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Biomedical subjects

T Nagata

Publications and source records attributed to T Nagata.

At least 559 records · Page 31Linked to original sources

[Phase I-II study of 7-N-(P-hydroxyphenyl)-mitomycin C (KW2083, M83)].

A phase I-II study of KW2083, an analog of mitomycin C (MMC) was performed in a total of 22 patients. KW2083 was escalated by single intravenous administration of 40, 50, 60, 70, and 80 mg/m2 doses. Treatments were repeated every 4-6 weeks unless unacceptable toxicities occurred. The median times taken to reach nadir for each dose level were 9-12 days for leukocytes and 7-13 days for platelets respectively. The median times taken for recovery were 8-22 days for leukopenia and 10-37 days for thrombocytopenia. Variable and non-predictable hematological toxicity was observed in some cases. Biphasic hematological toxicity was observed in 4 courses. Acute toxicity occurred in 17 courses for 11 patients and consisted of nausea (44%), vomiting (13%), diarrhea (2.7%) and stomatitis (2.7%). Nephrotoxicity (elevation of BUN, 8.1% and proteinuria, 5.4%) occurred in 3 patients who had no previous impairment of renal function. Alopecia (8.1%) was also observed. Marked elevations of hepatic enzymes were noted in one patient who developed acute fulminant hepatitis with the second dose of KW2083. Objective response was observed in one of 20 evaluable patients. From this preliminary study, the maximum tolerable dose is 70 mg/m2 and the optimal dose of KW2083 was determined to be 50 mg/m2 at 6-week intervals. KW2083 has been introduced as an MMC analog of potential interest. However, hematological and non of hematological toxicities are very similar to those of MMC and does not appear that KW2083 will supersede MMC.

Aged↗

[Ultrastructural observations of the dorsal lateral geniculate nucleus following non-surgical retinal lesion of the rats].

By intravitreal injection of arsenous pentoxide (As2O5), which had been used in the pulpectomy in the dentistry, the retina, including the ganglion cell layer, fell selectively into necrosis and the lesions were uniform throughout all part of the retina. Following these non-surgically induced retinal lesions, the dorsal lateral geniculate nucleus of the rats was examined by electron microscope over varying periods of time. From 2 days after the injection, dark atrophic axon terminals appeared in the dorsal lateral geniculate nucleus and these terminals were in most instances surrounded by swollen astrocytic processes with glycogen particles. The quantity of the degenerating terminals maximized at 6 to 7 days after injection and then decreased by 60 days. It was also shown that various features of the degenerating terminals were related to the postsynaptic dendrites. In early stages these degenerating axon terminals had dense, swollen mitochondria and many synaptic vesicles in the electron dense matrix. Then these terminals were deeply indented to the apposed dendrites and by this indentation the astrocytic process seemed to insinuate into the synaptic junction. In these situations, the cytoplasm of astrocytes increased in electron density around the terminals. The postsynaptic density and the subsynaptic organellas were clearly shown to be identical through the course of the degeneration. There were also dendro-astroglial junctions, and these junctions seemed to be one of the features of degeneration of the terminals. It was suggested that there was an obvious course of the degenerating terminals separated from their post-synaptic sites without disruption of integrity of the post-synaptic membrane specialization by astrocytic cell process in Wallerian degeneration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Immunocytochemical demonstration of retinol-binding protein in the lysosomes of the proximal tubules of the human kidney.

The localization of plasma retinol-binding protein (RBP) in the human kidney was determined by two immunocytochemical techniques, the PAP method and the protein A-gold technique. By using the affinity purified antibody against RBP obtained from the urine of the patients with cadmium poisoning (Itai-Itai disease), the immunoreactive substances were located by light microscopy in the proximal tubules of the human kidney. By immuno-electron microscopy, the stained organelles were identified as lysosomes in both S1 and S2 segments of the tubules. These data suggested that the reabsorption of low molecular weight plasma proteins like RBP can occur in the two segments. We inferred a similarity between the S1 and S2 segments concerning the reabsorption of RBP.

Histocytochemistry↗

Histochemical studies on the regeneration of aminergic nerves in rat cerebral artery after superior cervical ganglionectomy.

The course of regeneration of aminergic nerves in rat cerebral arteries was studied by means of histochemical methods, after uni- or bilateral cervical sympathectomy. Degeneration of aminergic nerves started on day 1 and was complete between days 3 and 7 after surgery. Between weeks 4 and 6, regenerating nerves started to appear from the proximal internal carotid artery. Regenerated aminergic nerve fibres were generally unbeaded and intensity of fluorescence was weak. The circular nerves appeared earlier than the longitudinal ones. The number of regenerating nerves reached the maximum, between months 9 and 12, at about half the normal level. AChE activity of the cerebral arteries showed no significant changes at any stage.

Acetylcholinesterase↗

Changing state of gastric cancer in Japan. Histologic perspective of the past 76 years.

One thousand thirty-eight patients with primary gastric cancer treated operatively during the past 20 year period were described. The results were compared with those in the period from 1904 to 1927 to illustrate the changes which have taken place in diagnosis and treatment of gastric cancer during the past 76 years in Japan. All data was from the Department of Surgery I, Kyushu University. After half a century of status quo, improvement started around the mid 1960s, which coincided with the introduction of newer, improved procedures for diagnosis of gastric cancer, such as double contrast roentgenography of the stomach, endoscopic observation, and biopsy of suspected lesions. A mass population survey for the presence of gastric cancer in persons of approximately 40 years of age has led to an ever increasing number of early gastric cancer cases. The emergence of early simulating advanced cancer with relatively good prognosis and the changing state of the Borrmann type of advanced cancer have contributed to the improvement. The present study demonstrates once again the importance of early detection of gastric cancer for an increased chance of cure, since conventional lymph node dissection seems to be unnecessary, and of even earlier detection of gastric tumors of less than 1 cm in diameter for the best chance of complete cure in the latter.

Adult↗

An ultrastructural study of the interaction of liposomes with plant protoplasts.

A one-step procedure using a mixture of glutaraldehyde and osmium tetroxide was devised to fix in situ large unilamellar liposomes of phosphatidylserine for transmission electron microscopy (TEM), since the conventional fixation method was found to be inadequate in this respect. The new fixation procedure enabled us to visualize the sequence of events in the interaction of liposomes with protoplasts from Vinca rosea suspension cultures in the presence of polyethylene glycol. Liposomes were thus found adhering to the surface of protoplasts, in association with invaginating plasmalemma, and within intracellular vesicles. These observations showed that liposomes enter plant protoplasts via endocytosis. Ultrastructural profiles indicating fusion of liposomes with protoplasts were not observed.

Cell Membrane↗

Clinical application of the enzyme immunoassay for pancreatic oncofetal antigen.

Pancreatic oncofetal antigen (POA) purified by us has been detected in sera of patients with carcinoma of the pancreas by the micro-Ouchterlony method. In an attempt to improve the sensitivity and clinical usefulness of the serum POA assay, we established an enzyme immunoassay for POA and reported the results with this method. In this study, we investigated serum POA levels in pancreatic cancer and other diseases. The tissue localization of this POA in the pancreas was also studied. For the establishment of the enzyme immunoassay, an anti-POA-F(ab')2 fragment prepared from absorbed antiserum was conjugated with beta-D-galactosidase. The solid-phase "sandwich" principle was used. The normal upper limit of the serum POA level was defined as 400 units/ml. Among 60 patients with pancreatic cancer, 44 had elevated levels (73.3%). Of 22 cases with chronic pancreatitis, 4 had elevated levels (18.2%). In malignant diseases other than pancreatic cancer, elevated levels of serum POA were seen in 17.6% to 48.5% of the patients, most of whom had only slightly elevated levels. These results indicate that enzyme immunoassay for POA is clinically useful for making a diagnosis of pancreatic cancer. Immunoperoxidase staining showed POA to be found at the apical surface of ductular cells in fetal pancreas, at the luminal surface of glandular structures in pancreatic cancer tissue, and also at the luminal surface of the small duct in normal pancreas. Thus it is suggested that a high level of serum POA in patients with pancreatic cancer is derived from pancreatic cancer tissue.

Adult↗

[Clinical studies of an ampicillin suppository (KS-R1) in children].

Clinical trials of KS-R1 have been carried out on 28 infections in children, including 8 pharyngitis, 11 tonsillitis, a pharyngolaryngobronchitis, 3 lymphadenitis and 5 urinary tract infections. The following results were obtained. KS-R1 30-50 mg/kg/day, was clinically effective in 27 out of 28 infections. Bacteriologically, the following routine clinical isolates were identified; Enterococci in 1 case, S. viridans 1 case, S. pneumoniae 1 case, S. pyogenes 2 cases, H. parainfluenzae 1 case, E. coli 5 cases and S. aureus + H. influenzae 1 case. Every isolated organism showed +++ sensitivity to the ABPC sensitivity disc in vitro without only 1 case of E. coli. The organisms were eradicated in 11 patients after the administration of KS-R1. Adverse effects did not occur in any patient without case 25, who complained of pollakiuria.

Acute Disease↗

[Combination of intra-arterial administration of anticancer agent and hemocarboperfusion in treatment of advanced cancer].

Nineteen patients with malignant tumors were treated with a combination of bolus administration of mitomycin C with direct hemoperfusion over charcoal, and 15 patients were valuable. Mitomycin C of 1 mg/kg was administered via a catheter placed into the regional artery. Seven out of 14 patients with genitourinary cancers: 4 out of 9 patients with urinary bladder, 2 of 4 patients with renal and one prostate responded to the therapy. There were 4 responders out of 8 in the one-shot administration group, on the other hand, 7 cases receiving continuous infusion of 60 to 120 minutes responded. In both the one-shot group and the continuous group nausea and vomiting were observed in 21% and 11% respectively. Three patients receiving continuous administration of mitomycin C had local ulcerations. Myelosuppressions such as leukocytopenia and thrombocytopenia were observed in 37% of the both groups.

Antibiotics, Antineoplastic↗

[Adjuvant chemotherapy for extranodal non-Hodgkin's lymphoma].

From 1976 to 1982, twenty-four cases with early stages (stage IE: 18, Stage IIE: 6) of extranodal non-Hodgkin's lymphomas were treated with combined modality of local treatment (radiation or operation) and an adjuvant chemotherapy consisting of vincristine, cyclophosphamide and prednisolone. Eighty-three percent of patients were diffuse histiocytic type. The most common sites of primary origin were in stomach; 13 patients and 7 patients in nasal or paranasal cavity. The disease-free survival rates at 5 years were 74% for stage IE and 80% for stage IIE, respectively. The result has suggested that adjuvant chemotherapy is a useful modality for extranodal non-Hodgkin's lymphoma.

Adult↗

[Non-Hodgkin's malignant lymphoma with central nervous involvement--report of 7 cases].

We encountered 7 non-Hodgkin's lymphomas involving the central nervous system (CNS) among 78 cases of lymphomas seen at the 3rd Dept. of Internal Med. between 1965 and 1980; 5 cases were diffuse histiocytic lymphomas (DH) and 2 were diffuse poorly differentiated lymphomas (DPDL). The age ranged from 27 to 66 years, there were 6 males and 1 female. In 4 cases, CNS involvement was the presenting symptom at the time of diagnosis of lymphoma. The diagnostic procedures in CNS lymphoma included complete neurological physical examination by a neurologist, spinal fluid cytology, surface marker study on lymphocytes of spinal fluid, if possible, computed tomography scan, and myelogram if spinal cord compression was suspected. The prognosis of patients with CNS involvement by lymphoma was poor even if early diagnosis was made. The conventional therapy for CNS lymphoma included cranial irradiation, systemic chemotherapy, and intrathecal instillation of methotrexate and/or cytosine arabinoside, or a combined modality; however, these treatments were only effective temporarily.

Adult↗