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Biomedical subjects

K Morgan

Publications and source records attributed to K Morgan.

At least 271 records · Page 15Linked to original sources
PubMed1989

Genealogical analysis of cystic fibrosis families and chromosome 7q RFLP haplotypes in the Hutterite Brethren.

In the 100-year period 1880-1980 the Hutterite population increased from about 442 to 23,000 individuals in North America. There are three endogamous subdivisions in this Caucasian genetic isolate. A total of 11 cystic fibrosis (CF) families from Canada and the United States were investigated, including at least two families from each of the three subdivisions, the Dariusleut, Lehrerleut, and Schmiedeleut. A study of RFLPs for the loci D7S8, D7S23, MET, and D7S18 (also called D7S16) in the region of the CF gene in 10 families shows considerable genetic variability. There were three different extended CF gene-region haplotypes on CF chromosomes (CF haplotypes), and there were 13 different extended CF gene-region haplotypes on normal chromosomes (normal haplotypes). The three CF haplotypes have different D7S23 and MET haplotypes. Parents who have the same CF haplotype are, on the average, more closely related than parents who have different haplotypes, but only within the same subdivision. A marriage node graph of 11 families illustrates the complexity of Hutterite genealogies. The frequency distribution of CF haplotypes in the Hutterite sample differs notably from those of larger agglomerates of family data from collaborative studies, with respect to D7S8, MET haplotypes, and D7S23 haplotypes. We propose that there were at least three CF carriers among the founders of the Hutterite population and that copies of a particular CF haplotype in current individuals are identical by descent. The alternative that one or more genetically distinguishable CF haplotypes resulted from recombination since the founding of the population is considered to be less likely.

Canada↗
PubMed1988

Familial predisposition to Wilms' tumour does not map to the short arm of chromosome 11.

Wilms' tumour of the kidney usually occurs sporadically, but can also segregate as an autosomal dominant trait with incomplete penetrance. Patients with the WAGR syndrome of aniridia, genitourinary anomalies, mental retardation and high risk of Wilms' tumour have overlapping deletions of chromosome 11p13 which has suggested a possible location for a Wilms' tumour locus. Moreover, many sporadic tumours have lost a portion of chromosome 11p. A second locus at 11p15 is implicated by association of the tumour with the Wiedemann-Beckwith syndrome and by tumour-specific losses of chromosome 11 confined to 11p15. Here we report a multipoint linkage analysis of a family segregating for Wilms' tumour, using polymorphic DNA markers mapped to chromosome 11p. The results exclude the predisposing mutation from both locations. In a second family, the 11p15 alleles lost in the tumour were derived from the affected parent, thus precluding this region as the location of the inherited mutation. These findings imply an aetiological heterogeneity for Wilms' tumour and raise questions concerning the general applicability of the carcinogenesis model that has been useful in the understanding of retinoblastoma.

Chromosomes, Human, Pair 11↗
PubMed1988

Prevalence, frequency, and duration of hypnotic drug use among the elderly living at home.

Details of consumption of hypnotic drugs derived from a nationally representative sample of elderly people were analysed in terms of the prevalence, duration, and likely frequency of use. Of 1020 randomly selected subjects aged 65 and over 16% (166) reported using (mainly benzodiazepine) hypnotic drugs, and of these 89% reported having taken such a drug the night before the interview. Most of these users (73%) had been taking hypnotic drugs for more than one year, with 25% reporting drug use for more than 10 years. These results suggest that for most elderly users of hypnotic drugs, patterns of consumption encourage the development of cumulative effects and benzodiazepine dependence.

Aged↗
PubMed1988

Characterization of Na+ transport in normal human fibroblasts and neoplastic H.Ep.2 cells and the role of inhibitin.

Na+ transport was characterized in normal human fibroblasts and neoplastic H.Ep.2 cells in order to investigate the role of the endogenous peptidic factor 'inhibitin' that is secreted by a variety of neoplastic cells (including H.Ep.2) and inhibits Na+/Na+ exchange in human erythrocytes. Although active (Na+,K+-ATPase mediated) Na+ fluxes were similar in the two cell types, H.Ep.2 cells maintained higher intracellular Na+ concentration (26 mM) compared to fibroblasts (12 mM). An analysis of passive Na+ fluxes showed a difference in the handling of Na+ via ouabain and bumetanide-insensitive transport between the two cell types: H.Ep.2 cells achieved net Na+ influx via an amiloride-sensitive pathway that was only demonstrated in fibroblasts when 10% fetal calf serum (FCS) was present. Kinetic studies were undertaken to investigate the interaction between Na+ flux via Na+/H+ and Na+/Na+ exchanges. For this purpose, an outwardly directed Na+ gradient was created by loading the cells with Na+ (Nai greater than 100 mM) to activate the reverse functioning of Na+/H+ exchange (i.e., Na+out H+in). The rates of ouabain- and bumetanide-insensitive Na+ efflux were measured over a range of extracellular Na+ concentrations (Na+o 14-140 mM). In the presence of 10% FCS, the two cell types showed different responses: in fibroblasts the Na+ efflux rate showed an inverse correlation with extracellular Na+ concentration, while H.Ep.2 cells significantly increased their rate of Na+ efflux as extracellular Na+ concentration increased. So although the thermodynamic force would direct net Na+ efflux when Na+i greater than Na+o, H.Ep.2 cells were under kinetic control to perform Na+/Na+ exchange. When exogenous inhibitin was tested on fibroblasts, the steady-state intracellular Na+ concentration increased from 14 to 19 mM (p less than 0.01). In Na+-loaded fibroblasts, serum-stimulated Na+ efflux was partially inhibitin sensitive and the maximal inhibitory effect was seen when extracellular Na+ concentration was 14 mM and presumably the Na+/H+ exchanger operating in the reverse mode. This study demonstrated that, in contrast to fibroblasts, H.Ep.2 cells have a modified Na+/H+ exchange system whereby it acts in the Na+in H+out mode without exogenous growth factor activation and resists functioning in the reversed mode. It is proposed that inhibitin is the endogenous modifier of this transport system in H.Ep.2 cells with the result that H.Ep.2 cells maintain a higher concentration of intracellular Na+ compared to fibroblasts.

Biological Transport↗
PubMed1988

Calcium retention and increased vascular reactivity caused by a hypothalamic sodium transport inhibitor.

1. Using a previously established method of isolating an active-sodium-transport inhibitor (ASTI) from hypothalamic cell culture medium, the inhibitor was isolated and partially purified from sequential passages through Sephadex G-25 and h.p.l.c., and its effects on de-endothelialized rabbit aortic strips were investigated. 2. ASTI caused a cumulative concentration-dependent increase in tension which reversed slowly after wash, and the wash showed an identical effect on fresh strips. 3. Ouabain, used as a control, also caused a concentration-dependent increase in tension which reached a plateau at a concentration of 10 mmol/l. Both ouabain and ASTI caused a significant potentiation of the vasoconstrictor effect of noradrenaline at concentrations of 1 nmol/l-0.1 mmol/l. 4. Both ASTI and ouabain caused a significantly greater (P less than 0.01) calcium retention than control medium in aortic strips. 5. Incubation of ASTI with prolidase, chymotrypsin and carboxypeptidase A destroyed the vasoconstrictor effects as well as its inhibitory effects on sodium, potassium-dependent adenosine triphosphatase and sodium efflux from erythrocytes, but leucine aminopeptidase was ineffective. 6. These studies suggest that hypothalamic cells in culture release a peptidic inhibitor of active sodium transport which increases vascular reactivity, potentiates vasoconstrictor effects of noradrenaline and causes calcium retention.

Animals↗
PubMed1988

Characteristics of subjective insomnia in the elderly living at home.

Profiles of sleeping habits, subjective sleep quality, and mental and physical well-being were obtained from 1023 elderly individuals randomly sampled from the Nottinghamshire Family Practitioner Committee's records. Subjective insomnia at least 'sometimes' was reported by 37.9% of the sample. Discriminant analysis of selected health and demographic variables indicated that symptoms of anxiety, sex and self-ratings of health were the factors most influential in predicting reports of problem sleep. Thus, respondents classified as subjective insomniacs tended to have significantly higher anxiety scores, to be women, and to rate their health as below average. Relative to the non-insomniac respondents, those complaining of sleep problems also perceived their sleep latency as longer, and their total sleep as shorter. These results emphasize that, in addition to apparently 'normal' age-related changes in the structure of sleep, subjective insomnia in old age may often be mediated by the physical and psychological disorders which can accompany ageing.

Aged↗
PubMed1988

Falls by elderly people at home: prevalence and associated factors.

Of 1042 individuals aged 65 years and over who were successfully interviewed in a community survey of health and physical activity, 35% (n = 356) reported one or more falls in the preceding year. Although the overall ratio of female fallers to male fallers was 2.7:1, this ratio approached unity with advancing age. Mobility was significantly impaired in those reporting falls. Asked to provide a reason for their falls, 53% reported tripping, 8% dizziness and 6% reported blackouts. A further 19% were unable to give a reason. There was no association between falls and the use of diuretics, antihypertensives or tranquilizers, but a significant association between falls and the use of hypnotics and antidepressants was found. Discriminant analysis of selected medical and anthropometric variables indicated that handgrip strength in the dominant hand and reported symptoms of arthritis, giddiness and foot difficulties were most influential in predicting reports of recent falls.

Accidental Falls↗
PubMed1988

Antibodies to type II and XI collagens: evidence for the formation of antigen specific as well as cross reacting antibodies in patients with rheumatoid arthritis.

Antigen specific and cross reacting antibodies to native and denatured types II and XI collagen were detected in the sera of rats immunised with either of these antigens. The antibodies from rats immunised with type XI collagen initially showed the strongest binding to the alpha 2(XI) chain of type XI collagen but later binding to the alpha 3(XI) chain was seen. Sera from patients with rheumatoid arthritis had antibodies that bound to both type II and XI collagens. Immunoblotting studies showed that most patients had antibodies which bound to the alpha 1(II) chain of type II collagen and to the alpha 3(XI) chain of type XI collagen. Some patients also had antibodies which bound to the alpha 1(XI) and to the alpha 2(XI) chains of type XI collagen. Thus antibodies to unique as well as to common epitopes on each of the two types of collagen molecule occur in some patients with rheumatoid arthritis.

Animals↗
PubMed1988

Levels of customary physical activity among the old and the very old living at home.

With an activity inventory designed specifically for use among elderly people, detailed profiles of customary physical activity were obtained from 507 old (aged 65-74 years) and 535 very old (aged 75 years and over) individuals randomly sampled from the community. Participation in four categories of activity was assessed: outdoor productive activities; indoor productive activities; leisure activities; and walking. Customary engagement in many activities was found to be low, age (old versus very old) and sex being among the most important determinants of participation. The method of assessment is described, and activity profiles normative for older age groups are presented.

Activities of Daily Living↗
PubMed1988

Histochemical localization of IGF-I and IGF-II mRNA in the rat between birth and adulthood.

We describe the postnatal ontogeny and localization of insulin-like growth factors I and II (IGF-I and -II) in the rat. We have used oligodeoxyribonucleotide probes for in situ hybridization (hybridization histochemistry) and for Northern blotting. IGF-II mRNA is strongly expressed in liver, skeletal muscle, perichondrium, leptomeninges and choroid plexus of the newborn. Demonstrable levels fall dramatically in the liver at 18-20 days postnatally but persist for longer periods in muscle and remain undiminished throughout life in the pia/choroid plexus, indicating that different control mechanisms operate in these tissues. IGF-I mRNA is predominantly found in the liver. Its level in this organ rises well before levels of IGF-II fall. This suggests that distinct factors govern the expression of IGF-I and -II genes.

Animals↗
PubMed1988

Single arterial puncture vs arterial cannula for arterial gas analysis after exercise. Change in arterial oxygen tension over time.

In an attempt to find the least invasive, safest, easiest, and cheapest method of obtaining resting and exercise samples of arterial blood, a comparison was made between samples from an arterial needle puncture and an arterial cannula. This study demonstrated that samples of arterial blood may be obtained by radial arterial puncture both at rest and during exercise in practically all cases without morbidity. Samples from arterial needle puncture provide the same results as those from arterial cannulas. In the very rare patient in whom arterial puncture during maximal exercise is unsuccessful, the arterial oxygen pressure (PaO2) measured at 10 seconds after exercise correlates very well with the PaO2 at maximal exercise, and the 15-second value correlates nearly as well. Arterial cannulas are needed in the infrequent case when arterial puncture is not accomplished during maximal exercise and the 10-second or 15-second PaO2 decreases from the resting value. In this instance, determination of the exact extent of the hypoxemia requires an exercise sample obtained by cannula; however, the decrease in PaO2 obtained by arterial needle puncture at 10 or 15 seconds will be all that is needed many times to make a clinical decision. Values obtained at 20 seconds after maximal exercise reflect less of the exercise measurement and cannot be used; however, all episodes of significant hypoxemia (PaO2 less than 60 mm Hg) were captured by the analysis at 20 seconds after exercise.

Adult↗
PubMed1988

Control of IGF-II mRNA levels by glucocorticoids in the neonatal rat.

Insulin-like growth factor-II (IGF-II) is thought to be a major growth factor during fetal and neonatal development. Levels of IGF-II mRNA fall dramatically in the liver - the major site of endocrine production - between 18 and 20 days post-natally. No information concerning the control of gene expression post-natally has hitherto been available. Using Northern blotting and in-situ hybridization, we show here that cortisone acetate rapidly extinguishes IGF-II mRNA expression in the neonatal rat liver. The effect at putative autocrine/paracrine locations such as skeletal muscle and choroid plexus is much less marked or absent. The repression by cortisone acetate is discussed in the light of the available IGF-II gene sequence.

Animals↗
PubMed1988

Genetic differences in lithium-sodium exchange and regulation of the sodium-hydrogen exchanger in essential hypertension.

The elevation of Vmax of red cell Li/Na exchange in some hypertensives and in their normotensive offspring is mainly accounted for by genetic factors. In order to understand the pathophysiological meaning of this finding, we have studied if it is an operational mode of H/Na exchange, a transport system involved in the regulation of cell pH in vascular and kidney cells. To define the relationship of the Li/Na exchange to the H/Na exchange pathway, we have investigated the kinetic effects of internal and external H+ on H/Na, H/Li, and Li/Na exchange. These three exchange modes have highly asymmetric affinities for H+ much greater than Li+ greater than Na+, are activated by internal H+ (Hi) with a high "Hill coefficient" (n = 2.5), and competitively inhibited by external H+ (Ho). Moreover, cell Li activates H/Na exchange while being transported by Li/Na exchange at a lower rate than Hi. These observations support the conclusion that Li/Na exchange is a mode of operation of H/Na exchange. Li+ discriminates better than cell H+ between regulatory and transport sites in red cells of normotensive subjects. Kinetic studies of H/Na exchange in red cells of hypertensive subjects with high Li/Na exchange indicate that the Vmax of both pathways are not linearly related. Thus, Li/Na exchange does not measure the number of Na/H sites but assesses the occupancy of an internal site. We found that H/Na exchange in hypertensive subjects has a reduced Hill coefficient for the cell pH dependence of Na influx, which is interpreted as a defective Hi regulatory site.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

IgG subclass distribution of antinative type II collagen and antidenatured type II collagen antibodies in patients with rheumatoid arthritis.

In 81 patients with rheumatoid arthritis (RA) with antibodies to native type II collagen, the frequencies of each IgG subclass to native type II collagen were IgG1 (70%), IgG2 (12%), IgG3 (84%) and IgG4 (6%) and to denatured type II collagen were IgG1 (86%), IgG2 (23%), IgG3 (86%) and IgG4 (6%). Thus serum antibodies to type II collagen in patients with RA were predominantly of the complement fixing subclasses IgG1 and IgG3.

Arthritis, Rheumatoid↗
PubMed1987

Genetic structure of the Utah Mormons: isonymy analysis.

Isonymy analysis is reported for a sample of 188,895 marriages extracted from the Utah Genealogical Database. Inbreeding rates estimated by isonymy are low, ranging from 0.005 for the earliest marriage cohort (1800-1809) to 0.0008 in the most recent cohort (1950-1959). The inbreeding values decrease considerably through time, but they are consistently higher than inbreeding values estimated from pedigrees. Several explanations are offered for this, including polyphyletism of surnames and the presence of Scandinavian patronyms in this population. Random isonymy between subdivisions is also compared with random kinship estimated from migration matrices. In terms of within-subdivision kinship, the two approaches yield similar results. However, the results are quite dissimilar for between-subdivision kinship. This reflects the recent and nonrandom settlement of Utah by different ethnic groups with different surname distributions. In later time periods, the correlations between the two types of kinship estimates increase, showing that migration patterns (which are strongly determined by geographic distance) exert an increasing influence on the distribution of surnames. Logistic regression is performed on a subset of marriages (n = 88,202), using isonymous vs. nonisonymous marriage as the dependent variable. The independent variables are year of marriage, geographic distance between husband's and wife's birthplaces, endogamous vs. exogamous marriage, and population sizes of husband's and wife's birthplaces. Year of marriage and geographic distance are shown to be significant independent predictors of isonymous marriage.

Christianity↗