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Biomedical subjects

C Johnston

Publications and source records attributed to C Johnston.

At least 235 records · Page 13Linked to original sources
PubMed1988

Alterations in T-lymphocyte subpopulations in type I diabetes. Exploration of genetic influence in identical twins.

To evaluate factors influencing the alteration in subsets of T-lymphocytes, we studied 24 pairs of identical twins discordant for insulin-dependent (type I) diabetes mellitus. Subsets were assessed by monoclonal antibodies and a pure preparation of peripheral blood mononuclear cells obtained by centrifugation of heparinized whole blood with a Ficoll/Triosil gradient. In 12 pairs studied within 5 yr of diagnosis, we observed a reduction in the percentage of cells reacting with OKT8 (recognizing the CD8 antigen present on the suppressor/cytotoxic subset) (P less than .05), but a similar level was detected in their nondiabetic cotwins. In 12 pairs studied greater than 5 yr after the diagnosis and in whom the nondiabetic twin is less likely to develop diabetes, the percentage of cells reacting with OKT8 was reduced in both the diabetic (P less than .05) and the nondiabetic (P less than .01) twins. Reductions were also seen with OKT3 (recognizing the CD3 antigen present on the total T-lymphocyte population) and OKT4 (recognizing the CD4 antigen present on the helper/inducer subset), but only in the diabetic twins from the group with longer discordance. We conclude that a reduced percentage of suppressor/cytotoxic cells is associated with type I diabetes, but the reduction appears to be genetically determined. Total T-lymphocytes are also reduced but mainly in the helper/inducer subset and only in diabetic patients of long duration. Such a reduction cannot therefore be primarily genetically determined.

Adolescent↗
PubMed1987

Depressed superoxide radical generation by neutrophils from patients with rheumatoid arthritis and neutropenia: correlation with neutrophil reactive IgG.

Neutrophils of 31 patients with neutropenia and rheumatoid arthritis (RA) have been studied to assess their ability to generate superoxide radicals (O-2) on activation. Seventeen patients had classical Felty's syndrome and 14 presumed chrysotherapy related neutropenia. Results were compared with those from age and sex matched controls with uncomplicated RA and from normal subjects. Neutrophils from patients with Felty's syndrome had a significantly reduced ability to generate superoxide radicals when compared with the other three groups. In addition, serum levels of IgG polymorphonuclear leucocyte binding activity (IgG PBA) were also raised in the group with Felty's syndrome. A statistically significant inverse correlation existed between O-2 generation and IgG PBA. It is concluded that neutrophil reactive IgG may have an important role in both quantitative and qualitative defects in neutrophil function in Felty's syndrome.

Agranulocytosis↗
PubMed1987

Beta-cell function and insulin sensitivity in nondiabetic HLA-identical siblings of insulin-dependent diabetics.

Insulin secretion and insulin sensitivity were compared in 12 HLA-identical siblings of insulin-dependent diabetics and nondiabetic controls. Only the maximum acute insulin response to intravenous arginine was lower in the siblings than in the matched controls (P less than .05); other measures of insulin secretion, including the acute insulin response to glucose or arginine, the second-phase insulin response to glucose, and the slope of glucose potentiation, were not significantly different. Insulin sensitivity, derived from an intravenous glucose tolerance test with a minimal-modeling technique, was lower in the siblings (P less than .01). In a large group of nondiabetic controls of various adiposity, insulin secretion and insulin sensitivity were inversely related. In view of the difference in insulin sensitivity between siblings and matched controls, a direct comparison of beta-cell function tests may be inappropriate, and the measures of insulin secretion were compared with those of nondiabetics when adjusted for differences in insulin sensitivity. This analysis revealed that all measures of insulin secretion were significantly lower in the siblings. We conclude that HLA-identical siblings of insulin-dependent diabetics show evidence of both insulin resistance and impaired beta-cell function and that analysis of beta-cell function in relation to insulin sensitivity shows a greater frequency of beta-cell secretory abnormalities than previously appreciated.

Adult↗
PubMed1987

Suppression of superoxide generation by normal polymorphonuclear leukocytes preincubated in plasma from patients with Felty's syndrome.

Polymorphonuclear leukocytes (PMN) isolated from patients with Felty's syndrome (FS) generate fewer superoxide anions (O-2) upon stimulation with fmet-leu-phe than PMN from normal controls or patients with rheumatoid arthritis (RA). In this study, plasma samples were obtained from 12 patients with RA and 12 patients with FS. Incubation of normal PMN in plasma from Felty patients resulted in a significant reduction in both the rate and total quantity of O-2 generation when activated with fmet-leu-phe. This was not observed with plasma from RA patients. The capacity of a plasma sample to suppress O-2 generation correlated with plasma IgG-PMN-binding activity (IgG-PBA) and, to a lesser extent, with the content of circulating immune complexes (CIC). These data suggest that IgG-PBA and possibly CIC have a pathogenetic role in both qualitative and quantitative defects in PMN in Felty patients.

Aged↗
PubMed1987

Felodipine compared to prazosin as additional therapy to a beta-blocking drug.

Felodipine was compared with prazosin in patients with essential hypertension whose blood pressure was not controlled by a beta-blocking drug. One hundred patients with a supine diastolic blood pressure greater than or equal to mm Hg after 4 weeks or more on a beta-blocking drug and placebo were randomly assigned to felodipine or prazosin tablets. The drugs were titrated at 2-week intervals if diastolic BP was greater than or equal to 90 mm Hg. Titration steps of felodipine were 5, 10, 20 mg b.i.d. and of prazosin were 1, 2, 4 mg b.i.d. The fall in blood pressure with felodipine 32/21 mm Hg was greater than the fall with prazosin 16/12 mm Hg (p less than 0.001); 36 patients achieved a diastolic blood pressure of less than 90 mm Hg with felodipine, which was a significantly greater number than the 20 patients who obtained such a level with prazosin (p less than 0.01). Both drugs were well tolerated, but more patients complained of vascular type side effects (flushing, peripheral edema) with felodipine than with prazosin. There was significant weight gain with prazosin but not with felodipine. Felodipine was shown to be a well-tolerated, effective antihypertensive agent when used with a beta-blocking drug and to be suitable for people with hypertension who fail to be controlled with a beta-blocking drug.

Adrenergic beta-Antagonists↗
PubMed1987

The effect of pregnancy on disease development and mortality in B/W F1 mice.

Pregnancy was encouraged in 15 B/W mice (Group 1) and the rate of development of FANA, anti-DNA antibodies, and proteinuria compared with that seen in 15 control mice (Group 2). The mean number of pregnancies for Group 1 mice was 5.2. No difference was seen in mortality rate or in the onset of serologic or urinary abnormalities between the 2 groups.

Animals↗
PubMed1987

Spine and femur density using dual-photon absorptiometry in US white women.

Bone mineral density (BMD) of the spine (n = 892) and femur (n = 634) was measured using dual-photon absorptiometry in normal white women from seven diverse locations. The same model commercial scanner with a 153Gd source was used in all locations (SD = 1.3% among locations). There was not an age-associated decrease of spinal BMD during young adulthood (20-40 years); the correlation of age and femoral BMD in this period was low but significant (r = -0.21). There was a narrow range of intra-population variation at all ages (10-12%). The cross-sectional data showed an average diminution of about 20% in the spine and 25% in the femur between 40 and 70 years of age, followed by a continued but slower, decrease of density in older women. Adjustment of values for height and weight was called for mainly at extremes of body size.

Aging↗
PubMed1986

Immune changes associated with insulin dependent diabetes may remit without causing the disease: a study in identical twins.

Activation of T lymphocytes and islet cell antibodies were studied in two groups of insulin dependent diabetics and their non-diabetic identical cotwins. Group 1 comprised 12 "short term" twin pairs (diabetic twin diagnosed less than five years previously) in whom only a third of the cotwins were likely to develop diabetes; 10 of the 12 non-diabetic cotwins showed increased values of activated T lymphocytes, islet cell antibodies, or both. Group 2 comprised 10 "long term" twin pairs (diabetic twin diagnosed more than 11 years previously) in whom none of the non-diabetic cotwins was likely to develop diabetes; these pairs were selected because all the non-diabetic cotwins had shown islet cell antibodies at some time in the past, but only two still did so (one with an increased value of activated T cells). There was relative glucose intolerance in the cotwins of the short term group but not in those of the long term group. Non-diabetic cotwins of diabetics may show the immune changes associated with insulin dependent diabetes and relative glucose intolerance, but these changes may remit without leading to diabetes.

Adolescent↗
PubMed1986

Effects of gold compounds on function of phagocytic cells. Comparative inhibition of activated polymorphonuclear leukocytes and monocytes from rheumatoid arthritis and control subjects.

The effect of sodium aurothiomalate and auranofin on the generation of superoxide anions (O2-) by polymorphonuclear leukocytes (PMNLs) and adherent mononuclear phagocytic cells (AMNCs) has been investigated. Sodium aurothiomalate at final concentrations of 1, 10, and 100 micrograms Au/ml and auranofin ranging from 0.1 to 2.0 micrograms Au/ml were used in the reactions involving all cell types. Results have been compared between cells drawn from normal controls and patients with active rheumatoid disease. The effect of gold compounds on both cell types was assessed following activation by phorbol myristate acetate (1 X 10(-8) M) and N-formyl-methionyl-leucyl-phenylalanine (1 X 10(-4) M) using a cytochrome c reduction method. Sodium aurothiomalate at the maximum concentration modestly inhibited O2- generation by PMNLs but not AMNCs. Auranofin inhibits O2- generation by both cell types. Inhibition of cells from patients with rheumatoid arthritis was greater than that seen with cells from normal controls.

Arthritis, Rheumatoid↗
PubMed1986

Chlorpropamide-alcohol flush reaction and isoenzyme profiles of alcohol dehydrogenase and aldehyde dehydrogenase.

To investigate the enzymatic basis of the chlorpropamide-alcohol flush reaction (CPAF) we compared the isoenzyme profiles of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) from liver biopsies, and of ALDH alone from erythrocytes and leucocytes, in CPAF-positive and CPAF-negative subjects. No differences were seen in ADH or ALDH phenotypes, or in the relative activities of the isoenzymes, between the two groups before chlorpropamide was given; in particular, no subjects showed the 'null' ALDH phenotype that is associated with the alcohol flush reaction in oriental subjects. There was a significant decrease in erythrocyte ALDH activity after 7 days' treatment with chlorpropamide in CPAF-positive individuals but no such difference was seen in CPAF-negative subjects. These results indicate that CPAF has a different enzymatic basis from the alcohol flush reaction of oriental subjects and suggest that in CPAF-positive subjects erythrocyte ALDH may be particularly susceptible to inhibition by chlorpropamide.

Alcohol Dehydrogenase↗
PubMed1986

Angiotensin converting enzyme (ACE), characterization by 125I-MK351A binding studies of plasma and tissue ACE during variation of salt status in the rat.

Angiotensin converting enzyme (ACE) was measured in rat plasma and tissues by analysis of the binding of the radio-inhibitor 125I-MK351A, a tyrosyl derivative of enalaprilic acid. Labelled 125I-MK351A bound to plasma and tissue ACE preparations and was displaced in a concentration-related manner by MK351A. Scatchard analysis yielded a single line from which MK351A binding sites/mg protein and MK351A dissociation constant were calculated. Tissue and plasma ACE from Sprague Dawley rats was studied over a wide range of sodium intakes (low salt, 0.026 +/- 0.012 mmol/24 h; normal salt, 0.58 +/- 0.09 mmol/24 h; and high salt, 10.4 +/- 1.3 mmol/24 h) and during high salt and DOCA treatment. Across the range of sodium states studied there were no consistent changes in plasma, lung, aorta, brain, epididymis or kidney MK351A binding sites/mg protein, or equilibrium dissociation constant. Calculated MK351A binding sites (nmol/mg protein) were 1.64 +/- 0.14 in lung, 0.47 +/- 0.04 in aorta, 0.44 +/- 0.05 in epididymis, 0.18 +/- 0.01 in brain and 0.053 +/- 0.004 in kidney preparations (n = 24 in each group) reflecting reported ACE enzymatic activity in these tissues. Equilibrium dissociation constant KD was uniform within each tissue, but varied between organs. The KD (mol/l X 10(-12)) was 50 +/- 2 in aorta, 57 +/- 2 in lung, 58 +/- 2 in epididymis, 61 +/- 3 in brain, 62 +/- 2 in plasma and 84 +/- 3 in kidney (n = 24 in each group).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1986

Cystosarcoma phyllodes.

We present four cases of cystosarcoma phyllodes in which mammograms revealed a small or large lobulated mass occupying the entire breast. Preoperative diagnosis was a benign lesion with a low probability of nodular carcinoma. Histologically, all tumors were classified as malignant. Although uncommon, cystosarcoma should be considered in the differential diagnosis of these masses, since local recurrence is frequent unless wide wedge resection or simple mastectomy is done.

Adult↗
PubMed1986

Further evaluation of the Scolitron treatment of idiopathic adolescent scoliosis.

One hundred forty-two patients were treated by the Scolitron method of lateral electric surface stimulation (LESS) for scoliosis. Using 10 degrees progression as a failure point, clinicians reported the following: 56.3% of patients were classified as failures, 26.8% as successes; and 16.9% were still under treatment. When broken down into individual groups, true protocol patients, at risk for progression, had the lowest success rate; whereas those that were nonprotocol, and least at risk, had the highest success rate. This method should still be considered experimental and cannot be considered an alternative to bracing at this time.

Adolescent↗