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Biomedical subjects

M L Smith

Publications and source records attributed to M L Smith.

At least 415 records · Page 23Linked to original sources
PubMed1982

Chromosome-bound mitotic factors: release by endonucleases.

Additional evidence is presented to support our recently reported conclusion that the mitotic factors of mammalian cells, which induce germinal vesicle breakdown and chromosome condensation when injected into fully grown Xenopus laevis oocytes, are localized on metaphase chromosomes. Chromosomes isolated from mitotic HeLa cells were further purified on sucrose gradients and digested for varying periods with either the micrococcal nuclease or DNase II. At each time point of digestion the amount of mitotic factors released was determined by injecting a supernatant of these fractions, obtained by high-speed centrifugation, into oocytes. The amount of DNA rendered acid soluble under the conditions of digestion used was 3% ot 5% of the total chromosomal DNA. The extent of release of mitotic factors with both nucleases was estimated to be about 30% to 40% as evidenced by the reextraction of the undigested chromosomal pellet with 0.2 M NaC1. Similar results were obtained when nuclei from G2 cells were digested under identical conditions. The release of these chromosome-bound mitotic factors by mild digestion with these nucleases though only partial, clearly demonstrates that a significant proportion of these factors are localized on metaphase chromosomes.

Animals↗
PubMed1982

Diphosphonates in the evaluation of metabolic bone disease.

The bone scan may be of value in the assessment of patients with metabolic bone disease. However the superiority of the bone scan when compared to radiology in conditions such as renal osteodystrophy, osteomalacia, primary hyperparathyroidism, and osteoporosis requires substantiation with the newer radiopharmaceuticals which have a higher affinity for bone. Two methods of quantitating skeletal uptake of tracer have been assessed to try to remove the subjective aspect of bone scan evaluation. Measurements of bone to soft tissue ratios have proved clinically disappointing, but 24 hour whole body retention of diphosphonate appears to provide a sensitive index of increased bone turnover.

Bone Diseases, Metabolic↗
PubMed1982

Regulation of nucleotide and pentose synthesis in resting and stimulated 3T6 fibroblasts.

A two-step procedure has been used to follow the activation of one metabolic system involved in the return of cells to a proliferative state after resting in a Go state as a result of serum limitation. One feature of the resting state is a limited capacity to synthesize nucleotides. The limitation apparently is in the rate of synthesis of 5-phosphoribosylpyrophosphate from glucose and indirectly in the capacity of the resting cells to turn over the triphosphopyridine nucleotide pair, NADPH:NADP+. A reaction utilizing NADPH is apparently greatly diminished in resting cells and is substantially increased by only brief contact of cells with the hormonal elements in dialyzed calf serum. Insulin together with platelet-derived growth factor can substitute for calf serum. Aside from stimulating the turnover of the pyridine nucleotide coenzyme pair, serum also stimulates the utilization and reformation of ATP, principally from AMP. Among the NADPH-linked reactions that have been examined for their physiological significance in the initiation of growth stimulation are two steps in the conversion of glutamate to proline in the cytoplasm. Pyrroline 5-carboxylate, an intermediate in this metabolic pathway, has been shown to stimulate PRPP synthesis when added to cultures of resting 3T6 cells. Proline, the product of the reduction of this 5-membered heterocycle is also a stimulant of PRPP synthesis. In addition, dehydroascorbic acid is a potent stimulant of PRPP synthesis. As a working hypothesis, we are exploring the role of a series of reactions that form a pyrroline 5-carboxylate/proline cycle operating between the cytoplasm and mitochondria. The net result is the oxidation of NADPH by molecular oxygen to yield NADP+ and water. The NADP+ is then used in the hexose monophosphate pathway for the conversion of glucose to PRPP. We wish to determine whether dehydroascorbate is operating in this cycle as an oxidant of proline in the mitochondria or whether it participates in some other reaction in the cell that redistributes the ratio of NADPH to NADP.

Cell Division↗
PubMed1982

Interaction of rotavirus and enterotoxigenic Escherichia coli in conventionally-reared dairy calves.

A study was made of the effects of rotavirus and/or enterotoxigenic Escherichia coli (ETEC) on dairy calves born and suckled on the farm and subsequently reared in isolation. Calves were orally inoculated at 6 days old with either rotavirus (5), ETEC (7), rotavirus and ETEC (5) or remained uninoculated controls (4), and their reactions were recorded by clinical, microbiological, and pathological observations. Rotavirus infection consistently produced diarrhoea, while ETEC inoculated alone did not colonise the intestine. In dual infections, both rotavirus and ETEC multiplied, although the severity of diarrhoea was not greater than that caused by rotavirus alone. Some ETEC-inoculated calves developed subsequent naturally-acquired rotavirus infections, but in these no ETEC multiplication occurred. The results suggest that prior or simultaneous rotavirus infection is necessary to enable ETEC colonisation of the intestine in conventional calves of this age.

Animals↗
PubMed1982

Influence of blood glucose concentration on brain lactate accumulation during severe hypoxia and subsequent recovery of brain energy metabolism.

The effects of hypoxaemia on regional cerebral blood flow (CBF) and brain cortical metabolite concentrations were investigated at different blood glucose concentrations in rats under nitrous oxide anaesthesia. Tissue hypoxia of 15-min duration was induced by a combination of arterial hypoxaemia, hypotension, and clamping of the right carotid artery. Blood glucose concentrations were manipulated by varying the food intake in the 24 h before the experiment, and by glucose administration. Cortical CBF doubled during hypoxia on the intact side, but did not differ significantly from control values on the clamped side. In the clamped hemisphere there was a substantial decrease in adenylate energy charge. At brain tissue glucose concentration of 1 mumol g-1 and above, there was an inverse correlation between adenylate energy charge and brain lactate concentration. In starved animals with mean brain glucose of 0.32 +/- 0.00 mumol g-1, lactate concentration was significantly lower, in spite of equally severe disruption of energy state. Recovery of brain adenylate energy charge was worse in fed and glucose-infused groups than in the fasted group. These results demonstrate that limitation of substrate supply during severe hypoxia in the rat allows enhanced recovery of brain energy metabolism following the hypoxic episode.

Animals↗
PubMed1982

Cystine accumulation and loss in normal, heterozygous, and cystinotic fibroblasts.

Cystinotic fibroblasts contain approximately 100 times more cystine than do normal control fibroblasts. When cystinotic fibroblasts were placed in the presence of 30 mM cysteine-glutathione mixed disulfide (CSSG) for 24 hr, their cystine content increased about 3-fold. Similar treatment of normal fibroblasts and fibroblasts from patients heterozygous for cystinosis resulted in a 6- to 7-fold increase in cystine content. In all three cell types, the intracellular free cystine is located within lysosomes. When placed in cystine-free medium after 24 hr in CSSG-containing medium, the normal and heterozygous fibroblasts rapidly lost their lysosomal cystine (t 1/2 = 20 min), but the cystine content of the cystinotic cells remained stable for over 90 min. In contrast to the findings in intact fibroblasts, cystine loss could not be demonstrated from isolated, cystine-loaded lysosomes from any of the three cell types.

Cell Survival↗
PubMed1982

Probing the energetics of proteins through structural perturbation: sites of regulatory energy in human hemoglobin.

The sites of energy transduction within the human hemoglobin molecule for the regulation of oxygen affinity have been determined by an extensive study of the molecule's energetic response to structural alteration at individual amino acid residues. For 22 mutant and chemically modified hemoglobins we have determined the total free energy used by the tetrameric molecule for alteration of oxygen affinity at the four binding steps. The results imply that the regulation of oxygen binding affinity is due to energy changes which are mostly localized at the alpha 1 beta 2 interface. They also indicate a high degree of "internal cooperativity" within this contact region--i.e., the structural perturbations at individual residue sites are energetically coupled. Cooperativity in ligand binding is thus a reflection of cooperativity at a deeper level--that of the protein-protein interactions within the alpha 1 beta 2 interfacial domain.

Allosteric Regulation↗
PubMed1982

What research says about the effectiveness of psychotherapy.

Meta-analysis is a new statistical technique used to integrate the results of many separate studies of a topic. The author, along with two colleagues, applied meta-analysis to 475 studies of the effectiveness of psychotherapy and 112 studies of the comparative effects of psychotherapy and psychoactive drugs. The investigators examined the studies' effect sizes--the standard mean difference on the outcome variable between the treated group and the comparison group. Since many studies had more than one outcome variable, the 475 studies actually produced 1,766 effect sizes. Meta-analysis of these data shows that psychotherapy is effective in enhancing psychological well-being, however it is measured by researchers. The patient's age and diagnosis, the therapist's training and experience, and the duration and mode of therapy bear little relation to the psychotherapy's outcome. Behavioral therapies are somewhat more effective than verbal ones, and drug therapy, while combining well with psychotherapy, is not more effective than psychotherapy alone.

Behavior Therapy↗
PubMed1982

Prolactin in seminal fluid.

Prolactin appears to modulate male reproduction by regulating hormone receptor levels in the testis and accessory sex organs and by facilitating spermatozoal biochemical processes associated with capacitation. A large portion of immunoreactive prolactin (iPRL) seems to be transported from blood to semen via the accessory sex organs and takes several days to make this transition. The iPRL in semen is heterogeneous in size and a unique portion may be associated with spermatozoa. Data from several clinical studies of seminal fluid prolactin are inconsistent. The variability of patient populations classified as fertile or infertile, the differences in prolactin assays used, and the lack of information about sample processing have been major causes of this difficulty.

Animals↗
PubMed1982

A series of inhibitors of azo dye hepatocarcinogenesis partially reverse the azo dye-induced decrease in liver RNA/DNA ratio.

The DNA and RNA content and the mitotic index were determined in the livers of rats pair-fed for 10 days on a control diet, and diets containing 0.06% 3'-methyl-4-dimethylaminoazobenzene (3'MeDAB), either alone or in combination with the inhibitors of azo dye carcinogenesis acetanilide (0.08%), p-hydroxypropiophenone (PHP, 1%), urea (5%), dehydroacetic acid (DHAA, 0.25%), butylated hydroxytoluene (BHT, 0.3%) and 3-methylcholanthrene (3MC, 0.067%). The liver RNA/DNA ratio was increased in rats fed the 3'MeDAB diet following ingestion of each of the inhibitor plus carcinogen-containing diets. The increases were significant except in the instance of urea. The increase was mainly due to increased RNA content in rats fed 3'MeDAB plus acetanilide, DHAA, BHT and 3MC when compared with rats fed 3'MeDAB alone. In rats fed PHP and 3'MeDAB, an increase in total liver DNA that was noted in rats fed 3'MeDAB alone did not take place, while total liver RNA content was similar in both groups; the RNA/DNA ratio was therefore greater in rats protected from 3'MeDAB carcinogenesis by PHP. The results are discussed in relationship to the effects of carcinogens on RNA forming genes and the role of the nucleolus in cell differentiation.

Acetanilides↗
PubMed1982

Diarrhoea in dairy calves reduced by feeding colostrum from cows vaccinated with rotavirus.

Forty-two dairy calves remained with their dams for two days after birth, and then were removed to a calf rearing shed. Calves were allocated to three groups for the next 14 days, and received twice daily either whole milk, whole milk with a 10 per cent supplement of pooled normal bovine colostrum or whole milk with 10 per cent supplement of colostrum from cows vaccinated with rotavirus. A natural outbreak of diarrhoea occurred, affecting 28 of the 42 calves. Feeding immune colostrum delayed the onset of diarrhoea, and reduced its incidence, duration and severity. Live weight gains were consequently improved. The group fed normal colostrum had diarrhoea intermediate in severity between that of control calves and those fed immune colostrum. The aetiology of the diarrhoea was complex, with calves excreting rotavirus, enteropathogenic Escherichia coli and cryptosporidia.

Animals↗
PubMed1982

Fluoride deposited by topical applications with stannous fluoride in human enamel.

The aim of this study was to quantify the fluoridating effect of a 4% aqueous solution of SnF2 applied for 5 min. and 30 min. resp., and to measure the amounts of KOH soluble fluoride and acquired fluoride separately (APF gel data being included for comparison). Blocks of intact enamel were treated with the topical agents and subsequently exposed to 1 M KOH solutions for 24 h. No significant amount of fluoride was dissolved from control specimens by this treatment. Subsequently, the acquired F in the enamel was determined by the acid etch technique. The amount of fluoride in the KOH solutions after 5 and 30 min. SnF2 application are comparable : 6.2 and 7.4 micrograms . cm(-2) resp. A single topical treatment of SnF2 of 5 and 30 min. did not produce a significant enrichment of fluoride in the enamel. The considerable accumulation of fluoride reaction products on the outer enamel surface was only 1/3 of the amount deposited by APF gels.

Acidulated Phosphate Fluoride↗
PubMed1981

Assessment of synthetic steroid (Org OD 14): effect on skeletal metabolism by 24-h whole-body retention of diphosphonate.

Using a 24-h whole-body retention (WBR) of Tc99m hydroxyethylidene diphosphonate (HEDP), a sensitive measure of skeletal metabolism, 24 women receiving the synthetic steroid hormone Org OD 14 were studied. OD 14 was found to have a powerful suppressive effect on skeletal metabolism in both oophorectomized and non-oophorectomized women when compared with control subjects (P less than 0.001 and P less than 0.01, respectively). The degree of suppression was similar to that found with oestrogen therapy. While it has previously been shown that OD 14 prevents bone mineral loss (as measured by photon-absorptiometry), the present study provides further evidence as to the efficacy of this compound in suppressing skeletal metabolism.

Alkaline Phosphatase↗