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Biomedical subjects

D Smith

Publications and source records attributed to D Smith.

At least 973 records · Page 54Linked to original sources
PubMed1986

Genetic counterselective procedure to isolate interspecific cell hybrids containing single human chromosomes: construction of cell hybrids and recombinant DNA libraries specific for human chromosomes 3 and 4.

Counterselection against genes on human chromosome 5 was applied to interspecific human-Chinese hamster cell hybrids which retained this and one additional human chromosome in order to generate cell hybrids retaining single, nonselected human chromosomes. Using this procedure, stable cell hybrids which retain human chromosome 3 exclusively or human chromosome 4 exclusively were isolated. Complete recombinant genomic DNA libraries were prepared from each hybrid using the lambda cloning vector EMBL-4. These libraries represent sources of human DNA fragments derived specifically from chromosomes 3 and 4, respectively. Low-copy or unique human DNA fragments isolated from both libraries were analyzed to confirm their chromosomal origin and to determine the complexity of their hybridization patterns to total human DNA. These single human chromosome libraries represent a means to efficiently saturate chromosomes 3 and 4 with informative, polymorphic genetic markers. DNA fragments from the chromosome 4 library will be particularly useful in identifying additional genetic markers close to the Huntington's disease gene. The same genetic counterselective procedure can be utilized to derive several additional cell hybrids with single human chromosomes.

Animals↗
PubMed1986

Amino acid and glucose metabolism in the postabsorptive state and following amino acid ingestion in the dog.

Amino acid and glucose metabolism was studied in nine awake 18-hour fasted dogs with chronic portal, arterial, and hepatic venous catheters before and for three hours after oral ingestion of amino acids. The meal was composed of a crystalline mixture of free amino acid, containing neither carbohydrate nor lipid. Following the amino acid meal, plasma glucose concentration declined slowly and this occurred despite a rise in hepatic glucose release. Portal plasma insulin rose transiently (30 +/- 7 to 50 +/- 11 microU/mL, P less than 0.05) while the increase in portal glucagon was more striking and persisted throughout the study (162 +/- 40 to 412 +/- 166 pg/mL). Over the three hours following amino acid ingestion, the entire ingested load of glycine, serine, phenylalanine, proline, and threonine was recovered in portal blood as was 80% of the ingested branched chain amino acids (BCAA). The subsequent uptake of these glucogenic amino acids by the liver was equivalent to the amount ingested, while hepatic removal of BCAA could account for disposal of 44% of the BCAA absorbed; the remainder was released by the splanchnic bed. During this time, ongoing gut production of alanine was observed and the liver removed 1,740 +/- 170 mumol/kg of alanine, which was twofold greater than combined gut output of absorbed and synthesized alanine. In the postcibal state, the total net flux of alanine and five other glucogenic amino acids from peripheral to splanchnic tissues (1,480 mumol/kg 3 h) exceeded the net movement of branched chain amino acids from splanchnic to peripheral tissues (590 mumol/kg/3 h).(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1986

Corynebacterium parvum followed by chemotherapy (actinomycin D and DTIC) compared with chemotherapy alone for metastatic malignant melanoma.

Seventy-nine patients with Stage III widely metastatic melanoma were prospectively randomised to a 'no treatment' control group who received on tumour progression DTIC (250 mg/m2 i.v. daily X 5) and Actinomycin D 1.5 mg/m2 on Day 1. A total of six courses at 3-week intervals was given. Chemotherapy was only given on progression of disease. The other group received initially Corynebacterium parvum (2 mg/m2) every 3 weeks for a maximum of eight courses and then the same chemotherapy on evidence of progressive disease. Minimum follow up time is 3 yr. The chemotherapy response rate (control 37%, C. parvum 24%) was not statistically different nor was the effect of chemotherapy on the site of individual metastases. Radiotherapy responses for irradiated soft tissue disease again were not significantly different, between the two patient groups. No significant differences in survival (control group median, 4 months, range 1-46; C. parvum median 3 months range 1-35) were observed and only one patient is alive at 35 months. The pattern of relapse was also similar in both groups. Reduction in haematological toxicity consequent on chemotherapy was not observed in the C. parvum-treated patients. No additional benefit was observed when C. parvum was followed by DTIC and Actinomycin D chemotherapy compared with the results from the chemotherapy given alone, although C. parvum on this schedule had minimal toxicity.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

HPLC as a replacement for the animal response assays for insulin.

The work describes the assay of the potency of insulin (drug substance) and its formulations by gradient elution reversed-phase high-performance liquid chromatography (HPLC). The methods are shown to differentiate between insulins of bovine, porcine and human sequence, and to be both reproducible and stability-indicating. The HPLC assay results show good agreement with those obtained by the mouse blood glucose assay. The advantages of the HPLC assays over the animal response assays are discussed. It is suggested that the animal response assays should now be replaced by the HPLC assays.

Journal Article↗
PubMed1986

Operative recovery of vasal sperm from anejaculatory men: preliminary report.

Sperm showing good motility and function, as demonstrated by the in vitro sperm penetration assay using hamster ova, were collected from the vas deferens of 3 men with ejaculatory failure. The collection procedure may be repeated over multiple ovulatory cycles. The sperm may be used to attempt artificial insemination or in vitro fertilization.

Adult↗
PubMed1986

The optomotor response and induced motion of the self.

Although the optomotor response in animals and induced motion of the self in humans occur under very similar stimulus conditions, they have not hitherto been related. Experiments with fish are reported which support the hypothesis that the optomotor response is based on the animal's attempt to nullify the unwanted experience of its own motion that is imposed upon it.

Animals↗
PubMed1986

The Aberdeen Mark II single-photon-emission tomographic scanner: specification and some clinical applications.

The construction, operation and physical characteristics of a single-section multi-detector single-photon-emission scanner are described. The machine has 24 detectors arranged along the sides of a square. Movements and data collection are under the control of a series of distributed microprocessors. Both head and trunk tomograms can be produced. The spatial resolution at the collimator focus is 9 mm in the transverse plane, and the effective slice thickness is 14 mm. The volume sensitivity is 300 counts/s kBq ml with a 20 cm diameter cylindrical phantom filled with 99Tcm solution. The application of this machine to the examination of the brain, liver and heart has been found to be clinically useful.

Brain↗
PubMed1986

Relationship of clinical diabetes and asymptomatic hyperglycemia to risk of coronary heart disease mortality in men and women.

This epidemiologic study explored the sex differential in risk of death from coronary heart disease in persons with or without clinically diagnosed diabetes or asymptomatic hyperglycemia. Use was made of 9-year follow-up data from the Chicago Heart Association Detection Project in Industry for 11,220 white men and 8,030 white women aged 35-64 years at entry to the Project (November 1967-January 1973). Both clinically diagnosed diabetes and asymptomatic hyperglycemia were associated with an increased risk of death from coronary heart disease. The extent of this association was greater in women than in men in regard to relative risk. However, absolute excess risk for both diabetics and those with asymptomatic hyperglycemia was larger for men than for women. Clinical diabetes appeared to be an independent risk factor for coronary heart disease in both men and women based on multivariate Cox regression analyses. On the other hand, for men, no significant independent effect of asymptomatic hyperglycemia was apparent. Women with asymptomatic hyperglycemia had significantly higher coronary heart disease death rates than normoglycemic women, with adjustment for major coronary heart disease risk factors; in multivariate analyses, the relationship of asymptomatic hyperglycemia to risk of coronary heart disease was of borderline significance (p = 0.054). This study indicates the independent associations of diabetes and possibly asymptomatic hyperglycemia with coronary heart disease mortality, with greater relative significance in women than in men.

Adult↗
PubMed1986

A comparative study of the morphology and viability of hyphae of Penicillium expansum and Phytophthora nicotianae during freezing and thawing.

The changes in morphology of Penicillium expansum Link and Phytophthora nicotianae Van Breda de Haan during freezing and thawing in a growth medium with and without the cryoprotective additive glycerol were examined with a light microscope fitted with a temperature-controlled stage. Viability of 0.5-1.0 mm diameter colonies of both fungi was determined after equivalent rates of cooling to -196 degrees C in the presence or absence of glycerol. In P. expansum shrinkage occurred in all hyphae at rates of cooling of less than 15 degrees C min-1; at faster rates intracellular ice nucleation occurred. The addition of glycerol increased the rate of cooling at which 50% of the hyphae formed intracellular ice from 18 degrees C min-1 to 55 degrees C min-1. This species was particularly resistant to freezing injury and recovery was greater than 60% at all rates of cooling examined. At rapid rates of cooling recovery occurred in hyphae in which intracellular ice had nucleated. In contrast, during the cooling of Ph. nicotianae in the growth medium, shrinkage occurred and no samples survived on thawing from -196 degrees C. However, on the addition of glycerol, shrinkage during freezing decreased and viable hyphae were recovered upon thawing; at rates of cooling over 10 degrees C min-1 the loss of viability was related to glycerol-induced osmotic shrinkage during cooling rather than to the nucleation of intracellular ice.

Cell Survival↗
PubMed1986

Mechanism of the dicrotic pulse.

The dicrotic pulse is an abnormal carotid pulse found in conjunction with certain conditions characterised by low cardiac output. It is distinguished by two palpable pulsations, the second of which is diastolic and immediately follows the second heart sound. In the course of open chest canine studies of the second heart sound, micromanometers and an electromagnetic flow meter were used to study proximal aortic haemodynamic function in both strong and weak beats. It was found that the incisural notch of the aortic pressure signal is not strongly dependent on the extent of left ventricular ejection, and is of essentially normal amplitude even in beats having greatly reduced aortic flow. In contrast, the magnitude of the systolic upstroke of the aortic pressure pulse is strongly determined by the magnitude of left ventricular ejection and is considerably reduced in weak beats. With low cardiac output the relative size of the incisural notch becomes exaggerated in comparison with the overall pulsation, thus creating the characteristic M shaped waveform of the dicrotic pulse.

Animals↗
PubMed1986

Clostridial myonecrosis in association with etoposide therapy presenting as severe thigh pain.

The case is described of a 68 year old man who was immunosuppressed as a result of receiving chemotherapy for small cell lung cancer and who presented with severe right thigh pain. This proved to be due to clostridial myonecrosis with none of the classical clinical features of clostridial infection. This is believed to be the first reported case of spontaneous clostridial infection associated with etoposide administration.

Aged↗
PubMed1986

Immobilization of operated ankle fractures.

Forty-three patients with stable internal fixation of fresh ankle fractures were treated at random with a plaster cast for 6 weeks without weight bearing or were only immobilized for 3 days, after which active movements were encouraged. The two groups were followed for a year. Only at 6 weeks were there significant differences between the groups.

Adolescent↗
PubMed1986

Regulation of hormone-stimulated cyclic AMP accumulation in intact human mononuclear leukocytes by blood plasma.

Several hormones, including catecholamines, histamine, and prostaglandin E1, regulate the function of human mononuclear leukocytes (MNL) by stimulating the accumulation of cAMP. Isoproterenol-stimulated cAMP accumulation in MNL isolated and washed at 4 degrees is five times greater than in cells prepared at ambient temperature. The current study was aimed at understanding this difference. cAMP accumulation in MNL prepared at ambient temperature could not be increased by chilling the cells for 4 hours. Warming MNL prepared at 4 degrees for 30 min, however, reduced later isoproterenol-, histamine-, and PGE1-stimulated cAMP accumulation by 65-85% without altering forskolin-stimulated cAMP accumulation and without altering cellular viability or ATP content. In broken cell preparations, there was no difference in either adenylate cyclase or phosphodiesterase activities, and no difference in the binding of isoproterenol to the beta-adrenergic receptors. The reduction in isoproterenol-stimulated cAMP accumulation in warmed intact cells was reversed when the MNL were incubated with autologous leukocyte-depleted blood or with plasma. These data suggest the presence of one or more factors in plasma that enhances hormone-stimulated adenylate cyclase activity in intact MNL.

Adenosine Triphosphate↗
PubMed1986

Homogeneous apoenzyme reactivation immunoassay for thyroxin-binding globulin in serum.

In this automated apoenzyme reactivation immunoassay system (Ames Optimate) for thyroxin-binding globulin (TBG), the sample and N6-aminohexylflavin adenine dinucleotide-labeled TBG react sequentially with antiserum. Then apoglucose oxidase is added to combine with the free fraction and generate glucose oxidase activity, which is measured colorimetrically. The assay requires 100 microL of sample and covers the clinically significant range for TBG (less than 2.5 to 55 mg/L). The first result is obtained in 16 min; assay of 29 samples and their blanks is completed in less than 1 h. The lower limit of detection is about 2.5 mg/L. Between-assay CVs (n = 9) were less than 9%, within-assay CVs (n = 5) were less than 6%, and analytical recovery of TBG was 103-112%. Reagents are stable at 4 degrees C for at least five months. Results by this method for serum TBG (y) compared well with those determined by radioimmunoassay (x): y = 1.029x--0.352 (r = 0.990, n = 49, Syx = 1.165 mg/L). In addition, with 39 other sera the ratio of total thyroxin (by RIA) to TBG compared well with free thyroxin measured by equilibrium dialysis (r = 0.930) and the free thyroxin index (r = 0.970).

Apoenzymes↗