Stem cells in prostatic epithelia

The normal prostate is, structurally and functionally, a highly complex glandular tissue in which populations of epithelial and stromal cells interact, one with the other, and are under a constant state of proliferation, differentiation, elimination and selective secondary replenishment so that functional integrity of the tissue is maintained. The ability of normal prostatic tissue to maintain its structure and function is dependent upon retention of cells, generally regarded as 'stem cells', which are able to respond by proliferation and selective differentiation within a wide range of phenotypic alternatives. With respect to cells in the epithelial compartment, replenishment is possible at several levels from within distinct pathways of normal cellular differentiation. It is now appreciated that fully differentiated prostatic epithelial cells retain a far greater degree of phenotypic 'plasticity' than was earlier apparent from morphological examination of the intact tissue. This inherent plasticity, coupled with the ability of the intact tissue to respond to diverse environmental (particularly humoral) stimuli by regenerating a wide and divergent spectrum of functional prostatic epithelial phenotypes is its strength--but also its weakness. Disturbance and distortion of the homeostatic regulatory mechanisms, whether physical or humoral, which control the normal sequence of epithelial proliferation, differentiation and elimination exposes these cells, particularly multipotent 'stem cells', to an increased probability of genetic change, thus resulting in either transient, or permanent, neoplastic transformation.     

Differences in risk factors for being either a hepatitis B carrier or anti-hepatitis C+ in a hepatoma-hyperendemic area in rural Taiwan

This is a study of the differences in the risk factors for being either hepatitis B surface antigen positive [HBsAg(+)] or antibody to hepatitis C virus positive [Anti-HCV(+)] in A-Lein, a rural area in southern Taiwan, an area which also has a high hepatoma mortality rate. Three hundred eighty-five patients age > or =40 years participated in hepatoma screening at the A-Lein Community Health Center during 1995. Those who were HBsAg(-) and anti-HCV(-) or had coinfection of HBsAg(+) and anti-HCV(+) were excluded, leaving 293 patients: 109 HBsAg(+) and 184 anti-HCV(+). The anti-HCV(+) patients had a lower socioeconomic status (as defined by level of education and type of occupation) and were older than HBsAg(+) patients (P < 0.05). Those with higher alanine aminotransferase levels (ALT) also had a higher anti-HCV(+) to HBsAg(+) odds ratio (OR), and a dose response relationship was found, P < 0.0001. Anti-HCV(+) patients were more likely than HBsAg(+) patients to have a spouse who shared the infection, OR = 5.11; 95% CI, 2.30-11.28. Anti-HCV(+) patients were more likely than HBsAg(+) patients to have had blood transfusions (OR = 2.66; 95% CI, 1.20-5.89), frequent medical injections (OR = 2.64; 95% CI, 1.62-4.31), or injections by non-licensed medical providers (OR = 1.91; 95% CI, 1.18-3.09). Multiple logistic regression analysis showed that the significant factors for anti-HCV(+) patients vs. HBsAg(+) patients are drinking habit (OR = 3.45; 95% CI, 1.02-11.60), age (OR = 6.33; 95% CI, 2.93-13.68), and frequent medical injections (OR = 2.88; 95% CI, 1.65-5.03). The transmission of hepatitis C in A-Lein is closely related to low socioeconomic status, age, alcohol abuse, spouses being anti-HCV(+), and frequent medical injections, especially from non-licensed medical providers, including both pharmacists and those with no medical licensing whatsoever. These nonlicensed medical providers sometimes reuse needles to save money, which is a likely route of infection.     

Effects of the intermediate retinoid metabolite retinal on the pattern of the dental lamina in vitro

Retinoids have important roles in pattern formation during embryonic development and might act as endogenous morphogens. They are necessary for normal odontogenesis and excess retinol alters the pattern of odontogenesis producing supernumerary buds of the dental lamina in the diastema region of the mouse mandible. Because the metabolism of retinoids in the developing mandible is unknown, the effects of retinal (an intermediate metabolite in the local conversion of retinol to retinoic acid) on the patterning of odontogenesis were examined. Retinal produces supernumerary buds and enhanced epithelial proliferation in day-9 mandibles in vitro. The endogenous levels of retinal in the mandible at the time of initiation of odontogenesis were also measured by high-performance liquid chromatography. Retinal was detected only at day 10 and not at later stages of development. Local metabolism of this intermediate retinoid may be a rate-determining step in the production of active retinoid metabolites that may control the pattern of the dentition, which is established at the time of the appearance of the dental lamina at embryonic day 12.     

Domain flexibility in retroviral proteases: structural implications for drug resistant mutations

Rigid body rotation of five domains and movements within their interfacial joints provide a rational context for understanding why HIV protease mutations that arise in drug resistant strains are often spatially removed from the drug or substrate binding sites. Domain motions associated with substrate binding in the retroviral HIV-1 and SIV proteases are identified and characterized. These motions are in addition to closure of the flaps and result from rotations of approximately 6-7 degrees at primarily hydrophobic interfaces. A crystal structure of unliganded SIV protease (incorporating the point mutation Ser 4 His to stabilize the protease against autolysis) was determined to 2.0 A resolution in a new space group, P3221. The structure is in the most "open" conformation of any retroviral protease so far examined, with six residues of the flaps disordered. Comparison of this and unliganded HIV structures, with their respective liganded structures by difference distance matrixes identifies five domains of the protease dimer that move as rigid bodies against one another: one terminal domain encompassing the N- and C-terminal beta sheet of the dimer, two core domains containing the catalytic aspartic acids, and two flap domains. The two core domains rotate toward each other on substrate binding, reshaping the binding pocket. We therefore show that, for enzymes, mutations at interdomain interfaces that favor the unliganded form of the target active site will increase the off-rate of the inhibitor, allowing the substrate greater access for catalysis. This offers a mechanism of resistance to competitive inhibitors, especially when the forward enzymatic reaction rate exceeds the rate of substrate dissociation.     

Differential effects of elevated potassium ion concentration and of theophylline on growth hormone release by rat adenohypophyses in vitro

The effects of 27 mM K+ and of 6.7 mM theophylline on the release of growth hormone (GH) by rat hemipituitaries in vitro were investigated using bioassay (rat tibia test) and radioimmunoassay (RIA). Both agents markedly increased the release of immunoreactive GH. High K+ also promoted the release of bioactive GH but to a much lesser degree than RIA-GH. Theophylline did not consistently affect the release of bioassay-detectable GH. The results suggest that these agents promote massive release of a form of immunoreactive GH (possibly "immature") that has little or no activity in the bioassay. Theophylline is relatively more effective in this regard than is elevated K+.     

Step slider bearing with viscoelastic lubricant

The performance of an idealized step slider bearing with a viscoelastic lubricant is investigated theoretically. The elasticity of the lubricant is characterized by a dimensionless number α. The effects of the elasticity of the lubricant on the pressure, load-bearing capacity, frictional resistance, coefficient of friction and maximum film thickness were studied in detail and are presented in several graphs and tables.     

Channel Models for Inter-body Communication in Ultra Wideband-Based Body Area Networks

Wireless Personal Communications - Body area networks (BANs) are evolving tremendously over the years and with the progress in the area of internet of things, the BANs are more important than ever....