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Biomedical subjects

H C Ford

Publications and source records attributed to H C Ford.

At least 37 records · Page 2Linked to original sources

A survey of the iodide concentration of human milk.

The iodide concentration of human milk from mothers living in the Wellington area and of six prepared infant formulae was measured. A total of 93 human milk samples were assayed, 14 from mothers of infants delivered at less than 35 weeks gestation and collected within 30 days of delivery (group A), 57 samples from mothers of infants delivered at 35 or more weeks gestation and collected within 60 days of delivery (group B) and 22 samples from mothers with infants aged greater than 60 days (group C). There was no significant (p greater than 0.05) difference between the means (SE) of groups A 1.14 mumol/L (0.20) and B 0.98 mumol/L (0.07). The mean for group C 0.39 mumol/L (0.03) was significantly less (p less than 0.05) than the means for both groups A and B. For groups A, B and C combined, there was a correlation (r = 0.44, p less than 0.01) between the milk iodide concentration and the iodide/creatinine ratio of a maternal urine specimen obtained immediately before or after the milk specimen. Formula milk preparations based on cow's milk contained higher concentrations of iodide than human milk.

Creatinine↗

Haemostasis in hypothyroidism.

Abnormalities that have been reported for platelet indices and function, coagulation factors and tests, and the fibrinolytic system in hypothyroidism are reviewed. These abnormalities, although usually of limited importance clinically, may occasionally lead to major bleeding episodes and to diagnostic confusion.

Blood Coagulation Disorders↗

Serum and red cell folate and serum vitamin B12 levels in hyperthyroidism.

Serum and red blood cell folate levels and serum B12 concentration were determined by radioassay in 20 hyperthyroid patients and compared with values obtained when the same patients had been euthyroid for at least 4 months. In hyperthyroidism, the levels of serum and red blood cell folate were significantly (P less than .01) higher than when euthyroidism was achieved. There was no significant change in serum B12 concentration. Declines in serum and red blood cell folate levels between hyperthyroidism and euthyroidism occurred in 15 and 16 of the 20 patients, respectively. Although the explanation for the relative elevations of serum and red blood cell folate levels in hyperthyroid patients is unclear at present, our findings do not support the view that hyperthyroidism in man is associated with depletion of folate stores or subclinical deficiency of the vitamin.

Adult↗

Human placental cytotrophoblast cells: identification and culture.

Methods of disaggregation of human placental tissue were assessed with the aim of maximising the yield of cytotrophoblast cells and minimising contamination with other cell types. Brief exposure to crude trypsin was found to be the best way to balance yield of trophoblast cells against contamination by cells of the villous core. Much higher yields of all cell types could be obtained by digestion with other enzymes. Staining for NADH diaphorase activity coupled with general morphology was found to be a reasonably specific, rapid and simple method of distinguishing cytotrophoblast cells in disaggregated mixtures. Alkaline phosphatase activity was an unreliable marker of trophoblast tissue in early placentas, and of the putative cytotrophoblast cells in mixtures of disaggregated cells. Cultures of cells obtained from term placentas were fairly homogeneous, whereas placentas of 6-12 weeks gestation gave heterogeneous cell cultures which became overgrown with fibroblasts.

Alkaline Phosphatase↗

Disturbances of calcium and magnesium metabolism occur in most hyperthyroid patients.

The concentrations in serum of total and ionised calcium, phosphate, magnesium, albumin and alkaline phosphatase activity were measured in patients when hyperthyroid and again when euthyroid. Significant declines in the mean values of ionised calcium, phosphate and alkaline phosphatase activity and significant increases in the mean concentrations of magnesium and albumin were observed. Similar changes were observed in most individual patients. Levels of ionised calcium greater than two standard deviations (representing between batch imprecision) above the upper limit of the reference range were present in 15.6% of hyperthyroid patients. The hyperthyroid levels of calcium, ionised calcium and alkaline phosphatase activity were highest in patients with the most severe thyrotoxicosis. Disturbances of calcium and magnesium metabolism are frequent in hyperthyroid patients.

Adolescent↗

Renal function and electrolyte levels in hyperthyroidism: urinary protein excretion and the plasma concentrations of urea, creatinine, uric acid, hydrogen ion and electrolytes.

In order to help clarify the effects of hyperthyroidism on renal function and electrolyte metabolism, we measured the venous plasma concentrations of urea, creatinine, urate, hydrogen ion and electrolytes, and the urinary concentrations of total protein, albumin, retinol-binding protein, N-acetyl-beta-D-glucosaminidase activity, and creatinine in patients when hyperthyroid and again after they had been euthyroid for at least 4 months. Significant (P less than 0.05) decreases in the mean plasma concentrations of urate and chloride and significant increases in creatinine, total CO2 and hydrogen ion mean concentrations were observed when the patients became euthyroid. The mean concentrations of sodium, potassium and urea did not change significantly. The values of the ratios total protein/creatinine, albumin/creatinine, N-acetylglucosaminidase/creatinine and retinol-binding protein/creatinine were all significantly (P less than 0.05) elevated in random urine specimens obtained from hyperthyroid patients as compared to the values when euthyroid. Mild proteinuria occurs in most thyrotoxic patients which does not appear to be due predominantly to either glomerular or tubular renal injury. The changes in plasma analytes that were observed may be attributed to increases in glomerular filtration rate and tissue nucleic acid turnover and a tendency to respiratory alkalosis in the hyperthyroid patients.

Acetylglucosaminidase↗

5'-Nucleotidase of human placental trophoblastic microvilli possesses cobalt-stimulated FAD pyrophosphatase activity.

An enzyme with FAD pyrophosphatase activity was extracted from human placental syncytiotrophoblast microvilli and purified to near-homogeneity. The enzyme has been identified as 5'-nucleotidase by several criteria. Throughout purification, parallel increases in the specific activities of FAD pyrophosphatase and AMP phosphatase were observed. The enzyme was a glycoprotein with a subunit molecular weight of 74,000. EDTA treatment resulted in a marked decline in both activities, and restoration of FAD pyrophosphatase activity but not 5'-nucleotidase activity was accomplished by the addition of Co2+ or, to a lesser extent, Mn2+. The substrate specificity of the 5'-nucleotidase activity that we observed agreed closely with the results of others. The pyrophosphatase activity was relatively specific for FAD. ADP, ATP, NAD(H), and FMN were not hydrolyzed, and ADP strongly inhibited both activities. For FAD pyrophosphatase activity, a Km of 1.2 x 10(-5) M and a Vmax of 1.1 mumol/min/mg protein were determined in assays performed in the presence of Co2+. In the absence of added Co2+, the Vmax declined but the Km was unchanged. For 5'-nucleotidase (AMP as substrate) the Km was 4.1 x 10(-5) M and the Vmax 109 mumol/min/mg protein. Hydrolysis of FMN to riboflavin was observed in partially purified detergent extracts of microvilli that contained alkaline phosphatase activity and lacked FAD pyrophosphatase and 5'-nucleotidase activity. The presence of both FAD pyrophosphatase and FMN phosphatase activities in syncytiotrophoblast microvilli supports the view that the placental uptake of vitamin B2 involves the hydrolysis of FAD and FMN to riboflavin which is then absorbed, a sequence postulated for intestinal absorption and liver uptake.

5'-Nucleotidase↗

Seasonality of thyrotoxicosis in Wellington.

The month of diagnosis of hyperthyroidism in 183 patients from the area of Wellington, for the period 1977-1986 was ascertained. A significantly greater proportion of cases (58%, p less than 0.05) were diagnosed in the warmer period of the year (November to April) than in the cooler period (May to October). Although seasonal environmental factors, such as changes in iodine intake; or other unrecognised factors, such as differences among the patients themselves, may possibly play an aetiological or pathogenetic role, the significantly greater proportion of thyrotoxic patients diagnosed during the warmer 6-month period of the year is presently best explained by the fact that symptoms tend to be less tolerable in warm weather.

Dairy Products↗

Mean platelet volume is increased in hyperthyroidism.

In 28 unselected patients with hyperthyroidism, platelet count, platelet hematocrit, mean platelet volume, and platelet distribution width were measured at the time of presentation and again when the patients were euthyroid. On return to the euthyroid state, there were highly significant falls in the mean values of the mean platelet volume (16% decline, P less than 0.001) and the platelet hematocrit (16% decline, P less than 0.001) and a slight but highly significant increase in the mean value of the platelet distribution width (2% increase, P less than 0.01). A decline in mean platelet volume was observed in 24 of 28 patients (86%); three patients showed no change. There was no significant change in the mean value of the platelet count. The observed effects of thyrotoxicosis on platelets appeared to be largely independent of the well-known effects on erythrocytes and white blood cells. An increase in mean platelet volume is a regular feature of hyperthyroidism that has not previously been described.

Adult↗

A double-label two-dimensional procedure for the analysis of membrane proteins.

A previously described double-label two-dimensional electrophoresis procedure (Wheeler et al., Anal. Biochem. 1986 159, 1-7) for the analysis of differences between two complex mixtures of soluble proteins has been modified to allow analysis of proteins requiring detergent for aqueous solubility. The samples are first disrupted by sonication and the insoluble proteins concentrated by high-speed centrifugation. The proteins are then solubilized with sodium dodecyl sulfate and further concentrated in a centrifugal concentrator to achieve protein mixtures suitable for labeling with 14C and 3H by reductive methylation and subsequent two-dimensional electrophoresis. The sample concentration step is quick, minimizes the concentration of sodium dodecyl sulfate in the final sample, and avoids the potential difficulties associated with lyophilization or precipitation. The modified procedure was applied to the analysis of erythrocyte membranes, platelets and isolated placental microvilli. The high resolving power of two-dimensional gel electrophoresis is retained and the procedure is sensitive because the conditions of labeling allow substantial incorporation of radioactivity into protein despite the presence of detergent.

Blood Platelets↗

Search for abnormal proteins in erythrocytes and plasma from patients with a major depressive episode.

A sensitive double-label two dimensional gel electrophoresis procedure has been used to search for abnormal proteins in plasma and erythrocyte plasma membranes from patients with major depressive illness. For both plasma and erythrocytes, minor qualitative and quantitative differences between the proteins in pooled samples from depressed and normal subjects were observed; however, these were shown to be artifacts and no consistent differences were found.

Blood Protein Electrophoresis↗

A search for protein abnormalities in erythrocyte membranes and platelets from patients with multiple sclerosis using double-label two-dimensional electrophoresis.

Proteins from erythrocyte membranes and whole platelets from patients with definite multiple sclerosis (MS) and normal subjects were compared using a double-label two-dimensional procedure. No consistent differences were found in the proteins adherent or intrinsic to erythrocyte membranes. The results of initial studies with platelets showed the absence of a group of three protein spots in the electrophoretic gels of the MS specimens. Further experiments suggested that these results were probably due to minor differences in the handling of the MS and normal specimens although the possibility of a difference in protease activity was not completely eliminated.

Blood Platelets↗

The haematology of hyperthyroidism: abnormalities of erythrocytes, leucocytes, thrombocytes and haemostasis.

The abnormalities of erythrocytes, leucocytes, thrombocytes and coagulation that have been reported, particularly in more recent years, to be associated with hyperthyroidism are surveyed. Several areas are highlighted where further investigations could lead to clinically useful insights, improved information about the haematological processes involved or to a better understanding of thyroid hormone action.

Blood Cells↗

High-affinity binding of riboflavin and FAD by immunoglobulins from normal human serum.

The binding of [3H]FAD and [3H]riboflavin to a pooled, human plasma immunoglobulin fraction was studied. For each flavin, the data fit best a model with two binding sites of high affinity and a class of sites of lower affinity. The dissociation constants estimated for the two high affinity sites were 1.73 nM and 0.078 nM for [3H]FAD and 2.43 nM and 0.068 nM for [3H]riboflavin. The results of studies with a series of possible competitors suggested that the flavin ring system was an important determinant of the binding. Other studies showed that the binding reaction was largely enthalpy-driven. Our findings show that normal human immunoglobulins contain one or more species that bind riboflavin and FAD with very high affinity.

Binding Sites↗

Hemoglobin A1 and serum fructosamine levels in hyperthyroidism.

The severity, prevalence and pathogenesis of abnormalities of carbohydrate metabolism in hyperthyroidism are incompletely defined. The extent of glycosylation of proteins provides an objective, retrospective index of glycemic control. We have measured the percent hemoglobin A1, random plasma glucose level and serum concentrations of fructosamine, total protein and albumin in hyperthyroid and euthyroid subjects attending a hospital-based thyroid clinic. A significant (p = 0.002) increase in the mean value for hemoglobin A1 and a significant (p = 0.0003) decrease in the mean values for fructosamine were found in the hyperthyroid group. The lower mean fructosamine value in the hyperthyroid group was attributed to a concomitant decline in the mean albumin concentration (p = 0.001). The mean value for glucose tended to be higher in the hyperthyroid group, but the difference did not reach significance at the 0.05 level (p = 0.09). The finding of a higher mean hemoglobin A1 concentration in hyperthyroid patients compared to euthyroid subjects is new evidence for a persistent abnormality in glycemic regulation in most thyrotoxic patients.

Adult↗