Decreased level of interleukin-10-producing B cells in patients with pemphigus but not in patients with pemphigoid.

BACKGROUND: While the frequency of interleukin (IL)-10-producing B (B10) cells is reported to have an inverse correlation with disease activity in some human autoimmune diseases, the association between B10 cells and autoimmune blistering diseases (AIBD) has not been well evaluated. Although several phenotypes of human regulatory B cells have been proposed, the most appropriate one in AIBD has not been established. OBJECTIVE: To evaluate B10 cells in AIBD including their phenotypes. METHODS: Peripheral blood mononuclear cells were isolated from 39 patients with AIBD, including 14 with pemphigus and 25 with pemphigoid, and 10 healthy controls. We investigated the frequencies of B10 cells and CD19+ CD24hi CD38hi B cells using flow cytometry. RESULTS: The frequencies of B10 cells and CD19+ CD24hi CD38hi B cells were significantly lower and higher, respectively, in patients with pemphigus compared with healthy controls. Comparing patients with pemphigoid and healthy controls, no significant difference in the frequencies of B10 cells and CD19+ CD24hi CD38hi B cells was observed. B10-cell level in pemphigus was not associated with disease severity but inversely correlated with the required dose of steroid for treatment. While no significant difference in the frequency of IL-10-producing cells among CD19+ CD24hi CD38hi B cells was observed, in CD9+ and CD27- B-cell subsets it was significantly decreased in patients with pemphigus compared with healthy controls. CONCLUSIONS: Our results suggest the association of B10 cells with pemphigus but not with pemphigoid. The decrease in B10-cell level in pemphigus is partly caused by the lower production of IL-10 in CD9+ and CD27- B-cell subsets.

Circulating sex hormones and breast cancer risk factors in postmenopausal women: reanalysis of 13 studies.

BACKGROUND: Breast cancer risk for postmenopausal women is positively associated with circulating concentrations of oestrogens and androgens, but the determinants of these hormones are not well understood. METHODS: Cross-sectional analyses of breast cancer risk factors and circulating hormone concentrations in more than 6000 postmenopausal women controls in 13 prospective studies. RESULTS: Concentrations of all hormones were lower in older than younger women, with the largest difference for dehydroepiandrosterone sulphate (DHEAS), whereas sex hormone-binding globulin (SHBG) was higher in the older women. Androgens were lower in women with bilateral ovariectomy than in naturally postmenopausal women, with the largest difference for free testosterone. All hormones were higher in obese than lean women, with the largest difference for free oestradiol, whereas SHBG was lower in obese women. Smokers of 15+ cigarettes per day had higher levels of all hormones than non-smokers, with the largest difference for testosterone. Drinkers of 20+ g alcohol per day had higher levels of all hormones, but lower SHBG, than non-drinkers, with the largest difference for DHEAS. Hormone concentrations were not strongly related to age at menarche, parity, age at first full-term pregnancy or family history of breast cancer. CONCLUSION: Sex hormone concentrations were strongly associated with several established or suspected risk factors for breast cancer, and may mediate the effects of these factors on breast cancer risk.

Fish intake and serum levels of organochlorines among Japanese women.

This study evaluates background serum levels of selected organochlorine compounds among Japanese women of reproductive age and investigates whether lifestyle factors, especially dietary factors, may be associated with these levels. A cross-sectional study was performed on 80 Japanese women, aged 26-43 years, who complained of infertility and were confirmed not to have endometriosis. The serum levels of total toxic equivalency (TEQ), 18 polychlorinated dibenzo-p-dioxins (PCDDs)/polychlorinated dibenzofurans (PCDFs), 4 coplanar polychlorinated biphenyls (cPCBs), 36 ortho-substituted polychlorinated biphenyls (PCBs), and 13 chlorinated pesticides or their metabolites were measured and data were collected on the women's age, residence, occupation, body mass index (BMI), smoking and alcohol habit and 6 dietary intakes (fish, meats, rice, vegetables, fruits and dairy products). The serum median level of total TEQ was 25.1 pg TEQ/g lipid, that of PCDDs/PCDFs/cPCBs was 11.5 pmol/g lipid, that of PCBs was 0.46 nmol/g lipid, and that of total pesticides was 1.32 nmol/g lipid. The serum levels of total TEQ, PCDDs/PCDFs/cPCBs, PCBs and pesticides were positively associated with age (P for trend=0.003, 0.01, 0.005 and 0.01, respectively) and frequent fish consumption (P for trend=0.002, 0.003, 0.0003 and 0.006, respectively). Other lifestyle factors were not associated with serum organochlorine levels. The present study suggests that Japanese women who consume fish frequently in their reproductive period tend to accumulate organochlorines in their bodies.

Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women.

BACKGROUND: Obesity is associated with increased breast cancer risk among postmenopausal women. We examined whether this association could be explained by the relationship of body mass index (BMI) with serum sex hormone concentrations. METHODS: We analyzed individual data from eight prospective studies of postmenopausal women. Data on BMI and prediagnostic estradiol levels were available for 624 case subjects and 1669 control subjects; data on the other sex hormones were available for fewer subjects. The relative risks (RRs) with 95% confidence intervals (CIs) of breast cancer associated with increasing BMI were estimated by conditional logistic regression on case-control sets, matched within each study for age and recruitment date, and adjusted for parity. All statistical tests were two-sided. RESULTS: Breast cancer risk increased with increasing BMI (P(trend) =.002), and this increase in RR was substantially reduced by adjustment for serum estrogen concentrations. Adjusting for free estradiol reduced the RR for breast cancer associated with a 5 kg/m2 increase in BMI from 1.19 (95% CI = 1.05 to 1.34) to 1.02 (95% CI = 0.89 to 1.17). The increased risk was also substantially reduced after adjusting for other estrogens (total estradiol, non-sex hormone-binding globulin-bound estradiol, estrone, and estrone sulfate), and moderately reduced after adjusting for sex hormone-binding globulin, whereas adjustment for the androgens (androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone) had little effect on the excess risk. CONCLUSION: The results are compatible with the hypothesis that the increase in breast cancer risk with increasing BMI among postmenopausal women is largely the result of the associated increase in estrogens, particularly bioavailable estradiol.

Type II glucocorticoid receptors are involved in neuronal death and astrocyte activation induced by trimethyltin in the rat hippocampus.

According to our previous study, trimethyltin (TMT), a neurotoxicant, induces the loss of pyramidal neurons in the rat hippocampus, which is preceded by a transient increase in plasma corticosterone concentration. To address whether this transient activation of the hypothalamopituitary-adrenocortical axis is related to neuronal loss in the hippocampus, we evaluated the effects of bilateral adrenalectomy (ADX) and the chronic supplemental treatment of glucocorticoid receptor agonists after ADX on TMT-induced hippocampal damage. Peroral administration of a single dose of TMT (9 mg/kg body wt) induced the extensive loss of CA3 pyramidal neurons and reactive astrocytosis in the hippocampus, as evidenced by results of vimentin and glial fibrillary acidic protein immunohistochemistry, and the effects were profoundly exacerbated by bilateral adrenalectomy. Prolonged administration of corticosterone not only attenuated the exacerbating effects of adrenalectomy but also partially reversed the TMT-induced neuronal loss and reactive astrocytosis. Dexamethasone, but not aldosterone, could be substituted for corticosterone, suggesting a novel neuroprotective action of type II glucocorticoid receptors in the hippocampus.

Magnetic fields (MF) of 50 Hz at 1.2 microT as well as 100 microT cause uncoupling of inhibitory pathways of adenylyl cyclase mediated by melatonin 1a receptor in MF-sensitive MCF-7 cells.

Magnetic fields (MF) of 60 Hz at 1.2 microT were previously shown to inhibit the antiproliferative effect of melatonin on MCF-7 cells (Liburdy,R.P., 1993, J. Pimeal Res. 14, 89-97). In addition, three laboratories (Blackman,C.F. and Benane,S.G., 1998; Luben,R.A. and Morgan,A.P., 1998; Morris,J.E., Chrisler,W.B., Miller,D.L., Sasser,L.B. and Anderson,L.E., 1998; 20th Annual Meeting of the Bioelectromagnetics Society, At. Pete Beach, FL) independently reported results consistent with this finding. In this study, we investigated the molecular basis of the biological effects of MF using MCF-7 cells. Only 1a melatonin receptors were identified by the [125I]melatonin binding assay and RT-PCR analysis. Moreover, preceding exposures to MF of 100 microT for 3, 5 and 7 days blocked the melatonin-induced inhibition of cAMP accumulation in a time-dependent manner, while none of the melatonin receptor functions or GTPase and adenylyl cyclase activities were affected. Estrogen-evoked cell proliferation was not altered by MF either. Exposure to 1.2 microT MF exerted the same effects on the melatonin-signaling pathway as that to 100 microT. Thus, this is the first study to provide evidence that MF may cause uncoupling of signal transduction from melatonin receptors to adenylyl cyclase.

Participatory assessment of the environment from children's viewpoints: development of a method and its trial.

To understand the actual viewpoints of children about daily life and the environment, the authors, adopting a participatory strategy, visited 21 classes of Japanese school children, improved in a stepwise process their ways of question-asking, and developed "WIFY"(what is important for you); a set of interactive questions composed of a basic question and three accompanying instructions. In applying WIFY, 59 fourth graders, 22 in Nagasaki, Japan and 37 in Beijing, China, reported their viewpoints in each of classroom settings. In both settings, when children were allowed to communicate with each other by the use of WIFY answering sheet, spontaneous exchanges arose and continued. WIFY itself is supposed to bring out and enhance mutual collaboration and spontaneous networking. In this instance, WIFY functioned as a communication tool. When answering sheets were collected and obtained responses were analyzed as cases, a rather materialistic view was suggested among Japanese children and a more disciplined view, which put much value on school and home, was suggested among Chinese children. Further studies are needed to confirm the changing environmental views of children from the collaborative research framework.

Effect of smoking on serum pepsinogen I level depends on serological status of Helicobacter pylori.

Serum pepsinogen (sPG) levels are used in gastric cancer screening programs. However, modification of sPG levels by smoking habit, according to the status of Helicobacter pylori (H. pylori) infection has been little investigated. This study investigated the effects of smoking on serum levels of pepsinogen I (PG I), pepsinogen II (PG II), and gastrin by IgG titer of antibody against H. pylori (Hp-IgG titer) using the data from 356 current-smokers and 262 non-smokers (133 never-smokers and 129 ex-smokers) in a cross-sectional study of 618 men aged 40 to 49 years. PG I, PG II, PG I / PG II ratio and gastrin were significantly associated with Hp-IgG titer in never-smokers [Spearman's correlation coefficient (95% confidence interval): 0.23 (0.07, 0.39), 0.52 (0.41, 0.63), -0.40 (-0.54,-0.27), and 0.25 (0.10, 0.41), respectively]. However, the correlation coefficients of PG I and PG II decreased in current-smokers, 0.02 (-0.1, 0.13) and 0.32 (0.22, 0.42), respectively. In H. pylori seronegative and low titer cases, the mean PG I level was significantly (P < 0.01) higher in current-smokers, compared with non-smokers. However, in high titer cases, the mean PG I level was lower in current-smokers. Mean PG II and gastrin levels, and PG I / PG II ratio did not differ according to smoking habits by Hp-IgG titer. The gastrin level was significantly correlated with PG II, but not PG I. These data indicate that current smoking influences the serum PG I level depending on Hp-IgG titer and the associations between sPGs and Hp-IgG titer. Gastrin is not involved in the modification of PG I levels by smoking.

Chronic exposure to ELF magnetic fields during night sleep with electric sheet: effects on diurnal melatonin rhythms in men.

The possible effects of repeated night-time exposure to an extremely low frequency magnetic field (ELF-MF) on melatonin were investigated in nine healthy male subjects aged 23-37 yr. The 16-week experiment consisted of 3 weeks of pre-exposure, 11 weeks of night-time exposure to MF generated from a nonheated electric sheet (ES), and 2 weeks of post-exposure recovery observation. The average MF intensity (rms, mainly 50 Hz AC) on the surface of the sheet was 0.7 microT at the head, 8.3 microT at the waist, and 3.5 microT at the feet of the subject. For each of the urine samples collected 5 times a day on scheduled sampling days, the urinary excretion rate (ng/h) of melatonin was determined, and 24 h rhythms were extracted for each subject and each experimental period (pre-exposure, first half and latter half exposure, and post-exposure periods) by the method of complex cosine curve fitting. Although estimates of the peak height, acrophase, and total daily amount of melatonin were characterized by significant variations among individual subjects, they did not reveal any statistically significant difference between exposure periods and nonexposure periods. Thus, the present study indicates that any profound effect of the MF originating from an ES on nocturnal melatonin production and its circadian rhythm is unlikely.

The expression and activation of matrix metalloproteinase-2 in rat brain after implantation of C6 rat glioma cells.

It has been reported that matrix metalloproteinases (MMPs) are highly expressed in malignant glioma cells and that this increased expression may facilitate the invasiveness of tumor cells. The authors investigated the expression and enzymatic activity of MMPs in rat brain during the growth of malignant gliomas at different time intervals. C6 rat glioma cells were unilaterally implanted into rat cerebral hemispheres. After 7 or 14 days, these brain tissues were prepared for SDS-PAGE zymography, Western blotting, immunohistochemistry, and in situ zymography. SDS-PAGE zymography and Western blotting revealed that the expression of proMMP-2 in rat brains with C6 glioma cells was significantly higher than that in normal or the sham-operated rat brains, and that the activated form of MMP-2 was detected only in the former but not in the latter. On immunohistochemistry, C6 glioma cells presenting invasive growth into the rat brain parenchyma and vessels demonstrated MMP-2 immunoreactivity. On in situ zymography, foci of invasive C6 glioma cells in rat brain tissue showed gelatinolytic activity. These results suggest that expression and activation of MMP-2 may be one of the crucial steps for glioma cell invasion into the brain parenchyma in vivo.

A prospective study of estradiol and breast cancer in Japanese women.

Few studies have prospectively examined endogenous hormone levels as risk factors for breast cancer. The present study compares prediagnostic hormone levels using stored serum from breast cancer cases and controls selected from the Life Span Study population of the Radiation Effects Research Foundation in Hiroshima and Nagasaki, Japan. Stored serum samples collected in 1968-1970 were assayed for 72 women subsequently diagnosed with breast cancer and 150 control subjects in 72 case-control sets matched on age, date of blood collection, exposure, radiation dose, and city. Serum levels were determined for sex hormone binding globulin, total estradiol (E2), bioavailable E2, dehydroepiandrosterone sulfate, and prolactin. Matched case-control comparisons of hormone levels were carried out by conditional logistic regression and were adjusted for menopausal status at the time of blood drawing. The odds ratio per unit log change in bioavailable E2 was 2.2 [95% confidence interval (CI), 1.02-5.31 for all subjects, and 2.3 (95% CI, 0.55-6.8) and 2.1 (95% CI, 0.55-9.7), respectively, based only on premenopausal or postmenopausal serum. The estimated odds ratios in each quintile of bioavailable E2 level, using the lowest quintile as referent, were 1.00, 1.89, 1.43, 3.45, and 3.37 (P for trend = 0.035). For sex hormone binding globulin, the overall odds ratio was 0.58 (95% CI, 0.14-2.26), and 1.00 (95% CI, 0.19-5.45) and 0.21 (95% CI, 0.02-1.88) based on premenopausal and postmenopausal serum, respectively. This study offers further prospective support for the hypothesis that a high level of biologically available E2 is a risk factor for the subsequent development of breast cancer.

Analysis of the proliferative potential of tumor cells after stereotactic radiosurgery for recurrent astrocytic tumors.

We analyzed the effectiveness of stereotactic radiosurgery (SRS) for recurrent astrocytic tumors histologically. Five patients were followed by pathological examination after radiosurgery treatment of recurrent astrocytic tumors. Histological diagnoses at the time of the last operation before SRS were Daumas-Duport grade II in two patients and grade IV (glioblastoma) in three patients. No histological diagnoses at the time of SRS were identified in any patients. Contrast enhanced lesions enlarged gradually on magnetic resonance (MR) images after SRS, and local control by SRS was judged as progressive disease radiologically in all patients. Four of five patients received re-operation after SRS, and the other patient died without re-operation and underwent post-mortem examination. After SRS, Ki-67 labeling indices (LIs) of recurrent astrocytomas initially diagnosed as grade II were 2.6% and 1.1%. These LIs were relatively lower than those of the control group of patients with recurrent grade II astrocytomas that were not treated by SRS. Ki-67 LIs of three glioblastomas after SRS were 23.5%, 18.6%, and 17.8%. These LIs were significantly lower than those before SRS (2.3%, 4.5%, and 0.9%). In the autopsy case, there was a significant difference between the LI of tumor cells in the radiosurgically treated region (0.9%) and that in the untreated region (29.2%). These results suggest that the proliferative potential of malignant astrocytic tumors in the radiosurgically treated area is reduced after SRS, and that radiological enlargement of enhanced lesions on MR images is due to propagation of the residual tumor cells that were not covered by radiosurgical target volume or to radiation necrosis. SRS may be a useful therapeutic tool in multidisciplinary treatment of malignant gliomas.

Prevalences of periodic limb movement-like and restless legs-like symptoms among Japanese adults.

Prevalences of periodic limb movement-like and restless legs-like symptoms among Japanese adults were investigated. The latter symptom was significantly associated with insomnia.

Prevalence of nocturia among Japanese adults.

The prevalence of nocturia among Japanese community-dwelling adults was associated with insomnia, taking into account other correlates of insomnia.

Helicobacter pylori infection and atrophic gastritis in middle-aged Japanese residents of São Paulo and Lima.

BACKGROUND: Helicobacter pylori infection and atrophic gastritis (AG) are markedly more prevalent in Japan than in other industrialized countries, however, the reasons for such a high prevalence are not fully understood. To add to information on H. pylori infection and its association with AG, the authors studied Japanese living in less developed countries. METHODS: Cross-sectional surveys were conducted of randomly selected Japanese residents aged 40-59 years in São Paulo, Brazil and Lima, Peru. Serum IgG antibody to H. pylori and pepsinogen I (PGI) and II (PGII) were measured as markers of AG. RESULTS: The prevalence of H. pylori infection was similar in both populations, 77% (95% CI: 70-83) in São Paulo and 75% (95% CI: 65-82) in Lima, and was within the range of five populations in Japan from our previous study. However, the prevalence of AG, defined by PGI < 70 ng/ml and PGI/PGII < 3.0 was more prevalent among Japanese in São Paulo (39% [95% CI: 32-47]), than Japanese in Lima (18% [95% CI: 12-27]). This difference was not explained by sex, age, generation or H. pylori infection. CONCLUSIONS: Helicobacter pylori infection among Japanese in less developed countries was similar to Japanese in Japan, although prevalence of AG varied. Factors other than H. pylori infection are important in the development of AG among Japanese.

Alterations of calcium/calmodulin-dependent protein kinase II activity in ischaemia-induced neuronal death and neuronal protection against ischaemia in the gerbil hippocampus.

To clarify the relation between neuronal protection against ischaemia and calcium/calmodulin-dependent protein kinase II (CaM kinase II) activity, we investigated temporal alterations of the kinase activity in the hippocampus after transient forebrain ischaemia under neuroprotective conditions, employing the gerbil bilateral carotid artery occlusion model. The hippocampal CA1 neuronal density at 2 hours after 5 minutes of forebrain ischaemia was 214.7 +/- 25.8/mm (mean +/- S.D.), and did not differ from the control significantly; however, it decreased to 11.7 +/- 4.2/mm at 7 days after the ischaemia. The neuronal density at 7 days after the ischaemia was 185.1 +/- 18.5 under the hypothermic conditions, 128.7 +/- 19.6 with the brief ischaemic pretreatment, 65.0 +/- 13.4 with administration of MK-801, and 20.5 +/- 4.2 with the repetitive hyperthermic pretreatment, respectively. The Ca2+/calmodulin-dependent activity of CaM kinase II in the hippocampal cytosolic fraction was decreased to 47.5% of the control value at 2 hours after the ischaemia, when CA1 neuronal death was not observed. In contrast, the activity was 98.8% of the control under the hypothermic conditions, 91.4% with the brief ischaemic pretreatment, 71.2% with administration of MK-801, and 47.9% with the repetitive hyperthermic pretreatment, respectively. These results indicated that the preservation of the Ca2+/calmodulin-dependent activity of cytosolic CaM kinase II after ischaemia parallelled the neuroprotective effect in the gerbil hippocampus. Thus, it is suggested that the preservation of the activity may be involved in the mechanism of neuronal protection against ischaemia.

Hemodynamic and metabolic changes following cerebral revascularization in patients with cerebral occlusive diseases.

Changes in cerebral hemodynamics and metabolism following cerebral revascularization were evaluated using positron emission tomography (PET). Ten patients who had received nonsurgical treatment for 3-6 months for minor completed stroke underwent superficial temporal artery to middle cerebral artery (STA-MCA) bypass surgery. All patients showed no extensive infarction on MR, and responsible vascular lesions were detected in the anterior circulation. A PET study of cerebral blood flow (CBF), oxygen extraction fraction (OEF), cerebral metabolic rate for oxygen (CMRO2), and cerebral metabolic rate for glucose (CMRGlu) measurements was performed before and 1.5 months after surgery using a steady state technique. Angiographically, anastomotic sites were patent in all patients. Seven patients showed neurological improvement after surgery and the others showed no improvement. The decreases in CBF, CMRO2 and CMRGlu recovered to some extent not only on the lesion side but also on the contralateral side after surgery. The increase in OEF values on the lesion side subsequently decreased after surgery. CMRO2 and CMRGlu showed parallel changes. It is concluded that the metabolic improvement afforded by the cerebral revascularization resulted in the neurological improvement, and that PET study is a powerful method for evaluating patients with cerebral occlusive diseases.

Direct interaction of lignin and lignin peroxidase from Phanerochaete chrysosporium.

Binding properties of lignin peroxidase (LiP) from the basidiomycete Phanerochaete chrysosporium against a synthetic lignin (dehydrogenated polymerizate, DHP) were studied with a resonant mirror biosensor. Among several ligninolytic enzymes, only LiP specifically binds to DHP. Kinetic analysis revealed that the binding was reversible, and that the dissociation equilibrium constant was 330 microM. The LiP-DHP interaction was controlled by the ionization group with a pKa of 5.3, strongly suggesting that a specific amino acid residue plays a role in lignin binding. A one-electron transfer from DHP to oxidized intermediates LiP compounds I and II (LiPI and LiPII) was characterized by using a stopped-flow technique, showing that binding interactions of DHP with LiPI and LiPII led to saturation kinetics. The dissociation equilibrium constants for LiPI-DHP and LiPII-DHP interactions were calculated to be 350 and 250 microM, and the first-order rate constants for electron transfer from DHP to LiPI and to LiPII were calculated to be 46 and 16 s-1, respectively. These kinetic and spectral studies strongly suggest that LiP is capable of oxidizing lignin directly at the protein surface by a long-range electron transfer process. A close look at the crystal structure suggested that LiP possesses His-239 as a possible lignin-binding site on the surface, which is linked to Asp-238. This Asp residue is hydrogen-bonded to the proximal His-176. This His-Asp...proximal-His motif would be a possible electron transfer route to oxidize polymeric lignin.

Serum concentrations of carotenoids, alpha-tocopherol, fatty acids, and lipid peroxides among Japanese in Japan, and Japanese and Caucasians in the US.

Serum concentrations of carotenoids, alpha-tocopherol, fatty acids, and thiobarbituric acid-reactive substances (TBARS) were measured in 217 Japanese residents of Japan, and in 99 Japanese and 100 Caucasian residents of the US, aged from 50 y to 74 y. In females, serum values of carotenoids such as beta-carotene (BC) and zeaxanthin & lutein (ZL) were highest among Japanese in Japan, followed by Japanese in the US and Caucasians in the US. In males, these values, except for serum BC values, were also highest among Japanese in Japan. Moreover, serum values of n-3 polyunsaturated fatty acids (n-3PUFAs) such as eicosapentaenoic acid and docosahexaenoic acid were significantly higher among Japanese in Japan than among Japanese and Caucasians in the US in both sexes. In contrast, serum values of n-6 polyunsaturated fatty acids such as linoleic acid and arachidonic acid were lowest among Japanese in Japan. For women, serum levels of n-9 unsaturated fatty acids were lowest among Japanese living in Japan. Serum TBARS values were highest among Japanese in Japan, followed by Japanese in the US and Caucasians in the US. A significant positive correlation was observed between serum values of TBARS and n-3 PUFAs among Japanese both in Japan and in the US. Serum TBARS values showed a significant inverse relationship with the serum values of BC and ZL among Japanese in Japan and with those of BC among Japanese in the US. These relationships were not always observed among Caucasians in the US. The results of this study suggest that the high TBARS values among Japanese in Japan may depend in part on lipid peroxidation induced in vitro by n-3PUFAs, while high reduction of lipid peroxidation could be expected among Japanese in Japan with high antioxidants such as BC and ZL. In conclusion, serum levels of nonprovitamin A carotenoids such as ZL may be a useful intake marker of vegetables. Dietary intakes of dark green vegetables and fish rich in n-3PUFAs might be more important in the prevention of some sites of cancer and of ischemic heart disease.

Production of amyloid beta protein precursor as a proteinase inhibitor by human astrocytic tumors.

The production of amyloid beta protein precursor (APP), which is a potent inhibitor of matrix metalloproteinases and serine proteinases, in human astrocytic tumors (n = 17) and normal brain tissues (n = 3) was investigated. We found proteinase inhibitory activity at around 120 kD by trypsin reverse zymography in the culture media of explant cultures of anaplastic astrocytomas and glioblastomas, but not in those of astrocytomas and normal brain tissues. Immunohistochemistry using a monoclonal antibody against human APP demonstrated that APP was detectable mainly in tumor and endothelial cells. Semiquantative analysis of western blotting revealed that immunoreactivity for APP in the culture media of tumor explant cultures appeared to be increased associated with the malignancy of astrocytic tumors. These findings suggest that APP production may be related to the malignant progression of human astrocytic tumors.