Ectopic cardiovascular fat in middle-aged men: effects of race/ethnicity, overall and central adiposity. The ERA JUMP study.

BACKGROUND/OBJECTIVES: Higher volumes of ectopic cardiovascular fat (ECF) are associated with greater risk of coronary heart disease (CHD). Identifying factors that are associated with ECF volumes may lead to new preventive efforts to reduce risk of CHD. Significant racial/ethnic differences exist for overall and central adiposity measures, which are known to be associated with ECF volumes. Whether racial/ethnic differences also exist for ECF volumes and their associations with these adiposity measures remain unclear. SUBJECTS/METHODS: Body mass index (BMI), computerized tomography-measured ECF volumes (epicardial, pericardial and their summation) and visceral adipose tissue (VAT) were examined in a community-based sample of 1199 middle-aged men (24.2% Caucasians, 7.0% African-Americans, 23.6% Japanese-Americans, 22.0% Japanese, 23.2% Koreans). RESULTS: Significant racial/ethnic differences existed in ECF volumes and their relationships with BMI and VAT. ECF volumes were the highest among Japanese-Americans and the lowest among African-Americans. The associations of BMI and VAT with ECF differed by racial/ethnic groups. Compared with Caucasians, for each 1-unit increase in BMI, African-Americans had lower, whereas Koreans had higher increases in ECF volumes (P-values<0.05 for both). Meanwhile, compared with Caucasians, for each 1-unit increase in log-transformed VAT, African-Americans, Japanese-Americans and Japanese had similar increases, whereas Koreans had a lower increase in ECF volumes (P-value<0.05). CONCLUSIONS: Racial/ethnic groups differed in their propensity to accumulate ECF at increasing level of overall and central adiposity. Future studies should evaluate whether reducing central adiposity or overall weight will decrease ECF volumes more in certain racial/ethnic groups. Evaluating these questions might help in designing race-specific prevention strategy of CHD risk associated with higher ECF.

REG Iα is a biomarker for predicting response to chemotherapy with S-1 plus cisplatin in patients with unresectable stage IV gastric cancer.

BACKGROUND: The regenerating gene Iα (REG Iα) is involved in gastric carcinogenesis as an antiapoptotic factor. Therefore, we investigated whether REG Iα confers resistance to chemotherapeutic drugs in gastric cancer (GC) cells and whether REG Iα expression is useful for predicting the response to chemotherapy and outcome in patients with GC. METHODS: A total of 70 patients with unresectable stage IV GC received first-line chemotherapy with S-1 and cisplatin (S-1/CDDP). The expression of REG Iα was evaluated immunohistochemically using biopsy samples obtained before chemotherapy, and its relationship to clinicopathological parameters was analysed statistically. The effects of REG Iα gene induction on resistance to 5-FU or CDDP treatment were examined by cell survival assay and flow cytometry. RESULTS: Of the 70 patients with unresectable stage IV GC, 19 (27%) were positive for REG Iα expression. The expression of REG Iα was independently predictive of poorer progression-free and overall survival in such patients (hazard ratio (HR) 2.46; P=0.002 and HR 1.89; P=0.037, respectively). The gene induction of REG Iα conferred resistance to cell death induced by 5-FU or CDDP in GC cells. CONCLUSION: In patients with stage IV GC, REG Iα, which confers resistance to chemotherapeutic drugs in GC cells, is a potential biomarker for predicting resistance to S-1/CDDP treatment.

Role of Necl-5 in the pathophysiology of colorectal lesions induced by dimethylhydrazine and/or dextran sodium sulphate.

Necl-5 is an immunoglobulin-like molecule that was originally identified as a poliovirus receptor. Although Necl-5 expression is often up-regulated in cancer cells, its pathophysiological significance in the development of cancer remains unclear. We investigated the roles of Necl-5 in the development of colitis-associated neoplasia. Necl-5-deficient mice were generated and treated with dimethylhydrazine (DMH) and/or dextran sodium sulphate (DSS) to induce colitis and its associated neoplasias. Colon tissues were examined for histology, Ki-67 expression by immunohistochemistry and K-ras gene mutation. Colon tumours occurred significantly less frequently in heterozygous (Necl-5(+/-)) or homozygous Necl-5-deficient (Necl-5(-/-)) mice than in wild-type (WT) mice with DMH/DSS treatment. Total ulcer index and inflammatory cell infiltration were significantly lower in Necl-5(-/-) mice than in WT mice with DSS alone or DMH/DSS treatment. Colon tumours in both WT and Necl-5(-/-) mice showed high cell proliferation ability but lacked K-ras mutation. The total Ki-67 labelling index in non-neoplastic colon epithelium was significantly higher in WT (45.9 +/- 0.94) than in Necl-5(+/-) (34.3 +/- 1.40) or Necl-5(-/-) (27.7 +/- 1.15) mice with DMH/DSS treatment (p < 0.001). Necl-5 plays a role in the development of colitis-associated cancer by up-regulating colonic mucosal cell proliferation.

Involvement of REG Ialpha protein in the regeneration of ductal epithelial cells in the minor salivary glands of patients with Sjögren's syndrome.

The regenerating gene (Reg) was originally isolated from regenerating rat pancreatic islets and revealed recently to constitute a multi-gene family in humans. REG Ialpha protein is known to be overexpressed not only in various human inflammatory diseases but also in various experimental models of inflammation in animal tissues. However, its involvement in pathophysiology of the minor salivary gland (MSG) is not clear. We investigated REG Ialpha expression in the MSG of patients with primary Sjögren's syndrome (SS) and assessed its role in ductal epithelial cell proliferation in such tissues. Lip biopsy specimens were obtained from 40 patients with primary SS and examined using immunohistochemistry for REG Ialpha protein, Ki67 and single-strand DNA (ssDNA). The relationships among clinicopathological factors and expression of REG Ialpha protein, Ki67 and ssDNA in the MSG were then analysed. REG Ialpha protein was expressed rarely in ductal epithelial cells of the normal MSG but was apparently overexpressed in those of patients with SS. The labelling indices for both Ki67 and ssDNA in the ductal cells of the MSGs were significantly higher in SS patients than in controls. Moreover, these labelling indices were significantly higher in REG Ialpha-positive than in negative SS patients. REG Ialpha protein may play a role in the regeneration of ductal epithelial cells in the MSGs of patients with SS.

Expression of SDF-1 alpha and nuclear CXCR4 predicts lymph node metastasis in colorectal cancer.

Although stromal cell-derived factor (SDF)-1 alpha and its receptor CXCR4 are experimentally suggested to be involved in tumorigenicity, the clinicopathological significance of their expression in human disease is not fully understood. We examined SDF-1 alpha and CXCR4 expression in colorectal cancers (CRCs) and their related lymph nodes (LNs), and investigated its relationship to clinicopathological features. Specimens of 60 primary CRCs and 27 related LNs were examined immunohistochemically for not only positivity but also immunostaining patterns for SDF-1 alpha and CXCR4. The relationships between clinicopathological features and SDF-1 alpha or CXCR4 expression were then analysed. Stromal cell-derived factor-1 alpha and CXCR4 expression were significantly associated with LN metastasis, tumour stage, and survival of CRC patients. Twenty-nine of 47 CXCR4-positive CRCs (61.7%) showed clear CXCR4 immunoreactivity in the nucleus and a weak signal in the cytoplasm (nuclear type), whereas others showed no nuclear immunoreactivity but a diffuse signal in the cytoplasm and at the plasma membrane (cytomembrane type). Colorectal cancer patients with nuclear CXCR4 expression showed significantly more frequent LN metastasis than did those with cytomembrane expression. Colorectal cancer patients with nuclear CXCR4 expression in the primary lesion frequently had cytomembrane CXCR4-positive tumours in their LNs. In conclusion, expression of SDF-1 alpha and nuclear CXCR4 predicts LN metastasis in CRCs.

Hypoxia induced by benign intestinal epithelial cells is associated with cyclooxygenase-2 expression in stromal cells through AP-1-dependent pathway.

Cyclooxygenase-2 (COX-2) plays important roles in tumor development. Especially in the early-stage colorectal tumors, COX-2 expression is often observed in the tumor stroma. However, the mechanism regulating such stromal expression of COX-2 remains unknown. In the present study, we simulated the indirect interaction between epithelial cells and stromal cells in the process of colorectal tumor development using an in vitro co-culture model in which NIH3T3 fibroblasts were co-cultured with 'sparsely' or 'densely' populated intestinal epithelial cells, Intestine-407 as a model of premalignant or benign intestinal epithelial cells, and DLD-1 and Caco-2 as models of malignant epithelial cells. COX-2 expression in NIH3T3 fibroblasts was upregulated when co-cultured with the 'dense' epithelial cells regardless of their character. Interestingly, there was pericellular hypoxia in the vicinity of NIH3T3 fibroblasts when co-cultured with 'dense' epithelial cells, and the recovery of the partial pressure of oxygen level resulted in the reduction of enhanced COX-2 expression only in NIH3T3 fibroblasts co-cultured with 'dense' Intestine-407 cells. Furthermore, COX-2 expression was also reduced by the inhibition of transcription factor AP-1. Thus, pericellular hypoxia of the stromal cells caused by densely populated epithelial cells may be one of the potent COX-2 enhancers before completion of malignant transformation during intestinal tumor development.

The Associations of C-Reactive Protein with Serum Levels of Polyunsaturated Fatty Acids and Trans Fatty Acids Among Middle-Aged Men from Three Populations.

BACKGROUND: C-reactive protein (CRP) and many fatty acids (FAs) have been linked to cardiovascular disease. Associations of serum CRP with FAs in different populations have not been established. METHODS: Participants were 926 men aged 40-49 (2002-2006) from a population-based sample; 310 Whites from Pennsylvania, U.S., 313 Japanese from Shiga, Japan, and 303 Japanese Americans from Hawaii, U.S. Serum CRP (mg/L) was measured using immunosorbent assay while serum FAs (%) were measured using capillary-gas-liquid chromatography. RESULTS: Whites had CRP (mg/L) levels higher than Japanese with Japanese Americans in-between (age-adjusted geometric mean "GM" 0.96, 0.38, 0.66, respectively). Whites had also higher levels of total n-6 FAs (%) and trans fatty acids (TFAs) but lower levels of marine-derived n-3 FAs compared to Japanese (41.78 vs. 35.05, 1.04 vs. 0.58, and 3.85 vs. 9.29, respectively). Japanese Americans had FAs levels in-between the other two populations. Whites had significant inverse trends between CRP and tertiles of total n-6 FAs (GM 1.20, 0.91 and 0.80; p=0.002) and marine-derived n-3 FAs (GM 1.22, 1.00 and 0.72; p<0.001) but a significant positive trend with TFAs (GM 0.80, 0.95 and 1.15; p=0.007). Japanese had a significant inverse trend between CRP and only total n-6 FAs (GM 0.50, 0.35 and 0.31; p<0.001). Japanese Americans had CRP associations with n-3 FAs, n-6 FAs, and TFAs similar to but weaker than Whites. CONCLUSIONS: With the exception of consistent inverse association of CRP with total n-6 FAs, there are considerable variations across the three populations in the associations of CRP with different FAs.

Human arterial smooth muscle cell proliferation in diabetes.

In the present study, we focus on the proliferation of human arterial smooth muscle cells (SMCs) from NIDDM patients (DM-SMCs) to clarify the reactivity to the growth factor(s) in fetal calf serum (FCS) and the factor(s) secreted by T-cells. The proliferation of DM-SMCs was significantly greater than SMCs from nondiabetic patients (nonDM-SMC). DM-SMC conditioned medium (DM-condMed) increased the growth of nonDM-SMCs. These results suggest that the growth factor is secreted from DM-SMCs as an autocrine system, which increases the proliferation of nonDM-SMCs. T-cells increased DNA synthesis of SMCs, and DM-SMCs strikingly reacted to T-cells. The present results support a function of T-cells in stimulating SMC growth. In conclusion, human arterial SMC proliferation is increased in diabetes in the same fashion as in experimentally induced diabetes in animals through responses to growth factors and an increased autocrine system. These results provide a mechanism for the increase in atherosclerotic disease in diabetes.

Development of a nosocomial outbreak investigation database.

A pilot web-based database was created to facilitate epidemiological investigation of nosocomial outbreaks. The database provides highly structured abstracts in a case study format to serve as a guide for investigations. Problems encountered in abstracting over 330 published reports included missing information and classification of study methods. The database offers a new way to review outbreaks, for example, in terms of their impact measured by various combinations of database fields, such as the number of cases, attack rate, pathogens, service/ward and mode of transmission. Feedback from users of the database suggests its usefulness. Creation of a large web-based database seems to be both desirable and feasible.

Impaired glucose tolerance is a risk factor for cardiovascular disease, but not impaired fasting glucose. The Funagata Diabetes Study.

OBJECTIVE: To determine whether the new category of impaired fasting glucose (IFG) recently proposed by the Expert Committee of the American Diabetes Association is a risk factor for cardiovascular disease. RESEARCH DESIGN AND METHODS: Death certificates and residence transfer documents from the cohort population consisting of participants of the diabetes prevalence study in Funagata, Yamagata prefecture, Japan, 1990-1992, were analyzed up through the end of 1996. First, the cohort population was classified into three groups: normal glucose tolerance (NGT) (n = 2,016), impaired glucose tolerance (IGT) (n = 382), and diabetic (n = 253). Then the same population was reclassified into normal fasting glucose (NFG), IFG, and diabetic. The cumulative survival rates among the groups were compared using the classical life-table method, and age-adjusted analyses, the person-year method, and Cox's proportional hazard model were adopted. RESULTS: At the end of seven observed years, the cumulative survival rates from cardiovascular disease of IGT and diabetes were 0.962 and 0.954, respectively, both significantly lower than that of NGT (0.988). The Cox's proportional hazard model analysis showed that the hazard ratio of IGT to NGT on death from cardiovascular disease was 2.219 (95% CI 1.076-4.577). However, the cumulative survival rate of IFG from cardiovascular disease was 0.977, not significantly lower than that of NFG (0.985). The Cox's hazard ratio of IFG to NFG on death from cardiovascular disease was 1.136 (0.345-3.734), which was not significant either. CONCLUSIONS: IGT was a risk factor for cardiovascular disease, but IFG was not.

Prevalence of diabetes and impaired glucose tolerance in Funagata area, Japan.

OBJECTIVE: To determine the prevalence of diabetes mellitus and IGT in the Funagata area of Japan. RESEARCH DESIGN AND METHODS: The total eligible subjects was 1163, all were > or = 45 yr of age, and 52 were known diabetic patients. Data collected included body height, weight, and answers to medical questionnaires. A 75-g OGTT was done in the morning. WHO criteria were used to classify the current diabetes status of study participants. RESULTS: Of the 1111 scheduled for the OGTT, 868 took the test; the participation rate was 77.8%. The prevalence of diabetes was 10.5 and 12.9%, and the prevalence of IGT was 14.7 and 18.0% for men and women, respectively. The prevalence of undiagnosed diabetes (4.9%) was almost equal to that of previously diagnosed diabetes (4.5%). CONCLUSIONS: The prevalence of diabetes in the Funagata area was two to four times higher than that of previous reports in Japan, in which many investigators used a urinary glucose test as a preliminary test. This difference is attributed to the method of determining the prevalence of diabetes.

Towards an internet civil defence against bioterrorism.

Approaches towards the public-health prevention of bioterrorism are too little, and too late. New information-based approaches could yield better homeland protection. An internet civil defence is presented where millions of eyes could help to identify suspected cases of bioterrorism, with the internet used to report, confirm, and prevent outbreaks.

Evaluating the reported prevalence of type 2 diabetes mellitus by the Oguni diabetes registry using a two-sample method of capture-recapture.

BACKGROUND: Capture-recapture methods have been widely employed in the study of wildlife populations and have recently been applied to count various human diseases and conditions. We have estimated the prevalence of type 2 diabetes mellitus by adjusting for the degree of undercount using a two-sample model of capture-recapture among men and women aged 50-69 in Oguni town, Japan. METHODS: Oguni town diabetes registry data were utilized as the first source. In the registry, only those who had experienced fasting plasma glucose of > or = 7.8 mmol/l (140 mg/dl) or 2 h plasma glucose after a 75 g oral glucose tolerance test (OGTT) of > or = 11.1 mmol/l (200 mg/dl) were counted as having diabetes. A second source was a sample study selecting 200 men and 200 women aged 50-69 randomly, which was conducted in August 1991. A 75 g OGTT was done in the morning. The 1985 World Health Organization criteria were used to classify the diabetes status of the participants. A two-sample model of capture-recapture methods was employed to estimate the total number of cases of diabetes and determine the ascertainment rates of the registry. RESULTS: The prevalence estimated by the diabetes registry was 7.1%. The prevalence from the sample study was 8.8% with a participation rate of 74%. Estimated prevalence employing the capture-recapture method was 13.1%. The ascertainment rate of the registry was 53.8%. CONCLUSIONS: Little is known about the prevalence of type 2 diabetes in local areas in Japan, the US and the world. Capture-recapture methods are likely to provide a means to accurately assess the prevalence of diabetes.

Coronary heart disease mortality trends in men in the post World War II birth cohorts aged 35-44 in Japan, South Korea and Taiwan compared with the United States.

BACKGROUND: Since World War II, people in Japan, South Korea, and Taiwan have been exposed to a westernized lifestyle. It is most likely that the post World War II cohorts (1950+) have been more exposed. We hypothesize that there would be an increase in mortality from coronary heart disease (CHD) in men aged 35-44 in these countries. METHODS AND RESULTS: Mortality from CHD in men aged 35-44 in South Korea and Taiwan has recently increased, and in Japan it has decreased. Mortality from CHD in men aged 35-44 is lower in Japan than in either South Korea or Taiwan, and much lower than in the US. National sample data and several epidemiological studies have shown that risk factors for CHD including hypercholesterolaemia and hypertension in the past decade were not much different between young adult men in Japan and the US. Based upon these risk factors, CHD death rates among post World War II cohorts should be similar in Japan and the US. However, the rates are five times higher in the US for men aged 35-44. The majority of deaths in the category of diseases of the heart were from heart failure in men in this age group in Japan; the mortality from heart failure was about three times higher than the mortality from CHD. Heart failure was rarely used in men aged 35-44 in the US. CONCLUSIONS: The continued low mortality rates from CHD in young men in Japan may be an artifact. It is possible that CHD death rates in post World War II birth cohort in Japan are similar to US rates.

Relapse of duodenal ulcers after successful eradication of Helicobacter pylori in gastric ulcer patients.

Relapse of duodenal ulcers was observed endoscopically after Helicobacter pylori eradication therapy for gastric ulcer patients in 2 of 32 successful cases. One patient, a 40-year-old woman, received dual therapy with lansoprazole 60mg and amoxicillin 1000mg for 2 weeks because of an intractable, easily-relapsing gastric ulcer accompanied by duodenal ulcer scars that had not relapsed for 5 years. The H. pylori status was assessed by a rapid urease test, light microscopy, culture, and anti-H. pylori antibody. At 24 months after the cure of H. pylori she had upper abdominal pain and showed relapse not of the gastric ulcer but of the duodenal ulcer. The H. pylori status remained negative. The other patient, a 44-year-old man, showed an active gastric ulcer and duodenal ulcer scars at the first endoscopy. He received the same regimen as described above. Ten weeks after completion of the eradication therapy, endoscopy showed healing of the gastric ulcer and relapse of the duodenal ulcer despite successful eradication. These two cases suggest that H. pylori eradication modifies the pathophysiological condition of gastric acid secretion and facilitates relapse of duodenal ulcers.

Insulin antibody does not cause insulin resistance during glucose clamping in rats.

Although it has often been stated that insulin antibodies cause insulin resistance, this concept is still controversial. The effect of insulin antibody GP30, commonly used in insulin radioimmunoassay, on insulin action was investigated in Wistar rats in vivo by the euglycemic glucose clamp technique. As a preliminary experiment, the equilibrium time required for insulin antibody to bind with endogenous insulin was examined. One hundred microliters/kg insulin antibody took 60 min or more to attain equilibrium, but 10 microliters/kg insulin antibody almost immediately equilibrated with endogenous insulin. During a 60-min glucose clamp study, 2 mU/kg/min porcine insulin was infused with 100 microliters/kg insulin antibody. At steady state, during the last 20-min period, the mean glucose infusion rate was 2.10 +/- 0.85 mg/kg/min (n = 5, mean +/- SD), significantly lower than the 5.77 +/- 1.61 mg/kg/min of the control, indicating insulin resistance before equilibrium was reached. However, the glucose infusion rates during the clamp with 10 microliters/kg insulin antibody and 100 microliters/kg insulin antibody infused 75 min before the insulin were 6.10 +/- 1.44 and 7.12 +/- 1.19 mg/kg/min, respectively, no different from the control. In these instances, free insulin levels measured by radioimmunoassay using the polyethyleneglycol method were 43.8 +/- 20.4 and 15.4 +/- 6.1 microU/ml, respectively, lower than the control (77.0 +/- 16.1 microM/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Is examination of fructosamine levels valuable as a diagnostic test for diabetes mellitus?

In order to develop a simple, one-point diagnostic test for diabetes mellitus in a mass population surveys, we measured levels of fructosamine (FRA), one of the glycated proteins. Seven hundred and thirty-eight people had their levels of fasting plasma glucose (FPG), FRA and hemoglobin A1c (HbA1c) examined before taking 75 g oral glucose tolerance tests (OGTT). The results of OGTT distinguished a diabetic group (DM) of 143 from a non-diabetic group (non-DM) of 595 subjects. Since there was a significant correlation between FRA levels and plasma glucose levels 2 h after OGTT (PG-2h), as well as between FPG and PG-2h, a discriminant analysis using FPG and FRA was carried out in order to separate the DM group from the non-DM group. According to this analysis, a positive f, where f = FPG-(mg/dl) + 12.0 FRA(mmol/l) - 150, would determine a subject to be a diabetic. However, the sensitivity of this analysis was only 0.521. It can be concluded that the sensitivity of a simple, one-point determination for diabetes mellitus using measured levels of FRA was insufficient, even by application of discriminant analysis, and that the OGTT is still needed for a diagnostic test for diabetes mellitus in mass population surveys.

Effects of seishin-renshi-in and Gymnema sylvestre on insulin resistance in streptozotocin-induced diabetic rats.

Although there is no concept of insulin resistance in traditional Kampo (Chinese) medicine and Indian medicine, we had the hypothesis that some drug in a mixture of crude drugs which was believed to ameliorate diabetes mellitus may have had the effect of improving insulin resistance. To test this hypothesis, the effects of Seishin-renshi-in (Chinese medicine) and Gymnema sylvestre (Indian medicine) on the insulin resistance of streptozotocin-induced diabetic rats was studied by the glucose clamp technique. Oral administration of Seishin-renshi-in (800 mg/kg/day) with injections of a minimum dose of Ultralente insulin decreased urine volume and urinary glucose excretion during a 7-day treatment period and improved the insulin stimulated glucose uptake in peripheral tissues, as well as improving the insulin suppressed hepatic glucose output during glucose clamp. However, G. sylvestre (120 mg/kg/day) treatment did not improve insulin resistance. We conclude that Seishin-renshi-in, with a small dose of insulin, improved insulin resistance in streptozotocin-induced diabetic rats, but Gymnema sylvestre did not.

Insulin resistance in septic rats--a study by the euglycemic clamp technique.

Male Wistar rats weighing 250 +/- 30g were made septic by cecum ligation and perforation. Peripheral and hepatic sensitivity to insulin was assessed by the euglycemic glucose clamp technique with simultaneous [3H]glucose infusion. Hepatic glucose output was not suppressed by the insulin infusion in the septic rats in contrast with the controls. Glucose utilization by the peripheral tissues was not significantly different between the septic and control rats. Counterregulatory hormone levels were higher in the septic group. Our data suggest that the liver is the site of insulin resistance in the septic state.

Anti-angiogenic effect of TGFbeta in aqueous humor.

Neovascularization is mediated by various factors in ocular tissues. Recent studies have emphasized the role of vascular endothelial growth factor in the induction of angiogenesis. We have previously reported that aqueous humor (AH) suppressed vascular endothelial cell growth and angiogenesis. We speculated that the anti-angiogenic effect of AH is mediated by transforming growth factor beta (TGFbeta). In order to clarify the presence of TGFbeta in bovine AH, we applied it on the heparin-sepharose affinity column and prepared two fractions (bound and unbound fractions). We measured TGFbeta concentration in each fraction and examined how the anti-TGFbeta antibody decreased the inhibitory effect of AH on human umbilical vein endothelial cell growth and on in vitro angiogenesis. We found the presence of TGFbeta2, but not TGFbeta1, in the heparin bound fraction, and the inhibitory effect was detected in the heparin-bound fraction. Anti-TGFbeta antibody completely and dose-dependently extinguished the inhibitory effect of AH. We propose that the inhibitory effect of AH on endothelial cell growth and in vitro angiogenesis are both mediated by TGFbeta2. Our results indicate TGFbeta2 is normally present in AH and protects the eye tissue against abnormal neovascularization.