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Biomedical subjects

R G Nelson

Publications and source records attributed to R G Nelson.

At least 19 recordsLinked to original sources
PubMed1997

Podocyte loss and progressive glomerular injury in type II diabetes.

Kidney biopsies from Pima Indians with type II diabetes were analyzed. Subjects were classified clinically as having early diabetes (n = 10), microalbuminuria (n = 17), normoalbuminuria, despite a duration of diabetes equal to that of the subjects with microalbuminuria (n = 12), or clinical nephropathy (n = 12). Subjects with microalbuminuria exhibited moderate increases in glomerular and mesangial volume when compared with those with early diabetes, but could not be distinguished from subjects who remained normoalbuminuric after an equal duration of diabetes. Subjects with clinical nephropathy exhibited global glomerular sclerosis and more prominent structural abnormalities in nonsclerosed glomeruli. Marked mesangial expansion was accompanied by a further increase in total glomerular volume. Glomerular capillary surface area remained stable, but the glomerular basement membrane thickness was increased and podocyte foot processes were broadened. Broadening of podocyte foot processes was associated with a reduction in the number of podocytes per glomerulus and an increase in the surface area covered by remaining podocytes. These findings suggest that podocyte loss contributes to the progression of diabetic nephropathy.

Adult↗
PubMed1997

Plasma lipoproteins and incidence of non-insulin-dependent diabetes mellitus in Pima Indians: protective effect of HDL cholesterol in women.

The role of plasma lipoproteins in the development of non-insulin-dependent diabetes mellitus (NIDDM) was studied in 787 non-diabetic (2-h glucose < 11.1 mmol/l) Pima Indians (265 men and 522 women). Subjects were followed for a mean of 9.8 (range: 1.8-16.4) years, during which 261 (76 men and 185 women) developed NIDDM. In men and women, very-low-density lipoprotein (VLDL) cholesterol, VLDL triglyceride, low-density lipoprotein triglyceride and total triglyceride, controlled for age, predicted NIDDM (P < 0.01 for each). These effects diminished when controlled for age, sex, body mass index, systolic blood pressure and 2-h glucose. However, high-density lipoprotein (HDL) cholesterol, controlled for age, body mass index, systolic blood pressure and 2-h glucose, was a significant protective factor for NIDDM in women (hazard rate ratio (HRR) = 0.35, 95% CI (0.23-0.54), P < 0.001, 90th compared with 10th percentile) but not in men (HRR = 1.04, 95% CI (0.53-2.05), P = 0.915). This association remained significant in women when controlled for fasting or 2-h plasma insulin concentrations, other estimates of insulin resistance or alcohol consumption. The protective effect of HDL cholesterol was similar among women with normal (2-h glucose < 7.8 mmol/1) or impaired (7.8 mmol/l < or = 2-h glucose < 11.1 mmol/l) glucose tolerance at baseline. These results indicate that lipoprotein disorders are an early accompaniment of the abnormalities that lead to NIDDM.

Adult↗
PubMed1996

Development and progression of renal disease in Pima Indians with non-insulin-dependent diabetes mellitus. Diabetic Renal Disease Study Group.

BACKGROUND: Non-insulin-dependent diabetes mellitus (NIDDM) is a major cause of end-stage renal disease. However, the course and determinants of renal failure in this type of diabetes have not been clearly defined. METHODS: We studied glomerular function at intervals of 6 to 12 months for 4 years in 194 Pima Indians selected to represent different stages in the development and progression of diabetic renal disease. Initially, 31 subjects had normal glucose tolerance, 29 had impaired glucose tolerance, 30 had newly diagnosed diabetes, and 104 had had diabetes for five years or more; of these 104, 20 had normal albumin excretion, 50 had microalbuminuria, and 34 had macroalbuminuria. The glomerular filtration rate, renal plasma flow, urinary albumin excretion, and blood pressure were measured at each examination. RESULTS: Initially, the mean (+/-SE) glomerular filtration rate was 143+/-7 ml per minute in subjects with newly diagnosed diabetes, 155+/-7 ml per minute in those with microalbuminuria, and 124+/-7 ml per minute in those with macroalbuminuria; these values were 16 percent, 26 percent, and 1 percent higher, respectively, than in the subjects with normal glucose tolerance (123+/-4 ml per minute). During four years of follow-up, the glomerular filtration rate increased by 18 percent in the subjects who initially had newly diagnosed diabetes (P=0.008); the rate declined by 3 percent in those with microalbuminuria at base line (P=0.29) and by 35 percent in those with macroalbuminuria (P<0.001). Higher base-line blood pressure predicted increasing urinary albumin excretion (P=0.006), and higher base-line urinary albumin excretion predicted a decline in the glomerular filtration rate (P<0.001). The initial glomerular filtration rate did not predict worsening albuminuria. CONCLUSIONS: The glomerular filtration rate is elevated at the onset of NIDDM and remains so while normal albumin excretion or microalbuminuria persists. It declines progressively after the development of macroalbuminuria.

Adolescent↗
PubMed1996

Genotyping human and bovine isolates of Cryptosporidium parvum by polymerase chain reaction-restriction fragment length polymorphism analysis of a repetitive DNA sequence.

In order to define transmission routes of cryptosporidiosis and develop markers that distinguish Cryptosporidium parvum isolates, we have identified 2 polymorphic restriction enzyme sites in a C. parvum repetitive DNA sequence. The target sequence was amplified by polymerase chain reaction from 100 to 500 oocysts and the amplified product was subjected to restriction enzyme digestion. Typing of 23 isolates showed that 10/10 calf isolates had the same profile. In contrast, 2 patterns were observed among human isolates: 7/13 displayed the calf profile, and 6/13 presented another pattern. The PCR-RFLP assay described here is a sensitive tool to distinguish C. parvum isolates.

Animals↗
PubMed1996

Parental hypertension and proteinuria in Pima Indians with NIDDM.

To determine if parental hypertension is associated with proteinuria in offspring with non-insulin-dependent diabetes mellitus (NIDDM), 438 diabetic Pima Indians (172 men, 266 women) aged 20 years or more and both of their parents were examined. Hypertension was defined as a systolic blood pressure 140 mm Hg or more, diastolic blood pressure 90 mm Hg or more, or treatment with antihypertensive medicine. Sixty-three percent of the fathers and 80% of the mothers had diabetes at the time their blood pressure was measured. Families in which either parent had proteinuria, defined as a urine protein-to-creatinine ratio > or = 0.5 g/g were excluded; 73 (16.7%) of the offspring had proteinuria. The prevalence rates of proteinuria in the offspring were similar if neither parent or only one parent had hypertension (8.9 and 9.4%, respectively), but was significantly higher if both parents had hypertension (18.8%), after adjustment for age, sex, duration of diabetes, and 2-h post-load plasma glucose concentration in the offspring and diabetes in the parents by logistic regression. The odds for proteinuria being present in the offspring if both parents had hypertension was 2.2 times (95% confidence interval, 1.2 to 4.2) that if only one parent had hypertension. When mean arterial pressure and blood pressure treatment in the offspring were added to the model the relationship remained (odds ratio = 2.2; 95% confidence interval, 1.1 to 4.3). Hypertension in both parents is associated with the development of proteinuria in offspring with NIDDM. This relationship was present even when controlled for the effects of blood pressure and its treatment in the offspring.

Adult↗
PubMed1996

Potential antifolate resistance determinants and genotypic variation in the bifunctional dihydrofolate reductase-thymidylate synthase gene from human and bovine isolates of Cryptosporidium parvum.

We have determined the nucleic acid sequences of a gene encoding the bifunctional enzyme dihydrofolate reductase-thymidylate synthase (DHFR-TS) from bovine and human AIDS isolates of Cryptosporidium parvum. THe DHFR-TS gene was isolated from genomic DNA libraries by hybridization with a probe amplified from C. parvum genomic DNA using generic TS primers in the polymerase chain reaction. Genomic Southern and electrophoretic karyotype analyses reveal C. parvum DHFR-TS is a single-copy gene on a 1200-kb chromosome. The DHFR-TS nucleic acid sequence contains no introns and the single 1563-bp open reading frame encodes a 179 residue N-terminal DHFR domain connected by a 55 amino acid junction peptide to a 287 residue C-terminal TS domain. The sequences of the DHFR-TS gene from the bovine and human C. parvum isolates differ at two positions in the 5'-flanking sequence and at 38 positions in the encoding sequence. These DNA sequence polymorphisms will provide a powerful probe to examine the genotypic diversity and genetic population structure of C. parvum. The two sequences encode identical TS domains which share all except one of the phylogenetically conserved amino acid residues identified among reported TS sequences. The predicted DHFR domain sequences contain nine amino acid differences; these polymorphisms all map to non-active site, surface locations in known DHFR structures. The C. parvum DHFR active site contains novel residues at several positions analogous to those at which point mutations have been shown to produce antifolate resistance in other DHFRs. Thus C. parvum DHFR may be intrinsically resistant ti inhibition by some antifolate DHFR inhibitors which may explain why cryptosporidiosis is refractory to treatment with the clinically common antibacterial and antiprotozoal antifolates.

Amino Acid Sequence↗
PubMed1996

Survey of the diet of Pima Indians using quantitative food frequency assessment and 24-hour recall. Diabetic Renal Disease Study.

OBJECTIVE: A dietary survey was conducted in the Gila River Indian Community in Arizona using two methods of dietary assessment--24-hour recall and quantitative food frequency (QFF) assessment--to determine the usual intake of the population. DESIGN: Interviews were conducted by Pima women who were trained and monitored by a research dietitian. Energy and nutrient intake were calculated using a computerized dietary database that included specific Pima foods. SUBJECTS: An age- and sex-stratified sample of 575 Pima Indians (273 men, 302 women) aged 18 to 74 years participated in the study. STATISTICAL ANALYSES: Spearman correlations were used to compare the results of the two survey methods for energy and each nutrient. Intraclass correlations were used to measure reproducibility. RESULTS: According to the 24-hour recall, mean reported energy intakes within decades of age were 95% to 112% of those in the US population for Pima women, and 76% to 94% of those in the US population for Pima men. Total energy intake assessed using QFF was 30% higher in men and 33% higher in women than the intake assessed using the 24-hour recall method. CONCLUSIONS: A large dietary survey conducted using lay interviewers in a Native-American community was as reproducible as studies conducted in the general US population. The Pima diet was distributed among the major nutrients in a proportion similar to the US diet.

Adolescent↗
PubMed1996

HLA*A2 confers mortality risk for cardiovascular disease in Pimans.

A sample of 1465 full heritage Piman Indians from Arizona were typed for the serological antigens of the HLA class I loci and then incorporated into a survival study that ended December 31, 1991. The total follow-up time was 11,749 person-years with an average of 8.0 years per person. During the study 298 persons died, 54 from cardiovascular disease (CVD). Allele HLA*A2 conferred a 4.94 fold rate for death from CVD (95% C.I. 1.91-12.77). When controlled for the potential confounding variables, cholesterol, mean blood pressure, smoking, body mass index, rheumatoid factor titer, and nephropathy, the mortality rate ratio (MRR) was 5.42 (95% C.I. 1.98-14.82). There was no statistically significant association of mortality with other HLA-A or HLA-B alleles, or for causes of death not related to cardiovascular disease.

Adult↗
PubMed1996

Survival during renal replacement therapy for diabetic end-stage renal disease in Pima Indians.

OBJECTIVE: To examine survival in Pima Indians receiving renal replacement therapy for end-stage renal disease attributed to NIDDM. RESEARCH DESIGN AND METHODS: Vital status through 1994 was determined for 136 diabetic Pima Indians from the Gila River Indian Community who began renal replacement therapy between 1973 and 1990. RESULTS: Median survival from the onset of renal replacement therapy was 39 months (95% Ci, 31-54), 31 months (95% Ci, 11-48) in those who began treatment between 1973 and 1981, and 44 months (95% Ci, 32-56) in those who began treatment between 1982 and 1990 (P = 0.020). During these periods, mean age at onset of treatment increased from 53.3 to 56.1 years (P = 0.166), and mean duration of diabetes at the onset of treatment increased from 16.5 to 20.2 years (P = 0.003). After adjustment for sex, duration of diabetes, initial dialysis type, and kidney transplantation by an age-stratified proportional-hazards analysis, the death rate after starting renal replacement therapy in the second half of the study was 0.54 times (95% CI, 0.33-0.88) that in the first half. If this analysis was restricted to those who survived at least 90 days of therapy, the difference between the time periods was diminished (death rate ratio = 0.76; 95% CI, 0.43-1.32). CONCLUSIONS: Survival in Pima Indians receiving renal replacement therapy improved significantly over the study despite an increase in the average age and diabetes duration of those beginning dialysis. Much of the improvement in survival is attributable to a reduction in the number of deaths within the first 90 days of therapy. The median survival of 47 months in Pima Indians < 65 years old at the initiation of therapy is substantially longer than the 30 months reported in blacks and 16 months reported in whites of similar age with NIDDM.

Adult↗
PubMed1996

Sequential trends in overall and cause-specific mortality in diabetic and nondiabetic Pima Indians.

OBJECTIVE: To compare sequential trends in overall and cause-specific death rates for diabetic and nondiabetic Pima Indians. RESEARCH DESIGN AND METHODS: Underlying causes of death in Pimas aged > or = 15 years old were determined for the years 1975-1989 from review of death certificates and medical records. Overall and cause-specific death rates were compared for consecutive intervals. RESULTS: The all-causes death rate, age- and sex-adjusted, did not change significantly between the first and second halves of the study for diabetic (death rate ratio [DRR] = 0.99, 95% CI 0.70-1.4) or nondiabetic Pimas (DRR = 0.92, 95% CI 0.74-1.1). Among diabetic Pimas, however, the death rate for diabetic nephropathy declined from 2.7 to 1.5/1,000 person-years (DRR = 0.55, 95% CI 0.33-0.93), with ischemic heart disease (IHD) replacing diabetic nephropathy as the leading cause in the second half (DRR = 1.5, 95% CI 0.91-2.6). For diabetic and nondiabetic Pimas combined, the death rate in three consecutive 5-year periods declined progressively for alcoholic liver disease (P = 0.024) and external causes of death (P = 0.016), the largest component of which was automobile accidents. CONCLUSIONS: The decrease in death rate for diabetic nephropathy may be a result of greater access to and improvements in renal replacement therapy. Because of shared risk factors, however, the IHD death rate increased and largely offset the decrease in diabetic nephropathy deaths. The decline in deaths from alcoholic liver disease and from automobile accidents parallels the national trend.

Adolescent↗
PubMed1996

A foot risk classification system to predict diabetic amputation in Pima Indians.

OBJECTIVE: To quantify the contribution of various risk factors to the risk of amputation in diabetic patients and to develop a foot risk scoring system based on clinical data. RESEARCH DESIGN AND METHODS: A population case-control study was undertaken. Eligible subjects were 1) 25-85 years of age, 2) diabetic, 3) 50% or more Pima or Tohono O'odham Indian, 4) lived in the Gila River Indian Community, and 5) had had at least one National Institutes of Health research examination. Case patients had had an incident lower extremity amputation between 1983 and 1992; control subjects had no amputation by 1992. Medical records were reviewed to determine risk conditions and health status before the pivotal event that led to the amputation. RESULTS: Sixty-one people with amputations were identified and compared with 183 control subjects. Men were more likely to suffer amputation than women (odds ratio [OR] 6.5, 95% CI 2.6-15), and people with diabetic eye, renal, or cardiovascular disease were more likely to undergo amputation than those without (OR 4.6, 95% CI 1.7-12). The risk of amputation was almost equally associated with these foot risk factors: peripheral neuropathy, peripheral vascular disease, bony deformities, and a history of foot ulcers. After controlling for demographic differences and diabetes severity, the ORs for amputation with one foot risk factor was 2.1 (95% CI 1.4-3.3), with two risk factors, 4.5 (95% CI 2.9-6.9), and with three or four risk factors, 9.7 (95% CI 6.3-14.8). CONCLUSIONS: Male Sex, end-organ complications of eye, heart, and kidney, and poor glucose control were associated with a higher amputation rate. Peripheral neuropathy, peripheral vascular disease, deformity, and a prior ulcer were similarly equally associated with an increased risk of lower extremity amputation.

Adult↗
PubMed1995

Plasmodium falciparum: D260, an intraerythrocytic parasite protein, is a member of the glutamic acid dipeptide-repeat family of proteins.

Members of a serologically cross-reacting family of proteins including Ag332 and Pf11.1, megadalton proteins of schizont-infected red blood cells, and gametocytes, respectively, and Pf155-RESA, a 155-kDa protein of ring-infected red blood cells, have been reported to share amino acid repeat sequences. These repeats are rich in glutamic acid dipeptides postulated to be involved in generating serologic cross-reactivity. We report the identification and characterization of another member of this cross-reacting family, a 260-kDa glutamic acid-rich intraerythrocytic protein. Human antibodies affinity purified on the 260-kDa region of Western boots of trophozoite proteins of Plasmodium falciparum were used to screen a trophozoite-stage lambda gt11 cDNA library. A 1.8-kb clone was identified and human antibodies were affinity purified on the expressing clone. Using this affinity-purified antibody and the 1.8-kb clone, the corresponding protein, its gene, and its chromosomal location were investigated. The 260-kDa corresponding protein serologically cross-reacts with Pf155-RESA, but is the product of a different gene. The 260-kDa protein is Triton X-100 soluble and is variable in molecular weight in different isolates. Immunoprecipitation of [35S]methionine-labeled infected red blood cells indicates that the protein is synthesized throughout the intraerythrocytic cycle but is most prominent in schizonts. The protein, as has been shown previously, is not immunoprecipitated from 125I surface-labeled infected red blood cells and is thus not PfEMP1, the antigen associated with cytoadherence. Indirect fluorescent antibody studies using fixed infected red blood cells suggest that the protein is localized to the periphery of the intraerythrocytic parasite.

Amino Acid Sequence↗
PubMed1995

The U-shaped association between body mass index and mortality: relationship with weight gain in a Native American population.

In order to determine whether weight loss explains high mortality rates in those with a low body mass index (BMI), the relationships between BMI, rate of weight gain and mortality were examined in Pima Indians. Subjects were 814 diabetic and 1814 nondiabetic participants in a longitudinal survey who had at least two examinations after age 20. Median duration of follow-up was 8.1 (range 0.03-25.1) years. BMI showed a U-shaped relationship with mortality rates in men with the lowest rates in the 30-35 kg/m2 category; an inverse relationship was seen in women. Subjects who were losing weight had higher mortality rates than those who were gaining. However, excess mortality among the lightest subjects was present among those who were gaining weight. Among nondiabetic subjects, the mortality ratio (MR) for BMI < 25 kg/m2 compared with 30-35 kg/m2 was 1.5 [95% confidence interval (CI) 1.0-2.2] unadjusted for weight gain, while the adjusted MR was 1.3 [95% CI 0.9-1.9]. Weight loss, which may reflect underlying illness, is associated with high mortality rates in Pima Indians but does not fully account for the high mortality in the lightest individuals.

Adult↗
PubMed1995

Progression of overt nephropathy in non-insulin-dependent diabetes.

The detection of overt albuminuria (> 300 mg/g creatinine) in the absence of azotemia was used to diagnose early nephropathy in 34 Pima Indians with NIDDM of 16 +/- 1 years duration. Differential solute clearances were performed serially to define the course of the glomerular injury over 48 months. At baseline, the GFR (107 +/- 5 ml/min), filtration fraction and sieving coefficients of relatively permeant dextrans (< 52 A) were all depressed below corresponding values in 20 normoalbuminuric Pima Indians with a similar duration of NIDDM. Over the ensuing 48 months the GFR (-34%) and filtration fraction (-13%) in the nephropathic patients declined further. The sieving coefficients of large, nearly impermeant dextrans (> 56 A radius) increased selectively and fractional clearances of albumin and IgG increased correspondingly by > 10-fold. Analysis of the findings with pore theory revealed: (1) a progressive decline in pore density and the ultrafiltration coefficient (Kf); and (2) broadening of glomerular pore-size distribution that resulted in greater prominence of large pores (> 70 A radius). We conclude that increasing loss of intrinsic ultrafiltration capacity is the predominant cause of the early and progressive decline in GFR that follows the development of nephropathy in NIDDM. We speculate that progressive impairment of barrier size-selectivity contributes to but does not fully account for the increasingly heavy proteinuria that is observed early in the course of this disorder.

Adolescent↗
PubMed1995

Preventing non-insulin-dependent diabetes.

Many risk factors for non-insulin-dependent diabetes mellitus (NIDDM), such as obesity, physical inactivity, and high-fat diet, can potentially be modified. Furthermore, some of the metabolic abnormalities, such as insulin resistance and impaired glucose tolerance, that predict diabetes can be improved by behavior modification and drug treatment. Thus, at least to some extent, NIDDM may be preventable. Several small clinical trials have addressed the hypothesis that NIDDM can be prevented by dietary modification, physical activity, or drug treatment. Some studies suggest a preventive effect, but the conclusions are limited by considerations of sample size, randomization, or intensity of the interventions. Consequently, the hypothesis that NIDDM is preventable requires further testing.

Behavior Therapy↗
PubMed1995

Incidence and determinants of elevated urinary albumin excretion in Pima Indians with NIDDM.

OBJECTIVE: To examine the incidence and determinants of elevated urinary albumin excretion in Pima Indians with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: The incidence of elevated urinary albumin excretion (> or = 30 mg albumin/g creatinine) and its relationship with baseline characteristics was determined in 456 Pima Indians > or = 15 years old with NIDDM who were followed for up to 11.6 years (median 4.7 years). RESULTS: Of these 456 subjects, 192 (42%; 58 men, 134 women) developed elevated urinary albumin excretion, 172 of whom (90%) were within the microalbuminuric range (30-299 mg/g). The incidence of elevated urinary albumin excretion was related to retinopathy, type, of diabetes treatment, longer duration of diabetes, lower body mass index, and higher values of mean arterial pressure, HbA1, and fasting and 2-h postload plasma glucose concentration at the baseline examination, but not to sex. A relationship with cholesterol was found in durations of diabetes of > or = 10 years. The cumulative incidence of elevated albumin excretion was 17% after 5 years of NIDDM. CONCLUSIONS: The incidence of elevated urinary albumin excretion in Pima Indians with NIDDM is at least as high as that reported previously in insulin-dependent diabetes mellitus, and its major determinants are the same as those shown previously to predict the development of more advanced renal disease in this population.

Adolescent↗