Protection of glucotoxicity by a tripeptide derivative of α-melanocyte-stimulating hormone in human epidermal keratinocytes.

BACKGROUND: Chronic skin ulcers are a major complication and a therapeutic challenge in patients with diabetes mellitus. Glucose-induced accumulation of reactive oxygen species (ROS) is considered to be an important pathogenetic factor in diabetes. OBJECTIVES: To characterize the impact of high glucose (HG) on normal human keratinocytes (NHKs) and examine if Lys-d-Pro-Thr (KdPT), a tripeptide derived from α-melanocyte-stimulating-hormone, has protective effects. METHODS: We investigated the key functions of NHKs under HG conditions with or without KdPT in vitro as well as ex vivo employing a skin organ culture model. RESULTS: HG impaired metabolic activity, cell proliferation, viability and migration of NHKs. As shown by atomic force microscopy HG altered the biophysical properties of NHKs, i.e. cell size and elasticity. Glucotoxicity in NHKs was paralleled by the induction of intracellular ROS and endoplasmic reticulum stress. KdPT attenuated HG-induced oxidative stress and antagonized the effects of glucose on cell viability, metabolic activity and migration. Importantly, KdPT also antagonized the suppressive effect of HG on epidermal migration in wounded human skin organ cultures. CONCLUSIONS: Our findings highlight a novel effect of KdPT that could be exploited for the future therapy of diabetic skin ulcers.

Internationally distributed frozen oyster meat causing multiple outbreaks of norovirus infection in Australia.

BACKGROUND: Between November 2003 and January 2004, outbreaks of norovirus in 3 Australian jurisdictions involving 83 cases of illness were associated with imported oyster meat. METHODS: Cohort studies were conducted in 2 jurisdictions to identify relative risks of illness for the consumption of oysters. A case series was conducted in the third jurisdiction. RESULTS: The cohort studies conducted in the first 2 jurisdictions identified relative risks of illness of 17 (95% confidence interval, 5-51) and 35 (95% confidence interval, 5-243), respectively, for the consumption of oysters. Multiple strains of norovirus were detected in fecal specimens from 8 of 14 patients and in 1 of the 3 batches of implicated oyster meat using seminested reverse-transcriptase polymerase chain reaction methods. Traceback investigations revealed that all oyster meat was harvested from the same estuary system in Japan within the same month. CONCLUSIONS: These outbreaks demonstrate the potential of foodborne disease to spread internationally and the need for national and international collaboration to investigate such outbreaks. Foodborne illness related to norovirus is underestimated because of underreporting of human cases and challenges in laboratory detection of viruses in foods, both of which can delay public health action.

Fasting glucose and cardiovascular risk factors in an urban population.

OBJECTIVE: To test the hypothesis that blood glucose levels in the range of normoglycemia are associated with increased cardiovascular risk we performed an epidemiological study in an urban population. METHODS: Randomly selected adults > or = 20 years were studied using stratified sampling. Target sample was 1800 (men 960, women 840) of which 1123 subjects participated. Blood samples were available in 1091 subjects (60.6%, men 532, women 559). Measurement of anthropometric variables, blood pressure, fasting blood glucose and lipids was performed. Cardiovascular risk factors were determined using US Adult Treatment Panel-3 guidelines. Pearson's correlation coefficients (r) of fasting glucose with various risk factors were determined. Fasting glucose levels were classified into various groups as < 75 mg/dl, 75-89 mg/dl, 90-109 mg/dl, 110-125 mg/dl and > 126 mg/dl or known diabetes. Prevalence of cardiovascular risk factors was determined in each group. RESULTS: There was a significant positive correlation of fasting glucose in men and women with body mass index (r = 0.20, 0.12), waist-hip ratio (0.17, 0.09), systolic blood pressure (0.07, 0.22), total cholesterol (0.21, 0.15) and triglycerides (0.21, 0.25). Prevalence (%) of cardiovascular risk factors in men and women was smoking/tobacco use in 37.6 and 11.6, hypertension in 37.0 and 37.6, overweight and obesity in 37.8 and 50.3, truncal obesity in 57.3 and 68.0, high cholesterol > or = 200 mg/dl in 37.4 and 45.8, high triglycerides > or = 150 mg/dl in 32.3 and 28.6 and metabolic syndrome in 22.9 and 31.6 percent. In various groups of fasting glucose there was an increasing trend in prevalence of overweight/obesity, hypertension, hypercholesterolaemia, hypertriglyceridaemia, and metabolic syndrome (Mantel-Haenzel X2 for trend, p < 0.05) and fasting glucose < 75 mg/dl was associated with the lowest prevalence of these risk factors. CONCLUSIONS: There is a continuous relationship of fasting glucose levels with many cardiovascular risk factors and level < 75 mg/dl is associated with the lowest prevalence.

Body-mass index, waist-size, waist-hip ratio and cardiovascular risk factors in urban subejcts.

BACKGROUND AND OBJECTIVE: Influence of obesity as determinant of cardiovascular risk factors has not been well studied. To determine association of obesity, measured by body-mass index (BMI), waist-size or waist-hip ratio (WHR), with multiple risk factors in an urban Indian population we performed an epidemiological study. METHODS: Randomly selected adults > or = 20 years were studied using stratified sampling. Target sample was 1800 (men 960, women 840). 1123 subjects (response 62.4%) were evaluated and blood samples were available in 532 men and 559 women (n=1091, response 60.6%). Measurement of anthropometric variables, blood pressure, fasting blood glucose and lipids was performed. Atherosclerosis risk factors were determined using current guidelines. Pearson's correlation coefficients (r) of BMI, waist and WHR with various risk factors were determined. BMI was categorized into five groups: <20.0 Kg/m2, 20.0-22.9, 23.0-24.9, 25.0-29.9, and > or = 30 Kg/m2; waist size was divided into five groups and WHR into six groups in both men and women. Prevalence of cardiovascular risk factors, smoking, hypertension, diabetes, metabolic syndrome and dyslipidaemias was determined in each group and trends analyzed using least-squares regression. RESULTS: There is a significant positive correlation of BMI, waist-size and WHR with systolic BP (r= 0.46 to 0.13), diastolic BP (0.42 to 0.16), fasting glucose (0.15 to 0.26), and LDL cholesterol (0.16 to 0.03) and negative correlation with physical activity and HDL cholesterol (-0.22 to -0.08) in both men and women (p<0.01). With increasing BMI, waist-size and WHR, prevalence of hypertension, diabetes, and metabolic syndrome increased significantly (p for trend <0.05). WHR increase also correlated significantly with prevalence of high total and LDL cholesterol and triglycerides (p <0.05). CONCLUSIONS: There is a continuous positive relationship of all markers of obesity (body-mass index, waist size and waist hip ratio) with major coronary risk factors- hypertension, diabetes and metabolic syndrome while WHR also correlates with lipid abnormalities.

Maturation of erythroid cells and erythroleukemia development are affected by the kinase activity of Lyn.

This study examined the impact of the tyrosine kinase Lyn on erythropoietin-induced intracellular signaling in erythroid cells. In J2E erythroleukemic cells, Lyn coimmunoprecipitated with numerous proteins, including SHP-1, SHP-2, ras-GTPase-activating protein, signal transducers and activators of transcription (STAT) 5a, STAT5b, and mitogen-activated protein kinase; however, introduction of a dominant-negative Lyn (Y397F Lyn) inhibited the interaction of Lyn with all of these molecules except SHP-1. Cells containing the dominant-negative Lyn displayed altered intracellular phosphorylation patterns, including mitogen-actiated protein kinase, but not erythropoietin receptor, Janus-activated kinase (JAK) 2, or STAT5. As a consequence, erythropoietin-initiated differentiation and basal proliferation were severely impaired. Y397F Lyn reduced the protein levels of erythroid transcription factors erythroid Kruppel-like factor and GATA-1 up to 90%, which accounts for the inability of J2E cells expressing Y397F Lyn to synthesize hemoglobin. Although Lyn was shown to bind several sites on the cytoplasmic domain of the erythropoietin receptor, it was not activated when a receptor mutated at the JAK2 binding site was ectopically expressed in J2E cells indicating that JAK2 is the primary kinase in erythropoietin signaling and that Lyn is a secondary kinase. In normal erythroid progenitors, erythropoietin enhanced phosphorylation of Lyn; moreover, exogenous Lyn increased colony forming unit-erythroid, but not burst forming uniterythroid, colonies from normal progenitors, demonstrating a stage-specific effect of the kinase. Significantly, altering Lyn activity in J2E cells had a profound effect on the development of erythroleukemias in vivo: the mortality rate was markedly reduced and latent period extended when either wild-type Lyn or Y397F Lyn was introduced into these cells. Taken together, these data show that Lyn plays an important role in intracellular signaling in nontransformed and leukemic erythroid cells.

Dominant action of mutated erythropoietin receptors on differentiation in vitro and erythroleukemia development in vivo.

J2E cells produce rapid, fatal erythroleukemias in vivo but still respond to erythropoietin (epo) in vitro by differentiating, proliferating and remaining viable in the absence of serum. Mutant epo receptors were introduced into these cells to determine whether they could influence the different biological responses to epo in vitro and the development of erythroleukemias. Three mutant receptors were used as cytoplasmic truncation mutants Delta257 and Delta321 (above box 1 and below box 2 respectively), and the cytoplasmic point mutant W282R (defective for JAK2 activation). Strikingly, the Delta321 mutation produced a hyper-sensitive response in vitro to epo-induced differentiation and viability, but not to proliferation. In contrast with the Delta321 receptor, the Delta257 and W282R mutants inhibited all biological responses to epo due to impaired JAK2 phosphorylation. Significantly, erythroleukemias took almost twice as long to develop with cells containing the W282R mutation, indicating that JAK2 plays an important role in the emergence of these leukemias. These data demonstrate that mutant epo receptors dominantly altered responses of J2E cells to epo in culture and the development of erythroleukemias. Oncogene (2000) 19, 953 - 960.

A novel ADP-ribosylation like factor (ARL-6), interacts with the protein-conducting channel SEC61beta subunit.

We report here the isolation of a new member of the ADP-ribosylation factor (ARF)-like family (ARL-6) present in the J2E erythroleukemic cell line, but not its myeloid variants. Consistent with this lineage-restricted expression, ARL-6 mRNA increased with erythropoietin-induced maturation of J2E cells, and decreased with interleukin 6-induced differentiation of M1 monoblastoid cells. In tissues, ARL-6 mRNA was most abundant in brain and kidney. While ARL-6 protein was predominantly cytosolic, its membrane association increased following exposure to GTP-gammaS, like many members of the ARF/ARL family. Using the yeast two-hybrid system, six molecules which interact with ARL-6 were identified including SEC61beta, a subunit of the heterotrimeric protein conducting channel SEC61p. Co-immunoprecipitation of ARL-6 confirmed a stable association between ARL-6 and SEC61beta in COS cells. These results demonstrate that ARL-6, a novel member of the ADP-ribosylation factor-like family, interacts with the SEC61beta subunit.

Unsupervised waveform classification for multi-neuron recordings: a real-time, software-based system. I. Algorithms and implementation.

We describe a new, mostly software-based device for the sorting of waveforms in an extracellular multi-neuron recording situation. The sorting algorithm is largely unattended, and, after an initial 'learning' process, works in real time. Shape comparisons are based on up to 8 time points in the waveform; these points (the reduced feature set) are chosen automatically by analyzing the current incoming data stream. A feasibility version has been implemented on a LSI-11/2 system, using FORTRAN for set-up calculations and assembler for the real-time operations. Detailed comparisons with performance of other sorting devices are presented in the companion paper.

Unsupervised waveform classification for multi-neuron recordings: a real-time, software-based system. II. Performance comparison to other sorters.

The companion paper has described a new, fully automatic device for the sorting of action potential waveforms in real time. We present here a brief comparison of performance between this new device and several of the older, more traditional devices used for this purpose. We include in the comparison the performance of 3 human observers.

c-erbB-2 amplification and overexpression in breast cancer: evaluation and comparison of Southern blot, slot blot, ELISA and immunohistochemistry.

The oncogene c-erbB-2 has been shown to be amplified in 17-30% of breast cancers, with similar levels of overexpression of the oncogene product p185, a transmembrane growth factor receptor glycoprotein. Amplification of c-erbB-2 is now generally considered to be a significant prognostic indicator in patients with breast cancer. A series of 74 consecutive breast carcinomas were analysed for c-erbB-2 amplification and p185 overexpression. The procedures of Southern blotting and slot blot were used for the analysis of oncogene amplification, while immunoperoxidase (IPOX) staining and enzyme-linked immunosorbent assay (ELISA) were used for the analysis of p185 overexpression. Detection of c-erbB-2 oncogene amplification by both the conventional Southern blotting technique and by the slot blot technique showed complete accord, with the amplified c-erbB-2 oncogene being detected in 14 of the 74 patients (18.9%). The c-erbB-2 oncoprotein, as measured by IPOX and ELISA, was found to be overexpressed in 21% and 19% of patients, respectively. Comparison was made between the results attained by all four methods, and further comparison of the techniques was made from the point of view of ease of use, expense and ease of introduction into routine diagnostic laboratories. Immunocytochemistry in combination with slot blotting procedures were considered to be the most cost effective methods for evaluation of overexpression and amplification in routine pathology laboratories.

Evaluation of the expression levels of nm23-H1 mRNA in primary breast cancer, benign breast disease, axillary lymph nodes and normal breast tissue.

Expression levels of nm23-H1 were evaluated in a variety of normal benign and malignant breast tissues by Northern and slot blot. Tissues from 153 patients presenting with palpable breast lesions were studied: 132 primary infiltrating breast cancers, 9 pure duct carcinoma in situ lesions, a phyllodes tumor, 9 benign lesions and 2 local recurrences of carcinoma. In addition to lesional tissue, 49 samples of macroscopically normal breast tissue, 37 axillary lymph nodes and 9 samples from patients undergoing cosmetic reduction mammoplasty were studied. Sets of normal breast tissue, primary tumor and lymph node tissue from individual patients were available for comparison in 37 cases. A wide range of gene expression was detected in the various tissue types. The highest levels of expression were detected in malignant samples with in situ carcinomas being associated with the highest levels of gene expression. The expression levels of nm23-H1 in normal breast tissue were lower than the corresponding tumors from the same patients (p < 0.0005). Benign breast lesions (including 6 fibroadenomas) had levels of gene expression approximating those of the normal tissue samples. Normal axillary lymph nodes had significantly lower levels of nm23-H1 expression than nodes with metastatic deposits (p < 0.03). No significant association was observed between nm23-H1 expression levels and axillary node status in patients with infiltrating carcinoma, although there was a slight trend toward lower nm23-H1 mRNA levels in the node negative group.(ABSTRACT TRUNCATED AT 250 WORDS)

What's new in breast cancer? Molecular perspectives of cancer development and the role of the oncogene c-erbB-2 in prognosis and disease.

The oncogene c-erbB-2 is frequently amplified in human breast carcinoma. The c-erbB-2 gene is present as a single copy in normal cells, and has been mapped to chromosome 17 in the region 17q 12-21.32. c-erbB-2 encodes a transmembrane glycoprotein known as p185. The intracellular component of p185 has tyrosine kinase activity; the extracellular domain has a structure resembling a growth factor receptor. c-erbB-2 amplification, p185 overexpression and levels of transcribed c-erbB-2 specific messenger RNA have been studied in a large number of breast carcinomas using a variety of techniques. In general, overexpression of p185 oncoprotein reflects various levels of DNA amplification, though in some cases amplification can be detected in the absence of overexpression of p185 and similarly overexpression of p185 can be present without detectable levels of c-erbB-2 amplification. This findings suggests that multiple mechanisms may be responsible for overexpression. c-erbB-2 amplification and/or overexpression occurs in almost all cases of high grade duct carcinoma in-situ, but has been reported in only 10%-40% of infiltrating duct carcinoma. c-erbB-2 amplification or overexpression occurs rarely in invasive lobular carcinoma, and has not been detected in ductal or lobular epithelial hyperplasia, or in atypical ductal or atypical lobular hyperplasia. It is generally believed that c-erbB-2 amplification/overexpression is an important independent prognostic indicator in breast carcinoma, identifying a subset of patients with poor prognosis tumours, particularly if axillary node metasases are present. However, many unanswered questions remain regarding c-erbB-2 and its role in breast cancer development and progression. The causes of c-erbB-2 amplification are unknown. There is no evidence of mutations in the human gene which might cause amplification or overexpression. The significance of the differences in levels of c-erbB-2 amplification/overexpression in in-situ duct carcinoma and associated invasive duct carcinoma has not been established. Amplification or overexpression have not been reported in atypical duct hyperplasia, a proposed precursor of duct carcinoma in-situ, yet overexpression occurs almost always in high grade duct carcinoma in-situ. c-erbB-2 may play a critical role in the development of a clonal in-situ, proliferation of high histological grade, yet does not obviously influence the acquisition of an invasive phenotype. We would postulated that this instability in amplification/overexpression is of biological significance, and if better understood may aid in the study of progression of human breast carcinoma.

The influence exerted by Nembutal on reactivity of the superior colliculus neurons.

Effects of a Nembutal upon responses of the superior colliculus neurons were analyzed in pretrigeminal cats. Most cells were studied during the spindly barbiturate pattern in the EEG. In this condition collicular neurons lose their spontaneous activity, become sluggish in their reactivity to stimuli moving at high velocity, and less sensitive to direction of movement. After a further increase in the anesthesia down to the isoelectric EEG pattern the responses of neurons were gradually depressed and finally neurons became non-driveable by visual stimulation. A possible mechanism responsible for the reduction of the cells excitability is discussed.

The velocity-response curves of the cat's superior colliculus neurons.

The velocity-response curves of the cat's superior colliculus neurons responding to moving stimuli mere studied quantitatively. They were fitted by logarithmic Gaussian curves described by three parameters: optimal stimulus velocity, amplitude and dispersion of the curve. Since reversal of the stimulus movement direction changed neither optimal stimulus velocity nor dispersion of the velocity tuning curve, then the fourth parameter, directional asymmetry, is postulated to describe fully, in conjunction with three parameters mentioned above, the dependence of the neuron response to velocity and direction on the stimulus motion. All parameters were roughly normally distributed and uncorrelated with each other in the sample of cells investigated. Some implications of our results for the classification of cells, and some arguments for population coding” against single cell trigger feature coding are discussed.

Effects of binocular deprivation of pattern vision on single unit responses in the cat superior colliculus.

Single unit responses in the superior colliculus of cats deprived of pattern vision from birth and of normally reared cats were studied in unanesthetized pretrigeminal preparations. Collicular units of deprived cats showed a diminished direction-selectivity but a somewhat better speed-selectivity compared to normals; they also preferred lowspeed stimuli, and reacted less frequently to diffuse flash. The impairment of direction-selectivity of collicular neurons may be partly responsible for the impairment of the pursuit eye movements in visually deprived cats.

Amplitude discriminator for biological impulses.

A simple amplitude discriminator with two ways of triggering DC-level monitoring is described. This system is based on easily available inexpensive integrated circuits.

Barbiturate influence upon organization of lateral geniculate receptive fields in cats.

Under different levels of Nembutal anesthesia the spatiotemporal characteristics of receptive fields of cells in the lateral geniculate nucleus were investigated. All units decreased their maintained activity and bursts of spikes occurred spontaneously after administration of the anesthetic. The excitatory domains of the receptive fields were also changed by shortening of the cell's sustained response and enhancement of the postinhibitory transient responses; the spatial extent of these domains being less affected. A qualitatively new excitatory tertiary” domain appeared in the receptive field surround with a latency of 170-300 ms. These effects together with enhancement of the spatiotemporal extent of inhibitory domains suggest that the suppressive action of barbiturate takes place beyond the retina.

Single-unit activity in cat's isolated midbrain.

The midbrain was isolated by two brainstem transections, pretrigeminal and premesencephalic. In the isolated midbrain, particularly within the reticular formation, EEG activity was greatly depressed. On the other hand, single-unit spike activity remained at a high level. The spatial density of active reticular units and the rate of their spontaneous activity were at least not smaller than those in the midbrain of the cat with only a pretrigeminal transection. Thus the flat EEG record is not necessarily a sign of the absence of neural activity.

Lipid abnormalities in coronary heart disease: a population-based case-control study.

BACKGROUND: We performed a case-control study to estimate lipid-cholesterol fractions in patients with coronary heart disease and compared them with population-based controls. METHODS AND RESULTS: A total of 635 newly diagnosed patients with coronary heart disease (518 males and 117 females) and 632 subjects (346 males and 286 females) obtained from an ongoing urban coronary heart disease risk factor epidemiological study were evaluated. Age-specific lipid values (total cholesterol, low-density lipoprotein, high-density lipoprotein, triglycerides, and total:high-density lipoprotein cholesterol ratio) were compared using the t-test. Age-adjusted prevalence of dyslipidemia as defined by the US National Cholesterol Education Program was compared using the Chi-square test. In all the age groups, and in both males and females, levels of total and low-density lipoprotein cholesterol were not significantly different. In males, the high-density lipoprotein cholesterol (mg/dl) was significantly lower in patients with coronary heart disease as compared to controls in the age groups 30-39 years (35.1+/-11 v. 43.7+/-9), 40-49 years (39.0+/-10 v. 47.1+/-8), 50-59 years (38.9+/-11 v. 43.8+/-9) and 60-69 years (38.6+/-11, v. 42.8+/-7) (p<0.05). In females, high-density lipoprotein cholesterol was less in the age groups 30-39 years (30.2+/-9 v. 40.7+/-9), 50-59 years (39.7+/-12 v. 44.7+/-8) and 60-69 years (35.6+/-11 v. 42.2+/-9). The level of triglycerides was significantly higher in male patients in the age groups 40-49 years (195.3+/-96 v. 152.8+/-78), 50-59 years (176.7+/-76 v. 162.9+/-97), 60-69 years (175.5+/-93 v. 148.1+/-65) and >70 years (159.8+/-62 v. 100.0+/-22); and in female patients in the age group 30-39 years (170.8+/-20 v. 149.9+/-9) (p<0.05). The total:high-density lipoprotein cholesterol ratio was significantly higher in all age groups in male as well as female patients with coronary heart disease (p<0.05). CONCLUSIONS: An age-adjusted case-control comparison showed that the prevalence of hypertension, diabetes, high total cholesterol (> or =200 mg/dl) (males 48.8% v. 20.2%; females 59.8% v. 33.4%) and high low-density lipoprotein cholesterol (> or =130 mg/dl) (males 42.1% v. 15.0%; females 52.1% v. 31.0%) was significantly more in cases than in controls. The prevalence of low high-density lipoprotein cholesterol (<35 mg/dl) (males 39.6% v. 6.2%; females 39.3% iv 9.5%), high total:high-density lipoprotein ratio (> or = 5.0) and high triglycerides (> or =200 mg/ dl: males 39.6%, v. 10.2%; females 17.1% v. 11.9%) was also significantly higher in cases (p<0.05).

Serial epidemiological surveys in an urban Indian population demonstrate increasing coronary risk factors among the lower socioeconomic strata.

OBJECTIVE: To determine trends of coronary risk factors in an Indian urban population and their association with educational level as marker of socioeconomic status. METHODS: Two successive coronary risk factor surveys were performed in randomly selected individuals. In the first study (in 1995) 2212 subjects (1415 men, 797 women) and in the second (in 2002) 1123 subjects (550 men, 573 women) were studied. Details of smoking, physical activity, hypertension, diabetes, coronary heart disease, body-mass index, waist-hip ratio, blood pressure and electrocardiography were evaluated. Fasting blood was examined for lipid levels in 297 (199 men, 98 women) in the first and in 1082 (532 men, 550 women) in the second study. Educational status was classified into Group 0: no formal education, Group I: 1-10 years, Group II: 11-15 years, and Group III: > 16 years. Current definitions were used for risk factors in both the studies. RESULTS: Prevalence of coronary risk factors, adjusted for age and educational status, in the first and second study in men was smoking/tobacco in 38.7 vs. 40.5%, leisure time physical inactivity in 70.8 vs. 66.1%, hypertension (> or = 140 and/or 90 mm Hg) in 29.5 vs. 33.7%, diabetes history in 1.1 vs. 7.8%, obesity (body-mass index > or = 25 Kg/m2) in 20.7 vs. 33.0%, and truncal obesity (waist:hip > 0.9) in 54.7 vs. 54.4%. In women, tobacco use was in 18.7 vs. 20.5%, leisure time physical inactivity in 72.4 vs. 75.3%, hypertension in 36.9 vs. 33.7%, diabetes history in 1.0 vs. 7.3%, obesity in 19.9 vs. 39.4%, and truncal obesity (waist:hip > 0.8) in 70.1 vs. 69.2%. In men, high total cholesterol > or = 200 mg/dl was in 24.6 vs. 37.4%, high LDL cholesterol > or = 130 mg/dl in 22.1 vs. 37.0%, high triglycerides > or = 150 mg/dl in 26.6 vs. 30.6% and low HDL cholesterol < 40 mg/dl in 43.2 vs. 54.9%; while in women these were in 22.5 vs. 43.1%, 28.6 vs. 45.1%, 28.6 vs. 28.7% and 45.9 vs. 54.2% respectively. In the second study there was a significant increase in diabetes, obesity, hypertension (men), total- and LDL cholesterol and triglycerides and decrease in HDL cholesterol (p < 0.05). In the first study with increasing educational status a significant increase of obesity, total cholesterol, LDL cholesterol and triglycerides and decrease in smoking was observed. In the second study increasing education was associated with decrease in smoking, leisure-time physical inactivity, total and LDL cholesterol, and triglycerides and increase in obesity, truncal obesity and hypertension (Least-squares regression p < 0.05). Increase in smoking, diabetes and dyslipidaemias was greater in the less educated groups. CONCLUSIONS: Significant increase in coronary risk factors--obesity, diabetes, total-, LDL-, and low HDL cholesterol, and triglycerides is seen in this urban Indian population over a seven year period. Smoking, diabetes and dyslipidaemias increased more in low educational status groups.