Biomedical subjects
Publications and source records attributed to S Resnick.
Traumatic asphyxia is a commonly used designation of a syndrome related to severe compressive trauma to the thorax. It is characterized by cranial cyanosis, subconjunctival hemorrhage, vascular engorgement of the head, mucosal petechiae, hemoptysis, esophageal and rectal hemorrhage, hematuria, and varying degrees of cerebral dysfunction. By 1985 approximately 210 cases had been reported world-wide. We present an illustrative case in a 24-year-old man.
Mutants of Pseudomonas putida mt-2 that are unable to convert benzoate to catechol were isolated and grouped into two classes: those that did not initiate attack on benzoate and those that accumulated 3,5-cyclohexadiene-1,2-diol-1-carboxylic acid (benzoate diol). The latter mutants, represents by strain PP0201, were shown to lack benzoate diol dehydrogenase (benD) activity. Mutants from the former class were presumed either to carry lesions in one or more subunit structural genes of benzoate dioxygenase (benABC) or the regulatory gene (benR) or to contain multiple mutations. Previous work in this laboratory suggested that benR can substitute for the TOL plasmid-encoded xylS regulatory gene, which promotes gene expression from the OP2 region of the lower or meta pathway operon. Accordingly, structural and regulatory gene mutations were distinguished by the ability of benzoate-grown mutant strains to induce expression from OP2 without xylS by using the TOL plasmid xylE gene (encoding catechol 2,3-dioxygenase) as a reporter. A cloned 12-kb BamHI chromosomal DNA fragment from the P. aeruginosa PAO1 chromosome complemented all of the mutations, as shown by restoration of growth on benzoate minimal medium. Subcloning and deletion analyses allowed identification of DNA fragments carrying benD, benABC, and the region possessing xylS substitution activity, benR. Expression of these genes was examined in a strain devoid of benzoate-utilizing ability, Pseudomonas fluorescens PFO15. The disappearance of benzoate and the production of catechol were determined by chromatographic analysis of supernatants from cultures grown with casamino acids. When P. fluorescens PFO15 was transformed with plasmids containing only benABCD, no loss of benzoate was observed. When either benR or xylS was cloned into plasmids compatible with those plasmids containing only the benABCD regions, benzoate was removed from the medium and catechol was produced. Regulation of expression of the chromosomal structural genes by benR and xylS was quantified by benzoate diol dehydrogenase enzyme assays. The results obtained when xylS was substituted for benR strongly suggest an isofunctional regulatory mechanism between the TOL plasmid lower-pathway genes (via the OP2 promoter) and chromosomal benABC. Southern hybridizations demonstrated that DNA encoding the benzoate dioxygenase structural genes showed homology to DNA encoding toluate dioxygenase from the TOL plasmid pWW0, but benR did not show homology to xylS. Evolutionary relationships between the regulatory systems of chromosomal and plasmid-encoded genes for the catabolism of benzoate and related compounds are suggested.
We used x-ray computed tomographic (XCT) scans to measure the degree of cerebral atrophy in brain regions defined by a region of interest (ROI) anatomy atlas. The same atlas was employed for quantitation of local cerebral glucose metabolic rates (LCMRglc) by PET. PET data were obtained from 9 young controls, 7 healthy elderly controls, and 10 patients with dementia. Cerebrospinal fluid (CSF) in atrophic brain regions was assumed to be metabolically inert, and LCMRglc measurements were corrected for the degree of atrophy. Significantly greater atrophy was seen for 7 of 8 regions in comparisons between demented patients and age-matched controls. This atrophy was most pronounced in superior parietal (SP) regions. Decreases in parietal LCMRglc in dementia patients and SP LCMRglc in old controls were no longer significant after correction for atrophy. These results emphasize the need to consider focal atrophy effects in regional quantitative analyses of emission tomographic data.
Two proteins (21 and 48 kilodaltons) purified from endospore-spherule culture filtrates of Coccidioides immitis are identified as precipitin and complement-fixing antigens, respectively. To allow specific structural comparison to antigens identified by other investigators and as a first step to eventual serodiagnostic antigen production by recombinant DNA technology, amino-terminal amino acid sequences were determined for these antigens.
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Coccidioides immitis is the causative agent of coccidioidomycosis (valley fever), a potentially disseminated fungal disease. We hypothesized that proteinases are expressed by the parasitic life cycle of C. immitis and that they might play an important role in the pathogenesis of coccidioidomycosis by facilitating spherule rupture, endospore dissemination, and tissue invasion and destruction. Filtrate from cultures of the parasitic life cycle of C. immitis was therefore assayed for proteolytic activity at neutral pH. The filtrate degraded 68% of a radiolabeled model of an elastin-rich extracellular matrix. The principal activity was against elastin and glycoprotein in the matrix. Degradation of purified elastin by filtrate was 222 micrograms/h per mg of filtrate protein at 37 degrees C. Denatured type I collagen (Azocoll) degradation was 13.5 mg/h per mg of filtrate protein at 37 degrees C. Proteinase activity peaked at 60 h of culture, correlating with release of endospores from mature spherules in the in vitro culture system. Elastase activity was attributed to a serine proteinase which exhibited an active-site preference for phenylalanine at the P1 site. The subunit molecular mass of the elastase determined by [3H]diisopropylfluorophosphate labeling was approximately 25 kilodaltons. Inhibition of the azocollytic activity of crude filtrate by 2 mM 1,10-phenanthroline and 10 mM EDTA, and stimulation by 2 mM CaCl2, suggested that a metalloproteinase was also present. Gelatin substrate gel electrophoresis with and without inhibitors confirmed that two proteinases were expressed, and they were separated by fast protein liquid chromatography.
A new method of stoma formation by using a new device has been described. The technical details of this procedure were first tested on 10 autopsy subjects before being applied in the clinical setting. After the autopsy trial was completed, the device was utilized for colostomy or ileostomy in 18 patients. The postoperative course was uncomplicated in all but one patient. Follow-up studies up to 2 years postoperatively revealed satisfactorally functioning stomas in all of the patients. The stoma was surrounded only by a thin, rather insignificant, scar. No cases of stenosis, prolapse, or parastomal hernia were found. Stoma formation with the device permits the creation of a precise abdominal wall aperture that corresponds to the size of the bowel and it prevents abdominal muscles from being cut. The preserved muscles can act like a sphincter around the stoma. Lastly, the procedure is simple, quick, and less traumatic than comparable procedures, and the healing conditions are optimal.
Regional cerebral blood flow (rCBF) was measured during resting baseline and the performance of a verbal and a spatial task in 19 unmedicated schizophrenics and 19 matched controls. Abnormalities in rCBF were evident in schizophrenics both for resting and activated measures. Resting flows were higher in the left hemisphere for schizophrenics, supporting the hypothesis of left hemispheric overactivation. This effect was stronger in the more severely disturbed patients. The pattern of rCBF changes during activation with the verbal and spatial tasks was also different in schizophrenics. Laterality of flow changes further supported the hypothesis of left hemispheric overactivation. Furthermore, whereas normals had greater increase in flow for the spatial than the verbal task, schizophrenics showed the reverse pattern. This effect also was more pronounced in the severely disturbed patients. Comparison with an earlier sample of medicated schizophrenics suggested that neuroleptics restore symmetry of resting flows before they produce symptomatic relief. Medication did not affect the abnormalities in pattern of rCBF changes during activation with cognitive tasks.
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During diagnostic cardiac catheterization for the evaluation of chest pain, His bundle electrograms were obtained in 32 male patients before and 2 to 5 minutes after each of two interventions known to acutely affect left ventricular volume and left ventricular end-diastolic pressure (the injection of 40 to 60 cc of contrast medium during left ventriculography and the administration of 0.4 mg of sublingual nitroglycerin). Changes in left ventricular end-diastolic pressure (18 +/- 6 vs 30 +/- 7 mm Hg, p less than 0.001 following ventriculography and 32 +/- 8 vs 19 +/- 8 mm Hg, p less than 0.005 following nitroglycerin administration) were accompanied by parallel alterations in HQ (48 +/- 8 vs 54 +/- 10 msec, p less than 0.005 following ventriculography and 57 +/- 10 vs 53 +/- msec, p less than 0.005 following nitroglycerin administration), but there were no significant changes in atrioventricular (AV) nodal conduction (AH). Significantly greater changes in HQ were seen in patients with triple-vessel coronary artery disease than in the remainder of the population, although there was clinical and/or ECG evidence of ischemia in only one patient. We conclude that factors other than progression of intrinsic conduction system disease may affect infranodal conduction. HQ should be interpreted cautiously in situations with rapidly changing hemodynamics, especially in patients with severe coronary artery disease.
The one-stage transcutaneous hypopharyngeal diverticulectomy has become the accepted procedure for treating most of Zenker's diverticula. Myotomy of the crico pharyngeus is simultaneously done as a safeguard for sac recurrence. Experience of our general-surgical colleagues with stapling devices has inspired us to use auto-suture technique for the resection of Zenker's diverticulum.
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Seventy-nine pups from 18 litters were changed to a carbohydrate-free diet between 7 and 19 weeks of age. It was found that if the diet change was made after pups were 17 weeks old, the pups remained clinically normal. If the change was made before pups were 17 weeks old, the survival rate was less than or equal to 45.5%.
After 3-hr food deprivation, rats with gastric fistulas ate liquid food with the fistula closed (normal feeding) or open (sham feeding). Meal size (MS) was larger, latency to rest (LR) after a meal was longer, and intermeal interval (IMI) was shorter during sham feeding than during normal feeding. The putative satiety signal cholecystokinin (CCK, 20% pure) decreased MS and LR and increased IMI during sham feeding. After CCK (30 U/kg) the MS, LR, and IMI were the same during sham feeding as during normal feeding. The synthetic octapeptide (OCT) of CCK, which has the known biological actions of the complete hormone, reproduced the effects of CCK (30 U/kg) on MS and LR but not on IMI. Ingestive behavior was not nonspecifically suppressed by CCK or OCT because water drinking was not inhibited by CCK or OCT. The CCK and OCT were also tested for their ability to serve as unconditioned stimuli (UCS) for the formation of a conditioned taste aversion (CTA) in the 3-hr food-deprived sham-feeding rat. The OCT (30 U/kg) did not serve as a UCS for a CTA in the same sham-feeding conditions in which OCT produced normal MS and LR. Impure CCK (30 U/kg), however, did serve as a UCS for a CTA under these conditions. The differential effectiveness of CCK and OCT for IMI and CTA may be due to non-CCK factors in the impure extract of CCK. These experiments demonstrate that the preabsorptive food-contingent stimuli of sham feeding plus exogenous CCK are sufficient for normal short-term satiety under certain conditions, and they provide further evidence consistent with the hypothesis that cholecystokinin produces satiety in rats.
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