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Biomedical subjects

H Ikeda

Publications and source records attributed to H Ikeda.

At least 775 records · Page 43Linked to original sources

Immunoreactive corticotropin-releasing hormone levels in the hypothalamus of female Wistar fatty rats.

We have studied immunoreactive corticotropin-releasing hormone (CRH) levels in the hypothalamus of female Wistar fatty rats, a strain with the fa gene transferred from the Zucker rat to the Wistar Kyoto rat, in an attempt to understand the role of CRH in the development of obesity. A study was conducted with 5-week- and 12-week-old female Wistar fatty rats and lean littermates. There was no significant difference in hypothalamic CRH levels between lean and obese rats at the age of 5 weeks (1887 +/- 99.6 vs. 1767 +/- 124 pg/tissue; mean +/- S.E.M.). Hypothalamic CRH immunoreactivities, however, were significantly lower in 12-week-old obese rats (2361 +/- 132 pg/tissue) than those in lean littermates (2992 +/- 118 pg/tissue; P less than 0.05). The difference of CRH contents between the lean and obese group becomes apparent as they grow up and develop obesity.

Aging↗

Characterization of a cis-acting regulatory element involved in human-aromatase P-450 gene expression.

The characteristics of a cis-acting regulatory region involved in the human-aromatase P-450 gene have been examined by transient expression analysis. The region spans from -242 - -166 relative to the cap site of the gene. A fragment containing the region excised from the gene enhances heterologous promoter activity as well as its own promoter activity in a position-independent and orientation-independent manner. The fragment exerts its enhancer activity in human BeWo choriocarcinoma cells in which the aromatase P-450 gene is expressed, but not in other cell lines tested. Deletion of 38 bp from the 3' end of the fragment results in a complete loss of enhancer activity. A gel-retardation assay with nuclear extracts from BeWo cells suggests the existence of a nuclear factor(s) which interacts with the fragment. These results suggest that the regulatory element in the fragment is involved in efficient transcription of the human-aromatase P-450 gene.

Animals↗

Search for neurotoxins structurally related to 1-methyl-4-phenylpyridine (MPP+) in the pathogenesis of Parkinson's disease.

Immunoassays sensitive to a broad range of compounds structurally related to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP) and 1-methyl-4-phenylpyridine (MPP+) have been developed and used to test for the presence of possible chemically related neurotoxins in the brains of Parkinson's disease patients. The sensitivity and chemical reactivity of the polyclonal antibodies used in these assays have been characterized with a range of endogenous and chemically related materials. Two methods were developed and tested for extraction followed by chromatographic separation which would be applicable to stored or accumulated substances. The immunoassays were tested and applied to the assay of tissue extracts from MPTP or MPTP-analogue exposed animals, and indicated detectability of MPP(+)-immunoreactivity greater than 8 weeks after exposure to MPTP in monkey brain. No difference in immunoactivity was measured in extracts from human brains of Parkinson's disease patients or controls, and particularly low levels of immunoreactivity were found in the striatum relative to the levels measured in several cortical regions. From these studies, there is no evidence for the role of an environmental neurotoxin chemically related to MPTP in the pathogenesis of Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

[Treatment results of radiotherapy for squamous cell carcinoma of the cheek mucosa].

The results of radiotherapeutic treatment in 71 patients with squamous cell carcinoma of the cheek mucosa were reviewed. The actuarial 5-year local control rate was 100% for T1 (8 patients), 62% for T2 (43), 65% for T3 (17) and 0% for T4 (3). The patients were divided into four groups according to treatment modality; group 1 was treated by radiotherapy alone (R), group 2 by radiotherapy combined with chemotherapy of BLM or PEP (R + C), group 3 by external radiotherapy followed by surgery (R + S) and group 4 by a combination of radiotherapy, chemotherapy and surgery (R + C + S). The 5-year local control rate was 44% for R (11 patients), 61% for R + C (39), 63% for R + S (6) and 80% for R + C + S (15). Nine of 14 cases or 64% of the surgical specimens in the R + C + S group showed no tumor cells microscopically, a rate comparable with the 5-year local control rate of the R + C group. Including the results of secondary treatment by surgery for recurrent cases, the ultimate local control rate was 83% in both the R and R + C groups. The local control rate was 88% for carcinoma located in the anterior half of the cheek and 53% for that in the posterior cheek. The results suggested that tumors extending to the bucco-alveolar sulci would be more difficult to control by radiotherapy alone, with or without chemotherapy.

Adult↗

Surface immunoglobulin-mediated signal transduction involves rapid phosphorylation and activation of the protooncogene product Raf-1 in human B-cells.

The protooncogene product, Raf-1, is a serine/threonine kinase and has been implicated as an intermediate in signal transduction mechanisms. We examined neoplastic and normal B cells for phosphorylation and activation of Raf-1 protein in response to anti-immunoglobulin antibody (anti-Ig). Anti-Ig induced rapid phosphorylation of Raf-1 protein in both neoplastic B-cells of hairy cell leukemia and normal tonsillar B-cells which proliferated well in response to anti-Ig. The increase in phosphorylation was due primarily to an increase in phosphoserine. The immune complex kinase assay using Histone V-S as an exogenous substrate also showed an increase in Raf-1-associated kinase activity. An inhibitor of protein kinase C, H7, inhibited the proliferation as well as the Raf-1 phosphorylation in response to the proliferative signal of anti-Ig. Further, downregulation of protein kinase C by the treatment with 12-phorbol 13-myristic acid significantly abrogated the induction of Raf-1 phosphorylation. These results suggest that, in human B-cells, Raf-1 protein may be involved in the signal transduction pathway mediated by surface immunoglobulin, and that it may be, at least partially, phosphorylated by activated PKC.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Spontaneous firing level distinguishes the effects of NMDA and non-NMDA receptor antagonists on the ganglion cells in the cat retina.

Different responses of retinal ganglion cells to iontophoretically applied NMDA receptor antagonists and non-NMDA receptor antagonists were studied in anaesthetized cats. Cells with normal range of spontaneous firing and those with abnormally high spontaneous firing levels showed a different response to these drugs. Both visually driven and spontaneous firing of cells with 'normal' spontaneous firing level were blocked by non-NMDA receptor antagonists, but not by NMDA receptor antagonists which often raised spontaneous firing. In contrast, the responses of cells with abnormally high spontaneous firing level were blocked effectively by NMDA antagonists including MK-801, an NMDA channel blocker, as well as by non-NMDA receptor antagonists. The results suggest that under normal physiological conditions, NMDA receptors which are not involved in synaptic transmission may play a role in reducing the resting discharge level of the retinal ganglion cells. NMDA receptors, however, appear to open ion channels in response to glutamate input when ganglion cells become abnormally depolarized.

2-Amino-5-phosphonovalerate↗

Intraoperative irradiation in resected carcinoma of the pancreas and portal vein.

We developed a new method that provides a wide retroperitoneal irradiation field for patients with cancer of the pancreas in whom a long invaded portal vein is resected during intraoperative radiotherapy. This method involves the use of a venous bypass with a heparinized catheter that does not require systemic anticoagulation or a pump. Anastomosis is completed after intraoperative radiotherapy. Mean (+/- SD) duration of the venous bypass was 3.0 +/- 1.5 hours (range, 2.0 to 6.6 hours), during which no abnormalities of systemic blood pressure, heart rate, and electrocardiographic activity and no signs of congestion of the intestines were observed. Eleven patients were treated with this method, and no complications ascribed to intraoperative radiotherapy or venous bypass were found. We recommend this method as safe and simple for expanding the irradiation field for intraoperative radiotherapy in patients with pancreatic cancer in whom the portal vein is resected.

Adult↗

Evidence that an iron chelator regulates collagen synthesis by decreasing the stability of procollagen mRNA.

Iron chelation has been shown previously to decrease collagen synthesis at a posttranslational level by inhibiting prolyl 4-hydroxylase, one of the key enzymes in collagen metabolism. On the other hand, recent in vivo studies of iron overload in rats suggest that iron could specifically activate collagen gene expression in liver tissues. These findings led us to investigate whether iron chelation might also affect collagen gene expression and posttranslational modification. Our data indicate that alpha,alpha'-dipyridyl, an iron chelator, at a concentration of 1 mmol/L, decreased steady-state levels of type I procollagen messenger RNA by 42% (p less than 0.001) without affecting beta-actin messenger RNA levels. Nuclear runoff studies demonstrated that transcription of the type I procollagen gene was unchanged by alpha,alpha'-dipyridyl. However, the turnover rate of type I procollagen messenger RNA was increased by 30%. This pretranslational inhibition of collagen synthesis was not due to decreased lipid peroxidation, because thiobarbituric acid-reactive substances were unchanged by alpha,alpha'-dipyridyl. However, cycloheximide totally abolished the effect, indicating that de novo protein synthesis was required.

2,2'-Dipyridyl↗

Palliative radiotherapy of bone metastasis.

We analyzed the effects of radiotherapy on 226 sites of metastatic bone tumors from 1981 to 1984, and on 157 sites of bone metastases of prostate cancer from 1970 to 1988. The radiation effect on pain relief was recognized in about 90% of cases within the dose of 20Gy to 30Gy, and there were not many differences in these effects according to the original tumors or histological types. In prostate cancer, the sites which needed re-irradiation were not recognized within 6 months after irradiation, and only 12 out of 80 sites (15%) that could be observed after more than 6 months needed re-irradiation due to recurring pain. As more than 60% of the patients with prostate cancer who needed irradiation to control bone metastases died within a year, to get pain relief by irradiation immediately and safely was thought to be very useful from the viewpoint of useful life. One patient was irradiated on 16 sites and 2 of these 16 sites received 4 treatments of irradiation and the shortest interval was 10 months and the longest one was 18 months.

Bone Neoplasms↗

Diurnal variations in the electroretinographic c-wave and retinal melatonin content in rats with inherited retinal dystrophy.

The inability of retinal pigment epithelium to phagocytose shed photoreceptor disks is a cause of retinal degeneration in the Royal College of Surgeons rat; retinal pigment epithelial phagocytosis and disk shedding are regulated by the diurnal rhythm of retinal melatonin level. The diurnal rhythms of the electroretinogram (particularly that of the retinal pigment epithelial potential, the electroretinographic c-wave) and retinal melatonin content were thus investigated in Royal College of Surgeons rats from postnatal day 17 to 24, the period preceding retinal degeneration. The amplitudes of both the b- and c-waves of the electroretinogram fell significantly during the peak time of rod disk shedding and rose after the time of expected light off in the control and dystrophic rats. While the b-wave rhythms did not differ between the two strains, diurnal changes in the c-wave were significantly less distinct in the dystrophic rats than in controls. This difference may reflect lack of phagocytosis in dystrophic rats. Furthermore, the ERG c-wave was significantly larger and prolonged, and the retinal melatonin content higher, in dystrophic rats of this age group than in controls. It appears that retinal melatonin metabolism may play an important role in the maintenance of retinal pigment epithelial and photoreceptor function.

Animals↗

Combined effects of ozone and cigarette smoke on airway responsiveness and vascular permeability in guinea pigs.

The effects of combined exposure to ozone and cigarette smoke on airway responsiveness and tracheal vascular permeability, compared with those of single exposure were examined in guinea pigs. Airway responsiveness was assessed by measuring the specific airway resistance (sRaw) as a function of increasing concentration of inhaled methacholine aerosol immediately, 5 hr, and 24 hr after exposure. In a parallel study, tracheal vascular permeability was quantified by measuring the tracheal extravasation of intravenously administered Evans blue dye. Neither exposure to 1 ppm ozone for 30 min nor 5 puffs of cigarette smoke increased airway responsiveness or vascular permeability at any time after exposure. Combined exposure to 1 ppm ozone for 30 min and 5 puffs of cigarette smoke caused airway hyper-responsiveness and increased vascular permeability immediately after exposure. Exposure to 1 ppm ozone for 90 min increased both airway responsiveness and vascular permeability immediately after exposure. Exposure to 10 puffs of cigarette smoke increased airway responsiveness but not vascular permeability immediately after exposure. Combined exposure to 1 ppm ozone for 90 min and 10 puffs of cigarette smoke increased both airway responsiveness and vascular permeability immediately after exposure. The combined exposure to ozone and cigarette smoke thus increased both airway responsiveness and tracheal vascular permeability to a greater extent than did exposure to a single agent, suggesting that a combination of air pollutants has a more deleterious effect both on airway responsiveness and on tracheal vascular permeability than does either agent alone in guinea pigs.

Airway Resistance↗

A case of Rathke's cleft cyst within a pituitary adenoma presenting with acromegaly--do "transitional cell tumors of the pituitary gland" really exist?

A case of multiple large Rathke's cleft cyst within a pituitary adenoma presenting with acromegaly is reported. Rathke's cleft cyst within a pituitary adenoma is rare condition, and this is the first report of such a case presenting with acromegaly. An electron microscopic and an immunohistochemical analysis proved that the cyst within the pituitary adenoma of this case differs from cysts found in the embryonic stage of the pituitary gland.

Acromegaly↗

The relationship between c-myc protein expression, the bromodeoxyuridine labeling index and the biological behavior of pituitary adenomas.

To clarify the relationship between the percentage of c-myc protein-labeled cells, the bromodeoxyuridine (BrdUrd) labeling index (LI) and clinical malignancy in pituitary adenomas, we studied 31 cases of pituitary adenomas. Tumor invasiveness, recurrence, tumor size and the length of illness were evaluated from operative findings, magnetic resonance imaging findings, and the clinical course. Each pituitary adenoma was scored to represent the degree of clinical malignancy. An hour before excision of the tumor, we administered BrdUrd intravenously. Surgical materials were fixed in 70% alcohol and embedded in paraffin. Both hematoxylin and eosin staining and immunohistochemical staining were performed using a monoclonal antibody for both anti-BrdUrd and anti-c-myc protein. Among pituitary adenomas, there was a significantly low percentage of c-myc protein-labeled cells in cases with acromegaly. The percentage of c-myc protein-labeled cells in the pituitary adenomas tended to increase with increase with the total scores of clinical malignancy. The BrdUrd LI was lower than 1% in almost all cases of pituitary adenomas, and it showed no correlation with their clinical malignancy. In conclusion, determination of the percentage of c-myc protein-labeled cells in pituitary adenomas proved to be useful for evaluating their clinical malignancy.

Adenoma↗

Cloning and characterization of a repetitive sequence from Pneumocystis carinii.

Four repetitive sequence clones measuring 10.9-23.4 kb in length were isolated from the genomic library of Pneumocystis carinii. Restriction enzymes mapping and cross-hybridization studies revealed that these clones are interrelated and that they derive from the common repeat unit, which is specific for P. carinii. Dot-blot analysis suggested that the copy number of the repeat sequence is about 100, assuming that the genome size is 1.5 x 10(7) bp. Interestingly, the repetition unit extended over at least 23.4 kb and included long, 5.2-kb inverted repeats, for example, A-B-A'-C, in which A' is the inversion of A.

Blotting, Southern↗

Prolonged lung retention of 123I-IMP in pulmonary fibrosis.

We compared radiographic findings and the retention of N-isopropyl- p[123I]-iodoamphetamine (123I-IMP) in 23 patients with pulmonary fibrosis. During the 30 minutes following a rapid injection of 55.5 MBq of 123I-IMP into the antecubital vein, the image of regional activity was stored. After this, 185 MBq of 99mTc-MAA was injected and its image was stored to determine the region of interest. The half time (T1/2) of 123I-IMP release from the lung was calculated in each pixel between 10 and 25 minutes after the injection. Chest roentgenograms were taken, and the lung field was divided into 6 portions (right upper, middle and lower, and left upper, middle and lower). A quantitative score was assigned to the radiographic finding (X-ray score). The T1/2 values in the above patients were longer than the T1/2 values in normal subjects. Prolonged T1/2 values were observed in the lung fields which had high X-ray scores. The X-ray scores and the T1/2 values in corresponding areas had a positive relation.

Amphetamines↗

Plasma growth hormone (GH) responses to corticotropin-releasing hormone in patients with acromegaly--the effect of dexamethasone pretreatment and the comparison with GH responses to thyrotropin-releasing hormone, gonadotropin-releasing hormone and GH-releasing hormone.

It has been reported that paradoxical GH responses to corticotropin-releasing hormone (CRH) occur in only few patients with acromegaly. However, we have observed such responses in 7 of 14 active acromegalic patients. Therefore, we have studied the GH responses to thyrotropin-releasing hormone (TRH) (500 micrograms, iv), gonadotropin-releasing hormone (LHRH) (100 micrograms, iv) and GH-releasing hormone (GHRH) (100 micrograms, iv) in these patients to examine the relationships between the GH responses to CRH and the responses to these hypothalamic hormones. Further, these patients received human CRH (1-41) NH2 (100 micrograms, iv) with or without dexamethasone (Dex) pretreatment (1 mg/100 ml saline, iv, from -30 to +30 min) to study the mechanism of CRH-induced GH secretion, and a perifusion experiment was performed using adenoma tissue obtained at surgery from one patient (10(-7) M CRH and TRH were added) to elucidate whether CRH acts directly at the pituitary level. Aberrant GH responses induced by CRH were found in 7 of 14 (50%) acromegalic patients (TRH responders: 10/13, 77%; LHRH responders: 2/9, 22%; GHRH responders: 10/12, 83%). In these patients, percent GH increment induced by CRH ranged from 81 to 144% (Mean +/- SE, 118 +/- 8%), and the GH peak (19 +/- 3 min) appeared as early as after TRH (23 +/- 4 min, N = 10).(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗