Effect of prostaglandin E1 on graft function of kidneys from living related donors

Prostaglandin E₁ (PGE₁) was used in renal transplant recipients with living related donors. The drug was given intravenously from day 1 to day 7 after transplantation at a dose of 40 µg/kg twice a day. A total of 45 patients were studied divided into two groups: 25 patients were treated with PGE₁ (group B) and the remaining 20 patients did not receive the drug (group A). In group B, 24-h creatinine clearance (Ccr) was 66 ± 12.8 ml/min compared with 40.3 ± 13.4 ml/min in group A on the fifth postoperative day (P < 0.05). Urinary levels of N-acetyl-β-d -glucosaminidase (NAG) and serum levels of platelet factor 4 (PF4) in group B were significantly lower than in group A. On the fourth postoperative day, the urinary excretion of thromboxan B₂ (TxB₂) in group A was higher than in group B, but not significantly (5.1 ± 3.0 ng/day and 2.8 ± 1.1 ng/day, respectively). Acute rejection occurred in four patients in group B and in 10 patients (40%) in group A. The percentage of Leu2a-positive lymphocytes in group B was higher than in group A. We conclude that postoperative administration of PGE₁ improves graft function in kidneys from living related donors.     

Spermidine/Spermine N-Acetyltransferase, a New Biochemical Marker for Epithelial Proliferation in Rat Bladder

We examined the activity of spermidine/spermine N ¹-acetyltransferase (SAT), a rate-limiting enzyme of the biodegradation of polyamines, in N -butyl- N -(4–hydroxybutyI)nitrosamine-induced transitional cell carcinoma (TCC) and melamine-induced papillomatosis of rat bladder, and compared the activity to that of ornithine decarboxylase (ODC). Both activities were higher in both lesions than in control rats. The difference between SAT and ODC activities in cancerous tissue and papillomatosis was not significant. Cells stained for proliferating cell nuclear antigen (PCNA) were abundant in papillomatosis. TCC had areas with much PCNA. The results indicated that an elevation of SAT activity occurs in both reversible and irreversible proliferation of bladder epithelium and could be important in bladder carcinogenesis.     

亚硝酸钠与AFB1相互作用对遗传物质影响的实验研究

以正常人外周血淋巴细胞的ＳＣＥ率作为细胞遗传学指标，研究了Ｎａ＿２ＳｅＯ＿３与ＡＦＢ＿１相互作用对细胞遗传物质的影响。结果表明，一定浓度的Ｎａ＿２ＳｅＯ＿３（１０￣（－５）ｍｏｌ）对ＡＦＢ＿１所诱发的ＳＣＥ有明显的抑制作用，但当浓度达到１０￣（－２）ｍｏｌ时，细胞增殖受到抑制，到１０￣（－１）ｍｏｌ时细胞出现毒性现象。提示Ｎａ＿２ＳｅＯ＿３具有抑变和细胞毒性双相作用。所以在Ｎａ＿２ＳｅＯ＿３与ＡＦＢ＿１相互作用的ＳＣＥ实验中应避免Ｎａ＿２ＳｅＯ＿３的浓度过高而损伤培养的细胞。     

Breast Cancer Genes

Abstract: The identification of familial breast cancer genes heralds an era of directed breast cancer treatment. Currently, two hereditary breast cancer genes have been identified, BRCA-1 and BRCA-2 . Although accounting for only approximately 5% of all breast cancers, they are being used to identify women with germ-line alterations that are at high risk of developing breast or ovarian cancer. With the identification of such genes comes a need for consideration of the ethical issues associated with testing. These genes are also being examined from a biochemical standpoint encompassing both their biological roles and biochemical pathways in which they reside. Such studies are likely to lead to novel breast cancer therapies.     

Evidence for differential effects of 8-OH-DPAT on male and female rats in the Anxiety/Defense Test Battery

The Proxemics/Activity test and the Eat/Drink test, two components of the Anxiety/Defense Test Battery, were developed to measure defensive reactions to situations associated with a natural predator (cat). In the present studies the behavioral effects of 8-OH-DPAT treatment (0.01–1.0 mg/kg, SC) were entirely consistent with anxiety/fear reduction. These effects included an increase in time spent near the cat compartment, and a complimentary decrease in time spent farthest from this compartment, together with an increase in transits and locomote behavior. 8-OH-DPAT (1.0 mg/kg) also increased eat frequencies and durations (highly preferred food) both during and following cat presentation, without influencing drinking. This finding is discussed with reference to previous findings with 8-OH-DPAT in studies assessing both food intake and anxiolysis. Interestingly, 8-OH-DPAT was more potent in a majority of its effects in female subjects, a finding consistent with recent neurochemical data. These findings provide important behavioral evidence for a sexual differentiation in 5-HT function, and support the case for greater emphasis on female subjects in animal models of anxiety.Supported by NIH MH42803 and RCMI Grants RR03061 and RR01825     

Localization and characterization of epidermal growth-factor receptors in the developing rat medial septal area in culture

The presence and binding properties of epidermal growth-factor receptors (EGF-Rs) in different cell types purified from the rat medial septal area in culture were investigated. We report that astrocytes, oligodendrocytes and neurons from this area possess EGF-Rs while microglia do not. EGF-binding sites are detectable on astrocytes derived from the medial septum of both embryonic and neonatal rats. Scatchard analysis of the data for astrocytes from the fetal rats show that EGF specifically binds to both high- (K_d = 7.21 × 10⁻¹⁰ M, B_max = 3602 receptors/cell) and low-affinity (K_d = 3.99 × 10⁻⁸ 10⁻⁸ M, B_max = 6,265 receptors/cell) receptors on these cells. On the other hand, astrocytes purified from neonatal tissue possess a greater number of high-affinity receptors (B_max = 10,938 receptors/cell) when compared with the embryonic astroglia. With time in culture, the number of both types of receptors on neonatal astrocytes decreases. Oligodendrocytes also possess high- and low-affinity EGF-Rs with dissociation constants of 3.25 × 10⁻¹⁰ M and 3.85 × 10⁻⁸ M, respectively. The number of receptors on oligodendrocytes is significantly lower than those on neonatal astrocytes (B_max = 1185 and 25,081 receptors/cell for high- and low-affinity binding sites, respectively). Finally, neurons from this area also exhibit two different EGF-R types with dissociation constants similar to those described for astrocytes. As the number of receptors/neuron (B_max = 136 and 1159 receptors/cell for high- and low-affinity binding sites, respectively) appears to be extremely low, it is possible that EGF specifically binds only to a subpopulation of neurons from this area. These studies demonstrate which cell types in the developing medial sepal area posses EGF-Rs and provide a detailed characterization of these binding sites. These EGF-R-bearing cells may be potential targets for this growth factor or for transforming growth factor α in this brain area.     

5-Hydroxytryptamine increases excitability of CA1 hippocampal pyramidal cells.

In the presence of spiperone to block the 5-HT1A-mediated inhibition of pyramidal cell activity, 5-hydroxytryptamine (serotonin, 5-HT) produces a rapid transient increase in amplitude of the extracellularly recorded population spike from area CA1 of the hippocampus. Intracellular recording techniques in area CA1 of rat hippocampal slices were used to identify the ionic mechanism and to characterize the 5-HT receptor mediating this excitatory response to 5-HT. Most of the experiments were conducted in the presence of spiperone to block the 5HT1A hyperpolarization. Since spiperone also has high affinity for 5-HT2 receptors, any response mediated by 5-HT2 receptors would also be blocked. Bath perfusion of the slice with 5-HT increased the rectification of pyramidal cells in the subthreshold region, increased the resistance, and increased the amplitude of subthreshold excitatory postsynaptic potentials (EPSPs) to initiate spike firing. The 5-HT2,1C-selective agonist DOI mimicked this effect of 5-HT, and the 5-HT2,1C antagonist ketanserin (1 microM) blocked the effect of DOI. There was no change in the amplitude of the slow afterhyperpolarization (sAHP) or the amplitude of evoked inhibitory postsynaptic potentials (IPSPs). The increase in rectification and EPSP amplitude by 5-HT occurred even in the presence of the 5-HT4-selective antagonist BRL 24924 to prevent the decrease in amplitude of the sAHP by 5-HT. We conclude that 5-HT produces a fast excitatory response by increasing subthreshold conductance in CA1 hippocampal pyramidal cells. The identity of the receptor mediating this response was not conclusively identified, but resembled the 5-HT1C receptor.     

Chronic occupational exposure to organic solvents

Summary Twenty-two persons (20 men and 2 women) were examined for their external and internal exposure to the glycol ether 1-methoxypropan-2-ol (PGME) during the production, leak testing and mounting of brake-hoses. For the measurement of external exposure, personal air monitoring was the method of choice. Average concentrations of PGME of 82.2 mg/m³ (22.3 ppm), 68.6 mg/m³ (18.6 ppm) and 11.3 mg/m³ (3.1 ppm) were found in the air of the brakehose production, leak test and mounting areas, respectively. For the estimation of internal exposure to PGME, this glycol ether was measured in both urine and blood. The biological samples were taken post-shift. The highest internal exposure levels were found in the brakehose production section and in the leak test area. The average post-shift concentrations for PGME in workers in the brakehose production section were 4.6 mg/l in urine and 13.5 mg/l in blood; the corresponding figures for workers in the leak test area were 4.2 mg/l in urine and 11.0 mg/l in blood. In blood and urine samples of workers engaged in the mounting area, PGME levels were below the detection limits. The elimination kinetics of PGME were also studied in three highly exposed persons, and mean excretion half-lives of PGME of approximately 4.4 h were found. On the basis of our results we made a rough calculation of a future biological tolerance value: we would except that concentrations of 38-109 mg per litre of blood and 10–31 mg per litre of urine would correspond to the German MAK value for PGME (375 mg/m³).     

Elevated serum levels of the apoptosis related molecules TNF-α, Fas/Apo-1 and Bcl-2 in oral lichen planus

BACKGROUND: The serum circulatory levels of apoptosis related molecules measured in patients with oral lichen planus (OLP) and healthy individuals in order to investigate possible alterations associated with the clinical forms of OLP. METHODS: Serum levels of tumor necrosis factor (TNF)-alpha, soluble Fas (sFas) and Bcl-2 studied by enzyme-linked immunosorbent assay in whole blood samples in 13 OLP reticular, 13 OLP atrophic-erosive form patients and 26 healthy subjects. RESULTS: Significantly elevated levels of TNF-alpha and sFas detected in OLP patients as compared with controls. Serum concentrations of Bcl-2 although increased in 17/26 patients, they were not statistically significant. Reticular OLP exhibited slightly elevated TNF-alpha and significantly elevated Bcl-2 serum levels, compared with erosive OLP. CONCLUSIONS: These data suggest that a putative dysfunction in the Fas/FasL mediated apoptosis might be involved in the OLP pathogenesis. A downregulation of Bcl-2 serum levels in the atrophic-erosive OLP may be associated with promotion of the disease activity.