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Biomedical subjects

R E Davis

Publications and source records attributed to R E Davis.

At least 181 records · Page 10Linked to original sources

Thiamin intakes and erythrocyte thiamin levels in eleven-year-old children in the Western Cape.

Dietary intake of thiamin has been evaluated in a series of 615 eleven-year-old children in Western Cape Province, South Africa. Thiamin intakes, determined by 24-hour recall and local food composition tables, were highest in rural white children (boys 1.49 mg/day, girls 1.11 mg), followed by rural black (Xhosa) children (1.33, 1.15 mg), and lowest in rural (1.18, 1.11 mg) and urban coloured (Euro-African-Malay) subjects (1.11, 0.85 mg). The group means exceeded WHO recommended daily intakes except for urban coloured girls. Thiamin nutritional status was determined by automated microbiological assay of thiamin in erythrocytes in a subsample of 69 children. One urban coloured child was thiamin deficient. The highest mean value (69.4 micrograms/l) was found in rural coloured children, followed by their urban counterparts (64.8 micrograms/l) and black rural children (63.6 micrograms/l). Rural white children had the lowest mean value (60.3 micrograms/l). In general, thiamin stores in these children appear to be adequate.

Child↗

Thiamine deficiency in black male hostel-dwellers. The need for thiamine supplementation of sorghum beer.

Some indices of nutrition have been examined in hostel- and non-hostel-dwelling groups of industrially employed black males. Hostel-dwellers in the large metropolitan areas have to prepare their own food and many are accustomed to excessive alcohol intake, especially of sorghum beer. In the two groups studied, blood levels of vitamin B12, folate, pyridoxal and albumin were similar, but erythrocyte thiamine levels were significantly lower in the hostel-dwellers. Although the proportion of subjects with elevated levels of gamma-glutamyltransferase, an index of alcoholic liver disease, was similar in the two groups, thiamine-deficient hostel-dwellers had a greater proportion of elevated values suggesting that thiamine deficiency was related to both inadequate diet and excessive alcohol consumption. Fortification of sorghum beer with thiamine might prevent or reduce thiamine deficiency in this group. The cost would not materially affect the price of the beer.

Adult↗

Spatial discrimination in goldfish following bilateral tectal ablation.

Goldfish were classically conditioned to discriminate between right and left or nasal and temporal presentations of a spot-of-light conditioned stimulus (CS). After the conditioning, the fish were administered bilateral optic tectum ablation followed by weekly sessions of conditioning trials to test for retention or relearning of the discrimination response. As their behavioral photosensitivity is greatly decreased, the ablates were dark-adapted prior to each session and trials were administered in darkness. Right x left discrimination was retained postoperatively but the nasal x temporal discrimination was blocked. Sham-operated controls discriminated between the nasal and temporal CS when dark-adapted and tested in darkness. Subsequent transection of the optic nerves obliterated response to the CS, indicating that tectum ablates detect and respond to the CS retinally and not extraretinally. We conclude that memory of visual spatial learning is mediated by non-tectal brain structures and that the ablate can discriminate between right- and left-eye input but sees the CS too diffusely to distinguish its location within the monocular field.

Animals↗

Tissue folates in fruit bats (Rousettus aegyptiacus) with nitrous oxide-induced vitamin B12 deficiency and neurological impairment.

1. Long-term exposure of the fruit bat Rousettus aegyptiacus to nitrous oxide, which inactivates methylcobalamin, leads to neurological impairment and ataxia. 2. In N2O-exposed animals, liver concentrations of total folates and methyl folates decreased to less than one-fifth that of control animals. Pediococcus cerevisiae-active folates were also reduced. 3. In brain, there were no changes in total or methyl folates, but P. cerevisiae-active folates were lower in N2O-exposed animals. 4. Supplementation with methionine retarded the development of neurological impairment and the fall in liver total and methyl folates, but not that in P. cerevisiae-active folates. 5. Supplementation with serine failed to retard the development of neurological impairment or fall in hepatic folates. 6. The present results suggest that the N2O-induced neurological impairment in the bat is not related to depletion of cerebral folates, but do not exclude changes in the subcellular distribution of folates.

Animals↗

Thyroid and glucocorticoid hormone regulation of specific protein abundance in cultured human skin fibroblasts.

Effects of 3,3',5-triiodo-L-thyronine (T3) and dexamethasone (Dex) on the abundance of proteins resolvable by two-dimensional gel electrophoresis were examined in cultured human skin fibroblasts. Confluent cultures were incubated in medium supplemented with thyroidectomized calf serum and were treated with either T3 (100 nM), Dex (100 nM) or both hormones for 2 days and then labelled with [3H]leucine for 1 day. Most of the greater than 100 resolvable radiolabelled proteins were unaffected by hormone treatment. However, both hormones could increase or decrease the abundance of a limited number (approximately 10) of specific proteins. Some of these affected proteins appear to be coregulated. This result is consistent with effects demonstrated previously in pituitary adenoma cultures and suggests that both hormones regulate protein metabolism in human fibroblasts. This may be an ideal model for studying the nature of resistance to thyroid and glucocorticoid hormones.

Cells, Cultured↗

Hyperthermia potentiates the activity of immunotoxin conjugates against common acute lymphoblastic leukaemia cells in vitro.

We studied the in-vitro cytotoxic effect of hyperthermia at 42 degrees C, both alone and in combination with ricin-linked immunotoxins, reactive with the common acute lymphoblastic leukaemia cell lines Reh and KM-3. Assessment of cytotoxicity was by incorporation of 3H-leucine and limiting dilutions analysis. The effect of immunotoxins alone and in combination with hyperthermia on normal human marrow progenitor cells was assessed by conventional colony forming units-granulocyte macrophage (CFU-GM) assay. We found that incubation of either of the cell lines with a mixture of the two immunotoxins, RPH-7-ricin and PHM-6-ricin, at 42 degrees C for one hour (h) potentiated the cytotoxic activity of the immunotoxins at 37 degrees C. At a concentration of 10(-8) mol/L, a 2.2-log kill was seen with KM-3 leukaemic cells at 37 degrees C and a 3.3-log kill at 42 degrees C, an increase of approximately 10 fold in cytotoxic activity. Survival of CFU-GM following treatment at 42 degrees C for one h with a similar concentration of immunotoxins was 26.2% (+/- 13.7%) (equivalent to 0.6 log kill) and 76.0% (+/- 1.83%) (0.1 log kill) when normal marrow was incubated with immunotoxins at 37 degrees C. This suggests relative sparing of normal marrow cells compared with the leukaemic cells tested as indicated by the 2.1-log kill difference (approximately 100 fold) between normal and leukaemic cells at 37 degrees C and the 2.7-log kill (approximately 500-fold) difference at 42 degrees C. We conclude that hyperthermia may have a role in addition to immunotoxins in the purging of marrow ex vivo to remove leukaemic cells.

Antibodies, Monoclonal↗

Monoclonal antibody-ricin conjugate cytotoxic to cells expressing the common acute lymphoblastic leukemia antigen (CALLA).

The monoclonal antibody PHM-6, which is specific for the common acute lymphoblastic leukemia antigen (CALLA), was conjugated to the plant toxin ricin. Binding of the PHM-6-ricin conjugate to cells via the ricin molecule was blocked by the presence of 100 mM lactose. The IC50 (concentration resulting in 50% inhibition) of the PHM-6-ricin conjugate for the CALLA-positive KM-3 cell line was 280-fold greater than for bone marrow stem cells, indicating the potential of this conjugate for immunological purging of autologous remission marrow.

Antibodies, Monoclonal↗

Thiamin status and biochemical indices of malnutrition and alcoholism in settled communities of !Kung San.

Thiamin status and biochemical indices of malnutrition and alcoholism have been studied in groups of settled !Kung San living in the northern Kalahari Desert of Namibia. One third of the men and 20% of the women had low red cell thiamin concentrations. Raised serum gamma glutamyl transferase (gamma GT) activities were present in 30% of the men and 11% of the women. gamma GT activities were negatively correlated with red cell thiamin concentrations (r = -0.321, P less than 0.01). Raised mean corpuscular volumes were observed in over half the subjects. Anaemia was rare. Plasma protein and albumin concentrations were satisfactory. Cholesterol concentrations were relatively low (mean 4.1 mmol 1-1). The present results identify a high prevalence of thiamin deficiency in settled !Kung San, and suggest that alcohol abuse is the main contributory factor.

Adult↗

Nicotine chewing gum: effectiveness and the influence of patient education in a family practice.

The effectiveness of nicotine chewing gum in a family practice setting was evaluated. Ninety-nine subjects who were given a prescription for nicotine chewing gum were evaluated after one year to determine smoking status. Forty-nine subjects received only the gum, and 50 received the gum along with extensive personal instruction regarding its use. The two groups were compared with a third control group of 40 smokers who expressed no desire to stop smoking. At the end of one year, 12.2 percent of those receiving only gum and 10 percent receiving gum and instruction had stopped smoking, compared with a 20 percent cessation rate for the control group. The observed difference was not statistically significant (P greater than .05). Results of this study suggest that the use of nicotine gum alone may not be a viable alternative for family physicians whose patients desire to quit smoking.

Adult↗

Intraocular colchicine inhibits competition between resident and foreign optic axons for functional connections in the doubly innervated goldfish optic tectum.

After unilateral optic tectum ablation in the goldfish, regenerating optic axons grow into the optic layers of the remaining ipsilateral tectal lobe and regain visual function. The terminal arbors of the foreign fibers are initially diffusely distributed among the resident optic axons, but within two months the axon terminals from each retina are seen to segregate into irregular ocular dominance patches. Visual recovery is delayed until after segregation. This suggests that the foreign fibers compete with the residents for tectal targets and that the segregation of axon terminations is an anatomical characteristic of the process. Here we investigate whether inhibiting axonal transport in the resident fibers inhibits competition with foreign fibers. The eye contralateral to the intact tectal lobe received a single injection of 0.1 microgram colchicine, which does not block vision with the intact eye. We measured visual function using a classical conditioning technique. Segregation of axon terminations was examined shortly following visual recovery by autoradiography. The no-drug control fish showed reappearance of vision with the experimental eye at 9 weeks postoperatively and ocular dominance patches were well developed. Colchicine administered to the intact eye (resident fibers) several weeks postsurgery decreased the time to reappearance of vision with the experimental eye by several weeks. Autoradiography revealed some signs of axonal segregation but the labeled foreign axons were mainly continuously distributed. Administration of colchicine at the time of tectum ablation, or of lumicolchicine at two weeks postoperatively produced normal visual recovery times. Fast axonal transport of 3H-labeled protein was inhibited by 1.0 and 0.5 microgram but not by 0.1 microgram of colchicine or by 1.0 microgram of lumicolchicine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Modified di- and tripeptides of the C-terminal portion of oxytocin and vasopressin as possible cognition activation agents.

A number of peptides and modified peptides were synthesized and studied for their ability to reverse electroconvulsive shock-induced amnesia in rodents. A few of these peptides were selected for secondary evaluation in tests of short-term memory in rats and aged rhesus monkeys. A number of the peptides and modified peptides were active in the amnesia reversal test. In selected secondary tests, however, the chosen compounds failed to show significant activity in enhancing memory. New methods for preparing methyleneamino and methyleneoxy isosteres of peptides are reported. Other modified peptides also included methylenethio, methylenesulfonyl, and ethylene isosteres in place of the normal peptide amide bond.

Animals↗

Serum thiamin, pyridoxal, cobalamin and folate concentrations in young infants.

Blood samples were obtained from 509 apparently healthy infants between the age of 3 and 54 weeks attending for routine checks at infant health centres. Serum was assayed for thiamin, pyridoxal, cobalamin and folate. Three hundred and five infants were being breast fed and results from these were used to construct a reference range-thiamin 2-17 micrograms/l, pyridoxal 8-39 micrograms/l, cobalamin 120-800 ng/l and folate 7-47 micrograms/l (95 percentile ranges). One hundred and thirty-four infants were being fed a manufactured milk formulation and the serum concentrations of thiamin, pyridoxal and cobalamin were significantly higher than those found in breast fed infants. Thirteen infants were receiving pasteurized cow's milk. This milk was found to have more than 3 times the folate content of human breast milk yet these infants had a significantly reduced serum level of folate.

Age Factors↗

Comparative neurotoxicity of tubulin-binding drugs: inhibition of goldfish optic nerve regeneration.

Intraperitoneal or intraocular (io) injection of tubulin-binding drugs in goldfish, Carassius auratus L., inhibited axonal regeneration or restoration of functional synapses in optic axons following optic nerve crush. One eye was used to detect effects on regeneration and the other was kept intact to detect effects on maintenance of established optic circuits. Regeneration was assessed by measuring the time to reappearance of a visually evoked branchial suppression response. Three drugs, vincristine, vinblastine, and podophyllotoxin, administered semiweekly by ip injection, each inhibited regeneration at doses that did not impair maintenance of response. Similar results were previously reported for ip colchicine. Vincristine was several times more potent than podophyllotoxin or colchicine and 25 times more potent than vinblastine. Picropodophyllotoxin, an isomer of podophyllotoxin which has low affinity for tubulin, did not inhibit regeneration. The io experiments showed that maintenance of vision was reversibly inhibited by a single injection of 0.05 micrograms/g of colchicine but unaffected by 0.01 microgram/g, and that administration of the lower dose immediately following optic nerve crush inhibited regeneration. Intraocular lumicolchicine, a colchicine photoisomer which has low affinity for tubulin, did not inhibit maintenance or regeneration. In contrast, an io dose of vincristine sufficient to inhibit visual recovery also blocked maintenance of vision. Thus regeneration and maintenance effects could not be dissociated for io vincristine suggesting its mechanism of action on retinal cells is different. A conditioning lesion was shown to decrease the time to reappearance of the visually evoked branchial response following optic nerve crush, which indicates that it is a sensitive index of the rate of axonal outgrowth to the optic tectum.

Analysis of Variance↗

Continuous low-level apomorphine administration induces motor abnormalities and hallucinogen-like behaviors.

Continuous low-level (0.825 mg/kg/h for 20 h) administration of AP through SC in-dwelling silicone reservoirs in the rat induced behavioral and biochemical changes that were similar to those induced by low levels (0.1 mg/kg) of acutely administered AP (decreased behavioral activity and decreased dopamine metabolism in the striatum). With longer periods of continuous AP exposure (40 h or more) the activity-depressing effects of low-level AP diminished. Concurrently a novel behavioral syndrome emerged characterized by limb flicks, body shakes, sudden orienting responses, and motor abnormalities, such as tremors of the jaw muscles, chewing movements, prominent tongue extensions, and body 'tics'. This behavioral syndrome became more apparent following cessation of drug treatment. These novel behavioral changes, which were accompanied by increased behavioral responsiveness to acutely administered AP and amphetamine, were correlated with increased levels of dopamine, homovanillic acid, and 3,4-dihydroxyphenylacetic acid in the striatum but not the nucleus accumbens. This novel behavioral syndrome appears to reflect a rebound increase in dopaminergic mechanisms in striatum following their chronic suppression by low levels of AP.

Animals↗

Vision in goldfish following bilateral tectal ablation.

Visual sensitivity of optic tectum-ablated goldfish was investigated using a classical conditioning technique. Intact fish were screened to obtain individuals which showed suppression of breathing movements in response to the visual conditioned stimulus (CS) in the presence or absence of adapting illumination. Following bilateral optic tectum ablation, responding was blocked in light-adapted but not dark-adapted fish. Response threshold testing revealed no significant postoperative changes in visual sensitivity. Small remnants of tectal tissue containing cellular elements of the periventricular gray zone and optic axon terminals were detected in some ablates but there was no evident relationship to response threshold. Optic nerve crush blocked responding in ablates and recovery occurred within 2-3 weeks postaxotomy confirming that the response was mediated by retinal as opposed to extraretinal photostimulation. The experiments support the findings by others that tectum ablation results in decreased visual sensitivity and that conditioned visual responding can be obtained. However, we find no support for the suggestion that visual sensitivity in the ablates depends on functional recovery of regenerating optic axons which innervate non-tectal visual nuclei. Instead, the results indicate that the normal retinal projections to the non-tectal nuclei can mediate visual responding and, in addition, that postoperative conditioning experience facilitates recovery of response in ablates which initially appear to be blind to the CS.

Animals↗