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Biomedical subjects

F Watson

Publications and source records attributed to F Watson.

At least 55 records · Page 3Linked to original sources
PubMed1990

Receptor expression and oxidase activity in human neutrophils: regulation by granulocyte-macrophage colony-stimulating factor and dependence upon protein biosynthesis.

Incubation of human bloodstream neutrophils with 50 u/ml recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) "primed" the respiratory burst (as assessed by fMet-Leu-Phe stimulated luminol-dependent chemiluminescence) and resulted in a rapid (within 15 min) up-regulation of expression of CD11b and CD18 (as measured by FACS analysis). This rapid "priming" and modulation of receptor expression was not inhibited by cycloheximide and hence appeared to be independent of de novo protein biosynthesis. When neutrophils were incubated for up to 5 h in culture, the fluorescence distributions of CD11b and CD18 declined indicating the loss of expression of these receptors as the neutrophils aged, but in rGM-CSF treated suspensions receptor expression was maintained. When neutrophils were incubated in the presence of cycloheximide, they progressively lost their ability to generate reactive oxidants in response to fMet-Leu-Phe so that by 5 h incubation with this inhibitor they could only generate about 25% of the oxidative response stimulated in untreated cells, and the expression of CD16 and CD18 was grossly impaired. Similar effects were observed in rGM-CSF treated suspensions except that cycloheximide required longer incubation times (typically 4-5 h) before impairment of function or receptor expression occurred. These data show that de novo protein biosynthesis is required for both the maintenance of neutrophil function and also for the continued expression of some plasma membrane receptors.

Antigens, CD↗
PubMed1989

Sequence of the variant thyroxine-binding globulin of Australian aborigines. Only one of two amino acid replacements is responsible for its altered properties.

A form of thyroxine-binding globulin (TBG) with reduced affinity for hormone and increased susceptibility to heat and acid denaturation has been identified in Australian Aborigines (TBG-A). Results of heat denaturation of TBG established that the TBGA allele is X linked and has a frequency of 50.9% in Western Australian Aborigines. The sequence of an isolated TBGA allele differed at two positions from that of the normal TBG allele (TBGC). One substitution was in codon 191, ACA (threonine) rather than GCA (alanine), and the other was in codon 283, TTT (phenylalanine) instead of TTG (leucine). These nucleotide substitutions resulted in the loss of sites for the enzymes Bgl 1 and Tth 111 II, respectively. The nucleotide substitutions in the TBG-A allele was confirmed by digestion of genomic DNA segments amplified using the polymerase chain reaction. The Bgl 1 and Tth 111 II sites were absent in the genes of two Aboriginal men expressing TBG-A and were present in those of three Aboriginal and six Caucasian males expressing TBG-C. The TBG gene of a seventh Caucasian male possessed the Bgl 1 site but had lost the Tth 111 II site; sequencing of this allele revealed only the substitution in codon 283 identical to that in the TBGA allele. As the biochemical properties of TBGPhe-283 expressed by this individual were indistinguishable from normal TBGLeu-283, we believe that the abnormal properties of TBG-A are due to substitution of alanine for threonine at residue 191.

Adolescent↗
PubMed1985

Variant thyroxine-binding globulin in serum of Australian aborigines: a comparison with familial TBG deficiency in Caucasians and American blacks.

About 40% of clinically euthyroid Australian Aborigines have low concentrations of total thyroxine (TT4) and triiodothyronine (TT3) in serum. While the finding of normal concentrations of serum thyrotropin (TSH) in such individuals is compatible with their eumetabolic state, the reason for the finding of a low free T4 index (FT4I) has been unclear. A genetic variant of T4-binding globulin (TBG) with reduced affinity for T4 has been suggested but decrease in the absolute concentration of TBG has also been reported. In this study, we measured various parameters of thyroid function in 20 serum samples from euthyroid Australian Aborigines selected for their low TT4 levels. Results were compared to those obtained in serum samples from Caucasians and American Blacks with inherited partial TBG deficiency, 15 of which were matched to the Aborigines by their TBG and 20 by their TT4 concentrations. Results were also compared with those from another group of 20 samples from Caucasians and American Blacks with normal TBG concentration, matched to the Aborigines by their serum TT4 concentration. TBG in serum from these Australian Aborigines was immunologically identical to that in Caucasians and American Blacks in terms of parallelism of serially diluted samples in the TBG radioimmunoassay (RIA).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Variant thyroxine-binding globulin in serum of Australian aborigines: its physical, chemical and biological properties.

Low serum total thyroxine (TT4) and triiodothyronine (TT3) is found in approximately 40% of Australian Aborigines. Studies were carried out to characterize the properties of thyroxine-binding globulin (TBG) in these Australian Aborigines to explain the observed reduction of thyroid hormone concentration in their serum. TBG from Aborigines with low serum TT4 concentrations was compared to TBG from Aborigines with normal TT4 concentration and Caucasians and American Blacks with normal or reduced serum TBG levels due to familial partial TBG deficiency. TBG from Aborigines with low serum TT4 concentrations had a reduced affinity for thyroid hormone (Ka). The Ka for T4 was 54% and for T3 30% of the Ka values for TBG from Aborigines with normal TT4 concentration or non-Aborigines. Maximal binding values were in agreement with TBG measurements by RIA for Aborigines with low or normal serum TT4 and for non-Aborigines. An increase in the rate of heat denaturation of TBG at temperatures from 54 to 60 C was also observed in sera from Aborigines with low TT4. The heat lability was lowered by 2 C. The low concentration of TT4 in serum of these Aborigines could not explain this higher heat lability of TBG since only addition of greater than 80-fold the physiologic T4 concentration obliterated the difference of heat inactivation by denaturation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Protection of recently shorn sheep against adverse weather using plastic coats.

Sheep cold stressed for 10.5 h had plastic coats applied then the cold stress was continued. In 9 of 10 sheep (test group) showing hypothermia at the time coats were applied, body temperatures had returned to near normal 2.5 h later and to normal in 13.5 h. One sheep severely hypothermic before the coat was applied did not improve and was killed after 2.5 h. Sheep that were cold stressed without coats (wet controls) developed marked hypothermia and were killed between 10.5 h and 21 h. Rectal temperatures remained normal in controls that were cold stressed with coats on (coated wet controls) and in the controls not subjected to wetting (dry controls). Plasma cortisol increased markedly in the cold stressed sheep until plastic coats were applied, but the levels had fallen to normal levels 20 h later. Serum thyroxine levels increased at a faster rate in the test group and in wet controls than in the dry controls and coated wet controls during the first 9 h of cold stress. In 4 sheep of the test group energy utilisation increased markedly and remained high for a variable time after coats were applied then gradually returned to pre-cold stress levels. Liver tyrosine aminotransferase levels of the wet controls were markedly elevated compared to levels found in the test group sheep killed 79.5 h after coats were applied. Histological changes in the spleen and liver of wet controls was absent or only mildly present in the test group sheep. There was severe depletion of muscle and liver glycogen in the wet controls compared with the test group sheep, which were similar to the dry controls and coated wet controls.

Animals↗
PubMed1983

Laboratory evaluation of thyroid function in Australian aborigines.

The presence of what we believe is a unique variant of thyroxine-binding globulin in a high proportion of Australian Aborigines causes difficulty in the interpretation of thyroid function tests in such subjects. We present reference ranges for the common tests of thyroid function and a suitable combination of tests for the laboratory investigation of thyroid function in Aborigines. We suggest that the thyroid status of Aborigines previously diagnosed as hypothyroid should be reviewed.

Australia↗
PubMed1981

A possible variant of thyroxine-binding globulin in Australian Aborigines.

We have recently described a major variation from the normal levels of serum thyroxine-binding globulin in many Australian Aborigines [1]. Subsequently we presented evidence that affected individuals were widely distributed throughout Australia, that "low values of thyroxine-binding globulin were not caused by environmental or health factors, but were inherited in an autosomal dominant fashion [2]. Refetoff [3] has shown that the cause of genetically determined low thyroxine-binding globulin levels in Caucasians is alteration in synthesis rate without any structural variation of the protein. Since however the "low" thyroxine-binding globulin of Aborigines is vastly more prevalent and genetically distinct from the X-linked type, we investigated the possibility that this may be a structural variant. Evidence suggestive of this includes results from heat inactivation, competitive binding of thyroxine to thyroxine-binding globulin to measure affinity, and use of a radioimmunoassay different from that used in the original work. The "Low thyroxine-binding globulin of Aborigines may be a protein with a structural variation at or near the binding site for thyroxine, resulting in low affinity for thyroxine and hence "low" results with assay methods which depend upon the thyroxine binding site. Since the Australoid peoples, to whom Australian Aborigines are racially related, are distributed widely throughout the southern hemisphere it is important to establish whether this variant is found outside Australia in order to avoid the likelihood of misdiagnosis of thyroid disease in such subjects.

Australia↗
PubMed1981

Endocrine function of the heterotopic pancreatic allotransplant in dogs. I. Normal and rejection.

After heterotopic pancreatic allotransplantation in dogs and in the absence of rejection there was a fasting normoglycemia with a marked hyperinsulinemia. On intravenous glucose tolerance testing and intravenous glucagon testing, the blood sugar response of dogs receiving no immunosuppression was normal but the response in dogs receiving immunosuppressive therapy was exaggerated. There was a marked increase in the insulin response compared with normal animals whether or not immunosuppressive therapy was administered. The first endocrine even during allograft rejection seemed to be a drop in the pancreatic insulin reserve as demonstrated by plasma insulin results during a glucagon test; occurring 2 to 3 days before clinically overt rejection. This was also found on glucose tolerance testing. A rise in the fasting plasma insulin occurred next, 1 to 2 days before a rise in the fasting blood sugar. As the rejection process progressed, the plasma insulin levels subsequently dropped until the death of the animal. If, during a rejection process, the blood sugar did not rise above 150 mg/100 ml and the plasma insulin level did not drop below the lower limit of normal the rejection was usually reversible with intravenous methylprednisolone.

Animals↗
PubMed1981

Endocrine function of the heterotopic pancreatic allotransplant in dogs. II. Immediate post-transplant period.

Pancreatic endocrine function was investigated in dogs after heterotopic pancreatic allotransplantation. A marked hyperinsulinemia was found in peripheral venous blood within the first 60 min postoperatively. This was associated with hypoglycemia and hypokalemia occurring within the next 2 to 3 hr resulting eventually in death. The hypoglycemia could be corrected by parenteral dextrose and potassium given during the first 2 hr postoperatively or prevented by parenteral hydrocortisone given at the time of transplantation.

Animals↗
PubMed1981

Endocrine function of the heterotopic pancreatic allotransplant in dogs.

After pancreatectomy and heterotopic pancreatic allotransplantation in dogs, there was a pattern of endocrine activity similar to that found following a combination of pancreatic denervation and total transposition of the pancreatic venous effluent from the portal of the systemic venous circulation. Denervation of the pancreas alone or total venous transposition alone did not mirror these results. The mechanism of the effect of these two factors is discussed.

Animals↗
PubMed1981

Multiple systems organ failure: VII. Reduction in plasma branched-chain amino acids--correlations with liver failure and amino acid infusion.

Lower fractional concentrations of branched-chain amino acids were found in trauma-septic patients who did not survive than in those who survived (p values less than or equal to 0.046 to 0.001). A liver dysfunction scale was constructed on the basis of the levels of plasma bilirubin, albumin, SGOT, prothrombin time, and neurologic encephalopathy. Increased liver dysfunction was associated with reduced plasma fractional branched-chain amino acids for all branched-chain amino acids in both the surviving and nonsurviving patients except for valine in the nonsurviving group. This decrease was statistically significant (p less than or equal to 0.041 to 0.001) for leucine and isoleucine in the nonsurvivors and for valine in the survivors. The infusion of amino acids was associated with a decrease in the fractional concentrations in the nonsurvivors for leucine while the fractional concentrations of isoleucine in the nonsurvivors and isoleucine and valine in the survivors rose. The statistically significant changes (p less than 0.018 to 0.001) were for leucine in the nonsurvivors and isoleucine and valine in the survivors. When the liver dysfunction and amino acid infusion related changes are taken in;to account there were no significant differences in the fractional branched-chain concentrations between survivors and nonsurvivors. Liver dysfunction and low fractional branched-chain amino acids were linked in magnitude in a way that is consistent with the low branched-chain amino acids producing the liver dysfunction.

Amino Acids↗
PubMed1980

Distribution and inheritance of low serum thyroxine-binding globulin levels in Australian Aborigines: a new genetic variation.

Evidence is presented that low serum thyroxine-binding globulin (TBG) levels in Aborigines are widely distributed throughout Australia, and that these are inherited rather than acquired. Levels of TBG in children, and lack of any correlation of low TBG levels with alcohol consumption or liver dysfunction, suggest that the low levels are not acquired in adult life. Genetic studies in eight families indicate (with one exception) an autosomal dominant pattern of inheritance with direct male-to-male transmission. These findings are in marked contrast to the much rarer X-linked pattern of inheritance of low TBG levels in Caucasians. This type of prevalent and inherited low level of TBG in serum appears so far to be unique to the Aboriginal race. The synthesis (or degradation) of TBG may be controlled by an autosomal gene in Aborigines.

Adolescent↗
PubMed1980

Prevalent low serum thyroxine-binding globulin level in Western Australian aborigines: its effect on thyroid function tests.

The first major variation from the normal human levels of thyroxine-binding globulin (TBG) in a racial group is reported in full-blood Aborigines of Western Australia. This finding has not only biochemical and anthropological interest, but also medical significance in that many common laboratory tests of thyroid function in this group are very liable to misinterpretation because of low TBG levels. In Aborigines in the Halls Creek area of Western Australia, 40% have TBG levels below the lower reference limit for Caucasians, and 18% have levels between half and one-third of the lower limit. Such subjects have low thyroxine levels by Caucasian standards, and frequently the results of triiodothyronine uptake (T3U) tests lend support to the false suggestion of hypothyroidism. Caucasian reference ranges are not valid in this large proportion of the Aboriginal population. It is not yet clear whether the low TBG levels are a normal feature in this racial population, or whether there is some other cause. The subjects of the study were not acutely ill and Aborigines with low TBG are well distributed throughout the State.

Australia↗