Human erythrocyte band 3 (EPB3) polymorphism: Analysis of blood and bloodstains by an immunodetection method and frequency of the EPB3* Memphis variant

Summary The erythrocyte band 3 (EPB3) variant, band 3 Memphis (EPB3*Memphis), was detected by immunoblotting with a monoclonal antibody to the 41 kDa cytoplasmic N-terminal domain of band 3 without protease treatment of erythrocytes. EPB3*Memphis was also detected by immunoblotting from 3-month-old bloodstains subjected to -chymotrypsin treatment. A population genetic study using this method indicated that the EPB3 variant would be useful for forensic work in Japan, since the frequency of this variant in Japanese (Wakayama prefecture) is relatively high (0.159).     

Prognostic impact of hypoxia-inducible factors 1alpha and 2alpha in colorectal cancer patients: correlation with tumor angiogenesis and cyclooxygenase-2 expression.

PURPOSE: Angiogenesis plays an important role in a multitude of biological processes including those of tumorigenesis and cancer progression. Hypoxia is the prime driving factor for tumor angiogenesis and the family of hypoxia-inducible factors (HIFs) plays a pivotal role in this process. The role of HIF in tumor angiogenesis has been underscored in different carcinomas but yet to be reported for colorectal carcinomas. EXPERIMENTAL DESIGN: In this study, we examined HIF [HIF-1alpha (HIF1) and HIF-2alpha (HIF2)] expression in 87 curatively resected colorectal carcinoma samples, and the results were correlated with clinicopathological factors, microvessel density, cyclooxygenase 2 expression, and patient prognosis. RESULTS: HIF1 (44.8%) was more frequently expressed than HIF2 (29.9%). Most of the clinicopathological factors representing the tumor aggressiveness were significantly correlated with overexpression of HIF2 but not with HIF1 expression. HIF2 expression had direct correlation with microvessel density and cyclooxygenase 2 expression. and, in contrast, HIF1 expression had a weak but significant inverse correlation in T1 and T2 tumors only. HIF2 expression alone and the combined expression of HIF1 and HIF2 had significant impact on patient survival. In the multivariate analysis, however, only the combined expression of HIF1 and HIF2 remained independently significant. CONCLUSIONS: Taken together, our results suggest that HIF2 expression may play an important role in angiogenesis and that the combined expression of HIF1 and HIF2 may play an important role in tumor progression and prognosis of colorectal carcinomas. Therefore, HIF expression could be a useful target for therapeutic intervention.     

Prolonged suppressed thyroid-stimulating hormone levels in hyperthyroidism in a neonate born to a mother with Graves' disease

Abstract We report here a case of neonatal hyperthyroidism born to a mother, whose pregnancy was complicated by poorly controlled Graves' disease. The patient demonstrated exophthalmos and marked goiter at birth, indicating the existence of thyrotoxicosis in utero. The mother's Graves' disease was well controlled in the third trimester, resulting in a slightly lower level of free thyroxine (FT₄) in the umbilical cord blood serum; however, thyroid-stimulating hormone (TSH) was undetectable. Thyroid-stimulating hormone remained undetectable for 2 months, while FT₄ levels varied in the course. This case suggests that severe and prolonged thyrotoxicosis in utero, due to poor control of pregnancy with Graves' disease, might induce unresponsiveness of the hypothalamo-pituitary system in the newborn.     

Lower rate of preeclampsia after antioxidant supplementation in pregnant women with low antioxidant status.

OBJECTIVE: To investigate maternal and neonatal outcomes after antioxidant supplementation relatively early in pregnancy (8 to 12 weeks) for pregnant women with low antioxidant status. METHODS: A randomized, double-blind, placebo-controlled trial of daily antioxidant supplementation was performed on pregnant women screening positive for low antioxidant status at 8 to 12 weeks of gestation. Low antioxidant status was defined as a superoxidedismutase (SOD) level below 1102 U/g Hb or 164 U/mL. The supplementation group received the following antioxidants daily: vitamins A (1000 IU), B6 (2.2 mg), B12 (2.2 microg), C (200 mg), and E (400 IU), folic acid (400 microg), N-acetylcysteine (200 mg), Cu (2 mg), Zn (15 mg), Mn (0.5 mg), Fe (30 mg), calcium (800 mg), and selenium (100 microg). The control group received Fe (30 mg) and folic acid (400 microg). Maternal (preeclampsia, abortion, and hypertension) and perinatal outcomes were assessed. RESULTS: In the supplementation group (29 subjects), we observed 2 cases of preeclampsia (6.8%, 1 mild and 1 severe), 1 of IUGR (birth weight 2300 g at 38 weeks), and 1 preterm delivery. In the control group (31 subjects), there were 8 abortions, 9 cases of preeclampsia (29%, 6 mild and 3 severe) with perinatal outcome: 3 preterm delivery cases and 1 IUGR (birth weight 2030 g at 39 weeks). Preeclampsia was significantly less frequent in the supplementation group when compared to the control group (2 vs. 9 cases, p = 0.043, OR = 0.18 [95% CI: 0.03, 0.92]). Finally we focused on the prediction of preeclampsia at 8 to 12 weeks. Combined sensitivity of markers of antioxidant status (SOD slutathione peroxidase, [GPx], and total anti-oxidant status [TAS]) was 33% (false-positive rate of 4.5%). CONCLUSION: Antioxidant supplementation was associated with better maternal and perinatal outcome in pregnant women with low antioxidant status than control supplementation with iron and folate alone. In a selected population already screened positive for low SOD, preeclampsia can be detected in 33% of asymptomatic cases in the first trimester using SOD, GPx, and TAS. It seems feasible that panels of both biochemical and molecular markers may be clinically useful in the prediction of this disease.     

Lack of toxicity or carcinogenicity of S-170, a sucrose fatty acid ester, in F344 rats.

A chronic combined toxicity and carcinogenicity study of S-170, a sucrose fatty acid ester, was performed in male and female F344 rats. S-170 was given ad libitum in the diet at levels of 0, 1.25, 2.5 or 5% to 10 rats/sex/group for 12 months to determine chronic toxicity and 0, 2.5 or 5% to 50 rats/sex/group for two years in the carcinogenicity study. Treatment with S-170 exerted no effect on survival in either sex. In the 12-month chronic toxicity study, no treatment-related effects on body weights, or hematological, blood biochemical, urinary and pathological parameters were demonstrated in any of the treated groups. In the carcinogenicity study, S-170 did not cause any dose-related significant increase in the incidences of tumors in any organs or tissues. Taken together, the results clearly demonstrate that S-170 has neither toxic nor carcinogenic activity in F344 rats under the conditions of the study. No observed adverse effect levels (NOAELs) calculated from the 12-month chronic toxicity and carcinogenicity study were 2.37 g/kg/day in males and 2.80 g/kg/day in females, and 2.12 g/kg/day in males and 2.42 g/kg/day in females, respectively.     

Mother-to-Child Transmission of Congenital Chagas Disease,Japan

We report a patient with congenital Chagas disease in Japan. This report reemphasizes the role of neglected and emerging tropical diseases in the era of globalization. It also indicates the need for increased vigilance for detecting Chagas disease in non–disease-endemic countries.     

First Japanese case of atypical progeroid syndrome/atypical Werner syndrome with heterozygous LMNA mutation

Atypical progeroid syndrome (APS), including atypical Werner syndrome (AWS), is a progeroid syndrome involving heterozygous mutations in the LMNA gene encoding the nuclear protein lamin A/C. We report the first Japanese case of APS/AWS with a LMNA mutation (p.D300N). A 53‐year‐old Japanese man had a history of recurrent severe cardiovascular diseases as well as brain infarction and hemorrhages. Although our APS/AWS patient had overlapping features with Werner syndrome (WS), such as high‐pitched voice, scleroderma, lipoatrophy and atherosclerosis, several cardinal features of WS, including short stature, premature graying/alopecia, cataract, bird‐like face, flat feet, hyperkeratosis on the soles and diabetes mellitus, were absent. In immunofluorescence staining and electron microscopic analyses of the patient's cultured fibroblasts, abnormal nuclear morphology, an increase in small aggregation of heterochromatin and a decrease in interchromatin granules in nuclei of fibroblasts were observed, suggesting that abnormal nuclear morphology and chromatin disorganization may be associated with the pathogenesis of APS/AWS.