Electrophysiological characterization of remote chemical synapses.
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Biomedical subjects
Publications and source records attributed to D Johnston.
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Measurements were performed in 143 patients with monoclonal gammopathy of the cellular substrate in the bone marrow, including analysis of DNA and RNA content and tritiated thymidine labeling index. Aneuploidy by DNA content was present in 80% of 115 patients with active multiple myeloma and in 4 of 9 patients with benign monoclonal gammopathy, but was absent in all 12 patients with myeloma in remission and in 7 individuals with Waldenström's macroglobulinemia. With regard to prognosis in multiple myeloma, a low pretreatment plasma cell labeling index of less than or equal to 1% heralded longer survival than that observed in patients with a labeling index less than 1%, independent of myeloma tumor burden and ploidy pattern, except for a subset of 17 patients with a low-degree hyperdiploid abnormality whose survival was not affected by the magnitude of the pretreatment labeling index. Thus, besides tumor burden, tumor proliferative activity and ploidy both appear to have additional prognostic importance for patients with multiple myeloma.
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According to one hypothesis, the paroxysmal depolarizing shift observed in the penicillin model of epilepsy results from a giant excitatory postsynaptic potential. This hypothesis has recently been questioned, primarily because it has never been subjected to rigorous experimental examination. Four quantitative predictions were derived from this hypothesis and tested in CA3 pyramidal neurons of the hippocampus. The four critical predictions concern the behavior of the paroxysmal depolarizing shift under current- and voltage-clamp conditions as a function of membrane potential. The experiments confirmed all four predictions.
Methods for the standardization of several currently used platelet function tests (bleeding time, capillary fragility, platelet retention, platelet aggregation, platelet factor 3, and platelet volume profiles) are presented, Different variables than may interfere with the reproducibility of the results of each assay were identified and standardized. Using the standardized techniques, the range of normal values for each test was determined in a large population of normal volunteers and used to identify disease states by comparing patient results with those of the normal population. A format for presenting the entire profile of platelet function parameters is proposed.
Recurrent peptic ulceration was diagnosed in 9 per cent of 433 patients who were treated by elective highly selective vagotomy (HSV) for duodenal ulcer (DU) between 1969 and 1980. In 233 patients followed up for 5-12 years (12 per cent being lost to follow-up), the incidence of recurrence was 10.7 per cent. The site of recurrence was duodenal in 23 patients, pyloric in 4, gastric in 6 and combined duodenal and gastric in 2 (total of 35 patients). One patient presented with a perforation, l4 with haemorrhage and 30 with epigastric pain. Asymptomatic patients were not endoscoped and so asymptomatic recurrence would have been missed. Nine patients were treated by reoperation (5 Polya partial gastrectomy, 4 vagotomy + antrectomy), the remainder with cimetidine. There was no mortality. When the 35 patients with recurrence were compared with the patients without recurrence, no preoperative factors could be identified that might be used to predict recurrence. Thus, for the two groups, the sex distribution, age, length of ulcer history, previous ulcer complications and preoperative acid outputs (basal and maximal) were very similar. This was true also when the data for patients with true recurrence in the duodenum were examined separately. Hence, contrary to some previous reports, no evidence was found that patients who are hypersecretors of acid, either basal or maximal, before operation should be treated by vagotomy combined with antrectomy. After HSV, however, patients with recurrent DU secreted more acid (basal, insulin and pentagastrin-stimulated) than patients without recurrence, the difference between the two groups being statistically significant for basal acid output (BAO) and the response to insulin. The only factor which was found to influence the incidence of recurrent ulceration after HSV strongly was the surgeon who performed the operation.
Ulcerative colitis and polyposis are both diseases of the mucosa. They can be cured by colectomy combined with selective mucosal proctectomy, without sacrifice of teh anal sphincters or damage to bladder or sexual function. Terminal ileum, either as a straight tube or in the form of a pouch, is drawn down through the denuded tube of anorectal muscle and anastomosed to the mid-anal canal. A temporary defunctioning ileostomy is always used. Caecum has also been used as a neorectum after mucosal proctectomy, but without long term success. Twenty-two patients, 20 with ulcerative colitis and 2 with polyposis, have been treated by mucosal proctectomy in the past 4 years, with no mortality. The caeco-anal procedure proved a failure because of recurrence of colitis, although the early functional results were good. After ileo-anal anastomosis, continence was perfect by day, but 2 patients had occasional lapses at night. The disadvantage of straight ileo-anal anastomosis is frequency of bowel action (6-9 times a day), even with codeine medication, although the patients considered the operation a success. Some form of pelvic reservoir is therefore desirable and our early experience with the triplicated ileal pouch is encouraging.
The normal spontaneous bursting behavior of hippocampal pyramidal neurons was investigated. Bursting frequency was found to be membrane potential dependent, the frequency increasing with maintained depolarization and decreasing upon hyperpolarization. Short depolarizing-current pulses would trigger bursts which outlasted the stimulus, and bursting continued when synaptic transmission had been blocked. The spontaneous bursts of these neurons, in contrast to bursts induced by convulsive agents, appear to exhibit the classical behavior of endogenous bursts as observed in invertebrate neurons. The endogenous bursts in hippocampal neurons may result, also, from an interplay of intrinsic membrane currents.
The passive electrical cable properties of CA3 pyramidal neurons from guinea pig hippocampal slices were investigated by applying current steps and recording the voltage transients from 25 CA3 neurons, using a single intracellular microelectrode and a 3-kHz time-share system. Two independent methods were used for estimating the equivalent electrotonic length of the dendrites, L, and the dendritic to somatic conductance ratio, p. The first method is similar to that used by Gorman and Mirolli (1972) and gave an average L of 0.96; the average p was 2.44. The second method is derived here for the first time and assumes a finite-length cable with lumped soma. It is an exact solution for L and p, using the slopes and intercepts of the first two peeled exponentials. The average L was 0.94; the average p was 1.51. The results, using both methods, are in close agreement. The average membrane time constant for all CA3 neurons was 23.6 ms. suggesting a large (23,600 omega cm2) average membrane resistivity. It is concluded that CA3 neurons are electronically short.
The exocrine pancreatic and biliary secretion in response to vagal stimulation by insulin hypoglycemia was measured in preoperative patients with duodenal ulcer and in patients who underwent highly selective vagotomy, bilateral selective vagotomy with pyloroplasty, and truncal vagotomy with pyloroplasty. Significant stimulation of both biliary and pancreatic secretion occurred only in patients with an intact vagal nerve supply. No evidence of increased lithogenicity of human bile was found up to 2 years after truncal vagotomy.
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The effects of sphincter-saving resections for carcinoma of the rectum on bladder function were studied prospectively. Twenty-seven patients, each acting as his or her own control, were studied before, shortly after and 9 months after operation by means of pressure/flow filling and voiding cystometry. After operation there was a significant and lasting increase in the residual volume of urine and a temporary decrease in the compliance of the bladder. There was a statistically significant decrease in detrusor contraction pressure after operation, which persisted throughout the period of study. This was probably due to partial denervation of the bladder. Four patients had signs of total or almost total denervation of the bladder. There was a significant correlation between proximity of the tumour to the anal verge and risk of damage to the nerve supply to the bladder. Thus sphincter-saving resections of the rectum for carcinoma are associated with a significant risk of bladder denervation. Many of the "minor" symptoms of bladder dysfunction which develop after this procedure are due to partial denervation of the bladder.
Four proteins of Mr = 89,000, 73,000, 35,000, and 27,000 are strongly induced in chick fibroblasts by sodium arsenite. Induction of these proteins is discoordinate as a function of arsenite concentration. Kinetically, all species appear 1 h after exposure to 50 microM arsenite, after 24 and 48 h of exposure, the 27,000 protein is still synthesized extensively, whereas normal cell proteins and the three other induced proteins are greatly reduced. The four proteins are unrelated by tryptic peptide-mapping procedures. Multiple subspecies of p89, p73, and p27 were observed in two-dimensional gels. The subspecies of p73 appear to be related as determined by partial proteolytic maps as are those of p27. Two-dimensional gel analysis of in vitro translation products from rabbit reticulocyte lysates primed with mRNA from uninduced and induced cells reveals that the amount of translatable mRNA specific for these proteins is increase by induction. This increase is attributable to new mRNA synthesis since actinomycin D prevent induction and new bands of RNA (Mr = 0.9 X 10(6) and 1.3 X 10(6)) appear in methyl mercury gels of oligo(dT) selected RNA from induced cells. These bands are assigned to p73 and p89 based on translation of electroeluted RNA from a similar preparative gel. A comparison is made between induction of these proteins and the heat shock response in Drosophilla melanogaster.
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