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Biomedical subjects

T Brown

Publications and source records attributed to T Brown.

At least 433 records · Page 24Linked to original sources

Observations by immunofluorescence microscopy and electron microscopy on the cytopathogenicity of Naegleria fowleri in mouse embryo-cell cultures.

The destruction of secondary mouse-embryo (ME) cells by Naegleria fowleri was studied by indirect immunofluorescence with ME-cell antiserum as a specific label to trace the fate of mammalian-cell cytoplasm. The appearance of naegleria-induced cytopathic effect in the cultures coincided with the accumulation of discrete particles containing granules of ME-cell antigen within the cytoplasm of amoebae, suggesting that the organisms ingested host-cell material. In cultures containing cytochalasin B, a non-lethal inhibitor of phagocytosis by N. fowleri trophozoites failed to acquire any granular fluorescence and were not cytopathogenic. The engulfment of mammalian-cell cytoplasm by the organisms was confirmed when thin sections of naegleria-infected ME-cell cultures were examined by electron microscopy. Amoebae were seen in the process of detaching portions of cytoplasm from whole ME cells by means of distinctive ingesting pseudopodia, and fragments of mammalian-cell cytoplasm were identified within the food vacuoles of trophozoites. There was no evidence for cytotoxic disruption of ME cells before or during engulfment of these fragments. It is concluded that N. fowleri trophozoites attack and destroy cultured ME cells by a phagocytosis-like mechanism alone, without the aid of any amoeba-associated cytotoxic or cytolytic agents. The possible significance of these findings with respect to the in-vivo pathocity of N. fowleri is discussed.

Amoeba↗

Emergency coronary artery revascularization: a possible therapy for acute myocardial infarction.

Cardiac muscle death caused by coronary artery occlusion is a dynamic process that often takes hours or days. Emergency revascularization (saphenous vein bypass graft (SVBG) during acute myocardial infarction (MI) can interrupt myocardial necrosis, salvage ischemic myocardium and revascularize vessels with obstructive lesions not involved in the MI. In this report we describe a preliminary experimental study of 75 patients in which emergency SVBG was the therapy for acute MI. Group 1, 16 patients, required vasoactive medications and/or intraaortic balloon pumping to maintain their blood pressure preoperatively. There was one operative death and two late deaths. Group 2 consisted of 59 hemodynamically stable patients. There were no deaths. The average preop CPK in group 1 was 892 vs 504 in group 2 (p greater than 0.05). Surgical techniques were routine. The average time from the onset of chest pain that continued to surgery was 6.5 hours. Forty patients were restudied. Post- vs presurgical hemodynamics revealed ejection fraction increased by 34% (p greater than 0.05), left ventricular end-diastolic pressure reduced by 40% (p greater than 0.01). End-systolic and end-diastolic volume reduced by 30% (p greater than 0.05), and 15% (p greater than 0.01), and stroke volume improved 25% (p greater than 0.05). Operative mortality was 1.3% and late mortality 2.8%. These results suggest that cautious continued trial of emergency SVBG in patients with evolving MI is warranted.

Acute Disease↗

Decrease in insulin receptors during Friend erythroleukemia cell differentiation.

The Friend erythroleukemia cell has an insulin receptor with all the properties of mammalian insulin receptors: rapid, reversible, and saturable binding of insulin; specific for insulin and insulin analogs; inversely proportional to temperatures; sharply pH dependent (optimum = 8.0); and demonstrated ligand-induced accelerated dissociation consistent with negative cooperativity. There were 17,200 sites per cell. After induction by dimethylsulfoxide, 80% of the cells became benzidine positive (i.e., contained hemoglobin). The receptor concentration dropped to 4300 sites per cell, while the remaining receptors retained all the initial binding characteristics. This loss of receptors could not be attributed directly to either dimethylsulfoxide or changes in cell size. Thus, during the process of differentiation, the concentration of insulin receptors in the Friend erythroleukemia cell decreases.

Animals↗

Inheritance of tooth size in Australian aboriginals.

The purpose of this study was to clarify the question of inheritance of tooth size, with particular reference to the role of the sex chromosomes. Data were obtained from the dental casts of Aboriginals living at Yuendumu in the Northern Territory of Australia, who had participated in a longitudinal growth study extending over 20 years. The compilation and verification of comprehensive genealogical records gathered over a number of years enabled the analysis of family data. Product-moment correlation coefficients between different full-sibling and half-sibling pairs were calculated for permanent tooth size. Values of individual and average correlation for both mesiodistal and buccolingual tooth diameters conformed with the theoretical correlations expected assuming polygenic inheritance. However, no evidence of sex chromosomal involvement was found.

Australia↗

Crown diameters of the deciduous teeth in Australian Aboriginals.

Mesiodistal and buccolingual crown diameters were measured from dental casts representing the deciduous dentitions of 197 Aboriginal children from the Northern Territory of Australia. Double determination analysis indicated that the semi-automatic recording procedure used was reliable leading to observer errors of no practical significance. Tooth-size was greater in the male subjects but the sexual dimorphism was less marked than in the permanent teeth of the same subjects. The mandibular teeth were more uniform than maxillary with respect to buccolingual size relative to mesiodistal. Extremes of general tooth-size were more marked in the deciduous dentition than in the permanent as a consequence of the relatively large deciduous second molar which in Aboriginals approximates in size the permanent first molar of many other ethnic groups.

Australia↗

Heritability of permanent tooth size.

The aim of this investigation was to quantify the relative contributions of genetic and environmental influences to the observed variability of permanent tooth size in a group of Australian Aboriginals. Tooth size data were obtained from dental casts of Aboriginals living at Yuendumu in the Northern Territory of Australia. The custom of polygyny practised by these people enabled the analysis of associations between full-siblings and half-siblings. Phenotypic variability of tooth size was partitioned into four variance components; between sides, between fathers, between mothers and between offspring. From these components, the relative genetic and environmental contributions were quantified and heritability estimates for tooth size derived. Additional estimates of heritability were obtained by regression analysis from a small sample of parent-offspring data. Results of the analyses suggested that about 64% of the total variability of permanent tooth size could be attributed to genetic factors, while a further 6% was due to common environment. Although the findings confirm a relatively strong genetic component, they emphasise the importance of non-genetic influences in the determination of tooth size variability.

Australia↗

Tooth emergence in Australian Aboriginals.

Patterns of dental development in 125 Australian Aboriginal boys and girls, in a growth study at Yuendumu in the Northern Territory of Australia, were compared with Australians of European origin using mean tooth emergence curves constructed from the emergence times of right and left side permanent teeth. There were two active phases of tooth emergence separated by a quiescent period of 1.4 years in boys and 1.0 years in girls. Phase one included emergence of the first 12 teeth, that is the first permanent molars and all incisors; phase two included emergence of the canines, premolars and second molars. In Aboriginal girls most teeth emerged earlier than in boys. Compared with the European-descended, the Aboriginal children displayed earlier emergence of most teeth during phase two and a shorter quiescent period between the two phases, an emergence pattern similar to that reported in other non-European populations. In Aboriginals the process tooth emergence and subsequent alignment is aided by adequate space and compensatory bone growth growth in the alveolar regions. These factors, as well as the genetic differences between groups, contribute to the earlier emergence of teeth during phase two in the Aboriginal children.

Adolescent↗

Observations by light microscopy on the cytopathogenicity of Naegleria fowleri in mouse embryo-cell cultures.

Naegleria fowleri, strain HB-1, caused a destructive cytopathic effect (CPE) in secondary mouse-embryo (ME) cells. No evidence was found to suggest that cell-free cytotoxic factors secreted by the amoebae play a part in ME-cell destruction. In culture systems designed for the study of cytopathic factors, mammalian-cell damage seemed to occur only as a result of direct contact with active amoebae. This was confirmed when the progressive destruction of individual ME cells was observed continuously by direct microscopy and time-lapse cinemicrography. The cytoplasmic shrinkage characteristic of naegleria-induced CPE appeared to be associated with phagocytic activity of trophozoites. Adjacent ME cells remained undamaged until they themselves were physically attacked. The apparently intracellular location of amoebae seen in fixed and stained preparations was considered to be an artefact created when trophozoites and ME cells were superimposed.

Amoeba↗

Effect of inorganic iodide on thyroglobulin hydrolysis in cultured thyroid glands.

The process of thyroglobulin hydrolysis in mouse thyroid glands labelled in vitro was studied from 2-24 h after they had been maintained in tissue culture. The culture medium was supplemented with mononitrotyrosine to prevent deiodination of iodotyrosines. Hydrolysis of labelled thyroglobulin, under these conditions, led to the release of labelled iodotyrosines and iodothyronines. The rate of formation of these compounds was measured as an index of thyroglobulin hydrolysis (TH). TH was markedly stimulated by TSH. NaI inhibited TSH stimulation of TH at a concentration of 10(-5)M or greater. NaI, at similar concentrations,also markedly diminished or abolished the incorporation of 131I into thyroidal proteins from radioiodide-supplemented media. The addition of various inhibitors of iodination effectively blocked the effect of iodide on TH. In experiments where radioimmunossay was used to measure medium hormone concentrations, the release of unlabelled thyroxine (T4) and triiodothyronine (T3) induced by TSH was found to be significantly decreased in the presence of 10(-4)M NaI. These studies demonstrate that iodide inhibits the hydrolysis of thyroglobulin at or near concentrations which also inhibit iodination of thyroidal proteins. The present data suggest that formation of an iodinated compound is necessary for the effect of iodide. In addition, these studies demonstrate the utility of this in vitro system for the investigation of thyroid physiology.

Hydrolysis↗

Transiently reduced activity of carbamyl phosphate synthetase and ornithine transcarbamylase in liver of children with Reye's syndrome.

Since Reye's syndrome is associated with hyperammonemia, we measured the urea-cycle enzymes in hepatic tissue of 13 patients. Expressed as nanomoles of citrulline per milligram of hepatic protein per minute, mean activity of carbamyl phosphate synthetase (6.27 +/- 2.45 S.D.) and ornithine transcarbamylase (136.19 +/- 41.83) in Reye's syndrome was reduced significantly (P less than 0.005) when compared with that of 25 "normal" controls (11.54 +/- 4.24 and 307.49 +/- 94.15, respectively). Activity was maximally reduced during the first days of clinical symptoms; it returned toward normal during the following week regardless of whether the disease ended in death or recovery. The activity of the two enzymes was normal in patients with salicylate intoxication or heritable argininosuccinic acid synthetase deficiency. The apparent Km of hepatic ornithine transcarbamylase for ornithine was in the normal range in patients with Reye's syndrome (mean 0.24 mM). These observations indicate that Reye's syndrome is associated with acquired and transient dysfunction of hepatic mitochondrial urea-cycle enzymes.

Age Factors↗

Skeletal ossification and the adolescent growth spurt.

Fourteen ossification events in the hand and wrist were studied in relation to the age of peak growth velocity in body height in fifty-two boys and thirty-six girls. The subjects were aborigines enrolled in a longitudinal growth study. Peak growth velocity and the ossification events occurred in aborigines at about the same ages as in Caucasian children. The results indicate that the ossification events can be used by the orthodontist to assess a child's growth activity. The accelerative phase of the adolescent growth spurt is accompanied by epiphyseal widths reaching diaphyseal widths in the fingers and radius and by ossification of the pisiform and hamate Stage 1. Peak growth velocity occurs at about the time of epiphyseal capping in the fingers and radius and ossification of the sesamoid and hamate Stage 2. The decelerative phase of growth is indicated by epiphyseal union in the third finger, progressively from distal to proximal phalanges, and in the radius. The value of these indicators in orthodontic practice is discussed.

Adolescent↗