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Biomedical subjects

T Gotoh

Publications and source records attributed to T Gotoh.

At least 127 records · Page 7Linked to original sources
PubMed1996

CCAAT/enhancer-binding protein beta (C/EBP beta) binds and activates while hepatocyte nuclear factor-4 (HNF-4) does not bind but represses the liver-type arginase promoter.

In an attempt to elucidate the mechanism governing liver-specific transcription of the arginase gene, we previously detected two protein-binding sites designated footprint areas A and B at positions around--90 and --55 bp, respectively, relative to the transcription start site of the rat arginase gene. Based on the finding that area A was bound by a liver-selective factor(s) related to CCAAT/enhancer-binding protein (C/EBP), we performed cotransfection assay and showed that C/EBP family members and a related factor, albumin D-element-binding protein (DBP) stimulate transcription from the arginase promoter. In addition to area A, a recombinant C/EBP beta protein bound to area B, which appeared to be primarily responsible for activation by C/EBPs. We unexpectedly found that the arginase promoter activity stimulated by C/EBPs and DBP was repressed by another liver-enriched transcription factor, hepatocyte nuclear factor-4 (HNF-4). Analysis of chimeras formed between the arginase promoter and the herpes simplex virus thymidine kinase promoter allowed us to delimit the negative HNF-4-responsive element into the region overlapping with footprint area B. However, no apparent binding of HNF-4 was observed in this negative element. We speculate that HNF-4 is involved in fine regulation of the arginase gene in the liver or shutdown of the gene in nonhepatic tissues without direct binding to the promoter region.

Animals↗
PubMed1996

Coinduction of nitric oxide synthase, argininosuccinate synthetase, and argininosuccinate lyase in lipopolysaccharide-treated rats. RNA blot, immunoblot, and immunohistochemical analyses.

Nitric oxide (NO) is synthesized from arginine by nitric oxide synthase (NOS), and citrulline which is generated can be recycled to arginine by argininosuccinate synthetase (AS) and argininosuccinate lyase (AL). Rats were injected with bacterial lipopolysaccharide (LPS), and expression of the inducible isoform of NOS (iNOS), AS, and AL was analyzed. In RNA blot analysis, iNOS mRNA was undetectable before the LPS treatment but was induced by LPS in the lung, heart, liver, and spleen, and less strongly in the skeletal muscle and testis. AS mRNA was induced in the lung and spleen, and AL mRNA was weakly induced in these tissues. AS and AL mRNAs were abundant in the control liver and remained unchanged after the treatment. Kinetic studies showed that iNOS mRNA increased rapidly in both spleen and lung, reached a maximum 2-5 h after the treatment, and decreased thereafter. On the other hand, AS mRNA increased more slowly and reached a maximum in 6-12 h (by about 10-fold in the spleen and 2-fold in the lung). AL mRNA in the spleen and lung increased slowly and remained high up to 24 h. In immunoblot analysis, increase of iNOS protein was evident in the lung, liver, and spleen, and there was an increase of AS protein in the lung and spleen. In immunohistochemical analysis, macrophages in the spleen that were negative for iNOS and AS before LPS treatment were strongly positive for both iNOS and AS after this treatment. As iNOS, AS, and AL were coinduced in rat tissues and cells, citrulline-arginine recycling seems to be important in NO synthesis under the conditions of stimulation.

Animals↗
PubMed1996

Death of germinal center B cells without DNA fragmentation.

During the selection of B cells within germinal centers (GC) on the basis of their affinity for T-dependent antigen, B cells not positively selected are eliminated within GC. This process of B cell death has been considered to be apoptosis. In a recent study, we have reported that, although a substantial number of thymocytes were considered to be dead because of their extremely small cell size and heavy chromatin condensation even though they were not yet phagocytosed (pyknosis), they were devoid of DNA fragmentation, the most characteristic feature for apoptosis. In this study, we examined in vivo the mechanism of B cell death within GC by using the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end-labeling (TUNEL) method to detect DNA double-strand breaks. TUNEL+ B cells were scattered throughout the upper dark and the light zones of GC. Double staining of the sections by the TUNEL method and acid phosphatase (AcP) activities showed that all the TUNEL+ B cells were phagocytosed by macrophages. Light microscopic and ultrastructural studies revealed the presence of small unphagocytosed B cells within the light zone. These cells are undoubtedly dead because they were much smaller than surrounding lymphoid cells and have a heavy chromatin condensation. Furthermore, ultrastructural detection of DNA fragmentation confirmed that these small unphagocytosed B cells were TUNEL-, implying that DNA fragmentation is not primarily involved in the cell death process of these small dead B cells. These results indicate that most B cells, not positively selected and thus destined to be eliminated, die within GC without DNA fragmentation, and are subsequently phagocytosed by macrophages and become TUNEL+. Typical apoptosis, characterized by DNA fragmentation in situ, is not the predominant type of cell death that occurs during the selection of B cells in GC.

Animals↗
PubMed1996

Cranial attachment of the gubernaculum associated with undescended testes.

Elongated epididymis is an abnormality encountered most frequently in patients who have an undescended testis (or testes). To clarify the implication of this anomaly in testicular descent, the anatomic configuration of paratesticular structures, especially the site of cranial attachment of the gubernaculum in relation to the configuration of the vas deferens, was evaluated in 54 undescended testes of 44 patients. Undescended testes were associated with an elongated epididymis in 42.5% of cases. Of these, the cranial gubernaculum was attached solely to the vas deferens in 73.9%. In this group, the cranial gubernaculum was attached to the most descended part of the loop of the vas deferens. No patient with a nonelongated epididymis had a gubernaculum attached solely to the vas deferens. These results suggest that the abnormal attachment of the cranial gubernaculum in the embryological stage might affect the mode of descent of adjacent paratesticular structures.

Child↗
PubMed1996

Insufficient calcium and iron intakes among general female population in Japan, with special reference to inter-regional differences.

Dietary intakes of calcium (Ca) and iron (Fe) were investigated in 227 women (mostly housewives) in 12 regions in Japan in 1991-1993 by the 24-hour food duplicate method. Nine regions out of 12 had been previously studied in 1977-1982. Utilizing Standard Food Composition database, mean Ca and Fe-intakes in 1991-1993 were estimated to be 602 and 10.4 mg/day, respectively; the former was barely sufficient and the latter was below sufficiency when compared with the Recommended Daily Allowance in Japan for pre-menopausal women. Ca- and Fe-intake did not increase in the 10-year period. Further analysis after classification of the women into three groups of farmers in Okinawa, farmers in Mainland Japan and urban residents showed that Ca and Fe insufficiency was most evident among Okinawa farmers. The leading Ca sources were milk, pulse, vegetables and fish-shellfish, but consumption of milk was generally low, especially among Okinawa farmers. Pulse, vegetables and fish-shellfish were 3 major Fe sources; Okinawa farmers depended more on vegetables and less on fish-shellfish.

Calcium↗
PubMed1996

Induction of the C/EBP beta gene by dexamethasone and glucagon in primary-cultured rat hepatocytes.

The synthetic glucocorticoid, dexamethasone, and glucagon cooperatively elevated the level of mRNA for the transcription factor CCAAT/enhancer binding protein beta (C/EBP beta) in primary-cultured rat hepatocytes. In response to dexamethasone and/or glucagon, C/EBP beta mRNA started to increase as early as 30 min, reached a maximum within 2 h, and then gradually decreased. The administration of cycloheximide, a protein synthesis inhibitor, led rather to an increase in C/EBP beta mRNA, which suggested that a labile negative protein factor(s) is involved in regulation of the C/EBP beta mRNA level. Cycloheximide further augmented the increases in C/EBP beta mRNA by dexamethasone and/or glucagon. Therefore, C/EBP beta mRNA accumulation in response to these hormones is apparently independent of ongoing protein synthesis. The elevation of the C/EBP beta mRNA level by these hormones was accounted for by increases in the rate of transcription of the C/EBP beta gene, as deduced on nuclear run-on analysis. Gel mobility shift analysis revealed that the DNA-binding activity of C/EBP beta was increased cooperatively by dexamethasone and glucagon. These results suggest that the C/EBP beta gene is primarily induced by glucocorticoids and/or glucagon and that the accumulated C/EBP beta protein is then involved in secondary activation of target genes in response to these hormones in the liver.

Animals↗
PubMed1996

Intrapleural pirarubicin (4'-O-tetrahydropyranyladriamycin) for treatment of malignant pleural effusion.

Pirarubicin (4'-O-tetrahydropyranyladriamycin), a new anthracyline derivative, was administered as a single agent into the pleural cavity of 42 patients (total 46 courses) with malignant pleural effusion at a dose of 20, 40, 60 or 80 mg/body. All 46 courses were evaluable for non-hematological toxicities. Fever and chest pain (> or = WHO grade 2) were seen in 67.4% and 13.0% of courses, respectively. Patients receiving a dose of 80 mg/body developed fever of > or = 39 degrees C in 45.5%, and chest pain lasting more than three days and requiring pentazocine more than three times in 36.4%. In contrast, patients receiving a dose of < or = 60 mg/body presented these toxicities in only 8.6% and 2.9%, respectively. Nausea-vomiting (> or = WHO grade 2) was observed in only 4.3% of the total 46 courses and alopecia was not observed. Thirty-eight courses (36 patients) were evaluable for hematological toxicities. Myelosuppression (leukocyte nadir count < or = 1900, WHO grade 3 or 4) was seen in four courses (10.5%), and thrombocytopenia (< or = 49,000, WHO grade 3 or 4) in only two (5.3%). Although the mean AUC (0-24) for pirarubicin in plasma during the four courses that produced myelosuppression was significantly higher than that during the 11 courses without myelosuppression, the difference in the mean dose was not significant. Furthermore, no significant correlation was shown between dose (mg/m2) and AUC in plasma. It is considered that myelosuppression is not a dose-related toxicity at a dose of 20-80 mg/body. The dose-limiting toxicity was fever or chest pain, although unexpected myelosuppression was also encountered. The maximum tolerated dose was 80 mg/body. With regard to clinical efficacy, the overall response rate was 73.7% in 38 evaluable courses (38 patients). The mean T(1/2) of pirarubicin concentration in pleural effusion and plasma was 22.1 h and 8.8 h, respectively. We recommend a dose of 40 or 60 mg/body pirarubicin for this pleurodesic treatment.

Adult↗
PubMed1996

Influence of paternal (252) Cf neutron exposure on abnormal sperm, embryonal lethality, and liver tumorigenesis in the F(1) offspring of mice.

Experiments were conducted to determine whether neutron-induced genetic damage in parental germline cells can lead to development of cancer in the offspring. Seven-week-old C3H male mice were irradiated with (252) Cf neutrons at a dose of 0, 50, 100, or 200 cGy. Two weeks or three months after irradiation, the male mice were mated with virgin 9-week-old C57BL females. Two weeks after irradiation, the irradiated male mice showed an increased incidence of sperm abnormalities, which led to embryo lethalities in a dose-dependent manner when they were mated with unirradiated female mice. Furthermore, liver tumors in male offspring of male mice in the 50 cGy group were significantly increased in 19 of 44 (43.2%) animals, in clear contrast to the unirradiated group (1 of 31; 3.2%) (P < 0.01). In the 100 cGy group, 6 of 39 (15%) mice had lesions. At 3 months after irradiation abnormal sperm and embryonal lethality were not significantly increased. The incidences of liver tumors in male offspring from the 50 cGy, 100 and 200 cGy groups were 6 of 20 (30%), 5 of 22 (23%) and 1 of 19 (5%), respectively, which are not significantly increased compared with the control. It is concluded that increased hepatic tumor risk in the F(1) generation may be caused by genetic transmission of hepatoma-associated trait(s) induced by (252) Cf neutron irradiation.

Animals↗
PubMed1996

[Prevention of infections in a case with myelodysplastic syndrome by an intermittent subcutaneous administration of G-CSF].

An 83-year-old male was admitted to our hospital because of pancytopenia and low grade fever on April 19, 1993. On admission, hematological data were as follows: WBC 1,000/microliters with 19% neutrophils, RBC 367 x 10(4)/microliters, Hb 9.5 g/dl and platelets 6.7 x 10(4)/microliters. Bone marrow examination revealed 6.6% myeloblasts and 33.5% erythroblasts. Morphological abnormalities included hypersegmentation, degranulation and pseudo-Pelger's nuclear anomaly in neutrophils. Based on these findings the diagnosis of refractory anemia with excess of blasts (RAEB) of the myelodysplastic syndrome (MDS) was made and therapy with low dose Cytarabine (Ara-C) was initiated in April 1993. The patient had two episodes of severe pneumonia in June and July. Therefore, 75 micrograms/day of G-CSF was given in addition to antibiotic therapy for the second episode of infection in July. Thereafter the severe infection subsided, and G-CSF administration was switched to an intermittent schedule (75 micrograms twice a week) since September. Cytarabine ocfosfate (100 mg/day) was added for 10-14 days at interval 1-2 months from October,1993. He has been well with no episode of infection for more than two year. One major concern regarding the clinical application of G-CSF in MDS patients is related to the possible stimulation of leukemic cell proliferation. Frequent hematological monitoring is necessary in patients with RAEB who are prone to develop acute myeloid leukemia. However, we administered G-CSF at a relatively low dose twice a week for over two year and could successfully prevent infections without inducing the leukemic changes.

Aged↗
PubMed1996

[Glycosaminoglycans in subepithelial opacity after excimer laser keratectomy].

We evaluated histochemically the characteristics of glycosaminoglycans and proteoglycans in the corneal subepithelial opacity after excimer laser keratectomy on rabbit corneas. We also performed the same evaluations on the cornea after mechanical keratectomy. Twenty days after the operations, the area immediately subjacent to the epithelium showed strong staining with toluidine blue, alcian blue, and colloidal iron. However, after treatment with chondroitinase ABC or chondroitinase AC, alcian blue staining in this area decreased dramatically. Antilarge proteoglycan antibody also reacted strongly in this area. Histochemical and immunohistochemical examination of the cornea where mechanical keratectomy was done showed basically similar findings with the cornea of excimer laser keratectomy. These results suggest that large-molecula proteoglycans with chondroitine sulfate side chains become localized in the subepithelial area after two different kinds of keratectomies. We presume from histochemical and immunohistochemical observations that the subepithelial opacity observed after excimer laser keratectomy is not a special reaction to excimer laser but simply a corneal scar formed after stromal resection.

Animals↗
PubMed1996

[Clinical studies of inverted papilloma of the bladder].

Clinical studies were conducted on 9 cases of inverted papilloma of the urinary bladder which were transurethrally resected between August, 1987 and July, 1995 at our hospital, in males between 29 and 81 years of age (mean:58.3). Six of the 9 inverted papillomas were localized at the bladder neck and 3 in the trigone. Cystoscopic examinations revealed that inverted papillomas were divided into two types, one with a thick and short stalk with a smooth surface and the other with a thin and long stalk with/without a partial papillary surface. The majority of the former was located in the trigone and all of the latter cases in the bladder neck, suggesting that the two types occurred at different sites. Pathological examination by Hematoxylin-Eosin staining demonstrated that 5 of the 9 cases were of the trabecular type and 4 were of the grandlar type. Immunohistochemically, none of the tumors were stained with the antiprostatic-specific-antigen antibody revealed. Follow-up periods after the operation were from 12 to 48 months(mean:26.6 months) and no recurrence was observed.

Adult↗
PubMed1996

[A case of cerebral infarction due to dissection in a branch of the middle cerebral artery].

A 65-year-old man developed left drop hand, dysarthria and emotional incontinence. Brain CT and MRI revealed multiple cerebral infarctions in the cortex and subcortical white matter of the right temporal and parietal lobes which were in the distribution of the right middle cerebral artery. Cerebral angiography disclosed segmental narrowing (string sign) and two pseudoaneurysms in the right angular artery which were diagnosed as dissecting aneurysm of a branch of the middle cerebral artery. In this case, cerebral angiography was more useful than MRI in diagnosis of dissecting aneurysm of a branch of the middle cerebral artery. This was a very rare case of dissecting aneurysm of the middle cerebral artery localized in one of its branches.

Aged↗
PubMed1996

[Recanalization of dural sinus occlusion following the disappearance of dural arteriovenous fistula: report of a case].

A 73-year-old female was admitted to our hospital because of disturbed consciousness and left-sided motor weakness. Computed tomographic scans demonstrated a hemorrhagic infarction in the right parietal region. Right carotid angiograms showed both the posterior portion of the superior sagittal sinus (SSS) and the entire left transverse sinus simultaneously occluded. Left carotid angiograms revealed an enlarged occipital artery, which had direct communications to the left sigmoid sinus and the superior petrosal sinus. These findings were consistent with dural arteriovenous fistula (D-AVF). The laboratory examinations yieled normal results. The patient was managed conservatively with glyceol and anticonvulsants for four weeks and eventually recovered with complete resolution of hemiparesis. Follow-up angiography carried out 6 weeks later showed the SSS, partially stenotic, but recanalized with no evidence of venous congestion. The D-AVF still remained opacified, but there was a marked reduction in retrograde flow to the sigmoid sinus. Further repeated angiograms obtained at 10 months after the onset confirmed complete recanalization of the SSS and disappearance of the D-AVF. From the timing of the angiographies, we considered that the sinus occlusion was caused by the high arterial flow to the fistula and its disappearance made recanalization of SSS possible.

Aged↗
PubMed1996

[Effective administration of recombinant granulocyte colony-stimulating factor to prevent granulocytopenia due to combination chemotherapy for testicular germ cell tumors].

A prospective randomized study on the administration of recombinant granulocyte colony stimulating factor (rG-CSF) was conducted on 15 patients with testicular germ cell tumors. The clinical stagings of all patients except one were minimal to moderate extent according to the Indiana University staging system. Combination chemotherapy using bleomycin, etoposide and cisplatinum (BEP) was performed as the initial treatment on the eligible patients. rG-CSF was administered by two different methods; 1) routine administration on the 6th day after BEP chemotherapy (group A), and 2) the same method, but after granulocytopenia of 1,500/mm3 had developed (group B). The administration of rG-CSF in group A significantly reduced the severity of leucocytopenia and also the incidence of stomatitis compared with group B. Although rG-CSF produced no significant side effects, the thrombocytopenia was prominent in the group A patients (not significant). BEP chemotherapy itself is an easily-tolerable and well established method for treating young adult patients. The method used in group B seems to be suitable in situations where thrombocytopenia and cost effectiveness.

Adult↗
PubMed1996

[The effect of calcium antagonist on ischemia-reperfusion injury of the rabbit retina].

We investigated the effect of nicardipine (NC), a calcium antagonist, on retinal ischemia-reperfusion injury. Electroretinogram (ERG) was recorded from rabbit eyes before and after ischemia produced by increasing intraocular pressure to 140 mmHg for 90 min after giving 0.01% NC (0.1 ml) intravitreally (n = 4). ERGs from intact (non-ischemic) rabbit eyes after injecting NC intravitreally was also recorded (n = 4) (NC group). The recovery rate of b-wave amplitude after reperfusion was significantly higher in the NC group than in the control group which was given saline without NC (p < 0.05). There were no significant differences between the NC and the control groups in a-wave amplitude and implicit time of the b-wave. No significant changes were detected in the a-wave or b-wave amplitude after intravitreal injection of NC into the intact eyes. We suggest that NC can prevent ischemia-reperfusion injury of the rabbit retina and could be considered for clinical use.

Animals↗
PubMed1996

[Tuberculous mediastinal lymphadenitis presenting as hoarseness].

A 70 year-old woman was admitted to our hospital complaining of hoarseness. Bronchoscopic examination revealed that the left vocal cord was fixed in the paramedian position, and therefore left recurrent nerve paralysis was suspected. Although a chest X-ray film showed no abnormal findings, a chest computed tomogram showed that pretracheal (#3) and subaortic (#5) lymph nodes were swollen (1 to 2 cm in diameter). An open biopsy was done. Histological examination of the resected mediastinal lymph nodes revealed an accumulation of Langhans giant cells and epithelioid cells in caseous necrosis. An acid-fast bacillus was seen after Ziehl-Neelsen staining. This was a rare case of mediastinal tuberculous lymphadenitis in which hoarseness was useful for early diagnosis. Fifty-three cases of tuberculous mediastinal lymphadenitis have been reported in Japan.

Aged↗
PubMed1996

[A case of bilateral infarction of medial pontomedullary junction].

A 69-year-old man suffered from dizziness and nausea after work, and was admitted to our hospital on the next day. On admission, he showed bilateral horizontal nystagmus and left hemiparesis. On the 3rd day he vomited frequently, and the dizziness became worse. Bilateral horizontal and upward gaze palsy and bilateral facial nerve palsy were observed. Brain MRI on the 5th day disclosed bilateral upper medial medullary infarction that extended to the pontomedullary junction. Cerebral angiography on the 13th day revealed occlusion of the right vertebral artery. This case did not show typical medial medullary syndrome. The mechanism was unknown, but similar cases were reported. Recently, many cases of medullary infarction are reported with the progress of MRI technology. It is suggested that the addition of the new concepts on the conventional syndromes of medullary infarction is necessary.

Aged↗