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Biomedical subjects

A Kagan

Publications and source records attributed to A Kagan.

At least 19 recordsLinked to original sources
PubMed2006

Gender differences in ambulatory blood pressure monitoring profile in obese, overweight and normal subjects.

The incidence of obesity has increased enormously in the past several decades, and has been described as a modern epidemic. Obesity is a major factor contributing to hypertension. To the best of our knowledge, no study of ambulatory blood pressure monitoring (ABPM) comparing men with women in relation to body mass indexes (BMI) has been performed. From December 2002 to May 2006, we performed 24-h ABPM in 5950 subjects (3102 men and 2848 women), with a wide range of BMI (range 15.9-53.2 kg/m(2)). We defined obese subjects as those with BMI> or =30.0 kg/m(2), overweight subjects as those with BMI>25.0 and <30.0 kg/m(2), and normal subjects as those with BMI< or =25.0 kg/m(2). Data on 989 subjects (501 men and 488 women) aged from > or =18 to < or =69 years without antihypertensive treatment, atrial fibrillation or diabetes were included for analysis. We consistently found that obese men had the expected increased heart rate compared to normal and overweight men, whereas women (normal, overweight and obese) had similar HRs. In addition, normal and obese women had similar diastolic blood pressures (BP), as opposed to obese men, who had raised diastolic BP. These results may indicate that different pathogenetic mechanisms may be involved in the relationship between obesity and hypertension in men and women.

Adolescent↗
PubMed2001

Analysis of the cyclic nucleotide binding domain of the HERG potassium channel and interactions with KCNE2.

Mutations in the cyclic nucleotide binding domain (CNBD) of the human ether-a-go-go-related gene (HERG) K+ channel are associated with LQT2, a form of hereditary Long QT syndrome (LQTS). Elevation of cAMP can modulate HERG K+ channels both by direct binding and indirect regulation through protein kinase A. To assess the physiological significance of cAMP binding to HERG, we introduced mutations to disrupt the cyclic nucleotide binding domain. Eight mutants including two naturally occurring LQT2 mutants V822M and R823W were constructed. Relative cAMP binding capacity was reduced or absent in CNBD mutants. Mutant homotetramers carry little or no K+ current despite normal protein abundance and surface expression. Co-expression of mutant and wild-type HERG resulted in currents with altered voltage dependence but without dominant current suppression. The data from co-expression of V822M and wild-type HERG best fit a model where one normal subunit within a tetramer allows nearly normal current expression. The presence of KCNE2, an accessory protein that associates with HERG, however, conferred a partially dominant current suppression by CNBD mutants. Thus KCNE2 plays a pivotal role in determining the phenotypic severity of some forms of LQT2, which suggests that the CNBD of HERG may be involved in its interaction with KCNE2.

Amino Acid Sequence↗
PubMed2001

Training volunteers as conversation partners using "Supported Conversation for Adults with Aphasia" (SCA): a controlled trial.

This article reports the development and evaluation of a new intervention termed "Supported Conversation for Adults with Aphasia" (SCA). The approach is based on the idea that the inherent competence of people with aphasia can be revealed through the skill of a conversation partner. The intervention approach was developed at a community-based aphasia center where volunteers interact with individuals with chronic aphasia and their families. The experimental study was designed to test whether training improves the conversational skills of volunteers, and, if so, whether the improvements affect the communication of their conversation partners with aphasia. Twenty volunteers received SCA training, and 20 control volunteers were merely exposed to people with aphasia. Comparisons between the groups' scores on a Measure of Supported Conversation for Adults with Aphasia provide support for the efficacy of SCA. Trained volunteers scored significantly higher than untrained volunteers on ratings of acknowledging competence [F(1, 36) = 19. 1, p < .001] and revealing competence [F(1, 36) = 159.0, p < .001] of their partners with aphasia. The training also produced a positive change in ratings of social [F(1, 36) = 5.7, p < .023] and message exchange skills [F(1, 36) = 17.6, p < .001 ] of individuals with aphasia, even though these individuals did not participate in the training. Implications for the treatment of aphasia and an argument for a social model of intervention are discussed.

Aphasia↗
PubMed2000

The dominant negative LQT2 mutation A561V reduces wild-type HERG expression.

HERG(1) K(+) channel mutations are responsible for one form of dominantly inherited long QT syndrome (LQT). Some LQT mutations exert a dominant negative effect on wild-type current expression. To investigate mechanisms of dominant-negative behavior, we co-expressed wild-type HERG with the A561V mutant in mammalian cells. Transfection with various cDNA ratios produced HERG K(+) current densities that approached a predicted binomial distribution where mutant and wild-type subunits co-assemble in a tetramer with nearly complete dominance. Using C terminus myc-tagged wild-type HERG we specifically followed the mutant's effect on full-length wild-type HERG protein expression. Co-expression with A561V reduced the abundance of full-length wild-type HERG protein comparable to the current reduction. Reduction of wild-type protein was due to decreased synthesis and increased turnover. Conditions facilitating protein folding (growth at 30 degrees C, or in 10% glycerol) resulted in partial rescue from the dominant effect, as did the 26 S proteosome inhibitor ALLN. Thus, for A561V, dominant negative effects result from assembly of wild-type subunits with mutant very early in production leading to rapid recognition of mutant channels and targeting for proteolysis. These results establish protein misfolding, cellular proofreading, and bystander involvement as contributing mechanisms for dominant effects in LQT2.

Animals↗
PubMed1999

Leptin in CAPD patients: serum concentrations and peritoneal loss.

BACKGROUND: To determine whether serum leptin concentrations in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) are influenced by peritoneal loss of leptin and to compare serum leptin levels of normal subjects with those of patients receiving renal replacement therapy such as haemodialysis (HD), CAPD, or kidney transplantation. SUBJECTS AND METHODS: Eighty-four individuals were investigated: six females and 14 males on standard CAPD; 13 females and 13 males on chronic HD; 10 female and eight male kidney transplant recipients, and 10 female and 10 male subjects as controls. Morning serum, 8-h and 24-h samples of peritoneal fluid concentrated to 6-20-fold by Centricon 3 (cutoff 3000 daltons), and 24-h urinary concentrations of leptin were measured with commercial RIA (Linco Research, Inc., USA). Venous blood and peritoneal fluid samples of albumin, beta2-microglobulin, glucose, urea, and creatinine were determined by standard laboratory techniques. Serum insulin levels were measured by radioimmunoassay. RESULTS: Patients (men and women) on CAPD and after kidney transplantation exhibited significantly higher serum concentrations of leptin and leptin/BMI ratios than control subjects. These increased values did not reach statistical significance in HD patients. Serum leptin concentrations were correlated very significantly with BMI in all cases (r=0.380, P<0.001). Moreover, in CAPD patients (r=0.630, P<0.007) and in HD patients (r=0.668, P<0.005), but not in kidney transplant recipients or control subjects, significant correlations were observed between serum leptin and insulin concentrations. Residual renal function (RRF) in the range 0-12.8 ml/min and serum beta2-microglobulin levels in the range 7.9-47.1 mg/l did not influence serum leptin levels in CAPD and HD patients. As expected, leptin was detected in the peritoneal fluid of CAPD patients. Twenty-four-hour peritoneal loss (30.95+/-21.05 ng/min) and 24-h peritoneal clearance (0.01+/-0.01 ml/kg/min) of leptin account for only 3.9% of estimated whole-body leptin production rate and 0.7% of leptin clearance from plasma respectively. Twenty-four-hour urinary losses of leptin in CAPD patients were negligible, accounting for 5.6+/-1.8% (range 0.3-15.2%) of total (peritoneal and urinary) loss of this hormone. CONCLUSIONS: These findings suggest that serum leptin levels are not affected by continuous peritoneal loss of leptin during CAPD and that insulin resistance and hyperinsulinaemia contribute to elevated serum leptin concentrations in CAPD and HD patients. The aetiology of increased serum leptin levels in kidney transplant recipients is probably different from that in dialysis patients.

Adult↗
PubMed1999

Reversal of nephrotic syndrome due to AA amyloidosis in psoriatic patients on long-term colchicine treatment. Case report and review of the literature.

A case of nephrotic syndrome due to AA amyloidosis in a young woman suffering from erythrodermic psoriasis and psoriatic arthropathy is reported. The nephrotic syndrome regressed completely during long-term (57 months) colchicine treatment. There are 39 case reports in the literature of psoriasis associated with amyloidosis. More than 85% of these patients had concomitant arthropathy. This suggests that arthritis may be an important factor in the appearance of amyloidosis. 59% of psoriatics with amyloidosis had renal failure and 56% of them died shortly after diagnosis of amyloidosis. These observations support the view that amyloidosis associated with psoriasis is an aggressive disease that may be fatal. However, the clinical course of our patient suggests that renal amyloidosis associated with psoriasis may be successfully treated by colchicine.

Adult↗
PubMed1999

Rotator cuff tears of the hip.

Pain over the lateral aspect of the hip commonly is attributed to trochanteric bursitis. Typical findings include local tenderness and weakness of hip abduction. When conservative measures fail to relieve symptoms, surgical release of the iliotibial band over the greater trochanter has been recommended. In the management of seven such patients, an unusual finding was encountered: partial tear of the gluteus medius tendon at its attachment to the greater trochanter. Each patient presented with increasing hip pain of duration of months to years. There were no diagnostic findings on physical examination. Magnetic resonance imaging showed an abnormal signal within the tendon of gluteus medius and fluid within the trochanteric bursa. The disrupted tendons were reattached to bone with heavy nonabsorbable suture. At a median followup of 45 months (range, 21-60 months), all patients were free of pain.

Aged↗
PubMed1997

Extracorporeal losses of insulin-like growth factor-I and insulin-like growth factor binding protein-3 in adult patients on CAPD.

The effects of extracorporeal (urinary plus peritoneal) losses of insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) on their respective serum levels were studied in 10 adult patients (aged 42-74 years) with end-stage renal failure and residual renal function of 0-4.5 mL/min. All patients had been on continuous ambulatory peritoneal dialysis (CAPD) for a period of 2-27 months. Morning serum, 24-hour urine, and 8-hour overnight peritoneal concentrations of IGF-I and IGFBP-3 were measured by radioimmuno- (Incstar) and immunoradiometric (Active) assays. CAPD patients showed extracorporeal losses (mean +/- SEM) of 118.7 +/- 10.6 micrograms (urinary 6.4 +/- 2.8 and peritoneal 112.3 +/- 8.5 micrograms) of IGF-I/24 hour and 1.5 +/- 0.1 mg (urinary 0.2 +/- 0.1 mg and peritoneal 1.3 +/- 0.1 mg) of IGFBP-3/24 hour. Extracorporeal losses of IGF-I accounted for about 4% of the daily production rate of this polypeptide, and the peritoneal and urinary concentrations of IGFBP-3 did not exceed 4% and 14%, respectively, of their serum levels. Serum concentrations of IGF-I (227.7 +/- 64.2 micrograms/L) and IGFBP-3 (5.3 +/- 2.4 mg/L) were not significantly correlated with extracorporeal, peritoneal, or urinary losses of these proteins or with residual renal function. We suggest that extracorporeal losses of IGF-I and IGFBP-3 in adult patients on CAPD do not influence their serum levels and that IGF-I may therefore be used as a marker of malnutrition.

Adult↗
PubMed1995

Role of peritoneal loss of albumin in the hypoalbuminemia of continuous ambulatory peritoneal dialysis patients: relationship to peritoneal transport of solutes.

The effects of peritoneal albumin loss and the consequences of heterogeneous peritoneal solute transport on serum albumin levels were investigated in 25 adult patients on standard continuous ambulatory peritoneal dialysis (0-58 months). The patients were divided into three groups according to their albumin concentrations (g/l/l.73 m2) in 8-hour overnight effluents: group 1 ( < 0.6, n = 5), group 2 (0.6-1.1; n = 14), and group 3 ( > 1.1;n= 6). Significant differences (mean +/- SD) were observed in serum albumin levels (4.4 +/- 0.2, 3.7 +/- 0.3, and 3.1 +/- 0.5 g/dl, respectively) and in net ultrafiltration (0.37 +/- 0.13, 0.19 +/- 0.21, and -0.06 +/- 0.20 liters/8 h/1.73m2, respectively). The serum albumin levels were strongly correlated with 8-hour peritoneal mass transfer, clearance of albumin, 8-hour effluent concentrations of protein and glucose, and ultrafiltration rate. Moreover, the serum albumin levels showed significant negative correlations with dialysate-to-serum ratios of small solutes (urea, creatinine, and uric acid) and macromolecules (IgG, IgA, and IgM) estimated from 8-, 4-, and 1-hour dwell times. In addition, an overnight dialysate glucose-to-protein ratio < 1.0 was highly predictive of low serum albumin levels ( < or = 3.5 g/dl) and poor ultrafiltration. From the results of this study we conclude that peritoneal loss of albumin as well as peritoneal transport of other solutes of wide size ('permeability') contribute to the low serum albumin levels during continuous ambulatory peritoneal dialysis, especially in patients with a high peritoneal permeability.

Adolescent↗
PubMed1995

Insulin-like growth factor-I in patients on CAPD and hemodialysis: relationship to body weight and albumin level.

The relationship between insulin-like growth factor-I (IGF-I), body weight, and serum albumin was studied in 17 patients on continuous ambulatory peritoneal dialysis (CAPD) and 17 patients on hemodialysis. Patients were matched for gender, age (33-83 years), body mass index (16.7-36.1 kg/m2), hematocrit, concentrations of serum growth hormone, and duration of dialysis (1-210 months). Serum IGF-I concentration was measured by radioimmunoassay (Incstar) and albumin by a standard laboratory technique. CAPD patients had significantly lower serum albumin concentrations than hemodialysis patients, whereas IGF-I levels in the two groups were similar and did not differ from those in 18 normal subjects. We did not find significant positive correlations between IGF-I and serum albumin levels in CAPD or in hemodialysis patients. On the other hand, IGF-I showed a strong positive correlation with body weight (for the CAPD group r = 0.523; for both groups together r = 0.493). Both groups (CAPD and hemodialysis) and CAPD patients who weighted less than 60 kg (44%) had significantly lower serum IGF-I levels (113.5 +/- 10.2 and 108.8 +/- 15.7 micrograms/l +/- SEM, respectively) than patients who weighed 60-80 kg (38.3%; 181.2 +/- 20.9 and 196.6 +/- 27.2 micrograms/L +/- SEM, respectively) or above 80 kg (17.6%; 205.2 +/- 37.7 and 229.5 +/- 43.5; micrograms/L +/- SEM, respectively). It therefore appears that a low serum IGF-I level is a better indicator of malnutrition in CAPD and hemodialysis patients than low serum albumin.

Adult↗
PubMed1994

Elevated serum cholesterol is a risk factor for both coronary heart disease and thromboembolic stroke in Hawaiian Japanese men. Implications of shared risk.

BACKGROUND AND PURPOSE: The relation between total serum cholesterol level and thromboembolic or nonhemorrhagic stroke is controversial. The Honolulu Heart Program cohort of Japanese-American men provides data which show that elevated serum cholesterol is an independent predictor of thromboembolic stroke as well as coronary heart disease (CHD). The data are presented to suggest that the association of elevated cholesterol with stroke is sometimes underestimated or underreported partly because of competing or shared risk with CHD, the other major atherosclerotic end point. METHODS: The data are based on 6352 men (aged 51 to 74 years) at baseline examination (1971 to 1974) who were free of clinical CHD and stroke and were followed an average of 15 years for new cases of both end points. Relative risks of serum cholesterol for CHD and thromboembolic stroke were calculated, controlling for other major cardiovascular covariates. RESULTS: There was a continuous and progressive increase in both CHD and thromboembolic stroke rates with increasing levels of serum cholesterol. The relative risk between the highest and lowest quartiles of serum cholesterol was 1.7 (95% confidence interval, 1.4 to 2.0) for CHD and 1.4 (95% confidence interval, 1.1 to 1.9) for thromboembolic stroke. There was a decline in the difference in relative risks between CHD and thromboembolic stroke in older men (aged 60 years and older) compared with younger men (aged younger than 60 years). CONCLUSIONS: These data provide additional evidence that elevated serum cholesterol should be considered a primary risk factor for thromboembolic stroke, presumably through its effect on both coronary and cerebrovascular atherosclerosis. It is suggested that this association is sometimes underestimated or underreported partly because of shared or competing risk with CHD, the clinical manifestation of atherosclerosis that generally occurs earlier in life and with greater frequency than thromboembolic stroke.

Aged↗
PubMed1994

Trends in stroke incidence and mortality in Hawaiian Japanese men.

BACKGROUND AND PURPOSE: Vital statistics show a sharp decline in stroke mortality since the late 1960s. It is not clear whether this has been associated with a decline in stroke incidence. METHODS: Since 1966 the Honolulu Heart Program has monitored the incidence and mortality of coronary heart disease and stroke in a target population of 11,136 men of Japanese ancestry living on Oahu. Trends were analyzed from January 1, 1969, through December 31, 1988. RESULTS: Of 7893 men aged 45 to 68 years and free of stroke at entry examination, 530 developed first episodes of stroke in the period 1969 to 1988 (389 cases of thromboembolic stroke, 124 cases of hemorrhagic stroke, and 17 cases of stroke of unknown type). Age-adjusted annual stroke incidence declined from 5.1 per 1000 person-years in 1969 to 1972 to 2.4 in 1985 to 1988. The incidences of thromboembolic stroke, hemorrhagic stroke, and total stroke decreased 3.5%, 4.2%, and 4.4% per year, respectively. The 1-month case-fatality rates for thromboembolic stroke decreased moderately; those for hemorrhagic stroke fell dramatically. CONCLUSIONS: These findings suggest that the decline in stroke mortality in the past two or three decades results from a decline in both incidence rates and early case-fatality rates in thromboembolic and hemorrhagic stroke and stroke of unknown type. The decreases may be related to changes in risk factors, such as the decline in blood pressure and the decrease in cigarette smoking, as well as improvements in diagnosis and treatment.

Age Factors↗
PubMed1994

Epidemiology of stroke among Japanese men in Hawaii during 24 years of follow-up: the Honolulu Heart Program.

This report present epidemiologic data on stroke incidence and mortality as well as on risk factors for total stroke and subtypes of stroke among Japanese men in Hawaii, who were known to have much lower stroke morbidity and mortality than indigenous Japanese men. Of 7,893 men aged 45 to 68 and free of stroke at baseline examination (1965-68), 587 developed first episodes of stroke during 24 years of follow-up through 1989. Comparing the distribution of stroke subtypes before and after the advent of CT scanning in 1976, there was an increase in thromboembolic stroke (67% to 74%), a decrease in subarachnoid hemorrhage (9% to 6%) and unknown type (7% to 2%), and little change in intracerebral hemorrhage (18% to 19%). Total stroke incidence declined from 5.1 to 2.4 per 1,000 person years between 1969 and 1988, with a mean annual rate of decline of 5%. Total stroke mortality in the target population (examined and nonexamined men combined) also declined markedly, at a rate similar to that reported for U.S. white men of comparable ages. The one-month case fatality ratio fell dramatically in hemorrhagic stroke (75% to 29%) and only slightly (13% to 11%) in thromboembolic stroke during the same period. Relationships between a variety of biological, sociocultural and lifestyle factors and the risk of stroke subtypes were evaluated by means of bivariate and multivariate Cox regression models. Hypertension was the strongest and most consistent risk factor for all subtypes of stroke. Other risk factors showed inconsistent patterns of association with stroke subtypes in multivariate analysis.

Age Factors↗