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Biomedical subjects

J Rogers

Publications and source records attributed to J Rogers.

At least 361 records · Page 20Linked to original sources
PubMed1988

Neural function: metabolism and actions of inositol metabolites in mammalian brain.

In the nervous system, a variety of cell types respond to external stimuli through the inositol lipid signalling pathways. The stimulus-coupled sequence of intracellular events has been investigated in a homogeneous model system, the cloned mammalian neural cell line NG115-401L. The neural peptide bradykinin stimulates a rapid production of identified inositol phosphate isomers and an intracellular Ca2+ discharge followed by a persistent plasma membrane influx. The temporal sequence suggests that Ins(1,4,5)P3 or Ins(1,3,4,5)P4 or both may coordinate these events in a neuronal cell, as has been suggested in other cell types. Thapsigargin, an irritant and tumour-promoting plant product, produces calcium transients in the absence of inositol phosphate production, and may provide a new tool for investigating the interactions between inositol phosphates and changes in cellular calcium homeostasis. In the 401L line, high levels of radiolabelled InsP5 and InsP6 have been detected, which has led to the evaluation of their possible occurrence and actions in normal brain. Both InsP5 and InsP6 are produced from a radiolabelled myo-inositol precursor in intact mature brain in a region-specific manner. This suggests that both inositol polyphosphates may be end products of regionally regulated biosynthetic pathways. When microinjected into a nucleus of the brainstem, or iontophoretically applied to the dorsal horn of the spinal cord, both InsP5 and InsP6, but not Ins(1,3,4,5)P4 isomers, appear to be potent neural stimulants. These results suggest that the inositol lipid signalling pathways may generate both intracellular and extracellular signals in brain.

Animals↗
PubMed1988

Kinetics of binding of phospholipase A2 to lipid/water interfaces and its relationship to interfacial activation.

The time-course of binding of phospholipase A2 and prophospholipase A2 to vesicles and micelles of a variety of substrate and nonhydrolyzable phospholipid analogs is obtained by monitoring the change in the fluorescence intensity of Trp-3 on the protein or of the 5-dimethylaminonaphthalene-1-sulfonyl (dansyl) chromophore on the surface of the vesicles. The time-dependent increase in the fluorescence intensity of phospholipase A2 is observed only under conditions where catalysis and equilibrium binding are also observed. The overall kinetics of binding is described by two rate constants. A rapid second-order rate constant (ka) for binding of both the proteins is 2.10(7) per s per mol expressed in terms of phospholipids as monomers, and 10(10) per s per mol expressed in terms of vesicles. This is probably a diffusion-limited encounter of the protein with vesicles as the first step in binding. An additional first-order rate constant (kb = 4 per s) was also discerned for the binding of phospholipase A2 but not for prophospholipase A2. The rate of desorption of the bound iphospholipase A2 in the presence of EGTA is very slow (less than 0.0002 per s), whereas the rate of desorption of the bound prophospholipase A2 is much more rapid (2.9 per s). The mechanistic significance of these rate constants is elaborated in terms of the differences in the rates of interfacial catalytic turnover of phospholipase A2 and prophospholipase A2. As shown elsewhere (Jain et al. Biochim. Biophys. Acta 860, 435-447) the hydrolysis of anionic vesicles by phospholipase A2 occurs in the scooting mode such that the bound enzyme remains on the target vesicles for several thousand catalytic turnover cycles. On the other hand, as shown in this paper, the kinetics of hydrolysis by prophospholipase A2 is dominated by its intervesicle exchange. Therefore, interfacial catalysis by prophospholipase A2 in the hopping mode would involve an on- and an off-step in each cycle, resulting in a catalytic turnover number of about 1.2 per s. A change from the hopping to the scooting mode of catalysis thus provides the kinetic basis for activation of interfacial catalysis by phospholipase A2 compared to that for prophospholipase A2.

Animals↗
PubMed1988

Structure of chick chromosomal genes for calbindin and calretinin.

The chick chromosomal gene for calbindin (the 28,000 Mr intestinal calcium-binding protein) was cloned, and all the exons and flanking regions were sequenced. The promoter region contains typical ATAAA and GGGCGG boxes, the latter being unusual in "non-housekeeping" genes. Three polyadenylation signals are found in the calbindin gene that correspond to the three known mRNAs. Transcription termination is not efficient because homology with consensus sequences found downstream from the polyadenylation signal is weak. There are ten introns, most of which do not fall at homologous positions, neither with respect to the sixfold repeating structure of the calbindin protein, nor with respect to previously sequenced genes for calmodulin and other calcium-binding proteins. The gene for the related protein calretinin was cloned and partially sequenced. The introns are in the same positions in the calretinin and calbindin genes. The introns have apparently been inserted during the divergence of the calcium-binding protein superfamily.

Animals↗
PubMed1988

Cyclic GMP inhibits protein kinase C-mediated secretion in rat pancreatic acini.

Dibutyryl cyclic GMP (Bu2cGMP) inhibited agonist-induced secretion of amylase from isolated rat pancreatic acini. In contrast to previous studies, this inhibitory action was not confined to butyryl derivatives of cyclic GMP, since the membrane-permeant cyclic GMP analogues Bu2cGMP and cyclic 8-bromo-GMP (8-Br-cGMP) were equipotent (IC50 2 nM) in their inhibition of amylase secretion stimulated by cholecystokinin-(26-33)-octapeptide (CCK8): at extracellular concentrations up to 1 mM, cyclic GMP itself was devoid of inhibitory activity. Both Bu2cGMP and 8-Br-cGMP also potently inhibited secretion stimulated by 4 beta-phorbol 12-myristate 13-acetate (PMA) (IC50 6 nM), but only partially inhibited responses elicited by bethanechol or bombesin and were without effect on A23187-evoked secretion. Furthermore, agents that are known to raise intracellular cyclic GMP levels (MB22948 (2-o-propoxyphenyl-8-azapurin-6-one) or nitroprusside) or antagonize the actions of protein kinase C (4 alpha-PMA or staurosporine), also inhibited CCK8- or PMA-stimulated secretion but not secretion elicited by bombesin, bethanechol, or A23187. It is concluded from these and other observations reported here that protein kinase C is the major intracellular mediator of amylase secretion stimulated by CCK8 and that this pathway may be regulated by cyclic GMP at a step that follows protein kinase C activation.

Amylases↗
PubMed1988

Lithium-induced downbeat nystagmus.

Two patients who were treated with lithium for psychiatric illness developed primary position downbeat nystagmus. Previous reports have suggested that lithium causes this type of nystagmus, but other known causes were present in most cases. Several months after stopping the lithium, one patient had marked resolution, while the second patient had only minimal improvement. Valproate sodium proved to be useful in suppressing the nystagmus in the second patient. Lithium carbonate is a cause of primary position downbeat nystagmus. The nystagmus may be permanent or require several months of abstinence for improvement.

Adult↗
PubMed1988

Temperature gradient between the rectum and the anal canal: evidence against the role of temperature sensation as a sensory modality in the anal canal of normal subjects.

Temperature difference between the rectum and anal canal is a fundamental requirement for the hypothesis that temperature sensation is of physiological importance in discrimination of anorectal contents occurring during the 'sampling reflex'. The temperature gradient between the rectum and the anal canal was measured in 47 normal subjects (mean age 51.6 years +/- 16.8 s.d., 24 men). The maximum mean difference in temperature between the rectum and the anal canal was 0.13 degrees C (0.06-0.19, 95 per cent confidence intervals) and occurred 4 cm from the anal verge. This difference is too small to be detected by the anal canal mucosa. Under normal physiological circumstances the conscious appreciation of temperature of faeces passing from the rectum to the anal canal is impossible during the anorectal sampling reflex.

Adult↗
PubMed1988

Extracranial and extraspinal nerve sheath tumors: computed tomographic evaluation.

Thirty-five patients with 37 peripheral nerve sheath tumors (NST) (16 schwannomas, 11 neurofibromas, 5 plexiform and 1 diffuse neurofibroma, and 4 malignant NST) were studied respectively. The benign NST usually appeared on CT as well-defined oval, spherical or fusiform masses, centered at the expected anatomic location of a cranial, spinal, autonomic or peripheral nerve with characteristic displacement of adjacent muscles and blood vessels. None of the schwannomas appeared homogeneously hypodense on IV enhanced CT, whereas close to half of neurofibromas and plexiform neurofibromas were so. This fact, which had not been reported in the past, may be related to differences in inherent vascularity and blood-nerve barrier (fenestrated blood vessels) between schwannomas and neurofibromas and may be a useful distinguishing CT feature. The most reliable, though not infallible criterion of malignant NST was poor definition of their margins. Ninety-two per cent of NST (34 out of 37) were diagnosed or included in a limited differential pre-operatively.

Female↗
PubMed1988

Evaluation of tolerance of and response to iron dextran (Imferon) administered by total dose infusion to pregnant women with iron deficiency anemia.

Six hundred twenty-three pregnant women with iron deficiency anemia received iron dextran Imferon by total dose infusion (TDI). Two dose levels were compared in respect of tolerance and hemoglobin response. The incidence of delayed reactions was significantly higher in the high dose group (P less than 0.01) but there was no significant difference in the incidence of reactions occurring during the infusion. These findings are discussed in relation to the hemoglobin response.

Adolescent↗
PubMed1988

Regional cerebral glucose metabolism in identical twins.

The present study reports on the degree of similarity in regional cerebral glucose metabolism in seven sets of female identical twins. All scans were done with subjects at rest. Glucose metabolism was measured with positron emission tomography (PET). Significant intraclass correlations were found for the orbital and prefrontal cortex as well as the basal ganglia (caudate/putamen). It is suggested that these correlations reflect the functional aspects of these areas, namely attention and posturing movements.

Adult↗
PubMed1988

Pre-emptive (neo-adjuvant) chemotherapy prior to radical radiotherapy for fit septuagenarians with bladder cancer: age itself is not a contra-indication.

Advanced age has often been cited as a contra-indication to the use of cytotoxic chemotherapy or aggressive combined treatment regimens. Fifteen patients, aged between 70 and 79 years (mean 73.1), have been treated for high grade, invasive bladder cancer using neoadjuvant intravenous cisplatin (80-100 mg/m2) plus radical radiotherapy (60 Gy in 6 weeks). Objective response was achieved in 14 patients. The median survival was 22 months, with 6 patients surviving 3 years or longer. Acute and late side effects were not excessive (no cases of W.H.O. grade IV toxicity), as demonstrated by clinical examination and the use of questionnaires (including linear analogue self-assessment scales) to assess quality of life. This aggressive treatment programme can achieve a high remission rate and prolonged survival in elderly patients with high risk bladder cancer without causing excessive morbidity.

Acute Disease↗
PubMed1988

Combined sensory and motor deficit in primary neuropathic faecal incontinence.

Eleven patients with idiopathic faecal incontinence (IFI) and nine normal controls were studied with techniques of mucosal electrosensitivity and rectal distention for the quantitative assessment of anal and rectal sensation and with manometric and electromyographic tests for the assessment of anorectal motor function. The tests of motor function showed pelvic floor motor neuropathy in the patients with IFI, compared with controls, anal canal resting and voluntary contraction pressures were significantly (p less than 0.05, p less than 0.002) lower, pudendal nerve terminal motor latency and external anal sphincter fibre density were significantly (p less than 0.05, p less than 0.05) raised. The results of mucosal electrosensitivity (MES) disclosed a sensory deficit in the anal canal in patients with IFI, compared with controls, MES threshold was significantly (p less than 0.002) higher. Sensory thresholds to rectal distension were similar in the two groups. This study shows that sensory deficit of the anal canal occurs in combination with the motor neuropathy of the anal canal musculature in primary neuropathic faecal incontinence.

Adult↗
PubMed1988

Pelvic floor neuropathy: a comparative study of diabetes mellitus and idiopathic faecal incontinence.

Twenty one patients with diabetic peripheral neuropathy, 18 with idiopathic faecal incontinence and 11 normal controls were studied with techniques of mucosal electrosensitivity, rectal distension for the quantitative assessment of anorectal sensation, and manometric and electromyographic tests for the assessment of anorectal motor function. An asymptomatic sensorimotor deficit was found in the anal canal of patients with diabetic peripheral neuropathy. Mucosal electrosensitivity thresholds in the anal canal were significantly higher (p less than 0.01 v controls) and fibre density of the external anal sphincter significantly raised (p less than 0.0001 v controls). Anal manometry and pudendal nerve terminal motor latencies were similar to controls. In patients with idiopathic faecal incontinence the tests of sensory and motor function also showed a sensorimotor neuropathy; compared with controls, mucosal electrosensitivity thresholds were significantly higher (p less than 0.002), anal canal resting and maximum squeeze pressures were significantly lower (p less than 0.05 and p less than 0.002 respectively), and pudendal nerve terminal motor latencies and fibre density of the external anal sphincter were significantly raised (both p less than 0.05). Sensory thresholds to rectal distension were similar in all groups. Pelvic floor sensorimotor neuropathy in diabetic patients has several features in common with that of patients with idiopathic faecal incontinence but its functional significance remains uncertain.

Adult↗