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Biomedical subjects

J Casey

Publications and source records attributed to J Casey.

At least 55 records · Page 3Linked to original sources

Isolation of proteins from crude mixtures with silica and silica-based adsorbents.

Silica and silica-based adsorbents have been used to isolate specific proteins from crude mixtures. Acid-activated Nugel silica and Nugel SP-Silica were used to extract human immune interferon from the conditioned medium of mixed lymphocyte cultures. Human interleukin-2 was extracted from the conditioned medium of Jurkat cells with LiChroprep RP-8. In each case, batch absorption was accomplished by gentle stirring in a microcarrier vessel. The adsorbate was collected by sedimentation, and either batch-eluted or packed into a column for gradient elution. A high degree of concentration and purification was achieved with a high recovery of biological activity.

Adsorption↗

Correlation of immune and nutritional status with wound complications in patients undergoing vascular operations.

The acquired failure of host immunocompetence that may result from significant protein and caloric malnutrition has been associated with an increased incidence of septic complications in patients undergoing operation. Wound infection in patients undergoing vascular surgical procedures may lead to exposure or contamination of a vascular graft, with the subsequent risk of hemorrhage, limb loss, or death. The present study was undertaken to correlate the immune and nutritional status of patients undergoing vascular surgical procedures with the development of significant wound complications. Seventy-nine patients undergoing a variety of vascular operations were subjected to comprehensive nutritional assessment, including anthropometric measurements (height, weight, midarm circumference, triceps skin fold), serologic testing (albumin, transferrin, lymphocyte count, serum zinc), cutaneous assessment of delayed hypersensitivity (anergy battery), and neutrophil functional analysis. After operation the patients were observed for the development of delayed wound healing or wound infection. Statistical analysis of measured variables was performed to identify immune and nutritional markers with prognostic value. Patients with serum albumin levels above 3 gm/dl were much more likely to have uncomplicated wound healing (P less than 0.001). Similarly, patients with serum transferrin levels above 150 mg/dl had significantly fewer wound problems (P less than 0.01). Only 29% of patients with cutaneous anergy had normal wound healing, while 56% of those with intact cutaneous reactivity healed primarily; this difference, however, was not statistically significant. Diabetics in this series were more likely to develop wound problems (P less than 0.05). Anthropometric measurements provided no predictive information regarding the likelihood of uncomplicated healing. Similarly, measurement of total lymphocyte count and serum zinc yielded no significant prognostic information. The urgent nature of many vascular surgical procedures may preclude preoperative immune and nutritional assessment; however, the outcome of these procedures may ultimately depend upon intact host defense. The contribution of protein and caloric malnutrition to immunocompromise can be easily assessed in these patients. The detection and subsequent reversal of immunoincompetence through the use of enteral or parenteral alimentation should provide a significant reduction in operative morbidity and mortality.

Aged↗

Incidence of lobular carcinoma in bilateral breast cancer.

The histology and clinical records of 52 patients with bilateral breast cancer recorded in a community tumor registry were reviewed. Previous studies have demonstrated the propensity of lobular carcinoma to occur bilaterally. This view is supported by the large number of lobular cancers found in our patients. Thirty-six percent of the patients with bilateral disease had lobular cancer in at least one breast. Those with lobular cancer tended to be younger and more likely to have simultaneous cancers than did patients with nonlobular carcinoma. In those patients in whom the occurrence of tumors was not simultaneous, they were smaller in the second breast but had similar rates of axillary metastases. This study raises the question of how best to manage the contralateral breast in patients with breast cancer. Lobular carcinoma is one marker of the likelihood for development of disease in the second breast; but if advantage is to be gained by this finding, investigation of the opposite breast is best done early. Finally, thorough examination of patients with nonlobular carcinoma must not be ignored because they still comprise the majority of bilateral breast cancers.

Adult↗

Impaired response of lymphocytes from non-insulin-dependent diabetics to staphage lysate and tetanus antigen.

We examined the blastogenic responses of lymphocytes to Staphylococcus aureus antigen in 49 uninfected non-insulin-dependent diabetic subjects and in 56 uninfected nondiabetic subjects. We found a significantly decreased response to this antigen in the diabetic patients (P less than 0.05). Diabetics whose blood sugar levels were less than 150 mg/dl showed significantly decreased responses, as did diabetics whose blood sugar levels were greater than 200 mg/dl. The use of fetal calf serum in place of autologous plasma did not correct the defect. In a smaller number of patients, we observed a decreased response to tetanus toxoid, which was significant (P less than 0.05). The response to phytohemagglutinin was not significantly different from normal controls (P greater than 0.4). These results indicated that non-insulin-dependent diabetics, as well as insulin-dependent diabetics (previously reported), show decreased responses to S. aureus antigen and to tetanus toxoid. This defect apparently is not related to blood glucose levels or other serum factors.

Adult↗

An experimental model of intraabdominal abscess in the rat.

Suitable small animal models of intraabdominal abscess are not available. We have developed a reliable model of intraabdominal abscess in the rat by fasting the animal overnight, devascularizing and ligating the cecum, and injecting 2.5 X 10(8) Escherichia coli and 2.5 X 10(9) Bacteroides fragilis into the ligated cecum. This model results in 39% coli acute mortalities within 48 hours from acute peritonitis, and abscess in 76% of survivals. Subsequent abscesses are 1.0--1.5 ml in volume and contain 4 X 10(8) E coli/ml of pus and 1.4 X 10(9) B fragilis/ml. This model allows chronic evaluation of sepsis in small animals and provides a convenient means to study the abscess microenvironment.

Abdomen↗

Formation of 3-hexaprenyl-4-hydroxybenzoate by matrix-free mitochondrial membrane-rich preparations of yeast.

It has been shown that a 10 000 x g matrix-free mitochondrial membrane-rich preparation from commercial bakers' yeast is able to synthesize 3-all-transhexaprenyl-4-hydroxybenzoate from 4-hydroxybenzoate and isopentenyl pyrophosphate. The synthesis is Mg2+ dependent and is stimulated markedly by the primer for polyprenylpyrophosphate synthesis of 3-hexaprenyl-4-hydroxybenzoate from 4-hydroxybenzoate, isopentenyl pyrophosphate and 3,3-dimethylallyl pyrophosphate the priming function of 3,3-dimethylallyl pyrophosphate can be performed by either geranyl pyrophosphate (most efficient) or farnesyl pyrophosphate. At high Mg2+ concentrations, however, geranyl pyrophosphate and farnesyl pyrophosphate act mainly as sources of preformed side chains and 3-diprenyl- and 3-tripenyl-4-hydroxybenzoate, respectively, are produced. In the presence of a source of preformed polyprenyl pyrophosphates the membrane preparations catalysed the polyprenylation of methyl-4-hydroxybenzoate, 4-hydroxybenzaldehyde, 4-hydroxybenzylalcohol and 4-hydroxycinnamate. No evidence was obtained for the involvement of either 4-hydroxybenzoyl CoA or 4-hydroxybenzoyl-S-protein in the formation of 3-polyprenyl-4-hydroxybenzoates.

Hydroxybenzoates↗

A testosterone-secreting adrenal cortical adenoma.

A virilizing, gonadotrophin-responsive adrenal cortical adenoma was removed from a 54-year-old woman. Following removal of the tumour, which contained and secreted androgens and estradiol, serum gonadotrophins rose to menopausal levels and the patient experienced menopausal symptoms. Pre-operative attempts to localize the source of androgens were unsuccessful.

Adenoma↗

Rates of formation and thermal stabilities of RNA:DNA and DNA:DNA duplexes at high concentrations of formamide.

The thermal stabilities of RNA:DNA hybrids are substantially greater than those of DNA:DNA duplexes in aqueous electrolyte solutions containing high concentrations of formamide. Association rates to form DNA:DNA duplexes and DNA:RNA hybrids have been measured in these solvents. There is a temperature range in which DNA:DNA rates are negligible and RNA:DNA rates close to optimal.

DNA, Neoplasm↗

Sequence homology of the mitochondrial leucyl-tRNA cistron in different organisms.

Sequence divergence of the mitochondrial leucytl-tRNA cistron in several eukaryotes has been examined by RNA-DNA hybridized. Rat mitochondria Leucyl-tRNA was hybridized with rat, mouse, guinea pig, monkey, chicken, and yeast mitochondrial DNAs (mtDNA) immobilized onfilters. Hybridization was carried out in 50% formamide (Tm -12degrees) or in 20% fromamide (Tm -21degrees). melting profiles of the hybrids were obtained for evaluation of the extent of base sequence micmatching. Under the more stringent hybridization conditions (50% formamide, Tm -12degrees), only mouse and quines pig mtDNAs hybridized with rat mitochondrial leucyl-tRNA. The Tm's of the heterohybrids were depressed by 2 and 9 degrees, respectively. Under less stringent hybridization conditions (Tm-21 degrees), monkey mtDNA also hybridized, and the Tm was depressed by about 15 degrees. Chicken and yeast mtDNAs did not form specific hybrids with rat mibochondrial leucyl-tRNA under these hybridization conditions. Mitochondrial leucyl-tRNA sequences in different eukaryotes appear to be conserved to a less extent than cytoplasmic rRNA, 5S RNA, or hemoglobin mRNA sequences.

Animals↗

Sequence homology between mitochondrial DNAs of different eukaryotes.

The sequence divergence of mitochondrial DNAs (mtDNA) from rat, mouse, guinea pig, monkey, and chicken has been examined by DNA-DNA hybridization. mtDNAs, isolated as closed circular molecules by propidium iodide-CsCl centrifugation, were labeled in vitro by use of Escherichia coli DNA polymerase I, and renatured (Tm-35 degrees) in the presence of a 2500-fold excess of heterologous mtDNA. Single-stranded and duples DNA were separated by hydroxylapatite chromatography. The thermal stability of heteroduplexes was compared to the homoduplex by thermal elution chromatography on hydroxylapatite columns. Heteroduplex fromation between the tritiated myDNAs and a 2500-fole excess of rar mtDNA were 70, 59, 37, and 22%, respectively, for mouse, guinea pig, monkey, and chicken. Similar results were obrained in reciprocal hybridizations where one of the other mtDNAs was present in excess. Considerable mismatching of sequences in all the heterohybrids was indicated by a 18-24 degrees depression in the te50 of the heteroduplexes compared with the homoduplex. There was no apparent change in heteroduplex formation when the concentration ratio of driving DNA in excess to [3H]mtDNA was varied between 1250 and 7500. Furthermore, a second renaturation with excess driving DNA after completion of the first reaction resulted in no detectable augmenting of heteroduplex formation. Similar sequences appear to be conserved preferentially in different organisms, since the presence of two of fouf different heterologous mtDNAs in excess resulted in only moderate and nonadditive increases in heteroduplex formation. Evolutionary divergence of mtDNA sequences appears to have occurred at rates similar to that for unique sequences nuclear DNA.

Animals↗

Treatment of severe diabetes mellitus by insulin infusion.

A new and simple form of insulin therapy for diabetic hyperglycaemia and ketoacidosis has been developed using a continuous intravenous infusion of insulin at a rate of 2.4 U/hr to maintain serum insulin concentration at physiological levels. This rate raises the mean serum insulin to 83 muU/ml and has a therapeutic effect which is not augmented by higher infusion rates. The response to such low doses of insulin indicates a need for a reappraisal of currently held theories about insulin resistance in diabetic ketoacidosis. In 11 diabetic patients with a mean plasma glucose of 514 mg/100 ml this therapy produced continuous falls in plasma glucose at a mean rate of 75 mg/100 ml/hr, and 10 out of 11 patients recovered within eight hours. This form of therapy is simple to institute, not complicated by hypoglycaemia, and avoids the confusion and empiricism of previously described forms of therapy.

Adolescent↗