Benz(F)isoquinolines as excitatory amino acid antagonists: An indication of their mechanism of action?

Using the technique of microelectrophoresis on cat and rat spinal neurones, the bridged benz(f)isoquinoline, LY154045, like ketamine and dextrorphan, was found to be a selective antagonist of N-methylaspartate, an amino acid used for characterizing excitatory amino acid synaptic receptors. The unbridged analogue, LY154005, was inactive as an amino acid antagonist. This result correlates well with the ability of LY154045, but not LY154005, to displace phencyclidine from CNS tissue and to mimic phencyclidine in behavioural tests. The potential role of N-methylaspartate antagonism in the aetiology of some of the behavioural effects of LY154045, phencyclidine and related drugs is considered.     

Computerized image analysis of nuclear shape as a prognostic factor for prostatic cancer

Computer assisted image analysis was used to determine quantitative and reproducible nuclear morphology of 17 totally excised pathological specimens from stage B-2 prostatic cancer in an attempt to correlate histopathological analysis with clinical prognosis for the individual patient. We describe a nuclear roundness factor that correlates with the clinical outcome of the individual patient. This nuclear shape factor appears to identify prostatic tumors with a high metastatic potential from tumors that are less aggressive. Quantitative nuclear image analysis, its accuracy, and reproducibility are described and discussed. This technique may provide the pathologist with a valuable tool for analyzing prostatic cancer cells in a quantitative manner, thereby contributing precise information to the urologist relevant to the prognosis of the individual patient.     

Effect of selenium in combination with cis-diamminedichloroplatinum(II) in the treatment of murine fibrosarcoma

cis-Diamminedichloroplatinum(II) (cis-DDP) is a well-known anticancer agent the use of which is limited by its toxicity. Since it has been demonstrated that selenium is able to combine with metals like cadmium and mercury and to reduce their toxicity, we decided to investigate whether it could reduce the toxicity of platinum. We treated fibrosarcoma-bearing mice with a combination of cis-DDP and selenium. The dose of 2 or 4 micrograms selenium/g animal weight had no effect on tumor growth. The i.p. injection of 16 micrograms cis-DDP/g led to early death of animals. The i.p. treatment of tumor-bearing animals with 2 or 4 micrograms of selenium reduced the early mortality induced by cis-DDP at a dose of 16 micrograms/g. Therefore, the addition of selenium allowed the administration of high doses of cis-DDP, which resulted in an improved antitumor effect. Clonogenic assays following drug exposure showed that selenium had no direct effect on tumor cells and did not modify the antitumor activity of cis-DDP. Electron microscopy showed reduced changes in renal cells when selenium was added to the cis-DDP treatment. Microanalysis showed no accumulation of either selenium or platinum within renal cells. These results suggest that the addition of selenium decreases the nephrotoxicity of cis-DDP.     

Regulation of synthesis of the neurosecretory egg-laying hormone of Aplysia: antagonistic roles of calcium and cyclic adenosine 3':5'-monophosphate

The potential role of cyclic nucleotides and calcium as regulators of neuropeptide biosynthesis was examined in the bag cell neurons of Aplysia, which produce and secrete a peptide egg-laying hormone (ELH). Elevated external potassium, which stimulates ELH biosynthesis, increased bag cell cAMP levels when assayed in the presence of a phosphodiesterase inhibitor. Dopamine and serotonin, which increase bag cell cAMP levels, both stimulated ELH synthesis, as did the phosphodiesterase inhibitor isobutylmethylxanthine, the specific adenylate cyclase activator forskolin, and the phosphodiesterase-resistant cAMP analogue 8-benzylthio-cAMP. The stimulatory effect on peptide biosynthesis appears to be specific for cAMP, as bag cell cGMP levels were not altered significantly by high potassium or forskolin, and 8-bromo-cGMP did not stimulate ELH synthesis. In contrast to cAMP, intracellular calcium inhibits ELH production: biosynthesis of the peptide was elevated in a 0 Ca2+/EGTA medium and reduced in the presence of the Ca2+ ionophore A23187. Synthesis was also elevated in the presence of the calmodulin inhibitor calmidazolium. Treatment of intact bag cells with 0 Ca2+/EGTA or A23187 did not alter cAMP levels significantly, suggesting that calcium exerts its effect on peptide synthesis independently of cAMP. The antagonistic effects of cAMP and calcium on ELH synthesis parallel their effects on bag cell excitability, suggesting that, in these cells, neuropeptide synthesis and secretion are co-regulated by the same intracellular messengers.     

Case report: Liver function abnormalities in a severe case of hyperreactio luteinalis

Rare causes of liver dysfunction in pregnancy may pose a challenge to the consulting gastroenterologist or hepatologist from both the diagnostic and therapeutic standpoints. We describe here liver function abnormalities in a case of hyperreactio luteinalis with light and electron microscopic findings.     

Evidence of contralateral ovulation in ectopic pregnancy

Patients with an ectopic pregnancy were studied for documentation of the site of ovulation in order to determine the frequency with which controlateral ovulation and ovum transport occurs. Analysis of data on 135 patients in whom the site of ovulation was documented at the time of surgery and on 24 patients who were studied ultrasonically before surgery indicates that contralateral ovulation and ovum transport occurs in at least a third of ovulatory events.     

Mounting and calibration of stairs on piezoelectric force platforms

To calculate the centre of pressure using piezoelectric force plates mounted on pads, no net tensile stresses may be imposed on the surface of the plate. This condition is violated when stairs are attached to the plates, unless the plates are preloaded. Typical shear forces encountered when climbing stairs were used to determine required preloads of approximately 16.4 N/cm step height. Vertical and horizontal loads were applied at known locations on the steps, and points of application were calculated. Deviations were within ± 3 mm. The effect of point of application inaccuracy on calculated joint moments is considerable. A 2 cm medial shift in the point of application resulted in calculated peak knee abduction/adduction moment errors of 35%.