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Biomedical subjects

R L Klein

Publications and source records attributed to R L Klein.

At least 55 records · Page 3Linked to original sources

Metabolism by human endothelial cells of very low density lipoprotein subfractions isolated from type 1 (insulin-dependent) diabetic patients.

The very low density lipoprotein (VLDL) fraction was isolated from 11 normolipidaemic Type 1 (insulin-dependent) diabetic patients in good to fair glycaemic control and from 11 age-, sex- and race-matched, non-diabetic, control subjects. The rate of receptor-mediated degradation by human endothelial cells was significantly greater (p < 0.02) for the total VLDL fraction isolated from diabetic patients compared to control subjects and averaged 1008 +/- 300 and 717 +/- 150 ng.mg cell protein-1.16 h-1, respectively. The total VLDL fraction was separated into three subfractions: VLDL-I, Sf 100-400 (Sf = Svedberg units); VLDL-II, Sf 60-100; VLDL-III, Sf 20-60. Rates of receptor-mediated degradation of VLDL-I and VLDL-II isolated from diabetic patients were significantly greater than the comparable subfraction isolated from control subjects and averaged 1023 +/- 279 vs 361 +/- 122 (p < 0.01) and 433 +/- 70 vs 294 +/- 70 ng.mg cell protein-1.16 h-1 (p < 0.03), respectively. Rates of receptor-mediated degradation of the V-III subfraction isolated from the two groups did not differ significantly. There were no significant differences in the chemical composition or in the plasma concentrations of the VLDL subfractions isolated from diabetic patients compared to control subjects. There was a significant increase in the apoprotein E content of VLDL-I (p < 0.01) and VLDL-II (p < 0.05) isolated from diabetic patients. There was a significant increase in the ratio of apoprotein C compared to apoprotein E (p < 0.03) in VLDL-I isolated from control subjects compared to the diabetic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Radiographic characteristics of isolated invaginated Meckel's diverticulum.

A 3-year-old boy with a radiographic finding of an isolated invaginated Meckel's diverticulum is presented. The abnormality simulates a polypoid filling defect in the distal small bowel on barium examination. This particular manifestation of Meckel's diverticulum is very rare and has been reported only once previously. This article re-emphasizes the need to think about this possibility when a polypoid filling defect is seen in the distal small bowel. At the time laparotomy was performed, the abnormality had progressed into a triple intussusception, a rare surgical finding.

Child, Preschool↗

Gastroschisis: an 18-year review.

From 1972 to 1990, 69 cases of gastroschisis were treated at Akron Children's Hospital Medical Center. Eighty-one percent of these patients underwent primary closure of their abdominal wall defect. Thirteen of 69 patients (19%) required Silastic silos with final closure in an average of 7.8 days. There was no sex predilection, the average birth weight was 2,473 g, and the mean gestational age was 36.3 weeks. Twenty-six percent had associated anomalies, the majority were intestinal atresia, volvulus, and/or undescended testicles. Seventy-seven percent of the infants were delivered vaginally. Fourteen children were delivered via cesarean section. Seven cesarean sections were done solely for prenatal ultrasonic identification of an abdominal wall defect. There was no improvement in hospital stay, complications, days until enteral feeds were tolerated, days intubated, or number of surgical procedures in this group. In 14 patients, mesh sheeting (Marlex, Silastic) was used in the final closure. Sixty-four percent of these incurred wound breakdown necessitating removal of the mesh. This compares with a 3.2% wound breakdown in the nonmesh group. The average hospital stay was 43.9 days and the average time to enteral feeds 20.2 days. Sixty-four percent of the patients required postoperative intubation for an average of 5.5 days. The overall mortality rate was 4.3%. The present data do not support gastroschisis alone as an indication for cesarean section. The data indicate that mesh be avoided in the final closure if possible and support a favorable prognosis for most babies.

Abdominal Muscles↗

The use of cultured epithelial autografts in the wound care of severely burned patients.

Commercially prepared cultured epithelial autografts permit closure of deep burn wounds when insufficient uninjured skin is available for split-thickness grafting. This technique was used in seven patients with a mean total body surface area (TBSA) burn of 66% and full-thickness burn of 52%. All patients survived with a mean initial take of 69% and final take of 80% for the cultured epithelial autografts. Patients with a TBSA burn greater than 80% required at least a second application of the grafts. We feel our approach to wound preparation and postoperative wound care has contributed to our success with this technique.

3T3 Cells↗

Serum lipoprotein(a) levels in elderly black and white men in the Charleston Heart Study.

Lipoprotein(a) [Lp(a)] is an important genetic trait associated with cardiovascular disease. While Lp(a) levels have been demonstrated to be approximately twice as high in black adults and children compared with whites, this relationship has not been assessed in the elderly. During the 1987 recall of the Charleston Heart Study cohort, plasma Lp(a) [mg/dl] was measured on 113 white men and 83 black men. The average age of those having Lp(a) measurements was 71 years (+/- 6) for white men and 72 years (+/- 9) for black men. The distribution of Lp(a) was skewed in both whites (mean = 14.8, median = 8.2 mg/dl) and blacks (mean = 18.1, median = 12.8 mg/dl). The skewed distribution in elderly black men was in contrast to the bell-shaped distribution commonly reported for younger blacks. The Charleston Heart Study data suggest a shift to lower values among elderly as compared to younger men, with the greatest shift occurring among the black men. For black men who have survived to the 7th, 8th, and 9th decades of life, Lp(a) levels appear to be approaching the lower levels of white men. Despite this shift in distribution among black men, there remained a statistically significant difference in Lp(a) between racial groups.

Aged↗

T-cryptantigen determination affects mortality in necrotizing enterocolitis.

Testing of infants suspected of having necrotizing enterocolitis for evidence of exposure of the Thomsen-Friedenreich cryptantigen (TCA) has been advocated, because patients with TCA exposure can have severe hemolytic reactions when undergoing transfusion with plasma containing blood products. We compared 62 patients who were managed with knowledge of TCA exposure status during a four year period with 66 patients who were not screened during a comparable four year period. Evidence of hemolysis after blood transfusion occurred significantly more frequently in patients who were not screened (42 versus 15 percent, p < 0.05) and there was significantly greater mortality (18.0 versus 4.5 percent, p < 0.05) in the group that was not screened. These findings suggest that screening for TCA exposure is not only of diagnostic and prognostic value in necrotizing enterocolitis, but is important for patient management and outcome.

Antigens, Tumor-Associated, Carbohydrate↗

The detection of occult renal tumors in children by elevated hematocrit on routine complete blood count: a report of two cases.

Wilms' tumor is a renal neoplasm usually found in young children and is rarely seen in teenagers. The production of erythropoietin by these tumors may result in secondary erythrocytosis, which should be reflected in complete blood counts (CBC). A search of the literature for reports of occult Wilms' tumors initially suspected on the basis of erythrocytosis was unrewarding. Two teenagers are reported in whom unexplained erythrocytosis was the initial indication of a Wilms' tumor. In both cases, a previous CBC showed elevations in hemoglobin and hematocrit that might have led to an earlier diagnosis. We conclude that unexplained erythrocytosis should sound the alert for further diagnostic studies to evaluate the possibility of occult renal neoplasia in older children.

Adolescent↗

GABAA receptor function and regional analysis of subunit mRNAs in long-sleep and short-sleep mouse brain.

The greater sensitivity of long-sleep (LS), as compared with short-sleep (SS), mice to ethanol is due in part to differences in GABAA receptor function in specific brain regions. To determine if differences in subunit composition of GABAA receptors contribute to this differential sensitivity, we measured alpha 1 and gamma 2 subunit mRNAs with Northern analysis and in situ hybridization and gamma 2S, gamma 2L and alpha 6 subunit mRNAs with polymerase chain reaction (PCR) amplification. No differences in mRNAs in whole brain were apparent by Northern analysis. In situ hybridization revealed that alpha 1 and gamma 2 subunit mRNAs were co-localized in many brain regions but that they still had distinct patterns of hybridization. However, the few differences observed between LS and SS mice in the levels of hybridization for these subunits did not show a regional distribution consistent with ethanol sensitivity differences. Similar ratios of gamma 2L, and gamma 2S subunit mRNAs were found in LS and SS mouse cerebral cortex and hippocampus, and both mouse lines expressed essentially only gamma 2L subunit mRNA in cerebellum. mRNA for the alpha 6 subunit was detected only in cerebellum and also was qualitatively similar between LS and SS mice. Studies of muscimol-stimulated 36Cl- uptake by cortical membrane vesicles confirmed earlier findings that ethanol does not enhance function of GABAA receptors in SS mice when assayed at 30 degrees C. However, at 34 degrees C ethanol did increase this function in SS mice although the enhancement remained greater in LS mice. These functional results, together with the results showing similar levels of alpha 1, gamma 2S, gamma 2L and alpha 6 subunits in LS and SS mice, suggest that the ethanol-insensitivity of SS mouse GABAA receptors cannot be due solely to lack of subunits required for ethanol action and further suggest that differences in catalytic mechanisms affecting post-translational processing may account for some genetic differences in ethanol sensitivity of GABAA receptors.

Animals↗

Controlled substance dispensing and accountability in United States anesthesiology residency programs.

Controlled substance dependence (CSD) among anesthesiology personnel, particularly residents, has become a matter of increasing concern. Opinions vary as to the effectiveness of controlled substances (CS) accountability in deterring, identifying, or confirming CSD. A survey of program directors of American anesthesiology training programs was conducted in the summer of 1990 to determine the level of CS dispensing and accountability within their programs. The survey demonstrated that CS dispensing and accountability varied considerably among programs, among hospitals associated with individual programs, and within geographically distinct anesthesia delivery areas within the separate hospitals. Nevertheless, most institutions were moving toward improved methods of CS dispensing and providing more and better CS accountability. The presence of significant CSD, particularly among anesthesiology residents, was reconfirmed. We were unable to correlate the level of accountability of CS with the incidence of CSD. It remains to be seen to what extent CS accountability will continue to develop and whether CSD prevalence will then be changed.

Anesthesia Department, Hospital↗

Influence of glycemic control on interaction of very-low- and low-density lipoproteins isolated from type I diabetic patients with human monocyte-derived macrophages.

The VLDL and LDL fractions were isolated from 29 patients with type 1 diabetes at the time of admission to the hospital to restore glycemic control and again at discharge. These lipoprotein fractions were incubated with human monocyte-derived macrophages, and the rates of macrophage CE synthesis were determined. The rates of CE synthesis in human macrophages were significantly greater (P less than 0.005) when incubated with VLDL isolated from type I diabetic patients before compared with after glycemic control was attained and averaged 1.84 +/- 0.52 and 1.09 +/- 0.27 nmol (1.20 +/- 0.34 and 0.71 +/- 0.18 micrograms) [14C]cholesteryl oleate synthesized.mg cell protein-1 x 20 h-1, respectively. In contrast, when LDL isolated from the same patient during the same period was incubated with human macrophages, the rates of cellular cholesteryl ester synthesis did not differ significantly and averaged 4.23 +/- 1.26 and 3.91 +/- 0.96 nmol (2.75 +/- 0.82 and 2.55 +/- 0.63 micrograms) [14C]cholesteryl oleate synthesized.mg-1 cell protein.20 h-1, respectively. There was a significant increase in the total cholesterol content of VLDL isolated before glycemic control compared with that isolated after glycemic control was attained (P less than 0.05) resulting from a significant increase in the FC and CE (P less than 0.05) contents of these VLDL particles. There was a significant decrease in the ratio of FC to PL in VLDL, but not LDL, isolated after glycemic control (P less than 0.05). The percentage of apoE in VLDL was significantly decreased (P less than 0.05) after glycemic control was attained.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Surgical satellite pharmacies in institutions with anesthesiology training programs for physicians.

The results of a survey on the use of surgical satellite pharmacies in hospitals with anesthesiology training programs are reported. In June 1990 a questionnaire was mailed to 158 directors of anesthesiology training programs for physicians. The questionnaire solicited information on the presence of surgical satellite pharmacies in the training hospitals and the nature of the services provided, including accounting for controlled substances. Responses were received from 102 program directors and their designees, for a 65% response rate. Some respondents returned questionnaires completed by affiliated hospitals; a total of 137 responses were accumulated. Surgical satellite pharmacies were present in 46 (34%) of the 137 hospitals. Of those 46 satellite pharmacies, only 14 dispensed all controlled substances to anesthetic-administration areas. Most of the satellite pharmacies provided services at least eight hours per day. All 46 pharmacies dispensed controlled substances, 31 provided i.v. admixtures, and 12 dispensed all i.v. solutions. Accountability for controlled drugs was provided through a daily inventory count (45 satellite pharmacies), daily comparison of agents received and returned (36), review of the anesthesia record (31), random audits of individual providers (18), or quantitative or qualitative analysis of residual drugs (16). Accountability was considerably better in hospitals with surgical satellite pharmacies than in hospitals without them. Surgical satellite pharmacies provided increased accountability for controlled substances in institutions with anesthesiology training programs but did not use all the available methods for preventing drug diversion.

Anesthesiology↗

Chromogranin A: localization and stoichiometry in large dense core catecholamine storage vesicles from sympathetic nerve.

Chromogranin A is present in both adrenal medullary chromaffin granules and sympathetic nerve large dense core catecholamine storage vesicles (LDVs), yet selective stimulation of sympathetic axons provokes only minor changes in chromogranin A in the circulation. We therefore examined the stoichiometry of chromogranin A storage in purified LDVs as compared to chromaffin granules. Chromogranin A was found in LDVs on immunocytochemical sections of sympathetic axons. Sedimentation of sympathetic axon homogenates on sucrose-D2O gradients localized chromogranin A, norepinephrine, enkephalins and dopamine-beta-hydroxylase to the same gradient particulate fractions, suggesting that they inhabit a particle of the same buoyant density, the LDV. Chromogranin A was identified in LDV by radioimmunoassay, immunoblotting and immunocytochemistry. Purified LDVs contained 17.8 +/- 4.8% of cell total chromogranin A, at 27.9 +/- 3.5-fold enrichment over the original axon homogenate. When LDVs were lysed, all of the chromogranin A immunoreactivity originated from the soluble vesicle core rather than the LDV membrane. Although chromogranin A/catecholamine ratios were similar in LDVs and adrenal chromaffin granules, chromogranin A was a quantitatively minor protein in LDVs, accounting for only 0.16 +/- 0.015% of total LDV protein, as compared to 35.2 +/- 1.4% of total chromaffin granule protein. Each LDV particle contained approximately 0.94 +/- 0.09 chromogranin A molecules. Immunocytochemical data suggested that chromogranin A is costored in large dense core noradrenergic vesicles in subpopulations of sympathetic axons, analogous to enkephalins and neuropeptide Y. Thus, only profound changes in exocytotic catecholamine release from sympathetic axon LDVs would be expected to perturb circulating chromogranin A concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗

A novel synaptic vesicle-associated phosphoprotein: SVAPP-120.

Generation of antibodies and direct protein sequencing were used to identify and characterize proteins associated with highly purified synaptic vesicles from rat brain. A protein doublet of low abundance of 119 and 124 kDa apparent molecular mass [synaptic vesicle-associated phosphoprotein with a molecular mass of 120 kDa (SVAPP-120)] was identified using polyclonal antibodies. SVAPP-120 was found to copurify with synaptic vesicles and to be enriched in the purified synaptic vesicle fraction to the same extent as synapsin I. Like synapsin I, SVAPP-120 is not an integral membrane protein because it was released from synaptic vesicles by high salt concentrations. This protein was demonstrated to be brain specific, and its distribution in various brain regions paralleled the distribution of synapsin I and synaptophysin. During the postnatal development of the rat cortex and cerebellum, its expression correlated with synaptogenesis. SVAPP-120 was demonstrated to be a phosphoprotein both in vivo and in vitro. It was shown to be phosphorylated on serine and to a lesser extent on threonine residues. These results provide evidence that SVAPP-120 represents a novel synaptic vesicle-associated phosphoprotein. In addition, aldolase, a glycolytic enzyme, and alpha c-adaptin, a clathrin assembly-promoting protein, were identified on purified synaptic vesicles by direct protein sequencing.

Aging↗

Serotonin organelles of rabbit platelets contain synaptophysin.

Synaptophysin, an integral membrane protein of synaptic vesicles in nerve terminals and a class of small translucent vesicles in neuroendocrine cells, was detected in intact rabbit platelets by immunoblotting, immunofluorescence staining and immuno-electron microscopy. In a highly purified preparation of serotonin organelles isolated from rabbit platelets, synaptophysin was enriched approximately 10-15-fold over platelet homogenate. About 80% of total platelet synaptophysin was present in this purified fraction. The apparent molecular mass (approximately 38 kDa) and the extent of glycosylation of platelet-derived synaptophysin was more similar to the neuronal than to the neuroendocrine form of the protein. Immunofluorescence microscopy revealed that synaptophysin was compartmentalized in intact rabbit platelets and immuno-electron microscopy of subcellular fractions showed that it was localized exclusively to the membrane surface of serotonin organelles. No synaptophysin-like immunoreactivity was detected in platelets from other species such as human, guinea pig and rat. Another integral membrane protein of synaptic vesicles, p65, and a family of synaptic vesicle-associated phosphoproteins, the synapsins, were not detected in platelets of any species tested. These results provide evidence that serotonin organelles from rabbit platelets share a subset of protein components with synaptic vesicles from neurons. Synaptophysin in serotonin organelles from rabbit platelets, as suggested for small synaptic vesicles in neurons, might play a role in the formation of protein channels for the exocytotic release of serotonin.

Animals↗

Metabolism of very low- and low-density lipoproteins isolated from normolipidaemic type 2 (non-insulin-dependent) diabetic patients by human monocyte-derived macrophages.

The very low- and low-density lipoprotein fractions were isolated from 16 normolipidaemic Type 2 (non-insulin-dependent) diabetic patients in good to fair glycaemic control and from corresponding age-, sex-, and race-matched, non-diabetic control subjects. Rates of cholesteryl ester synthesis averaged 268 +/- 31 vs 289 +/- 40 pmol 14C-cholesteryl oleate.mg cell protein-1.20 h-1 for very low- and 506 +/- 34 vs 556 +/- 51 pmol 14C-cholesteryl oleate.mg cell protein-1.20 h-1 for low-density lipoproteins isolated from the Type 2 diabetic patients and control subjects, respectively, when they were incubated with human macrophages. A group of approximately one-third of the patients was selected for separate analyses because very low-density lipoproteins isolated from these patients did stimulate more cholesteryl ester synthesis when incubated with macrophages. There were no significant differences in the lipid composition of the lipoproteins isolated from the three groups of subjects. The relative proportion of apoprotein C to apoprotein E was significantly decreased (p less than 0.002) in the very low-density lipoproteins from diabetic patients and was further decreased in samples from these selected diabetic patients. The apoprotein C-I content of very low-density lipoproteins isolated from diabetic patients was increased compared to control subjects and was further increased in samples from the selected diabetic patients (p less than 0.02). There were no significant differences in the proportions of apoproteins C-III-0, C-III-1, or C-III-2 among the three groups. These studies suggest that in normolipidaemic Type 2 diabetic patients, the apoprotein composition of VLDL is abnormal and this may alter VLDL macrophage interactions and thus contribute to the increased prevalence of atherosclerosis in diabetic patients.

Apolipoproteins↗

Placental emboli from a fetus papyraceous.

A syndrome in monozygotic twins that consists of a macerated twin fetus (fetus papyraceous) and a live-born twin with various anatomical defects has been described. The etiology is thought to be placental transfer of emboli or thromboplastic material through vascular shunts. Thromboplastic material precipitates disseminated intravascular coagulation (DIC) in the fetus, with a resultant hypercoagulable state due to relative fetal antithrombin III deficiency. Two cases of this syndrome will be discussed. The case of a live-born twin with intestinal atresia, who developed in utero with a fetus papyraceous, is reported. Emboli were demonstrated in vascular shunts of the diamniotic-monochorionic placenta. The hypothesis of intestinal atresia as a result of a vascular accident is reviewed. Another case involving a live-born twin with congenital skin defects, who developed in utero with a fetus papyraceous, is also reported. The skin defects were a congenital disruption from fetal DIC with resultant hypercoagulable state. Several other manifestations of the placental emboli syndrome will be discussed and the vascular etiology of the disruptions explained.

Adult↗

Neuronal and adrenal enkephalins and catecholamines in response to acute CNS ischemia and reserpine in pig.

Co-storage of enkephalins and catecholamines in coronary artery, mesenteric artery and vein, middle cerebral artery, vas deferens and adrenal medulla was studied in domestic pig (Sus scrofa). Responses to acute CNS ischemia were correlated with time to peak plasma levels of central venous and adrenal vein outflow samples in controls, during reserpine treatment and after drug withdrawal. Endogenous enkephalins are co-stored in chromaffin granules of adrenal epinephrine-type cells and large dense cored vesicles of noradrenergic terminals. After a lag period, reserpine at near 'therapeutic' doses caused an apparent induction of opioid peptide precursor synthesis accompanied by processing to enkephalins in adrenal medulla up to 8-fold by 30 days and in mesenteric vein up to 4.5-fold by 14 days. Upon 14 days recovery from reserpine, elevated adrenal enkephalins were maintained and depleted catecholamines were largely replenished. Acute CNS ischemia produced rises in MAP (approx. 80 mmHg), marked net depletions of noradrenergic enkephalin stores, and net increases in adrenal vein outflow and central venous levels of enkephalins and catecholamines. Noradrenergic terminals contributed significantly to circulating enkephalins as well as norepinephrine. Reserpine for 7 days nearly abolished all tested responses to acute CNS ischemia, but immediate net 200-400% elevations of endogenous enkephalin stores occurred in coronary artery and mesenteric artery and vein (apparent processing of reserpine-induced neuronal precursor stores). Thus, induction of new synthesis of precursor opioid peptides by reserpine, with or without parallel processing to enkephalins, occurs in noradrenergic terminals in many tissues. All effects of reserpine on endogenous enkephalins implicate a central mechanism to inhibit sympathoadrenal outflow to the periphery. At 14 days recovery from reserpine, when near normal cardiovascular responses to acute CNS ischemia were regained, there was increased net release of the elevated adrenal enkephalins, exaggerated peak plasma enkephalin concentrations, but only minimal depletions of enkephalins from noradrenergic terminals.

Acute Disease↗