Biomedical subjects

S Sakuma

Publications and source records attributed to S Sakuma.

At least 163 records · Page 9Linked to original sources

PubMed1994

[Clinical application of AMI-25 (superparamagnetic iron oxide) for the MR imaging of hepatic tumors: a multicenter clinical phase III study].

We performed phase III clinical study of AMI-25 (Superparamagnetic iron oxide) for hepatic tumors in 163 cases at the 17 institutions in Japan. In overall evaluation, 141/159 cases (88.7%) were evaluated "useful" or "very useful" for clinical usefulness. For efficacy including the signal to noise ratio (S/N) of liver and the tumor-liver contrast to noise ratio (C/N), 89.6% of hepatocellular carcinomas and 95.0% of metastatic liver cancers were evaluated "effective" or "very effective", respectively. The mild adverse reactions were shown in 10 cases (6.1%), but they disappeared within 25 minutes. The serum iron and ferritin increased and the unsaturated iron binding capacity (UIBC) decreased, but they were showing a tendency to go back to their normal ranges. The AMI-25 (10 mumoles Fe/kg) was proved to be useful and safe contrast agent for the liver tumors in MRI.

Adolescent↗

PubMed1994

Identification of mutation sites of a temperature-sensitive mutant of HCMV DNA polymerase activity.

The human cytomegalovirus (strain Towne) temperature-sensitive mutant ts 256 exhibits a virus specific DNA polymerase-negative phenotype. The position of the mutation of ts 256 was determined by three step marker-rescue assays to be within a 5.1 kb XbaI-BamHI fragment between map unit 0.33 and 0.35 in a HindIII-D fragment located in a long unique region. Nucleotide sequencing showed that the 5.1 kb fragment contained three open reading frames corresponding to those of the genes for UL52, UL53 and UL54 (DNA polymerase gene), respectively, of strain AD169. The functions of UL52 and UL53 are unknown. Comparison of the DNA sequences of the 5.1 kb fragments of the wild-type and ts 256 mutant revealed two base changes within UL53 and UL54, respectively, which result in amino acid substitutions. The mutation in the UL54 gene was located within a distinct conserved region VI common to alpha-like DNA polymerases, suggesting that this base change would be responsible for DNA negative phenotype.

Amino Acid Sequence↗

PubMed1994

Effect of 13-hydroperoxy-9,11-octadecadienoic acid (13-HPODE) on arachidonic acid metabolism in rabbit platelets.

1. The effect of 13-hydroperoxy-9,11-octadecadienoic acid (13-HPODE) on the formation of thromboxane (TX) B2, 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT) and 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) from exogenous arachidonic acid in washed rabbit platelets was examined. 2. 13-HPODE inhibited TXB2 and HHT formation without affecting 12-HETE production. 3. 13-Hydroxy-9,11-octadecadienoic acid which was produced rapidly from 13-HPODE, did not suppress the formation of TXB2 and HHT, indicating the requirement of the hydroperoxy moiety for the inhibitory effect of 13-HPODE on TXB2 and HHT formation. 4. Experiments utilizing mannitol and dimethyl sulfoxide (hydroxy radical scavengers) revealed that the action of 13-HPODE is not due to hydroxy radicals which are expected to be formed from 13-HPODE. 5. These results suggest that 13-HPODE is a selective inhibitor of platelet cyclo-oxygenase and may have functional effects within platelets.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

PubMed1994

Detection of the human cytomegalovirus gene in placental chronic villitis by polymerase chain reaction.

Placental chronic villitis was observed in 44 cases (2.12%) of 2,073 histologically examined placentas. Infiltrating lymphocytes in chronic villitis were determined by immunohistochemistry to be predominantly helper/inducer T cells. Detection of the cytomegalovirus (CMV) gene was performed on paraffin-embedded sections by polymerase chain reaction (PCR) using two different primers (CMV immediate early gene and CMV late antigen gp 64). Both CMV immediate early gene and late antigen gp 64 gene were detected in one case. Cytomegalovirus late antigen gp 64 gene was observed in only three cases. Among these four cases, the cytomegalic inclusion body was observed only in a single case with light microscopic examination. In two cases generalized CMV infection was manifested during the early infantile period and the patient died of the disease. The other two cases were asymptomatic. Our data suggest that approximately 9% of the cases of chronic villitis are caused by CMV infection, and most of them are difficult to detect morphologically. Detection of CMV gene by PCR using primers, especially late antigen gp 64 gene, is very useful for assessing the cause of placental chronic villitis.

Antigens, Viral↗

PubMed1994

Inhibition of 15-hydroxy prostaglandin dehydrogenase activity in rabbit gastric antral mucosa by 13-hydroperoxyoctadecadienoic acid.

The effect of 13-hydroperoxyoctadecadienoic acid (13-HPODE), a hydroperoxy adduct of linoleic acid (LA), on the activities of prostaglandin (PG) synthesizing and catabolizing enzymes in rabbit gastric antral mucosa was examined. 13-HPODE had no effect on the synthesis of PGE2, PGF2 alpha and PGD2 from exogenous arachidonic acid in the microsomal fraction of the gastric mucosa at concentrations ranging from 5-20 microM. On the other hand, at 1-10 microM, it inhibited the activity of 15-hydroxy PG dehydrogenase (PGDH), which catalyzes the initial step of catabolism of PGs, in a dose-dependent manner. The concentration required for 50% inhibition was approximately 1 microM. Experiments utilizing LA, 13-hydroperoxyoctadecadienoic acid and Fe2+ indicated the requirement of the hydroperoxy moiety for the inhibitory effect of 13-HPODE on the PGDH activity. These results suggest that 13-HPODE has the potential to increase the levels of biologically active PGs in gastric mucosa by preventing their inactivation and may have functional effects within the stomach.

Animals↗

PubMed1994

A case of cytomegalovirus mononucleosis associated with pleural effusion.

A 5 year old boy had a spiky fever accompanied by a mild pharyngitis, cervical lymphadenopathy and hepatosplenomegaly. Laboratory findings revealed leukocytosis with 26% atypical lymphocytes, and liver dysfunction. A chest X-ray showed pneumonia and a considerable amount of pleural effusion. Serum antibody titers for cytomegalovirus (CMV) were elevated significantly and CMV-DNA (polymerase chain reaction) was detected in the pleural effusion. Only 13 cases of pleural effusion associated with infectious mononucleosis have been reported previously in the literature, but there was no documentation that proved CMV infection. The case reported here suggests that the pleural effusion was caused by the infiltration of mononuclear cells to the pleura as a result of systemic inflammation, and the possible alternative of host immune response against CMV was related to recent Varicella zoster virus infection.

Antibodies, Viral↗

PubMed1994

Induction of the conversion of xanthine dehydrogenase to oxidase in rabbit liver by Cu2+,Zn2+ and selenium ions.

Effects of Cu2+,Zn2+,Fe2+ and selenium ions on the conversion of xanthine dehydrogenase to oxidase in rabbit liver were examined. Under basal conditions, xanthine oxidase activity represented only 16% of the total xanthine oxidase plus dehydrogenase activity. Cu2+ (2-10 microM), Zn2+ (5-30 microM) and selenium ions (5-100 microM) brought about the conversion of xanthine dehydrogenase to oxidase in a dose-dependent manner. The concentrations of Cu2+,Zn2+ and selenium ions required for increasing xanthine oxidase activity by 50% was approximately 4, 10 and 20 microM, respectively. On the other hand, Fe2+ had no effect on the conversion of the enzyme up to 100 microM. These results suggest that Cu2+,Zn2+ and selenium ions have the potential to modulate the conversion of xanthine dehydrogenase to oxidase in rabbit liver.

Allopurinol↗

PubMed1994

The first case of equine motor neuron disease in Japan.

A 9-year-old male horse showed emaciation, weakness and trembling and was euthanatized. Histopathological examinations revealed loss, swelling and chromatolysis of motor neurons throughout the spinal ventral horns, axonal degeneration of the ventral spinal roots. Eosinophilic cytoplasmic inclusions were distributed in degenerated spinal ventral neurons. Ultrastructurally, the inclusions consisted of aggregations of granular dense material and a few vesicles. They reacted positively with polyclonal antibody against ubiquitin. The present case was diagnosed as equine motor neuron disease, which has recently been reported in North America and the United Kingdom.

Animals↗

PubMed1994

Myocardiopathy and expression of atrial natriuretic peptide in rats with monocrotaline-induced pulmonary hypertension.

Myocardiopathy in rats with monocrotaline (MCT)-induced pulmonary hypertension was investigated morphologically and immunohistochemically. A single subcutaneous injection of MCT (60 mg/kg body weight) to SD rats produced progressive cardiac lesions. Histologically, the lesions were characterized by myocardial hypertrophy and myocardial degeneration followed by mononuclear cell infiltration and fibroblast proliferation in the right atrium and ventricle. Such histological changes began to be seen 3 weeks after injection and thereafter progressively developed in rats killed 4 and 5 weeks after injection. These findings indicate progressive hypertrophic myocardiopathy, due probably to pulmonary hypertension induced by MCT. Immunohistochemically, atrial natriuretic peptide (ANP)-positive myocardial cells were frequently observed in the left and right ventricle in MCT-treated rats killed 4 and 5 weeks after injection. The intensive immunopositive reaction was observed mainly in hypertrophic myocardial cells in the subendocardium of the right ventricle and also present in hypertrophic myocardial cells around injured areas consisting of degenerated myocardial cells, mononuclear cell infiltration and fibrosis. These findings suggest a close relationship between the ANP expression and cardiac hypertrophy in MCT-treated rats.

Animals↗

PubMed1994

Adrenocorticotropic hormone-independent bilateral adrenocortical macronodular hyperplasia: a case report and immunohistochemical studies.

A 55-year-old woman developed Cushing's syndrome due to ACTH-independent bilateral adrenocortical macronodular hyperplasia. Plasma ACTH was undetectable, and was not stimulated by administration of metyrapone, CRH, or insulin. Hypercortisolism was not suppressed by a high dose of dexamethasone, but was responsive to ACTH. Both adrenal glands were enlarged with a total weight of 200 g, and contained multiple nodules composed of two cell types (large clear cells and small compact cells). In immunohistochemical studies, P450c17 immunoreactivity was predominantly observed in small compact cortical cells, while that of 3 beta HSD was observed exclusively in large clear cortical cells. This pattern of expression of steroidogenic enzymes as well as histological and clinical features is considered to be unique to ACTH-independent bilateral adrenocortical macronodular hyperplasia.

Adrenal Cortex↗

PubMed1994

Antiproliferative effect of tumor necrosis factor-alpha on human glioblastoma cells linked with cell cycle arrest in G1 phase.

The effects of tumor necrosis factor-alpha (TNF) on proliferation and cell cycle alterations in human malignant glioma cell lines, SF-188 and LN-382, were investigated by flow cytometry with the bromodeoxyuridine-propidium iodide dual staining technique. Low concentrations of TNF (1-100 U/ml) suppressed the growth of SF-188 assessed by cell count, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, and thymidine incorporation assay, but not that of LN-382. After TNF treatment, the percentage of SF-188 cells in the G0/G1 phase increased, while the percentage of cells in the S phase decreased. LN-382 cells did not show any marked change in cell kinetics. TNF arrests certain human glioma cells in the G0/G1 phase resulting in reduction of deoxyribonucleic acid synthesis in the subsequent S phase, suppressing the proliferation pathway.

Brain Neoplasms↗

PubMed1994

High density lipoprotein inhibits platelet 12-lipoxygenase activity.

The effects of high density lipoprotein (HDL) and low density lipoprotein (LDL) on the formation of 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE), thromboxane (TX) B2 and 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT) in washed rabbit platelets were examined. HDL had a powerful inhibitory effect on 12-HETE formation, while it produced only a small increase in TXB2 and HHT formation. LDL did not affect the formation of 12-HETE, TXB2 and HHT. These results suggest that HDL is a selective inhibitor of platelet 12-lipoxygenase and may play a protective role in atherogenesis by preventing the generation of 12-HETE.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

PubMed1994

Effect of 13-hydroperoxyoctadecadienoic acid on prostaglandin synthesis in rabbit kidney medulla microsomes.

The effect of 13-hydroperoxyoctadecadienoic acid (13-HPODE) on the synthesis of prostaglandins (PGs) was examined in rabbit kidney medulla microsomes. Medulla microsomes were incubated with arachidonic acid in 0.1 M-Tris/HCl buffer (pH 8.0) containing reduced glutathione and hydroquinone and the PGE2, PGF2a and PGD2 formed were measured by high-pressure liquid chromatography using 9-anthryldiazomethane for derivatization. Under our incubation conditions rabbit kidney medulla was found to produce mainly PGE2. The addition of 13-HPODE inhibited the production of all three PGs to a similar extent. 13-Hydroxyoctadecadienoic acid did not suppress the formation of PGs, indicating the requirement of the hydroperoxy moiety for the inhibitory effect of 13-HPODE on PG formation. Experiments utilizing the native fatty acid linoleic acid and tert-butyl hydroperoxide suggested the importance of the fatty acid-derived hydroperoxide in PG synthesis by kidney medulla. We conclude that 13-HPODE is an inhibitor of renomedullary cyclooxygenase and may have functional effects within the kidney.

Animals↗

PubMed1993

[Kinetics of flomoxef sodium monitored with in vivo 19F NMR spectroscopy].

The potential usefulness of in vivo 19F NMR spectroscopy for the monitoring of flomoxef sodium (FMOX) kinetics was evaluated. In the experimental study using phantom the minimum concentration of FMOX of which signals could be monitored with 19F NMR spectroscopy was 16 micrograms/ml. In patients with intravenous bolus injection and drip infusion of FMOX (2 g/100 ml), signals from normal heart, liver, and kidney were clearly monitored with 19F NMR spectroscopy. In normal lung any signal was not detected, but in a lung with a cancer associated massive atelectasis the monitoring of signals was possible with 19F NMR spectroscopy in both intravenous and intraarterial injections. Monitoring of FMOX kinetics with in vivo 19F NMR spectroscopy will be useful in clinical applications.

Cephalosporins↗

PubMed1993

Responses of human glioblastoma cells to human natural tumor necrosis factor-alpha: susceptibility, mechanism of resistance and cytokine production studies.

Responses and susceptibility of 14 human glioblastoma cell lines to human natural tumor necrosis factor-alpha (TNF) were studied in vitro. Susceptibility of glioblastoma cells to TNF varied in experimental conditions applied. Most of glioblastoma cell lines were resistant to cytotoxic activity of TNF in a MTT assay at concentrations below 16 U/ml for 72 h exposure. However, TNF at higher dose, in prolonged exposure and against low density of target cells was antiproliferative for certain glioblastoma cultures. TNF exposure at 10 U/ml for 48 h suppressed DNA synthesis in 9 of 14 glioblastoma cultures, but increased in 3 cultures. In addition, colony forming assay showed anti-clonogenic activity of TNF in 5 of 6 glioblastoma cell lines tested. In spite of their low susceptibility to TNF, glioblastoma cells well responded to TNF stimulation at low dose (10 U/ml) for a short period in the absence of cell damage. Productions of Interleukin-6 (IL-6), IL-8-like activity, granulocyte-macrophage colony stimulating factor (GM-CSF), prostaglandin E2 (PGE2) and manganous superoxide dismutase (Mn-SOD) were enhanced or induced by the low-dose TNF stimulation. Mn-SOD, a protein protective against oxidative cell damage, was well induced in time- and dose-dependent manner, however did not correlate with TNF resistance. Whereas the levels of PGE2 in TNF-susceptible cell lines, H-4 and SF-188, were higher than those of other lines. In conclusion, most of glioblastoma cells are resistant to TNF cytotoxic effects, but highly responsive to TNF stimulation. Its effect on glioblastoma cells appears to modulate cell differentiation rather than to kill the cells.

Cell Division↗

PubMed1993

Human glioblastoma cells produce 77 amino acid interleukin-8 (IL-8(77)).

The production of interleukin 8 (IL-8), a neutrophil chemotactic factor, and its amino acid sequence were examined in glioblastoma cell lines in vitro. Neutrophil chemotactic activity was demonstrated in 9 conditioned media of 15 human glioblastoma cell lines. Tumor necrosis factor (TNF)-alpha stimulated secretion of the activity in 7 lines and induced secretion in 4 other lines. ELISA quantification disclosed that the conditioned media contained interleukin 8 (IL-8) in an amount equivalent to the chemotactic activity. The IL-8 secretion increased with the stimulation by TNF-alpha. Northern blot analysis and the RT-PCR method confirmed expression of mRNA in the glioblastoma cells and its augmentation by TNF-alpha and/or IL-beta. Reversed-phase HPLC following ion-exchange chromatography revealed that the chemotactic activity was a single peptide, which was determined to be IL-8 by the retention time and ELISA. Furthermore, amino acid analysis disclosed that a major part of the glioblastoma-cell derived IL-8 peptide was 77 amino acid IL-8 (IL-8(77); with the N-terminal sequence AVLPRSAKELRCQCI-).

Amino Acid Sequence↗

PubMed1993

Cellular and cytokine responses of the human central nervous system to intracranial administration of tumor necrosis factor alpha for the treatment of malignant gliomas.

To elucidate the role of tumor necrosis factor alpha (TNF alpha) as a biological response modifier, we studied cellular and cytokine responses of the central nervous system to TNF alpha administered intracranially in a phase I clinical trial for patients with malignant gliomas. Six patients received injections of TNF alpha (1.25 x 10(3)-10 x 10(3) U/injection) into the tumor cavities, and regional fluids (RF) and lumbar cerebrospinal fluids (CF) were serially sampled before and after the injections. Recruitment of neutrophils occurred, mostly peaking 8 h after TNF alpha injection, and fewer numbers of CD4+ T cells and monocytes/macrophages migrated, subsequently peaking at 24 h. The CF leukocytosis persisted for 48 h and was associated with an increased level of neutrophil chemotactic activity in the CF. This neutrophil chemotactic activity was attributed to interleukin-8 (IL-8) by HPLC. The level of IL-6 activity in the CF and RF consistently increased; beginning 2 h after TNF alpha injection and reaching the maximum between 8 h and 12 h. It returned to the basal level within 48 h. IL-1 beta was detected in the CF of three patients, its level peaking at 8 h. Prostaglandin E2 also increased after injection of TNF alpha, peaking between 4 h and 12 h and then gradually decreasing. Transforming growth factor beta was found in all cases tested and one patient showed a significant change after TNF alpha injection. IL-2 activity, interferon alpha (INF alpha) activity, IFN beta, and granulocyte/macrophage-colony-stimulating factor were not detected in the CF or RF. In conclusion, TNF alpha is biologically effective in inducing migration of immune cells and generating multiple cytokine responses in the human central nervous system.

Adult↗

PubMed1993

Recurrent malignant glioma: detection with 131I labeled monoclonal antibody G-22, positron emission tomography and magnetic resonance imaging.

A 45-year-old man with suspected recurrent malignant glioma was evaluated by magnetic resonance imaging (MRI), positron emission tomography (PET) and 131I labeled monoclonal antibody G-22 (G-22) scan. Following Gadolinium-DTPA, a TI-weighted spin echo image (TR 500 msec, TE 20 msec) demonstrated a large mass with an irregular margin in the left temporo-parietal area. An 18F labeled fluorodeoxyglucose PET study demonstrated marked accumulations in the left temporo-parietal area. Serial 131I-G-22 scintigraphy was obtained for a week after the injection. The uptake was most increased on the 2nd day after the injection. 131I G-22 was specific for tumor-associated antigens.

Glioma↗