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Biomedical subjects

H Naganuma

Publications and source records attributed to H Naganuma.

At least 109 records · Page 6Linked to original sources
PubMed1993

Protective effect of N-acyl amino acids (NAAs) on cephaloridine (CER) nephrotoxicity in rabbits.

The protective effect of N-acyl amino acids (NAAs) against cephaloridine (CER)-induced nephrotoxicity was studied in rabbits. A large single intravenous dose of CER (more than 100 mg/kg) induced severe proximal tubular necrosis. Simultaneous treatment with several NAAs (at dosages of 100, 200 mg/kg, etc., i.v.), such as N-benzoyl-beta-alanine (NBBA), N-benzoyl-6-aminocaproic acid, and N alpha,epsilon-dibenzoyl-D,L-lysine, remarkably suppressed the histopathological damage in the kidney induced by CER. NAAs have generally low toxicity in laboratory animals (e.g., the LD50 of NBBA was more than 3,000 mg/kg, i.v. in rats), and NAAs were suggested to be good candidates for reducing the nephrotoxicity of CER and other beta-lactam antibiotics.

Alanine↗
PubMed1992

Proliferating cell nuclear antigen (PCNA) immunostaining as an alternative to bromodeoxyuridine (BrdU) immunostaining for brain tumours in paraffin embedded sections.

Immunohistochemical staining for proliferating cell nuclear antigen (PCNA) and BrdU using anti-PCNA and anti-BrdU monoclonal antibodies, respectively, was performed in 16 human brain tumours, including 3 glioblastomas multiforme, 2 anaplastic astrocytomas, 1 cerebellar astrocytoma, 2 recurrent meningiomas, 4 non-recurrent meningiomas, 3 neurinomas and 1 medulloblastoma. Patients with brain tumours received an injection of bromodeoxyuridine (BrdU) intravenously during surgery, and tumour specimens were fixed in 70% ethanol and embedded in paraffin. The percentage of positive cells for PCNA was compared with a BrdU labelling index using adjacent paraffin-embedded sections. The percentage of PCNA-positive cells was correlated with the BrdU labelling index and the histological malignancy of the brain tumours. The correlation coefficient was 0.84. This suggests that the immunohistochemical staining for PCNA in paraffin sections is a good alternative to the BrdU labelling index.

Antigens, Neoplasm↗
PubMed1992

Gastrointestinal endoscopy in Henoch-Schönlein purpura.

Gastrointestinal (GI) endoscopy was performed in seven patients with Henoch-Schönlein purpura (HSP). In two patients there were no cutaneous lesions at the time of endoscopy, but inflammation of the duodenum, especially of the second part, led to suspicion of the disease. Upper GI endoscopy showed abnormalities in six of seven cases, and sigmoidoscopy in one of four cases. The changes were more marked in the second part of the duodenum rather than in the bulb or the stomach. The endoscopic findings included redness, swelling, petechiae or haemorrhage, erosions and ulceration of the mucosa. Histology of the mucosal biopsy specimens revealed non-specific inflammation with positive staining for IgA in the capillaries, but failed to show vasculitis. Upper GI endoscopy, including study of IgA, can be useful in the diagnosis of HSP. Colonoscopy is less helpful, especially if limited to the sigmoid colon.

Adolescent↗
PubMed1992

Diverse effect of cytokine treatment of tumor cells on specific versus non-specific cytotoxicity.

The effect of IFN-gamma and TNF-alpha treatment of an ovarian carcinoma line on the sensitivity to lysis by specific CTL clones and non-specific Tumor Associated Lymphocytes (TAL), isolated from the ascites fluid, was analyzed. The in vitro established TAL line displayed a non-specific lytic activity against the autologous tumor as well as against several allogeneic tumor lines. Pretreatment with IFN-gamma alone, or in combination with TNF-alpha, rendered the carcinoma line less susceptible to lysis by the autologous TAL line. Conversely, susceptibility to lysis by tumor specific T cell clones, isolated from the TAL line, was increased as a result of cytokine pretreatment. Several TCR-alpha/beta+, CD8+ T-cell clones showing a more specific pattern of lysis against the autologous tumor were isolated. Lysis of the autologous tumor by these clones involved the TCR-alpha/beta via a MHC-class I restricted mechanism dependent on the adhesion molecules ICAM-1 and LFA-3, as inferred from antibody blocking studies. The enhanced sensitivity to specific CTL clones seen after cytokine treatment may be related to the enhanced expression of ICAM-1 molecules on the ovarian carcinoma. These results have implications for cytokine based immunotherapy, where IFN-gamma may enhance the effects of tumor associated specific CTL while decreasing that of non-specific effector cells.

Ascitic Fluid↗
PubMed1992

De novo expression of aromatase in gastric carcinoma. Light and electron microscopic immunohistochemical and immunoblot study.

We have performed immunohistochemical and immunochemical studies of steroidogenic enzymes involved in estrogen biosynthesis in 30 cases of gastric carcinoma in order to investigate possible in situ production of estradiol (E 2) in carcinoma cells. Positive incidence of immunoreactivity for E 2, testosterone (T), cholesterol side-chain cleavage enzyme (P-450 scc) and aromatase (P-450 arom) were 17/30 (56.7%), 11/30 (36.7%), 3/30 (10.0%) and 23/30 (76.7%), respectively on light microscopy. Estrogen receptor (ER) immunoreactivity was not observed in any of the 30 cases examined. Normal gastric mucosa was negative for P-450 arom and P-450 scc. Examination of serial sections revealed that immunoreactivity of E 2 and P-450 arom were located in the same cells of carcinomatous glands. Immunoelectron microscopy demonstrated that E 2 and P-450 arom were located along the membrane and cisternae of smooth endoplasmic reticulum (sER). Western blot analysis showed one major band of 55 kDa of P-450 arom in the gastric carcinoma tissues examined. Retrospective analysis of immunohistochemistry of E 2 in 108 cases of gastric carcinoma revealed that E 2 positive carcinoma cases were likely to demonstrate better survival rate than negative cases. These results above strongly suggest that E 2 is produced by de novo expressed aromatase in gastric carcinoma cells and is possibly involved in the biology of gastric carcinoma cells.

Aromatase↗
PubMed1992

An autopsy case of Kawasaki disease with reference to occurrence of acute coronary thrombosis in the convalescent stage.

A one-year, four month-old boy who had suffered from Kawasaki disease died suddenly during convalescence despite intensive gamma-globulin treatment. Autopsy revealed a) sausage-like aneurysms of the left and right coronary arteries and fresh thrombosis in the right coronary aneurysm, b) fresh transmural myocardial necrosis in the whole wall of the left ventricle and the anterior part of the wall of the right ventricle, and c) swelling of the cervical lymph nodes and thymus (60 g). Histologically, fibrocellular thickening of the intima and destruction of the media and internal elastic lamina were conspicuous in the area of the aneurysm, but those of the intima and media in the areas adjacent to the aneurysm were mild. Abrupt narrowing of the lumen at the border between the aneurysm and periphery of the right coronary artery was detected, and this may have been responsible for formation of the thrombus in the right coronary aneurysm. In the systemic arteries, perivascular fibrosis was very noticeable despite less severe injury to the intima and media. These findings suggest that severe inflammation of the periarterial regions was present in the acute phase. The lymph system still showed inflammation, supporting the infectious or toxic nature of Kawasaki disease.

Acute Disease↗
PubMed1992

Prediction of human pharmacokinetics of panipenem-betamipron, a new carbapenem, from animal data.

The pharmacokinetic behavior of panipenem (PAPM)-betamipron (BP), a new carbapenem, in humans was successfully predicted from data collected from six animal species. PAPM and BP were biphasically eliminated from plasma after intravenous (i.v.) administration of PAPM-BP to mice, guinea pigs, rats, rabbits, monkeys, and dogs. Elimination rates of PAPM and BP were correlated with animal size: the larger the animal was, the slower the elimination was. As for PAPM and BP, log-log plots of total plasma clearance (CLtot) versus body weight and log-log plots of distribution volume at steady state (VSS) versus body weight for six animal species were linear, with high correlation coefficients. These allometric equations were extrapolated to predict CLtot and VSS for PAPM and BP in humans. In addition, concentration in plasma-time profiles for humans were predicted by using two-exponent equations fitted to the complex Dedrick plot of animal data. Predicted values for CLtot and VSS for PAPM and BP in humans agreed well with observed values in humans given 750/750 mg of PAPM-BP as an i.v. drip infusion for 30 min. Predicted concentration in plasma-time profiles for humans approximated observed profiles. Thus, the pharmacokinetics of PAPM-BP extrapolated well from animal species to humans when allometric equations and the complex Dedrick plot were used.

Animals↗
PubMed1992

Analysis of tumor necrosis factor and lymphotoxin secreted by incubation of lymphokine-activated killer cells with tumor cells.

This study investigated the secretion of a tumor necrosis factor (TNF) and lymphotoxin (LT) from lymphokine-activated killer (LAK) cells during co-culture with glioblastoma cell lines, autologous glioma cells, and other non-gliomatous tumor cell lines (K562 and Daudi). Cytokine secretion from peripheral blood mononuclear cells (PBMC) was also examined. The TNF activity of culture supernatants was measured by L cell cytotoxic assay, and a neutralization test using anti-TNF and/or anti-LT antibodies determined whether the cytotoxic activity was due to TNF or LT. The results show that LAK cells secrete both TNF and LT during monoculture and release increased amounts of TNF and LT with non-gliomatous tumor cell stimulation, but PBMC secrete only TNF with tumor cell stimulation. Glioblastoma or anaplastic astrocytoma cells, however, did not stimulate cytokine secretion from either LAK cells or PBMC. This indicates a discrepancy between the capability of LAK cells to lyse malignant glioma cells and cytokine secretion from LAK cells, and suggests that malignant glioma cells may produce some factors which inhibit cytokine secretion from LAK cells.

Astrocytoma↗
PubMed1992

Antiproliferative cytokines secreted by lymphokine-activated killer cells stimulated with tumor cells.

Antiproliferative cytokine secretion by lymphokine-activated killer (LAK) cells during coculture with glioblastoma cell lines, autologous glioma cells, and nongliomatous tumor cell lines (Daudi and K562 cells) was assessed, as was the antiproliferative activity of the culture supernatants against the T98G (glioblastoma) cell line. A neutralization test using agents against interferon-gamma (IFN-gamma), tumor necrosis factor (TNF), and lymphotoxin (LT) showed that antiproliferative activity was due to IFN-gamma, but not to TNF or LT. Nongliomatous tumor cells stimulated LAK cells to secrete cytokines, but gliomatous tumor cells did not. It was found that there is a discrepancy between the LAK cell capability to lyse malignant glioma cells and the ability to secrete cytokines. This may be due to the factors secreted by glioblastoma cells.

Astrocytoma↗
PubMed1991

Continued blood cell formation in spherical bodies in a long-term mouse spleen culture.

During the primary culture of spleen fragments of newborn mice, a spherical body (d = circa 200 to 300 microns) as a three-dimensional cellular organization was formed. Continued production of blood cells from the spherical body was observed without changing its size for about 2 months of culture. Without growth factor, the spherical bodies produced mainly lymphocytes and macrophages. Addition of interleukin-3 enhanced their granulocyte formation, and this enhancement was observed even after a prolonged maintenance without growth factors. The spherical bodies were composed of a uniform mixture of endothelial cells and fibroblasts within the body, and cell-cell contacts between lymphocytes and fibroblasts were notable in the periphery. With prolonged culture, the spherical bodies showed a definite change in their structure by sorting two cell types and the blood cell production gradually decreased. These results suggested that a three-dimensional structure was required for the maintenance, growth, and differentiation of blood cell progenitors in the long-term spleen culture.

Animals↗
PubMed1991

Increased susceptibility of IFN-gamma-treated neuroblastoma cells to lysis by lymphokine-activated killer cells: participation of ICAM-1 induction on target cells.

We have investigated the effect of interferon-gamma (IFN-gamma) treatment of neuroblastoma cells on the susceptibility to lysis by lymphokine-activated killer (LAK) cells and examined the participation of cell-adhesion molecules on the target cells in LAK cell lysis. Untreated neuroblastoma cells expressed lymphocyte-function-associated antigen 3 (LFA-3) and neural-cell-adhesion molecule (NCAM), but did not express MHC-class-I, MHC-class-II, or intercellular-adhesion molecule I (ICAM-I). IFN-gamma treatment of neuroblastoma cells induced the expression of MHC-class-I and ICAM-I antigens, but did not affect the expression of MHC-class-II, LFA-3, and NCAM. This was accompanied by an increased susceptibility to lysis by LAK cells. Anti-ICAM-I antibody inhibited partially the increased sensitivity of IFN-gamma-treated neuroblastoma cells to LAK cell lysis, and blocked completely the increase in binding of LAK cells observed after IFN-gamma treatment of the target cells. These results suggest that the increased LAK sensitivity of IFN-gamma-treated neuroblastoma cells is partially attributable to the induction of ICAM-I on neuroblastoma cells and indicate that post-binding events also play a role in the increased sensitivity to LAK cell lysis observed after IFN-gamma treatment.

Cell Adhesion Molecules↗
PubMed1991

Cerebrospinal fluid placental alkaline phosphatase in the intracranial germinomas: results of enzyme antigen immunoassay.

The authors investigated the placental alkaline phosphatase (PALP) activity in cerebrospinal fluid (CSF) by enzyme-antigen immunoassay using polyclonal antibody as a marker for intracranial germinomas in 17 patients with germ cell tumors and 20 with other disorders. The detection limit of PALP activity was 0.072 optical density units equivalent to 5.9 ng/ml. Five of nine germinomas demonstrated high CSF PALP activities before treatment. These high PALP activities became undetectable following radiation therapy. The other tumors were small or had no CSF contact. CSF PALP activity is a useful tumor marker for pure germinomas.

Adolescent↗
PubMed1991

[Neuro-otological study on Behçet disease].

It seems acceptable that pathological brain stem lesions exist in the patient with Neuro-Behçet disease (NB). However, only few reports have been published in this field. We report the neuro-otological findings in 33 patients who fulfilled the diagnostic criteria of Behçet disease completely or incompletely. The patients were classified into 2 groups: one is group of NB and the other is a group of Behçet disease without NB (non-NB). Furthermore, the latter was divided into 2 subgroups of patients with dysequilibrium and patients with normal equilibrium. They underwent equilibrium function tests, such as body balance test, gaze test, spontaneous and positional nystagmus test, eye tracking test (ETT) and optokinetic pattern test (OKP) by using electro-nystagmography (ENG). The following results were obtained. 1. Cerebellar and brain stem lesions were confirmed in all cases of NB group. 2. Most cases (6 of 8 cases) in the subgroup of dysequilibrium of the non-NB group showed peripheral vestibular disturbance. The other two patients were diagnosed to be vertebro-basilar insufficiency (VBI) and vascular Behçet disease with CNS disorder, respectively. 3. Nine of 13 patients in the normal equilibrium subgroup of the non-NB group were diagnosed to be neuro-otologically normal. However, we found two patients with peripheral vestibular disturbance and CNS disorder associated with hearing disturbance of the retrocochlear origin, respectively. 4. The neuro-otological examination is assumed to be useful to diagnose neuro-Behçet disease, to reveal the lesion site and the state of dysequilibrium in patients with Behçet disease.

Adolescent↗
PubMed1990

Enantiospecific assay for mammalian carbonyl reductase by liquid chromatography with fluorescence detection.

A fluorogenic substrate with an unsymmetrical carbonyl for the sensitive assay of mammalian carbonyl reductase activities, 4-(6-methoxy-2-benzoxazolyl)acetophenone (I), has been prepared. The fluorescence quantum yield of I in acetonitrile is 0.12 at the emission maximum of 448 nm. The corresponding racemic alcohol produced by the chemical reduction of I, (+/-)-sec.-[4-(6-methoxy-2-benzoxazolyl)]phenethyl alcohol (II), exhibits ca. three- to fourteen-fold higher fluorescence at a shorter wavelength emission maximum of 370 nm in conventional solvents. Each enantiomer of II is sufficiently resolved on a chiral cellulose high-performance liquid chromatographic column without derivatization and quantified with high reproducibility. The detection limit for II is 20 fmol per injection at a signal-to-noise ratio of 3. The validity and applicability of I are evaluated with cytosols of mammalian tissues. The optimal pH for metabolic reduction of I in rabbit liver cytosol preparations is 6.2 in the presence of NADPH. The metabolism is proved to be highly stereoselective. The resulting alcohol produced by mammalian tissue preparations, except rabbit kidney, is predominantly of the S-(-)-configuration.

Alcohol Oxidoreductases↗
PubMed1990

High-performance liquid chromatographic determination of loxoprofen and its diastereomeric alcohol metabolites in biological fluids by fluorescence labelling with 4-bromomethyl-6,7-methylenedioxycoumarin.

A simple and sensitive high-performance liquid chromatographic procedure to determine loxoprofen and its diastereomeric alcohol metabolites in biological specimens is described. The analysis involves liquid-liquid extraction with benzene, pre-column derivatization with a highly fluorogenic reagent, 4-bromomethyl-6,7-methylenedioxycoumarin (BrMDC) and subsequent separation on a reversed-phase column. Loxoprofen, its pharmacologically active metabolite, trans-alcohol, and less active cis-alcohol were completely separated within 20 min with a mobile phase of 55% of aqueous acetonitrile containing acetic acid. Any endogenous substances do not interfere in the analysis of either plasma or urine samples. The quantitation limit was 0.01 micrograms/ml for human plasma and 0.05 micrograms/ml for urine. The method was applied to a pharmacokinetic study in healthy human subjects who had received 60 mg of loxoprofen sodium.

Adult↗
PubMed1990

Immunoelectron microscopic localization of aromatase in human placenta and ovary using microwave fixation.

In this study we investigated the immunohistochemical localization of a unique aromatase, a single protein of 51,000 daltons, in the human placenta and ovary at light and electron microscopic levels. Microwave fixation was adopted for the immunoelectron microscopic study because it is an excellent method for preserving antigenicity and subcellular structures in frozen sections. Tissue samples from four immature human placentas, four full-term human placentas, and two human ovaries fixed in 10% formalin were examined by light microscopy. In addition, tissues from three full-term human placentas and one immature human placenta fixed in 4% paraformaldehyde were examined by electron microscopy. By light microscopy, immunoreactivity for this aromatase was located in the syncytiotrophoblast and a part of the cytotrophoblast of the placenta and in the lutein and granulosa cells of the ovary. Immunoelectron microscopy revealed that the aromatase antigen was localized on the surface of the microvilli, the lateral plasma membrane, and in the endoplasmic reticulum (ER) in the syncytiotrophoblast of the placenta. The positive immunoreactivity in the syncytiotrophoblast ER is consistent with previous results using antibodies for other types of aromatase, whereas the reactivity on the microvilli has not been previously described. The present report describes the fine localization of this unique aromatase in placental and ovarian tissues; its localization on the plasma membranes requires further physiological investigation.

Adult↗