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Biomedical subjects

B Robinson

Publications and source records attributed to B Robinson.

At least 19 recordsLinked to original sources
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↗
PubMed1992

Epidemiology considerations in peptic ulcer disease.

Peptic ulcer disease is a common clinical problem. The lifetime risk of peptic ulcer disease is at least 10%. Millions of Americans are affected each year, imposing a major economic burden on the health care system. The overall hospitalization and mortality rates for peptic ulcer disease seem to have decreased substantially over the past few decades. There is much to suggest, however, that these changes were occurring even before effective medical therapy became available. In addition, other influences, such as increasing age of the population at risk, changes in smoking prevalence, and increasing use of nonsteroidal anti-inflammatory drugs, have impacted on the changing epidemiology of peptic ulcer disease. Hospitalization rates for patients with complications of peptic ulcer disease have remained relatively stable or, especially in the case of elderly women with gastric ulcers, increased significantly in recent years. Understanding the epidemiology of peptic ulcer disease will allow improved assessment of the effects of medical and surgical therapy and, hopefully, provide better clues to the etiology of this diverse group of diseases.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1991

Cancer and health screening in Canterbury general practices.

The general practitioners in the Canterbury Area Health Board area were surveyed for their screening policies for cancer and medical conditions. Responses were obtained from 210 (79%), 55% of whom had age/sex registers. Ninety-seven percent provided cervical smears, usually at 1-2 year intervals; 62% offered a female smear taker. Smears were initiated opportunistically by 76%, by age/sex register (47%) or on request by 27%. Breast cancer was screened by 69% using mammography and by 59% using breast physical examination; 73% taught breast self examination. Mammography was recommended every two years for women aged 50-64 years by 45% of responders, and annually to women aged 40-50 years by 19%. Mammography was initiated opportunistically by 88%, on request by 70% and using an age/sex register by 21%. Melanoma was screened by 66%, colorectal cancers in those at high risk by 42%. Testicular self examination was promoted by 43%. Ninety-one percent screened for hypertension, and 51% for hyperlipidaemia, 54% for diabetes mellitus in people without risk factors. Smoking (97%) and alcohol intake (82%) were usually inquired for, and safe sex practices by 59%. Established screening modalities were recommended by most practitioners, but the frequency exceeded current guidelines in many cases; opportunistic screening predominated.

Family Practice↗
PubMed1991

Vertical transmission of human immunodeficiency virus from seronegative or indeterminate mothers.

UNLABELLED: OBJECTIVE--To describe the identification of human immunodeficiency virus (HIV)-infected infants born to women who were seronegative or indeterminate during pregnancy. RESEARCH DESIGN--Longitudinal cohort study. SETTING--Inner-city medical center. PARTICIPANTS: A series of children born to women with histories of risk factors for HIV infection were followed up for studies of the natural history of HIV-infected infants. These children were identified through risk factor assessment of pregnant women presenting for obstetric care. INTERVENTIONS--Counseling and testing to detect HIV. RESULTS--Three women were retrospectively identified who were infected with HIV during pregnancy but whose test results showed them to be either seronegative or indeterminate. Two of these women transmitted HIV infection to their children. Subsequently, all three women were confirmed to be infected. CONCLUSIONS--Standard serologic testing to detect HIV infection will not identify all infected pregnant women. Perinatal transmission of HIV can occur in women with negative results of enzyme-linked immunosorbent assay or indeterminate results of Western blot analysis during pregnancy.

AIDS Serodiagnosis↗
PubMed1991

Milk proteins in the etiology of insulin-dependent diabetes mellitus (IDDM).

The etiology of insulin-dependent diabetes mellitus (IDDM) is multifactorial. The final cause of the disease, the specific destruction of the islet beta-cells, is the result of a cellular/humoral autoimmune process that operates in individuals with a particular genetic background in response to an external triggering factor(s). The most likely environmental triggers are virus infections and dietary factors. Among the latter group dietary proteins, mainly cow milk proteins, have been found to be important. Elimination of intact cow milk proteins from the diet significantly reduced the incidence of IDDM in the spontaneously diabetic BB rat, the elimination being most effective when it occurs during the pre-weaning period. Conversely, in newly discovered diabetics (both rats and children) increased levels of antibodies to cow milk proteins as compared with non-diabetic controls were found. These higher titres of antibodies were against beta-lactoglobulin and anti-bovine serum albumin. In further studies we found that antibodies to bovine serum albumin cross-react with a beta-cell membrane protein of Mr 69,000 and that this protein is likely induced by interferon. At the molecular level, a region of the bovine serum albumin has distinct homology to the beta-subunits of the MHC class II proteins Ia, DQ and DR, and antibodies raised against this bovine serum albumin region identified the same 69K beta cell membrane protein, in the same manner as antibodies to the third hypervariable region of DR-beta did. Our hypothesis is that bovine milk proteins (mainly bovine serum albumin) might be an important environmental factor providing specific peptides that share antigenic epitopes with host cell proteins.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Geriatric tinnitus: causes, clinical treatment, and prevention.

1. Tinnitus is seldom recorded in the clinical database of the elderly, despite the fact that next to hearing loss, tinnitus is the most commonly reported ear problem by the elderly population. 2. Common problems of the elderly that demand special counseling and teaching skills of the nurse are decreased tolerance to tinnitus due to coexistent complex morbidity, social problems, and losses; worry that the tinnitus is a sign of an impending crisis, such as stroke, brain tumor, or insanity; and boredom with excess time with little to do but to listen to one's tinnitus. 3. Tinnitus in aging is a symptom that is usually due to an identifiable disease, and is rarely of subjective type, high-pitched quality, chronic, irreversible, idiopathic, and bilateral. 4. The common causes and aggravating factors about tinnitus in aging can provide the clues to effective nursing-initiated measures, many of which are simple household activities or personal interactions.

Aged↗
PubMed1991

Staphylococcal scalded skin syndrome in a woman with chronic renal failure exposed to human immunodeficiency virus.

A twenty-eight-year-old woman seropositive for the human immunodeficiency virus and undergoing hemodialysis for end-stage renal disease sustained an infection of her arteriovenous graft. Multiple erythematous erosions appeared and a diagnosis of staphylococcal scalded skin syndrome was made when a frozen section of a fresh skin peel revealed an intraepidermal split through the granular layer and Staphylococcus aureus group II, phage type 71 was cultured from the wound and blood. Twenty-six cases of adult patients with staphylococcal scalded skin syndrome have been reported. Although this includes one patient with AIDS-related complex, this is the first case of an adult with staphylococcal scalded skin syndrome who showed seropositive results of testing for human immunodeficiency virus.

Adult↗
PubMed1990

Aldose reductase from human skeletal and heart muscle. Interconvertible forms related by thiol-disulfide exchange.

Aldose reductase was purified from human skeletal and heart muscle by a rapid and efficient scheme involving Red Sepharose chromatography, chromatofocusing on Pharmacia PBE 94, and hydroxylapatite high pressure liquid chromatography. The scheme afforded homogeneous enzyme, 65% recovery, in 2 days. All muscle samples express aldose reductase but not the closely related aldehyde reductase. Aldose reductase is isolated in one of two forms that are distinguishable by their kinetic patterns with glyceraldehyde as substrate and which are interconvertible by treatment with dithiothreitol. Both forms are capable of catalyzing the reduction of glucose (Km = 68 mM), and both are highly sensitive to inhibition by aldose reductase inhibitors. The reduction of glucose was shown to be nearly stoichiometric with production of sorbitol (92 +/- 2%). Dialysis of aldose reductase in the absence of thiols or NADP converts it into a form that shows markedly different kinetic properties, including very weak catalytic activity toward glucose and insensitivity to aldose reductase inhibitors. This modified form can be converted back into the native form by dithiothreitol. Thiol titration of the two forms of aldose reductase with Ellman's reagent indicated that two thiol groups were lost when the enzyme was dialyzed in the absence of dithiothreitol or NADP.

Aldehyde Reductase↗
PubMed1990

Aldehyde and aldose reductases from human placenta. Heterogeneous expression of multiple enzyme forms.

Aldehyde reductase (ALR1) and aldose reductase (ALR2) were purified from human placenta by a rapid and efficient scheme that included rapid extraction of both reductases from 100,000 x g supernatant material with Red Sepharose followed by purification by chromatofocusing on Pharmacia PBE 94 and then chromatography on a hydroxylapatite high performance liquid chromatography column. Expression of ALR1 and ALR2 in placenta is variable with ALR1/ALR2 ratios ranging from 1:4 to 4:1. ALR1 and ALR2 are immunochemically distinct. ALR1 shows broad specificity for aldehydes but does not efficiently catalyze the reduction of glucose due to poor binding (Km = 2.5 M). ALR1 exhibits substrate inhibition with many substrates. ALR2 also shows broad specificity for aldehydes. Although glucose is a poor substrate for ALR2 compared with other substrates, the affinity of ALR2 for glucose (Km = 70 mM) suggests that glucose can be a substrate under hyperglycemic conditions. ALR2 shows normal hyperbolic kinetics with most substrates except with glyceraldehyde, which exhibits substrate activation. Treatment of ALR2 with dithiothreitol converted it into a form that exhibited hyperbolic kinetics with glyceraldehyde. Dithiothreitol treatment of ALR2 did not alter its properties toward other substrates or affect its inhibition by aldose reductase inhibitors such as sorbinil (2,4-dihydro-6-fluorospiro-[4H-1-benzopyran-4,4'-imidazolidine]-2' ,5'- dione), tolrestat (N-[[6-methoxy-5-(trifluoromethyl)-1-naphthalenyl]thioxomethyl]-N- methylglycine), or statil (3-[(4-bromo-2-fluorophenyl)methyl]-3,4-dihydro-4-oxo-1-phthalazineac etic acid).

Alcohol Dehydrogenase↗
PubMed1990

Characterization and agonist regulation of muscarinic ([3H]N-methyl scopolamine) receptors in isolated ventricular myocytes from rat.

Cell surface muscarinic cholinergic receptors have been characterized and quantified for the first time, in intact, isolated adult rat cardiomyocytes. The cells were previously established as functionally fully compatible with cellular responses in intact cardiac tissue. The specific binding of the hydrophilic radioligand, [3H]-NMS, (N-methyl-[3H]-scopolamine methylchloride) was found to be stereo-specific, saturable, reversible and of high affinity. Binding of [3H]-NMS demonstrated appropriate drug specificity and was positively correlated with increasing cell concentrations. Bmax for [3H]-NMS binding to ventricular myocytes, enzymatically dissociated from adult male rats, was 15.8 +/- 1.03 fmol/25 x 10(3) cells (at 4 degrees C) and KD was 0.27 +/- 0.05 nM (n = 14). Binding assays performed at a higher incubation temperature (30 degrees C) yielded a higher Bmax value (22.1 +/- 1.6 fmol/25 x 10(3) cells; n = 11; P less than 0.005 vs. Bmax at 4 degrees C) but an unchanged KD (0.23 +/- 0.06 nM). Pretreatment of myocytes with the muscarinic agonist carbachol (1 mM) at 37 degrees C resulted in a reduction (down-regulation) in specific binding of the hydrophilic ligand [3H]-NMS. The magnitude of this reduction and its rate of recovery were dependent on the time of the exposure to carbachol. Exposures of 30-60 min elicited down-regulated by 35% (Bmax = 14.29 +/- 1.66 changed to 9.5 +/- 1.79 fmol/25 x 10(3) cells, without change in KD P less than 0.01, n = 4). The down-regulation of the muscarinic receptors by carbachol was insensitive to application of bacitracin - an inhibitor of endocytosis. On the other hand preincubation with 10(-9)M atropine, a muscarinic antagonist, hindered the agonist-induced receptor "loss" from the cell surface confirming the muscarinic nature of these receptors. We conclude that our preparation of intact, isolated ventricular cardiomyocytes is ideally suited for the study of cell surface muscarinic receptor regulation under physiological and pathological conditions.

Animals↗
PubMed1990

Sensitization versus tolerance to haloperidol-induced catalepsy: multiple determinants.

The effects of dose, administration frequency, and behavioral testing conditions on the development of tolerance versus sensitization to haloperidol-induced catalepsy were tested in rats. Animals received daily or weekly injections of haloperidol (0.05-5.00 mg/kg SC) for up to 22 days. Catalepsy assessments were made either once or repeatedly using two tests: the horizontal bar and the inclined screen. Tolerance was found only in animals treated daily with haloperidol (1.5 mg/kg) and tested repeatedly on the horizontal bar. In contrast, sensitization was observed with various haloperidol doses, daily or weekly administration schedules (for most doses), either horizontal bar or inclined screen catalepsy tests, and repeated or single testing. Sensitization developed most strongly following weekly drug administration and repeated testing on the horizontal bar. No single experimental variable produced a definitive pattern of change in catalepsy over time. Dose, drug administration schedule, and behavioral test conditions all influenced the evolution of catalepsy during chronic haloperidol treatment.

Animals↗
PubMed1990

Particle distribution in lung and lymph node tissues of rats and dogs and the migration of particle-containing alveolar cells in vitro.

Whole rat lungs and individual dog lung lobes were instilled either with low numbers (10(7)) or high numbers (10(9)) of fluorescent polystyrene microspheres (PLM), or with saline alone. Particle distributions in dog and rat lung lobes and tracheobronchial lymph nodes (TBLN) were studied up to several weeks after particle instillations using methacrylate-embedded tissues and epifluorescence light microscopy. Free alveolar cells were obtained from rats and dogs by lung lavage 1 or 7 d after particle instillations. Lavaged cells were tested for directed migration toward the chemoattractant N-formylmethionyl-leucyl-phenylalanine (FMLP). Random migration in the absence of the FMLP was used as a control. The dog lung interstitium contained many more particles than did the rat lung interstitium, and particle numbers in interstitial and TBLN cells of dogs were higher than in those of rats. FMLP enhanced the number of migrating cells about twofold. Increasing particle numbers in lavaged phagocytes (greater than 10 particles/phagocyte in dogs; greater than 20 particles/phagocyte in rats) decreased their ability to migrate. The higher fractions of particles in the dog lung interstitium are thought to be an important reason for prolonged retention and increased TBLN transport of deposited particles in dogs as compared with rats. Our results suggest that cell mobility is lost after ingestion of high numbers of particles, and that this occurs earlier with dog than with rat lung cells.

Animals↗
PubMed1990

Childhood peptic ulcer disease in Jamaica.

Thirty-one children with peptic ulcer disease (PUD) were diagnosed in two major hospitals in Jamaica between 1979 and 1988. There were 21 girls and 10 boys with a mean age of 9 years. There were 26 duodenal ulcers and 5 gastric ulcers. Five patients (19 per cent) with a duodenal ulcer had a family history of peptic ulcer. Recurrent abdominal pain was the predominant presenting feature in 68 per cent and pain was present for a mean of 20 months. Bleeding occurred in seven patients (23 per cent). Twenty-nine patients were successfully treated medically. Two with duodenal ulcers required surgery. The majority of patients have remained well after a mean follow-up of 14 months. Although uncommon in children peptic ulcers should be considered in patients with recurrent abdominal pain. The majority will respond to medical treatment.

Adolescent↗