Association of the GNAS1 gene variant with hypertension is dependent on alcohol consumption.

The beta-adrenoceptor (beta-AR)-stimulatory guanine nucleotide-binding (Gs) protein system has been shown to play important roles in the cardiovascular system. The gene encoding the alpha-subunit of Gs proteins (GNAS1) is a candidate genetic determinant for hypertension. Because alcohol consumption is known to affect blood pressure partly through the beta-AR-Gs protein system, we examined the possible interaction between GNAS1 T393C polymorphism and drinking status in the association with hypertension in the present study. As a result, a non-significant but reasonable trend supporting the presence of an interaction was shown (p = 0.076). In line with this trend, the T393C polymorphism significantly interacted with drinking status in the association with systolic blood pressure (p = 0.028). Moreover, supporting the presence of an interaction, T allele carriers consistently had a higher probability of hypertension, higher systolic blood pressure, and higher diastolic blood pressure than CC homozygotes in non-drinkers and light drinkers. In contrast, CC homozygotes consistently had a higher probability of hypertension, higher systolic blood pressure, and higher diastolic blood pressure than T allele carriers in moderate to heavy drinkers. The present study also showed a significant interaction between the T393C polymorphism and drinking status in the association with pulse pressure (p = 0.026), reflected by a significant association between the T393C polymorphism and pulse pressure in moderate to heavy drinkers (p = 0.026). These findings may be helpful in conducting further molecular and biological studies on the relationship among the effects of alcohol, the beta-AR-Gs protein system, and hypertension.     

Lethal midline granuloma (peripheral T-cell lymphoma) after lymphomatoid papulosis.

A Japanese woman with an 8-year history of lymphomatoid papulosis (LP) had lethal midline granuloma (LMG) develop at the age of 51 years. There were histologic similarities between LP and LMG seen in this patient. Surface phenotypic studies on nasal and cutaneous lesions demonstrated a population of T-cells expressing CD2, CD4, CD25, CD30, and histocompatibility antigen-DR (HLA-DR). Genotypic analyses of nasal and skin biopsy specimens disclosed a clonal rearrangement of the beta T-cell receptor gene with the same rearrangement pattern. These data indicate that this patient had LMG characterized by clonal peripheral T-cell lymphoma, which probably resulted from progression of the LP.     

A muscle-derived factor antagonizes the neurotoxicity of glutamate in dissociated cell cultures of chick telencephalic neurons.

Excitatory amino acids including glutamate are known to reveal considerable neurotoxicity in various nervous systems. Our previous studies revealed that the chick muscle extract contains a factor which promotes the survival of telencephalic neurons. Further investigations clearly showed that this extract contains the factor that antagonizes the neurotoxicity of glutamate in a dissociated telencephalic neuronal culture system optimized for detection of the toxicity. This factor reduced at least the toxicity mediated by non-N-methyl-D-aspartate (non-NMDA) receptor.     

Ubiquitous Presence in Mammalian Cells of Enzymatic Activity Specifically Cleaving 8-Hydroxyguanine-containing DNA

Here we report the finding of enzymatic activity that specifically cleaves DNA containing 8-hydroxyguanine (oh⁸Gua) residues in various mammalian cells. To detect this activity, we used a synthetic double-stranded DNA containing a single oh⁸Gua at a defined position as the substrate, and analyzed the products of enzymatic digestion by polyacrylamide gel electrophoresis. Two cleavage sites near the oh⁸Gua residue were detected with partially purified fractions from cow brain and rat liver, and also with preparations from all mammalian tissues examined. These results suggest that enzymatic activity for the removal of oh⁸Gua from DNA is widely distributed in mammalian cells.     

Prostatic carcinoma in a young adult: a case report]

We report a case of carcinoma of the prostate in a 30-year-old man. Serum acid phosphatase was normal. A transrectal biopsy of the prostate demonstrated an undifferentiated carcinoma. Total prostatocystectomy was performed and subsequent pathologic report stated that the mass was an undifferentiated carcinoma of the prostate gland. Metastases to the intrapelvic lymph node were present. Although immunohistochemical prostatic acid phosphatase (PAP) activity was not demonstrated, prostatic specific antigen (PSA) staining revealed a positive reaction within the tumor cells, confirming prostatic carcinoma. The patient's course has been uneventful without any recurrence by the intermittent adjuvant chemotherapy 8 months postoperatively. Review of the literature in Japan disclosed 16 cases (including our case) of carcinoma of the prostate in patients under 40 years of age.     

Comparative pharmacokinetics of pipecuronium bromide, pancuronium bromide and vecuronium bromide in anesthetized man

The pharmacokinetics of pipecuronium bromide was studied in 9 male patients (ASA class 1-2, 20-65 years of age). Following a single intravenous dose of pipecuronium 0.08 mg.kg-1, plasma levels were measured by capillary gas chromatography. Plasma concentration-time curves were evaluated by fitting the data to a bi-exponential equation. The pharmacokinetic parameters of pipecuronium were compared with those of pancuronium (0.08 mg.kg-1) and vecuronium (0.08 mg.kg-1) previously obtained under the same anesthesia (66% N2O, 33% O2 and 1% halothane). With pipecuronium, following pharmacokinetic parameters were obtained; distribution half-life; T1/2 alpha = 3.9 +/- 0.7 min (mean +/- SEM), elimination half-life; T1/2 beta = 102 +/- 12 min, volume of the central compartment; V1 = 95 +/- 13 ml.kg-1, volume of distribution at steady state; Vdss = 264 +/- 41 ml.kg-1, clearance; Cl = 1.8 +/- 0.2 ml.min-1.kg-1. Microconstants of two-compartment open models (k12, k21, k10) were also calculated. Using Mann-Whitney's U-test, these parameters of pipecuronium were compared with those of pancuronium (n = 3) and vecuronium (n = 4). V1 and Vdss of pipecuronium were significantly larger than those of pancuronium (V1; 38 +/- 12 ml.kg-1 and Vdss; 120 +/- 4 ml.kg-1) (both P less than 0.10). Reflecting the larger central volume of pipecuronium, pipecuronium tended to have a larger clearance than that of pancuroniumu (Cl; 1.1 +/- 0.2 ml.min-1.kg-1).(ABSTRACT TRUNCATED AT 250 WORDS)     

Transepithelial movement of non-polar and polar compounds in male rat reproductive tubule examined by in vivo microperifusion and in vivo micropuncture

Proluminal movement of 3H-testosterone and 3H-sucrose from peritubular to intratubular fluids of the adult rat testis and epididymis was investigated by using in vivo microperifusion and subsequent micropuncture of seminiferous tubules and caput, corpus, and cauda epididymal tubules. Tubules were perifused with Minimum Essential Medium containing 3H-testosterone or 3H-sucrose. 14C-polyethyleneglycol was included in the perifusion fluid as a marker for contamination of intraluminal fluid by interstitial fluid. Radioactivity of isotopes in perifusion and intraluminal fluids was determined at one and two hours after perifusion and the percentage of peritubular isotopes appearing in intraluminal fluid was determined. Net entry of 3H-sucrose into the seminiferous and epididymal tubules was significantly reduced. Proluminal movement of 3H-androgen across the seminiferous epithelium was also restricted. In contrast, intraluminal 3H-androgen concentrations in caput epididymal fluid were 200 to 300% of those in peritubular fluid at both one and two hours after perifusion. Similar results were found in the corpus epididymidis. 3H-androgen concentrations in cauda epididymal fluid were approximately 125% of peritubular isotope concentrations. The exact mechanism underlying this uphill proluminal movement of 3H-androgen into the rat epididymal lumen remains to be elucidated.     

Determination of the exposure concentration of propylene oxide to produce neuropathy in rats

Although propylene oxide, which is similar in chemical structure to ethylene oxide, is expected to produce neuropathy, there is no convincing evidence of the degeneration of the peripheral nervous system. To determine the exposure concentration of propylene oxide necessary to produce neuropathy in male Wistar rats, we subjected them to repeated exposures of propylene oxide at concentrations of 500, 750, 1000, 1500 and 2000 ppm. The test rats were subjected to a single 6 hour exposure of propylene oxide at a concentration of 1500 parts per million 5 times a week for 3 weeks. They developed a significant decrease in body weight, abnormal posture of the hindlegs and axonal degeneration of myelinated fibers in the peroneal and sural nerves, the nerves to the soleus muscle, and in the fasciculus gracilis of the spinal cord. Therefore, it was concluded that propylene oxide induces neuropathy in rats characterized by axonal degeneration, similar to that produced by ethylene oxide, and that the exposure to the higher concentration of propylene oxide is more necessary to produce neuropathy than in the case of ethylene oxide neuropathy in rats.     

Herpes zoster ophthalmicus complicated by hyphema and hemorrhagic glaucoma

We treated two patients with herpes zoster ophthalmicus in whom hyphema and hemorrhagic glaucoma occurred. Case 1 complained of facial skin eruption, and was given intravenous acyclovir for 7 days. Hyphema and high intraocular pressure occurred in the left eye 10 days after the onset of the skin eruption. Case 2 had severe pain and blisters on her face, and was given intravenous acyclovir for 7 days. An intracameral hemorrhage and glaucoma developed in the right eye 15 days after the onset of the skin lesion. Intravenous acyclovir may be necessary for longer than 7-day periods if the iridocyclitis remains.