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Biomedical subjects

K Morgan

Publications and source records attributed to K Morgan.

At least 325 records · Page 18Linked to original sources

A passive sodium transport inhibitory factor (inhibitin) released from leukaemic promyelocytes in culture.

Previous studies have shown that myeloid leukaemic blast cells contain a heat stable factor which inhibits bidirectional sodium transport in normal erythrocytes. This study was undertaken to establish whether leukaemic promyelocytes in culture secrete this factor. Two cell-lines of leukaemic promyelocytes (HL-60 and JR) were grown and culture media from both reduced significantly the ouabain-insensitive sodium efflux rate constant, whereas conditioned culture medium (incubated like the cells in culture) had no inhibitory effect. Promyelocyte extract reduced significantly (P less than 0.01) the total sodium efflux rate constant from 0.393 +/- 0.030 (SD) to 0.311 +/- 0.060, and ouabain-insensitive efflux rate constant from 0.131 +/- 0.008 to 0.079 +/- 0.009 (P less than 0.001). The inhibitory factor was heat stable (80 degrees C for 30 min) and it inhibited sodium efflux through a pathway which was not inhibited by ouabain or frusemide. These studies suggest that leukaemic promyelocytes secrete the previously identified passive sodium transport inhibitory factor.

Biological Transport, Active↗

Reliability of a test of cardiovascular fitness.

The reliability of a simple, cheap and portable test for estimating cardio-respiratory fitness (the Canadian Home Fitness Test) was assessed by the test/retest method. Substantial intra-subject variation was demonstrated which was between 49% and 85% of the observed group variation. At the 95% confidence level, this intra-subject variation represented an error of between 19.2% and 25.9% on the key measurement (mean post-exercise heart rate) depending on the degree of work done. The probable reason for this poor repeatability was observer error and this is discussed. It is concluded that this test is not suitable for either clinical or population research and alternative methods, such as historical review of physical activity, may be more useful.

Adult↗

Diffuse endobronchial polyposis following a titanium tetrachloride inhalation injury.

We report a case of diffuse endobronchial polyps contributing to continued respiratory failure in a patient 5 wk after titanium tetrachloride inhalation injury. After the institution of corticosteroid therapy, the total number and size of remaining polyps were markedly reduced at which time the subject was successfully weaned from the ventilator. Follow-up bronchoscopy at 2 months, 5 months, and 1 yr postinjury revealed gradual but complete resolution of all polyps accompanied by improvement in the patient's obstructive airways disease. This delayed complication of inhalation injury has been previously reported as a complication of thermal respiratory injury, and may be an important contributing factor in prolonged or late respiratory failure in burn patients.

Adrenal Cortex Hormones↗

Isolation of a sodium transport inhibitory factor, inhibitin, from cultured leukemic promyelocytes.

Previous studies have shown that leukemic blood contains a factor that has an inhibitory effect on bidirectional sodium transport in erythrocytes. This study was designed to isolate this factor from cultured leukemic promyelocytes. An extract from the promyelocytes reduced significantly (P less than 0.001) the ouabain-insensitive sodium efflux rate, from 0.096 +/- 0.009 to 0.056 +/- 0.003 SD. Using the inhibition of ouabain-insensitive sodium transport in erythrocytes as an assay to identify the factor, we ran the crude promyelocyte extract through Sephadex G-25 and G-10, with an intermediate ion-exchange step on DE-32, and finally subjected the active fraction to reverse-phase high-performance liquid chromatography. The specific inhibitory activity of the final fraction was 180-fold higher than that of the crude promyelocyte extract. The inhibitory activity could be destroyed by acid hydrolysis and by enzymatic digestion with several proteases but not by heating at 80 degrees C for 30 min; these characteristics suggest that the active factor, called inhibitin, is a peptide. Inhibitin is released by immature myeloid cells but not by differentiated white cells or by leukemic lymphocytes. It has no effect on potassium influx but inhibits sodium/sodium exchange in erythrocytes.

Amino Acids↗

Release of an active sodium transport inhibitor (ASTI) from rat hypothalamic cells in culture.

To investigate the hypothesis whether the hypothalamus releases an active (ouabain-sensitive) sodium transport inhibitor, we cultured hypothalamic and cortical cells from day 17 fetal rats. Culture media from hypothalamic cells reduced the total erythrocyte sodium efflux rate constant from 0.487 +/- (SE) 0.014 to 0.408 +/- 0.013 (P less than 0.001), and the ouabain-sensitive rate constant from 0.305 +/- 0.015 to 0.240 +/- 0.016 (P less than 0.01). Hypothalamic media also showed a dose-dependent displacement of [3H]-ouabain-binding to erythrocyte membranes. Neither cortical nor conditioned media (incubated without cells) had any effect. Various well-characterized hormones of hypothalamic origin failed to inhibit sodium efflux rate constant. These studies demonstrate that fetal rat hypothalamic cells contain and release a factor which inhibits sodium transport in human erythrocytes.

Animals↗

Native type II collagen-induced arthritis in the rat. Studies of the humoral response to collagen at the cellular level.

In rats immunized with native type II collagen the number of lymphocytes secreting anti-type II collagen antibodies was enumerated in the lymph nodes using the direct hemolytic plaque assay. Arthritic rats had more lymphocytes, more plaque forming cells to native type II collagen and higher levels of serum IgM antibody to native type II collagen than nonarthritic rats. In vitro incubation of lymphocytes with native type II collagen before the plaque assay greatly increased the number of plaque forming cells from arthritic rats but not from nonarthritic rats. These findings suggest that arthritic rats had greater reactivity to native type II collagen and were less able to control the humoral response to collagen than were nonarthritic rats.

Animals↗

Patterns of cancer in geographic and endogamous subdivisions of the Hutterite Brethren of Canada.

The Hutterite Brethren comprise a religious isolate and live on communal agricultural farms (colonies) in North America. In 1976 there were approximately 15,000 Canadian Brethren living in 179 colonies of the three endogamous subdivisions, the Dariusleut, Lehrerleut, and Schmiedeleut. Dariusleut and Lehrerleut colonies are located in both Alberta and Saskatchewan, and the Schmiedeleut are in Manitoba. Brethren were identified on population-based cancer registries of the three Prairie Provinces and among death registrations in the vital statistics of Alberta and Saskatchewan. The method of ascertainment was by a search for the 15 contemporary surnames and verification by address. 89 male and 91 female Brethren were identified who had cancer during the period, 1956--1975. The numbers of observed cancers were less than expected from provincial incidence rates for males and females in each province. The largest deficits were for female Brethren in Manitoba and Saskatchewan. There is a marked deficiency of cancer of the uterine cervix among female Brethren. In males there is a significant deficit of lung cancer. The Hutterite way of life contributes to a low risk for cancers of smoking-associated sites. However, there is evidence that male Brethren in Alberta may be at relatively increased risk for stomach cancer and leukemias. The site distribution patterns of cancers among the three endogamous leut are similar.

Canada↗

Sedative-hypnotic drug use and ageing.

Behavioural disadvantages associated with the use of sedative-hypnotic drugs in the elderly are considered in relation to four aspects of drug usage reported in the epidemiological literature between 1960 and 1982, viz. (1) the prevalence of drug usage; (2) the type of drug, and the dose used; (3) the typical duration of usage; and (4) the typical frequency of usage. Demographic characteristics of elderly hypnotic users are also examined. The pattern and prevalence of usage over the past 20 yr show many consistent features. In particular, the prevalence of drug usage among the elderly has remained relatively high, especially within institutional settings. Sex differences in the prevalence of sleeping drug usage, frequently reported for elderly populations, appear to be related to bereavement, health status, and age. The advanced age of hypnotic drug users, however, does not appear to influence the choice of hypnotic drug prescribed. Moreover, drugs and dosages typically prescribed, and the duration and frequency of use typically reported, do not reflect a consistent approach to the problem of minimizing some of the adverse behavioural consequences associated with sedative-hypnotic drug use in the elderly.

Aged↗

Physicochemical speciation of toxic fractions of wastewaters.

A physicochemical speciation scheme in tandem with bioassays identified the toxic fractions of the wastewater from a base metal refining and fertilizer complex. The toxic fractions were the leachates from suspended solids, purgeables, and bound metals of the dissolved fraction. Most of the metals were bound to macrosolutes of Mr greater than 30,000 and exchangeable by cation- and weak anion-exchange resins. In contrast, total chromium and surfactants were bound strongly to microsolutes of Mr less than 1500, removable only by strong anion-exchange resin.

Animals↗

Trazodone enhances sleep in subjective quality but not in objective duration.

Nine volunteer poor sleepers, of mean age 61 years, took trazodone 150 mg nightly for 3 weeks, preceded by 2 weeks and followed by 1 week of matching blanks, in order to examine the effects of electrophysiologically-recorded and subjectively-rated sleep. The second of the initial weeks of matching blanks served as a baseline week. In the subjective ratings, sleep improved in quality on trazodone, significantly so in the first and second weeks of intake, though with significant rebound insomnia on the second withdrawal night. Trazodone halved the frequency of arousals interrupting sleep, and it reduced the time spent in stage 1 (drowsiness). It increased the duration of slow-wave sleep (stages 3 + 4), with a negative rebound following withdrawal. It reduced the time spent in REM sleep, with a rebound above baseline levels after withdrawal. Trazodone did not change total sleep duration, nor the time required to fall asleep. The effects of trazodone were sustained or became enhanced during the period of intake. They persisted for over 24 h after the last dose, and rebound effects were maximal on the second withdrawal night.

Aged↗

Patterns of neuroleptic use among the institutionalised elderly.

A survey was conducted of neuroleptic use amongst the residents of Local Authority homes for the elderly, and elderly patients in geriatric, psychogeriatric and general hospital wards in one of the London boroughs. Some 13% of the residents and patients surveyed were found to have received neuroleptics in the 24 h preceding the survey. Marked variation between homes and between wards and hospitals was observed, although for the sample overall associations were observed between disturbed behaviour and mood and the likelihood of receiving neuroleptics. Issues regarding the use of neuroleptics in the non-psychotic elderly are discussed.

Activities of Daily Living↗

Native type II collagen-induced arthritis in the rat. III. Relationship between the cellular immune response to native type II collagen and arthritis.

The relationship between cell mediated immunity to collagen and arthritis was studied with lymphocytes from arthritic and nonarthritic rats after immunisation with native bovine type II collagen. With the in-vivo radiometric ear assay arthritic rats gave a significantly higher response to native type II collagen than did nonarthritic rats. However, there was an overlap of values, and some arthritic rats gave no response to collagen even on the day of onset of arthritis. There was no difference in the response of lymphocytes from arthritic and nonarthritic rats with in-vitro transformation to native type II collagen, responses being found in both groups. All rats which developed arthritis had serum antibodies to native type II collagen, but not all responded to the tests for cell mediated immunity. These findings suggest that antibodies to collagen are more associated with the development of arthritis than is cell mediated immunity to collagen.

Animals↗

Localisation of collagen types and fibronectin in cartilage by immunofluorescence.

Collagens type I, II, III, IV, and V and the minor cartilage collagens, 1 alpha 2 alpha 3 alpha, C-PS 1, and C-PS 2, were purified, antibodies raised, and then used in immunofluorescence studies on bovine nasal cartilage (BNC). Punctate localisation was seen with the type II antibody. However, pretreatment of sections with hyaluronidase to remove the proteoglycan resulted in diffuse staining over all the section with this antibody. Antibodies to 1 alpha 2 alpha 3 alpha, C-PS 1, and C-PS 2 collagens gave no staining on untreated BNC sections, but after treatment with hyaluronidase all 3 antibodies showed as a diffuse 'halo' round each chondrocyte lacuna. Anti-type I, anti-type III, and anti-type IV collagen antibodies did not stain untreated or enzyme treated BNC. Type V collagen antibodies gave a bright ring in the pericellular region of the lacunae of hyaluronidase-treated BNC. This was unexpected, as we could not detect type V collagen biochemically in the same cartilage. Anti-fibronectin antibodies stained areas distant from the chondrocytes, these areas being distinct from those stained by 1 alpha 2 alpha 3 alpha and C-PS antibodies, suggesting that fibronectin is not associated with these collagens in BNC. These results suggest that different collagen types may have different locations within the cartilage matrix, that proteoglycans may inhibit antibody association with collagen, and that fibronectin is normally not associated with all types of collagen.

Animals↗

1 Alpha 2 alpha 3 alpha collagen is arthritogenic.

Native 1 alpha 2 alpha 3 alpha collagen (500 micrograms per rat) was both immunogenic and arthritogenic in Alderley Park rats (46% developed arthritis) but only immunogenic in Sprague-Dawley rats. Conversely, native type II collagen (500 micrograms per rat) was immunogenic and arthritogenic in both strains (64% arthritic in Alderley Park strain, 57% arthritic in Sprague-Dawley strain). The inflammatory polyarthritis induced by 1 alpha 2 alpha 3 alpha collagen was similar to that produced by native type II collagen in clinical appearance, time of onset, and histology. Antibodies raised to native bovine type II collagen cross-reacted with native 1 alpha 2 alpha 3 alpha collagen and vice versa. Thus the minor collagen component of cartilage, the 1 alpha 2 alpha 3 alpha collagen, as well as the major collagen component, type II collagen, are immunogenic and arthritogenic in the rat, with strain differences.

Animals↗

The influence of polycyclic hydrocarbons on the activity of NAD(P)H-dehydrogenating enzymes in rat thymus. A biochemical and histochemical study.

The action of benzo(a)pyrene, 3-methylcholanthrene and 7,12-dimethylbenzo(a)anthracene in the activity of the rat thymus D-T diaphorase (EC 1.6.99.2) and the NAD(P)H cytochrome C (EC 1.6.99.3) reductases of particulate fractions were studied in intact and adrenalectomized animals. These polycyclic hydrocarbons increased severalfold the activity of the D-T diaphorase in intact and adrenalectomized animals. The activities of the particulate enzymes were not affected by the carcinogens. Dicumarol suppresses the inducing effects of benzo(a)pyrene and adrenalectomy does not influence the inducing effects of benzo(a)pyrene and 3-methylcholanthrene. The histological distribution of the enzyme NAD(P)H-nitroblue tetrazolium reductase was studied and a marked increase in its activity in lymphocytes, macrophages and epithelial cells was found after the administration of the carcinogens.

9,10-Dimethyl-1,2-benzanthracene↗

Role of charged groups in factor XI/XIa activity.

To elucidate the role of charged groups in expression of factor XI coagulant activity, the charged groups of purified human blood coagulation factor XI/XIa containing 125I-XI/XIa were derivatized: free amino groups by succinylation, guanido groups of arginine by reaction with phenylglyoxal hydrate, and free carboxyl groups by reaction with ethylenediamine. The modified proteins were tested for: 1) ability to adsorb to glass, 2) ability to be cleaved by trypsin or factor XII-high molecular weight kininogen, 3) coagulant activity. The amino group-modified factor XI had a significantly decreased ability to bind to glass; modification of arginine or carboxyl groups did not affect adsorption. Trypsin cleaved factor XI with modified free amino, guanido, or carboxyl groups. Factor XII-high molecular weight kininogen could cleave only the arginine-modified factor XI. Amino group-modified factor XI and carboxyl group-modified factor XI lost all their factor XI assay activity, whereas arginine-modified factor XI retained 50% of the original activity. Amino group-modified factor XI could not be activated by trypsin, but arginine-modified and carboxyl group-modified factor XI could be activated by trypsin to 50% of the original activity. Succinylation of the amino groups of factor XIa destroyed all its factor XIa activity. Arginine-modified and carboxyl group-modified factor XIa retained 50% of their factor XIa activity. We conclude that epsilon-amino groups are essential for adsorption; activation by factor XII-high molecular weight kininogen requires free amino and carboxyl but not guanido groups; free amino, carboxyl, and guanido groups in factor XIa all appear to be critical for interaction of factor XIa with factor IX.

Blood Coagulation↗