Heparin effect on ionised calcium concentration

The effect of heparin on plasma ionised calcium was studied by adding it in increasing amounts to whole blood from 10 normal subjects. There was no significant change in ionised calcium from the addition of 1 U/ml but a significant fall of 0.02 mmol/1 when 2 U/ml were added and a progressive further fall with increasing concentrations. Heparin from three different manufacturers produced similar results. The effect of heparinisation in vivo was studied during regular haemodialysis on 10 patients with chronic renal failure. Following intravenous injection of 10000 U of heparin there was a consistent and significant fall averaging 0.03 mmol/l.     

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.     

Electrochemotherapy significantly inhibits the growth of colon 26 tumors in mice

Electrochemotherapy is a novel antitumor treatment involving the systemic administration of bleomycin followed by the delivery of electrical pulses to the tumor. The present study investigates the effects of electrochemotherapy on the growth of colon 26 cells inoculated subcutaneously into the backs of BALB/c mice. The mice were divided into the following four experimental groups: 20 that received no further treatment after the inoculation of colon 26 cells (control group); 20 that received 500 μg of bleomycin intraperitoneally 7 and 9 days after the inoculation (BLM group); 20 that received electric pulses to the tumor 7 and 9 days after the inoculation (EP group); and 30 that received electrochemotherapy 7 and 9 days after the inoculation (ECT group). During 28 days of observation, no deaths due to tumor progression occurred in the ECT group, but there were 18 in the control group, 11 in the BLM group, and 18 in the EP group. While weight loss was observed in all groups, it was most remarkable in the control group. Tumor growth was significantly inhibited in the ECT group, compared to the other experimental groups (P<0.01). The results of this study demonstrated that electrochemotherapy significantly inhibited the growth of colon 26 tumors in mice, without causing any remarkable adverse effects.     

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.     

Studies on the relationship between transaldolase activity and testosterone synthesis in Leydig cells of pubertalmice

Objective: To study the relationship between transaldolase activity, protein expression and testosterone synthesis in Leydig cells of pubertal mice. Methods: Leydig cells were cultured for 2 hours and 8 hours, to the Stimulation Group, hCG was added and to the Controls, only the vehicle. The testosterone concentration was then determined by enzyme-linked immunoadsordent assay (ELISA) and the transaldolase activity and protein expression by Western blot. Results: (1) Both the testosterone concentration and the transaldolase activity in both Stimulation Groups were significantly higher than those in the corresponding Controls (2 h: p<0.05-0.01; 8 h: P<0.001); (2) The ratios of the A isoform, the B isoform and the total transaldolase protein to β-actin between the Stimulation and Control Groups did not differ signifi-cantly. Conclusion: hCG stimulates the transaldolase activity as well as the testosterone synthesis in the Leydig cells of pubertal mice, indicating a positive relationship between them.     

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.