Evoked potentials and decompression.
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Biomedical subjects
Publications and source records attributed to R W Hamilton.
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To determine factors involved in peritoneal dialysis-associated peritonitis and catheter loss, all point prevalent peritoneal dialysis patients in Health Care Finance Administration (HCFA) end-stage renal disease (ESRD) Network 9 were followed throughout 1991 for peritonitis events and throughout 1991 to 1992 for catheter survival. Data were collected by questionnaires compiled by the dialysis facility and validated by network staff. Peritonitis was reported 1,168 times in 729 of the 1,930 patients. By gamma-Poisson regression, a significantly increased risk for peritonitis was observed for patients with previous peritonitis, black race, and those dialyzing with standard connectors or cyclers compared with disconnect systems. Decreased risks were observed for patients with longer ESRD experience and when prophylactic antibiotics were administered before catheter insertion. Postinsertion leakage, diabetes, visual problems, previous or current immunosuppression, and physical activity were not risk factors. Infection of any kind caused the removal of 68% of the 414 catheters lost. Patients with downward-directed tunnels were less likely to experience concomitant exit site/tunnel infections associated with peritonitis. Peritonitis episodes with Staphylococcus epidermidis-like organisms were more likely to resolve with a single course of antibiotics. Perhaps because of their higher infection rate, blacks were more likely than whites to use a disconnect system. In general, the outcome of peritonitis in blacks was similar to that in whites, except that blacks were less likely to be hospitalized and were less likely to die.
This paper applies a general mathematical system for characterizing and scaling functional connectivity and information flow across the diffuse (EC) and discrete (DG) input junctions to the CA3 hippocampus. Both gross connectivity and coordinated multiunit informational firing patterns are quantitatively characterized in terms of 32 defining parameters interrelated by 17 equations, and then scaled down according to rules for uniformly proportional scaling and for partial representation. The diffuse EC-CA3 junction is shown to be uniformly scalable with realistic representation of both essential spatiotemporal cooperativity and coordinated firing patterns down to populations of a few hundred neurons. Scaling of the discrete DG-CA3 junction can be effected with a two-step process, which necessarily deviates from uniform proportionality but nonetheless produces a valuable and readily interpretable reduced model, also utilizing a few hundred neurons in the receiving population. Partial representation produces a reduced model of only a portion of the full network where each model neuron corresponds directly to a biological neuron. The mathematical analysis illustrated here shows that although omissions and distortions are inescapable in such an application, satisfactorily complete and accurate models the size of pattern modules are possible. Finally, the mathematical characterization of these junctions generates a theory which sees the DG as a definer of the fine structure of embedded traces in the hippocampus and entire coordinated patterns of sequences of 14-cell links in CA3 as triggered by the firing of sequences of individual neurons in DG.
A number of O- and N-alkylated derivatives of the antinociceptive, orally active, mu-opioid-selective truncated enkephalin analog L-2,6-dimethyltyrosyl-N-(3-phenylpropyl)-D-alaninamide (2, SC-39566) were synthesized to explore the structure-activity relationships of the series. The parent molecule is quite forgiving of substitution on the tyrosyl phenolic moiety and on the alanyl nitrogen. The tyrosyl and (phenylpropyl)amide NH sites, however, appear to be critical to interactions with the receptor, for even modest changes at these sites cause great loss of binding potency.
This case study reveals an unusual finding of rapidly proliferative crescentic glomerulonephritis in a patient treated with rifampin who had no other identifiable causes for developing this disease. This patient underwent a 10-month regimen of rifampin and isoniazid for pulmonary tuberculosis and was discovered to have developed signs of severe renal failure five weeks after completion of therapy. Renal biopsy revealed severe glomerulonephritis with crescents, electron dense fibrillar deposits and moderate lymphocytic interstitial infiltrate. Other possible causes of rapidly progressive glomerulonephritis were investigated and ruled out. This report documents the unusual occurrence of rapidly progressive glomerulonephritis with crescents and fibrillar glomerulonephritis in a patient treated with rifampin.
Several aspects of the environment of divers should increase their susceptibility to motion sickness: a) sensory conflicts, b) body fluid redistribution, and c) nitrogen narcosis. We tested motion sickness susceptibility by placing subjects on a rotating platform and having them perform stylized heat movements that produced cross-coupled angular accelerations in vestibular end organs until nausea developed. This test was performed once each day on 9 consecutive days while subjects were immersed at the end of 3-4 h of diving. The test was also carried out while subjects were nonimmersed with no preceding diving on the day immediately before and after this 9-day period. Compared with nonimmersed conditions, significantly fewer head movements were required to elicit nausea while immersed (P less than 0.01). We conclude that individuals are more susceptible to motion sickness while immersed in open water than while on dry land.
In order to evaluate the contributions that histidine residues might play both in the catalytic activities of endonuclease V and in binding to nontarget DNA, the technique of oligonucleotide site directed mutagenesis was used to create mutations at each of the four histidine residues in the endonuclease V gene. Although none of the histidines were shown to be absolutely required for the pyrimidine dimer specific DNA glycosylase activity or the apurinic lyase activity, conservative amino acid changes at His16 produced enzymes with little or no catalytic activity. In addition, the evaluation of conservative and radical amino acid substitutions at positions 34, 56, and 107 is consistent with the interpretation that each of these histidines may be involved in nontarget DNA binding. The data supporting this conclusion are that histidine changes to lysine at positions 34 and 107 enhance the nontarget DNA binding activity of the mutant enzymes while neutralization of charge at His56 reduces nontarget DNA binding.
Micrococcus luteus UV endonuclease incises DNA at the sites of ultraviolet (UV) light-induced pyrimidine dimers. The mechanism of incision has been previously shown to be a glycosylic bond cleavage at the 5'-pyrimidine of the dimer followed by an apyrimidine endonuclease activity which cleaves the phosphodiester backbone between the pyrimidines. The process by which M. luteus UV endonuclease locates pyrimidine dimers within a population of UV-irradiated plasmids was shown to occur, in vitro, by a processive or "sliding" mechanism on non-target DNA as opposed to a distributive or "random hit" mechanism. Form I plasmid DNA containing 25 dimers per molecule was incubated with M. luteus UV endonuclease in time course reactions. The three topological forms of plasmid DNA generated were analyzed by agarose gel electrophoresis. When the enzyme encounters a pyrimidine dimer, it is significantly more likely to make only the glycosylase cleavage as opposed to making both the glycosylic and phosphodiester bond cleavages. Thus, plasmids are accumulated with many alkaline-labile sites relative to single-stranded breaks. In addition, reactions were performed at both pH 8.0 and pH 6.0, in the absence of NaCl, as well as 25,100, and 250 mM NaCl. The efficiency of the DNA scanning reaction was shown to be dependent on both the ionic strength and pH of the reaction. At low ionic strengths, the reaction was shown to proceed by a processive mechanism and shifted to a distributive mechanism as the ionic strength of the reaction increased. Processivity at pH 8.0 is shown to be more sensitive to increases in ionic strength than reactions performed at pH 6.0.
The biological action of glucocorticoids is dependent upon tissue-specific levels of the glucocorticoid receptor (GR). During stress, the hypothalamic-pituitary-adrenal axis is stimulated, and high levels of glucocorticoids circulate. This axis is modulated by negative feedback by glucocorticoids, which inhibit hypothalamic and pituitary hormone secretion and downregulate GR gene expression. To study the developmental tissue-specific regulation of the GR, we measured the relative concentration of GR mRNA in fetal, neonatal, adult, and aged rats and examined the effects of dexamethasone on GR gene expression. Three different tissue-specific developmental patterns of GR mRNA accumulation were found. In addition, there was an age-dependent tissue-specific pattern in the feedback regulation of GR mRNA by glucocorticoids. In the fetus and neonate, GR mRNA abundance was not regulated by circulating glucocorticoids. The adult pattern of glucocorticoid feedback inhibition of GR mRNA expression appeared between 2 and 7 d of life in liver, and after 7 but before 14 d of age in brain. The GR was biologically active in the 2-d-old neonate, however, since dexamethasone enhanced gene expression of angiotensinogen, which is another glucocorticoid responsive gene. These data demonstrate that the GR gene is regulated by both developmental and tissue-specific factors, and provide another molecular basis for ontogenic variations in the hypothalamic-pituitary-adrenal response to stress.
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An increased risk of skin and lymphoreticular malignancies is well documented in renal transplant patients receiving long-term immunosuppressive therapy, but squamous cell carcinoma of the esophagus is rare. We have reported the first case in the English literature in which there is a strong association between long-term immunosuppressive therapy and squamous cell carcinoma of the esophagus. It occurred in a 28-year-old white man ten years after cadaveric kidney transplantation.
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Sclerosing peritonitis has recently emerged as a complication of peritoneal dialysis associated with a high morbidity and mortality. These patients experience the characteristic syndrome of nausea, vomiting, abdominal pain, partial small bowel obstruction, and impaired ultrafiltration. A pathologic finding is the replacement of mesothelial cells with a thick layer of nondistensible fibroconnective tissue. We report here a 58-year-old white woman who developed peritoneal sclerosis after 4 years of peritoneal dialysis, including 3 years of continuous ambulatory peritoneal dialysis. Risk factors included peritoneal exposure to low concentrations of formaldehyde and a 1-week exposure to long-dwell acetate dialysate. Laparotomy for partial small bowel obstruction with resection of the involved segment was complicated by enterocutaneous fistulae, which improved only on cessation of oral intake and treatment with home parenteral nutrition. We have reviewed the literature to find 20 cases of sclerosing peritonitis in patients on peritoneal dialysis. A 78% mortality rate is reported in cases that had surgical intervention. We conclude that the use of long-term parenteral nutrition with cessation of oral intake may be necessary in the management of sclerosing encapsulating peritonitis.
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The occurrence of hypersensitivity reactions in patients dialyzed on artificial kidneys is well recognized in the dialysis community, but has received little attention in the medical literature. We report 4 cases of dialyzer hypersensitivity reactions and review the previously reported cases. Dialyzer hypersensitivity syndrome presents as an acute anaphylactoid reaction, the symptoms of which may range from mild to life threatening in severity. The cause of this syndrome is unknown, but affected patients appear to have a high incidence of positive radioallergosorbent tests to a conjugate of human serum albumin and ethylene oxide, suggesting that ethylene oxide, a substance used to dry sterilize artificial kidneys, may be an offending allergen.
The MEL1 gene in Saccharomyces cerevisiae is required for the production of alpha-galactosidase and for the catabolism of melibiose. Production of alpha-galactosidase is induced by galactose or melibiose and repressed by glucose. Inducibility is controlled by the positive and negative regulatory proteins GAL4 and GAL80, respectively. We have cloned the MEL1 gene to study its transcriptional expression and regulation. Evidence is presented that the MEL1 gene encodes alpha-galactosidase and that mel0 is a naturally occurring allele which lacks the alpha-galactosidase-coding sequences. RNAs prepared from wild-type cells and from cells carrying either the noninducible gal4-2 or GAL80S-100 allele grown on three different carbon sources were examined by Northern hybridization analyses. In wild-type cells under noninducing conditions, such as growth on glycerol-lactic acid, the MEL1 transcript was detected at a basal level which was 1 to 2% of the fully induced level. The basal level of expression was diminished in cells carrying the gal4-2 mutant allele but not in cells carrying the GAL80S-100 allele. The basal and induced RNA levels are repressed by glucose. Size determinations of the MEL1 transcripts detected in glycerol-lactic acid- and galactose-grown cells provided no evidence for two distinct transcripts.
In Saccharomyces cerevisiae, the transcriptional expression of the galactose-melibiose catabolic pathway genes is under the control of at least three regulatory genes, GAL4, GAL80, and GAL3. We have isolated the GAL80 gene and have studied the effect of a null mutation on the carbon-controlled regulation of the MEL1 and GAL cluster genes. The null mutation was achieved in vivo by replacing the chromosomal wild-type GAL80 allele with an in vitro-created GAL80 deletion-disruption mutation. Enzyme activities and RNA levels for the GAL cluster and MEL1 genes were constitutively expressed in the null mutant strain grown on glycerol-lactate and were higher than in the isogenic wild-type yeast strain when compared after growth on galactose. Carbon catabolite repression of the GAL cluster and MEL1 genes, which occurs at the level of transcription, is retained in the null mutant. Deletion of the GAL80 gene in a gal4 cell does not restore GAL cluster and MEL1 gene expression. The data demonstrate that (i) the GAL80 protein is a purely negative regulator, (ii) the GAL80 protein does not mediate carbon catabolite repression, and (iii) the GAL4 protein is not simply an antagonizer of GAL80-mediated repression.