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Biomedical subjects

Y Suda

Publications and source records attributed to Y Suda.

At least 109 records · Page 6Linked to original sources
PubMed1990

Env-derived gp55 gene of Friend spleen focus-forming virus specifically induces neoplastic proliferation of erythroid progenitor cells.

A group of retroviruses carrying truncated viral genes has recently been suggested as the cause of new patterns of diseases. One such virus is the replication defective component of the Friend murine leukemia virus (F-MuLV) complex, called Friend spleen focus forming virus (F-SFFV). This virus induces erythroblastosis, and a virion envelope-related glycoprotein, gp55, encoded by F-SFFV has been suggested as the pathogenic gene. The role of the gp55 gene is, however, yet unclear in the apparently multistep erythroleukemogenesis. By separately producing transgenic mice harboring the whole F-SFFV DNA, the gp55 gene alone under the control of the retroviral long terminal repeat (LTR) and the gp55 gene under the control of cytoplasmic beta actin transcriptional regulatory unit, we show here that the gp55 gene is capable of inducing neoplastic proliferation of erythroid progenitor cells specifically in the absence of helper virus and other F-SFFV sequences. Under the control of the viral LTR the gp55 expression was detected only in leukemic tissues, but under the control of cytoplasmic beta-actin regulatory sequences, the gp55 was also expressed in a variety of normal tissues including preleukemic normal spleens. The development of erythroleukemia was suppressed under the genetic background of C57B1/6 mouse (resistant to F-MuLV; Fv-2rr), and required additional events even under the background of DDD mouse (susceptible to F-MuLV; Fv-2ss). The p53 and Spi-1 genes were frequently aberrant in transplanted tumors and cell lines derived from them, but were not in primary leukemic spleens.

Animals↗
PubMed1990

Induction of a variety of tumors by c-erbB2 and clonal nature of lymphomas even with the mutated gene (Val659----Glu659).

The c-erbB2 gene is expressed uniquely in fetal epithelium in vivo and has been suggested to contribute to the development and/or progression of adenocarcinomas in man. In order to assess the oncogenicity of the c-erbB2 gene in vivo, normal c-erbB2 and mutant c-erbB2 encoding glutamic acid instead of valine at position 659 within the transmembrane domain were introduced into mice under the transcriptional regulatory unit of mouse mammary tumor virus long terminal repeat (MMTV-LTR) or immunoglobulin enhancer--SV40 early gene promoter (Ig/Tp). In transgenic mice with normal c-erbB2 under MMTV-LTR, not only adenocarcinomas but also a variety of tumors including B lymphomas were induced at relatively late onset. Induction of pre-B cell lymphomas with normal c-erbB2 was also observed using the Ig/Tp regulatory unit within 6-10 months in some members of one transgenic family among seven lines established. In contrast, with the mutant c-erbB2 under the Ig/Tp regulatory unit, the lymphoma was induced neonatally in all members of four transgenic families among ten lines obtained. However, the immunoglobulin heavy chain gene rearrangement pattern indicated that even with the mutant c-erbB2 the induced lymphomas were clonal.

Adenocarcinoma↗
PubMed1990

Amino acid study of cerebral gliomas using positron emission tomography--analysis of (11C-methyl)-L-methionine uptake index.

Sixteen patients with gliomas (7 low grade, 9 high grade) were examined using positron emission tomography (PET) with intravenous administration of 22.2 MBq/kg (0.6 mCi/kg) of (11C-methyl)-L-methionine (C-11 Met). The tracer uptake in regions of interest was calculated on PET images taken 45 minutes after injection; the uptake index was represented as a percentage of the total count in the arterial blood summed over 45 minutes. C-11 Met uptake indices in the tumors ranged from 0.020 to 0.041% with a mean of 0.032% for the low-grade gliomas and from 0.013 to 0.044% with a mean of 0.036% for the high-grade gliomas. These indices significantly increased as compared with those in the contralateral gray matter (0.008-0.032% with a mean of 0.023%; p less than 0.01 vs. low-grade gliomas, p less than 0.001 vs. high-grade gliomas). In the low-grade gliomas, C-11 Met PET images clearly depicted the existence and even the extent of the tumors, although x-ray computed tomography (CT) did not always distinguish tumoral lesions. In the high-grade gliomas, the areas of tracer accumulation regionally extended to peritumoral low density on CT scans, where malignant tumor cell infiltration was proved by operative and follow-up CT findings. C-11 Met may be a useful radiopharmaceutical for differential diagnosis of gliomas, and the accuracy of tumor localization will give us a better rationale in therapeutic strategies for surgery and radiation therapy of gliomas.

Adolescent↗
PubMed1990

[Activity of cytochrome P450 in the stomach, with special reference to postoperative survival rate of patients with gastric cancer treated by tegafur].

In routine histological preparation of gastric wall and liver specimens, immunohistochemical study of P450 was performed in the total of 116 absolutely noncurative resection of gastric cancer which followed by postoperative administration of tegafur. P450 in the liver, which considered to play a main role of tegafur activation, was strongly stained and correlated well with that of the stomach. Divided the cases into 3 groups from the degree of immunohistochemical staining of P450, postoperative survival was significantly correlated with the intensity of staining in the stomach. And the more the stage of gastric cancer advanced, the less the tissue P450 was stained. From the results obtained, reasonable consecutive administration of tegafur would be possible by immunohistochemical checking the P450 in the gastric wall.

Combined Modality Therapy↗
PubMed1990

[A superficial carcinoma arising from a solitary hepatic cyst].

Reported is a rare superficial papillary adenocarcinoma arising from a congenital cyst, along with a survey of pertinent cases in the world literature. A 43-year-old male with a huge hepatic cyst was admitted to hospital for further examination. Since the cystic drainage done for alcoholic fixation was seromucinous initially but later contaminated by bile, an operation was initiated for dome resection and the closure of the biliary communication. At the time of the deroofing, however, small granulomas were found. And those were confirmed as being malignant by frozen section. Thus, an extended right lobectomy was performed for therapy. From its history and nature, this was considered to be a cancer arising in a congenital hepatic cyst.

Adenocarcinoma, Papillary↗
PubMed1990

[Biliary and pancreatic excretion of methotrexate (MTX) and 5-FU on the MTX/5-FU sequential therapy].

On the postoperative adjuvant MTX/5-FU sequential therapy, biliary and pancreatic excretion of both drugs was studied through the hepatic and pancreatic drainages in pancreatoduodenectomized patients. MTX: 100 mg/m2 of bolus injection and 5-FU: 800 mg/m2 of sequential one hour drip infusion were used in this series. Biliary excretion of MTX was reached peak concentration at 90 min, its mean value being 5 fold of serum concentration. During the observation period of 4.5 hours, the recovery of MTX in bile was calculated as 3-12% which presumed to be more because of still continuing biliary excretion on the terminal observation. Pancreatic excretion of MTX was minimal and not so as to have further clinical meaning. Though the serum concentration of 5-FU was raised up with its infusion, biliary and pancreatic outputs of 5-FU were small, each value showing one third compared with at a single shot of the same doses. From the obtained mode and time lag of concentration curves of both drugs, the rationale of per oral and earlier administration of Leucovorin was discussed as a possible way of removal of MTX from intestine.

Adult↗
PubMed1990

[A type IIa early carcinoma in multiple submucosal cysts of the stomach--a case report].

The case of a 60-year-old Japanese man with an early gastric carcinoma in submucosal multiple cysts is presented, and the morphology and histogenesis had complained of dysphagia, and an upper gastrointestinal barium study and endoscopy revealed an irregular-shaped, flat polypoid tumor in the antral mucosa. The resected stomach had a polypoid lesion, 11.0 x 12.0 cm, but no erosion or ulcer in the greater antral curvature was seen, and cut section showed many cysts containing mucus. A subsequent histological examination revealed a well differentiated adenocarcinoma of the mucosal layer. This early carcinoma was sited on and surrounded by multiple cystic lesions. These histological findings suggested that this carcinoma had developed from the mucosa that had an underlay of submucosal cysts.

Adenocarcinoma↗
PubMed1989

[Prognostic significance of regional blood flow, blood volume, oxygen extraction fraction, and metabolic rates of oxygen and glucose as measured by positron emission tomography in patients with gliomas].

We tested clinical significance of hemocirculatory and metabolic values and ratios as determined by positron emission tomography (PET) in twenty-three patients with cerebral gliomas. Regional cerebral blood flow (rCBF), blood volume (rCBV), oxygen extraction fraction (rOEF), and metabolic rates of oxygen (rCMRO2) and glucose (rCMRGl) were measured prior to treatment using PET with 15O2, C15O, 15O2, and 18F-fluorodeoxyglucose tracers. For the quantitative analysis, regions of interest were delineated on tumor regions including peak activity, the contralateral gray and white matter. The regional values and the ratios of tumor/gray matter and tumor/white matter were compared to performance status (PS) according to the five functional grades system which are defined by the Japan Society for Cancer Therapy, tumor progression-free time (PFT), survival time (ST) from the time of the PET study, regardless of type of therapy. As with rCMRGl, the tumor values and the ratios of tumor/gray matter and tumor/white matter correlated significantly with PS (tumor/gray: p less than 0.05, tumor/white: p less than 0.01). Both the gray rCBF and the tumor/gray rCBF ratio had close relation with PS and/or PFT (p less than 0.05). The gray matter rCMRO2 and the tumor/gray matter rCMRO2 ratio related significantly (gray matter: p less than 0.01, tumor/gray: p less than 0.05) to each clinical parameter of PS, PFT, and ST. These indicate that values and ratios as determined by PET can be useful in predicting the prognosis of glioma patients.

Adolescent↗
PubMed1989

A spider toxin (JSTX) inhibits L-glutamate uptake by rat brain synaptosomes.

Joro spider toxin (JSTX), a specific blocker of glutamate receptors, was found to exert a prominent suppressive action on the Na+-dependent binding of L-glutamate to synaptic membranes and on glutamate uptake by synaptosomes in a dose-dependent manner. In contrast, the synthesized 2,4-dihydroxyphenylacetylasparagine (2,4-DHPA-ASN), a common moiety of spider toxins, which has been shown to exhibit almost the same activity as intact JSTX with respect to the inhibition of Na+-independent glutamate binding to its synaptic membrane receptors, shows lower potency in inhibiting Na+-dependent binding and uptake of L-glutamate. From these findings, it is clear that JSTX has the ability to inhibit not only L-glutamate binding to its synaptic membrane receptors but also L-glutamate uptake by synaptosomes, and that polyamines linked to 2,4-DHPA-ASN in the molecule of spider toxins may participate in the inhibition of L-glutamate uptake.

Animals↗
PubMed1989

Thymic atrophy characteristic in transgenic mice that harbor pX genes of human T-cell leukemia virus type I.

The human T-cell leukemia viruses (HTLV) are associated with T-cell malignancies in humans. The malignant transformation occurs after a long latency in some carriers, and its mechanism appears to be distinct from that of other classes of retroviruses which induce transformation through viral or cellular oncogenes. A widely postulated explanation is that the products of novel pX genes transactivate endogenous cellular genes which lead to tumor development in T cells. To directly examine the pathological effects of pX genes in vivo, we produced transgenic mice harboring the HTLV type I pX genes under several regulatory units: HTLV type I long terminal repeat, immunoglobulin enhancer-simian virus 40 promoter, and mouse mammary tumor virus long terminal repeat. Atrophy of the thymus was characteristic in these mice no matter which regulatory unit directed the expression of the genes.

Animals↗
PubMed1989

5-Fluorouracil derivatives with serum protein binding potencies.

To develop an optimal delivery system for 5-fluorouracil (5FU) using serum protein as a drug carrier, a series of its benzyl derivatives was synthesized. Then their binding to the serum protein was investigated by equilibrium dialysis. The benzyl derivatives of 5FU were strongly bound to rat plasma protein or human serum albumin. The bound percentage increased with increasing hydrophobicity. It was suggested that the benzyl derivative of 5FU existed in the blood as a complex with serum albumin and circulated for a long time as a polymeric drug does.

Animals↗
PubMed1989

[Radiochemotherapy-related changes in the brain parenchyma of glioma patients evaluated repeatedly by C15O2, C15O, 15O2, and 18F-fluorodeoxyglucose (FDG) PET].

The aim of this study was to evaluate effects of radiochemotherapy on blood flow and metabolism using C15O2, C15O, 15O2, and 18F-fluorodeoxyglucose positron emission tomography (PET). Conventional, external radiotherapy (180-200 cGy/5 fractions/week) using 60Co or a 10 MV linear accelerator was given in conjunction with chemotherapy of nimustine hydrochloride (ACNU) and tegafur (FT-207) in eight patients with gliomas. Regional cerebral blood flow (rCBF), blood volume (rCBV), oxygen extraction fraction (rOEF), oxygen consumption (rCMRO2), and glucose consumption (rCMRG1) were longitudinally examined before the treatment, and at an early stage (within one month) and a late stage (three to thirty-one months with a mean of 12 months) after radiochemotherapy. Contralateral gray and white matter to the tumor was selected as regions of interest (ROIs), because these portions were irradiated with larger doses compared to other brain parenchymal regions through parallel opposing fields. Maximum doses to the ROIs varied between 20 and 61 Gy. Calculated as a function of time-dose-fractionation, nominal standard doses (NSD) ranged from 566 to 1729 ret, and 344 to 1062 neuret; equivalent doses (ED) equaled 432 to 1327 rads. At the early stage, rCBF and rCBV increased in the contralateral gray and white matter; gray matter rOEF decreased significantly (p less than 0.05 by a paired-t test) from that of the pretreatment study, probably due to decompression of the tumor bulk and radiochemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Immunological response and oesophageal varices in PBC.

A retrospective study was made of the clinical features, especially oesophageal varices, of 93 patients with PBC. The 5 year survival rate of asymptomatic PBC patients was 88.7% and that of symptomatic PBC was 43.7%. The 5 year survival rate of the group with oesophageal varices was 44.0% and that of the group without varices was 68.8%. The 5 year survival rate of the patients with high-risk varices was 39.1% and of those without high-risk varices was 67.9%. Management of variceal bleeding in PBC patients was considered very difficult. In prognostic study, the patients with the prophylactic therapy were better than the patients with emergency or elective therapy. The antiM8 (a subtype of antimitochondrial antibody) positive patients had poor prognosis compared with antiM8 negative patients. Therefore, it was concluded from these data that some kind of treatment was necessary for patients with high-risk varices. In particular, it was considered necessary to monitor closely the patients whose serum alkaline phosphatase levels had remained high.

Adult↗
PubMed1989

[Malignant astrocytoma following radiotherapy in pituitary adenoma: case report].

A case of malignant astrocytoma following radiotherapy for pituitary adenoma is presented in detail with a review of the literature. A 38 year-old housewife had developed a growth-hormone secreting pituitary adenoma, and received a total of 50 Gy at the pituitary region. Four years and six months later, she began suffering headache and vomiting. Computed tomography showed an extensive low density with ring enhancement in the right temporal region, corresponding to the previously irradiated field. A right frontotemporoparietal craniotomy was carried out, and a soft and reddish tumor was partially removed. The histological diagnosis was that of malignant astrocytoma. The patient was submitted to postoperative radiochemotherapy, receiving a total of 60 Gy, nimustine hydrochloride (ACNU), and tegafur (FT). Subsequently, after three months of clinical relief, she developed tumor regrowth, and died four months later. The present case fulfills the criteria for radiation-induced tumor established by Cahan et al.: A tumor location within irradiated area, no evidence of tumor prior to radiotherapy, a long latency period between radiation and tumor occurrence, and histological verification of the tumor. Thirty-nine cases of radiation-induced gliomas including the present case have been reported in the literature. It is noteworthy that the majority occur in the younger age bracket. Male preponderance is noted as it is in primary cerebral gliomas. The primary lesions for radiation frequently include leukemia and lymphoma. Craniopharyngioma, pituitary adenoma, and medulloblastoma etc are also included.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗
PubMed1988

Early and late stage positron emission tomography (PET) studies on the haemocirculation and metabolism of seemingly normal brain tissue in patients with gliomas following radiochemotherapy.

Haemocirculatory and metabolic changes in seemingly normal brain tissue following radiochemotherapy including nimustine hydrochloride (ACNU) and tegafur (FT) were analyzed using oxygen-15 and fluorine-18 positron emission tomography (PET) in seven patients with gliomas. At an early stage (within one month) after radiochemotherapy, marginal increases in regional cerebral blood flow (rCBF) and cerebral blood volume (rCBV) were found contralateral to the tumour in gray matter which was apparently normal brain structure, as seen on computerized tomography (CT). The oxygen extraction fraction (rOEF) decreased significantly (p less than 0.05 by a paired-t test) from that of the pretreatment study, due to surgical decompression and radiochemotherapy. At the late stage (three to thirty-one months with a mean of thirteen months), rCBF decreased significantly from the early stage study (p less than 0.05); oxygen consumption (rCMRO2) fell in all cases significantly from the pretreatment study (p less than 0.01) and from the early stage study (p less than 0.05); consequently, rOEF remained unchanged at a level similar to the early stage study. Glucose consumption (rCMRG1) increased slightly as compared with the early stage study but failed to be restored to the level of the pretreatment study. Noteworthy was a coupling reduction of rCBF and rCMRO2--presumably, a late delayed effect of radiochemotherapy. These preliminary results indicate that with PET studies it may be possible to predict damage to normal brain tissue after radiochemotherapy.

Adolescent↗
PubMed1988

Active ras and myc oncogenes can be compatible, but Sv40 large T antigen is specifically suppressed with normal differentiation of mouse embryonic stem cells.

The pathobiological effects of oncogenes on normal differentiation of mouse embryonic stem cells from 4-day embryos were examined by introducing active ras, myc, and SV40 large T genes, all driven by mouse metallothionein I enhancer and promoter. Stem cell clones R5, M3, and T2 for ras, myc, and SV40 T genes, respectively, were particularly chosen for analyses because of their higher levels of transgene expression and their diploid chromosomal constitutions. These stem cells were then introduced into host 4-day embryos and the embryos were allowed to develop in the uterus of foster mothers. The stem cells colonized the tissues as extensively as the parent cells and gave rise to adult chimera with no apparent loss or abnormality of the embryos. The active ras and myc oncogenes introduced were expressed not only in the stem cells, but also in the developing embryos and in a variety of tissues of adult chimeras. However, although T antigen was originally expressed in the stem cells, it was not expressed in either developing embryos or tissues of adult chimeras. Induced by retinoic acid treatment in vitro or by subcutaneous grafting, this suppression of T-gene expression was also confirmed in differentiated progeny cells from several stem cell clones expressing T antigen. Permanent lines of fibroblast-like cells could be established at higher frequency from primary cultures of tissues of chimera, subcutaneous differentiated cells, and in vitro differentiated cells derived from T2 cells, and all these clones reexpressed T antigen. The results suggest that active myc and ras genes can be compatible with normal differentiation of the stem cells, but the expression of T antigen is specifically suppressed with recognition of its coding domain.

Animals↗
PubMed1988

MR imaging vs CT in subacute sclerosing panencephalitis.

The MR findings in three patients with subacute sclerosing panencephalitis were reviewed and compared with CT findings in the same patients. Long-T2 lesions were demonstrated in each case, although their distribution varied with the clinical stage of the disease. MR, especially T2-weighted imaging, appears to be of great utility in the assessment of subacute sclerosing panencephalitis.

Adolescent↗