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Biomedical subjects

M Ohta

Publications and source records attributed to M Ohta.

At least 865 records · Page 48Linked to original sources
PubMed1989

Sugar sequences of allergenically active oligosaccharide alcohols isolated from a large-molecular-size sea squirt antigen termed H-antigen.

O-Glycosidically linked oligosaccharide chains were liberated as oligosaccharide alcohols (HPG-beta 2) by beta-elimination treatment from a glycopeptide fraction (HPG, Mr ca. 10(5)) that was isolated from a Pronase digest of a large-size sea squirt antigen termed H-antigen (Mr 10(6)-2 X 10(7)). After HPG-beta 2 was divided into a neutral (HPG-beta 2-N) and an acidic (HPG-beta 2-A) fraction, 11 neutral saccharitols were isolated from HPG-beta 2-N, and their sugar sequences were determined by methylation/GC-MS, FAB-MS, and/or DI/EI-MS. By skin tests specific to patients with sea squirt allergy, it was found that six saccharitols were allergenically active but five were inactive. Furthermore, active saccharitols were all of branched structure containing two nonreducing terminal GalNAc (t-GalNAc) residues, whereas the inactive saccharitols contained one or no t-GalNAc. Since the allergic reaction in skin should depend on the crosslinking of IgE antibodies by certain allergens carrying two or more epitopes, three types of N-acetylgalactosaminyl disaccharide units, GalNAc1----2Fuc1----, GalNAc1----3/4GalNAc1----, and GalNAc1----3/4GlcNAc1----, were nominated as the major components of the allergy-specific epitopes in the active saccharitols. Such multiplicity of the epitope structures might reflect the polyclonality of the specific IgE antibodies.

Allergens↗
PubMed1989

Recombinant human granulocyte colony-stimulating factor as an activator of human granulocytes: potentiation of responses triggered by receptor-mediated agonists and stimulation of C3bi receptor expression and adherence.

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) enhanced superoxide release and membrane depolarization in parallel in human granulocytes stimulated by the receptor-mediated agonists, N-formyl-methionyl-leucyl-phenylalanine and wheat germ agglutinin, but not by the Ca2+ ionophore ionomycin and phorbol myristate acetate, which bypass the receptors to stimulate the cells. The optimal effect was obtained by pretreatment of cells with 25 to 50 ng/mL (1.3 to 2.6 nmol/L) rhG-CSF for 10 minutes at 37 degrees C. rhG-CSF produced by bacteria and mammalian cells had identical biological effects on a molar basis. rhG-CSF neither affected stimulus-induced increase in cytoplasmic free Ca2+ nor changed the number and affinity of N-formyl-methionyl-leucyl-phenylalanine receptors. The priming effect of rhG-CSF was temperature dependent and did not require new protein synthesis. rhG-CSF increased the expression of C3bi receptors on human granulocytes and enhanced granulocyte adherence to nylon fiber. The optimal effect was obtained by pretreatment of cells with 25 to 50 ng/mL rhG-CSF for 30 minutes at 37 degrees C. rhG-CSF had no effect on human monocytes. These findings demonstrate that rhG-CSF can selectively stimulate mature granulocyte functions.

Calcium↗
PubMed1989

Isolation and characterization of a tumor-derived human pancreastatin-related protein.

A protein with pancreastatin-like immunoreactivity has been isolated and purified from liver metastasis of a patient with insulinoma. NH2-terminal sequence analysis in conjunction with the use of antibodies specific for the C-terminal structure of pancreastatin identified this protein as a 186-amino acid residue protein corresponding to human chromogranin A-116-301. Using a sensitive radioimmunoassay it was found that serum from the patient with insulinoma contains two peptide species; one comigrates with the 186-amino acid residue pancreastatin and the other the 48-residue pancreastatin.

Amino Acid Sequence↗
PubMed1989

Clinical trial with surgery and intraperitoneal hyperthermic perfusion for peritoneal recurrence of gastrointestinal cancer.

To treat six patients with peritoneal recurrence after radical operation for gastrointestinal cancer, an intraperitoneal hyperthermic perfusion (IPHP), combined with surgical resection of recurrent tumors, intestinal by-pass anastomosis, or both, was carried out. Immediately after complete resection of the intraperitoneal recurrent tumors, a 2- to 3-hour IPHP was performed under hypothermic general anesthesia at about 32 degrees C, using a perfusate containing 10 micrograms/ml or 20 micrograms/ml of mitomycin C (MMC) warmed at the inflow temperature of 46.6 degrees C to 46.9 degrees C. The apparatus used for IPHP was designed for intraperitoneal perfusion as a closed circuit. Although five of the six patients had a malignant peritoneal effusion at the time of admission, the effusion disappeared soon after IPHP, and no cancer cell was present in the lavage from Douglas' pouch. The other patient had a recurrent tumor at the anastomotic region after low anterior resection for rectal cancer and complete resection of the recurrent tumor, combined with IPHP, was carried out. One patient with a recurrent gastric cancer died of hepatic metastasis and cancerous pleuritis 5 months after this treatment, and the other five are in good health 12.8 +/- 5.1 months after IPHP. On the other hand, five patients with intra-abdominal recurrent gastric cancer, who received only surgical treatment within the same period of time, died 3.0 +/- 2.1 months after the surgery. Postoperatively, in the six patients with IPHP, transitory hepatic dysfunction, hypoproteinemia, and thrombocytopenia occurred. These results show that IPHP using MMC combined with surgery is a safe, reliable treatment for patients with peritoneal recurrence of gastrointestinal cancer.

Adult↗
PubMed1989

Identification of protein-bound riboflavin in rat hepatocyte plasma membrane as a source of autofluorescence.

The presence of flavin compound(s) giving a yellowish-green autofluorescence in rat hepatocyte plasma membrane has recently been reported (Nokubo, M. et al. (1988) Biochim. Biophys. Acta 939, 441-448). The fluorophore can quantitatively be extracted with water at 80 degrees C from isolated plasma membranes. Gel filtration of the extract eluted with water showed two peaks, the fluorescence of which closely resembled that of riboflavin. The major peak comigrated with proteins and the minor one displayed a position identical to authentic riboflavin. When the components of the major peak were rechromatographed after acetic acid treatment and eluted with 20 mM of acetic acid, the fluorescent compound separated from the proteins and eluted at the same position as riboflavin. In paper chromatography and HPLC, the behavior of the fluorescent compound (separated by acid treatment from the proteins) was identical to that of riboflavin. SDS gel filtration of subcellular fractions of rat liver revealed that riboflavin was the dominant flavin, whereas FAD and FMN were not detectable in the plasma membrane. Microsomes and mitochondria contain predominantly FAD and FMN, and only minor quantities of riboflavin. The presence of riboflavin in the plasma membrane is a novel finding, the functional significance of which is still unclear; however, a hypothesis can be forwarded on the basis of the ability of flavins to generate superoxide anion radicals during their autoxidation.

Animals↗
PubMed1989

Elevation of sialyl stage-specific mouse embryonic antigen levels in pleural effusion in patients with adenocarcinoma of the lung.

Sialyl stage-specific mouse embryonic antigen (SSEA-1) levels were measured in pleural effusions obtained from patients with lung cancer and benign pulmonary disease, using a solid-phase immunoradiometric sandwich assay. The mean (+/- SEM) levels (unit/ml) of pleural fluid sialyl SSEA-1 were 3620 +/- 1419 in adenocarcinoma (n = 25), 123 +/- 30 in nonadenocarcinoma (n = 13) and 95 +/- 19 in benign pulmonary disease (n = 13), respectively. The positive rate was 64% in adenocarcinoma, 7.7% in nonadenocarcinoma, and 0% in benign pulmonary disease, respectively, when a cutoff level was defined as the mean + 3 SD value (300 unit/ml) based on pleural fluid sialyl SSEA-1 levels in benign pulmonary disease. There was a significant positive correlation between pleural fluid levels of sialyl SSEA-1 and those of carcinoembryonic antigen in adenocarcinoma patients (r = 0.8246, P less than 0.01). Pleural fluid sialyl SSEA-1 levels correlated with cytologic findings in adenocarcinoma patients. These observations suggest that sialyl SSEA-1 in pleural effusion is a useful marker to discriminate malignant from nonmalignant and adenocarcinoma from nonadenocarcinoma of the lung.

Adenocarcinoma↗
PubMed1989

[Hematopoietic recovery after autologous bone marrow transplantation in high-dose chemotherapy of cancer patients].

In order to evaluate the possible utility of autologous bone marrow transplantation (ABMT), eighteen cancer patients were treated with high-dose combination chemotherapy supported by ABMT. We investigated CFU-GM/kg infused as well as bone marrow nucleated cells/kg to predict for hematopoietic recovery. Although hematopoietic recovery was not related to the nucleated cell number of the transfused bone marrow, CFU-GM infused related significantly to neutrophil recovery to 500/mm3 (correlation coefficient, r = -0.73, p less than 0.001) and platelet recovery to 50,000/mm3 (r = -0.69, p less than 0.001). Furthermore, a significant relationship of CFU-GM infused to the period of neutropenia below 500/mm3 was observed (r = -0.67, p less than 0.001). Taken together, CFU-GM dose can predict for neutrophil and platelet recovery, suggesting that ABMT can shorten the period of bone marrow suppression following high-dose chemotherapy.

Adult↗
PubMed1989

Surgical treatment of patients with small cell carcinoma of the lung: a histochemical and immunohistochemical study.

Thirty-three patients with small cell carcinoma of the lung were treated surgically, and immunohistochemistry of the cell differentiations was examined in detail. The overall 5-year survival rate was 38% and the rates in patients with stage I or stage III were 57% and 11%, respectively (P less than 0.05). Survival rates in patients with the oat cell type and intermediate type were 24% and 44%, respectively, but with no significant difference. This carcinoma seemed to originate from primitive multipotential stem cells, i.e., those of a neuroendocrine or epithelial nature. Histochemically and immunohistochemically, argyrophilic granules and neuron-specific enolase, neuroendocrine markers, were detected more frequently in the oat cell type rather than in the intermediate type. In contrast, keratin, epithelial membrane antigen, and carcinoembryonic antigen, epithelial origin markers, were present more frequently in the intermediate type than in oat cell type. However, the difference was significant only in case of detection of argyrophilic granules and the carcinoembryonic antigen (P less than 0.05). Our current recommendation is that surgical resection should be done in the earlier stage in both subtypes. A more favorable prognosis can be expected when adjuvant chemotherapy is prescribed.

Adult↗
PubMed1989

Adenoid cystic carcinoma of the tracheobronchial tree: clinicopathology and immunohistochemistry.

Adenoid cystic carcinoma of the tracheobronchial tree in five patients was treated surgically and the clinicopathologic manifestations and histogenesis were examined in detail. Symptoms such as cough, dyspnea, hemoptysis, and atelectasis on chest X-ray were present in four patients, and the other patient was asymptomatic. Histologically, growth patterns were classified as tubular, cribriform, and solid. The solid pattern was the most aggressive with extensive perineural invasion. Immunohistochemically, secretory component, lactoferrin, and epithelial membrane antigen were present in the cells lining the gland-like lumen of tissues with the tubular and cribriform patterns, but was rare in those with a solid pattern. Desmin and S-100 protein were detected in the nonlining cells of tissues with all three patterns. These findings suggest that this tumor originates from the myoepithelial cells of the bronchial gland and that the solid pattern was the most poorly differentiated form.

Adult↗
PubMed1989

Blood transfusion and the prognosis of patients with gastric cancer.

A retrospective analysis was undertaken of the association between blood transfusion and long-term results for 218 patients with stage III gastric cancer who were curatively treated by partial gastrectomy. One hundred and fifty-two patients received blood transfusion within the perioperative period. The postoperative 5-year survival rates were 49.3% for the transfused patients and 62.1% for the non-transfused patients (P less than 0.05). Furthermore, the postoperative survival of patients who had been transfused preoperatively was significantly lower than that of the non-transfused patients. The preoperatively transfused group of patients were found to have tumors that were larger than those of the non-transfused group. On the basis of the above data, it appears that the prognosis of patients with advanced gastric cancer is poorer when such patients receive preoperative blood transfusion than when patients do not receive transfusions, and that this adverse effect in the transfused patients is probably attributable to the larger size of their tumors, even though the stage of advancement of gastric cancer is the same in both groups of patients.

Adult↗
PubMed1989

Lipofuscin-like substances accumulate rapidly in brain, retina and internal organs with cysteine protease inhibition.

The protease inhibitor, leupeptin, has been previously shown to cause an accumulation of lysosomally associated intracytoplasmic dense bodies resembling lipofuscin when administered intraventricularly to the brains of young rats (Ivy et al., Science, 226:985, 1984). These findings support the idea that lipofuscin formation during normal aging involves perturbed proteolytic degradation. In the current study, we delineate more precisely the proteolytic mechanisms in question and examine the effects of protease inhibition on other tissues and species. Four sets of experiments were done. In the first, rats were administered leupeptin (L; an inhibitor of cysteine and some serine proteases), E-64C (a cysteine protease inhibitor), chloroquine (C; a lysosomal enzyme inhibitor), aprotinin (A; a serine protease inhibitor) or physiological saline (S) into the lateral ventricle of the brain at a constant rate for two weeks using an osmotic mini-pump. In the second set, beagle dogs were administered L or S intraventricularly in a similar fashion. In the third set, young rats received intraocular injections of L, E64C, C, A or S from 1 to 9 days at 24 hr intervals. In the fourth set, young rats and mice were administered L, E-64C or S intraperitoneally via an osmotic mini-pump for 2 or more weeks. The tissue of all animals was processed for light and electron microscopy as well as for fluorescence analysis. In rat brain cells (especially hippocampus and cerebellum), substances which by morphological, histochemical and fluorescence emission criteria resemble lipofuscin, accumulated following L, C or E64C, but not A or S treatment. A similar buildup of lipofuscin-like substance occurred in canine brain following L but not S infusion. In retinal pigment epithelial cells, undigested rod outer segment discs accumulated after L, C or E-64C and possibly A, but not after S injections. With increasing survival times, the accumulated substances became morphologically more similar to lipofuscin. Cells of liver (both hepatocytes and non-parenchymal cells) and kidney (mainly renal tubule cells) also accumulated substances resembling lipofuscin in response to L but not S infusion; other internal organs were differentially affected. These results demonstrate 1) that specific inhibition of cysteine proteases is sufficient to cause accumulation of lipofuscin-like substances in brain and retina and 2) that several species and organ systems are similarly affected by protease inhibition. Taken together, these findings are consistent with the idea that defective or decreased proteolysis by lysosomal cysteine proteases is responsible for lipofuscin accumulation during normal aging.

Aging↗
PubMed1989

Morphological, physiological and biochemical alterations in livers of rodents induced by protease inhibitors: a comparison with old livers.

A "Protease inhibitor model of aging" has been proposed primarily based on observations on brain tissues exposed to a thiol protease inhibitor, leupeptin (Ivy et al., 1984a). In order to validate this model in terms of a mechanism of cellular aging, as well as of lipofuscin formation in particular, attempts have been made to induce lipofuscin in hepatocytes in young rodent (rat and mouse) livers by continuous i.p. infusion of two different thiol protease inhibitors, leupeptin and E-64C. With doses of leupeptin higher than 1.0 mg/100g/day for 2 wks, a fine granular lipofuscin-like deposition with distinct yellowish-green fluorescence was induced in young rat hepatocytes. The deposition became greater in degree with increasing leupeptin doses. In Kupffer cells and other endothelial cells, fluorescent granules were also induced. In contrast to rat livers, lipofuscin-like pigments induced in hepatocytes in mice were much less, even with a higher dose (20 mg/100 g/day). E-64C also induced the accumulation of lipofuscin-like pigments at a dose of 5 mg/100 g/day, their characteristics being very similar to those induced by leupeptin, but the accumulation being smaller in degree. The fluorescence of leupeptin induced lipopigments was yellowish-green having a peak around 520 nm in emission profile, closely resembling that observed in old rat livers. The hepatobiliary transport functions such as biliary transport maximum (Tm) for sulfobromophthalain and the biliary recovery of iv injected ouabain which are known to decline with age tended to decline in young (6-wk-old) rats administered with leupeptin at a dose of 5 mg/100 g/day for 2 wks. On the other hand, dolichol concentration in leupeptin treated livers was not increased in comparison to control livers, whereas in old rat livers, the dolichol concentration was more than 2 times greater than in young livers. A clear-dose-dependent deposition of ceroid-lipofuscin induced in young rodent livers by protease inhibitors strongly suggests that the "Protease inhibitor model" is generally valid not only for the brain but for other tissues such as the liver, and for two different thiol protease inhibitors.

Aging↗
PubMed1989

Serological response to P-fimbriae of Escherichia coli in patients with urinary tract infections.

The antibody response to P-fimbriae of Escherichia coli in patients with upper urinary tract infections was investigated. In the sera of patients with pyelonephritis obtained at the initial visit to hospital (3 to 7 days after the onset of symptoms), a high incidence of antibodies to P-fimbriae was detected (12 out of 14 patients). P-fimbriated Escherichia coli strains were isolated from urine samples in all of these antibody-positive patients. Antibodies detected by ELISA using purified antigen were essentially IgG and specifically recognized P-fimbriae. These antibodies inhibited completely, or in some cases partially, mannose-resistant hemagglutination with P-fimbriated Escherichia coli.

Antibodies, Bacterial↗
PubMed1989

Thermotolerance of xenografted human gastric cancer.

To compare the thermotolerance in vivo of two human gastric cancers with different doubling times, the xenografted tumors were warmed twice at 43.5 +/- 0.1 degree C in a water bath for 20 minutes at a predetermined interval. In the tumors with doubling times of 5.2 and 10.9 days, a 7-day interval heat treatment resulted in a prolongation in tumor tripling times by 156 per cent and 132 per cent, respectively, compared with a single heat treatment for 40 minutes. On the contrary, two heat treatments given at intervals of 3 to 5 days had a short tumor tripling time, compared to that of the 40-minute single treatment. Thus, the thermotolerance of these human gastric cancers gradually increased to a maximum within a 3- to 4-day interval and disappeared completely after a 7-day interval. These results indicate that the times required to reach maximal thermotolerance in these human gastric cancers were longer than those previously demonstrated for human and rodent cancer cell lines in vitro. The development and decay of thermotolerance in these human gastric cancers need to be considered in the design of multiple-fractionated regimens.

Adenocarcinoma↗
PubMed1989

Multimodality therapy for small cell carcinoma of the lung--the role of surgical treatment.

Reviewing the outcome of 70 cases of clinically localized small cell lung cancer (SCLC) treated with combined modality treatment, we attempted to define the role of resection in this disease. The survival rate for all cases was 37 per cent at 2 years and 23 per cent at 3 years with a median survival time (MST) of 14 months. For 25 resected cases the overall 5-year survival rate was 37 per cent with an MST of 26 months. According to clinical staging, 5-year survival was 64 per cent for stage I and 20 per cent for stage II. However, none of the stage III cases achieved long-term survival, of over 3 years. In 45 non-resected cases, the overall response rate was 84 per cent with a 44 per cent complete response. The overall survival rate was 27 per cent at 2 years and 14 per cent at 3 years with an MST of 11 months. The 20 cases who achieved complete response had an MST of 26 months with 51 per cent alive at 2 years and 19 per cent at 5 years. Thus, we consider that lung resection is definitely indicated in cases with stage I and probably stage II SCLC. For stage III, however, particularly in cases with N2 disease, resection seems to offer no special benefit in favor of survival compared to combination chemotherapy and radiotherapy.

Adult↗