Effects of neoadjuvant chemoradiotherapy on postoperative morbidity and mortality associated with esophageal cancer.

We compared the surgical outcomes between 114 patients who did not receive neoadjuvant therapy (group 1) and 92 others who received neoadjuvant chemoradiotherapy (nCRT) (group 2), and assessed the preoperative and surgical factors that influence postoperative morbidity to determine the impact of nCRT on morbidity and mortality after esophagectomy via cervical, right transthoracic, and abdominal approaches. The overall postoperative morbidity rates were 44.7% and 55.4% in groups 1 and 2, respectively (P = 0.13). Rates of anastomotic leak (8.8% vs. 16.3%; P = 0.10), pneumonia (9.6% vs. 13.0%; P = 0.44), recurrent nerve palsy (15.8% vs. 10.9%; P = 0.31), and all other complications did not significantly differ between the groups. Multivariable analysis revealed cervical lymph node dissection (odds ratio [OR], 1.97; 95% confidence interval [CI], 1.01-3.84; P = 0.047) as the sole independent covariate for overall morbidity. Furthermore, a history of cardiovascular disease (OR, 2.90; 95% CI, 1.03-8.24; P = 0.045), the retrosternal reconstruction route (OR, 15.15; 95% CI, 3.56-62.50; P = 0.0002), and a longer surgical duration (OR, 1.01; 95% CI, 1.002-1.02; P = 0.01) were independent covariates for anastomotic leakage, and advanced age (OR, 1.08; 95% CI, 1.01-1.15; P = 0.02) and lower body mass index (OR, 1.16; 95% CI, 1.01-1.33; P = 0.04) were independent covariates for pneumonia. However, whether or not patients received nCRT was irrelevant. We found that nCRT is safe for three-incision esophagectomy and it does not increase the incidence of postoperative morbidity and mortality relative to esophagectomy alone.

Clinical trial: the effect of Johrei on symptoms of patients with functional chest pain.

BACKGROUND: Patients with functional chest pain (FCP) represent a therapeutic challenge for practising physicians. AIM: To determine the efficacy of Johrei as compared to wait-list in improving symptoms of FCP patients. METHODS: Patients with chest pain of noncardiac origin for at least 3 months were enrolled into the study. All patients had to have negative upper endoscopy, pH testing and oesophageal manometry prior to randomization. Subsequently, patients were randomized to either Johrei or wait-list control. Patients received 18 Johrei sessions from a Johrei practitioner for 6 weeks. RESULTS: A total of 21 FCP patients enrolled into the Johrei group and 18 into the wait-list group. There was no difference in symptom intensity score between Johrei group and wait-list group at baseline (20.28 vs. 23.06, P = N.S.). However, there was a significant pre- and post-treatment reduction in symptom intensity in the Johrei group (20.28 vs. 7.0, P = 0.0023). There was no significant reduction in symptom intensity score between baseline and at the end of the study in the wait-list group (23.06 vs. 20.69, P = N.S.). CONCLUSION: This pilot study shows that Johrei may have a role in improving FCP symptoms; however, future studies are needed to compare Johrei treatment with sham Johrei or supportive care.

Inhibition of apoptosis by menadione on exposure to UVA.

Quinones are widely distributed in the environment, both as natural products and as pollutants. This paper reports that one of the simplest quinones, 2-methyl-1,4-naphthoquinone (menadione), effectively inhibited apoptosis in the presence of UVA. Menadione suppressed the apoptosis induced by serum depletion and cell detachment. This effect was significantly enhanced by UVA irradiation. An antioxidant, N-acetylcysteine, completely inhibited the antiapoptotic effects of both menadione itself and menadione plus UVA, and peroxidation of the cells after treatment was observed using a probe to detect the intracellular production of peroxides. By contrast, 2-hydroxy-1,4-naphtoquinone (lawsone) showed no antiapoptotic effect in the presence or absence of UVA. Lawsone is reported not to undergo the redox process that produces reactive oxygen species. These results indicated that intracellular peroxidation contributed to the antiapoptotic effects of both menadione itself and menadione plus UVA. Dysregulation of the apoptotic process is critical to carcinogenesis. The photosensitization of quinone compounds as it relates to the inhibition of apoptosis should be examined in the future.

Ionizing radiation-induced macrophage activation: augmentation of nitric oxide production and its significance.

Radiation is an important therapy for many kinds of cancer. However, it can result in the inflammation and accompanying injury. Recently, it is being recognized that the nitric oxide (NO) produced in macrophages activated by ionizing radiation is an important mediator. Ionizing radiation has been confirmed to potentiate NO production in macrophages, though the mechanism is not clear. We have shown that the increase of NO production in irradiated macrophages contributed to tumoricidal activity, with the activation mechanisms differing between high-dose and low-dose irradiation. High-dose irradiation activates macrophages directly, whereas low-dose irradiation acts indirectly through interaction with neighboring cells and the paracrine induction of cytokines. In this review, we discuss the augmentation of NO production in macrophages by ionizing radiation and its mechanism and significance. In radiotherapy, the control of NO levels both in whole-body and in the tumor is important to prevent irradiation-induced injury and for the cancer to regress.

Phosphatidylserine induces apoptosis in CHO cells without mitochondrial dysfunction in a manner dependent on caspases other than caspases-1, -3, -8 and -9.

Treatment of Chinese hamster ovary K1 cells with phosphatidylserine (PS) caused typical apoptosis with distinct morphological and biochemical features in a dose- and time-dependent manner. However, unlike camptothecin-induced apoptosis, changes in mitochondrial transmembrane potential were not observed. In addition, cytochrome c release did not occur in PS-induced apoptosis. A pan caspase inhibitor, Z-VAD, significantly inhibited the apoptosis, but inhibitors of caspase-1, -3, -8 and -9 did not. Activities of caspase-1, -3, -8 and -9 were increased by treatment of the cells with camptothecin, but not with PS. These results suggest that PS-induced apoptosis occurs without the collapse of mitochondrial transmembrane potential and without the release of cytochrome c, in a manner independent of caspase-1, -3, -8 and -9.

Inhibitory action of leptin on early follicular growth differs in immature and adult female mice.

In order to investigate the action of leptin on early follicular growth, preantral follicles, 95-115 microm in diameter were mechanically isolated from the ovaries of BDF1 hybrid immature (11-day-old) and adult (8-wk-old) mice, and cultured for 4 days in vitro. Follicular growth was assessed by daily changes in follicular diameter and by the amount of estradiol and immunoreactive (IR)-inhibin released into the culture medium at Day 4. Preantral follicles from immature mice showed a significant development in follicular growth as a result of stimulation by GH (1 mIU/ml), insulin-like growth factor (IGF)-I (100 ng/ml) + FSH (100 mIU/ml), and GH (1 mIU/ml) + FSH (100 mIU/ml). Although leptin at concentrations of 1-1000 ng/ml did not have any significant effect on follicular growth stimulated by IGF-I or GH, it significantly inhibited follicular growth in a dose-related manner when follicles were stimulated by IGF-I + FSH and GH + FSH, respectively, suggesting that leptin attenuated the additive effect of FSH. On the other hand, preantral follicles from adult mice were cultured in the presence of FSH, and FSH-dependent follicular growth was inhibited by leptin in a dose-related manner. Because FSH stimulates cAMP production, we investigated the involvement of cAMP in the inhibitory mechanisms of leptin. Preantral follicles from immature and adult mice were cultured in the presence of either 8-Br-cAMP or forskolin. Both 8-Br-cAMP and forskolin significantly increased follicular diameter and hormone secretion in both immature and adult mice. However, 8-Br-cAMP and forskolin-stimulated follicle growth and hormone secretion were significantly inhibited in immature mice by coadministration of leptin, whereas growth of preantral follicles from adult mice was not inhibited by addition of leptin to cultures. These results indicate that leptin causes an inhibitory effect on the early follicular development of both immature and adult mice, but the inhibitory mechanisms of leptin are different.

UVA irradiation induces energy-independent phospholipid-flip in mammalian plasma membrane.

Translocation from the outer to the inner membrane leaflet (flip) of phospholipids after ultraviolet A (UVA) irradiation was investigated in Chinese hamster ovary cells. Fluorescent 1-palmitoyl-2-[6-[(7-nitro-2-1,3-benzox- adiazol-4-yl)amino]caproyl]-sn-glycero-3-phosphoserine (NBD-labeled phosphatidylserine [NBD-PS]) was used to assay transbilayer lipid movement. A marked increase in flip of NBD-PS was observed immediately after low-dose UVA irradiation which was not lethal and returned to the basal level after 6 h. UVA-induced flip was not attributed to the increase of permeability by UVA irradiation because cells that were negative for staining with propidium iodide also showed increased flip of NBD-PS. Furthermore, the enhancement was independent of adenosine 5'-triphosphate, demonstrating the lack of involvement of phospholipid translocase. Marked increases were also observed in flip of both NBD-phosphatidylethanolamine and NBD-phosphatidylcholine immediately after UVA irradiation, showing that the increase was independent on the head groups of phospholipids. These findings indicated that UVA changes the flip-flop of phospholipids and that the cell membrane is a molecular and cellular target of UVA.

Catalytic Activity of Hexokinase in Reversed Micelles.

Reversed micelles can control the size of water pools and the physical property of water by changing W(0)(=[water]/[surfactant]). Hexokinase (HK) activity seems to be easily affected by the microenvironment in the neighborhood of the enzyme because it is assumed that HK binds to the outer mitochondrial membrane by insertion of its hydrophobic NH(2) tail. The catalytic activity of HK was examined in reversed micelles in order to study the effect of the microenvironment in the neighborhood of HK on the activity. Sodium bis(2-ethylhexyl)sulfosuccinate (AOT), hexadecyltrimethyl ammonium chloride (HTAC), and octaoxyethylene dodecyl ether (C(12)E(8)) were used as anionic, cationic, and nonionic surfactants, respectively. HK activity was obtained by measuring ATP and ADP amounts with HPLC. The high electrostatic inner surfaces of AOT and HTAC reversed micelles were not favorable for HK to exhibit the catalytic activity, but the activity in HTAC reversed micelles was 2-3 times higher than that in AOT reversed micelles and the activities in both reversed micelles revealed an optimum at W(0)=10. The phenomenon was discussed in connection with the location of HK, nonuniform distribution of substrates, and the size and physical properties of the water pools. On the other hand, HK activity was much higher in C(12)E(8) reversed micelles than in AOT and HTAC reversed micelles and increased with the concentration of C(12)E(8). This suggests that HK activity is easily revealed in hydrated ethylene oxide chains. In conclusion, it was demonstrated that HK activity depends on the microenvironment such as the electrostatic field, the physical properties of water, and the hydrophobicity. Copyright 2001 Academic Press.

Mutation analysis of the Smad6 and Smad7 gene in human ovarian cancers.

The Smad6 and Smad7 genes are members of the Smad family, involved in the transforming growth factor-beta (TGF-beta) signaling pathway. Mutations in TGF-beta receptors and their cytoplasmic elements of transduction signals commonly accompany various cancers. Using PCR-SSCP analysis we searched for the presence of Smad6 and Smad7 gene mutations in 30 human ovarian cancers and 4 ovarian cancer cell lines, and found that 12 cases (35.3%) had a polymorphism in intron 2 of the Smad6 gene and that 8 cases (23.5%) had a polymorphism at codon 208 in the Smad7 gene. Because these polymorphisms were not accompanied by amino acid substitution, the present results show that the mutations in the Smad6 and Smad7 genes are unlikely to be involved in human ovarian cancers.

Enhancement of O2- production from resident peritoneal macrophages by low-dose in vivo gamma-irradiation.

Superoxide anion (O2-) production after very low-dose in vivo irradiation (4 cGy) was examined in resident peritoneal macrophages. The level of production rapidly increased following treatment with the PKC activator, phorbol 12-myristate 13-acetate (PMA), but no further enhancement by low-dose in vivo irradiation was observed. On the other hand, treatment with zymosan A gradually induced O2- production, which was further increased in low-dose in vivo irradiated macrophages. The amounts of phagocytosis of zymosan A were not changed by in vivo irradiation. This indicated that the enhancement of O2- production was not due to an increase in phagocytotic activity by low-dose in vivo irradiation. Our results show that low-dose in vivo irradiation induces production of reactive oxygen species by macrophages, not only nitric oxide as reported in our previous paper but also O2-. This may contribute to the increase of cytolytic activity of macrophages after low-dose in vivo irradiation.

Analysis of specific gene mutations in the transforming growth factor-beta signal transduction pathway in human ovarian cancer.

Several proteins, including transforming growth factor beta (TGF-beta) receptor type I (RI), TGF-beta receptor type II (RII), Smad2, Smad3, and Smad4/DPC4, have been identified in the transduction pathway of the tumor suppressor TGF-beta. Mutations in TGF-beta RI, TGF-beta RII, Smad2, and Smad4/DPC4 genes are associated with several human cancers. The present study examines these gene mutations in 32 human ovarian cancers and 14 patient-matched normal tissues. For the first time, mutations in the Smad2 and Smad4 genes were analyzed in relation to human ovarian cancer. Gene mutations of TGF-beta RI, TGF-beta RII, Smad2, and Smad4 were analyzed using specific primers by PCR-single-strand conformational polymorphism (SSCP), and the results revealed a frameshift mutation at codons 276-277 (CTCTGG-->CTGCGTGG) in exon 5 of TGF-beta RI in 10 of 32 tumor samples (31.3%). This mutation was associated with reduced or absent expression of TGF-beta RI protein and p53 protein in tumor tissues. We detected SSCP variants of TGF-beta RII in exon 2 in 20 of 32 tumors. Sequence analysis of these variants revealed an A to G transition at the seventh band of intron 2. In this A to G polymorphism in intron 2, 12 samples (37.5%) had A/A alleles, 12 (37.5%) had A/G alleles, and 8 (25%) had G/G alleles. We detected Smad2 SSCP variants in exon 4 in 12 of 32 tumors (37.5%). Sequence analysis revealed a 2-bp deletion in the polypyrimidine tract of intron 3, which is located at position -39 to -56 in the splice acceptor site of the intron 3-exon 4 junction. No SSCP variants were detected in the Smad4 gene. These findings suggest that mutations in the TGF-beta RI and in its signal transduction pathway are likely responsible for human ovarian carcinogenesis.

Effect of 1,25(OH)2D3 on expression of estrogen receptor-alpha mRNA on rat osteosarcoma cell line (ROS 17/2.8).

In order to investigate the regulatory mechanisms of estrogen receptors (ER) in bone cells, changes in ER-alpha mRNA levels of rat osteosarcoma cell line (ROS 17/2.8) before and after exposure to 1,25(OH)2D3 and 17-beta estradiol respectively were measured by quantitative polymerase chain reaction using an internal standard. ER mRNA levels in the ROS 17/2.8 cultured with the medium alone had 5.029 +/- 1.623 mol/g total RNA x 10(-13) and were not statistically different from those cultured in the presence of 1,25(OH)2D3 at concentrations of 10(-12) M and less. ER mRNA levels in the ROS 17/2.8 cell line showed a small but a significant increase as a result of stimulation by 1,25(OH)2D3 at concentrations of 10(-10) and 10(-11) M. However, ER mRNA levels in ROS 17/2.8 cultured in the presence of 1,25(OH)2D3 at concentrations of 10(-9) M were not statistically different from those of the control. On the other hand, the expression of ER in ROS 17/2.8 cells cultured for 3 hours with various doses of 1,25(OH)2D3 showed, by immunoblotting methods, a significant increase at the dose of 10(-10) M in the expression of ER. Although a physiological significance is obscure, these observations suggest that 1,25(OH)2D3 plays a part in the expression of ER in ROS 17/2.8. No significant changes were seen in the expression of ER mRNA and the synthesis of ER as a result of stimulation by the estradiol.

Do assisted reproductive technologies have effects on the demography of monozygotic twinning?

PIP: This study examined the incidence of monozygotic twinning of one embryo with the use of cycles in which only one embryo, treated by various assisted reproductive technologies (ART), was transferred. It also examined the possibility of demographic alterations in the overall incidence of monozygotic twinning in Japan induced by ART. A total of 134 clinics or institutes participated in this study. Overall, it is noted that the incidence of monozygotic twinning in Japan has been almost constant (0.402%). In ART treatments, the monozygotic twinning rate was significantly higher than that of natural pregnancies (P = 0.0204). For in vitro fertilization (IVF) treatment cycles, the monozygotic twinning rate was also higher than that of natural pregnancies (P = 0.6285). However, this difference was not statistically significant because of the small number of IVF pregnancies. Moreover, in the context of microinsemination cycles, the monozygotic twinning rate was significantly higher than that of natural pregnancies (P = 0.0285) or IVF (P = 0.0006). In terms of the possible impact of ART on the demography of monozygotic twinning, adoption of mechanically assisted hatching for all embryos in Japan may alter the demography of monozygotic twinning.^ieng

Expression of adrenomedullin in the human corpus luteum.

OBJECTIVE: Adrenomedullin (AM) is a potent hypotensive peptide found in human pheochromocytoma tissue. In the present study, the expression of AM mRNA in the human ovary was examined. DESIGN: Ovarian mRNA was analyzed in the follicle, the corpus luteum of mid-luteal phase, and early pregnancy. SETTING: Gunma University School of Medicine, Gunma, Japan. PATIENT(S): Premenopausal women with histologically normal ovary who were undergoing salpingoophorectomy. INTERVENTION(S): The dominant follicle and corpora lutea were isolated and total RNA was extracted from these tissues. MAIN OUTCOME MEASURE(S): Northern blot analysis of AM, receptor activity-modifying protein 2 (RAMP2), and LH/hCG receptor mRNA in human samples. RESULT(S): An AM mRNA transcript of 1.6 kilobases (kb) was detected in corpus luteum tissue; this transcript was identical to that which has been detected in placenta and fetal membrane. The AM and LH/hCG receptor mRNA levels were low in the mature follicle but increased in the corpus luteum of the mid-luteal phase and were maintained during early pregnancy. A single transcript of 0.8 kb for RAMP2 was also seen in the follicle and corpus luteum, the level of RAMP2 mRNA was relatively high in the preovulatory follicle and RAMP2 was present in the corpus luteum. CONCLUSION(S): The expression of AM, its receptor, and LH/hCG receptor may be an important component in the process of development and differentiation of the corpus luteum.

Expression of gonadotropin and activin receptor messenger ribonucleic acid in human ovarian epithelial neoplasms.

Activin receptors (ActRs) and gonadotropin receptor mRNA expression were investigated in 18 human ovarian epithelial neoplasms. Northern blot analysis showed the presence of 3.0-kb type Ia ActR, 6.0- and 3.0-kb type IIa ActR, and 5.0-kb type IIb ActR mRNA transcripts in total RNA prepared from the cancer tissues. One carcinoma showed two major transcripts of a follicle-stimulating hormone receptor (FSH-R) gene, 4.1 and 2.4 kb, whereas the other two carcinomas showed two major transcripts of the luteinizing hormone/human chorionic gonadotropin receptor (LH-R) gene, 5.4 and 2.4 kb. These results were further analyzed by studying the corresponding PCR-amplified FSH and LH-R cDNA obtained by reverse transcription of total RNA. Expression of FSH-R mRNA was confirmed in about half of the cancer tissues. The size of the FSH-R reverse transcription-PCR product was the same as in normal ovarian follicles. Similarly, expression of LH-R mRNA was also detected in about half of the cancers. Normal ovaries and cancer tissues were homogenized, and activin concentrations were measured in extracts. Activin levels in normal ovarian tissue were around 0.59 +/- 0.01 ng/mg protein (mean +/- SE; n = 5), and activin production was detected in every cancer tissue, except one--serous adenocarcinoma. The findings in this study demonstrated that activin and ActRs are present in and synthesized by human ovarian epithelial neoplasms. Thus, activin seems to be available as an autocrine/paracrine factor in epithelial neoplasms and may contribute to the expression of FSH-R, although the roles of activin and gonadotropin in tumorigenesis has yet to be defined.

A clinical study on suicide among schizophrenics.

We conducted a clinical investigation of 80 suicides who met the DSM-III-R criteria for schizophrenia. The results using this approach showed no significant difference with those of preceding studies, and general features regarding the phenomenology of suicide among schizophrenics worldwide were recognized. The present study, however, served to underscore the following points: (i) suicide of schizophrenics must be considered a concern at all stages of the disease; (ii) the subjective strength of the will to die may be more important for the committing suicides than the lethality of the methods employed; and (iii) a change in the environment, for example, a hospital admission or discharge, may trigger suicide. A control group of 80 living schizophrenics with no past attempted suicide was then matched to the suicide group with respect to sex and illness duration, in order to identify the predictors of suicide. In a logistic regression analysis, the presence of suicidal ideation, degree of anxiety estimated by positive and negative syndrome scale, and birth order were revealed as predictors of suicide. As to the birth order, the risk is higher in middle children.

An autopsy case with clinically and molecular genetically diagnosed Huntington's disease with only minimal non-specific neuropathological findings.

An autopsy case with clinically and molecular genetically diagnosed Huntington's disease (HD) accompanied with minimal non-specific neuropathological features was reported. When the patient was 45 years old, he had faulty memory, mood swing, personality change and agitation. Neurological and psychiatric examinations revealed choreoathetoid movements in limbs and trunk, generalized hyperreflexia and mental deterioration. However, cerebellar ataxia and muscle rigidity were not disclosed. Neuroimaging study did not show a definite atrophy of heads of caudate nuclei. Neuroacanthocytosis and Wilson's disease were ruled out by the peripheral blood examination and serum Cu and ceruloplasmin examination. At the age of 55 he died of pneumonia. Post-mortem examination revealed minimal non-specific neuropathological features for HD (Vonsattel's grade 0), that is, no visible fibrillary gliosis in the striatum, and few neuronal loss and only proliferation of astrocytes (astrocytosis) in the striatum. Molecular-genetic study the patient's brain tissues and his youngest son's blood was performed. These studies revealed 40 CAG repeats in the patient, 56 CAG repeats in his youngest son. These results suggest they may be HD. Vonsattel et al. [ 1998] insist that grade 0 comprises 1% of all HD brains, and grade 1 comprises 4% of all HD brains. But we could not find any reports in which the clinical and neuropathological features were described in detail on the cases with clinically and molecular genetically diagnosed HD without specific pathological findings. Therefore, we present in detail the clinical and neuropathological features of such case.

Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on the expression of follicle-stimulating hormone receptors during cell differentiation in cultured granulosa cells.

Dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin; TCDD) is a common environmental pollutant causing public concern. Using a cell culture system derived from rat granulosa cells that provides unique advantages for studying the molecular mechanisms underlying the action of TCDD, the influences of TCDD on FSH receptor (FSH-R) induction were examined. The treatment with FSH produced, as expected, a substantial increase in specific FSH-R expression, whereas concurrent treatment with the environmental amount of TCDD (10 pM) resulted in a significant decrease in FSH-R after being cultured from 24-72 h. Cotreatment with FSH (30 ng/ml) and increasing doses of TCDD inhibited the levels of FSH-induced FSH-R messenger RNA (mRNA) in a dose-dependent manner. Treatment with 8-Br-cAMP (1 mM) produced a significant increase in FSH-R mRNA; concurrent treatment with TCDD (10 pM) produced a significant attenuation of 8-Br-cAMP action. These findings suggest that the ability of TCDD to interfere with FSH action, as regards the induction of FSH-Rs, is exerted at sites distal to those involved in cAMP generation. Because a single transcript of 5.2 kb was seen for the Ah receptor in this granulosa cell system, the effects of TCDD may be mediated by this specific receptor. The rates of FSH-R mRNA gene transcription, assessed by nuclear run-on transcription assay, were decreased by the addition of TCDD. The effect of TCDD on FSH-R mRNA stability was determined by measuring the decay of FSH-R mRNA under conditions known to inhibit transcription. The decay curve for the 2.4-kb FSH-R mRNA transcript was not significantly changed after the addition of TCDD. These findings showed that the effect of TCDD on FSH-R mRNA was, at least in part, the result of decreased transcription.

Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on the expression of luteinizing hormone receptors during cell differentiation in cultured granulosa cells.

Dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) is a common environmental pollutant causing public concern. By use of a cell culture system derived from rat granulosa cells that provides unique advantages for studying the molecular mechanisms underlying the action of TCDD, the influence of TCDD on luteinizing hormone receptor (LHR) induction was examined. Treatment with follicle-stimulating hormone (FSH) produced, as expected, a substantial increase in specific LHR expression; concurrent treatment with TCDD (10 pM) resulted in a significant decrease in LHR after 24 h. Cotreatment with 30 ng/ml FSH and increasing doses of TCDD inhibited the levels of FSH-induced LHR mRNA in a dose-dependent manner, and 1 pM TCDD inhibited FSH-induced LHR significantly after 48 h. The rate of LHR mRNA gene transcription, assessed by nuclear run-on transcription assay, was found to decrease after addition of TCDD. The decay curves for the 5.4-kb LHR mRNA transcript showed a significant decrease after addition of TCDD.

Lack of interaction in recombinant human FSH receptor and both TSAb and TSBAb.

Since cross-reactivity of TSH with the human FSH receptor has been reported, in this study we tested the effect of thyroid-stimulating antibody (TSAb) and thyroid stimulation-blocking antibody (TSBAb) on Chinese hamster ovary cells expressing human FSH receptor (CHO-hFSH-R cells). We examined the TSBAb activity of sera from hypothyroid patients who had a positive TBII to determine whether these sera also block the effect of FSH on CHO-hFSH-R cells. Although human FSH I-3 (0.25-16 ng/ml) stimulated the production of intracellular cAMP in CHO-hFSH-R cells with dose-responsive manner, neither TSAb nor TSBAb had such an effect on the cells.