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Biomedical subjects

J Bell

Publications and source records attributed to J Bell.

At least 361 records · Page 20Linked to original sources

Arthrin: a new actin-like protein in insect flight muscle.

There are one or more proteins of 50,000 to 60,000 Mr in the thin filaments of insect flight muscle. A protein of 55,000 Mr has been isolated from insect fibrillar flight muscle and called arthrin. Despite its higher molecular weight, arthrin is in many ways like actin. The amino acid composition of arthrin was similar to that of actin. There were similarities in the peptides produced by digesting the denatured proteins and mild digestion of polymerized proteins cleaved similar-sized fragments from arthrin and actin. Polymerized arthrin activated the Mg2+ ATPase of myosin to the same extent as actin and the ATPase was regulated by rabbit or Lethocerus troponin and tropomyosin. Arthrin did not itself act as troponin-T. Electron microscopy of negatively stained specimens showed that arthrin and actin filaments were similar in structure and that arthrin could be decorated by rabbit subfragment-1 to form normal-looking arrowheads. Arthrin formed paracrystals at an optimum concentration of MgCl2 (25 mM) that was somewhat lower than the optimum for actin paracrystals. Optical diffraction showed that the structure of the paracrystals was similar to those formed from actin. The mass of arthrin and actin filaments relative to phage fd was measured by scanning transmission electron microscopy; the relative mass of arthrin and actin was 1.33, in agreement with molecular weight estimations. Therefore arthrin has the properties of a heavy form of actin. The proportion of actin, arthrin and troponin-T in Lethocerus myofibrils was six moles of actin to one mole of arthrin and one mole of troponin-T. The function of arthrin is not known.

Actins↗

Cholinergic REM sleep induction response correlation with endogenous major depressive subtype.

We compared central cholinergic responsiveness (using the latency to induction of rapid eye movement sleep after arecoline challenge as a response marker) in 90 subjects: patients with major depressive disorder (MDD) (n = 53), nonaffective psychiatric controls (n = 17), and normal controls (n = 20). MDD patients as a whole showed a supersensitive cholinergic response compared to nonaffective patients and normal subjects. Further analysis indicated a strong association between cholinergic supersensitivity and endogenous subtype of MDD, including a significant correlation with specific endogenous features such as distinct quality of mood, anhedonia, lack of reactivity, and agitation. Unlike rapid eye movement (REM) latency (a more conventional physiological marker), cholinergic sensitivity did not correlate with age or severity of illness but only with the presence of endogenous features. Previously described sleep physiological correlates such as REM latency and REM density of the first REM period also distinguished between endogenous and nonendogenous MDD. There was a statistically significant correlation between REM latency and arecoline REM induction response.

Adult↗

Protons decrease the single channel conductance of the sarcoplasmic reticulum K+ channel in neutral and negatively charged bilayers.

The conductance of rabbit sarcoplasmic reticulum K+ channels incorporated into artificial bilayers of varying lipid composition was measured at different K+ and proton concentrations. Protons competitively inhibit the K+ conductance with a Ki of 0.5 microM. In negatively charged membranes, the conductance is well described by Gouy-Chapman-Stern theory modified to include the inhibitory effect of protons of the conductance and assuming that the channel mouth is isolated by 5-10 A from bilayer surface.

Animals↗

Cardiac involvement in myotonic muscular dystrophy.

Cardiac illness in myotonic muscular dystrophy (MyD) is infrequent, but subclinical cardiac involvement in MyD is very common (found in 42 of 46 subjects) and may be responsible for sudden death. In this series, we found ECG abnormalities in 72%, left ventricular dysfunction in 70%, mitral valve prolapse in 37%, and sudden death in 4%. Four deaths during the study period were due to acute left ventricular failure, one to sepsis and respiratory insufficiency, and one was unexplained. We did not find ominous bradyarrhythmias or atrioventricular block, evidence of congestive heart failure, noninvasive evidence of coronary artery disease, or any correlation of type or amount of cardiac involvement with any clinical parameter such as age, sex, or severity of systemic dystrophy. We feel tachyarrhythmias may play as important a role in sudden death of myotonic muscular dystrophy subjects as bradyarrhythmias, and coronary artery disease in addition to cardiac dystrophy may produce arrhythmias and myocardial dysfunction in myotonic muscular dystrophy. In addition, some subjects have an unusual form of resting left ventricular dysfunction which improves with exercise. The most important problem in the clinical management of myotonic muscular dystrophy subjects is sudden death, and the solution does not appear to be empiric ventricular pacing. Our recommendations for prophylaxis of sudden death in myotonic muscular dystrophy are noninvasive investigation of coronary artery disease in subjects with significant risk factors, with angiography and surgery if indicated: detailed evaluation of syncopal and presyncopal events, including electrophysiologic testing, with pacemaker or antiarrhythmic drug therapy if indicated; and consideration of ventricular pacing of asymptomatic subjects if severe bradycardia or marked intraventricular conduction delay develops during follow-up, serial 12-lead ECGs. The documentation of tachyarrhythmias during sudden death and syncopal episodes in myotonic muscular dystrophy subjects makes ventricular pacing alone an uncertain modality for prevention of sudden death in subjects with only mildly lengthened PR or QRS intervals, and suggests a combination of pacemaker and antiarrhythmic drug therapy for the myotonic muscular dystrophy subject with syncope of no apparent cause.

Adult↗

Survival in trisomy 18. Life tables for use in genetic counselling and clinical paediatrics.

Clinical management of neonates with Trisomy 18 depends on a knowledge of life expectancy. True estimates of potential life span are required for genetic counselling purposes when parents interpret the genetic threat, not only in terms of the mathematical odds involved, but also in terms of the quality and length of life of an affected infant, should such be born. This paper reports the findings from a study to generate life tables for Trisomy 18. This study is a total population study over 10 years based on a primary population of 2.2 million. Forty-eight cases of Trisomy 18 were identified, five at amniocentesis. Four of the 43 clinical cases (9%) were mosaics. The median life expectancy for live-born infants was five days (range one hour to 18 months). Mean age at death was 48 days. Life tables, by sex and by sub-types (associated congenital abnormalities) are presented. The annual incidence is 14 per 100,000 total births, with a prevalence estimate of 0.06 per 100,000 total population.

Chromosomes, Human, 4-5↗

The cellular infiltrate in the liver in auto-immune chronic active hepatitis: analysis with monoclonal antibodies.

The mononuclear cell infiltrate in the liver was analyzed, using a panel of monoclonal antibodies (MAbs) of known specificity, in 10 patients with auto-immune chronic active hepatitis and, for contrast, in 14 with other types of chronic parenchymal liver diseases. In all cases, the mononuclear cell (MNC) infiltrate in the liver consisted mostly of T lymphocytes. Helper (Th) cells were more frequent than suppressor/cytotoxic T cells (Tsc) in the portal tracts and cirrhotic scar tissue, while Tsc were more common in the hepatic parenchyma. The number of Tsc cells in the parenchyma was greatest in patients with histologically active CAH and least in patients with quiescent cirrhosis. "Plasmacytoid" cells with the morphology of plasma cells, a hallmark of the MNC infiltrate in auto-immune CAH, were more frequent in histologically active CAH than in quiescent cirrhosis. These plasmacytoid cells were T200 + ve, and hence of bone marrow origin, but the majority expressed neither membrane nor cytoplasmic immunoglobulin nor any lineage-specific marker antigens, and hence did not fulfil criteria for B lymphocytes; however, these cells were positive for OKT10 and HLA DR. No difference was evident between the MNC infiltrate in the liver in auto-immune CAH and that in the other acute or chronic liver diseases studied, including HBV-associated CAH; hence immunohistological studies do not point to any pathological processes uniquely responsible for the pattern of hepatocyte damage seen in auto-immune CAH.

Antibodies, Monoclonal↗

Mutations preventing expression of sup3 tRNASer nonsense suppressors of Schizosaccharomyces pombe.

Suppression of nonsense codons in Schizosaccharomyces pombe by sup3-e tRNASerUGA or sup3-i tRNASerUAA is reduced or abolished by mutations within the suppressor locus. Twenty-five suppressor-inactive sup3-e genes and thirteen mutant sup3-i genes were isolated from S. pombe genomic clone banks by colony hybridization. Sequence analysis of these revertant alleles corroborates genetic evidence for mutational hotspots within the sup3 tRNA gene. Fifteen types of point mutations or insertions were found. Many of these replace bases which are highly or completely conserved in eucaryotic tRNA genes. Transcription of the altered sup3 genes in a Saccharomyces cerevisiae extract enabled the identification of mutations which affect the rate of 5'-end maturation or splicing of the tRNA precursors or both. A total of seven mutations were found which alter transcriptional efficiencies. Of these, five are located outside the internal transcription control regions.

Ascomycota↗

Rates of noninsulin-mediated glucose uptake are elevated in type II diabetic subjects.

Although insulin is extremely potent in regulating glucose transport in insulin-sensitive tissues, all tissues are capable of taking up glucose by facilitated diffusion by means of a noninsulin-mediated glucose uptake (NIMGU) system. Several reports have estimated that in the postabsorptive state the majority of glucose disposal occurs via a NIMGU mechanism. However, these estimates have been either derived or extrapolated in normal humans. In the present study we have directly measured NIMGU rates in 11 normal (C) and 7 Type II noninsulin-dependent diabetic subjects (NIDDM; mean +/- SE fasting serum glucose, 249 +/- 24 mg/dl). To accomplish this, the serum glucose was clamped at a desired level during a period of insulin deficiency induced by a somatostatin infusion (SRIF, 550 micrograms/h). With a concomitant [3-3H]glucose infusion, we could isotopically quantitate glucose disposal rates (Rd) during basal (basal insulin present) and insulin-deficient (SRIF) conditions. With this approach we found that (a) basal Rd was greater in NIDDM than in C, 274 +/- 31 vs. 150 +/- 7 mg/min, due to elevated hepatic glucose output, (b) NIMGU composes 75 +/- 5% of basal Rd in C and 71 +/- 4% in NIDDM, (c) NIDDMS have absolute basal NIMGU rates that are twice that of C (195 +/- 23 vs. 113 +/- 8 mg/min, P less than 0.05), (d) when C were studied under conditions of insulin deficiency (SRIF infusion) and at a serum glucose level comparable to that of the NIDDM group (250 mg/dl), their rates of NIMGU were the same as that of the NIDDM group (186 +/- 19 vs. 195 +/- 23 mg/min; NS). We conclude that (a) in the postabsorptive state, NIMGU is the major pathway for glucose disposal for both C and NIDDM; (b) for a given glucose level the efficiency of NIMGU (NIMGU divided by serum glucose level) is equal in C and NIDDM, but since basal Rd is elevated in NIDDMs their absolute basal rates of NIMGU are higher; and (c) elevated basal rates of NIMGU in NIDDM may play a role in the pathogenesis of the late complications of diabetes.

Adult↗

Biochemical characterization of the 94- and 78-kilodalton glucose-regulated proteins in hamster fibroblasts.

This report concerns further characterization of the 94-kDa and the 78-kDA glucose-regulated proteins which are the major proteins overproduced in hamster fibroblasts when the cells are starved of glucose. Using a temperature-sensitive mutant, K12, which synthesizes high levels of these proteins at the nonpermissive temperature, we purified both proteins by two-dimensional gel electrophoresis and determined their amino acid compositions as well as the NH2-terminal sequences. Both proteins contain an unusual NH2-terminal sequence rich in glutamic and aspartic acid residues. Biochemical fractionation of these proteins demonstrated that the 78-kDa glucose-regulated protein is present in the nuclear fraction. In addition, we show that phosphate incorporation into the 78-kDa protein is specifically affected in the K12 mutant cells.

Amino Acid Sequence↗

Behaviour of some models of myelinated axons.

In this paper we discuss several approaches to modelling myelinated axons and examine the qualitative behaviour of the models. To facilitate our goal of understanding in detail the differences in mechanisms modelling myelination, we impose at the nodes the simplest nonlinear current-voltage relation which allows the models to possess appropriate threshold behaviour and propagating action potentials (travelling waves). Our type of model is a nonlinear differential-difference system and the resulting travelling wave must satisfy a nonlinear delay-differential equation of mixed type. Another type of model is a diffusion equation coupled nonlinearly to ordinary differential systems whose solutions represent boundary data for the diffusion equation. We give some threshold results and derive a relationship between conduction speed and various model parameters for a few classes of these models.

Animals↗

Paediatric telephone consultation--a neglected area of health service delivery.

Telephone enquiries to a large paediatric institution were monitored over a 4 week period. Of the 1764 calls handled during this period (an average of 63 per day), over 75% sought advice regarding symptoms of illness in their children. The commonest were to do with vomiting and diarrhoea, fever, infectious disease, respiratory symptoms and feeding problems. It is suggested that it is no longer appropriate for such calls to be handled in an ad hoc manner as is the custom in most hospitals, but that specific telephone protocols be developed and evaluated to address this important area of paediatric consultation.

Ambulatory Care↗

Effect of left atrial size on the oesophageal transit of capsules.

The oesophageal transit time of barium sulphate capsules was measured using X ray fluoroscopy in 20 patients with mitral valve disease and 12 control patients in the erect and supine positions when swallowed with both 15 ml and 60 ml of water. An erect barium swallow was performed, and from a lateral radiograph the area of indentation of the oesophagus caused by the cardiac impression was measured. Left atrial diameter was derived from M mode echocardiography. In 19 patients with mitral valve disease one or more capsules remained in the oesophagus for five minutes and disintegrated there, whereas this occurred in only six control patients. Capsule transit time was significantly slower in the study patients than in the control patients in the supine position with 15 ml water. There was a significant correlation between the area of indentation and mean capsule transit time and supine 15 ml transit time. The area of indentation closely correlated with the left atrial diameter. When capsules were delayed in the oesophagus, this occurred mainly at the level of the left atrial impression in the study patients and at the lower oesophageal sphincter in the control patients. Patients with mitral valve disease are more likely than control patients to have delayed oesophageal transit of capsules because of the anatomical deformity caused by enlargement of the left atrium.

Adult↗

Improving profoundly mentally retarded adults' performance on a position discrimination.

The relative importance of stimulus manipulations antecedent to or consequent on the response was investigated in three experiments related to position discrimination. In the first experiment, two different stimuli (either a piece of candy or a toy cat) were hidden under one of three boxes in full view of 2 profoundly mentally retarded adults. The behavior of uncovering the hidden object was measured using a combined multiple baseline and reversal design. In Experiment II, an entire unit of profoundly retarded adults was screened to determine the prevalence of the effects observed in Experiment I. In Experiment III, an attempt was made to determine whether the difference in antecedents (candy vs. kitty) or consequences accounted for the superior performance when the candy was hidden. In this experiment, using a reversal design with four profoundly retarded adults, we found that the antecedent manipulation (hiding the candy vs. hiding the toy cat) resulted in better performance than did the manipulation of the consequence (handing subjects the candy or allowing them to uncover and consume it).

Adolescent↗

Vaginal cancer after hysterectomy for benign disease: value of cytologic screening.

Of 87 patients who were treated at the author's institution for primary cancer of the vagina, 31 had undergone total hysterectomy for benign disease. In this group of 31 patients, vaginal bleeding was the most common presenting symptom, although there were eight patients who were entirely asymptomatic and were diagnosed on routine examination. The stage of cancer was more advanced in the symptomatic patients than in the asymptomatic patients. There were seven patients with stage 0 disease, and four of these were asymptomatic and diagnosed by routine Papanicolaou smear. Overall, Papanicolaou smears were positive in 12 of 19 patients tested, a sensitivity rate of 63%. The authors recommend that patients who have a hysterectomy for benign disease continue to have Papanicolaou smears taken from the vaginal vault at regular intervals.

Adenocarcinoma↗