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Biomedical subjects

M Ohta

Publications and source records attributed to M Ohta.

At least 973 records · Page 54Linked to original sources

A case of large prolactinoma supposed to be cured by bromocriptine therapy.

The authors reported a patient with a large prolactinoma (PRL 1,716 ng/ml) who was treated with bromocriptine for two years and followed up for a subsequent 36 months. After the start of the therapy, the tumor size was dramatically reduced, and finally the disappearance of the tumor was confirmed by high resolution coronal CT. The serum prolactin level and pituitary function were normalized. The tumor has not regrown and the blood prolactin level has remained normal for 36 months since the discontinuation of bromocriptine administration. This is a very rare case report on the eradicative effect of bromocriptine on such a large prolactinoma. Another characteristic of this case was that the prolactin reserve was maintained not only before the therapy but also during the early stage of the therapy.

Adult↗

Presence of high concentration of 7B2 in pleural effusion.

7B2 (a novel pituitary protein) is a secretory protein in the neuroendocrine tissues and an increase in the plasma 7B2 concentration was noted in some patients with various endocrine tumors, including small cell carcinoma of the lung and acromegaly, suggesting that 7B2 is a possible marker for these tumors. Using a radioimmunoassay, the 7B2 concentration was measured in pleural fluid samples obtained from 36 patients with lung cancer and benign pulmonary disease to assess its concentration as a marker for small cell carcinoma of the lung (SCCL) or malignant effusion. 7B2-immunoreactivity (IR) was present in pleural fluid and its concentration was much higher than in plasma. However, there was no significant difference between pleural fluid 7B2 in patients with SCCL and in other histological types of lung carcinoma or in malignant and nonmalignant patients. In the chromatographic analysis of pleural fluid on gel permeation chromatography and reverse-phase high-performance liquid chromatography, there was no molecular heterogeneity between malignant and nonmalignant effusion. These results suggest that pleural fluid 7B2-IR is not a useful marker for SCCL or malignant effusion.

Chromatography, Liquid↗

A case of progressive muscular dystrophy with numerous arterioluminal vessels.

A 48-year-old man had histologically demonstrated cardiac involvement associated with progressive muscular dystrophy. On coronary arteriography, numerous vascular communications between the coronary arteries and the left ventricular chamber were found. These vascular communications are considered to be the arterioluminal vessels. This is the first report of a case of progressive muscular dystrophy with numerous arterioluminal vessels.

Coronary Angiography↗

[Benefits of cisplatin-based polychemotherapy in non-small cell bronchogenic carcinoma. Kyushu Lung Cancer Chemotherapy Study Group].

We studied the efficacy of cisplatin-based polychemotherapy for non-small-cell lung cancer. One hundred nineteen patients with adenocarcinoma or large cell carcinoma were randomized to receive cyclophosphamide, adriamycin, cisplatin and mitomycin C (CAPM) or mitomycin C, cytosine arabinoside and tegafur (MCT), and 48 patients with squamous cell carcinoma were randomized to receive cisplatin, adriamycin and peplomycin (PAP) or mitomycin C, cyclophosphamide, tespamine, toyomycin and tegafur (MCTTT). Radiation was given to the chest in patients with stage I-III disease. The response rates were CAPM, 34.5%; MCT, 13.1% (p less than 0.01) and PAP, 63.3%; MCTTT, 42.3%. A significant difference in response rate between the CAPM and MCT regimens was observed only in stage IV patients and not in stage I-III patients. The median survival was 9.5 months in the CAPM arm vs. 6.5 months in the MCT arm (p less than 0.007), and 8.5 months in the PAP arm vs. 6.5 months in the MCTTT arm. Improved median survival for the CAPM regimen was noted only in stage IV patients and not in stage I-III patients when compared to patients given the MCT regimen, respectively. Nausea and vomiting were significantly increased in patients with cisplatin-based polychemotherapy. Myelosuppression was more severe with the CAPM regimen than with the other chemotherapy regimens. We concluded that cisplatin-based polychemotherapy, CAPM and PAP therapy were of more benefit to patients with disseminated non-small-cell lung cancer than MCT and MCTTT therapy.

Adult↗

Pathologic changes in the cytokeratin pericanalicular sheath in experimental cholestasis and alcoholic fatty liver.

The architectural framework of the pericanalicular sheath composed of cytokeratin intermediate filaments (IFs) was examined after phalloidin treatment, bile duct ligation, and alcoholic fatty liver in rats to assess the role of IFs in experimental cholestasis. Electron microscopy examination of whole mount unembedded extracted liver slices was employed to visualize the cytoskeleton. Immunofluorescence staining and immunoelectron microscopy of the sheath were also performed using monoclonal antibodies to rat hepatocyte cytokeratins CK49 and CK55. The thickness of the wall and the diameter of the lumens were measured. In the phalloidin-treated rats, the pericanalicular sheath was markedly dilated and thickened. Immunofluorescence staining showed that the CK49 and CK55 IFs were localized in the pericanalicular region, particularly in the pericentral area. Immunoelectron microscopy documented that the IFs at the thickened pericanalicular sheath consisted of both CK49 and CK55, which means that the thickening of the bile canaliculus was in part due to an increase of IFs and not just due to an increase in actin filaments. In the livers where the bile duct was ligated, the pericanalicular sheath was irregularly dilated and some parts of the sheath appeared thinned out or missing. The belt desmosome also appeared absent focally in the pericanalicular sheath. Immunofluorescence studies showed that the staining for CK49 and CK55 was reduced focally in the pericanalicular region. The CK55 antibody stained the cytoplasm of hepatocytes in the periportal area more intensely when compared with the controls. These results indicated that the pericanalicular sheath and the belt desmosome were focally disrupted in response to extrahepatic bile duct obstruction. In the ethanol-fed rats, the pericanalicular sheath was dilated, thickened and tortuous, and appeared focally flattened by large fat droplets. IFs in the cytoplasm were pushed to the cell periphery and were compressed against each other by the fat droplets. CK55 and CK49 appeared increased as indicated by the observed immunofluorescence at the pericanalicular region. Immunoelectron microscopy showed that IFs of the thickened pericanalicular sheath were composed of CK55 and CK49. It is suggested that the pericanalicular sheath functions to mechanically provide a scaffolding for the bile canaliculus which is vulnerable to the different forces involved in cholestasis of different pathogenesis such as focal compression and distortion by fat, hypertrophy in response to increased F actin and focal destruction by increased intracanalicular pressure.

Actins↗

Ubiquitin is present on the cytokeratin intermediate filaments and Mallory bodies of hepatocytes.

To investigate the relationship of cytokeratin intermediate filaments (IFs) and Mallory bodies (MBs) to the regulatory protein ubiquitin, the griseofulvin-fed mouse was examined by double-label immunocytochemistry. In controls, immunofluorescence of hepatocytes showed that an antiserum specific to ubiquitin stained the cell border and the cytoplasm as well as the nuclear rim. In griseofulvin-fed liver cells, the MBs induced by this treatment were stained in an identical pattern by the antiserum to ubiquitin and a monoclonal antibody specific to cytokeratin (TROMA 1). Upon examination of the immunoreaction at the ultrastructural level, the ubiquitin antiserum decorated the cytokeratin filaments as well as MB filaments. Particularly striking was the coincidence of localization of TROMA 1 and ubiquitin epitopes, many IF surrounding MBs being either intensely decorated or alternatively nonimmunoreactive. These results suggest that normal cytokeratin IFs are lightly ubiquitinated, whereas MBs are heavily ubiquitinated. Immunoblot analysis of extracted cytoskeletal proteins separated by gel electrophoresis showed that extensive ubiquitination of peptides was present in the livers of the griseofulvin-fed mice. Further, the lack of ubiquitin and TROMA 1 epitopes in some liver IF suggest that loss of the TROMA 1 epitope may lead to concomitant loss of the ability to bind ubiquitin. Although the role ubiquitin plays in Mallory body formation remains to be elucidated, we suggest that its significance here may be related to its normal association with cytokeratin.

Animals↗

Changes in the organization and antigenic determinants of intermediate filaments of rat hepatocytes after infusion of cytochalasin B in vivo.

The changes in cytokeratin intermedial filaments (IFs) after cytochalasin B (CB) infusion of rat liver in vivo were studied by light and electron microscopy, immunofluorescent staining (IMF), and immunoelectron microscopy (IEM). The CB treatment caused a change in the IFs at the cell border associated with a change in the distribution of microfilaments. The IFs at the cell border were partially disrupted. Actin aggregates were localized at points where IFs had condensed together. The pericanalicular sheath was intact but very dilated. These results indicated that the CB treatment caused an irregular distribution of the microfilaments at the cell periphery but spared the actin at the bile canaliculus. Cytokeratin staining by IMF was markedly decreased or absent; however, IEM clearly showed the presence of nonstaining IFs after CB treatment. These results indicated that the antigenic determinant of normal cytokeratin IFs became masked after CB treatment. The results indicate that F-actin disassembly induced by CB affects both the organization and conformation of cytokeratins associated with loss of integrity of the plasma membrane and vesicular uptake of plasma proteins by hepatocytes.

Actin Cytoskeleton↗

Distribution of hematoporphyrin derivative in normal and malignant tissue.

The distribution of [14C]hematoporphyrin derivative (HpD) has been studied in mice bearing human lung tumor and in guinea pig bearing Line 10 tumor. The amount of [14C]HpD in the transplanted tumor tissue of mice at various times following drug administration (20 mg/kg) was higher than in skin or muscle tissue but was less than in liver, kidney, spleen, lung and heart tissue. The distribution pattern of [14C]HpD in guinea pig at 2 days following injection was also similar to that in mice. Our data were different from those that suggested the selectivity of uptake and retention of HpD by malignant tissues, using fluorometric techniques.

Animals↗

[Cholecystolithiasis causing Mirizzi's syndrome with a rare anomaly of the extrahepatic bile duct in a child. Report of a case].

A 14 year-old girl, who was admitted to our hospital due to increasing jaundice, intermittent right upper quadrant pain and fever, underwent operation based on the diagnosis of the Mirizzi's syndrome. Calculi filled the cystic duct and compressed the right hepatic duct. The right and left hepatic ducts lay closer to the duodenum than usual. The operation was limited to cholecystectomy alone. The calculi showed laminar cut surfaces and were composed of bilirubin lime. In addition to reporting our case, the literature dealing with this particular entity is reviewed.

Adolescent↗

[Role of autologous bone marrow transplantation in cancer chemotherapy].

Over the past 9 years, total number of 147 patients with various types of malignant solid tumors were treated 220 times with high-dose chemotherapy supported by autologous bone marrow transplantation. Two most frequently used chemotherapeutic protocols were: cyclophosphamide 1,600 mg/m2 + adriamycin 80 mg/m2 + ACNU 3 mg/kg and cyclophosphamide 1,600-2,400 mg/m2 + adriamycin 80 mg/m2 + CDDP 100-120 mg/m2. There were 89 patients with advanced and/or recurrent diseases. The overall response (CR + PR) rate was 44.1% with the complete response (CR) rate, being 11.8% among 68 evaluable patients in this group. The most favorable response was obtained in breast cancer patients with 77.3% response rate and 13.6% CR rate. Nearly 50% of patients with gastric, lung, gynecological and pediatric malignancies responded, whereas poor responses were observed in the cases of pancreato-biliary, colorectal, esophageal cancers and melanoma. In 8 complete responders, three are alive and well without any evidence of disease 5 years after the treatment. There were 58 patients who underwent this treatment in adjuvant settings. There are 5 patients with breast cancer who have been followed over 5 years after treatment. All of them are alive and well without any demonstrable diseases. Four of them were in stage IIIa and histologically examined axillary nodes were positive in 14/15, 11/17, 37/44, 22/25. Autologous bone marrow transplantation seems to be instrumental in shortening the period of myelosuppression, thus allowing safe dose escalation in chemotherapy. Adequacy of cryopreserved marrow as marrow inoculum was ascertained with mononuclear cell count, cellular viability, CFU-GM, CFU-E, BFU-E and CFU-Mk.

Antineoplastic Combined Chemotherapy Protocols↗

[Chemosensitization with nitroimidazole to human gastric cancer transplanted into nude mice].

Combined chemotherapy for human gastric cancer Transplanted into nude mice has been performed to determine whether misonidazole (MIS) and metronidazole (MTR), derivatives of nitroimidazole, would enhance the antitumor activity of MMC. MTR, 500 mg/kg, MIS 500 mg/kg, and MMC 2.0 mg/kg were administered ip twice during a 48-hour interval. The antitumor efficacies of MMC only, MTR only, or MIS only were seen to be much the same as in the controls. The combined treatment with MMC and MTR surpassed the controls in antitumoral activity after the 12th day, whereas it did not surpass a regimen with MMC alone. The addition of MIS to MMC showed an enhanced antitumoral activity after the 10th day compared to the controls and, further, after the 10th day it exceeded the results of MMC only. Tumor tripling time in cases of MMC only, MTR only, MIS only, MMC plus MTR, and MMC plus MIS was 123, 132, 144, 144, and 178 hours, respectively, compared to 110 hours in the controls. Thus, these results suggest that MIS has a chemosensitizing activity under these conditions, while MTR has little activity.

Animals↗

[Enhancement of hyperthermochemotherapy with hypoxic cell radiosensitizers].

Hyperthermochemotherapy with hypoxic cell radiosensitizers has been carried out using human gastric cancer xenotransplanted into the nude mouse. Misonidazole (MIS) and metronidazole (MTR), hypoxic cell radiosensitizers, were administered singularly or in combination with an ip dose of 500 mg/kg each, and after 60 minutes, an ip dose of MMC of 2.0 mg/kg was given. Subsequently, hyperthermia was applied, twice at a 48-hour interval, by a water bath at 43.5 +/- 0.1 degrees C for 23 minutes. The antitumor activity of hyperthermia with MTR was similar to that of hyperthermia alone, whereas hyperthermia with MIS surpassed hyperthermia alone, at 0.03237 less than p less than 0.05038. Hyperthermia combined with MIS and MMC enhanced the antitumor effects, as compared to hyperthermia with MMC, and with MMC plus MTR. Tumor volumetric tripling times in case of MMC plus heat, MTR, MMC plus heat, and MIS, MMC plus heat were about 229, 213, and 398 hours, respectively, compared to about 110 hours in the control and 160 hours in the case of hyperthermia alone. Thus, these data suggest that the antitumor efficacy of hyperthermochemotherapy with MIS may be the result of a synergistic phenomenon of thermo-chemosensitization.

Animals↗

[Extended treatment for gastric cancer patients with peritoneal seeding].

Fourteen patients with far-advanced gastric cancer were treated surgically followed by intraperitoneal hyperthermic perfusion (IPHP) with mitomycin C (MMC) and misonidazole (MIS), a thermosensitizing drug. Immediately after extensive resection of the abdominal tumors, a 2-hour IPHP was performed at the inflow temperature 47.4 +/- 0.5 degrees C and at the outflow temperature 45.3 +/- 0.5 degrees C, using equipment designed for treatment of cancerous peritoneal seeding, as a closed circuit, and under hypothermic general anesthesia at 31.2 +/- 0.5 degrees C. In 6 of the 14 patients, cancerous ascites was absent after IPHP. Repeated cytologic examination of the lavage from pelvic cul-de-sac were negative, in all cases. The postoperative courses were uneventful except for 2 patients, in whom slight leakage occurred. All patients were discharged, and 4 in the 14 patients died of recurrence in the liver, abdominal and/or pleural cavities 8.8 +/- 2.1 months after IPHP. The remaining 10 are in good health 12.1 +/- 3.1 months after IPHP. Transient hepatic dysfunction and hypoproteinemia occurred after hyperthermia in all cases. This extensive surgery combined with IPHP using MMC and MIS was well tolerated and is a safe anti-tumor treatment for gastric cancer with peritoneal dissemination. Neurotoxicity due to MIS was nil.

Combined Modality Therapy↗

[The relationship between thermotolerance and the tissue oxygen tension in human gastric cancer tissue].

To study the relationship between thermotolerance and post-thermal phenomenon, tumor pO2 (TpO2) in xenoplanted gastric cancer tissue (H-23) has been measured by a polarographic method. The heat treatment was done in a water bath at 43.5 +/- 0.1 degrees C for 23 minutes. In order to produce thermotolerance, the second treatment was carried out at an interval of 24 hours, or, alternatively at 72 hours, or at 5 days or at 7 days. The thermotolerance of the H-23 tumor reached its maximum at the 72 hour-interval and was seen to disappear completely at 7 days. The TpO2 in the H-23 tumor decreased immediately after a single heat treatment and returned to its pre-treated value after 10 hours. In cases of the second heat treatment, the 72-hour interval group returned to its pre-treated value in 2-6 hours, whereas the 24-hour, 5-day, and 7-day interval groups showed a longer recovery time. The relationship between thermotolerance and TpO2 recovery was inverse at r = -0.858 and p = 0.035. Thus, our study suggests that not only is the thermotolerance affected by the alteration of the intra-cellular components, but also by the post-thermal changes in the tumor vessels.

Animals↗