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Biomedical subjects

S Harris

Publications and source records attributed to S Harris.

At least 217 records · Page 12Linked to original sources
PubMed1991

Effect of vitamin D supplementation on wintertime and overall bone loss in healthy postmenopausal women.

OBJECTIVES: To determine whether relative vitamin D deficiency during the winter months contributes to age-related bone loss and whether rates of change in hard- and soft-tissue mass vary during the year. DESIGN: Double-blind, placebo-controlled, 1-year trial in 249 women in which equal numbers of women were randomized to either placebo or 400 IU of vitamin D daily. All women received 377 mg/d of supplemental calcium largely as calcium citrate malate. PATIENTS: Healthy, ambulatory postmenopausal women with usual intakes of vitamin D of 100 IU/d. MEASUREMENTS: Duplicate spine and whole-body scans were done by dual energy x-ray absorptiometry at 6-month intervals that were timed to periods when 25-hydroxyvitamin D levels were highest and lowest. Period 1 was June-July to December-January and period 2 was December-January to the next June-July. Serum parathyroid hormone and plasma 25-hydroxyvitamin D levels were measured during periods 1 and 2. MAIN RESULTS: In the placebo group, spinal bone mineral density increased in period 1, decreased in period 2, and sustained no net change. Women treated with vitamin D had a similar spinal increase in period 1 (1.46% compared with 1.40% in placebo), less loss in period 2 (-0.54% compared with -1.22%, CI for the difference, 0.05% to 1.31%, P = 0.032) and a significant overall benefit (0.85% compared with 0.15%, CI for the difference, 0.03% to 1.37%, P = 0.04). In period 2, 25-hydroxyvitamin D levels were lower and parathyroid hormone levels were higher in the placebo than in the vitamin D group. Whole-body lean and fat tissue and bone mineral density varied during the year but did not change overall. CONCLUSIONS: At latitude 42 degrees, healthy postmenopausal women with vitamin D intakes of 100 IU daily can significantly reduce late wintertime bone loss and improve net bone density of the spine over one year by increasing their intake of vitamin D to 500 IU daily. A long-term benefit of preventing vitamin D insufficiency in the winter seems likely although it remains to be shown. Observed changes in bone as well as in fat and lean tissue appear to be related to season.

Absorptiometry, Photon↗
PubMed1991

Effect of Towne live virus vaccine on cytomegalovirus disease after renal transplant. A controlled trial.

OBJECTIVE: To test the efficacy of vaccination with the Towne live attenuated cytomegalovirus vaccine. DESIGN: A double-blind, randomized, placebo-controlled trial in candidates for renal transplantation. The cytomegalovirus serologic status of both recipients and donors were determined, and the recipients were followed for periods of 6 months to 7 years after transplant. SETTING: A university transplant center. PATIENTS: The analyses were made on 237 patients who were given either vaccine or placebo, received renal transplants, and were followed for at least 6 months. INTERVENTION: Subcutaneous inoculation with Towne live attenuated virus or with placebo. MAIN OUTCOME MEASURES: The presence of cytomegalovirus infection was defined by virus isolation and antibody tests. If infection occurred, a prearranged scoring system for cytomegalovirus disease was used to objectify disease severity. RESULTS: The vaccine was well tolerated, and there were no discernible long-term adverse effects. Recipients who were originally seropositive did not clearly benefit from vaccination. Protective efficacy was analyzed in the group at highest risk for cytomegalovirus disease; recipients who were seronegative at the time of vaccination and who received a kidney from a seropositive donor. Compared with placebo recipients, vaccinated patients in this group had significantly less severe cytomegalovirus disease, with a significant reduction in disease scores (P = 0.03) and 85% decrease in the most severe disease (95% CI, 35% to 96%), although infection rates were similar. Graft survival at 36 months was improved in vaccinated recipients of cadaver kidneys (8 of 16) compared with unvaccinated recipients (4 of 16) (P = 0.04). CONCLUSIONS: Previous vaccination of seronegative renal transplant recipients with live cytomegalovirus results in reduction of disease severity mimicking the action of naturally derived immunity.

Adult↗
PubMed1991

Cigarette smoking increases the risk of albuminuria among subjects with type I diabetes.

The effect of cigarette smoking on diabetic renal and retinal complications was evaluated in 359 young subjects with insulin-dependent diabetes mellitus. The prevalence of increased albumin excretion rates was 2.8 times higher in smokers than nonsmokers. Mean glycohemoglobin levels and duration of diabetes were also significant factors in the development of diabetic nephropathy and retinopathy in a logistic regression model. Smoking remained a significant factor in the logistic regression model for albuminuria (but not retinopathy) when controlled for glycohemoglobin level, duration of diabetes, age, gender, and blood pressure. The progression of albuminuria and of retinopathy was also greater in smokers. Albuminuria improved significantly when subjects ceased smoking. It is concluded that cigarette smoking is an independent risk factor and is associated with the development and progression of early diabetic renal damage (albuminuria) and with the worsening of retinal disease in young subjects with diabetes.

Adolescent↗
PubMed1991

Developmental regulation of the sheep beta-lactoglobulin gene in the mammary gland of transgenic mice.

beta-Lactoglobulin (BLG) is the most abundant whey protein in sheep milk but it is not present in mouse milk. We have previously shown that transgenic mice carrying the BLG gene express it specifically in the mammary gland and secrete BLG into milk at high concentrations. Here we demonstrate that BLG transcription is correctly initiated in mice and that BLG synthesis is restricted to the secretory epithelial cells of the mammary gland. We have also determined the temporal pattern of milk protein gene expression and find that the BLG transgene is regulated coordinately with mouse beta-casein and that the patterns of regulation of BLG in mouse and sheep share some similarities.

Animals↗
PubMed1991

Serum ionized calcium, as well as phosphorus and parathyroid hormone, is associated with the plasma 1,25-dihydroxyvitamin D3 concentration in normal postmenopausal women.

Serum parathyroid hormone (PTH) and low-normal serum phosphorus (P) concentrations have well-known trophic effects on renal 1-hydroxylase. A role for serum ionized calcium (Ca2+) in the day-to-day regulation of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] has not been identified in normal humans. The associations between serum Ca2+, PTH, P, and plasma 1,25-(OH)2D3 were evaluated in a cross-sectional study of 275 healthy postmenopausal women. Partial correlations of Ca2+, PTH, and P (each controlled for the other two) with 1,25-(OH)2D3 were sought within quintiles of Ca2+. At low-normal concentrations (less than 1.26 mmol/liter, quintile 1) Ca2+ was inversely correlated with 1,25-(OH)2D3 (rp = -0.30, p = 0.028). At mid-normal concentrations Ca2+ was not significantly correlated with 1,25-(OH)2D3. At high-normal concentrations (greater than 1.32 mmol/liter, quintile 5) Ca2+ attenuated the positive associations of both PTH and low-normal P with 1,25-(OH)2D3. In quintile 5 Ca2+, PTH, and P together accounted for none of the variability in 1,25-(OH)2D3 (R2 = 0.03, p = 0.671). Women with Ca2+ below 1.32 mmol/liter were next examined by quintile of P. As expected, at low-normal concentrations (less than 1.03 mmol/liter, quintile 1) P was significantly correlated with 1,25-(OH)2D3 (rp = -0.32, p = 0.047). The association between PTH and 1,25-(OH)2D3 was statistically significant only at mid-normal concentrations of P (rp = 0.52, p = 0.001, quintile 3). We conclude that Ca2+, along with PTH and P, is associated with the plasma concentration of 1,25-(OH)2D3 in normal postmenopausal women.

Calcitriol↗
PubMed1991

Targeting expression to the mammary gland: intronic sequences can enhance the efficiency of gene expression in transgenic mice.

We are studying the tissue-specific expression of the sheep milk-whey protein gene, beta-lactoglobulin. We have used sequences derived from this gene to target the expression of biomedical proteins into milk with the intention to exploit this technology in transgenic sheep as a means of protein production. In the present study, a series of beta-lactoglobulin hybrid genes and beta-lactoglobulin minigenes were evaluated for expression in the mammary gland of transgenic mice. In particular, we have assessed whether there is a requirement for introns for efficient transgene expression in the mammary gland, since the coding sequences of many candidate proteins are available only as cDNAs. The results suggest that the inclusion of natural introns in constructs can enhance the efficiency of transgene expression. Thus, a hybrid construct comprising 4.3 kb of the immediate 5' flanking sequences of beta-lactoglobulin fused to a genomic minigene encoding human alpha-antitrypsin (alpha 1AT) was expressed much more efficiently than an alpha 1AT-cDNA construct containing the same beta-lactoglobulin segment. Similarly, the intact beta-lactoglobulin gene was expressed more efficiently than the corresponding intronless beta-lactoglobulin minigene. This effect was not seen in transient expression experiments in baby hamster kidney cells when beta-lactoglobulin-alpha 1AT constructs were driven by SV40 enhancer sequences. The effect cannot be explained by a simple requirement for splicing, since the inclusion of the first beta-lactoglobulin intron into cDNA constructs encoding human alpha 1AT or beta-lactoglobulin itself failed to enhance the efficiency of transgene expression. It is concluded that sequence elements within introns may interact with the upstream 5' flanking sequences of beta-lactoglobulin and enable the latter to function efficiently in the mammary gland of transgenic mice.

Animals↗
PubMed1991

Use of the pen delivery system for intensive insulin therapy in college-age students with type I diabetes.

The present report describes our experience with 16 adolescents and young adults with insulin-dependent diabetes mellitus (IDDM; Type I) who switched from two injections of insulin per day to the NovolinPen and four insulin injections a day. Their mean age at the initiation of therapy was 19.2 years with a duration of diabetes of 8.9 years. Sixteen random computer-matched (for age, sex, and duration of diabetes) controls who remained on two insulin injections a day were evaluated for comparison. Most subjects were preparing to leave home for college. After a minimum of 1 year of using the pen, the mean weight gain of the test subjects was significantly greater (P less than .05) than for the computer-matched controls. Glycemic control, as monitored by mean HbA1c values, were similar for the NovolinPen and the control groups (10.8 versus 10.9, respectively) after almost 2 years. The main advantage to the pen expressed by the users was a sense of freedom of lifestyle.

Adolescent↗
PubMed1991

Long-term outcome after corneal transplantation. Visual result and patient perception of success.

Snellen acuity, reading line, and keratometry were measured in a cohort of 60 patients at 2 or more years after penetrating keratoplasty was performed. Patients were asked to complete a questionnaire to elicit information on their perceptions of visual function and the success of the procedure. Using preferred correction, a Snellen acuity of 6/18 or better was achieved by 65%, and a reading line of N8 or better was achieved by 57% of index grafts. Thirty-eight percent had more than 5 diopters (D) of astigmatism in the graft. Approximately 75% of patients reported satisfaction with their graft (satisfaction being associated with better acuity in the grafted eye than the other eye), graft clarity, and a perceived improvement in lifestyle. Dissatisfaction appeared to be associated with graft failure and problems with contact lens wear. The findings have implications for patient selection for corneal transplantation and for the measurement of outcome.

Adolescent↗
PubMed1991

Retinal changes and alterations in blood pressure and albumin excretion rate (AER) during exercise in type 1 diabetes.

The association of retinal changes with exercise microalbuminuria and with changes in systolic and diastolic blood pressure (BP) were evaluated in 162 young subjects with insulin-dependent (type 1) diabetes mellitus. Higher systolic and diastolic BPs at rest or after 10 or 20 min of exercise were significantly associated with more severe retinal changes in the subjects with diabetes compared to controls (P less than 0.02; global ANOVA). The mean (+/- SEM) exercise albumin excretion rate (AER) was 17.6 +/- 3.1 if there was no evidence of retinopathy compared to 81.5 +/- 23.5 when only microaneurysms were detected and 467.1 +/- 133.3 when more severe retinopathy was present. The percentage of subjects with abnormal AERs for these three retinal groups was 13, 30 and 60, respectively. (P less than 0.0001, chi-square test). It is clear that retinal changes relate to early renal changes, as monitored by exercise AERs and changes in resting and exercise BPs. It is concluded that the renal and retinal microvascular changes occur concurrently in young subjects with type 1 diabetes.

Adult↗
PubMed1991

Giant cell arteritis associated with pericarditis and large vessel disease.

Giant cell arteritis is well recognised to affect branches of the external carotid artery and to cause systemic symptoms, but may also involve branches of the aorta producing a clinical syndrome that may be difficult to diagnose. A patient is described who presented with limb ischaemia, pericarditis and systemic symptoms. Treatment with corticosteroids improved the systemic manifestations but not the ischaemia. The patient died of bowel infarction four months after treatment was commenced.

Aged↗
PubMed1991

Evidence that the seasonal antler cycle of adult Reeves' muntjac (Muntiacus reevesi) is not associated with reproductive quiescence.

Data were obtained from post-mortem investigations of 190 culled and road-killed muntjac bucks between 1967 and 1989. Although adult bucks (i.e. those having undergone at least one antler cycle) have a synchronous annual antler cycle, unlike temperate-zone cervids there was little seasonal variation in testis size or activity, or in the size and activity of the epididymidis or accessory reproductive glands. Spermatogenesis was not abated when the antlers were in velvet and year-round fertility was achieved without additional sperm storage. There was little seasonal change in plasma testosterone concentrations in samples obtained from captive and free-living bucks although castration caused antler casting and prevented mineralization. Hence the data are equivocal as to the role of steroids in driving the antler cycle; experimental work on this species would be valuable in examining the mechanisms which regulate the antler cycle.

Animals↗
PubMed1991

Recognition of telegraphy disturbed by noise at different S/N-ratios and different telegraphy speeds. A comparison to short-tone audiometry.

The ability to recognize telegraphy at different S/N ratios and telegraphy speeds was compared for 10 normal-hearing men trained in detecting telegraphy. The ability to recognize telegraphy disturbed by noise decreased with increasing telegraphy speed and reduced S/N ratio. The recognition of telegraphy disturbed by noise seems to follow the relations known from experiments with short-tone audiometry.

Adult↗
PubMed1991

Borderline increases in albumin excretion rate and the relation to glycemic control in subjects with type I diabetes.

We evaluated "borderline" increases in overnight albumin excretion rates (AERs)----i.e., those between the upper 95th percentile of normal (7.6 micrograms/min) and the lowest value currently considered predictive of nephropathy (30 micrograms/min)----to determine their importance and to see whether glucose control influenced subsequent changes in the "borderline" AER values. Between 1985 and 1990, we studied 190 subjects with insulin-dependent diabetes mellitus (Type I), analyzing a mean of 6.5 timed overnight urine samples collected per subject. Above-normal AERs were associated with a significantly (by ANOVA) higher mean age (P = 0.03), longer duration of diabetes (P = 0.0002), and greater mean glycohemoglobin values (P = 0.002). The transition rate between borderline and abnormal AERs was significantly higher (P less than 0.0001, chi-square test) than the direct transition rate between normal and abnormal AERs, thus showing the borderline AER to be a definite intermediate stage. Good and poor glucose control were clearly associated with improvement and worsening, respectively, of the borderline AER values (P = 0.032, chi-square test of trend). More attention to borderline AER values is clearly indicated.

Adolescent↗
PubMed1990

Accelerated bone loss in hypothyroid patients overtreated with L-thyroxine.

OBJECTIVE: To compare the rate of bone mineral loss in thyroxine-treated women with low thyrotropin (thyroid stimulating hormone, TSH) levels with that in women without known thyroid disease. DESIGN: Cases selected from a prospective calcium trial. SETTING: Subjects were recruited from the Boston area. MEASUREMENTS AND MAIN RESULTS: Of 361 women enrolled in a 2-year calcium supplement trial, 18 received thyroxine for hypothyroidism. Of these, 10 were considered overtreated, because they had low TSH levels. Rates of loss of bone mineral density from the radius, spine, and hip during 1.9 +/- 0.6 years were measured by single- and dual-photon absorptiometry. When compared with women with no known thyroid disease (236 controls for the spine, 246 for the radius, and 237 for the femoral neck), women with low TSH levels had greater annualized, adjusted mean rates of bone loss from the spine (-2.89% +/- 0.65% compared with -1.13% +/- 0.13%, P = 0.009) and similar but not significant trends at the radius (-1.18% +/- 0.75% compared with -0.13% +/- 0.17%) and femoral neck (-1.39% +/- 0.80% compared with -0.28% +/- 0.19%). These means were adjusted for variables that affected the rate of loss in the control group (baseline bone mineral density and body mass index, calcium intake, and years since menopause). There were no statistical differences between the low TSH and control groups for any laboratory variables measured, including serum calcium, phosphorus, parathyroid hormone or alkaline phosphatase, plasma 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D, or 24-hour urine calcium-to-creatinine ratio. CONCLUSIONS: Thyroxine-treated women with low TSH levels lose bone mineral from the spine more rapidly than do women without known thyroid disease. These patients are therefore at increased risk for osteoporosis. The absence of detectable biochemical changes in women with low TSH levels may result from their relatively modest degree of overtreatment.

Aged↗
PubMed1990

Vitreous fluorophotometry in insulin-dependent diabetes mellitus. Correlation with microalbuminuria and diastolic blood pressure.

Vitreous fluorophotometry was performed on 240 eyes of 120 young subjects who had insulin-dependent diabetes mellitus (type I) and various grades of retinopathy. The concentration of fluorescein was measured in the anterior chamber and posterior vitreous 1 hour after intravenous injection of fluorescein. There was a significant association (P less than .001) between the grade of retinopathy and the level of posterior vitreous leakage. The amount of posterior vitreous leakage in each eye also had a significant association with borderline elevation of diastolic blood pressure. Subjects with excessive posterior vitreous leakage had significantly higher levels of urinary microalbumin excretion. In a multiple linear regression analysis for posterior vitreous leakage, retinal grade consistently entered the model at a significant level (P less than or equal to .00001 to .003). Blood pressure also entered the model for posterior vitreous leakage at a significant level for retinal grades of the right and left eyes and of the worst eye. These results demonstrate an association between leakage of retinal and renal vessels, possibly linked at least in part to elevation in diastolic blood pressure.

Adolescent↗
PubMed1990

Morphometric analysis of thoracic muscles in wildtype and in bithorax Drosophila.

The tergotrochanteral (TTM) "jump" muscles in the second (T2) and third (T3) thoracic segments of the fruit fly, Drosophila melanogaster, were analyzed morphologically and morphometrically in wildtype (Canton-S) and bithorax mutants (abx bx3 pbx/Df(3R)P2). In the transformed T3 segments of mutant flies, the TTMs were greatly increased in fiber number (330% of wildtype), length (141%), and volume (460%), thus manifesting both hyperplasia and hypertrophy. In contrast, TTMs in the "untransformed" T2 segments of mutant flies were both hypoplastic and hypotrophic, in that significant decreases in fiber number (93% of wildtype), length (90%), and volume (80%) were observed. Two relationships emerged from analysis of the morphometric data: 1) Although the fiber numbers and volumes of the transformed T3 TTMs in bithorax flies were greatly increased, the total combined volumes of the TTMs in T2 + T3 remained approximately the same in bithorax compared to wildtype flies. 2) The changes in TTM volumes in bithorax flies compared to those in wildtype were proportional to the relative changes in fiber numbers times the relative changes in muscle lengths. These observations suggest that the genes of the bithorax complex influence the number and the length of tubular muscles fibers of the TTMs, but do not significantly affect the mean cross-sectional areas of these fibers. Fibrillar muscle fibers, which are not found at all in T3 segments in wildtype flies, were observed in the transformed T3 segments of bithorax mutants in 11 of 18 cases (61%), but typically as wisps, not in complete muscles. We suggest that, in the T3 segment of the bithorax flies, the relative differences between the massive transformation of tubular TTMs vs. the minimal appearance of fibrillar muscles may be related, in part, to the relative availability of muscle precursors.

Animals↗