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Biomedical subjects

A Morris

Publications and source records attributed to A Morris.

At least 235 records · Page 13Linked to original sources

Ophthalmic survey of a diabetic clinic. I: Ocular findings.

A medical diabetic clinic was examined for evidence of diabetic eye disease. Of 681 patients invited for ocular examination 96.6% attended for screening. The results for insulin dependent diabetics (IDDs) and non-insulin dependent diabetics (NIDDs) were analysed separately and the major findings were: Cataracts were present in 40.8% of IDDs and 46.2% of NIDDs, with an increased incidence with advancing age. For younger age groups there were significantly more cataracts in IDDs than in NIDDs (p less than 0.001). Cataract extraction was required in 4.2% of the patients, which is higher than the general population. The presence of retinopathy was related to the duration of diabetes (p less than 0.001) but not to age of onset of diabetes. Retinopathy was found in 43.4% of IDDs and 20.1% of NIDDs. Sight threatening retinopathy was present in 13.3% of IDD and 4.3% of NIDD eyes. Advanced diabetic eye disease was seen in 0.6% of eyes.

Adolescent↗

Ophthalmic survey of a diabetic clinic: II. Requirements for treatment of retinopathy.

The eyes of 658 patients attending a district general hospital diabetic clinic were examined for retinopathy requiring treatment by photocoagulation or vitreoretinal surgery. Although the majority of patients with serious retinopathy were already under ophthalmic supervision, 39 cases (52 eyes) were found which required treatment. Eighty eyes had had previous photocoagulation, and treatment was recommended for maculopathy in 40 eyes, proliferative retinopathy in seven eyes, and combined maculopathy and proliferative retinopathy in five eyes. This suggested that existing referral criteria for photocoagulation in the population studied were reasonably accurate for proliferative retinopathy, but maculopathy was more frequently overlooked. In insulin dependent patients (IDDs) undetected maculopathy was found in 17/416 eyes, (4.0%) and in non-insulin dependent patients (NIDDs) 28/899 (3.1%). Untreated proliferative retinopathy was discovered in 5/416 (1.2%) IDD eyes and 7/899 (0.8%) of NIDD eyes. Vitreoretinal surgery was required in six eyes (0.5%) for vitreous haemorrhage or traction retinal detachment. Equipment for the treatment of diabetic retinopathy is now almost universally available in ophthalmic departments, but time for patient management by trained staff may be inadequate. Each UK ophthalmic consultant needs approximately 100 sessions per year to monitor and treat known cases of retinopathy apart from time required to train junior staff.

Adolescent↗

Identification of two binding sites for wheat-germ agglutinin on polylactosamine-type oligosaccharides.

The carbohydrate-binding properties of wheat-germ agglutinin (WGA) have been studied by using glycopeptides isolated from the cell surfaces of a cultured murine myeloid cell line (416B). The glycopeptides were passed through affinity columns of lentil lectin (LCA), concanavalin A (Con A) and WGA arranged in series so that material reaching the WGA column had failed to bind to LCA or Con A. WGA-binding glycopeptides were step-eluted with 0.01 M, 0.1 M and 0.5 M-N-acetylglucosamine (GlcNAc), to yield weak (WGA-W), intermediate (WGA-I) and strong (WGA-S) affinity fractions. WGA-W and WGA-I contained 'N'- and 'O'-linked oligosaccharides bound to separate polypeptides. WGA-S consisted almost entirely of N-linked components. Our analytical work was concentrated mainly on the N-linked fractions. In these carbohydrates WGA affinity was directly proportional to molecular size but inversely related to N-acetylneuraminic acid content. The binding of the weak-affinity fraction was dependent on N-acetylneuraminic acid, but the intermediate- and strong-binding species interacted with the lectin by N-acetylneuraminic acid-independent mechanisms. N-linked glycopeptides in each WGA-binding class were almost totally degraded to monosaccharides by the concerted action of the exoglycosidases neuraminidase, beta-galactosidase and beta-N-acetylglucosaminidase. Treatment with endo-beta-galactosidase caused partial depolymerization, yielding some disaccharides but also a heterogeneous population of partially degraded components. These findings suggest that WGA binds with high affinity to internal GlcNAc residues in large oligosaccharides containing repeat sequences of Gal beta(1----4)GlcNAc beta(1----3) (i.e. polylactosamine-type glycans). N-Acetylneuraminic acid is involved only in low-affinity interactions with WGA. WGA therefore displays an intricate pattern of saccharide specificities that can be profitably utilized for structural analysis of complex carbohydrates.

Amino Sugars↗

Interferon gamma produced by mitogen-activated T lymphocytes does not directly mediate lymphoproliferation.

Human interferon gamma (IFN-gamma) endogenously produced during mitogenic stimulation of human peripheral blood mononuclear cells or human T lymphocyte-enriched cultures was neutralized in situ by the addition of a polyclonal antiserum (anti-L) raised in a rabbit against partially purified natural IFN-gamma derived from peripheral blood mononuclear cells. Small decreases in mitogen-induced [3H]thymidine incorporation (lymphoproliferation) were demonstrated under these conditions. However, an antiserum (anti-G) raised in a sheep against highly purified recombinant IFN-gamma (E. coli-derived) which strongly neutralized the antiviral effect of IFN-gamma either had little effect on mitogen-induced lymphoproliferation or caused slight enhancement of mitogenesis. The interleukin 2 responsiveness of activated T lymphocytes following mitogenic stimulation was not found to be different in the presence of anti-G to that of control cultures incubated in the presence of normal sheep serum. These results suggest that IFN-gamma is not a direct requirement for lymphoproliferation.

Antibodies↗

Effects of monoclonal antibodies to the alpha and beta chains of the human lymphocyte function-associated (H-LFA-1) antigen on T lymphocyte functions.

The ability of two antibodies, one specific for the alpha chain, p180, and the other for the beta chain, p95, of the human lymphocyte function-associated (LFA-1) antigens, to inhibit T cell function was measured. Both antibodies inhibited T cell-mediated lysis of virus-infected target cells and of K562 cells. Only the anti-beta chain antibody inhibited natural killer cell lysis of K562. The antibodies inhibited cytotoxic T lymphocyte cell (CTL) lysis of HLA-mismatched target cells in the presence of concanavalin A at 6.25-12.5 micrograms/ml, but at higher doses of Con A no inhibition was seen. When the lytic process was divided into calcium-independent (adherence) and -dependent (lysis) steps the antibodies were found to block at the initial step of conjugate formation. The effects of these antibodies on T cell proliferative responses showed that responses to antigens, alloantigens, mitogens and anti-CD3 (UCHT1) antibody were greatly inhibited. All of these responses are adherent cell dependent and proliferation of adherent cell-depleted mononuclear cells to Sepharose-coupled UCHT1 was not inhibited by anti-LFA-1 antibodies. Proliferation to paired anti-CD2 (T11) antibodies was also only weakly inhibited. Release of interferon-gamma by CTL on contact with target cells was also inhibited by anti-LFA antibody. These results are evidence that the LFA antigen is necessary for a nonspecific interaction with antigen-presenting cells that is essential for activation of T cells through the CD3-T cell receptor complex.

Antibodies, Monoclonal↗

Role of protein synthesis in induction of interferon-gamma by mitogens in human lymphocytes.

The effect of inhibition of protein synthesis on interferon gamma (IFN-gamma) mRNA induction has been examined in human peripheral blood leukocytes and growing T lymphoblasts. Inhibition of protein synthesis by cycloheximide or puromycin when lymphocytes were stimulated with mitogen alone had little effect on the steady-state levels of IFN-gamma mRNA induced. Activation of the IFN-gamma gene appears to occur independently of synthesis of protein factors. Synergistic induction of IFN-gamma by mitogen plus the phorbol ester mezerein was at least in part accounted for by increased levels of IFN-gamma mRNA in both fresh lymphocytes and growing lymphoblasts. Inhibition of protein synthesis abolished the synergistic effect on mRNA leading to levels similar to those observed in cells treated with mitogen alone. Synergistic induction is dependent upon synthesis of protein factors either within the cells or produced as soluble mediators; these factors are not simply lymphokines since addition of exogenous factors to the cultures did not reverse the block on synergy by the inhibition. These data suggest that protein factors though they may be important in exerting qualitative control on the level of production of IFN-gamma have no role in the initial activation of the gene.

Blood Proteins↗

Keratin gene expression in simian virus 40-transformed human keratinocytes.

Previous reports from this laboratory indicate that cultured simian virus 40 (SV40)-transformed human keratinocytes express keratin proteins characteristic of simple epithelia that are not found in their untransformed counterparts. In this study we show by in vitro translation and RNA transfer blot analysis that the altered keratin synthesis reflects changes in the abundance of specific keratin mRNAs. SV40-transformed keratinocytes have a reduced abundance of transcripts for 58-, 56-, 52-, 50-, 48-, and 46-kDa keratin species, compared with uninfected cultured keratinocytes, but express significant levels of transcripts for 52-, 45-, and 40-kDa keratins, typical of simple epithelia. The SV40-transformed cells also express mRNA for a 48-kDa keratin that is unique to SV40-transformed keratinocytes. Analysis of the keratin genome with keratin-specific cDNAs as probes indicates that the changes in keratin transcription are not correlated with gross rearrangements of the keratin genome. These results suggest that analysis of viral transformation of cultured keratinocytes affords a novel approach to study mechanisms regulating keratin gene expression.

Cell Transformation, Viral↗

Long-term results, hemodynamics, and complications after combined heart and lung transplantation.

During the first 31/2 years of the Stanford heart-lung transplant program, 23 transplants have been carried out in 22 patients with severe pulmonary vascular disease. Actuarial survival curves predict 1 and 2 year survival rates of 71% and 57%, respectively, for all patients. As a result of increasing experience, the early mortality of 26% has been reduced, with only one early death occurring in the last eight patients; prior cardiac surgery was a contributing factor in three of the six patients suffering early deaths. Two late deaths occurred in the series 14 and 15 months after operation. One patient died suddenly as a result of an acute myocardial infarct and the other patient died because of respiratory failure. At autopsy, both patients had severe proliferative coronary atherosclerosis with obliterative bronchiolitis affecting the lungs. An additional patient required a retransplant for obliterative bronchiolitis 37 months after the initial procedure, and he too was found to have severe coronary artery disease. Hemodynamics and left ventricular function were normal in patients studied 1 and 2 years after undergoing the transplantation procedure. Thus, the early mortality and morbidity of combined heart and lung transplantation has been significantly reduced, but the long-term complications, particularly graft atherosclerosis and obliterative bronchiolitis, are yet to be fully controlled.

Actuarial Analysis↗

Family expressed emotion and relapse in schizophrenia in 24 urban American patients.

The authors examined the correlation between family expressed emotion and relapse in 24 schizophrenic patients in a predominantly inner-city American setting. They found a significant correlation between relapse and high expressed emotion in family members; the level of family expressed emotion was somewhat higher than that reported in previous studies. The findings suggest that the impact of expressed emotion may vary in different sociocultural populations.

Attitude to Health↗

Macrophage interaction with skeletal muscle: a potential role of macrophages in determining the energy state of healing wounds.

A decrease in ATP and creatine phosphate (CP) is characteristic of local injury to skeletal muscle. Recent data have suggested adequate potential for high-energy phosphate production in the wounded tissue. Thus, an adequate explanation for the deficit in the high-energy tissue content in wounds was lacking. Since the wound has multiple components (muscle + cellular infiltrate), the tissue content represents the summation of these components. Therefore, a technique to separate these components was designed. Using a 0.5% solution of lambda-carrageenan as the wounding agent, the extensor digitorum longus muscles (EDL) of male Fisher rats were unilaterally wounded with intramuscular injections. Five days later, both wounded and contralateral nonwounded muscles were incubated in a standardized fashion. The groups of EDL were: wounded as described, contralateral nonwounded, or contralateral nonwounded with the addition to the incubate of 6 X 10(6)/ml lambda-carrageenan elicited peritoneal macrophages. Following incubation, the individual component parts of the system (muscle and macrophage) were rapidly frozen and assayed for high-energy phosphate and DNA content. Examination of the high-energy phosphate content of the separate components of a wound demonstrated that macrophages increased the ATP and CP content of normal skeletal muscle. Yet when total high-energy phosphate content was normalized for total DNA (muscle + macrophages) in the reconstituted system, the values approximated those of wounded muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

Management of spontaneous rupture of the membranes in the absence of labor in primigravid women at term.

One hundred and thirty-five healthy primigravid women at or near term with spontaneous rupture of the membranes without uterine contractions were submitted to a prospective trial of management. Rupture of the membranes was diagnosed by speculum examination. If labor did not commence, induction was performed by oxytocin infusion starting at 9 AM following admission. One hundred and five women went into labor spontaneously before induction became necessary. Sixty-three of these women required augmentation with oxytocin. Twenty-seven percent of the induced group required cesarean section delivery compared to 10% of those in spontaneous labor augmented by oxytocin and to none of those who did not require oxytocin (p less than 0.01). Ninety-four percent of those in spontaneous labor were delivered vaginally compared to 73% of the induced group (p less than 0.01). Forty-one percent of the augmented group were delivered by forceps. Awaiting the spontaneous onset of labor for 24 hours or less did not result in clinical maternal or neonatal infection. We would therefore advocate awaiting the spontaneous onset of labor after spontaneous rupture of membranes without contractions at or near term in healthy primigravid women for up to 24 hours because it seems to confer significant advantages without producing any additional hazard.

Adolescent↗

The E receptor regulates interferon-gamma production: four-receptor model for human lymphocyte activation.

The E receptor (binds sheep erythrocytes) is found on virtually all human T cells. Here we show that a monoclonal antibody 9.6, which recognizes and binds the E receptor, inhibited interferon-gamma production by human peripheral blood mononuclear leukocytes induced with the mitogens phytohemagglutinin, concanavalin A, Staphylococcal enterotoxin A and the monoclonal antibody OKT3. Metabolic activation (RNA and DNA synthesis) in human peripheral blood mononuclear leukocytes in response to mitogens was also sharply inhibited by 9.6. This inhibitory effect occurred early during the induction phase since 9.6 had much diminished inhibitory effects when added 15-24 h after induction; peak IFN-gamma production and DNA synthesis occurred 3-4 days post induction. An early event inhibited by 9.6 appeared to be interleukin 2 (IL 2) receptor formation since: (a) the ability of mitogen-stimulated peripheral blood mononuclear leukocytes to absorb IL 2 was inhibited by 9.6, and (b) lines of T lymphocytes which already expressed IL 2 receptors were largely resistant to the inhibitory effects of 9.6 on IFN-gamma production and DNA synthesis. The tumor promoters 12-O-tetradecanoyl phorbol-13-acetate and teleocidin largely reversed the inhibition by 9.6 of IFN-gamma production and metabolic activation induced by mitogens. A model for the control of IFN-gamma induction involving four receptors, those for mitogens, tumor promoter, IL 2 and erythrocyte, is proposed.

Antibodies, Monoclonal↗

Effect of starvation on the local and systemic metabolic effects of the lambda-carrageenan wound.

The contribution that starvation makes to the altered glucose metabolism in injured rats was evaluated. Food intake, weight change, nitrogen balance, and muscle tissue concentrations of glycogen, glucose, and the glycolytic intermediates were determined in these animals. This study concluded that the wounded and pair fed control groups presented adequately represent the metabolic states associated with injury and semistarvation in experimental animals, decreased food intake plays a major role in the weight loss and nitrogen balance in this wound model, wounding overrides two of the controlling steps of glycolysis (hexokinase and phosphofructokinase) in skeletal muscle during starvation, the finding of similar pyruvate dehydrogenase activity after wounding and starvation as demonstrated by tissue lactate to pyruvate ratios and lactate and pyruvate concentrations suggest that lactate production in wounded tissue may not be simply a manifestation of an altered redox state secondary to anaerobic conditions.

Animals↗

Evidence for aerobic glycolysis in lambda-carrageenan-wounded skeletal muscle.

Classically, increased lactate production in wounded tissue is ascribed to anaerobic glycolysis although its oxygen consumption has been found to be similar to normal tissue. This apparent inconsistency was studied in a standardized isolated perfused wound model. Male Sprague-Dawley rats were wounded (group W) with intramuscular injections of lambda-carrageenan and fed ad lib.; not wounded and pair fed to the decreased food intake of the wounded animals (group PFC); or not wounded and fed ad lib. (group ALC). After 5 days, the hindlimbs of animals from each group were either perfused using a standard perfusate with added [U-14C]glucose or [1-14C]pyruvate or assayed for the tissue content of lactate and pyruvate. In addition, the effect of a 30% hemorrhage on the tissue lactate and pyruvate concentration was examined. Wounding increased glucose uptake and lactate production by 100 and 96%, respectively, above that seen in ALC animals. Oxygen consumption was unchanged by wounding (5.74, 5.14, and 5.83 mumole/min/100 g in W, PFC, and ALC, respectively). Glucose and pyruvate oxidation were also unaltered among the groups. Hemorrhage resulted in a comparable increase in lactate and pyruvate in tissue from wounded and pair-fed control animals (above those concentrations found in tissue harvested without preexisting hemorrhage). As a consequence, the same relationship in L/P ratio was maintained after hemorrhage. Taken together, these results confirm the presence of aerobic glycolysis in wounded tissue (unchanged oxygen consumption, glucose, and pyruvate oxidation). In addition, pyruvate dehydrogenase activity in the wound was apparently the same as that found in muscle from pair-fed control animals.

Aerobiosis↗