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Biomedical subjects

D Johnston

Publications and source records attributed to D Johnston.

At least 325 records · Page 18Linked to original sources
PubMed1985

The outcome following sphincter-saving resection and abdominoperineal resection for low rectal cancer.

The introduction of new techniques has enabled more patients with low rectal carcinoma to undergo sphincter-saving resection (SSR). This policy, however, has provoked controversy concerning the adequacy of excision and fear of increased rates of recurrence compared with abdominoperineal resection (APER). We have therefore compared our results of SSR for low and mid-rectal cancers performed between 1978 and mid 1982 with those obtained with APER before this period. One hundred and fifty-nine patients presented with tumours between 3 and 12 cm from the anal verge; 153 (96 per cent) underwent resection, of whom 46 (30 per cent) had disseminated disease. One hundred (68 per cent) underwent SSR, 33 (22 per cent) had an APER and 16 (10 per cent) had a local procedure. Operative mortality was 4 per cent following APER and 7 per cent after SSR (n.s.). Patients were followed for a mean of 4.6 years (range 2-6 years), only four (2.5 per cent) being lost to follow-up. The incidence of recurrence after radical SSR (n = 74) was compared with the historical control group which underwent radical APER, the two groups being matched for Dukes' stage and height of the lesion. After 2 years, local recurrence cumulative rates were 13.6 per cent after SSR and 18.8 per cent after APER. Distant recurrence rates were 14.5 and 20 per cent respectively. Ten patients (13.5 per cent) died of their disease within 2 years of a radical SSR, 15 (15 per cent) after radical APER. Corrected 5-year survival and recurrence rates were similar. Thus, SSR does not appear to carry an increased risk of recurrent disease compared with APER after an equivalent follow-up period.

Adenocarcinoma↗
PubMed1985

Immune recovery following allogeneic bone marrow transplantation.

A total of 144 evaluations of cell surface markers and cellular immune functions were carried out in 57 patients undergoing allogeneic bone marrow transplantation for acute leukemia in remission and relapse and for aplastic anemia. The periods tested were pretransplant, and 1-3, 4-6, 7-12 and more than 12 months posttransplant. The determination consisted of lymphocyte counts; lymphocyte surface marking using OKT3, OKT4, and OKT8 antibodies; and determination of adherent cells, lysozymes and antibody dependent cellular cytotoxicity (ADCC) against chicken red blood cells, human red blood cells, and CEM cells. Natural killer cells were determined against K562 target cells. Lymphoblastic responses were tested after stimulation with pokeweed mitogen (PWM), concanavalin-A (Con-A), and phytohemagglutinin (PHA). We found that the progression in the leukemic state (first remission, second remission, and relapse), prior to transplantation was paralleled by a decrease in T4 lymphocytes (976/microliter +/- 462; 411/microliter +/- 222; 372/microliter +/- 419; P = .04). There was a lack of helper cells and an inverted T4:T8 ratio beyond one year posttransplant independent of graft-versus-host disease status. Lymphocyte functions persisted to be depressed for more than one year. We found a direct correlation of T4 helper cells and an inverse correlation of T8 suppressor cells with lymphoblastic responses to mitogens. It is hoped that the longitudinal evaluations of immune functions after allogeneic bone marrow transplantation, and the characterization of the immune defects seen may lead to better immunorestorative treatments.

Adolescent↗
PubMed1985

Double blind controlled trial of oral vancomycin as adjunctive treatment in acute exacerbations of idiopathic colitis.

A prospective double blind trial of vancomycin vs placebo was undertaken in 40 consecutive adult patients with exacerbation of idiopathic colitis (33 ulcerative colitis, seven Crohn's disease). Vancomycin or placebo (500 mg six hourly) was given for seven days in addition to routine medical therapy. Although there was no significant overall difference in outcome between the two groups, there was a trend towards a reduction in the need for operative intervention in patients with ulcerative colitis treated with vancomycin compared with controls. The efficacy of vancomycin was not attributable to its known action against C difficile, which was not isolated from any of the patients. The data suggest that microbiological factors may play a part in the pathogenesis of ulcerative colitis and that further studies using antimicrobials are desirable.

Adult↗
PubMed1985

Rectification of single GABA-gated chloride channels in adult hippocampal neurons.

The properties of single chloride channels activated by gamma-aminobutyric acid (GABA) were investigated with hippocampal slices from adult guinea pigs. After the slices were treated with proteolytic enzymes, gigaseal recordings were made from excised patches of pyramidal or granule cell membranes. This newly developed preparation permits the application of patch-clamp techniques to the adult mammalian central nervous system. Guinea pig hippocampal slices were prepared in a conventional manner. Once prepared, the slices were treated with two different enzymes for brief periods and gently agitated. Slices generally split apart along the boundaries of the cell body regions, exposing neuronal somata. Standard patch-clamp techniques were used for the gigaseal recordings from excised patches. Solutions for both sides of the patches consisted of symmetrical concentrations of chloride, with all cation channels blocked. GABA at concentrations of 0.5-1.0 microM was added to the solution for the extracellular side of the patches. At transmembrane potentials negative to the chloride reversal potential (0 mV), the conductance through the GABA-gated chloride channels was approximately 20 pS. When the transmembrane potential was changed to positive values, the chloride conductance increased dramatically. For example, at +40 mV the conductance through the GABA-gated channels was almost 40 pS. Ramp-clamp commands were used to measure the current-voltage (I-V) relationship through single open channels. The open-channel I-V curves displayed outward rectification. The relationship between open-channel conductance and voltage could be fitted reasonably well by a single energy-barrier model for the channel, with the higher energy barrier placed near the cytoplasmic side of the membrane (at a fractional distance through the membrane of 0.73).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Epileptiform activity induced by changes in extracellular potassium in hippocampus.

Using extra- and intracellular recording techniques, we investigated the induction and frequency modulation of spontaneous epileptiform activity produced by changes in the concentration of extracellular potassium ([K+]o). This paper describes a quantitative relationship between [K+]o and the frequency of spontaneously occurring epileptiform events. Recordings were made from the CA3 subfield of the rat in vitro hippocampal slice preparation. Intracellular microelectrodes were filled with 2 M Cs2SO4 and connected to a 3-kHz, time-share, single-electrode current- and voltage-clamp device. The frequency of spontaneous epileptiform (interictal) discharges was determined from extracellular recordings as a function of [K+]o. Current- and voltage-clamp techniques were used to characterize the intracellular correlate of these epileptiform events. The frequency of bicuculline-induced spontaneous epileptiform discharges was dependent on [K+]o. Below 4 mM [K+]o, spontaneous discharges occurred sporadically in the presence of 10 microM bicuculline. Increasing [K+]o from 5 to 10 mM caused a fivefold increase in the rate of spontaneous discharges. Spontaneous epileptiform discharges also occurred in the absence of bicuculline when [K+]o was increased above 6.5 mM. The rate of these discharges was dependent on [K+]o in much the same way as the discharges induced by bicuculline. For any given [K+]o concentration greater than 6.5 mM, however, the resultant discharge rate was faster than that obtained when bicuculline was present in the bathing solution. Simultaneous intra- and extracellular recordings revealed that the spontaneous high-[K+]o-induced interictal discharge was accompanied by a large depolarization of the membrane potential that appeared similar to the paroxysmal depolarizing shift (PDS) seen with other convulsants. The intracellularly recorded event fulfilled the criteria for a synaptically mediated PDS. The waveform of the PDS was complex and dependent on the membrane potential. When the membrane potential was held at 0 mV, spontaneously occurring hyperpolarizing potentials were noted during the inter-PDS interval. These events were blocked by picrotoxin or bicuculline and were probably spontaneous inhibitory postsynaptic potentials. The complexity of the PDS waveform suggested that more than one synaptic conductance was involved in the generation of the PDS. The mean measured reversal potential of the depolarizing phase was -10.7 mV. Voltage-clamp techniques were used to measure the conductance underlying the depolarizing phase of the high-[K+]o-induced PDS. The mean measured conductance was 51.5 nS, with a reversal potential of -7.9 mV.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

Effect of tunicamycin on release of macromolecules and tumor antigens by human melanoma cells.

Tunicamycin, an inhibitor of glycosylation, was used to examine whether glycosylation is required for shedding of tumor antigens and other macromolecules by human melanoma cells. Cellular proteins were labeled with [35S]methionine, glycoproteins with [14C]glucosamine, and external surface components with 125I by the lactoperoxidase method; 0.5 and 2.5 microgram tunicamycin/ml effectively inhibited glycosylation without significantly reducing protein synthesis. We found that release of labeled macromolecules in the presence or absence of tunicamycin was similar. Tunicamycin-treated cells released 10.2% of [35S]methionine, 29.8% of [14C]glucosamine, and 57.2% of 125I-labeled macromolecules in 24 h compared to 5.5, 14.9, and 50.8%, respectively, for untreated control cells; 62.5% of the radioactivity associated with cell-surface melanoma-associated antigens defined by specific antiserum were released in 24 h as opposed to 50.4% by untreated cells. These results indicate that release of many cellular proteins, including glycoproteins, external surface proteins, and some melanoma-associated antigens, does not require glycosylation.

Antigens, Neoplasm↗
PubMed1985

Heterogeneity of non-Hodgkin's lymphoma probed by nucleic acid cytometry.

Flow cytometric analyses of cellular DNA, RNA, and double-stranded RNA content were performed on lymph nodes and extranodal tissue from 177 patients with non-Hodgkin's lymphoma. With increasing histologic grade, a higher incidence of aneuploidy, higher proliferative activity, and higher total and double-stranded RNA content were found. Despite considerable cytometric heterogeneity within histologic grades and morphologic subdivisions, conformity between cytometric and morphologic classifications was observed in 85% of cases. Among intermediate-grade and high-grade lymphomas, increased proliferative activity and diploidy were associated with more frequent responses to treatment. Thus, nucleic acid-derived parameters relate to morphologic subtypes and permit an objective approach to lymphoma classification based on ploidy, proliferation, and RNA characteristics that also had prognostic implications.

Aneuploidy↗
PubMed1984

Frequency-dependent noradrenergic modulation of long-term potentiation in the hippocampus.

Norepinephrine, briefly superfused during high-frequency stimulation of the mossy fibers in the rat hippocampal slice in vitro, produced a reversible increase in the magnitude, duration, and probability of induction of long-term synaptic potentiation in the CA3 subfield. Similar results were obtained with isoproterenol, whereas propranolol or timolol reversibly blocked long-term potentiation. Norepinephrine had little apparent effect on responses obtained during low-frequency stimulation of the mossy fibers. These data suggest that norepinephrine can mediate long-lasting, frequency-dependent modulation of synaptic transmission in the mammalian brain. Furthermore, the results suggest a plausible mechanism for some of the known associative interactions between synaptic inputs to hippocampal neurons.

Adrenergic Fibers↗
PubMed1984

The synaptic nature of the paroxysmal depolarizing shift in hippocampal neurons.

It is well known that there are two types of neuronal burst discharges: endogenous and network driven. Frequently, the two types are similar in appearance. But careful analysis has shown them to be quite different mechanistically and to share few common properties. Endogenous bursts are a common feature of certain hippocampal neurons. Application of a convulsant agent to a hippocampal slice, however, results in the appearance of interictal discharges whose intracellular correlate is the paroxysmal depolarizing shift (PDS). In contrast to the normal endogenous burst, the PDS is a network-driven burst. It has been proposed that the underlying depolarization of the PDS constitutes a large, compound, excitatory synaptic potential. In support of this hypothesis, recent voltage clamp experiments have demonstrated that a large synaptic conductance underlies the PDS. In this report we review those experiments and others that have established the synaptic nature of epileptiform activity in the hippocampus.

Animals↗
PubMed1984

Survival and recurrence after sphincter saving resection and abdominoperineal resection for carcinoma of the middle third of the rectum.

Sphincter saving resections (SSR) are being performed with increasing frequency in patients with carcinoma of the lower two-thirds of the rectum. It is not clear, however, whether local and distant recurrence and long term survival after these operations will be comparable with those following abdominoperineal resection (APER). In this retrospective study, we have compared survival and recurrence in patients with carcinoma of the middle third of the rectum (7.5-12 cm from the anal verge) who were treated by APER (n = 83) or low SSR (n = 71). There was a higher proportion of men in the APER group, the mean age was higher and APER patients had tumours with less favourable pathological features. To minimize bias between the two groups, patients with tumours with similar pathological characteristics were compared. The overall cancer specific 5-year survival rate after SSR was 74 per cent and after APER was 62 per cent; the overall recurrence rates were 27 per cent after SSR and 41 per cent after APER; the incidence of local recurrence was 11 per cent after SSR and 8 per cent after APER. In these comparisons and when the patients' tumours were matched for one or two pathological variables, no significant difference was found between the two groups. These results suggest that patients with carcinoma of the middle third of the rectum who are treated by SSR will fare as well as patients who are treated by APER, with respect both to recurrence and to survival. A prospective controlled trial, however, is required to provide final proof of these points.

Aged↗
PubMed1984

Mechanism of autodegradation of cell-surface macromolecules shed by human melanoma cells.

The mechanism of autodegradation of cell-surface macromolecules shed by human melanoma cells was studied by incubating radio-iodinated shed macromolecules with unlabeled sister cells and measuring the appearance of acid-soluble radioactivity. After a preliminary latent period of 1-3 h, degradation continually increased up to 24 h and was concentration-dependent. By contrast, binding to cells was very rapid reaching half-maximal value within 15 min. Autodegradation was markedly reduced (44-82%) by pharmacological agents which interfere with endocytosis or lysosomal enzyme activity, including drugs which inhibit receptor migration into coated pits (dansylcadaverine), endocytosis and intracellular transport (colchicine, cytochalasin B, and monensin), and the activity of lysosomal enzymes (chloroquine, ammonium chloride, leupeptin). Degradation was almost totally suppressed (95%) at 4 degrees C. These data suggest that surface macromolecules shed by melanoma cells are autodegraded in part by re-uptake into melanoma cells followed by degradation in lysosomes.

Ammonium Chloride↗
PubMed1984

Bile reflux and degree of gastritis in patients with gastric ulcer: before and after operation.

The incidence and degree of bile reflux and gastritis has been measured in normal subjects and in patients with gastric ulcer before operation and after treatment by highly selective vagotomy with ulcer excision, Billroth 1 partial gastrectomy, and truncal vagotomy and drainage. Before operation patients had significantly higher (P less than 0.001) bile acid concentrations in the stomach than normal subjects. Treatment by highly selective vagotomy resulted in significantly lower bile acid concentrations than those before operation and those found after Billroth 1 partial gastrectomy. Antral and body gastritis was significantly less in normal subjects than in the preoperative and all postoperative groups. There was no significant difference in antral or body gastritis between the preoperative gastric ulcer patients and the patients after any of the surgical procedures despite the significant differences in bile acids. Though highly selective vagotomy in the treatment of gastric ulcer results in a reduction in duodenogastric reflux of bile there is no improvement in the gastritis that is present.

Adult↗
PubMed1984

The true predictive value of the human tumor stem cell assay: does a workable assay select for treatment responders?

In practice, the human tumor clonogenic assay is workable for less than half of the patient population to which it is applied, since the remainder of the specimens fail to produce sufficient numbers of colonies. Thereby a bias may be introduced which could result in a false predictive value positive of the test. It is therefore necessary to compare the responses to treatment of patients whose tumors could be assayed in vitro to those whose tumors failed to grow adequately, to assure that the prevalence of treatment responders has not changed within the group of patients for which the assay worked. From an analysis of the treatment response of 70 patients with stage III and IV ovarian carcinomas and 70 patients with stage IV breast cancer, no selection bias did occur and no preferential in vitro growth of tumor samples from patients with treatment response was found.

Antineoplastic Combined Chemotherapy Protocols↗