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Biomedical subjects

R J Walker

Publications and source records attributed to R J Walker.

At least 181 records · Page 10Linked to original sources
PubMed1988

Renal disease in diabetics--which patients have diabetic nephropathy and what is their outcome?

From August 1974 to January 1985, 53 patients (26 men; seven Maoris) mean age 45 (SD 15) years, with diabetes mellitus for a mean of 12 (SD nine) years had a renal biopsy and were followed. Indications for biopsy were nephrotic syndrome, proteinuria, renal impairment (five) and hematuria (one). Mean plasma creatinine concentration was 0.22 (SD 0.18) mmol/L and protein excretion 3.4 (SD 2.5) g/24 h. Diabetic nephropathy was demonstrated in 39 patients and significantly associated with retinopathy and insulin dependent diabetes mellitus (IDDM). Of the 39 patients followed for 25.7 (SD 22.8) months, 18 had died (nine myocardial infarction, six uremia, two sepsis, one stroke) and nine had begun dialysis. The five-year cumulative renal survival was 28%. The presence of the nephrotic syndrome and the plasma creatinine concentration at presentation were the best predictors of survival. Diabetics with IDDM of 20 years duration, retinopathy and heavy proteinuria, who survive the other complications of their disease, are likely to have diabetic nephropathy requiring renal replacement therapy.

Adult↗
PubMed1988

ZAPA, (Z)-3-[(aminoiminomethyl)thio]-2-propenoic acid hydrochloride, a potent agonist at GABA-receptors on the Ascaris muscle cell.

This study is the first report of a compound which is equal in efficacy to gamma-aminobutyric acid (GABA) at the nematode Ascaris muscle GABA-receptor. The GABA-receptor at the Ascaris muscle cell which mediates a membrane hyperpolarization and muscle relaxation has eluded classification. The structure-activity profile of this receptor is not typical of GABAA or GABAB-receptors. Here we report that the isothiouronium compound ZAPA is as potent as GABA at this receptor. This finding has important implications for the characterization of the Ascaris GABA-receptor and the design of novel anthelmintics.

Acrylates↗
PubMed1988

Synergistic toxicity of cyclosporin A and streptomycin in renal epithelial cell cultures.

Cyclosporin A (CSA) nephrotoxicity was examined in two renal epithelial cell cultures, the LLC-PK1 cell line and the MDCK cell line. Acute changes in cell growth and cellular DNA and protein synthesis were investigated at 2 hours, 20 hours and 5 days. The potential synergistic interaction between streptomycin (a standard additive to most culture media) and CSA was examined. CSA produced significant alterations in cell function as early as 2 hours after exposure and this became more noticeable with increased exposure to CSA. Streptomycin potentiated the toxicity effects on cellular metabolism that was seen with CSA. The use of cell culture models to investigate CSA toxicity must avoid the use of potential agents which may have a synergistic effect on the development of toxicity.

Animals↗
PubMed1987

Transcriptional signals of a U4 small nuclear RNA gene.

The signals controlling the expression of a chicken U4 small nuclear RNA (snRNA) gene have been studied by microinjection into Xenopus oocytes. At least two distinct regions in the 5'-flanking DNA contribute to U4B RNA gene expression. The proximal regulatory element, which is inactivated by a 5'-flanking DNA deletion to position -38, provides a basal level of U4B RNA synthesis. The distal regulatory region, centered near position -200, acts as a transcriptional enhancer. It provides a 4-5 fold stimulation of U4B RNA gene expression above the basal level, and, like mRNA enhancers, is composed of multiple functional motifs. One of these, the octamer sequence ATGCAAAG, has previously been recognized as an important element of U1 and U2 snRNA gene enhancers, as well as being involved in the expression of a number of mRNA genes. However, the octamer sequence is not sufficient for U4B enhancer activity. An additional element, an "Sph motif," is located 12 base pairs downstream of the octamer and is an essential component of the U4B enhancer. Transcriptional competition studies indicate that the U4B and U1 snRNA genes utilize a common set of transcription factors.

Animals↗
PubMed1987

Localization of ARG-vasopressin-like material in central neurones and mechanism of action of ARG-vasotocin on identified neurones of the snail Helix aspersa.

Immunocytochemical and electrophysiological studies were made on neurones in the suboesophageal ganglia of Helix aspersa. A group of neurones in the anterior dorsal surface of each parietal ganglion showed positive immunoreactivity to an antibody to arginine vasopressin (AVP), as did the neuropile and the nerves associated with the parietal and visceral ganglia. The only peripheral tissue to exhibit positive immunoreactivity to AVP was the optic tentacle, where positive immunoreactive fibres were present in the optic nerve and cell bodies below the retinal cell layer. Two central neurones, F1 and E13 were excited by arginine vasotocin (AVT), threshold 1-10 nM, and the ionic mechanism associated with this response was investigated. This excitation involved both sodium and calcium ions with an overall increase in resistance. In low sodium Ringer, the AVT response was greatly reduced, while in calcium-free 3 mM cobalt Ringer, the response was potentiated. Changing the external concentrations of potassium and chloride ions had no apparent effect on the response. The amplitude of the excitation induced by AVT was enhanced when the cells were hyperpolarized. Most of the other neurones tested failed to respond to AVT though the excitatory response of certain cells to acetylcholine was enhanced by 0.1 microM AVT. Excitation by 5-hydroxytryptamine was unaffected in the cells tested. This study provides further evidence for a role for an AVT-like peptide in the nervous system of Helix.

Acetylcholine↗
PubMed1987

An analysis of the adenosine receptors responsible for modulation of an excitatory acetylcholine response on an identified Helix neuron.

1. Electrophysiological recordings were made from an identified neuron, F1, in the isolated suboesophageal ganglionic mass of Helix aspersa. 2. Bath applied adenosine (AD) (60-600 nM) depressed the depolarisation induced in the cell F1 by bath or iontophoretically applied acetylcholine (ACh). L-Phenylisopropyladenosine (L-PIA) also depressed the ACh response but NECA had no depressive effect. This effect of AD or L-PIA is inhibited by 12 microM 8-phenyltheophylline and is believed to be mediated by an A1 receptor. 3. If the proportion of the excitatory ACh response that was carried by calcium ions was increased, the percentage depression of this modified response by AD was significantly greater. 4. There was a residual current evoked by ACh in high calcium/sodium free Ringer. This ACh induced current was antagonized by 3 mM cobalt or 50 microM verapamil suggesting that it was calcium mediated. This residual current was also completely abolished by 0.6 microM AD. 5. Lower bath concentrations of AD (0.6-6 nM) and L-PIA than caused the depression of the ACh response and also adenosine triphosphate (ATP) (0.7 microM) and alpha,beta-methylene ATP (0.6 microM), enhanced the ACh D response. The relative potencies of AD and its two analogues 5'-N-ethylcarboxamideadenosine (NECA) and L-PIA in causing this enhancement of the ACh response were: NECA greater than AD greater than L-PIA. This is the potency ranking described for an A2 receptor.

Acetylcholine↗
PubMed1987

Comparison of the effects of FMRF-amide and pQDPFLRF-amide on identified Helix neurons.

Intracellular recordings were made from a selection of identified neurons in the sub-oesophageal ganglia of Helix aspersa, and their responses to the molluscan neuropeptides FMRF-amide and pQDPFLRF-amide compared. While FMRF-amide excited certain neurons and inhibited others, pQDPFLRF-amide did not produce excitation in any of the cells tested. A few cells were unresponsive to pQDPFLRF-amide, but most were inhibited with varying potency. FMRF-amide was generally 10-100 times more potent than pQDPFLRF-amide, but one cell, E13 in the visceral ganglion, showed equal sensitivity to the two peptides. On most cells there was no clear evidence for cross desensitization between the two peptides, although it is possible that in some cases where both peptides are inhibitory they may be acting on a single receptor.

Action Potentials↗
PubMed1987

Multiple functional motifs in the chicken U1 RNA gene enhancer.

The DNA sequence requirements of chicken U1 RNA gene expression have been examined in an oocyte transcription system. An enhancer region, which was required for efficient U1 RNA gene expression, is contained within a region of conserved DNA sequences spanning nucleotide positions -230 to -183, upstream of the transcriptional initiation site. These DNA sequences can be divided into at least two distinct subregions or domains that acted synergistically to provide a greater than 20-fold stimulation of U1 RNA synthesis. The first domain contains the octamer sequence ATGCAAAT and was recognized by a DNA-binding factor present in HeLa cell extracts. The second domain (the SPH domain) consists of conserved sequences immediately downstream of the octamer and is an essential component of the enhancer. In the oocyte, the DNA sequences of the SPH domain were able to enhance gene expression at least 10-fold in the absence of the octamer domain. In contrast, the octamer domain, although required for full U1 RNA gene activity, was unable to stimulate expression in the absence of the adjacent downstream DNA sequences. These findings imply that sequences 3' of the octamer play a major role in the function of the chicken U1 RNA gene enhancer. This concept was supported by transcriptional competition studies in which a cloned chicken U4B RNA gene was used to compete for limiting transcription factors in oocytes. Multiple sequence motifs that can function in a variety of cis-linked configurations may be a general feature of vertebrate small nuclear RNA gene enhancers.

Animals↗
PubMed1986

Effect of doxazosin on blood pressure and renal haemodynamics of hypertensive patients with renal failure.

Doxazosin, a quinazoline derivative, has alpha 1- adrenoreceptor antagonist properties similar to those of prazosin. This antihypertensive agent has a longer elimination half-life than prazosin. The pharmacokinetic properties of doxazosin are not significantly different in patients with renal insufficiency compared with healthy controls. In this study eight hypertensive patients with renal insufficiency were studied during a two week washout period, followed by a two week single blind placebo phase and an eight week open doxazosin treatment period. Doxazosin was commenced in a dose of 1 mg daily and titrated if necessary, with the dose being doubled every two weeks. In all but one patient doxazosin was successful in controlling the blood pressure. Treatment with doxazosin for eight weeks had no adverse effects on the effective renal plasma flow or glomerular filtration rate of these patients. Six of the eight patients suffered side effects attributable to doxazosin.

Adult↗
PubMed1986

Lupus nephritis: a 13-year experience.

Over a 13-year period 42 patients (35 women) with systemic lupus erythematosus and renal disease had a renal biopsy. Renal involvement as the first and only manifestation of systemic lupus erythematosus was common in men. The commonest reason for renal biopsy (23/42) was the finding of proteinuria with or without haematuria. One-half of all patients had diffuse proliferative glomerulonephritis. Twenty-seven patients were treated with both prednisone and azathioprine and 10 with prednisone alone at some stage during follow-up. The renal biopsy findings were useful in assessing the severity of renal involvement and prognosis. A five-year renal survival of 72% was observed. Diffuse proliferative glomerulonephritis with renal insufficiency was associated with a poor prognosis. Those patients who were established on the dialysis/transplant programme became symptom free on no treatment.

Adolescent↗
PubMed1986

B cell lymphoma presenting as carcinoma of the lung.

A patient presented with superior vena caval obstruction caused by a tumour which resembled carcinoma of the lung both clinically and histologically. However, immunologic and cytogenetic analyses carried out on the mediastinal biopsy and on pleural fluid revealed that the tumour was of B cell origin, Burkitt-like in sub-type, and had the t(8;14) translocation. The nature of many poorly differentiated tumours may be more clearly identified with the help of immunological and cytogenetic analyses.

Antigens, Neoplasm↗
PubMed1986

Substance P-like immunoreactivity in the retina and optic lobe of the squid.

The distribution of substance P-like immunoreactivity within the squid retina and brain was studied by immunofluorescence. Positive immunoreactivity was observed as a single layer of fibres in the retina. The retina was devoid of tyrosine-hydroxylase, serotonin, gamma-aminobutyric acid, cholecystokinin, neuropeptide Y, somatostatin, enkephalin and vasoactive intestinal peptide immunoreactivities. Substance P immunoreactivity was particularly abundant in the optic lobe. The optic lobe had a distinct layer of substance P fibres near the periphery. Immunoreactive cell bodies, fibres and varicosities were additionally present in various areas of the optic lobe. Substance P immunoreactivity in the other ganglia of the brain was restricted to a few scattered fibres.

Animals↗
PubMed1986

Henoch Schönlein nephritis.

Glomerulonephritis is the main determinant of mortality in the Henoch Schönlein syndrome. We report a prospective study on 17 patients with the Henoch Schönlein nephritis who underwent a renal biopsy during a 12-year period. Three patients have developed end-stage renal failure, 13 are alive with normal renal function and one was lost to follow-up. We recommend that patients with Henoch Schönlein nephritis be followed up, with urinalysis and assessment of renal function, for at least five years.

Adolescent↗
PubMed1986

Comparison of netilmicin with ceftriaxone for the treatment of severe or complicated urinary tract infections.

A randomised trial was undertaken to compare the efficacy of netilmicin and ceftriaxone for the treatment of severe or complicated urinary tract infections. Forty-seven patients completed the study. Twenty-three of 24 patients treated with netilmicin and 21 of 23 treated with ceftriaxone were cured. One patient treated with netilmicin had a mild, reversible disturbance of renal function. Six patients developed diarrhoea after ceftriaxone treatment.

Adolescent↗
PubMed1986

Localization of a substance P-like material in the central and peripheral nervous system of the snail Helix aspersa.

A monoclonal antibody against substance P was used for immunocytochemical staining of the central ganglia of the snail Helix aspersa and several peripheral tissues including the gut, reproductive system, cardiovascular system, tentacle and other muscles. Within the central ganglia many neurons, and many fibres in the neuropile and the nerves entering the ganglia, were stained for the SP-like material. The largest numbers of reactive cell bodies were in the pleural ganglia and on the dorsal surfaces of the pedal ganglia. A group of cells was also found, surrounding the right pedal-cerebral connective, that did not fluoresce, but were enveloped by reactive processes terminating directly onto the neurone somata. Specific staining was observed in all peripheral tissues examined and always appeared to be concentrated in nerve terminals. Most particularly these occurred in the heart and aorta, the pharyngeal retractor muscle and the tentacle. Although mostly present in muscular tissues, some fluorescence was also observed in the nervous layer surrounding the retina. The tentacular ganglion also contained immunoreactive cell bodies.

Animals↗
PubMed1986

The ionic mechanism associated with the action of putative transmitters on identified neurons of the snail, Helix aspersa.

Intracellular recordings were made from identified neurons in the suboesophageal ganglionic mass of the snail, Helix aspersa. The ionic mechanisms associated with acetylcholine excitation and inhibition, dopamine excitation and inhibition, gamma-aminobutyric acid (GABA) excitation and inhibition and serotonin excitation were investigated. Acetylcholine excitation was found to involve an initial increase in sodium conductance while acetylcholine inhibition was a pure chloride event which reversed at membrane potentials more negative than the chloride equilibrium potential. Dopamine excitation appeared to involve only an increase in sodium conductance while serotonin excitation involved an increase in conductance to both sodium and calcium ions. Dopamine inhibition was associated with an increase in potassium conductance but failed to reverse at membrane potentials more negative than the potassium equilibrium potential. GABA excitation involved conductance increases to both sodium and chloride ions while GABA inhibition was a pure chloride event. An attempt was made to estimate the degree of co-operativity of the putative transmitters with their receptors using log-log and Hill plots. The slopes of the line for the log-log plots for acetylcholine excitation and inhibition were 0.88 and 1.1, respectively, suggesting the interaction of one molecule of acetylcholine with the receptor. The slope of the log-log plot for dopamine inhibition was 0.46 while that for serotonin excitation was 0.75. The Hill plots for GABA excitation and inhibition were 1.64 and 1.42, respectively, suggesting that two molecules of GABA are required for receptor activation.

Acetylcholine↗