Biomedical subjects

S Kojima

Publications and source records attributed to S Kojima.

At least 397 records · Page 22Linked to original sources

PubMed1996

Distribution of hepatitis C virus RNA in the liver and its relation to histopathological changes.

To investigate a cellular mode of HCV-infection in the liver and its pathological implications in relation to histopathological changes or clinical data, we studied the distribution of HCV-RNA in the livers of 21 patients with HCV-related chronic liver disease (chronic active hepatitis, 14 cases; cirrhosis, 7 cases) using the in situ hybridization technique. In situ hybridization was performed on 4% paraformaldehyde-fixed frozen sections with digoxigenin-labeled DNA probe deduced from the core region of HC-J4. In situ hybridization showed positive signals in the liver specimens of 20/21 cases. The signals were localized in the cytoplasm of hepatocytes. The distribution pattern of positive cells was individually different, whereas the pattern was identical in the right and left lobes. There were no correlations of the HCV-positive cell number with serum aminotransferase levels at biopsy or with genotypes of HCV. The positive hepatocytes were occasionally associated with infiltrating mononuclear cells, and they were sparsely distributed in the area of piecemeal necrosis. These findings suggest that factors such as host immunoreaction to the virus may be more important than its direct cytopathy in the pathogenesis of chronic hepatitis C virus infection.

Alanine Transaminase↗

PubMed1996

Extragonadal germ cell tumor followed by metachronous testicular tumor. A case report.

We here present a patient with an extragonadal germ cell tumor followed by a metachronous testicular tumor 7 years later. The histological findings of the extragonadal tumor and the subsequent testicular tumor were quite different; the former was of a mixed type with teratoma, embryonal carcinoma and yolk sac tumor, and the latter a pure seminoma. Such a long clinical time lag as 7 years and the histological differences between the two tumors suggest that they occurred independently. To our knowledge, this may be the first case report in the literature, in which a testicular tumor occurred metachronously after extragonadal tumor extirpation.

Adolescent↗

PubMed1996

Effects of atropine and loperamide on the agitating force and GI transit time in dogs in drug absorption studies.

There are difficulties in drug absorption studies using dogs because of different gastrointestinal (GI) conditions between these animals and humans, including shorter intestinal transit time and strong agitation force in the GI tract. We attempted to modify the agitation force and GI transit time using atropine and loperamide. The agitation force was examined based on in vitro/in vivo correlation for two controlled release (CR) formulations of acetaminophen. Atropine treatment considerably reduced the agitating force whereas that of loperamide did not.

Acetaminophen↗

PubMed1996

Enhancement of the antitumor effect of gamma-ray irradiation in combination with camptothecin against human colorectal adenocarcinoma.

The effect of gamma-ray irradiation and camptothecin (CAM) on human colorectal adenocarcinoma (LS 174T) growth was examined. On inhibition of DNA synthesis of LS 174T cells, almost all combined treatments presented a synergistic effect, excepting that the additive effects were shown at the lowest or the highest doses of CAM prior to the gamma-ray (137Cs) irradiation. The in vivo antitumor activity of 131I-NCC-CO-411 monoclonal antibody against carcinoembryonic antigen in combination with CAM was assessed by a tumor growth rate in LS 174T tumor-bearing nude mice. The tumor growth of the combined group was supra-additively suppressed in comparison with that of the individual group. The results suggest that the efficacy of radioimmunotherapy may be enhanced by combination treatment with CAM. A clinical protocol involving a combination treatment with CAM is underway.

Adenocarcinoma↗

PubMed1996

Inhibitory effects of traditional Chinese medicine Shimotsu-to and its included crude fractions on adjuvant-induced chronic inflammation of mice.

Effects of a traditional Chinese medicine, Shimotsu-to (a combined prescription of cnidium rhizome, peony root, angelica root and rehmannia root), and its included crude fractions were investigated on an adjuvant-induced chronic inflammation model of mice. The aqueous extract (30, 100 and 300 mg/kg, i.p.) of Shimotsu-to reduced the carmine content, granuloma weight, inflammation cell count and pouch fluid weight in the inflammation model, respectively. The extract of Shimotsu-to without cnidium at the same doses did not produce significant changes in these four inflammatory parameters. The same doses of extracts of Shimotsu-to without peony, and without angelica, weakly reduced these parameters, except for pouch fluid weight. The extract (30, 100 and 300 mg/kg) of cnidium significantly reduced these four parameters. The same doses of peony extract reduced carmine content, granuloma weight and pouch fluid weight, but less than those of the cnidium extract. The extract of cnidium and peony at the same doses reduced in an additive manner these inflammatory parameters in their combination. These results demonstrated that the Shimotsu-to extract reduced angiogenesis, granuloma formation, inflammatory cell migration and pouch fluid exudation in the adjuvant-induced chronic inflammation model. Cnidium represented the main ingredient for producing the anti-chronic inflammatory effects of Shimotsu-to extract. Cnidium and peony exhibited additive anti-inflammatory effects in combination.

Animals↗

PubMed1996

Accumulation of NCC-CO-411 monoclonal antibody in human colorectal adenocarcinoma through binding of the released carcinoembryonic antigen in nude mice.

NCC-CO-411, an anti-carcinoembryonic antigen (CEA) monoclonal antibody (MoAb) showed a dose-dependent reactivity with standard CEA, but did not bind to the CEA anchoring with cell membranes. When LS 174T cells, one of the CEA-producing cells, were treated with phosphatidylinositol-specific phospholipase C, NCC-CO-411 MoAb recognized the released CEA containing glycosylphosphatidylinositol as well as the standard CEA. The binding activity of NCC-CO-411 MoAb with CEA was also demonstrated by the immunostaining of the LS 174T colorectal tumor xenograft tissues. The biodistribution study showed that NCC-CO-411 MoAb was mainly taken up by tumor and kidney, while the anti-hCEA MoAb was largely concentrated in liver and spleen rather than in the tumor. These results suggest that NCC-CO-411 MoAb recognizes the released CEA and gives an excellent tumor image in LS 174T tumor-bearing mice.

Adenocarcinoma↗

PubMed1996

Preservation of endothelium-dependent vascular relaxation in cholesterol-fed mice by the chronic administration of prazosin or pravastatin.

The relaxation of aortic rings in response to acetylcholine (ACh) was significantly decreased in cholesterol-fed mice. The attenuated relaxation in cholesterol-fed mice was preserved by the chronic administration of prazosin (20 mg/kg/day) or pravastatin (12.5 mg/kg/day). Serum low-density lipoprotein (LDL) levels were significantly increased in mice given cholesterol. The increased serum LDL levels in cholesterol-fed mice were returned to normal by the chronic administration of prazosin and pravastatin. A prior incubation of aortic rings with lysophosphatidylcholine (LPC) significantly attenuated ACh- and A23187-induced endothelium-dependent relaxation. The inhibitory effects of LPC on endothelium-dependent relaxation were not affected by indomethacin or superoxide dismutase. The sodium nitroprusside-induced relaxation of aortic rings was not changed by LPC. The inhibitory effects on ACh-induced relaxation by NG-monomethyl-L-arginine were restored by a prior exposure to L-arginine, whereas the inhibition of endothelium-dependent relaxation by LPC was not affected by L-arginine. These results suggest that cholesterol-fed mice are useful animal models of hypercholesterolemia, and chronic administration of prazosin or pravastatin can preserve endothelium-dependent relaxation by lowering serum LDL in these animals. It is further suggested that LPC derived from oxidized LDL may be involved in the reduced endothelium-dependent relaxation in hyperlipidemia.

Acetylcholine↗

PubMed1996

Effect of 5,6,7,8-tetrahydroneopterin on oxidative modification of low-density lipoprotein, and its uptake in the macrophage-like cell line J774.

Since oxidative modification of low-density lipoprotein (LDL) and uptake of the oxidized LDL by macrophages are closely related to the pathogenesis of atherosclerosis, we examined the inhibitory effect of 5,6,7,8-tetrahydroneopterin (NPH4) on Cu(II)-induced lipid peroxidation of LDL. NPH4 significantly inhibited both lipid peroxidation and the associated increase of electrophoretic mobility of ApoB protein. Furthermore, NPH4 suppressed the uptake of oxidized [14C]oleyl-esterified LDL by the macrophage-like cell line J774. NPH4 may be a candidate for the treatment of atherosclerosis and other active oxygen-related diseases.

Antioxidants↗

PubMed1996

Different effects of alcohol and salt on 24-hour blood pressure and heart rate in hypertensive patients.

To compare the influences of alcohol and salt intake on 24-h blood pressure (BP), we studied short-term effects of repeated alcohol ingestion and dietary salt intake in hypertensive patients. Thirty-two Japanese men with mild to moderate essential hypertension (54 +/- 1 years old, mean +/- SE) were examined. Sixteen patients were given alcohol (1 ml/kg) with dinner for 7 d after a 7-d control period with an isocaloric beverage. Another group consisting of 16 age- and weight-matched patients consumed a low-sodium diet (25 mmol/d) for 7 d, followed by a high-sodium diet (250 mmol/d) for 7 d. Twenty-four-hour BP was measured at the end of each period. Average 24-h BP in the alcohol period (137 +/- 4/83 +/- 2 mmHg) was similar to that in the control period (138 +/- 4/84 +/- 2 mmHg). However, BP in the alcohol period was significantly lower in the evening, but significantly higher in the morning than that in the control period. Heart rate increased for several hours after alcohol ingestion, resulting in a significant increase in 24-h heart rate (67 +/- 2 vs. 64 +/- 2 beats/min). Average 24-h BP was higher in the high salt period (144 +/- 4/89 +/- 4 mmHg) than in the low salt period (135 +/- 3/85 +/- 3 mmHg, p < 0.05). The pressor effect of high salt intake was sustained throughout the day and was associated with a decrease in 24-h heart rate (60 +/- 2 vs. 66 +/- 2 beats/min). In conclusion, short-term repeated intake of alcohol may have little effect on average 24-h BP while it causes an evening fall and a morning rise in BP, and high salt intake raises BP throughout the day. Alcohol consumption increases and salt loading decreases 24-h heart rate.

Adult↗

PubMed1996

Immunohistochemical localization of metallothionein in the olfactory pathway of dogs.

Dogs raised in the open air were used in this study. Metallothionein (MT) immunoreactivity was observed in the nucleus and/or cytoplasm of sustentacular cells of the olfactory epithelium in the nasal mucosa, whereas there was few MT-positive cells in the respiratory epithelium. MT immunoreactivity was also observed in astrocytes in all layers of the the olfactory bulb cortex; glial cells surrounding the glomeruli in the olfactory bulb showed prominent immunoreactivity for MT. Adult dogs exhibited stronger immunoreactivity for MT than young. Northern blot analysis demonstrated substantial levels of MT mRNA in the olfactory mucosa and olfactory bulb. Physiological roles of MT localized in the olfactory pathway of dogs were discussed.

Age Factors↗

PubMed1996

Selective radiofrequency catheter ablation of the slow pathway for common and uncommon atrioventricular nodal reentrant tachycardia.

The utility of selective radiofrequency catheter ablation of the slow pathway for the treatment of common and uncommon atrioventricular nodal reentrant tachycardia (AVNRT) was studied in 110 consecutive patients, 94 with slow-fast form common AVNRT, and 11 and 5, respectively, with the fast-slow and slow-slow forms of uncommon AVNRT. Ablation sites were determined by mapping a late and spiky "slow pathway potential" in the posterior right atrial septum in common AVNRT, and also the earliest retrograde atrial activation over the retrograde slow pathway in uncommon AVNRT. AVNRT was successfully eliminated in all patients with a mean number of radiofrequency pulses of 2.9 +/- 3.0 and a mean total energy applied of 3536 +/- 2996 joules. There were no early or late complications, except for transient AV block for 15 sec immediately after energy application in one common AVNRT patient, and no recurrence of AVNRT in a mean follow-up period of 24 +/- 13 months. There were no significant differences between common and uncommon AVNRT in success rate, mean application number and total energy applied. However, the AVN physiology post-ablation was different. Slow pathway conduction was eliminated in only 32% of the patients post-ablation in common AVNRT, while it was elininated in 100% in uncommon AVNRT. Selective radiofrequency catheter ablation of the slow pathway can cure common and uncommon AVNRT effectively and safely. Common AVNRT can be eliminated irrespective of the persistence of slow pathway conduction, while uncommon AVNRT can be eliminated by the eradication of slow pathway conduction.

Adolescent↗

PubMed1996

Short report: development of a new diagnostic method for Plasmodium falciparum infection using a reverse transcriptase-polymerase chain reaction.

We describe here a reverse transcriptase-polymerase chain reaction method for the detection of malaria parasites. Ten in vitro-cultured isolates of Plasmodium falciparum and 16 specimens from patients infected with P. falciparum were used to examine the specificity and sensitivity of the test. The sensitivity of the test was 0.3 parasites per microliter of blood. Specificity was determined by matching the sequences of the specimens' DNA to published sequences of 18S ribosomal RNA genes in the species-specific region. The test proved to be very sensitive and specific for the detection of P. falciparum infection.

Animals↗

PubMed1996

Survey for Pneumocystis carinii infection of wild-born and laboratory-bred monkeys by indirect immunofluorescence and cyst-staining methods.

A serosurvey for Pneumocystis carinii infection of laboratory-bred and wild-born monkeys was made by the indirect immunofluorescence method. The antibody titers of wild cynomolgus (Macaca fascicularis) and Japanese monkeys (Macaca fuscata fuscata) to P. carinii (Pc) were higher than those of laboratory-bred cynomolgus monkeys; 54.9% of the wild cynomolgus and 40% of Japanese monkeys had antibody titers higher than 1:40, although only 9.4% of the laboratory-bred cynomolgus monkeys did so. Pc cysts in the lungs were examined in the laboratory-bred cynomolgus monkeys by using toluidine blue O stain, and the number of cysts in the lung was small, when compared with those in the lungs of SIV-infected monkeys showing severe pneumosystosis. The results obtained from the studies suggested the possibility that P. carinii infection was more widely epidemic in the wild-born monkeys than in laboratory-bred monkeys.

Animals↗

PubMed1996

[Clinical evaluation of intra-operative radiotherapy combined with subtotal cystectomy for invasive bladder carcinoma].

From 1981 to 1994, intra-operative radiotherapy after subtotal cystectomy was performed on 22 patients with invasive bladder carcinoma on whom radical cystectomy could not be recommended because of old age or condition. All the patients received 25 to 30 Gy of radiotherapy focused on trigonum and internal urethral orifice after subtotal cystectomy with uretero-cutaneostomy. Of 22 patients, 15 patients died. Five patients died of bladder cancer, one died of gastric cancer, one died of rectal cancer and the others died of pneumonia, heart failure, sepsis and senility. The five-year survival rate was 41% and the cause-specific five-year survival rate was 75%. Local recurrence was seen only in one patients, who received second intra-operative radiotherapy and recovered well in complete remission. We believe that intra-operative radiotherapy after subtotal cystectomy is useful for patients with invasive bladder carcinoma on whom radical cystectomy could not be recommended because of old age or condition.

Aged↗

PubMed1996

[Effect of a nitric oxide donor on optic nerve head circulation].

Recently the endothelium-derived relaxing factor was proved to be nitric oxide (NO) and it has been found to play an important role in the regulation of local blood flow. In this paper, we studied the effect of S-nitroso-N-acetyl-DL-penicillamine (SNAP), a NO donor, on the optic nerve head (ONH) circulation in rabbits, using a hydrogen gas clearance flowmeter etc. Intravitreal application of SNAP (20 nmol) increased the caliber of the retinal artery at the edge of the ONH 60 to 120 minutes later and capillary blood flow in the ONH 90 to 135 minutes later. A dose-response relation was found between 2 and 20 nmol. These changes were thought to be caused by NO produced from SNAP because they were inhibited by pretreatment with a NO trapping agent. Blood pressure and IOP were reduced 30 to 45 minutes later and 60 to 120 minutes later, respectively. It was considered that intravitreal injection of SNAP first reduced both the resistance of the ONH blood vessels and the perfusion pressure in the ONH and that the latter then rose, followed by an increase of the capillary blood flow in the ONH.

Animals↗

PubMed1996

Optimal radiolabeled liposomes for tumor imaging.

UNLABELLED: We conducted a systematic study of the effects of liposome formulation and encapsulated radionuclides on imaging ability. METHODS: Various types of liposomes were prepared and labeled with 67Ga, 111In or 99mTc. Their tumor-imaging potential was evaluated in terms of tumor accumulation and tumor-to-blood ratios of radioactivity delivered by the liposomes. Mouse sarcoma 180 and Ehrlich solid tumor were the tumor models. RESULTS: Liposomes could be labeled rapidly and with high efficiency, which was sufficient for clinical application. Tumor accumulation of liposome-encapsulated radionuclides that have intrinsic tumor affinity, such as 67Ga-NTA or 111In-NTA, was larger than that of the other nuclides. Liposomes that were fairly small, cholesterol-rich and composed of so-called rigid phospholipids, could deliver large amounts of encapsulated radionuclides to the tumor. We also found that tumor uptake of such liposomes was large and their blood retention was prolonged. Liposomal lipid dose also influenced tumor delivery and blood retention. The results suggest that these factors extended liposomal blood retention and, consequently, increased tumor uptake of the liposomes and tumor delivery of encapsulated radionuclides. Not all liposomes with long blood retention, however, are suitable for tumor imaging. Incorporation of monosialo-ganglioside in the liposomal membrane greatly extended blood retention but increased tumor uptake only slightly and, consequently, made the tumor-to-blood value worse. One of the 67Ga-labeled liposome formulations resulted in high tumor uptake and tumor-to-blood ratios in various tumor models as well as clearly visualized tumors clearly in sarcoma 180-bearing mice. CONCLUSION: For tumor imaging with radiolabeled liposomes, we should choose liposomal formulations and dose to give prolonged blood retention for large tumor delivery. We must then select liposomes that give good tumor-to-blood values. For the best results, the radionuclide should have intrinsic tumor affinity. Labeled liposomes that meet these criteria result in excellent tumor images.

Animals↗

PubMed1996

[Necessity for searching for cerebral aneurysm in thunderclap headache patients who show no evidence of subarachnoid hemorrhage: investigation of 8 minor leak cases on operation].

The study included 562 patients with headache who visited our clinic from January 1988 to December 1993. In these patients, the possibility of subarachnoid hemorrhage was denied from CT findings and color of cerebrospinal fluid by lumbar puncture. Cerebral aneurysm was found in 52 out of 562 patients (9.3%), and minor leak was found during 46 surgery cases in 8 patients with cerebral aneurysm. These 8 patients (32-51 years old, 5 males and 3 females, period from onset to hospital visit; 1-6 days) were examined concerning characteristics of headache and concomitant symptom, cerebrospinal fluid and operative findings. Headache attack occurred at rest in 6 patients (75%) and suddenly in all patients. It continued over 24 hours in 7 patients (87.5%). All patients felt that they had never experienced such a headache. Pulsating headache was observed in 5 patients (62.5%). Nausea and vomiting were complications in all patients. The site of headache was in the forehead region, and circumorbital pain was a complication in four patients. Six patients (75%) had unilateral pain, and 5 patients (62.5%) had headache at the same side as the cerebral aneurysm. Increase of cell count ( > or = 10/mm3) in cerebrospinal fluid was found in 4 patients (50%). In all cases, lymphocytes were dominant. Arachnoid adhesion and hypertrophy with hemorrhage were found during surgery in 4 patients (50%). In these patients, the period from onset to surgery (average 16.5 days) was longer than that of the patients with hemorrhage alone (average 6 days). The site of the hemorrhage was located in the cistern of the cerebral aneurysm in all cases. In patients suffering sudden headache, screening for cerebral aneurysm should be thoroughly performed though early findings on CT and cerebrospinal fluid indicated no abnormalities.

Adult↗

PubMed1996

[Comparative measurement of optic nerve head circulation using laser speckle circulation analyser of ocular fundus and a hydrogen clearance method].

The microcirculation in the optic nerve head (ONH) was measured using the recently developed laser speckle circulation analyser for the ocular fundus. The measurements were compared to those of the capillary blood flow (CBF) obtained by the hydrogen clearance method. The ONH blood flow was measured using both methods simultaneously in six normal albino rabbits. The blood flow was increased by inhalation of carbon dioxide (CO2) and reduced by systemic administration of endothelin-1 (ET-1). 10%CO2 inhalation showed a CBF increase of about 22% in the ONH in the hydrogen clearance method, and intravenous injection of ET-1 at 10(-10) mol/kg decreased the reading by about 19%. A significant correlation (r = 0.92, p < 0.01) was found between the relative values of NB (Normalized blur, by laser speckle method) and CBF in the ONH. This result indicates that the change of NB in the ONH shares the same accuracy as hydrogen clearance method within the range of our present experiment. This study provides a fundamental basis for the clinical application of the laser speckle method in measuring ONH circulation.

Animals↗