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Biomedical subjects

N Itoh

Publications and source records attributed to N Itoh.

At least 289 records · Page 16Linked to original sources

Making the in-vitro model closer to actual B lymphopoiesis in the bone marrow.

After more than a decade since Whitlock and Witte established an in-vitro long-term culture of bone marrow B lineage cells, c-kit+IL-7-receptor(R)+B precursor cells in fresh bone marrow are now able to be grown under a fully defined culture condition containing only BSA, transferrin, IL-7 and the ligand for c-kit(Kit-ligand;KL) as protein components. On the other hand, previous studies indicated that the actual intramarrow B-cell-genesis is a complex process involving multiple stromal cell-derived molecules. Thus, the next step for the culture of B-cell genesis is to develop this simple culture into a new defined culture of B-cell-genesis that is closer to the actual process. In this article, we will describe how this defined culture condition has developed from the original Whitlock-Witte type culture, how the B precursors under this culture-condition are different from that in the bone marrow, and finally our biased view on the future direction to which this defined culture should develop.

Animals↗

Enhancement of gamma-actin protein during liver regeneration: its accumulation in a region adjacent to the hepatocyte plasma membrane.

We identified a protein with a molecular weight of about 44 kDa in an extract of rat regenerating liver. This protein was undetectable in normal, sham-operated, and completely regenerated liver. We also purified this 44-kDa protein from an extract of rat liver remnant after partial hepatectomy. The partial amino acid sequences of the purified protein were identical to those of gamma-actin in non-muscle cells. In addition, anti-pan actin antibody recognized the purified 44-kDa protein, whereas anti-muscle actin and anti-beta-actin antibodies did not. Thus, we concluded that the 44-kDa protein was non-muscle gamma-actin. An immunohistochemical study revealed that the non-muscle gamma-actin accumulated next to the plasma membrane of liver parenchymal cells during regeneration. Moreover, the gamma-actin level was augmented in primary cultured rat hepatocytes prior to DNA synthesis. Intracellular gamma-actin in cultured hepatocytes was distributed across the entire basal plane after stimulation with hepatocyte mitogens. This change in the distribution of gamma-actin correlated with the cell spreading that occurred during the G1/S phase transition. These findings indicated that gamma-actin plays specific roles in the growth of liver parenchymal cells during liver regeneration.

Actins↗

Inhibitory effects of medroxyprogesterone acetate on mouse endometrial carcinogenesis.

The present study was undertaken to examine the effects of cyclic administration of low-dose progestogen on endometrial carcinogenesis in mice. A total of 115 female ICR mice, 10 weeks of age, were divided into four experimental and control groups. Mice in groups 1-3 received laparotomy and were injected with N-methyl-N-nitrosourea (MNU) solution at a dose of 1 mg/100 g body weight to the left uterine tube and with normal saline to the right uterine tube. From one week after the MNU exposure, groups 1 and 2 were given 5 ppm 17 beta-estradiol (E2)-containing diet throughout the experiment. Mice in group 1 received 5 s.c. injections of medroxyprogesterone acetate (MPA) (2 mg/mouse) at intervals of 4 weeks from week 7. Group 3 was treated with MNU/normal saline alone. Group 4 consisted of mice treated with MPA alone. At the termination of the experiment (week 30), all animals were killed and autopsied for pathological examinations. It was found that adenocarcinomas and preneoplastic lesions developed in the bilateral uterine corpora in mice of groups 1-3. MPA treatment significantly decreased the weight of the uterine corpus (P < 0.05) and the incidences of endometrial adenocarcinoma and atypical or adenomatous (P < 0.001) but not cystic glandular hyperplasias in the MNU/E2-treated groups. Additionally, MPA treatment tended to decrease the proliferating cell nuclear antigen-labeling index in endometrial glandular cells. These data indicate that MPA, even at low dose, has an inhibitory effect on mouse endometrial carcinogenesis induced by MNU and E2.

Animals↗

Influence of hypertensive vascular changes in intratesticular arteries on spermatogenesis in SHRSP.

1. The process of the spermatogenetic damage induced by hypertensive vascular changes was studied with stroke-prone spontaneously hypertensive rats (SHRSP). 2. In SHRSP, hypertensive changes in intratesticular arterioles developed from 19 weeks of age. 3. At 23 weeks of age, a severe reduction in the number of mature and immature spermatids was observed. 4. The transferrin concentration in testicular cytosol was decreased at 23 weeks of age, suggesting that Sertoli cell function in SHRSP had regressed. 5. In conclusion, it was suggested that the decline in Sertoli cell function as a result of hypertensive vascular changes is part of the mechanism whereby spermatogenic damage occurs in SHRSP.

Animals↗

Protective effects of manidipine on spermatogenesis in stroke-prone spontaneously hypertensive rats.

1. We evaluated the protective effects of manidipine on spermatogenic damage induced by the hypertensive vascular changes in stroke-prone spontaneously hypertensive rats (SHRSP). 2. Blood pressure reached more than 250 mmHg in SHRSP at 15 weeks of age, and thereafter the hypertensive changes in testicular arterioles developed. Manidipine reduced both the blood pressure and the hypertensive vascular changes. 3. Although immature and mature spermatids greatly diminished in SHRSP at 23 weeks of age, manidipine could preserve almost normal spermatogenesis even at 23 weeks of age. Transferrin concentration in testicular cytosol, which was considered to be indicative of the Sertoli cell function, in SHRSP with manidipine administration was significantly higher than that in SHRSP with no treatment at 23 weeks of age. 4. In conclusion, manidipine could prevent the development of the hypertensive changes in intratesticular arterioles and maintain normal Sertoli cell function. As a result, manidipine protected spermatogenic damage in SHRSP.

Animals↗

Conversion of glomerular histology from a mesangiopathic to a membranopathic pattern in serum sickness nephritis with prolonged sensitization.

In order to examine the effect of prolonged sensitization on glomerular injury, serum sickness nephritis was induced in Fischer rats by administration of egg albumin (EA). Animals were divided into A, B and C groups with 4-week, 6-week and 8-week sensitization, respectively. The experimental results were as follows: Both group A (4 weeks) and group B (6 weeks) showed mesangial immune complex deposition with proliferation (mesangiopathic pattern), but in the latter both the size and the amount of the deposits were larger than those in the former; while group C (8 weeks) demonstrated predominant distribution of deposition along the capillary walls (membranopathic pattern). It is suggested that such conversion of deposition from mesangiopathic to membranopathic pattern after prolonged repeated sensitization may be the result of the change of the host immune response to antigen, and/or the character of the antibody.

Animals↗

Mass screening for prostate carcinoma: a study in Hokkaido, Japan.

Although there has been controversy about the early detection of prostate carcinoma by mass screening, we carried out an investigational study of such screening, using digital rectal examination (DRE) and serum prostate-specific antigen (PSA) determination in Hokkaido, Japan. We determined the detection rate and some profiles of the carcinoma detected by screening in Japanese men 50 years old and older. The detection rate of carcinoma was 1.10% in 1,639 participants. The rate linearly increased with aging from 0.25% for men in their fifties to 2.29% for those in their seventies. Two thirds of the carcinomas were T1(c) or T2, the frequency of which seemed to be higher than that of patients who visited medical institutions. The simultaneous use of both DRE and serum PSA determination showed a higher positive predictive value than either alone. Our current results indicated that the detection rate of carcinoma was higher than we previously anticipated for Japanese men, and that simultaneous use of DRE and serum PSA determination yielded a higher positive predictive value than either alone.

Aged↗

Frontal intermittent rhythmic delta activity (FIRDA) in pituitary adenoma.

We report a case of FIRDA in the EEG of a patient diagnosed as major depression with pituitary adenoma and hyponatremic encephalopathy. The pituitary adenoma appeared to be a major factor responsible for FIRDA in this case. Although other factors associated with this case, i.e., diffuse encephalopathy and administration of antipsychotic drugs, have been reported to be causative, FIRDA remained in the EEG after these other factors diminished. Although size of the pituitary adenoma that might be associated with FIRDA in the EEG recording was not identified in this study, FIRDA may be associated with a small pituitary adenoma less than 10 mm in diameter. We think a diligent search for additional pathology is recommended if FIRDA is seen in the EEG of an otherwise normal patient.

Adenoma↗

Insulin receptor-related receptor messenger ribonucleic acid in the stomach is focally expressed in the enterochromaffin-like cells.

The insulin receptor-related receptor (IRR) is a member of the insulin receptor family. In contrast to the widespread expression of insulin receptor and insulin-like growth factor-I receptor messenger RNA (mRNA), the expression of IRR mRNA is highly restricted to the kidney and stomach. IRR mRNA in the kidney is focally expressed in the renal distal tubule cells. However, the cellular localization of IRR mRNA in the stomach remains to be elucidated. Here, we examined the cellular localization of IRR mRNA in the rat stomach by in situ hybridization. IRR mRNA in the stomach was abundantly localized in the basal third of the oxyntic glands of the fundic stomach. IRR mRNA in the stomach was colocalized with mRNA for histidine decarboxylase, a marker for the enterochromaffin-like (ECL) cells, indicating that the expression was restricted to ECL cells. ECL cells actively produce and store histamine, which is an important physiological stimulant of acid secretion from the parietal cells. The preferential localization of IRR mRNA in ECL cells suggests that the IRR plays an important role in the function of these cells.

Animals↗

Autoimmune endocrine disease induced by recombinant interferon-alpha therapy for chronic active type C hepatitis.

To elucidate the role played by interferon-alpha (IFN alpha) in the pathogenesis of autoimmune endocrine disease, we determined the autoantibody status, thyroid function test results, hemoglobin-A1c levels, and clinical symptoms of 58 patients who received IFN alpha for treatment of chronic active type C hepatitis. Each patient was treated for 6 months with a total dose of 391 +/- 140 x 10(6) U (mean +/- SD). Thyroid microsomal and/or thyroglobulin antibodies newly appeared or were increased in titer in 6 patients, 2 of whom developed hypothyroidism during IFN alpha therapy. Neither islet cell antibodies nor insulin-dependent diabetes mellitus developed during IFN alpha therapy, although hemoglobin-A1c levels were increased in 2 patients. One patient became positive for antimitochondrial antibodies, and another patient with preexisting antimitochondrial antibodies also manifested deterioration in liver function test results. Parietal cell antibodies and smooth muscle cell antibodies were the most frequent newly developed antibodies in 7 patients. Adrenal medullary cell antibodies and nuclear antibodies newly developed in 2 and 1 patients, respectively. At least 1 of 8 autoantibodies newly appeared in 19 patients (32.8%) and hypothyroidism developed in 2 patients (3.4%) during IFN alpha therapy. On the other hand, in 19 age- and sex-matched patients who did not receive IFN alpha, no autoantibody appeared, and no autoimmune disease developed during a follow-up period of 3 months. These findings suggest that IFN alpha acts as an immunomodulatory agent, inducing autoantibody production and the development of autoimmune disease in susceptible patients. Special attention should be paid to the development of hypothyroidism during IFN alpha therapy.

Adult↗

Studies on the activation mechanisms of guanylyl cyclase by serotonin, probably through a novel subtype of serotonin receptor (5-HTGC).

Characterization of the serotonin-induced increase in guanosine 3',5'-cyclic monophosphate (cyclic GMP) was investigated and compared with that induced by atrial natriuretic peptide (ANP) in NG108-15 cells. The cyclic GMP formed by serotonin or ANP was transported in a similar manner to the extracellular medium, although the cyclic GMP formed by bradykinin was not. Serotonin and ANP raised cyclic GMP additively. Serotonin-induced cyclic GMP formation was completely inhibited by pretreatment with 100 nM 12-o-tetradecanoylphorbol 13-acetate (TPA), although that induced by ANP was only partially inhibited and the effects were blocked by pretreatment with staurosporin. In membrane preparations, ANP stimulated cyclic GMP formation in the presence of ATP, but serotonin did not. Serotonin-stimulated cyclic GMP formation was found to occur in neuroblastoma N18TG-2, but not in glioma C6Bu-1. These results suggest that a novel subtype of serotonin receptors (5-HTGC) which stimulates membrane-bound guanylyl cyclase, different from that stimulated by natriuretic peptide, may exist especially in neurons.

Animals↗

Hinokitiol induces differentiation of teratocarcinoma F9 cells.

Hinokitiol, a constituent of the wood of Chamaecyparis taiwanensis, was found to induce differentiation of teratocarcinoma F9 cells. When examined by the agar-overlay method, in which expression of plasminogen activator as a differentiation marker protein was detected, this compound exhibited a dose- and time-dependent induction. Induction of differentiation by hinokitiol occurred irreversibly and required its addition for more than 12h. Among its structure-related compounds tested, tropolone and two colchicine-related compounds exerted potent activities comparable to that of hinokitiol. These findings indicate that free tropolone structure in the molecules plays an essential role in inducing differentiation of F9 cells. Hinokitiol showed a strong inhibitory effect of DNA synthesis in very early stages of culture, suggesting that this effect may be responsible for triggering differentiation of F9 cells.

Animals↗

Histopathological features of atrophic thyroiditis with blocking type-TSH binding inhibitor immunoglobulins.

To investigate the histopathological features of atrophic thyroiditis (AT) with blocking type-TSH binding inhibitor immunoglobulins (TBII), the present morphological observations were carried out employing additional immunohistochemical procedures. Moreover, these were compared with examples of goitrous Hashimoto's thyroiditis showing negative TBII (HT). There exist apparent differences between AT and HT. In particular, significant follicular atrophy with epithelial flattening including decreased positive staining of the follicular epithelial cells for thyroglobulin in AT was characteristically observed. These results suggest that the mechanism for the development of hypothyroidism in AT with blocking type-TBII might be due to suppression of thyroid cell function through the inhibition of endogenous TSH stimulation by the blocking antibody with subsequent epithelial degenerative destruction.

Adult↗

[Clinical studies of spermatogenic damage in patients with testicular cancer].

We investigated the spermatogenic function of patients with testicular cancer, and the influences of anti-cancer chemotherapy on testicular function in these patients. Fifty-one patients with testicular cancer were selected for evaluation of their testicular function, including spermatogenesis and endocrinological function, before and after chemotherapy with anti-cancer agents. Before chemotherapy with anti-cancer agents, 22 of 49 patients (44.8%) had a sperm concentration of less than 20 x 10(6)/ml, and 8 patients (16.3%) showed azoospermia. The mean sperm concentration of the patients with testicular cancer was 29.0 x 10(6)/ml before therapeutic chemotherapy with anti-cancer agents, but within 3 months after chemotherapy, it decreased to 3.86 x 10(6)/ml (p < 0.01). Fifteen of 19 patients (73.7%) were revealed to have azoospermia. Damage to spermatogenesis became more severe with the number of chemotherapy treatment. No patients had a detectable sperm count at the completion of 3 or more courses of chemotherapy. But some patients who received 3 courses or more of chemotherapy showed recovered sperm counts after 2 or more years. Thus, a lack of sperm after chemotherapy for cancer did not necessarily indicate inability to recover spermatogenesis over 2 years after chemotherapy. Serum FSH levels of the patients were 5.62 +/- 3.43 mIU/ml before chemotherapy, and 19. 70 +/- 17.06 mIU/ml (p < 0.05) at the time of its completion. Serum FSH levels could reflect damage to spermatogenesis in these cases. Cases in which spermatogenesis did not recover may have higher serum FSH levels than those with recovery of spermatogenesis.

Adolescent↗

Prophylaxis of genetically determined diabetes by diazoxide: a study in a rat model of naturally occurring obese diabetes.

The study was carried out using a new rat model of naturally occurring obese, nonketotic diabetes, Otsuka Long-Evans Tokushima Fatty rat (Kawano et al., Diabetes 41: 1422-1428, 1992), which closely resembles obese noninsulin-dependent diabetes in human. At the age of 3.5 wk, body weight, glucose tolerance and plasma insulin level after glucose load were normal in Otsuka Long-Evans Tokushima Fatty rats, indicating the animals are at nonobese, prediabetic phase. At this age, however, glucose-stimulated insulin release by pancreatic islets in vitro was abnormally exaggerated whereas the islet insulin content and glucose metabolism by the islet cells were normal. Administration of diazoxide (0.2% in diet), an inhibitor of insulin secretion, to Otsuka Long-Evans Tokushima Fatty rats from the age of 4 to 12 wk completely prevented the development of obesity and insulin resistance, which was accompanied by marked improvement of glucose tolerance and disappearance of exaggerated B cell response to glucose in vitro. This is the first report of successful pharmacological prevention of genetically determined obese diabetes.

Animals↗

Tissue expression of rat ciliary neurotrophic factor (CNTF) mRNA and production of the recombinant CNTF.

We used the polymerase chain reaction to show that CNTF mRNA is widely expressed in the brain, heart, lung, liver, kidney and testis of the rat, in addition to preferential expression in the sciatic nerve. We produced the recombinant CNTF in E. coli using rat sciatic nerve cDNA and obtained high yields of pure CNTF. The biological activity of the recombinant protein was comparable to that of native rat CNTF in its support of the survival of cultured embryonic day-8 chick ciliary ganglions. Western Blot analysis using antibody against the recombinant CNTF clearly showed the presence of CNTF protein (25kD) in rabbit sciatic nerve.

Animals↗

[A case of primary intracranial malignant lymphoma showing a spontaneous regression].

An eighty-year-old woman, who had been admitted with disorientation and gait disturbance, was revealed to have multiple intracranial tumors in the right temporal lobe and cerebellar vermis on CT and MRI. Following intravenous injection of dexamethasone (8 mg/day) for three days, isosorbide (90ml/day) was given in order to decrease brain edema, and the tumors increased in size rapidly in the next four months. However, most of the lesions disappeared or became markedly small without any specific therapy three months after the exacerbation of the disease. The brain tumors recurred one year thereafter, and the pathological diagnosis of primary intracranial malignant lymphoma, diffuse large B-cell type was done by autopsy examination. This patient was considered to have shown a spontaneous regression during the clinical course, and the clinicopathological descriptions of the case are presumed to present characteristic features of primary, intracranial malignant lymphoma.

Aged↗