Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuropeptide Y (NPY) is a 36 amino-acid peptide. It is localized within the brain but is also present peripherally. It is a well substantiated orexigenic peptide with several other endocrine and behavioural effects. In this study NPY mRNA levels were measured, using the polymerase chain reaction amplification technique, in the hypothalamus of pre-obese (unweaned 13-day-old), young (weaned 28-day-old) and adult (11-week-old) obese fa/fa rats and compared to those of lean age-matched controls. Before weaning, pre-obese pups had the same NPY mRNA levels as controls. After weaning NPY mRNA levels were increased 2-fold in young 28-day-old and 4-fold in adult obese rats, relative to corresponding controls. When adult obese rats were intracerebroventricularly-treated with ovine corticotropin-releasing hormone (oCRF) for 7 days, they stopped gaining body weight relative to vehicle-infused obese controls. Upon measuring NPY mRNA levels in the hypothalamus of these two groups of animals, it was shown that the high NPY mRNA levels of vehicle-treated (control) obese rats were decreased by 3-fold following the intracerebroventricular oCRF administration. It is proposed that: 1) hypothalamic NPY may play a role in the establishment and maintenance of the genetic obesity syndrome of the fa/fa rat, and 2) maintenance of the genetic obesity syndrome of the fa/fa rat, and 2) hypothalamic NPY could be partly regulated by central CRF.
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PMID:Hypothalamic neuropeptide Y messenger ribonucleic acid levels in pre-obese and genetically obese (fa/fa) rats; potential regulation thereof by corticotropin-releasing factor. 840 61

To evaluate the principal determinants of the MCR and plasma t1/2 of unbound (free) GH in man, we performed steady state infusions of 3 doses of recombinant human GH during pharmacological suppression (iv octreotide) of endogenous GH secretion in 24 healthy adults and 12 patients (6 adults and 6 children) with chronic renal failure (CRF). Free plasma GH was calculated from total plasma GH (measured by immunoradiometric assay) and GH-binding protein activity (radioligand assay). The MCR of free GH was determined from free plasma GH and the rate of recombinant human GH infusion. The t1/2 of free plasma GH, and the concentration and the in vivo dissociation constant (Kd) of GH-binding protein (GHBP) were estimated by dynamic modeling of the postinfusion total plasma GH concentration decay curves. The MCR of free GH decreased and the plasma GH t1/2 increased significantly with increasing plasma GH concentrations. The MCR of free GH over its physiological concentration range was positively correlated with the body mass index as a measure of relative obesity and negatively related to age, but only at supraphysiological GH concentrations. In the adult patients with CRF, the MCR of free GH was decreased at each infusion rate by 25-38%, and the t1/2 was increased by 80-170%. Children with CRF showed a significantly lower MCR and higher t1/2 of plasma free GH than adult patients. Modeling and direct measurements of the off-rate of GH from its high affinity GHBP indicated normal dissociation rate constants but decreased molar concentrations of the GHBP in uremic plasma. We conclude that the rate of elimination of free GH from plasma in man is controlled by 1) plasma total free GH concentrations, 2) relative obesity, and 3) renal function within the physiological GH concentration range, whereas 4) age is a negative predictor of MCR only at supraphysiological GH concentrations.
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PMID:Multifactorial control of the elimination kinetics of unbound (free) growth hormone (GH) in the human: regulation by age, adiposity, renal function, and steady state concentrations of GH in plasma. 855 Jul 55

Organs were donated by a small number of relatives (54/146=37%), genetically related or familial, who volunteered to give a kidney to a relative or spouse at our institution in 1991-1994. The most common reason for not accepting them was an immunological incompatibility (30 cases), followed by a diagnosis of hypertension and/or renal disease (24 cases). Other medical contraindications-including heart/lung disease, obesity, latent diabetes, and hepatic disease-were found in 14 potential donors. One woman (22 years of age) was judged too young for donation. Five ESRD patients died before the investigation of the donor had been completed. Eighteen potential donors changed their minds and decided not to donate a kidney. Interestingly, there was a high percentage of denial of spouses due to positive crossmatches.
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PMID:Reasons for not accepting living kidney donors. 861 Apr 28

Bardet-Biedl syndrome is a rare autosomal recessive disease characterized by dysphormic extremities, retinal dystrophy, obesity, hypogenitalism in males, and renal structural abnormalities. Because the clinical outcome of these patients is not well known, 21 families with Bardet-Biedl syndrome (BBS) were studied to determine the natural history of the disease. In a prospective cohort study, 38 patients with the syndrome and 58 unaffected siblings were identified. Patients were studied in 1987 and again in 1993. Age of onset of blindness, hypertension, diabetes, renal impairment, and death was determined. The prevalence of obesity, gonadal dysfunction, and renal structural abnormalities was assessed. All but 5 BBS patients (86%) were legally blind, 26% being blind by the age of 13 years and 50% by 18 years. Eighty-eight percent were above the 90th percentile for height and weight. Twenty-five (66%) patients had hypertension, 25% of BBS patients by age 26 years, and 50% by age 34 years, whereas in the unaffected group, 25% had hypertension by age 49 years (P < 0.0001). Twelve (32%) BBS patients developed diabetes mellitus, compared with none of the unaffected group. Only 2 patients were insulin dependent. Twenty-five percent of BBS patients had diabetes by the age of 35 years. In 12 women of reproductive age, 1 (8%) had primary gonadal failure. In 10 men, 4 had primary testicular failure. Nine (25%) patients developed renal impairment, with 25% of the BBS group affected by the age of 48 years. Imaging procedures of the kidney were performed in 25 patients with normal renal function. Whereas fetal lobulation and calyceal cysts/diverticula/clubbing were characteristic, occurring in 96% of patients, 20% (n = 5) had diffuse and 4% (n = 1) focal cortical loss. Eight patients with BBS died, 3 with end-stage renal failure and 3 with chronic renal failure. On life-table analysis, 25% of BBS patients had died by 44 years, whereas at that age 98% of unaffected siblings were still alive (P < 0.0001). Bardet-Biedl syndrome has an adverse prognosis, with early onset of blindness, obesity, hypertension, and diabetes mellitus. Renal impairment is frequent and an important cause of death. Survival is substantially reduced.
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PMID:The importance of renal impairment in the natural history of Bardet-Biedl syndrome. 865 Dec 40

Expression of CRF messenger RNA (mRNA) and heteronuclear RNA (hnRNA) as well as the mRNAs encoding the CRF receptors of type 1 (CRF1R) and type 2 alpha (CFR2R) in the brain has been investigated in lean (Fa/?) and obese (fa/fa) Zucker rats. Exonic and intronic in situ hybridization histochemistry was employed to measure the mRNA and hnRNA levels in rats killed before (resting state), during, and 120 min after a treadmill running session. The resting expression of CRF hnRNA in the hypothalamic paraventricular nucleus (PVN) of obese rats was minimal and comparable to that of lean rats. However, during treadmill running, this expression was higher in obese than in lean rats. In obese rats, the transcription of the CRF1R mRNA in the PVN was high under resting conditions, dropped considerably during running, and rose again to elevated levels 120 min after the treadmill session. In lean rats, CRF1R mRNA in the PVN was minimal before and during running, but rose to a value similar to that in obese rats 120 min after running. In the PVN of obese rats, expression of the CRF1R gene measured during resting conditions was comparable to the level seen after running and proved to be dependent upon the feeding state of the rats. Expression of the CRF2R transcript was reduced in the ventromedial nucleus of the hypothalamus (VMH) of the obese rat. Plasma ACTH concentrations during treadmill running were lower in obese than in lean animals. Basal and postrunning levels of circulating corticosterone were higher in fa/fa than in Fa/? rats. However, there was no difference in corticosterone levels between lean and obese animals during running. The present results provide evidence for differences between lean and obese rats in the expression of CRF and its receptor within selective hypothalamic nuclei. Given the anorectic and thermogenic properties of CRF and the roles of PVN and VMH in the regulation of energy balance, it can be argued that the observed alterations in the biosynthesis of CRF and its receptors within the PVN and VMH might be related to the development of obesity.
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PMID:Expression of corticotropin-releasing factor and its receptors in the brain of lean and obese Zucker rats. 889 48

Little is known about hypertension in Haitians. We performed a pilot survey of ambulatory Haitian patients in a multispecialty clinic at a large public teaching hospital. Approximately 10% of the clinic population was of Haitian origin. Clinical data were collected on 88 consecutive Haitian patients. Of these 88, 77 (87.5%) were hypertensive (SBP > or = 140 or DBP > or = 90 mm Hg or taking antihypertensive medication). The characteristics of the hypertensive patients were: age 54.1 +/- 13.0 (s.d.) years; 27 men, 50 women; 12/64 (19%) smoked; 7/63 (11%) used alcohol. Diabetes was present in 21/77 (27%). In patients for whom height and weight were available, obesity was present in 52%. Using JNC V criteria, 18 (23%) had Stage 1, 16 (21%) Stage 2, 18 (23%) Stage 3, and 25 (33%) Stage 4 hypertension. Despite 63/77 (82%) being treated for hypertension, only 20 (26%) were controlled (< 140/< 90 mm Hg). Of those under treatment, 29 were taking one drug; 18 (two drugs); 12 (three drugs); and four (four drugs). Target organ damage was evident in 37 (48%), including coronary artery disease (8), CHF (6), chronic renal failure (15), stroke (9), and LVH by ECG (19). There was evidence of severe noncompliance in 32 (42%). We conclude that in this clinic sample, hypertension was highly prevalent and unusually severe in terms of blood pressure (BP) level, refractoriness to treatment, and target organ consequences. Further studies are indicated.
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PMID:Hypertension in Haitians: results of a pilot survey of a public teaching hospital multispecialty clinic. 900 4

Serum lipoprotein(a) [Lp(a)] concentrations in chronic renal failure patients were investigated in relation to the degree of renal insufficiency, treatment by maintenance hemodialysis, and correction of uremia by renal transplantation with or without cyclosporin immunosuppression. Fast serum levels of Lp(a) (mg/100 mL) were determined in 34 chronic renal failure patients not in need of maintenance dialysis (16 with serum creatinine 2.0-4.0 mg/100 mL; 18 with serum creatinine higher than 4.0 mg/100 mL), 40 patients treated by hemodialysis, 55 successful renal transplant recipients (28 under cyclosporin treatment and 27 receiving no cyclosporin), and 34 healthy controls. Age and sex distributions were similar among groups. Pregnant women; non-White individuals; subjects with obesity, diabetes, nephrotic syndrome, and hepatic and thyroid diseases; and those treated with oral contraceptives or lipid-lowering drugs were excluded from the study. Compared to controls, median Lp(a) was increased in nondialyzed renal failure patients (11 vs. 47.5 p < 0.001) and this was the only lipid abnormally observed in the group. There was no significant difference in Lp(a) levels between nondialized renal failure patients with serum creatinine 2.0-4.0 and > 4.0 mg/100 mL (47 vs. 49, NS). Moreover, Pearson correlation coefficient (r = 0.01, NS) showed that Lp(a) values were not related to serum creatinine in nondialyzed patients, In hemodialysis subjects Lp(a) concentrations (median = 29) were intermediate between those observed in nondialyzed patients and controls but the differences were not significant. Lp(a) levels in renal transplant patients treated with cyclosporin (median = 6) and not receiving cyclosporin (median = 13) were similar and did not differ from controls. Serum Lp(a) increases and attains maximum levels with mild/moderate reduction in renal function, and does not seem to change through late renal failure stages or in relation to the introduction of maintenance hemodialysis treatment. Correction of uremia by successful renal transplant caused normalization of Lp(a) levels regardless of the use of cyclosporin. Increased Lp(a) levels may be the earliest and more consistent lipid alteration seen in predialysis renal failure.
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PMID:Early elevation of lipoprotein(a) levels in chronic renal insufficiency. 904 61

Coronary heart disease (CHD) is more common in patients with chronic renal failure and is a major cause of death after renal transplantation. Elevated serum levels of lipoprotein(a) (Lp(a)) are a known risk factor for CHD in the general population and levels have been reported to be increased in renal transplant recipients. It has been suggested that cyclosporin may elevate Lp(a) levels. We therefore measured the serum concentration of Lp(a) in 50 renal transplant recipients who were receiving cyclosporin alone as immunosuppressive therapy and 50 who were treated with azathioprine and prednisolone, but not cyclosporin. The patients attended two renal transplant centres, one where cyclosporin alone was used as immunosuppressive treatment when possible and another where many patients commenced on azathioprine and prednisolone remain on this medication rather than cyclosporin. Patients in each group were matched for age and sex, but the time since transplantation was greater in those not receiving cyclosporin. Transplant function, obesity and the underlying cause of renal disease were similar in both groups of patients. Median Lp(a) concentration in the cyclosporin monotherapy group was 32.0 (range <0.8-140.3) mg/dl and was significantly (p < 0.05) greater than that of the azathioprine and prednisolone group which was 18.3 (range <0.8-167.7) mg/dl. The serum high-density lipoprotein (HDL) cholesterol concentration, which was 1.24 +/- 0.39 mmol/l (mean +/- SD) in patients receiving cyclosporin, was significantly (p < 0.05) less than that of those treated with azathioprine and prednisolone in whom it was 1.41 +/- 0.40 mmol/l. The lower level in those on cyclosporin was due to a decrease in the HDL2 subfraction. Serum lipid and lipoprotein concentrations were otherwise similar in the two groups of patients. The serum level of Lp(a) after renal transplantation may be influenced by the choice of immunosuppressive therapy.
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PMID:Influence of immunosuppressive therapy on lipoprotein(a) and other lipoproteins following renal transplantation. 906 48

New Zealand is a country in the South Pacific with a high proportion of Polynesians. While the prevalence of diabetes appears the same in New Zealand Europeans as Europeans elsewhere, Maori and Pacific Islands people have a 2 to 4-fold excess prevalence of diabetes. Although Europeans make up the majority of diabetic New Zealanders, the greatest concern lies with the Maori and Pacific Islands patients who experience an earlier age at diagnosis, greater obesity, higher rates of smoking (in Maori), poorer diabetes knowledge, poorer glucose control, and more end stage renal failure and blindness. Efforts are now being made to control the current epidemic.
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PMID:The epidemiology of diabetes and its complications in New Zealand. 916 14

The prevalence and natural history of severe proteinuria in mild to moderate hypertension are not completely defined. We screened 1635 men with a history of hypertension and randomized 1292 with untreated diastolic blood pressure (DBP) 95-109 mmHg to single-drug treatment with either hydrochlorothiazide, atenolol, captopril, clonidine, diltiazem-SR, prazosin, or placebo in a double-blind prospective trial. Twenty-seven of 1635 patients (1.7%) satisfying clinical criteria for primary hypertension were found to have developed proteinuria > 1000 mg/24 hours and were removed from the study. Follow-up data were obtained on 19 of these 27 patients. One patient was found to have focal segmental sclerosis and progressed to end-stage renal disease. Three other patients developed severe (serum creatinine > 3.5 mg/dl) chronic renal failure (one with diabetic nephropathy), one progressed from serum creatinine 1.4 to 2.2 mg/dl, but 14 of the 19 remained with stable serum creatinine < 2.0 mg/dl on follow-up for 6-9 years. Data were available for 1076 of 1155 (93%) treated study patients at end titration, 522/600 (87%) at one year and 322/444 (73%) at two years. There were significant associations for proteinuria with obesity and higher systolic blood pressure. There was a trend toward significant difference in mean 24-hour protein excretion rates at baseline between black (127 mg) and white (139 mg) patients (p = 0.07). There were no statistically significant changes in urinary protein excretion/24 hours between or within the different treatment groups (including placebo). Eighteen patients were removed from the study during the active treatment phase for proteinuria > 1000 mg/24 hours: hydrochlorothiazide 4, placebo 3, diltiazem 3, prazosin 3, atenolol 2, clonidine 2, and captopril 1. We conclude: (1) the prevalence of severe (> 1 g/24 hours) proteinuria in the hypertensive population is significant but does not necessarily imply a poor prognosis; (2) mean 24-hour urinary protein excretion rates did not vary in response to the different classes of antihypertensive drugs; and (3) there was no drug-specific increase in proteinuria detected in this study.
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PMID:Proteinuria in mild to moderate hypertension: results of the VA cooperative study of six antihypertensive agents and placebo. Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents. 918 Dec 78


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