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Biomedical subjects

J C Chan

Publications and source records attributed to J C Chan.

At least 37 records · Page 2Linked to original sources

Urinary epinephrine and norepinephrine interrelations with obesity, insulin, and the metabolic syndrome in Hong Kong Chinese.

The metabolic syndrome is characterized by a clustering of cardiovascular risk factors including type 2 diabetes mellitus, hypertension, dyslipidemia, and obesity. Elevated plasma insulin and urinary norepinephrine (noradrenaline) and reduced urinary epinephrine (adrenaline) excretion are associated with obesity in Caucasian populations. We examined the interrelationships between obesity, plasma insulin, and urinary catecholamine excretion in Chinese subjects with various components of the metabolic syndrome. A total of 577 Chinese subjects (aged 38 +/- 10 years; 68% with type 2 diabetes mellitus, hypertension, dyslipidemia, obesity, and/or albuminuria and 32% healthy subjects) were studied, all of whom had a plasma creatinine less than 150 micromol/L. The blood pressure, height, weight, waist and hip circumference, and fasting plasma glucose, insulin, lipid, and creatinine levels were measured. A 24-hour urine sample was collected for measurement of albumin and catecholamine excretion. The body mass index (BMI) and waist circumference were used as measures of general and central obesity, respectively. The insulin resistance index was estimated by the calculated product of fasting plasma insulin and glucose concentrations. Patients with an increasing number of components of the metabolic syndrome (type 2 diabetes mellitus, hypertension, dyslipidemia, obesity, and/or albuminuria) were more obese, hyperglycemic, dyslipidemic, and albuminuric and had higher blood pressure, plasma insulin, insulin resistance indices, and 24-hour urinary norepinephrine excretion but lower urinary epinephrine output (all P < .005). Increasing quintiles of BMI in the whole population or waist circumference in both sexes were associated with increasing trends for adverse lipid profiles, plasma insulin, insulin resistance indices, and urinary norepinephrine excretion but a decreasing trend for urinary epinephrine output (all P < .001). There were close associations between age, obesity, blood pressure, fasting plasma glucose, lipid, insulin, insulin resistance indices, and urinary catecholamine excretion. Using stepwise multiple regression analysis (all P < .001), 34% of the variability of the BMI and 45% of that of the waist circumference were independently related to gender (waist higher in males and BMI higher in females), increased plasma insulin, triglyceride, and urinary norepinephrine excretion, and decreased high-density lipoprotein (HDL) cholesterol and urinary epinephrine output. In Chinese subjects with different manifestations of the metabolic syndrome, hyperinsulinemia, insulin resistance, elevated norepinephrine, and reduced epinephrine excretion were closely associated with general and central obesity. Based on these findings, we postulate that complex interactions between the insulin and sympathoadrenal systems may lead to the development of obesity and the metabolic syndrome.

Adult↗

Association of retinopathy with a microsatellite at 5' end of the aldose reductase gene in Chinese patients with late-onset Type 2 diabetes.

Recent experimental data suggest that a microsatellite polymorphism at 5' end of the aldose reductase gene may be associated with the development of diabetic retinopathy. In the present study, we examined the allele distribution of the polymorphism in 384 Hong Kong Chinese patients who had late-onset (age at diagnosis > or =35 years) Type 2 diabetes, but no clinical evidence of cataract. Approximately 17% of them (n = 64) had retinopathy. The patients with retinopathy were older (52 +/- 11 years vs. 60 +/- 9 years, p < 0.01) and had a higher HbA1c (8.9 +/- 2.2% vs. 7.7 +/- 2.0%, p < 0.01 with adjustment for age) than those without the complication. Amongst all of the patients, we detected 10 microsatellite alleles and found that allele Z-4 was overpresented in those with retinopathy (9% vs. 4%, p < 0.05). There were no significant differences in allelic distributions of the major alleles Z + 2, Z, and Z-2, which accounted for more than 80% of the overall frequency, between the two groups of patients. Using multiple logistic regression analysis (R2 = 0.17, p < 0.01), we found that age (p < 0.01) and HbA1c (p < 0.05) were associated with retinopathy. In conclusion, our data suggest that the occurrence of diabetic retinopathy in the Chinese population may be influenced by clinical and metabolic factors. The aldose reductase gene may be implicated, but is not likely to play a major role.

Adult↗

Lower BMI cut-off value to define obesity in Hong Kong Chinese: an analysis based on body fat assessment by bioelectrical impedance.

There is increasing evidence suggesting that the cut-off values for defining obesity used in the Western countries cannot be readily applied to Asians, who often have smaller body frames than Caucasians. We examined the BMI and body fat (BF) as measured by bioelectrical impedance in 5153 Hong Kong Chinese subjects. We aimed to assess the optimal BMI reflecting obesity as defined by abnormal BF in Hong Kong Chinese. Receiver operating characteristic curve (ROC) analysis was used to assess the optimal BMI predicting BF at different levels. The mean age and SD of the 5153 subjects (3734 women and 1419 men) was 51.5 (SD 16.3) years (range: 18.0-89.5 years, median: 50.7 years). Age-adjusted partial correlation (r) between BMI and BF in women and men were 0.899 (P < 0.001) and 0.818 (P < 0.001) respectively. Using ROC analysis, the BMI corresponding to the conventional upper limit of normal BF was 22.5-23.1 kg/m(2), and the BMI corresponding to the 90 percentiles of BF was 25.4-26.1 kg/m(2). Despite similar body fat contents, the BMI cut-off value used to define obesity in Hong Kong Chinese should be lower as compared to Caucasians. We suggest a BMI of 23 kg/m(2) and 26 kg/m(2) as the cut-off values to define overweight and obesity respectively in Hong Kong Chinese.

Absorptiometry, Photon↗

Differential expression of fibroblast growth factor receptors in human digital development suggests common pathogenesis in complex acrosyndactyly and craniosynostosis.

The Apert hand is characterized by metaphyseal fusions of the metacarpals and distal phalanges, symphalangism, and soft-tissue syndactyly. More subtle skeletal anomalies of the limb characterize Pfeiffer and Crouzon syndromes. Different mutations in the fibroblast growth factor receptor 2 (FGFR2) gene cause these syndromes, and offer the opportunity to relate genotype to phenotype. The expression of FGFR1 and of the Bek and KGFR isoforms of FGFR2 has, therefore, been studied in human hand development at 12 weeks by in situ hybridization. FGFRs are differentially expressed in the mesenchyme and skeletal elements during endochondral ossification of the developing human hand. KGFR expression characterizes the metaphyseal periosteum and interphalangeal joints. FGFR1 is preferentially expressed in the diaphyses, whereas FGFR2-Bek expression characterizes metaphyseal and diaphyseal elements, and the interdigital mesenchyme. Apert metaphyseal synostosis and symphalangism reflect KGFR expression, which has independently been quantitatively related ex vivo to the severity of clinical digital presentations in these syndromes. Studies in avian development implicate FGF signaling in preventing interdigital apoptosis and maintaining the interdigital mesenchyme. Herein is proposed that in human FGFR syndromes the balance of signaling by means of KGFR and Bek in digital development determines the clinical severity of soft-tissue and bony syndactyly.

Acanthosis Nigricans↗

Smoking and diabetes in Chinese men.

Smoking is a major cardiovascular risk factor and cause of death. Diabetes mellitus is also associated with an increased mortality and morbidity. Evidence concerning whether smoking increases the incidence of diabetes remains conflicting. Glycaemic status and smoking habits were analysed in 3718 Chinese subjects in order to assess the possible association between smoking and risk of diabetes in the Chinese population. The World Health Organisation 1998 criteria were used for the diagnosis of glucose intolerance. Smoking was defined as current cigarette smoking or ex-smoking without regard to daily consumption. The smoking habits of the studied subjects were correlated with glycaemic status. There were 3003 (80.8%) women and 715 (19.2%) men. The mean age (SD) was 38.4 (12.8) years (median 35.0, range 12-88 years). Of the 3718 subjects, 786 (21.1%) had diabetes, 708 (19.1%) had impaired glucose tolerance, and 2224 (59.8%) had normal results. Of the 3003 women, only 87 (2.9%) were smokers. The female smokers were younger, heavier, and had higher alcohol consumption than non-smokers. The prevalence of diabetes was similar between female smokers and non-smokers after adjustment for age, body mass index, family history of diabetes, and alcohol. Of the 715 men, 175 (24.5%) were smokers. The male smokers were younger, had lower blood pressure, and higher alcohol consumption. After adjustment for age, body mass index, family history of diabetes and alcohol, the male smokers had lower blood pressure, higher one hour plasma glucose, and more diabetes. Using logistic regression analysis (stepwise forward) with age, body mass index, alcohol, smoking, and family history of diabetes as independent variables to predict the risk of having diabetes, age and body mass index are independently associated with diabetes in both men and women. In addition, smoking is independently associated with the risk of diabetes in men, the odds ratio (95% confidence interval, CI) being 1.705 (1.106 to 2.630). Family history of diabetes is independently associated with the risk of diabetes in women, and the odds ratio (95% CI) is 1.643 (1.314, to 2.053). In conclusion, it was found that smoking is independently associated with diabetes after adjustment for age, body mass index, alcohol, and family history of diabetes in Hong Kong Chinese men, the odds ratio being 1.7. The prevalence of smoking in Hong Kong Chinese women is low and its association with diabetes is inconclusive.

Adolescent↗

Renal tubular acidosis: a new look at an old problem.

Although the definition of renal tubular acidosis (RTA) is simple, understanding the physiologic basis underlying the various types of this clinical entity is much more difficult. The pathophysiology of this disorder is reviewed using the normal acid-base functions of the involved segments of the nephron as a guide to understanding. Clinical and laboratory features of the subtypes of RTA are addressed, and diagnosis and treatment discussed. New developments in the knowledge and understanding of the associated growth disturbances, mineral metabolism, and molecular biology of RTA are also reviewed to provide the most current view of this relatively common pediatric entity.

Acidosis, Renal Tubular↗

Pediatric hematuria and thin basement membrane nephropathy: what is it and what does it mean?

Hematuria is seen frequently in the pediatric population and may signal either benign or serious renal patholosis. A significant proportion of children with asymptomatic hematuria will have thin basement membrane nephropathy (TBMN), a benign disorder, yet there is little information about this entity outside the nephrology literature. This article is designed to provide an information base for pediatric practitioners to assist them in making appropriate decisions regarding diagnosis and care. A review of experience over a decade with 9 children with biopsy-proven TBMN, including follow-up to the present; is presented. In addition, review of literature regarding TBMN, Alport's and Berger's syndromes, which comprise the major clinical entities associated with asymptomatic pediatric hematuria, is presented. Each patient was evaluated for asymptomatic, documented and persistent hematuria. Renal biopsy was performed after clinical evaluation and follow-up. TBMN and Berger's disease (IgA nephropathy) are separable only by renal biopsy results; TBMN is benign and IgA nephropathy may be progressive, mandating referral to a nephrologist. The prognosis of TBMN is excellent.

Adolescent↗

Obstructive nephropathy in children: long-term progression after relief of posterior urethral valve.

BACKGROUND: Approximately one third of children with end-stage renal disease have the illness because of urinary tract malformations, obstructive uropathy, and hypoplasia/dysplasia. The significant drop in infant mortality from obstructive uropathies in recent decades, attributable to prenatal diagnosis with renal ultrasonography and coordinated surgical and medical care, necessitated a reevaluation of the long-term outcome. METHODS: To that end, we examined the long-term progression of obstructive nephropathy after neonatal relief of posterior urethral valves in our center over a span of 21 years, with diagnosis and care being provided by the same pediatric and urology team. RESULTS: The 10 consecutive cases of posterior urethral valves represented 7% of all patients with congenital malformative uropathies seen over this period. The following procedures were performed: primary valve ablation (90%) and vesicostomy (40%). Seventy percent of patients progressed to end-stage renal disease over a (mean +/- standard error of the mean) follow-up of 11.3 +/- 2.1 years. The linear plot of the log of the inverse of serum creatinine versus time suggested unrelenting progression. The rate of progression was rapid after serum creatinine exceeded 5 mg/dL but the rate was slow and steady from serum creatinine of 1.5 to 5 mg/dL. CONCLUSIONS: To test the effect of a therapeutic intervention to ameliorate the rate of progression, this steady and prolonged progression of 0.5 mg/dL per year between serum creatinine concentration of 1.5 to 5 mg/dL would seem the optimal study.

Adolescent↗

Renin-angiotensin system gene polymorphisms, blood pressure, dyslipidemia, and diabetes in Hong Kong Chinese: a significant association of tne ACE insertion/deletion polymorphism with type 2 diabetes.

OBJECTIVE: In Chinese populations, hypertension is common and is a major risk factor for cerebrovascular and coronary heart disease, particularly when associated with diabetes. The clustering of these disorders and dyslipidemia and obesity is termed the metabolic syndrome and is increasing in prevalence in the populations of modernizing Asian nations. The renin-angiotensin system (RAS) helps maintain blood pressure and salt homeostasis and may play a role in the pathogenesis of aspects of the metabolic syndrome. We investigated three RAS gene polymorphisms--the ACE insertion/deletion (I/D), angiotensinogen (AGT) M235T, and angiotensin II type 1 receptor (AT1R) A1166C polymorphisms--for a possible role in modulating these disorders in 853 Chinese subjects with varying components of the metabolic syndrome. RESEARCH DESIGN AND METHODS: The three gene polymorphisms of this cross-sectional study were detected using polymerase chain reaction-based protocols. The genotype frequencies were compared between the controls (n = 119) and both overlapping and nonoverlapping groups of patients with type 2 diabetes, hypertension, and dyslipidemia using chi2 test. Differences in levels of the biochemical parameters between the genotypes were determined using analysis of variance. RESULTS: No significant relationship was identified between these polymorphisms and blood pressure in this population. Although the AT1RA1166C polymorphism was not associated with any aspect of the metabolic syndrome examined, there was limited evidence to suggest that the AGT M235T polymorphism may be associated with cholesterol levels. The ACE I allele was significantly more frequent in each group comprising subjects with type 2 diabetes/glucose intolerance (GIT), and the I allele was associated with higher fasting plasma glucose levels. CONCLUSIONS: These findings suggest that these polymorphisms are unlikely to be involved in the pathogenesis of hypertension. The ACE I/D polymorphism was associated with the metabolic syndrome, having a higher frequency of I allele-containing genotypes in those groups, but this appeared to result predominantly from the relationship with type 2 diabetes/GIT in this population of Chinese subjects.

Adult↗

Factors predicting the age when type 2 diabetes is diagnosed in Hong Kong Chinese subjects.

OBJECTIVE: To examine the factors predicting age at diagnosis of type 2 diabetes in Hong Kong Chinese. RESEARCH DESIGN AND METHODS: The relationships between age at diagnosis and parental history of diabetes as well as an array of clinical and metabolic factors were examined using a hospital clinic-based diabetes registry involving 3,414 index patients with type 2 diabetes Patterns of age at diagnosis in successive generations were also examined using 21 affected child-parent pairs and 7 affected child-parent-grandparent trios. RESULTS: Approximately 29% of the index patients were diagnosed with type 2 diabetes at < or = 35 years of age (hereby defined as early-onset). Compared with the patients diagnosed at >35 years of age (hereby defined as late-onset) the early-onset patients had higher rates of positive paternal (16 vs. 5%) and maternal (22 vs. 12%) history of diabetes (both at P < 0.01) and had poorer metabolic profiles. In the overall index patients, male sex, higher HbA1c waist-to-hip ratio (WHR), and systolic blood pressure (sBP); lower HDL cholesterol level; and a positive paternal was well as maternal history of diabetes predicted younger age at diagnosis. More senior age and higher BMI and diastolic blood pressure predicted olderq age at diagnosis. Predictors for younger age at diagnosis in the male patients were higher HbA1c and sBP and a positive paternal history of diabetes Predictors for younger age at diagnosis in the female patients were higher HbA1c WHR, and sBP and a paternal as well as maternal history of diabetes. In the affected child parent pairs and clild-parent-grandparent trios there was a decrease in age at diagnosis in successive generations. CONCLUSIONS: Our data indicate that both familial (possibly genetic) and metabolic factors affect the age of onset of type 2 diabetes in the Chinese population. The results also suggest an onset and progression pattern of the disease that is compatible with the phenomenon of anticipation.

Adult↗

Familial early-onset type 2 diabetes in Chinese patients: obesity and genetics have more significant roles than autoimmunity.

OBJECTIVE: We examined the prevalence of different forms of diabetes in Hong Kong Chinese patients with familial early-onset type 2 diabetes and compared their clinical features with patients with familial late-onset type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 145 young patients with early-onset diabetes (age and age at diagnosis < or = 40 years) and a family history of diabetes were studied. They were screened for mutations in the genes encoding glucokinase, hepatocyte nuclear factor (HNF)-4alpha, and HNF-1alpha. The mitochondrial DNA A-->G at nucleotide 3243 (mt3243) and amyLin S20G mutations were studied, and antibodies to GAD (anti-GADs) were also examined. RESULTS: The prevalence of putative diabetogenic gene mutations and autoimmune markers were 4% for glucokinase, 0% for HNF-4alpha, 5% for HNF-1alpha, 3% for mt3243, 2% for amylin 520G, and 4% for anti-GAD. Compared with late-onset patients, the patients with early-onset diabetes had a higher prevalence of a parental history of diabetes and were generally more obese. When classified by obesity indexes (BMI and waist circumference), the obese patients, especially those with early-onset diabetes, had a clustering of cardiovascular risk factors and increased rates of retinopathy and albuminuria. CONCLUSIONS; Genetic factors (up to 14%) and obesity (55%) play more significant roles than autoimmunity (4%) in familial type 2 diabetes in young Chinese patients. The significance of obesity-related genes and other gene-gene and gene-environment interactions in these young patients remains to be determined.

Adult↗

Albuminuria and the renin-angiotensin system gene polymorphisms in type-2-diabetic and in normoglycemic hypertensive Chinese.

BACKGROUND: Albuminuria predicts nephropathy-related mortality in Caucasian and Chinese populations. The involvement of renin-angiotensin system (RAS) gene polymorphisms in the pathogenesis of nephropathy has been described predominantly in Caucasian populations. We have previously suggested that the angiotensinogen 235T variant may be associated with nephropathy in diabetic Chinese. PATIENTS AND METHODS: To validate these findings and extend them to include non-diabetic nephropathy, we examined the association of albuminuria and gene polymorphisms of the angiotensinogen M235T, angiotensin-converting enzyme insertion/deletion and angiotensin II type I receptor A1166C polymorphisms in 614 Chinese subjects (66% type 2 diabetic, 16% normoglycemic hypertensives and 18% controls). RESULTS: Obesity and higher blood pressure were associated with albuminuria in both diabetes and normoglycemic hypertension. In the diabetic group, albuminuria was also associated with increased insulin resistance and glycemic indices, duration of diabetes and adverse lipid profiles. Only the ACE gene polymorphism showed evidence of association with albuminuria, with the D allele being less frequent in the normoglycemic hypertensive patients with albuminuria (25.0%) than the controls (41.4%) or normoalbuminuric group (39.6%) and in those hypertensives at increased risk (albumin-to-creatinine ratio > 5.6 mg/mmol) of end-stage renal disease than those at lower risk (all p < 0.05), but not in the diabetic group. The D allele was also less prevalent in the total (31.9%) and normoalbuminuric (32.2%) diabetic groups than in the controls (p < 0.05). CONCLUSION: In this cohort of Chinese subjects, the ACE gene polymorphism D allele was less frequent in normoglycemic hypertensive patients with albuminuria and in type 2 diabetes.

Adult↗

How to minimize missing those subjects with high 2HR plasma glucose but 'normal' fasting plasma glucose levels?

Among the subjects with 'normal' fasting plasma glucose (PG) levels (< 7.0 mmol/L), some of them are actually suffering from impaired glucose tolerance and diabetes, which can only be diagnosed by 2hr PG levels. We aim to find out a proper clinical approach in order to minimize missing those subjects with high 2hr PG but 'normal' fasting PG levels. We analyzed data collected from a previously published population-based prevalence survey for glucose intolerance in 1486 Hong Kong Chinese subjects who had no past history of diabetes. Of the 1468 subjects, there were 138 subjects (9.4%) having "missed glucose intolerance". Compared to the diabetic subjects (fasting plasma glucose > or = 7.0 mmol/L) after adjustment for age, the subjects with missed glucose intolerance had similar characteristics except lower glycemic level. Compared to the normal subjects (fasting plasma glucose < 7.0 mmol/L) after adjustment for age, subjects with missed glucose intolerance had more obesity (both general and central), more hypertension, worse glycemic status and lipid profile in both men and women. There were 38 subjects (2.6%) having impaired fasting glucose. Of these 38 subjects, 24 (63.2%) had missed glucose intolerance. The detection of missed glucose intolerance increased from 9.7% of overall male subjects to 23.1% in men with hypertension to 52.9% in men with both hypertension and family history of diabetes. Similarly, the detection of missed glucose intolerance increased from 9.0% of overall female subjects to 25.7% in women with obesity to 45.2% in women with both obesity and hypertension. If only fasting plasma glucose is performed, 4% of subjects will be diagnosed to have diabetes or impaired fasting glucose while up to 10% of subjects having impaired glucose tolerance or diabetes will be missed in Hong Kong Chinese. The latter 2 groups of subjects have similar cardiovascular risk factors to those with fasting PG > or = 7.0 mmol/L. We recommend that for those with a family history of diabetes, hypertension or obesity, an oral glucose tolerance test instead of fasting plasma glucose should be used in the first place for the diagnosis of glucose intolerance. For those with impaired fasting glucose, a routine follow-up oral glucose tolerance test should also be performed. This clinical approach may improve the detection of those subjects with glucose intolerance, who will be otherwise missed by using fasting plasma glucose alone.

Adult↗

Glycaemic control and obesity are the major determinants of diabetic dyslipidaemia in Hong Kong Chinese.

OBJECTIVES: Dyslipidaemia plays a major role in the increased mortality in diabetes. Our aim was to address the quantitative abnormalities and determinants for lipid abnormalities in Chinese Type 2 diabetic patients. MATERIAL AND METHODS: In this study, we examined 1 279 Chinese type 2 diabetic patients and compared them with 959 non-diabetic control subjects. RESULTS: Of the 1 279 Type 2 diabetic patients, 588 (46.0%) were men and 691 (54.0%) were women. The mean age was 40.4 +/- 8.1 years (median: 41.0 years, range: 16-72 years). Compared to the 959 age- and sex-matched non-diabetic controls, diabetic patients were more obese, had higher blood pressure and adverse lipid profile characterized by high triglycerides and low high-density lipoprotein cholesterol. After adjusting for age, sex, smoking, obesity, use of lipid-lowering drugs and anti-diabetic agents, diabetic patients had higher risk of having hypertriglyceridaemia (>=2.3 mmol/L) and low high-density lipoprotein cholesterol (<0.9 mmol/L) than non-diabetic subjects. The corresponding odds ratios were 2.9 and 1.5, respectively. With multiple regression analysis (stepwise), dyslipidaemia was mainly associated with glycaemia, obesity and age in diabetic patients, and obesity, male gender and age in non-diabetic subjects. CONCLUSION: We have confirmed the high prevalence and increased risk of dyslipidaemia in Chinese type 2 diabetic patients. The long-term significance of these lipid abnormalities and their synergism on clinical outcomes requires further evaluation.

Adolescent↗

Hairy cell leukemia in Hong Kong Chinese: a 12-year retrospective survey.

BACKGROUND: Hairy cell leukemia (HCL) is a unique chronic B cell lymphoproliferative disease (B-LPD), with distinct clinical and pathological features, and excellent treatment response to 2-chlorodeoxyadenosine (2-CDA) and pentostatin. There have been few reports of HCL from oriental countries. PATIENTS AND METHODS: A retrospective survey of HCL in six major hematology units in Hong Kong over a 12-year period. RESULTS: There were 18 cases of HCL identified. Most patients presented with fever, splenomegaly and monocytopenia. Lymphadenopathy was present in three patients, and open biopsy revealed tuberculosis infection in two cases. Seven cases received interferon and 12 cases received 2-CDA. Four patients died from bronchogenic carcinoma, cerebral vascular accident, fulminant hepatitis B virus reactivation and malignant melanoma. The remaining 14 patients are in clinical remission at a median of 6 years' follow-up; two are also surviving from second malignancies (thyroid papillary carcinoma and renal cell carcinoma). CONCLUSIONS: Parallel to the low incidence of B-LPD in Chinese, the incidence of HCL (0.035/100000 population per year) is much lower than in Western series. Other clinical features such as male dominance, clinical presentation, response to 2-CDA treatment, and association with second malignancy are similar to Western reports. However, two common complications in the Chinese population are the fulminant reactivation of hepatitis B infection and disseminated tuberculosis infection.

Adult↗

Dipolar coupling information in multispin systems: application of a compensated REDOR NMR approach to inorganic phosphates. Rotational echo double resonance.

An experimental strategy has been developed for measuring multiple dipole-dipole interactions in inorganic compounds using the technique of rotational echo double resonance (REDOR) NMR. Geometry-independent information about the dipole couplings between the observe nuclear species S (arbitrary quantum number) and the heteronuclear species I (spin-12) can be conveniently obtained from the experimental curve of DeltaS/S(0) versus dipolar evolution time by limiting the analysis to the initial data range 0 < delta S/S(0) < 0.30. Numerical simulations have been carried out on a three-spin system of type SI(2) in order to assess the effect of the I-I homonuclear dipole-dipole coupling and the influence of experimental imperfections such as finite pulse length and misadjustments of the 180 degrees pulses applied to the I-spin species. The simulations show further that within the initial data range the effects of such misadjustments can be internally compensated by a modified sequence having an additional 180 degrees pulse on the I channel in the middle of the dipolar evolution periods. Experimental (27)Al¿(31)P¿ REDOR results on the multispin systems Al(PO(3))(3), AlPO(4), [AlPO(4)](12)(C(3)H(7))(4)NF, and Na(3)PO(4) confirm the general utility of this approach. Thus, for applications to unknown systems the compensation strategy obviates calibration procedures with model compounds.

Computer Simulation↗

Alpha-tocopherol modulates lipoprotein cytotoxicity in obstructive nephropathy.

Oxidative stress in unilateral ureteral obstruction (UUO) contributes to the development of glomerular and tubulointerstitial lesions. The present study investigated whether oxidized low-density lipoprotein (oLDL) contributes to the pathogenesis of kidney injury in UUO, and whether alpha-tocopherol modulates such cytotoxicity and promotes repair. Male Sprague-Dawley rats weighing 100-125 g were assigned to three groups of 6 animals each: (1) sham, regular chow; (2) UUO, regular chow; and (3) UUO, alpha-tocopherol supplementation. We found a significant increase in the level of oxidative stress in the UUO group as measured by malondialdehyde (MDA) content in both plasma and kidneys. The LDL isolated from this group was cytotoxic to rat mesangial cells. The level of oxidation and cytotoxicity was significantly reduced when animals were treated with alpha-tocopherol. Plasma cholesterol concentration, kidney MDA, and transforming growth factor beta1 mRNA expression were all significantly increased in the UUO animals, and partially reduced in alpha-tocopherol-treated animals. Our data suggest that oxidative modification of LDL is associated with the renal injury in UUO. Taken together, our data support the concept that alpha-tocopherol can modulate LDL oxidation and its cytotoxic effects on rat mesangial cells in vitro.

Animals↗