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Biomedical subjects

B Robinson

Publications and source records attributed to B Robinson.

At least 91 records · Page 5Linked to original sources
PubMed1994

Premature atherosclerosis with photomyoclonic epilepsy, deafness, diabetes mellitus, nephropathy, and neurodegenerative disorder in two brothers: a new syndrome?

We describe two brothers with sensorineural deafness, diabetes mellitus, progressive neurological deterioration with photomyoclonic epilepsy, and progressive deterioration in renal function, resulting in death in the third decade of life. Autopsy showed diffuse atherosclerosis and arteriolosclerosis of the systemic vasculature. There was no evidence of these abnormalities in the patients' 2 sisters or either parent. Mitochondrial enzyme analysis documented partial deficiencies of Complex III and IV of the respiratory chain. This deficiency was expressed in skin fibroblasts, kidney and liver but not in muscle. This suggests that the disease-causing mutation is either in the mitochondrial or nuclear DNA. Various modes of inheritance are considered, including maternal, autosomal recessive, or X-linked recessive. We suggest this is a new genetic syndrome characterized by an underlying metabolic disease and premature atherosclerosis, possibly of mitochondrial origin.

Adult↗
PubMed1994

The effect of hypercapnia and hypoxemia on the cardiovascular responses to isoproterenol.

BACKGROUND: The reason for the increased risk of death with fenoterol and isoproterenol in asthma is unknown but may relate to their cardiovascular effects. Deaths from asthma usually occur outside hospital where hypoxemia, with or without hypercapnia, may exist. Both of these states can influence the cardiovascular system. We investigated whether different gas mixtures modified the cardiovascular effects of isoproterenol. METHOD: Nine healthy men were randomly assigned to receive each of three gas mixtures to achieve (1) normoxia-normocapnia, (2) hypercapnia (end-tidal PaCO2, 50 mm Hg), (3) hypoxemia-hypercapnia (arterial oxygen saturation, 90%; PaCO2, 50 mm Hg). Isoproterenol was administered with each of the gas mixtures. Cardiovascular measurements of heart rate, blood pressure, cardiac index, ejection fraction, fractional shortening, electromechanical systole, and the QTc interval were made before administration of the gases, as well as before and 5 minutes after isoproterenol administration. RESULTS: The changes after hypercapnia were not significantly different from those after normoxia-normocapnia. Hypoxemia-hypercapnia increased heart rate, systolic and diastolic blood pressure, QTc interval, cardiac index, ejection fraction, and fractional shortening. Isoproterenol increased heart rate, systolic blood pressure, QTc interval, cardiac index, ejection fraction, and fractional shortening while the subjects breathed the normoxia-normocapnia gas mixture. It caused similar changes with the other gas mixtures. The changes were additive. CONCLUSION: Isoproterenol and hypoxemia-hypercapnia will increase myocardial oxygen demand and could prove to be detrimental in severe asthma.

Adult↗
PubMed1994

Adult-directed communications of youth with mental retardation using the system for augmenting language.

This study characterizes the success and effectiveness of adult-directed communications of youth with mental retardation and little or no functional speech who used the System for Augmenting Language (SAL), in concert with vocalizations and gestures, to communicate over a 2-year period. Subjects were introduced to the SAL, a speech-output communication device used during daily interactions, to encourage attempts at communication either at home or school. All subjects used the SAL at home and at school during the second year. Results indicate that subjects used the SAL with their extant forms of communication, particularly vocalizations. Extant communications were more successful than SAL communications, although the environment influenced the success of all the youth's communications. The SAL, however, was more effective than vocalizations or gestures in conveying information and interacting with adults in both environments. Maintenance, generalization, and implications for practice are discussed.

Adolescent↗
PubMed1994

Reversible disassembly of an intestinal epithelial monolayer by prolonged exposure to phorbol ester.

This article describes a model of reversible disassembly of a cultured human intestinal epithelial monolayer by prolonged exposure to the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA). Prolonged phorbol ester exposure reduces protein kinase C (PKC) levels in numerous cell types including T84, as shown here. Under PKC-downregulated conditions, T84 monolayers, which simulate the highly organized structure of native intestinal crypt cells, become disassembled into 2 or 3 layers of rounded cells. Proliferation does not account for these morphological changes as assessed by thymidine incorporation studies. The effects of structural disorganization on epithelial barrier function was also examined. The permeability of disassembled monolayers was significantly greater than that of controls. Flux studies localized the permeability defect to the tight junction. PKC-associated alterations in the perijunctional ring of actin and myosin, one of the putative regulators of flow across the tight junction, were found to correlate with the observed functional changes. Most interesting was the fact that monolayer reassembly to the original columnar epithelial phenotype and reestablishment of barrier function occurred upon normalization of PKC levels. This model of reversible monolayer disassembly will allow investigation into the relationship between epithelial structure and function and examination of factors that govern monolayer formation.

Actins↗
PubMed1994

Influence of dietary protein and starch on production and metabolic responses of dairy cows.

The effects of starch and CP degradability on ruminal digestion, milk yield, and milk composition were evaluated using a 4 x 4 Latin square design. Thirty-six Holstein cows (15 multiparous; 21 primiparous) and 4 ruminally cannulated cows were assigned randomly to four diets. The experiment was conducted during wk 4 through 16 postpartum. Diets contained 60% concentrate and 40% bromegrass hay. Treatments were barley plus canola meal and soybean meal; barley plus corn gluten meal, fish meal, and meat and bone meal; corn plus canola meal and soybean meal; and corn plus corn gluten meal, fish meal, and meat and bone meal. Intake of DM was not influenced by starch source, but CP intake was higher for diets based on corn than for those based on barley. Yields of milk, milk protein, and lactose were higher for diets based on fish meal than canola meal but were not altered by dietary starch source. Milk protein percentage and 4% FCM yield were not altered by dietary protein source. The 4% FCM and milk fat yields were higher for cows fed diets based on corn than for cows fed diets based on barley. Cows fed diets based on corn had significantly lower concentrations of most short- and medium-chain fatty acids and elevated concentrations of C18:0, C18:1, and C18:2 in milk. Protein source significantly influenced milk yield, and milk composition was altered by starch source. However, no interaction was observed between starch and protein sources.

Animal Feed↗
PubMed1994

Atrial myxoma.

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Adult↗
PubMed1993

Aldose and aldehyde reductases from human kidney cortex and medulla.

Aldose reductase and aldehyde reductase were purified to homogeneity from multiple samples of human kidney cortex and medulla. A single form of aldose reductase is expressed in kidney that is kinetically and immunochemically indistinguishable from aldose reductase expressed in other human tissues. The results support the conclusion that there is a single human aldose reductase, and that aldose reductase is expressed in a reduced form, characterized by high sensitivity to aldose reductase inhibitors and ability to catalyze the reduction of glucose. Aldose reductase is easily oxidized to a form that is insensitive to aldose reductase inhibitors and unable to catalyze the reduction of glucose. This form does not appear to exist in vivo, even in kidney from diabetics. There is wide variation in the level of expression of aldose reductase in kidney, especially in cortex. The immunochemically separate but similar aldehyde reductase is also expressed in kidney as a single enzyme indistinguishable from aldehyde reductase from other human tissues. Aldehyde reductase levels exceed those of aldose reductase, both in cortex and medulla.

Aldehyde Reductase↗
PubMed1993

Lyme cordial.

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Ambulatory Care Information Systems↗
PubMed1993

Effect of stress management on blood pressure in mild primary hypertension.

OBJECTIVE: To establish whether stress management had a larger effect than a control treatment on resting blood pressure, ambulatory blood pressure, and left ventricular mass. DESIGN: A 12 week baseline period of habituation to measurement of blood pressure was followed by randomisation to either stress management or mild exercise for six months and follow up six months later. SETTING: General practice, district general hospital, and medical school. PATIENTS: Of the 184 patients aged under 60 with mild primary hypertension who entered the baseline habituation period, 88 were excluded because they failed to meet the entry criteria or they withdrew from the study. The remaining 46 men and 50 women underwent treatment. INTERVENTIONS: 10 clinical sessions and daily practice at home of either stress management based on relaxation or non-aerobic stretching exercises. Mildly stressful 15 minute interviews before and after treatment. MAIN OUTCOME MEASURES: Diastolic and systolic blood pressure in the clinic and during 12 hours of ambulatory recording, and left ventricular mass measured by echocardiography. RESULTS: The patients' blood pressure fell during habituation (systolic pressure from 152 mmHg to 140 mmHg, diastolic pressure from 98 to 93 mm Hg), but neither resting nor ambulatory blood pressure was changed by the treatments. Left ventricular mass was also unchanged. Blood pressure rose during the stressful interview, but this rise was reduced by stress management (systolic pressure rose by 7.4 mmHg before treatment and by 3.7 mmHg after treatment). CONCLUSION: Stress management of a type advocated for treating mild primary hypertension is ineffective in lowering blood pressure in patients who are well habituated to measuring blood pressure.

Adult↗
PubMed1993

Second messenger regulation of mRNA for corticotropin-releasing factor.

An understanding of how second messengers and their ligands are coupled to CRF gene activation is necessary if we are to understand the regulation of the CRF gene in physiological and pathological states. The protein kinase A, protein kinase C and glucocorticoid second messenger systems mediate most of the regulation of the CRF gene. In in vitro systems, CRF gene expression is stimulated 20-30-fold by activation of either the protein kinase A or the protein kinase C system. Glucocorticoid is able to inhibit stimulation via both pathways, but appears to be more effective in repressing activation mediated by protein kinase C. Glucocorticoid negative regulation requires the presence of glucocorticoid receptor possessing an intact DNA-binding domain, suggesting that this effect involves binding of the receptor to the CRF promoter. These in vitro studies should serve to guide investigators towards the possible mechanisms underlying CRF gene regulation in vivo.

Animals↗
PubMed1993

Effects of in utero administration of alcohol on glutathione levels in brain and liver.

Previous studies in our laboratory have shown that the ontogenic development of gamma-glutamyltranspeptidase (gamma-GTP) activity is delayed by the in utero administration of alcohol. gamma-GTP is responsible for the degradation and recycling of glutathione (GSH) via the gamma-glutamyl cycle. In this study, we examined the effects of the in utero administration of alcohol on GSH levels in gestational age 21-day-old (g21) rats. Pregnant rats were placed on a liquid diet containing either 35% ethanol-derived calories (35% EDC) or a pair-fed (PF) diet or a lab chow (LC) diet starting on day 1 of gestation and maintained on their respective diets until gestational day 21. On gestational day 21, the pups were delivered by Cesarean section and brains and livers removed and prepared for analysis of GSH, gamma-GTP, or gamma-glutamyl-cysteine synthetase (gamma-GCSyn). GSH levels in brain and liver were found to be significantly lower in the offspring of the 35% EDC-treated mothers than from the PF and LC controls. gamma-GTP activity was higher in brain and liver of the 35% EDC group than the PF group. gamma-GCSyn, the enzyme involved in the rate-limiting step of GSH synthesis, was not affected in liver, but was found to be decreased in brain of the 35% EDC and PF groups when compared with the LC group. GSH is involved in many cellular reactions that appear to protect the cell from damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

The mechanisms of IgE uptake by human alveolar macrophages and a human B-lymphoblastoid cell line (Wil-2wt).

Human alveolar macrophages (HAM) internalized more IgE (81%) than human Wil-2wt B-lymphoblastoid cells (28%) suggesting a difference in the metabolic processing of the specific IgE receptor (CD23) or, alternatively, the presence of another functionally distinct receptor. The mannose receptor (MR), demonstrated to be present on the AM, may fulfil this role as IgE is heavily mannosylated and binds to a greater extent to concanavalin A (Con A) (which has specificity for oligomannose oligosaccharide chains) than other antibody isotypes. The hypothesis of a second IgE receptor was tested using mannan which is a competitive inhibitor of ligand binding to the MR and mannosylated bovine serum albumin (MBSA) which binds with avidity to the MR. Mannan (0.1 mg/ml) decreased internalized MBSA uptake in the HAM at 37 degrees suggesting the presence of the specific MR. In contrast, Wil-2wt cells did not bind MBSA. Mannan also reduced IgE uptake in the HAM at 37 degrees but had no effect on IgE uptake by Wil-2wt cells. Anti-CD23 monoclonal antibody (mAb) 135 also partially reduced membrane IgE uptake in HAM while completely inhibiting it by Wil-2wt cells. However, there did not appear to be competition for binding sites between IgE and MBSA in HAM. If only CD23 is involved in IgE uptake by HAM its function appears to be different to that in Wil-2wt cells. Definite involvement of the MR in IgE uptake will require further investigation as it may have an important role in allergic states.

B-Lymphocytes↗
PubMed1992

Reduction of trioses by NADPH-dependent aldo-keto reductases. Aldose reductase, methylglyoxal, and diabetic complications.

The substrate specificities of human aldose reductase and aldehyde reductase toward trioses, triose phosphates, and related three-carbon aldehydes and ketones were evaluated. Both enzymes are able to catalyze the NADPH-dependent reduction of all of the substrates used. Aldose reductase shows more discrimination among substrates than does aldehyde reductase and is generally the more efficient catalyst. The best substrate for aldose reductase is methylglyoxal (kcat = 142 min-1, kcat/Km = 1.8 x 10(7) M-1 min-1), a toxic 2-oxo-aldehyde that is produced nonenzymatically from triose phosphates and enzymatically from acetone/acetol metabolism. D- and L-glyceraldehyde and D- and L-lactaldehyde are also good substrates for aldose reductase. The aldose reductase-catalyzed reduction of methylglyoxal produces 95% acetol, 5% D-lactaldehyde. Further reduction of acetol produces only L-1,2-propanediol. Acetol and propanediol are two products that accumulate in uncontrolled diabetes. Both acetol and methylglyoxal were compared with glucose for their abilities to produce covalent modification of albumin. All three of these carbonyl compounds reacted with albumin to produce modified proteins with new absorption and emission bands that are spectrally similar. Both methylglyoxal and acetol are much more reactive than glucose. A new integrative model of diabetic complications is proposed that combines the aldose reductase/polyol pathway theory and the nonenzymatic glycation theory except that emphasis is placed both on methylglyoxal/acetol metabolism and on glucose metabolism.

Acetone↗
PubMed1992

Prognostic markers of colorectal cancer: an evaluation of DNA content, epidermal growth factor receptor, and Ki-67.

Between January 1989 and August 1991, 62 patients undergoing resection for colorectal adenocarcinoma were assessed in a prospective fashion on the basis of various tumor characteristics that are thought to indicate prognosis. Parameters measured included epidermal growth factor receptor (EGFr) expression, a cell membrane receptor known to be overexpressed in a variety of tumors, Ki-67, a monoclonal antibody marker of cell proliferation, as well as flow cytometry and standard histologic examination. Statistical analysis included chi square with Yates correction when appropriate, Wilcoxon W, and multivariate logistic regression. EGFr positive tumors were associated with worse Dukes' stage (27% of EGFr negative tumors were Dukes' C or D vs. 58% of EGFr positive tumors, P = 0.03), as well as more aneuploid characteristics by flow cytometry (48% EGFr negative = aneuploid vs. 82% EGFr positive = aneuploid, P = 0.01). Lymphatic invasion was more frequent in EGFr positive tumors (P = 0.03). These factors proved to be independent of each other by multivariate analysis. Ki-67 did not correlate with any of the measured parameters and was of extremely limited use in the evaluation of the study population. Multivariate analysis indicated that aneuploid tumors were associated with worse Dukes' stage than diploid tumors. Histologic parameters such as lymphatic and vascular invasion as well as histologic grade are compared to the other parameters involved with prognosis.

Adenocarcinoma↗
PubMed1992

Alpha-ketoglutarate dehydrogenase deficiency presenting as congenital lactic acidosis.

We report an inborn error of the tricarboxylic acid cycle, alpha-ketoglutarate dehydrogenase deficiency, in three siblings with hypotonia, metabolic acidosis, and hyperlactatemia immediately after birth. Neurologic deterioration resulted in death at about 30 months of age. We propose low molar ratios of ketone bodies in plasma of neonates with congenital lactic acidosis as an indication of dysfunction of the tricarboxylic acid cycle.

Acidosis, Lactic↗
PubMed1992

A new method for the determination of the characteristic shape of an isokinetic quadriceps femoris muscle torque curve.

It has been suggested that visual analysis of isokinetic quadriceps femoris muscle torque curve (TC) shapes may have potential use in the diagnosis and prognosis of knee pathologies. The primary purpose of this pilot study was to develop a method for analyzing the shape of an isokinetic TC. Our method normalizes and averages the TC, and then uses curvilinear analysis of the TC shape to aid in diagnosis and prognosis. For demonstration, the method was applied to isokinetic quadriceps femoris muscle TC data collected using a LIDO digital dynamometer from 25 healthy volunteer subjects and retrospectively acquired from the uninvolved limbs of 37 patients with unilateral knee pathologies. The preliminary results revealed (1) that a common quadriceps femoris muscle TC shape existed for the volunteer group at 60 degrees and 180 degrees/s; (2) that the uninvolved limbs of the patient group exhibited the same shape at 60 degrees/s, but not at 180 degrees/s; and (3) that the quadriceps femoris muscle TC shape demonstrated no significant differences with respect to limb dominance or gender for either group. Further testing of this quantitative method on a larger sample is needed to determine its usefulness in the analysis and implications of TC shape concerning pathology and diagnosis.

Adult↗