Search PubMed⌕ Search

Biomedical subjects

D Johnston

Publications and source records attributed to D Johnston.

At least 217 records · Page 12Linked to original sources
PubMed1992

Influence of myectomy, ileal valve, and ileal reservoir on the ecology of the ileum.

Fecal bacteriology, fecal volatile fatty acids, and ileal mucosal morphology were studied in dogs after ileoanal anastomosis alone, ileoanal anastomosis and myectomy, ileoanal anastomosis and myectomy with ileoileal valve, and ileoanal anastomosis with duplicated (J) ileal reservoir. The ratio of anaerobes to aerobes was significantly less in stool from dogs which had undergone ileoanal anastomosis compared with each of the other three groups (P less than 0.01). The numbers of streptococci and clostridia both were significantly less in stool from dogs with ileoanal anastomosis alone than in any other group. The concentrations of fecal acetic and propionic acids were significantly less in dogs with ileoanal anastomosis alone than in any other group (P less than 0.05), but there were no significant differences in the concentrations of fecal butyric or valeric acids. The severity of mucosal inflammation and degree of villous atrophy were more marked in the ileum of J reservoirs (P less than 0.01), and the percentage of stool retained after defecation was greater (P less than 0.05) in dogs with J reservoirs than in any other group. Therefore, the use of myectomy resulted in significant changes in the ecology of the distal ileum although changes typical of pouchitis were seen only in dogs with J reservoirs.

Animals↗
PubMed1992

Induction of B16 melanoma melanogenesis by a serum-free synthetic medium.

Cultured murine B16 melanoma cells normally grow as spindle-shaped cells firmly attached to tissue culture flasks. Pellets obtained from harvested B16 melanoma cells are white to grey in color. When the same cells were grown in synthetic, serum-free AIM V medium, cellular morphology and pigmentation were radically altered. Within 3 days of subculture in AIM V, cells rounded up and grew in clusters in suspension. Melanin content increased to greater than 30 times and tyrosinase activity was found to be 10-50 times higher in cells grown in AIM V medium compared to those cultured in normal medium. A concomitant increase in the level of immunoreactive tyrosinase was also induced. The individual growth factors and hormones present in AIM V medium were examined to determine which component(s) stimulates melanogenesis. Only those cells grown in the presence of 2.5% human albumin were stimulated to synthesize melanin. These findings suggest that albumin, or a component associated with albumin, has a major effect upon the regulation of melanogenesis in these cells.

Animals↗
PubMed1992

Comparison of triplicated (S) and quadruplicated (W) pelvic ileal reservoirs. Studies on manovolumetry, fecal bacteriology, fecal volatile fatty acids, mucosal morphology, and functional results.

Capacity and compliance, efficiency of evacuation, fecal bacteriology, fecal volatile fatty acids, mucosal morphology, and functional outcome were studied in 20 patients with triplicated (S) and 20 patients with quadruplicated (W) reservoirs after ileal pouch-anal anastomosis. Compared with patients with S reservoirs, patients with W reservoirs were found to have greater efficiency of evacuation of radiolabeled synthetic stool [97% (91%-98%) vs. 74% (62%-89%); P less than 0.05], and their reservoirs were more capacious [350 mL (320-400 mL) vs. 228 mL (175-290 mL); P less than 0.01] and compliant [16.0 mL/cm H2O (13.8-19.0 mL/cm H2O) vs. 12.3 mL/cm H2O (7.4-14.6 mL/cm H2O); P less than 0.01]. Effluent from S reservoirs contained significantly greater numbers of bacteroides (P less than 0.05) and concentrations of acetic and propionic acids (P less than 0.05) than effluent from W reservoirs. The degree of mucosal inflammation and villous atrophy in each design of reservoir was not significantly different. The ratio of anaerobes to aerobes in pouch effluent was significantly correlated with the degree of mucosal inflammation (rs = 0.433; P = 0.035). Fecal volatile fatty acids were significantly correlated with the percentage of stool retained after defecation and degree of mucosal inflammation. The frequency of bowel action was significantly less in patients with W reservoirs than in patients with S reservoirs [3.5/day (3-4/day) vs. 6.0/day (4-7/day); P less than 0.01]. The results indicate marked differences between these two ileal reservoir designs.

Adolescent↗
PubMed1992

The enantiomeric resolution of ciprofibrate and related compounds by HPLC using chiral stationary phases.

The attempted chromatographic resolution of the drug ciprofibrate and a range of related compounds, containing the chiral moiety 2,2-dichlorocyclopropylbenzene, using five different chiral stationary phases is described. Aqueous mobile phases were used throughout and the successful separation of nine out of 12 pairs of enantiomers was achieved. Structures remote from the chiral centre were seen to affect chiral recognition.

Cellulose↗
PubMed1992

Synaptically activated increases in Ca2+ concentration in hippocampal CA1 pyramidal cells are primarily due to voltage-gated Ca2+ channels.

Changes in intracellular Ca2+ concentration ([Ca2+]i) in the soma and dendrites of hippocampal CA1 pyramidal neurons were measured using intracellularly injected fura-2. A large component of the [Ca2+]i elevation caused by high frequency stimulation of the Schaffer collaterals was correlated with the Na+ spikes triggered by the excitatory postsynaptic potentials (EPSPs). These spikes were generated in the soma and proximal dendrites and stimulated Ca2+ entry through voltage-gated Ca2+ channels. Suppressing spikes by hyperpolarizing the soma or by injecting QX-314 revealed a smaller nonspike component of Ca2+ entry. A substantial fraction of this component was mediated by the action of the EPSPs on voltage-gated Ca2+ channels, because it persisted in 2-amino-5-phosphonovaleric acid and because it was usually reduced when Ca2+ channel activity was suppressed by hyperpolarization. Ca2+ entry through the N-methyl-D-aspartate receptor channel could not be detected with certainty, perhaps because it was highly localized.

2-Amino-5-phosphonovalerate↗
PubMed1992

Evidence for the indirect utilization of glucose for the synthesis of hepatic glycogen in man.

1. This study was designed to test the hypothesis that three-carbon intermediates can be used in the 'indirect' pathway of glycogen synthesis in human liver (i.e. a route additional to the use of glucose by the 'direct' pathway). 2. After an overnight fast, 13 patients were given an infusion of 20% (w/v) glucose before elective abdominal operation. All received a 2.5 g bolus of 2220 kBq of selectively 3H- and 14C-labelled glucose before removal of a 1 g biopsy of liver. 3H and 14C were determined in purified glycogen as well as in glucose and lactate from samples of peripheral blood. 3. The ratio and specific activities of 3H and 14C in glycogen were found to be significantly lower than those in administered glucose. By calculation, 7-74% of glycogen repletion occurred by indirect pathways and not all of this was from the glucose supplied. 4. This study suggests that the operation of a direct pathway in man is not exclusive and that significant repletion of hepatic glycogen occurs by an indirect route.

Adult↗
PubMed1992

Modified adriamycin-vincristine-dexamethasone (m-VAD) in primary refractory and relapsed plasma cell myeloma: an NCI (Canada) pilot study. The National Cancer Institute of Canada Clinical Trials Group.

The purpose of this single arm phase II study was to test a modified version of the three drug combination vincristine, adriamycin and dexamethasone (m-VAD), in which intravenous vincristine (0.4 mg/d) and adriamycin (9 mg/m2 per day) infusions are administered for only 2 h on days 1-4 of each 28 d cycle, in patients with refractory multiple myeloma. In addition, only two 4 d courses of dexamethasone 40 mg/d was given during each cycle. The entry criteria for 44 patients included plasma cell myeloma and a measurable monoclonal peak, either refractory to initial treatment with melphalan and prednisone, or resistant to melphalan and prednisone after initially responding (resistant relapsed disease, 27 patients). Patients treated previously with chemotherapy other than melphalan and prednisone were excluded. There were no complete responses. Of the 41 evaluable patients who completed at least one course of therapy 11 had a partial response (27%, 95% C.I. 14-40%). The response rates were 19% for primary refractory disease patients, and 32% for those with resistant relapsed disease. The median duration of response was 4 months. The median survival for all 44 patients was 7.6 months (5.5 months for primary refractory patients, and 10 months for relapsed resistant disease patients). Episodes of documented bacterial infection occurred in 12 patients, and 10 patients had minor viral infection. The dexamethasone dose was reduced in 12 patients. The median neutrophil nadir was 1.2 x 10(9)/l, and median platelet nadir was 147 x 10(9)/l. Five deaths were judged as treatment related and occurred during marrow cytopenia. The results of this modified form of VAD are inferior to that reported previously for 4 d continuous infusions of vincristine and doxorubicin. This could be related to either patient selection factors, or to a reduction of the efficacy of the drug combination produced by either the shortened intravenous infusions and/or omission of one 4 d course of dexamethasone.

Aged↗
PubMed1992

Early gastric cancer: 46 cases treated in one surgical department.

Forty six consecutive patients with early gastric cancer were treated between 1970 and 1990. The proportion of cases of early gastric cancer increased significantly (p < 0.01) from 1% of all cases in the first five year period to 15% in the last five year period, because of greater awareness of the condition and more widespread use of endoscopy. There were 33 men and 13 women, of median age 69 years (range 38-86). Most patients (91%) presented with symptoms indistinguishable from those of peptic ulceration. The median duration of symptoms was four months (range 0.1-36 months). All 46 patients were treated surgically. Three patients (6.5%) died after operation and a further 10 (22%) suffered postoperative complications. None of the surviving patients has been lost to follow up and 25 have been followed up for a minimum period of five years. Five year survival by life table analysis was 98%. These findings suggest that in Britain in the 1990s, as in Japan, it may be possible to diagnose an increasing proportion of patients with gastric cancer at a relatively early pathological stage, when most patients can be cured by radical surgical resection with lymphadenectomy.

Adult↗
PubMed1992

NMDA-receptor-independent long-term potentiation.

Although NMDA-R-dep LTP in the hippocampus has received much attention, it is clear that many types of LTP do not involve NMDA receptors. While early studies of NMDA-R-indep LTP were done in invertebrates, an NMDA-R-indep LTP is also seen in at least three excitatory pathways of the hippocampus. There would appear to be quite diverse mechanisms of induction of NMDA-R-indep LTP, although in most cases there is evidence, or at least a suggestion, that Ca2+ is involved. At the hippocampal CA3 MF synapse, activation of voltage-gated Ca2+ channels has been proposed as a trigger for LTP induction, and this may also be the case for certain types of LTP at the SC synapse in CA1 (25, 40). The modulation of both MF LTP and Ca2+ channels by beta-adrenoreceptor and muscarinic agonists suggests that specifically the L-type channel is critical for MF LTP induction. L-type Ca2+ channels may also be involved in NMDA-R-indep LTP at SC synapses (6, 40). Clearly more work is needed to test these possibilities. In addition, it will be interesting to discover whether voltage-gated Ca2+ channels play a role in LTP in other areas of the brain such as the cerebral cortex and amygdala (24).

Animals↗
PubMed1992

Perforated patch-clamp analysis of the passive membrane properties of three classes of hippocampal neurons.

1. Perforated patch-clamp recordings were made from the three major classes of hippocampal neurons in conventional in vitro slices prepared from adult guinea pigs. This technique provided experimental estimates of passive membrane properties (input resistance, RN, and membrane time constant, tau m) determined in the absence of the leak conductance associated with microelectrode impalement or the washout of cytoplasmic constituents associated with conventional whole-cell recordings. 2. To facilitate comparison of our data with previous results and to determine the passive membrane properties under conditions as physiological as possible, recordings were made at the resting potential, in physiological saline, and without any added blockers of voltage-dependent conductances. 3. Membrane-potential responses to current steps were analyzed, and four criteria were used to identify voltage responses that were the least affected by activation of voltage-dependent conductances. tau m was estimated from the slowest component (tau 0) of multiexponential fits of responses deemed passive by these criteria. RN was estimated from the slope of the linear region in the hyperpolarizing direction of the voltage-current relation. 4. It was not possible to measure purely passive membrane properties that were completely independent of membrane potential in any of the three classes of hippocampal neurons. Changing the membrane potential by constant current injection resulted in changes in RN and tau 0; subthreshold depolarization produced an increase, and hyperpolarization a decrease, in both RN and tau 0 for all three classes of hippocampal neurons. 5. Each of the three classes of hippocampal neurons also displayed a depolarizing "sag" during larger hyperpolarizing voltage transients. To evaluate the effect of the conductances underlying this sag on passive membrane properties, 2-5 mM Cs+ was added to the physiological saline. Extracellular Cs+ effectively blocked the sag in all three classes of hippocampal neurons, but the effect of Cs+ on RN, tau 0, and the voltage dependence of these parameters was unique for each class of neurons. 6. CA1 pyramidal neurons had an RN of 104 +/- 10 (SE) M omega and tau 0 of 28 +/- 2 ms at a resting potential of -64 +/- 2 mV (n = 12). RN and tau 0 were larger at more depolarized potentials in these neurons, but the addition of Cs+ to the physiological saline reversed this voltage dependence. 7. CA3 pyramidal neurons had an RN of 135 +/- 8 M omega and tau 0 of 66 +/- 4 ms at a resting potential of -64 +/- 1 mV (n = 14).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Comparison of visual and CAS-200 quantitation of immunocytochemical staining in breast carcinoma samples.

Using the CAS-200 image analysis system, we compared the relationship between semiautomated computer measurements (QIC score) and visual scoring (H score) on 30 breast cancer fine needle aspirates (FNAs) and corresponding tissue specimens stained by the estrogen receptor immunocytochemical assay. These results were compared to the corresponding biochemistry assays for ER. We also investigated whether the computerized system could decrease false-negative staining for ER in 32 cryostat sections. QIC scores were generated using fixed nuclear and antibody thresholds after standardizing the illumination. Computer quantitation was essentially as precise as visual semiquantitation for FNAs: a small but significant correlation was found between tumor ER content and QIC score (r = .504, P less than .02) as compared with H score and ER content (rs = .55, P less than .005). The computerized system did not decrease the false-negative rate in cryostat sections. In all, computerized quantitation was no better than visual analysis of ER staining in these breast carcinomas.

Antibodies, Monoclonal↗
PubMed1991

Effect of cell wall skeleton and monophosphoryl lipid A adjuvant on the immunogenicity of a murine B16 melanoma vaccine.

We examined the effect of a new adjuvant consisting of purified mycobacterial cell wall skeleton (CWS) and monophosphoryl lipid A (MPL) on the immunogenicity of a murine melanoma vaccine. C57BL/6 mice were immunized to partially purified B16 melanoma vaccine given alone or together with different dose levels of adjuvant, or with saline or adjuvant alone. Humoral response, delayed-type hypersensitivity (DTH), in vitro cytotoxicity, and tumor-protective immunity to melanoma were measured following three biweekly immunizations. The adjuvant potentiated the antibody response to some, but not all, melanoma antigens in a dose-dependent fashion. The adjuvant also potentiated cellular immunity as measured by in vitro cytotoxicity assays. No potentiation of tumor-protective immunity was detected. In comparison to Freund's complete adjuvant, cell wall skeleton plus monophosphoryl lipid A (CWS:MPL) induced fewer cutaneous toxic effects and stronger antibody and DTH responses but resulted in no greater in vitro cytotoxicity or tumor-protective immunity. Thus, the adjuvant had a selective and dose-dependent effect on humoral responses to vaccine immunization but did not potentiate a tumor-protective immunity to B16 melanoma.

Adjuvants, Immunologic↗
PubMed1991

N-methyl-D-aspartate receptor activation increases cAMP levels and voltage-gated Ca2+ channel activity in area CA1 of hippocampus.

Tetanic stimulation of the Schaffer collateral inputs into area CA1 of the hippocampus causes N-methyl-D-aspartate (NMDA) receptor activation, an effect that contributes to the induction of long-term potentiation (LTP) in this region. The present studies demonstrate that LTP-inducing tetanic stimulation in rat hippocampal area CA1 elicited increased levels of cAMP. The elevation of cAMP was blocked by the NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid (APV). Bath application of NMDA also resulted in an increase in cAMP in CA1, an effect that was blocked by both APV and removal of extracellular Ca2+. These findings suggest that activation of NMDA receptors elicits a Ca(2+)-dependent increase in cAMP, and taken together with the data from tetanic stimulation, suggest that NMDA-receptor-mediated increases in cAMP could play a role in the induction of LTP in area CA1. One role for cAMP may be to increase Ca2+ influx through voltage-gated Ca2+ channels, as it was observed that application of either 8-bromo-cAMP or NMDA increased the fractional open time of high-threshold Ca2+ channels in CA1 pyramidal cells. Our results raise the possibility that a positive-feedback loop for Ca2+ influx in area CA1 exists. In this model, NMDA receptor-mediated Ca2+ influx leads to an enhancement of further Ca2+ influx via intermediate steps of increased cAMP and subsequent increased voltage-gated Ca2+ channel activity.

2-Amino-5-phosphonovalerate↗
PubMed1991

Correlation between laboratory findings and clinical outcome after restorative proctocolectomy: serial studies in 20 patients with end-to-end pouch-anal anastomosis.

Clinical function and anorectal physiological function were assessed and correlated in 20 patients with ulcerative colitis before restorative proctocolectomy and 3, 7, and 12 months after operation. The entire anal sphincter was preserved by means of a stapled pouch-anal anastomosis. Before operation, the median resting anal pressure was 79 cmH2O (interquartile range 70-89 cmH2O), the rectoanal inhibitory reflex was present in all patients and anorectal 'sampling' was noted in 16 of 20 patients. Three months after operation, resting anal pressure was 68 cmH2O (range 50-87 cmH2O) (P less than 0.001), the reflex was present in only three patients (P less than 0.001) and sampling was observed in one patient. After 7 months, resting anal pressure was 76 cmH2O (range 64-89 cmH2O), the reflex was present in 11 patients and sampling was observed in nine patients. At 12 months, resting anal pressure was 84 cmH2O (range 66-94 cmH2O), the reflex was present in 19 patients and sampling was observed in 17 patients. The compliance and capacity of the reservoir increased significantly. Ability to discriminate flatus from faeces was associated with return of the rectoanal reflex and sampling.

Adaptation, Physiological↗
PubMed1991

Myectomy reduces ileal motility after ileoanal anastomosis.

The hypothesis tested was that myectomy of the distal ileum would produce a long-lasting decrease in ileal motility, and so render single-lumen ileum more suitable for use as a rectal substitute in the course of restorative proctocolectomy, without the need for a pelvic ileal reservoir. Ileal motility, both spontaneous and in response to intraluminal volatile fatty acids (VFA), was studied after proctocolectomy in 25 female adult beagles, at least 6 months after ileoanal anastomosis alone (IAA, n = 6), IAA with myectomy (n = 8), IAA with myectomy and an ileal valve (n = 5) or IAA with a duplicated (J) ileal reservoir (n = 6). VFA were found to stimulate ileal motility significantly in each group. Myectomy significantly reduced the number of ileal contractions (P less than 0.01), the mean amplitude of contractions (P less than 0.05) and the motility index (P less than 0.01). The addition of the valve to myectomy made no significant difference.

Anal Canal↗
PubMed1991

Cellular immune recognition of HLA-G-expressing choriocarcinoma cell line Jeg-3.

Jeg-3 choriocarcinoma cells express class-I MHC HLA-G and low levels of a novel HLA-C product. The functional significance of such novel MHC class-I expression in regard of the cellular immune response has been investigated. Jeg-3 cells are NK-insensitive, but susceptible to LAK cytotoxicity, some of which is mediated by T cells. No Jeg-3-specific CTL or proliferative responses could be generated in allogeneic responder PBMC from several different donors. There was no detectable xenogeneic recognition of Jeg-3 cells even when preceded by in vivo priming. Jeg-3 cells are able to suppress proliferative responses in humans and others species. This is not reproduced by conditioned medium from the Jeg-3 cells, but can be overridden by IL-2. The ability of the Jeg-3 choriocarcinoma (trophoblast) cells to suppress in the MLR may reflect the processes which are shared to enable the survival of the foetus in a semi-allogeneic mother or a tumour in its host. It is not clear whether there is any relationship between the unusual class-I-MHC expression by trophoblast and the putative regulatory properties of the latter.

Animals↗