responses from HTLV-I seronegative patients with chronic myelopathy and MS in Japan

Human T lymphotropic virus type I (HTLV-I) is a human retrovirus etiologically linked to Adult T cell leukemia (ATL) and HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP). Although most HAM/TSP patients have high anti-HTLV-I antibody titers in their sera, HTLV-I infected but seronegative patients with neurological diseases have been reported. To clarify whether seronegative, HTLV-I related neurological disease may exist, we have developed a method that measures the production of interleukin-2 (IL-2) from HTLV-I synthetic peptide-stimulated peripheral blood lymphocytes (PBL) of HTLV-I infected persons. This method is sensitive enough to detect exposure to HTLV-I before seroconversion or even before detection by PCR. We examined 12 patients with chronic progressive myelopathy and eight patients with multiple sclerosis (MS) in central Japan, where the prevalence rate of HTLV-I is between one and four percent among asymptomatic blood donors, using the IL-2 production assay. None of them were positive by the assay, suggesting seronegative HTLV-I myelopathy is very rare among patients with chronic progressive myelopathy and MS in Japan.     

Antihistamines reduce blood-retinal barrier permeability in type I (insulin-dependent) diabetic patients with nonproliferative retinopathy. A pilot study

The bioassay technique and high-performance liquid chromatography (HPLC) method were used to establish chloroquine (CQ) concentration equivalents in serum samples collected from Aotus and Saimiri monkeys after administration of CQ. The results indicate some differences in CQ metabolism between the two simian species. They also indicate a strong positive relationship (rs = 0.96) between data obtained by the bioassay and HPLC technique. The findings suggest that the use of the bioassay in these small primates, using only a fraction of the serum required for HPLC analysis, should provide a useful mean for obtaining preliminary information about the degree and duration of serum antimalarial activity of promising experimental drugs. Apart from reducing the number of monkeys required for drug evaluation, this in vivo-in vitro model should also decrease the overall cost and duration of developing new antimalarial agents.     

Characterization of insulin autoantibodies in relatives of patients with type I diabetes

We studied in detail the anti-insulin autoantibodies in 29 nondiabetic relatives of patients with type I diabetes. The affinity of the autoantibodies for [125I]human insulin was high (1.34 x 10(9)-20.71 x 10(9) L/mol), and the capacity was low (0.84 x 10(-12)-37.80 x 10(-12) M). The product of affinity x capacity of each relative's antibodies directly correlated (r = 0.99) with the level of antibodies determined in our standard radioassay. The autoantibodies from each of the subjects studied had the same rank order of affinities for insulin from different species. Guinea pig, fish insulin, and insulin containing Trp rather than Leu in position 13 of the A-chain inhibited minimally the human insulin binding. Human proinsulin, insulin containing Gln rather than Glu in position 17 of the A-chain, and desoctapeptide insulin (des B23-30) all inhibited binding effectively. Insulin autoantibodies in relatives of patients with type I diabetes share common epitope(s), which suggests a common pathogenic mechanism for production of such antibodies. The epitopes from this initial analysis appear to include amino acids B1-B3 and A8-A13. The region recognized can be distinguished from the insulin receptor binding domain.     

Pilot study of 5-azacytidine (5-AZA) and carboplatin (CBDCA) in patients with relapsed/refractory leukemia

The principle of bowel detubularization to decrease peristaltic pressure and increase reservoir capacity is applied in contemporary continent urinary diversions. The process of detubularization and refashioning of the spatulated bowel segment approximates 1 of operating time and is the most time-consuming aspect of pouch construction. The employment of devices applying absorbable staples ("absorbable staplers") has substantially reduced the time required to fashion bowel reservoirs. This article reviews the adaptation of the absorbable stapler to continent urinary diversion using small- and large-bowel segments.     

Empirically supported treatments or type I errors? Problems with the analysis of data from group-administered treatments.

When treatments are administered in groups, clients interact in ways that lead to violations of a key assumption of most statistical analyses-the assumption of independence of observations. The resulting dependencies, when not properly accounted for, can increase Type I errors dramatically. Of the 33 studies of group-administered treatment on the empirically supported treatments list, none appropriately analyzed their data. The current authors provide corrections that can be applied to improper analyses. After the corrections, only 12.4% to 68.2% of tests that were originally reported as significant remained significant, depending on what assumptions were made about how large the dependencies among observations really are. Of the 33 studies, 6-19 studies no longer had any significant results after correction. The authors end by providing recommendations for researchers planning group-administered treatment research. (PsycINFO Database Record (c) 2010 APA, all rights reserved)