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Biomedical subjects

D S Miller

Publications and source records attributed to D S Miller.

At least 253 records · Page 14Linked to original sources
PubMed1976

Na-K-ATPase localization in teleost urinary bladder by [3H]ouabain autoradiography.

Previous studies on the urinary bladder of the seawater-acclimated winter flounder (pseudopleuronectes americanus) demonstrated that active Na and Cl transport were ouabain sensitive. This suggested a relationship between the Na pump and Na-K-ATP-ase. The specific binding of [H]ouabain to Na-K-ATPase provides a means of localizing the site of active Na transport. In isolated bladders, a positive linear correlation (r= 0.89) was found between the active Na transport rate and the Na-K-ATPase activity. Ouabain binding by the bladder surface appeared to be saturable and relatively specific, e.g., was reduced by a high K concentration. When only the mucosal side of the bladder was exposed to 5 muM ouabain, both inhibitory effects and binding were small and are explained by finite permeability of the bladder to ouabain. In contrast, binding and inhibitory effects from the serosal side were much greater. Autoradiographs demonstrated that [3H]ouabain was bound only to the serosal side of the epithelial cells. Ultrastructural examination revealed that the area of ouabain binding coincided with the basal and lateral plasma membranes.

Adenosine Triphosphatases↗
PubMed1976

The energetics of "catch up" growth.

Animals, prevented from growing and then refed a good diet ad libitum, growth faster than normal and this is called "catch up" growth. This experiment was designed to show whether this is achieved by eating more food or by a greater efficiency of energy utilisation. Groups of rats (either 3 or 5 weeks old) were maintained at constant weight for a month, either by reducing the quantity of a good diet or by reducing the proportion of dietary protein. Food intake and carcass gain were measured for a period of 6 days "catch up" growth and compared with the control growth of rats with the same starting weight. It is concluded that "catch up" growth is associated with increased energy intake and increased efficiency when expressed as food conversion and gross energetic efficiency. There are, however, specific age differences in the metabolism of "catch up" growth which may be due to variation in either the maintenance requirement or the efficiency of protein and fat synthesis. This experiment emphasizes the differences between the various available expressions of energy utilisation.

Age Factors↗
PubMed1976

Human acute myelomonocytic leukemia: serologic studies with simian antisera.

Simian antisera to human leukemia cells were able to distinguish antigens specific for lymphocytic types of leukemia from those expressed on certain myeloid leukemia cells. In this investigation, cells from acute myelomonocytic leukemia patients (AMML) were examined for their membrane-associated leukemia antigens. Simian antisera to both lymphocytic and myelogenous leukemia cells lysed cells from AMML donors. Monkey antisera to AMML cells, by direct microcytotoxicity testing, were cytotoxic for cells from all AMML patients, as well as for cells of certain patients with myeloid leukemia. Cells from patients with lymphatic leukemia were nonreactive. However, absorption studies indicated an antigen present on cells from patients with chronic lymphocytic leukemia which cross-reacted with AMML cell antigens. Sequential analyses of the serologic reactivity of cells from AMML patients undergoing chemotherapy corresponded with the clinical course of the patient, even though there was little correlation between the percentage of blast cells present and the per cent cytotoxicity with the antisera. At certain times a higher percentage of seropositive cells could be detected over that seen on morphological evaluation. The estimation of leukemic cells by serologic means could aid in the diagnosis and management of AMML patients during chemotherapy.

Animals↗
PubMed1976

The demographic and social characteristics of patients with Crohn's disease in the Nottingham area.

All 260 patients diagnosed as having Crohn's disease between 1958 and 1973, in the Nottingham area, were sought and demographic and social characteristics obtained by personal interview. These were compared with the general population, using the 1971 census data. We found significantly high proportions of patients who were female; married; in the age groups 20-39 and 60-54; and in managerial or skilled manual occupations.

Adolescent↗
PubMed1976

5-Azacytidine (NSC 102816): a new drug for the treatment of myeloblastic leukemia.

The pyrimidine analog, 5-azacytidine (NSC 102816), was administered by continuous intravenous infusion in Ringer's lactate in increasing doses to sets of patients with metastatic cancer to establish a dose sufficient to produce mild toxicity. Twenty-one patients (23 trials) were treated with doses of 50-200 mg/sq/m/day for 5 days every 2-4 wk. Nausea and vomiting were moderate and easily preventable. Doses of 100-200 mg/sq/m for 5 days every 14 days produced granulocytopenia, usually after two courses. Less toxicity was observed when courses were given every 21-28 days. Forty-five patients with previously treated and refractory acute myeloblastic leukemia were treated. The majority received doses of 150 mg/sq m for 5 days every 2 wk. Eleven (24%) complete remissions and four partial remissions were observed. The number of courses to achieve remission averaged three and required an average of 59 days. Nine patients with blastic crisis of chronic myeloblastic leukemia and four with refractory acute lymphoblastic leukemia failed to respond. 5-Azacytidine administered by continuous infusion is well tolerated and is an active compound in acute myeloblastic leukemia.

Agranulocytosis↗
PubMed1976

Case-control method for seeking evidence of contagion in Crohn's disease.

All cases of Crohn's disease in the Nottingham area were ascertained and dates and places of domicile and work before and after onset of symptoms were noted. Similar information was taken from matched control subjects and the Pike and Smith (Biometrics 30:263-279, 1974) case control technique for evaluating clustering of patients in time and space was applied. These results do not support the infectious hypothesis.

Crohn Disease↗
PubMed1975

After the hospital episode.

A scheme by which clinical students follow, after discharge from hospital, the progress of patients for whom they have had responsibility in the ward supplements students' knowledge of the natural history of disease and emphasises the importance of communication and the use of community resources. By commitment to a patient and his problems for a long period, the student can take an active role in care and, in presenting his patient's progress, finds himself in the role of teacher.

Education, Medical, Undergraduate↗
PubMed1975

Comparative study on conformational stability and subunit interactions of two bacterial asparaginases.

The denaturation and reconstitution of Erwinia carotovora and Escherichia coli L-asparaginases has been followed by optical rotatory dispersion, circular dichroism and analytical ultracentrifugation. Denaturation in urea results in dissociation of the native enzyme (mol. wt. 140 000 approx.) to produce unfolded subunits (mol. wt. 35 000 approx.); the Erwinia L-asparaginase subunits can be refolded by dilution or dialysis in alkaline conditions, pH 10.5, without aggregation to the active tetramer, to give a rather unstable solution of a monomer possibly in equilibrium with dimer. These alkaline-reconstituted subunits undergo a conformational change to a more ordered state in the presence of sodium dodecylsulphate, similar to those produced by the action of sodium dodecylsulphate on the native enzyme. If the denatured subunits are reconstituted in the pH range 5.0-7.5, the enzymically active tetramer is reformed in up to 80% yield, depending upon the conditions of temperature and concentration. Kinetic data for these various transitions suggest that dissociation is a rate-limiting step while conformational changes of the polypeptide chains are relatively much more rapid. The possible significance of these different rates of change to therapeutic considerations is discussed.

Asparaginase↗
PubMed1975

Resistance to slimming: adaptation or illusion?

Twenty-nine women who claimed that they could not lose weight on prescribed diets were isolated in a country house and fed 1500 kcal. per day for 3 weeks. Nine women maintained weight within plus or minus 1 kg. and were characterised by low basal (B.M.R.) and daily metabolic rates and by a long previous history of dieting. The remaining women did lose weight, but there was much individual variation. B.M.R. is a good indicator of probable weight loss as a result of dieting. In the group as a whole it was more closely related to body fat than to lean body mass. It was also related to fat-cell number as determined by biopsy, but not to fat-cell size. These findings suggest that among a group of would-be slimmers who claim to be unable to lose weight there will be some who have become metabolically adapted to a low-energy diet and others whose inability to lose weight is illusory.

Adaptation, Physiological↗
PubMed1975

Crohn's disease in Nottingham: a search for time-space clustering.

All cases of Crohn's disease in the Nottingham area were ascertained and the date and place of domicile and work at the time of onset of symptoms noted. Applying the Knox and Pike and Smith tests for clustering of patients in time and space, no significant results were observed. Further analysis of differences in time-space clustering between a group of patients and matched controls is in hand.

Animals↗
PubMed1975

Bulking agents in the treatment of obesity.

The effect of two bulk-forming appetite depressants, methylcellulose and gum guar, on food intake has been studied in 11 (4 male, 7 female) healthy volunteers--3 of whom were overweight. 10 g of active ingredient were given in two equal doses daily for periods of 1 week of each agent. Individually weighed dietary intakes were obtained over four consecutive weeks; the first and third weeks were without medication. Both gum guar and methylcellulose were equally effective in reducing appetite by 10%.

Adult↗
PubMed1975

Membrane-bound immunoglobulins on human leukemic cells. Evidence for humoral immune responses of patients to leukemia-associated antigens.

Immunoglobulins were detected on the membranes of human leukemic cells by a microcytotoxicity technique. A significant percentage of lymphocytes from normal donors failed to react with goat antisera to human heavy chain determinants or to lambda-light chains. Lymphocytes from some normal donors, however, did react with antisera to k-light chains. A high percentage (50-90) of cells from some leukemia patients were killed by antisera to light chains and by one or more antisera to heavy chain determinants. Trypsin treatment of leukemic cells resulted in a loss of cytotoxic activity with all immunoglobulin antisera. Reactivity with the k-light chain antiserum was detectable 2 h after trypsinization of chronic myeloid leukemic (CML) cells and 8 h after treatment of acute lymphocytic leukemic (ALL) cells. Reactivity with the antisera to heavy chain determinants and lambda-light chains could not be detected 8 and 48 h after trypsinization of CML and ALL cells, respectively. The cytotoxic activity of the immunoglobulin antisera to heavy chains was abolished by absorption with the specific immunoglobulin used to define the antisera by precipitation. Eluates (pH 3.2) prepared from leukemic cells which reacted by cytotoxicity with the immunoglobulin antisera were shown to contain immunoglobulins of different heavy chain classes. In addition, some of the eluates had cytotoxic antibody activity to human leukemia cells. The specificity of the eluted antibodies is similar to the specificity previously described for cytophilic antibodies from leukemic patients and nonhuman primate antisera to human leukemia cells. The possible in vitro detection and in vivo significance of the eluted non-complement-fixing antibodies is considered.

Cytotoxicity Tests, Immunologic↗