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Biomedical subjects

S Hughes

Publications and source records attributed to S Hughes.

At least 199 records · Page 11Linked to original sources
PubMed1989

Immunocytochemical analysis of the perinatal development of cat masseter muscle using anti-myosin antibodies.

The developmental changes in myosin gene expression in the masseter muscle of embryonic and juvenile kittens were examined immunocytochemically using anti-myosin heavy chain antibodies of various specificities. In the mature cat, this muscle contains only two phenotypes, the majority of fibres are superfast, the rest being slow fibres. In foetal tissues, the histological appearance of bundles of myotubes, comprising a large central myotube surrounded by a rosette of smaller myotubes, strongly suggest the existence in the jaw muscle of primary and secondary fibres during development. Immunocytochemical data are consistent with the hypothesis that there are four types of fibre; two types of primary fibre as well as two types of secondary fibre. (1) Slow primaries stain strongly with an anti-slow myosin antibody throughout the period under study. These fibres transiently express embryonic but not foetal myosin. (2) Superfast primaries stain for embryonic/foetal and slow myosins in the perinatal period but progressively replace these myosins with superfast myosin during postnatal development. (3) Superfast secondaries initially express embryonic/foetal myosins, but later, beginning around the time of birth progressively replace these myosins with superfast myosin. These fibres do not express slow myosin. (4) Slow secondaries, which initially also express embryonic/foetal myosins, but which postnatally express slow or slow and superfast myosins and express only slow myosin in the adult. These four types of fibres are homologous to the four isotypes of limb muscle fibres and may be derived from distinct lineages of myoblasts.

Animals↗
PubMed1989

Differential expression and regulation of the glucokinase gene in liver and islets of Langerhans.

Glucokinase, a key regulatory enzyme of glucose metabolism in mammals, provides an interesting model of tissue-specific gene expression. The single-copy gene is expressed principally in liver, where it gives rise to a 2.4-kilobase mRNA. The islets of Langerhans of the pancreas also contain glucokinase. Using a cDNA complementary to rat liver glucokinase mRNA, we show that normal pancreatic islets and tumoral islet cells contain a glucokinase mRNA species approximately 400 nucleotides longer than hepatic mRNA. Hybridization with synthetic oligonucleotides and primer-extension analysis show that the liver and islet glucokinase mRNAs differ in the 5' region. Glucokinase mRNA is absent from the livers of fasted rats and is strongly induced within hours by an oral glucose load. In contrast, islet glucokinase mRNA is expressed at a constant level during the fasting-refeeding cycle. The level of glucokinase protein in islets measured by immunoblotting is unaffected by fasting and refeeding, whereas a 3-fold increase in the amount of enzyme occurs in liver during the transition from fasting to refeeding. From these data, we conclude (i) that alternative splicing and/or the use of distinct tissue-specific promoters generate structurally distinct mRNA species in liver and islets of Langerhans and (ii) that tissue-specific transcription mechanisms result in inducible expression of the glucokinase gene in liver but not in islets during the fasting-refeeding transition.

Animals↗
PubMed1989

The keys to successful diversification: lessons from leading hospital systems.

Hospitals have engaged in a variety of diversification activities over the past five years--many of which have not met expectations. Based on a nationwide study of 570 hospitals belonging to eight leading hospital systems (both investor-owned and not-for-profit), four key factors are identified that differentiate the winners from the losers. These include strategies for working effectively with physicians; learning to combine centralized and decentralized strategic planning approaches; understanding partially related diversification; and effectively applying the experience curve. Putting these lessons to work will increase the probability of a more effectively diversified health care system in the future.

Data Collection↗
PubMed1989

The surgical treatment of adrenal disease.

Since the advent of cortisone replacement therapy in 1950 made adrenal surgery possible, it has had the reputation of being fraught with medical and technical difficulties. However, with good endocrine medical cooperation, expert anaesthesia and sound technical expertise, excellent results are obtainable.

Adrenal Cortex Hormones↗
PubMed1988

Heroin inhalation and asthma.

Opiate addiction is an increasing social problem, and there has been a change from taking opiates intravenously to inhaling them in many areas of Britain. Three patients with asthma who required mechanical ventilation soon after heroin inhalation were described. Two subsequently died of acute severe asthma. The patients were reluctant to admit to their addiction and persisted inhaling heroin despite medical advice and counselling. Opiate inhalation can provoke life threatening asthmatic attacks and should be considered in patients at risk of abusing drugs who have poorly controlled asthma.

Administration, Inhalation↗
PubMed1988

Effect of nerve section on beta-endorphin and alpha-melanotropin immunoreactivity in motor nerves of normal and dystrophic mice.

beta-Endorphin and alpha-melanotropin immunoreactivity was demonstrated in some motor nerves in histological sections of soleus and extensor digitorum longus muscles of the mouse. In two strains (C57BL/6J and 129/ReJ) which can inherit muscular dystrophy, the proportion of immunoreactive nerves was greater in the dystrophic individuals than in their healthy littermates. At 24 h after section of the sciatic nerve in the normal mice the proportion of immunoreactive nerve profiles had increased significantly in the denervated muscles even though most of the nerve axons had degenerated. Similar increases were also seen in nerves in the unoperated contralateral muscles.

Animals↗
PubMed1988

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Persons with Disabilities↗
PubMed1988

Immunocytochemical and electrophoretic analyses of changes in myosin gene expression in cat limb fast and slow muscles during postnatal development.

Changes in myosin synthesis during the postnatal development of the fast extensor digitorum longus (EDL) and the slow soleus muscles of the kitten were examined using immunocytochemical techniques supplemented by pyrophosphate gel electrophoresis and gel electrophoresis-derived enzyme linked immunosorbent assay (GEDELISA) of myosin isoforms. The antibodies used were monoclonals against heavy chains of slow and fast myosins and a polyclonal against foetal/embryonic myosin. In both muscles in the newborn kitten, there was a population of more mature fibres which stained strongly for slow but weakly for foetal/embryonic myosin. These fibres were considered to be primary fibres. They formed 4.8% of EDL fibres and 26% of soleus fibres at birth, and continued to express slow myosin in adult muscles. The less mature secondary fibres stained strongly for foetal/embryonic myosin, and these could be divided into two subpopulations; fast secondaries in which foetal/embryonic myosin was replaced by fast myosin, and slow secondaries in which the myosin was replaced by slow myosin. At 50 days the EDL had a large population of fast secondaries (83% of total fibres) and a small population of slow secondaries which gradually transformed into fast fibres with maturity. The vast majority of secondary fibres in the soleus were slow secondaries, in which slow myosin synthesis persisted in adult life. There was a restricted zone of fast secondaries in the soleus, and these gradually transformed into slow fibres in adult life. It is proposed that the emergence of primary fibres and the two populations of secondary fibres is myogenically determined.

Animals↗
PubMed1988

Immunocytochemical and electrophoretic analyses of changes in myosin gene expression in cat posterior temporalis muscle during postnatal development.

Changes in myosin gene expression during the postnatal development of the homogeneously superfast kitten posterior temporalis muscle were examined using immunocytochemical techniques supplemented by pyrophosphate gel electrophoresis and gel electrophoresis-derived enzyme linked immunosorbent assay (GEDELISA) of myosin isoforms. The antibodies used were polyclonals directed against the heavy chains of superfast and foetal myosins and monoclonals against the heavy chains of slow and fast myosins. The fibres of the posterior temporalis in the newborn kitten stained almost uniformly with the anti-foetal myosin antibody and the largest of these fibres stained strongly for superfast myosin. A subpopulation of fibres staining for superfast myosin also stained lightly for slow myosin. These slow staining fibres were evenly distributed in the centres of muscle fibre bundles, reminiscent of primary fibres in limb fast muscle. During subsequent development, slow myosin staining disappeared and superfast myosin replaced foetal myosin so that by 50 days the muscle was virtually homogeneously superfast as in the adult. Fast myosin was never expressed at any stage. It is proposed that fibres staining transiently for slow myosin are superfast primary fibres which are homologous to fast primary fibres recently described in regions of limb muscles devoid of slow fibres in the matured animal. Other jaw-closing muscles have significant populations of slow fibres in the mature animal and it is postulated that there exists in these muscles a second class of jaw primary fibres, the slow primary fibres, in which slow myosin synthesis would be sustained in the adult. It is suggested that the myogenic cells of jaw-closing and limb muscles are of two distinct types preprogrammed to express different muscle genes.

Animals↗
PubMed1988

Myogenic and neurogenic regulation of myosin gene expression in cat jaw-closing muscles regenerating in fast and slow limb muscle beds.

Immunocytochemical techniques were used to study changes in myosin gene expression during the regeneration of the cat posterior temporalis muscle transplanted into the bed of either the fast extensor digitorum longus (EDL) or the slow soleus muscle. Strips of the posterior temporalis, a homogeneously superfast muscle, were treated with Marcaine and then transplanted into limb muscle beds which had been completely cleared of host muscle fibres. The regenerates were examined 6 to 224 days after surgery. Early regenerates in both muscle beds reacted with antibodies against the heavy chain of foetal, slow and superfast myosins, but not with antibodies against fast myosin. In the long-term, regenerates innervated by the EDL nerve expressed only superfast myosin whereas in the regenerates innervated by the soleus nerve most fibres expressed only slow myosin and only a few fibres reacted exclusively with the anti-superfast myosin antibody even after 210 days. In contrast, EDL and soleus muscles regenerating in their own beds expressed foetal, slow and fast myosin, but did not express superfast myosin. The isometric contraction times of the various types of regenerates reflected the types of myosin synthesized. It is concluded that jaw and limb muscle cells exist as two distinct allotypes, each having a distinct repertoire for the expression of adult isomyosins, and that within that repertoire isomyosin gene expression can be modulated by the nerve. Thus, myosin gene expression in skeletal muscle fibres is regulated by both myogenic and neurogenic mechanisms.

Animals↗
PubMed1988

Proviral-activated c-erbB is leukemogenic but not sarcomagenic: characterization of a replication-competent retrovirus containing the activated c-erbB.

Avian leukosis virus (ALV) induces erythroblastosis in chickens by integrating its DNA into the host c-erbB locus and by activating expression of truncated c-erbB transcripts. Although there is a 100% correlation of c-erbB activation with ALV-induced erythroblastosis, direct evidence that the activated c-erbB is oncogenic has not been established. We have constructed a replication-competent retrovirus containing the activated c-erbB to investigate its transforming potential. The Rous c-erbB virus (REB-c) was constructed by inserting the activated c-erbB cDNA into a Rous sarcoma virus vector in place of src. When transfected into transformed quail fibroblasts (QT6), the REB-c construct stably integrates and expresses c-erbB-specific transcripts and produces infectious virus. The REB-c retrovirus produces short-latency polyclonal erythroblastosis in chickens. However, in contrast to avian erythroblastosis virus which contains v-erbB, the REB-c construct does not transform chicken embryo fibroblasts in vitro, nor does the REB-c virus produce sarcomas when injected into the wing web of chickens. Our results provide the first direct evidence that the activated c-erbB which lacks the amino-terminal extracellular domain but which retains the entire carboxy-terminal sequences is leukemogenic but not sarcomagenic.

Alpharetrovirus↗
PubMed1988

Chicken homolog of the mos proto-oncogene.

We compared the sequence and properties of the chicken mos homolog with the previously characterized mouse and human c-mos genes. Sequence analysis revealed one major open reading frame of 1,047 base pairs encoding a protein of 349 amino acids. Both the nucleotide sequence and the deduced amino acid sequence showed 62% overall homology to mouse and human c-mos, but regions of higher conservation (approximately 70%) occurred in the putative ATP-binding and kinase domains. We detected mos transcripts by Northern (RNA) analyses in RNA prepared from chicken and quail ovaries and testes. Evidence for low levels of mos RNA expression in adult chicken heart, kidney, and spleen and in the entire embryo was obtained by S1 nuclease protection experiments. In contrast to the low transforming efficiency of human c-mos when linked to a mouse retroviral long terminal repeat element, chicken c-mos transformed NIH 3T3 cells as efficiently as mouse c-mos did. We also show that chicken primary embryo fibroblasts were morphologically altered when infected with an avian retroviral vector containing the chicken c-mos coding region.

Amino Acid Sequence↗
PubMed1988

Evaluation of ELISA, RPLA, and Vero cell assays for detecting Clostridium perfringens enterotoxin in faecal specimens.

Three hundred and ninety two faecal specimens from 70 separate outbreaks of suspected Clostridium perfringens food poisoning were examined by enzyme linked immunosorbent assay (ELISA), reversed passive latex agglutination (RPLA), and Vero cell assays for the presence of enterotoxin. Although the most time consuming method, ELISA was the most specific and reproducible. RPLA was slightly more sensitive than ELISA, but it showed some non-specific reactions. The Vero cell assay was the least sensitive and least reproducible method, being affected by some non-specific cytotoxic and cytotonic reactions. Normal rabbit serum should be included in the Vero cell assay as a control for the neutralisation of cytotoxic effects.

Animals↗
PubMed1987

Lithium clearance in man: effects of dietary salt intake, acute changes in extracellular fluid volume, amiloride and frusemide.

1. The effects of amiloride and frusemide on lithium clearance were studied during changes in dietary sodium chloride intake and during infusion of 0.9% NaCl in normal human volunteers. 2. Lithium and fractional lithium clearances were less on the low than on the high salt diet. Values for the medium salt diet were intermediate. Acute extracellular fluid volume expansion with 0.9% NaCl infusion and extracellular fluid volume contraction 3-4 h after intravenous frusemide caused lithium and fractional lithium clearances to increase and decrease respectively. 3. Amiloride caused small changes in lithium and fractional lithium clearances on a low salt diet, but was without effect when salt intake was medium or high. 4. Increases in lithium clearance occurred immediately after frusemide irrespective of dietary salt intake and in subjects infused with 0.9% NaCl. Only in salt-depleted subjects did frusemide cause a substantial increase in fractional lithium clearance. Changes induced under other circumstances were small. 5. It is concluded that the lithium clearance method for assessment of proximal tubule salt and water reabsorption can be used with some degree of confidence in certain circumstances (medium and high salt intake as well as in acute volume expansion) but may not be reliable when dietary salt intake is low.

Adult↗
PubMed1986

An assessment of the preregistration year experience.

All 115 graduates qualifying at Liverpool University Medical School in one year were sent a questionnaire in the final week of their preregistration year to assess the experience they had gained. Of the 105 graduates (92%) who replied, 99 (94%) considered the supervision that they had received to be adequate, 89 (85%) received most of their teaching from other junior doctors, and only 47 believed that they had learnt a considerable amount from their consultant colleagues. Half of the doctors received little or no training in terminal care. Although 100 (95%) felt competent in dealing with various medical emergencies, cardiopulmonary resuscitation skills were less developed; only 71 (68%) were confident in using a defibrillator, and 37 (35%) considered themselves to be competent in dealing with cardiac arrhythmias. A fifth of the doctors found interviewing relatives stressful. Of the 105 doctors who replied, 77 (73%) thought that their preregistration experience had had little or no effect on their choice of career.

Attitude of Health Personnel↗