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Biomedical subjects

C J Smith

Publications and source records attributed to C J Smith.

At least 253 records · Page 14Linked to original sources

The effect of an intensive education programme on the glycaemic control of type I diabetic patients.

The effect of patient education on glycaemic control in insulin-dependent diabetes mellitus was assessed in 20 patients selected from the Diabetes Clinic, Groote Schuur Hospital. Education in all aspects of self-care was given to small groups of between 5 and 7 patients. Biochemical tests including measurement of fasting blood glucose (FBG) and glycosylated haemoglobin (HbA1c), were performed during a 6-week 'control' period before the educational course, and again during a 6-week 'test' period after it. The mean HbA1c fell from 10.05 +/- 0.43% at the end of the control period to 8.47 +/- 0.25% at the end of the test period (P less than 0.001). FBG levels dropped from 13.53 +/- 0.84 mmol/l at the commencement of the study to 10.83 +/- 1.29 mmol/l before the educational course, and to 9.41 +/- 0.72 mmol/l at the completion of the study. We therefore conclude that intensive education of this nature is of benefit in improving glycaemic control, at least in the short term.

Adult↗

A histological study of the chronology of initial mineralization in the human deciduous dentition.

Accurate dating of initial mineralization in the dentition was derived from fetuses aged according to the maternal history, assessment of gestational age by obstetricians, paediatricians and pathologists, histological evaluation of their cerebellar and renal development, and accurate measurements of crown-rump length, skull circumference, brain and body weight. Serial sections of the jaws of 121 fetuses ranging from 10 to 26 weeks post-menstrual age first showed mineralized dentine in the deciduous central incisor at 15-19 weeks, in the lateral incisor at 16-21 weeks, in the canine at 19-22 weeks, in the deciduous first molar at 16-19 weeks and in the second molar at 20-22 weeks. These age ranges differ from those for initial mineralization common in textbooks, particularly for the molars.

Cuspid↗

Extrachromosomal systems and gene transmission in anaerobic bacteria.

Obligately anaerobic bacteria are important in terms of their role as medical pathogens as well as their degradative capacities in a variety of natural ecosystems. Two major anaerobic genera, Bacteroides and Clostridium, are examined in this review. Plasmid elements in both genera are reviewed within the context of conjugal transfer and drug resistance. Genetic systems that facilitate the study of these anaerobic bacteria have emerged during the past several years. In large part, these developments have been linked to work centered on extrachromosomal genetic systems in these organisms. Conjugal transfer of antibiotic resistance has been a central focus in this regard. Transposable genetic elements in the Bacteroides are discussed and the evolution and spread of resistance to lincosamide antibiotics are considered at the molecular level. Recombinant DNA systems that employ shuttle vectors which are mobilized by conjugative plasmids have been developed for use in Bacteroides and Clostridium. The application of transmission and recombinant DNA genetic systems to study these anaerobes is under way and is likely to lead to an increased understanding of this important group of procaryotes.

Bacteroides↗

Allergic etiology of benign fibrocystic changes of the breast.

We postulate that fibrocystic changes in the female breast are the end result of a series of biochemical events initiated by the mast cell degranulation products histamine and heparin. Two mechanisms are proposed which could lead to mast cell degranulation in breast tissue. First, low progesterone levels lead to decreased intracellular cAMP levels in mast cells which enhance mast cell degranulation. Second, low progesterone levels lead to increased solubilization of breast collagen during tissue turnover. Susceptible individuals may undergo an allergic reaction to soluble collagen resulting in further mast cell degranulation. The degranulation products histamine and heparin may stimulate increased stromal proliferation and vascularization respectively. We provide evidence for the occurrence of histamine release by demonstrating an increased incidence of allergic symptoms in white women with fibrocystic breast changes.

Collagen↗

Are there hunger and satiety factors in the blood of domestic fowls?

The presence of blood-borne hunger and satiety factors in domestic fowls was investigated in two experiments. In the first, birds that had previously been fed ad libitum or fasted for 24 h ate less after their blood had been transfused with that of fed or fasted donors than they did after two control treatments. Blood from fed donors suppressed intake more than did blood from fasted donors, but not significantly so. In the second experiment, previously fed birds ate less in the first hour after intravenous injection of reconstituted plasma from 24-h fasted donors, than after control injections of saline. The same treatments had little or no effect with subjects that had previously been fasted for 24 h. These results consistently indicate an absence of any hunger factor, but are less conclusive with regard to the presence of a satiety factor, for which there is recent evidence in fowls from central administration of plasma. It is suggested that hunger and satiety may be associated with scarcity and abundance of the same humoral factor(s), and that monitoring of blood composition may provide the necessary feedback for longer-term adjustments in food intake, modifying short-term control based on emptying and filling of part(s) of the alimentary tract.

Animals↗

Pulsatile secretion of bioactive luteinizing hormone in adult male rhesus macaques: acute and chronic effects of orchidectomy.

Serum concentrations of bioactive luteinizing hormone (LH) and of testosterone were measured in adult male rhesus macaques at the time of, and at least 6 wk after orchidectomy. The effects of anesthesia alone and of sham surgery on the secretion of these hormones were also studied. Contrary to expectations based on current notions of the negative feedback actions of testosterone on gonadotropin secretion, pulsatile LH release was absent for an average of 9.3 h immediately after removal of the testes. Animals that were subjected to sham surgery or anesthesia alone showed a delay of 4.4 h in the reappearance of LH secretion, similar to the lull in LH pulsations normally observed at the time of day. When LH secretion resumed in the acutely castrated animals, the pulses continued for the remainder of the sampling period and did not show the midmorning decrease in activity characteristic of intact or sham-operated animals. In the animals that were castrated, circulating cortisol was elevated approximately twofold above levels observed in sham-operated animals for a period of 8 h, beginning immediately after castration. In the long-term (greater than 6 wk) castrated male macaques, circulating bioactive LH levels were eightfold greater (24 micrograms/ml) than levels observed in intact animals (3 micrograms/ml). The frequency of LH pulses in the castrated animals, as determined by PULSAR analysis, was significantly influenced by sampling frequency. When blood samples were taken at 15-min intervals for 24 h, LH pulse frequency averaged 7 pulses/12 h. If samples were collected every 7 min for 12 h, the frequency increased to 13 pulses/12 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A competitive immunosorbent assay for detection of Pseudomonas pseudomallei exotoxin.

The development of monoclonal antibody and enzyme-linked immunosorbent assay (ELISA) techniques has made possible the detection of specific antigens at extremely low concentrations. Diagnosis of recalcitrant diseases such as melioidosis depends upon either early isolation and identification of the causative organism or the identification of a specific marker antigen, Pseudomonas pseudomallei exotoxin, in serum; the latter is better because it allows more rapid and simple diagnosis. A method of detecting exotoxin concentrations of greater than 16 ng/ml by an ELISA based on a monoclonal antitoxin is here described; it is significantly more sensitive than the mouse lethality test (lower threshold 30 micrograms/ml) currently in use and an in-vitro cytotoxicity test (lower threshold 10 micrograms/ml) that we have developed and describe here.

Animals↗

Identification of polysaccharide hydrolases involved in autolytic degradation of zea cell walls.

Cell walls of Zea mays (cv L.G.11) seedlings labeled with (14)C were treated with alpha-amylase from Bacillus subtilis to remove starch and mixed linkage glucans. These walls released arabinose, xylose, galactose, and galacturonic acid in addition to glucose when they were allowed to autolyze. Methylation analysis was performed on samples of wall which had been incubated autolytically and the results indicated that degradation of the major polymer of the wall, the glucoarabinoxylan, had occurred. A number of glycanases could be dissociated from the wall by use of 3 m LiCL. The proteins which were released were found to contain a number of exoglycosidase activities in addition to being effective in degrading the polysaccharide substrates, araban, xylan, galactan, laminarin, mannan, and polygalacturonic acid. The effects of these enzymes on the wall during autolysis appear to result from endo-activity in addition to exo-activity. The structural changes that occurred in the cell walls during autolysis were found to be related to the changes previously found to occur in cell walls during auxin induced extension.

Journal Article↗

Nucleotide sequence analysis of Tn4551: use of ermFS operon fusions to detect promoter activity in Bacteroides fragilis.

The Bacteroides pBI136 clindamycin resistance (Ccr) determinant from the composite transposon Tn4551 was cloned onto the shuttle plasmid pFD160, and the regions necessary for expression in Bacteroides fragilis were determined. These results suggested that transcriptional regulatory signals required for Ccr were located in the Tn4551 direct repeat sequence (DRS) adjacent to the resistance determinant. Analysis of the nucleotide sequence of this region revealed that the Ccr structural gene, 798 base pairs (bp), was located 17 bp from the terminus of the DRS and that this gene (ermFS) differed from ermF (pBF4) by one amino acid. The DRS element was found to be 1,155 bp and appeared to contain the ermFS transcription start signals. The DRS structure was typical of insertion sequence elements isolated from other bacterial species, and its termini were characterized by 25-bp regions of imperfect dyad symmetry. The DRS was dominated by a 978-bp open reading frame, which terminated in the left inverted repeat 27 bp from the ermFS start codon, and weak amino acid sequence homology was observed with the putative transposase of IS3. Promoter activity of the DRS in B. fragilis was demonstrated by in vitro construction of operon fusions with a promoterless ermFS gene followed by transformation of the recombinant plasmids with selection for resistance to clindamycin. The location of one DRS promoter was identified by using the ermFS fusions and then verified by in vitro mutagenesis of the site with single-stranded linkers. Northern blot (RNA blot) analysis of total RNA from B. fragilis strains containing pBI136 or ermFS recombinant plasmids confirmed the location of this promoter and indicated that it was used in vivo by Tn4551. A second DRS promoter, which activated ermFS transcription by readthrough of the large DRS open reading frame, was also identified by the Northern blot analysis. The bicistronic ermFS message was not observed in strains containing a complete copy of Tn4551, and the possibility of transcriptional regulation is discussed.

Amino Acid Sequence↗

Transposition of Tn4551 in Bacteroides fragilis: identification and properties of a new transposon from Bacteroides spp.

Tn4551, a clindamycin resistance (Ccr) transposon from the R plasmid pBI136, was cloned onto an Escherichia coli-Bacteroides shuttle vector which could replicate normally in E. coli but was maintained unstably in Bacteroides fragilis. To aid in cloning and to ensure maintenance of Tn4551 in E. coli, a kanamycin resistance determinant (Kmr) was inserted in the transposon. The transposon-bearing shuttle vector pFD197 was transformed into B. fragilis 638, and putative insertions of Tn4551::Kmr were identified by screening for resistance to clindamycin and plasmid content. Southern hybridization analyses were used to verify integration of the transposon in the B. fragilis chromosome, and the frequency of insertion was estimated at 7.8 X 10(-5) events per generation. In 57% of the isolates tested a second integration event also occurred. This second insertion apparently involved just a single copy of the 1.2-kilobase repeat sequence which flanks the transposon. In addition, Tn4551::Kmr appeared to function as a transposon in E. coli. Evidence for this was obtained by the isolation of transposon insertions into the bacteriophage P1 genome. Finally, the transposon vector, pFD197, could be mobilized to other B. fragilis strains in which transposition was detected. Mobilization from the strain 638 background was via a conjugation like process, but occurred in the absence of known conjugative elements or other detectable plasmids. This result suggested the presence of a host-encoded transfer system in this B. fragilis strain.

Bacteroides fragilis↗

Nicotinic receptor abnormalities in Alzheimer's and Parkinson's diseases.

The status of cholinergic receptors in dementia is related to the question of potential cholinergic therapy. Whilst muscarinic receptor binding is generally reported to be normal or near normal, findings are reported which indicate substantial reductions of hippocampal nicotinic (high affinity nicotine) binding (occurring in conjunction with decreased choline acetyltransferase) in both Alzheimer's and Parkinson's but not Huntington's disease. A further indication that nicotinic receptor function may be abnormal in Alzheimer's disease is the extensive loss of an endogenous compound, detected for the first time in human brain, which inhibits normal nicotinic binding. Both receptor binding and the inhibitor are also substantially decreased with increasing age in the normal hippocampus.

Adult↗

Circadian periodicity in circulating cortisol is absent after orchidectomy in rhesus macaques.

Circadian/ultradian patterns of plasma cortisol were assessed in four intact and four gonadectomized male rhesus macaques. Concomitant measures of testosterone (T) were analyzed in the intact animals. Blood samples were drawn every 15 min for 28 h via an indwelling catheter. Plasma concentrations of cortisol and T were determined by RIA. Inverse diurnal patterns of cortisol and T secretion were documented in the control group. The circadian pattern of plasma cortisol was characterized by a progressive rise during the early morning hours (0200-0800 h), followed by a gradual decline until lowest levels were reached at 1600-1900 h. T levels were lowest from 0800-1200 h (2-4 ng/ml) and reached a zenith from 2200-0200 h (8-10 ng/ml). Surprisingly, circadian fluctuations in cortisol were absent after orchidectomy. Cortisol levels in castrates were less (P less than 0.05) than those during peak levels of cortisol secretion in the intact animals (6.25 vs. 10.1 micrograms/100 ml) and elevated (P less than 0.01) compared to concentrations in the intact animals at their nadir (6.4 vs. 2.5 micrograms/100 ml). The loss of circadian fluctuation was not associated with a significant change in frequency of pulsatile cortisol release or a change in the daily mean level. These results are the first in nonhuman primates to demonstrate that the testes modulate circadian activity in the hypothalamic-pituitary-adrenocortical axis. The data differ from previous findings in rodents suggesting that castration increases the synthesis and release of ACTH/corticosterone.

Animals↗

Influence of the gonads on cortisol secretion in female rhesus macaques.

Circadian and ultradian patterns of plasma cortisol were assessed in four intact female rhesus macaques during both the late follicular (days 9-10) and midluteal (days 21-22) phases of the menstrual cycle and compared to patterns in four ovariectomized macaques. Blood samples were drawn from a remote site at 15-min intervals for 24 h via an indwelling catheter. Measures of estrogen and progesterone were obtained for each subject. For purposes of data analyses, group cortisol measurements were collapsed across hourly intervals and submitted to analysis of variance. Pulsatile characteristics of cortisol release were determined for each subject using the PULSAR computer program. Circadian cortisol patterns, present in all three groups, were characterized by a progressive rise during early morning hours (0300-0600 h), followed by a decline of short duration. All groups then displayed an unexpected midday peak (0900-1400 h), at which time cortisol levels reached their daily zenith. In each of the three groups, cortisol levels reached a nadir during late afternoon hours shortly after the light phase ended. The amplitude of circadian changes and daily mean levels of cortisol were significantly reduced by ovariectomy, without alterations in pulsatile characteristics of cortisol secretion. Daily mean cortisol levels decreased from approximately 8 micrograms/100 ml in intact subjects to 4.5 micrograms/100 ml after ovariectomy. No significant differences in the circadian/ultradian periodicity of cortisol secretion were detected between the follicular and luteal groups. When data in the intact female groups were combined and compared to those previously obtained from gonadally intact adult male macaques, similar 24-h patterns of cortisol secretion were detected. Surprisingly, amplitude changes in cortisol concentrations after ovariectomy were temporally and quantitatively similar to those in orchidectomized males. In both male and female animals, circadian patterns of cortisol secretion were reduced by gonadectomy. These results are discussed in terms of the activational influence of gonadal steroids on hypothalamic-pituitary-adrenocortical function.

Animals↗

Cortical neuropathological and neurochemical substrates of Alzheimer's and Parkinson's diseases.

Whilst the neuropathological correlates of Alzheimer type dementia--cortical neurofibrillary tangles and senile plaques--are well defined, the prevalence of these cortical abnormalities in Parkinson's disease and their relation to dementia is unclear. In a series of 46 consecutive cases of clinically and pathologically established Parkinson's disease the prevalence of mild Alzheimer-type pathology (exceeding the normal but not as extensive as in Alzheimer's disease) was increased 2 to 3 fold compared with an age-matched control group, although there was no obvious relation to the presence or severity of dementia. In a subgroup of Parkinsonian cases (both demented and non-demented), examined neurochemically, there were both similarities (decreased choline acetyltransferase, nicotinic and serotonergic S 1 receptor activities) and distinctions (increased muscarinic receptor binding--particularly to the "L" subtype, and normal serotonergic S 2, somatostatin, and D-aspartate binding together with normal levels of an endogenous nicotine binding inhibitor) compared with a group of cases with Alzheimer's disease. Amongst the various pathological and chemical indices examined, only presynaptic cholinergic markers (including the number of Meynert neurons) and S 1 receptor binding were related to dementia in Parkinson's disease. It is suggested that whilst coincidental classical Alzheimer's disease is infrequent in Parkinson's disease (5% in the present series) Alzheimer's disease itself is distinguished from Parkinson's disease by the formation of numerous neocortical neurofibrillary tangles and a reduction in glutamate uptake, serotonergic S 2 receptors and possibly in endogenous nicotine binding inhibitor.

Adult↗

Efficacy of ivermectin against the pig mange mite Sarcoptes scabiei var. suis.

The efficacy of a single subcutaneous dose of ivermectin at 300 micrograms/kg was evaluated against Sarcoptes scabiei in a commercial herd of 146 pigs of which more than 80% were naturally clinically affected with mange. All pigs, except 6 control animals, were treated with ivermectin on Day 0. Scrapings for mite recovery were made from 12 treated animals and 6 controls at the time of treatment and 28 and 42 days later. No mites were recovered from pigs after treatment while live mites were present in scrapings from all control animals. No treated pigs had active lesions at examination on Day 42. The results are discussed in relation to recommendations for a control program for Sarcoptes scabiei in pigs.

Animals↗