Pole structures in nuclear and particle physics.
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Journal Article↗
Biomedical subjects
D Morgan
Publications and source records attributed to D Morgan.
Meson dynamics beyond the quark model: Study of final-state interactions.
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Journal Article↗
Preservation of neck dissection for histological study.
Dissection of lymphatic nodes in the neck--whether radical or partial, functional or prophylactic--forms an integral part of the surgical management of cancer of the head and neck. Accurate orientation and fixation of the surgical specimen is a prerequisite for correct histopathological study of the extent of the disease and for a complete clinicopathological interpretation, which is of significant therapeutic and prognostic importance.
Histological Techniques↗
Liability for medical education.
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Education, Medical↗
Cultivation of murine hair follicles as organoids in a collagen matrix.
Techniques are described for the isolation and cultivation of functionally intact mouse hair follicles. Follicles were isolated by collagenase digestion of dermis from 5-day-old mice and purified by differential centrifugation and filtration. Purified follicles were cultured in a Type 1 collagen matrix using Medium 199 and 8% fetal calf serum as the basic nutrient. Viability of follicles was maintained in culture since the cultures incorporated thymidine into DNA and methionine into proteins for at least 7 days. Furthermore, follicles isolated from the collagen matrix after 7 days could reattach to a plastic culture substrate or be further cultivated in a fresh collagen matrix. Functional integrity of cultured follicles was maintained since some follicle-specific cytoskeletal proteins were synthesized in vitro, and follicles isolated from the collagen matrix after 7 days formed a haired skin when recombined with dermal fibroblasts and grafted to a skin site on nude mice. Only a minority of follicles appeared to produce a mature hair shaft in vitro by morphologic criteria, however, and synthesis of the total complement of hair proteins was not observed. Cholera toxin was a strong mitogen for cultured follicles, whereas epidermal growth factor was slightly mitogenic. Epidermal growth factor stimulated the release of a Type 1 collagenase by follicle cells, however. This model system provides an opportunity for the systematic analysis of factors required for the induction of hair growth and the underlying physiology of hair follicle development. This model should also be useful for studying the role of the hair follicle in skin carcinogenesis.
Animals↗
Competitive fixed-interval performance in humans.
Two persons responded in the same session in separate cubicles, but under a single schedule of reinforcement. Each time reinforcement was programmed, only the first response to occur, that is, the response of only one of the subjects, was reinforced. "Competitive" behavior that developed under these conditions was examined in three experiments. In Experiment 1 subjects responded under fixed-interval (FI) 30-s, 60-s, and 90-s schedules of reinforcement. Under the competition condition, relative to baseline conditions, the response rates were higher and the pattern was "break-and-run." In Experiment 2, subjects were exposed first to a conventional FI schedule and then to an FI competition schedule. Next, they were trained to respond under either a differential-reinforcement-of-low-rate (DRL) or fixed-ratio (FR) schedule, and finally, the initial FI competition condition was reinstated. In this second exposure to the FI competition procedure, DRL subjects responded at lower rates than were emitted during the initial exposure to that condition and FR subjects responded at higher rates. For all subjects, however, responding gradually returned to the break-and-run pattern that had occurred during the first FI competition condition. Experiment 3 assessed potential variables contributing to the effects of the competitive FI contingencies during Experiments 1 and 2. Subjects were exposed to FI schedules where (a) probability of reinforcement at completion of each fixed interval was varied, or (b) a limited hold was in effect for reinforcement. Only under the limited hold was responding similar to that observed in previous experiments.
Journal Article↗
The human insulin receptor cDNA: a new tool to study the function of this receptor.
The human insulin receptor (hIR) is an integral transmembrane glycoprotein comprised of two alpha and two beta subunits. An immediate consequence of insulin binding to the extracellular alpha subunit is the autophosphorylation of tyrosine residues on the intracellular domain of the beta subunit. The placental hIR cDNA has been cloned and sequenced, providing the primary structural features of the protein. In order to investigate the functions of the beta subunit and particularly the role of autophosphorylation and tyrosine phosphokinase (TPK) activity (a feature shared by other receptors and oncogene proteins) in transmembrane signalling, we designed an expression system of the hIR cDNA in eucaryotic cells. Superexpressing CHO cell lines that contain about 10(6) functional hIR/cell have been developed. In these cells half maximum stimulation of glucose uptake occurs at 5 X 10(-10)M insulin, whereas normal CHO cells require 5 X 10(-12)M insulin. In this expression system we have carried out site-directed mutagenesis experiments in which domains of the molecule have been deleted or particular amino acids have been replaced by others. The replacement of either or both the tyrosine residues 1162 and 1163 compromise an autophosphorylated site that is important for kinase function and the insulin response. Expression of an isolated membrane-bound form of the beta-subunit produces a 6 fold increase in glucose uptake. This insulin-independent effect disappears if the twin tyrosines are mutated or if the beta subunit is expressed in the cytoplasm. These studies also show that the C terminal 112 amino acid portion of the beta subunit is important for the stability of this protein.
Amino Acid Sequence↗
Malaria in foreign visitors to Britain.
Malaria cases reported in Britain are increasing. Foreign visitors ill with malaria while visiting Britain form an important category. This paper reviews notifications to the Malaria Reference Laboratory (M.R.L.) of cases of malaria in foreign visitors in 1985. There were 427 cases reported in this group which is nearly 20% of the total number reported. It was found that the foreign visitors had a higher proportion of Plasmodium falciparum and that a third of the cases were aged 20-29 years. Sixty per cent of the cases were born in Nigeria or India and 7.5% claim to have become ill on the day they arrived in Britain. The behaviour of the malaria and the individual with malaria were also studied.
Adult↗
Cell cycle and organelle enzyme changes in the regenerating liver of the alcoholic rat.
Chronic ethanol effect on regenerating post-partial hepatectomy rat liver was studied from 0 to 80 hr to evaluate sequential changes. The rate of restoration in liver mass was comparable between controls (C) and ethanol (E) treated rats. Cell cycle changes included a decrease in magnitude and duration of the early peak in DNA synthesis (24 hr). However, the second peak (40 hr) was increased in magnitude so that the net change was negligible. Histone synthesis increased markedly, whereas thymidine kinase activity was moderately increased. The net effect was an accelerated accumulation of DNA (0.18 mg of DNA/g liver/hr vs 0.29 mg of DNA/g liver/hr; C vs E). The M phase of the cell cycle was initially delayed by ethanol, but once initiated, it exhibited greater numbers of mitoses reaching significance at 72 hr. It is concluded that although ethanol induces multiple changes, the overall process of restoring liver mass and cell number (DNA synthesis) is not impaired.
Alcoholism↗
Childhood feeding practices and their effects on nutrition in a rural area of The Gambia.
We have studied the nutritional status of 118 children of the Serahuli tribe aged 0-5 years from Badjakunda, a village in North Bank, Upper River Division (URD) of The Gambia. Throughout the 9 month study period malnutrition was identified in a larger proportion of children than in similar recent studies elsewhere in The Gambia. We have found a relationship in villages in North Bank URD between the percentage of Serahulis in the population and the percentage of children with malnutrition. Serahulis in Badjakunda generally do not introduce weaning foods until the child is aged 1 year, while Mandinkas in the same area usually start such foods before their children are 6 months old. Children aged between 6 months and 2 years were at particular risk of malnutrition, this may be attributable to the feeding practices of Serahulis.
Anthropometry↗
Maintenance chemotherapy for anaplastic small cell carcinoma of the bronchus: a randomised, controlled trial.
Since March 1980, 309 patients with anaplastic small cell carcinoma of the bronchus (ASCB) have received remission induction therapy prior to randomisation to maintenance (M) or no maintenance (NM) chemotherapy. Induction therapy consisted of six courses of vincristine, doxorubicin and cyclophosphamide (VAC) given IV every 3 weeks. Those with limited disease also received mediastinal irradiation. Consenting patients with no unequivocal residual disease were randomised to have no further treatment until relapse or a further eight courses of VAC, at a lower dosage, every 4 weeks. Patients failing to achieve randomisation status received palliative treatment only. The median survival for all patients with limited disease (LD) is 363 days and that for patients with extensive disease (ED) is 272 days (P less than 0.00001). Sixty-one patients with ED were randomised. Those having maintenance chemotherapy lived significantly longer (median 372 days) than those who did not continue therapy (median 259 days) (P = 0.006). An imbalance in the proportion of 'complete remitters' randomised to maintenance therapy does not account for this difference. There is no significant difference between the M and NM groups in the 32 randomised LD patients. Continuing treatment during remission with agents used to induce the remission can prolong survival in patients with extensive stage ASCB.
Antineoplastic Combined Chemotherapy Protocols↗
The effects of rate and route of nutrient intake on protein metabolism.
Isotopic measurements of protein kinetics are useful for the investigation of metabolic protein disorders during surgical illness. The effects of rate and route (oral vs parenteral) of nutritional substrate intake have not been well defined. Fischer 344 rats were infused with a total parenteral nutrition (TPN) solution at either 25, 100, or 175% of their normal substrate intake or were fed an oral diet ad libitum. After 4 days, [15N]glycine was infused at 0.138 mg 15N/hr for 24 hr. Whole-body protein turnover (WPT), synthesis, and catabolism were determined by 15N urea enrichment. Fractional synthesis rates (FSR) of liver and muscle protein were calculated by analyzing 15N tissue enrichment. WPT (r = 0.93, P less than 0.001) and liver FSR (r = 0.57, P less than 0.01) increased linearly with TPN infusion rates. All rats had protein synthesis rates greater than catabolism rates except for the rats infused with 25% TPN. Although caloric intake was the same in rats fed orally and those infused with 100% TPN, the orally fed rats had faster WPT (P less than 0.001), synthesis (P less than 0.05), catabolism (P less than 0.001), and liver FSR (P less than 0.05) than the TPN rats. Muscle FSR was not significantly affected by either the route of feeding or the TPN infusion rate. In this study, rate and route of substrate intake affected protein kinetics in the whole animal and liver, but not in muscle. Rate and route of nutrient intake need to be carefully specified and controlled during isotopic studies of protein kinetics.
Animal Nutritional Physiological Phenomena↗
Cultivation and characterization of cells derived from mouse skin papillomas induced by an initiation-promotion protocol.
Methods to culture cells from papillomas induced by an initiation-promotion protocol in SENCAR mice were developed, and the resultant cell lines have been characterized. Using Eagle's medium with 0.05 mM Ca2+ conditioned by dermal fibroblasts and supplemented with 1 ng/ml epidermal growth factor (EGF) in culture dishes coated with collagen and fibronectin, six cell lines (PA, PB, PC, PD, PE and PF) were established from separate pools of papillomas. When tested for tumorigenicity in nude mice by injection of a cell suspension or implantation of cells growing on a plastic liner, two of the lines (PC and PF) produced no tumors at any passage. In contrast, cells of the lines PA and PE produced highly differentiated squamous cell carcinomas from the earliest passage tested. The results with PB and PD were variable on tumorigenicity testing with some passages positive and others negative. When tested for responsiveness to Ca2+ (greater than 0.1 mM) as a differentiation stimulus, all lines responded. In the higher Ca2+ medium there was a 50-95% decrease in colony-forming efficiency, a slight decrease in [3H]thymidine incorporation (except for PA) and an increase in the number of cornified cells (except for early passage PF). Epidermal transglutaminase activity, a marker for terminal differentiation, was increased in the presence of medium with Ca2+ greater than 0.1 mM. However, unlike normal cells, only a fraction of the cells from each of the papilloma-derived cell lines terminally differentiated in response to Ca2+ while the remaining cells continued to proliferate, although at a slower rate. Responsiveness to phorbol ester tumor promoters was also examined in papilloma cell lines. 12-O-Tetradecanoylphorbol-13-acetate (TPA) treatment increased colony forming efficiency, DNA synthesis and colony size in all lines in medium with either 0.05 mM Ca2+ or 1.2 mM Ca2+. TPA treatment also increased ornithine decarboxylase activity in all lines, even at the higher Ca2+ concentration, although normal keratinocytes respond only when grown in medium with low Ca2+. TPA treatment caused only a slight increase in the number of cornified cells and no increase in epidermal transglutaminase activity in papilloma cells while it causes 10-fold or greater increases in these differentiation markers in normal keratinocytes. Thus papilloma cells appear to differ from normal keratinocytes in their ability to maintain a proliferating population under conditions favoring terminal differentiation, their consistent proliferative response to phorbol esters under these same conditions, and their reduced sensitivity to phorbol ester-induced terminal differentiation.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Schizophrenia and mania in identical twin brothers.
Each of a pair of identical twin brothers was independently remanded for mental health assessment. The results of the assessment reliably revealed schizophrenia in one twin and mania in the other. The implications for genetic models of mental disorder are discussed.
Adult↗
Labelling and immunoprecipitation of thyroid microsomal antigen.
Human thyroid microsomes have been solubilized, labelled with 125I, immunoprecipitated with microsomal antibody and analysed by gel electrophoresis. The analysis indicated that two peptides of relative molecular masses 108 and 118 kDa, under reducing conditions, were specifically immunoprecipitated by microsomal antibody. Similar values were obtained under non-reducing conditions indicating that the two peptides were not linked by disulphide bridges to each other or to different peptides. These results suggest that the microsomal antigen contains two components which may be linked by non-covalent bonds to form a single protein of 230 kDa. Studies with lectin affinity columns suggested that the antigen was glycosylated.
Antigens↗
Myelomatous ascites.
Ascites is an unusual feature of multiple myeloma. We report a case of ascites occurring early in the course of a patient with myeloma in whom there was no evidence of intra-abdominal plasmacytoma, and the skeleton was relatively spared. The serum contained predominantly polymeric IgA, a feature not investigated in previous cases. We reviewed the relevant literature and will discuss the suggestion that human myelomas presenting with the triad of ascites, relative or absolute sparing of the skeleton, and an IgA paraprotein bear an analogy to mouse myelomas induced by intraperitoneal instillation of irritants. The relevance of polymeric IgA is discussed with respect to tissue origin of the paraprotein. Seventeen cases were identified consistent with a definition of "myelomatous ascites" (malignant myeloma in which plasma cells and/or monoclonal immunoglobulin can be demonstrated in ascitic fluid). IgA immunoglobulin class was present at three times the incidence seen in myelomas in general (five of seven cases were specified). In twelve patients there was no identifiable intra-abdominal plasmacytoma although liver infiltration was common. Amyloidosis was reported in only one case, and no cases of uncomplicated plasma cell leukemia were noted. Ascites was a presenting feature in five cases. In each of these five there was absolute or relative sparing of the skeleton, four had no evidence of plasmacytoma, and the paraprotein was IgA in three, IgG in one, and unreported in one. In no case was there a known history of chronic intra-abdominal irritation.
Aged↗
The geographical distribution of thyrotoxicosis in England according to the presence or absence of TSH-receptor antibodies.
In a prospective study of the incidence of thyrotoxicosis sera from 216 thyrotoxic patients in seven English towns were assayed for TSH-receptor antibodies. The incidence of antibody negative thyrotoxicosis correlated closely with the previous prevalence of endemic goitre in the towns (r = 0.9) indicating a high current incidence of toxic nodular goitre in previously goitrous towns. Antibody positive thyrotoxicosis, an indicator of Graves' disease, showed no correlation with goitre although there was statistically significant geographical variation in incidence. The percentage of all thyrotoxic patients who were antibody positive varied between towns, from 35% to 92%.
Adolescent↗
Correlation of initiating potency of skin carcinogens with potency to induce resistance to terminal differentiation in cultured mouse keratinocytes.
The induction by chemical carcinogens of resistance to terminal differentiation in cultured mouse keratinocytes has been proposed to represent a cellular change associated with the initiation phase of skin carcinogenesis. Previous results with this culture model indicated that the number of differentiation-resistant foci was correlated with the dose and known potency for several chemical carcinogens. Assay conditions were optimized to provide quantitative results for screening a variety of carcinogens for their potency as inducers of foci resistant to terminal differentiation. Eight skin initiators of varying potency and from different chemical classes and ultraviolet light were studied for their activity to induce this alteration in cultured epidermal cells from newborn BALB/c mice. There was an excellent positive correlation for the potency of these agents as initiators in vivo and as inducers of altered differentiation in vitro. The induction of resistant foci was independent of the relative cytotoxic effects of each agent except where cytotoxicity was extensive and reduced the number of foci. The results support the hypothesis that initiation of carcinogenesis in skin results in an alteration in the program of epidermal cell differentiation. The results also suggest that the assay is useful for identifying relative potency classes (strong, moderate, weak) of initiating agents.
9,10-Dimethyl-1,2-benzanthracene↗