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Biomedical subjects

H Inaba

Publications and source records attributed to H Inaba.

At least 163 records · Page 9Linked to original sources

Localized necrotizing arteritis. A report of two cases involving the gallbladder and pancreas.

We report two cases of localized necrotizing arteritis, one involving the gallbladder and one involving the pancreas. Both cases were found incidentally in surgically resected specimens. Vascular changes in both cases were similar to those seen in classic polyarteritis nodosa, involving medium-sized muscular arteries characterized by fibrinoid necrosis and panarterial and periarterial inflammations varying from active to resolving stages. Both patients had no constitutional symptoms or underlying serologic abnormalities suggestive of systemic angitis. To our knowledge, pancreas-limited arteritis has not previously been described. Whether these lesions represent an early manifestation of a systemic arteritides syndrome, a variant of polyarteritis nodosa, or a distinct entity should be prudently judged through a long-term follow-up.

Adult↗

Absence of the Staub-Traugott effect in endotoxicosis.

Intravenous glucose tolerance tests (IVGTTs) using 1.2 g/kg of D-glucose in fasted, male rats were repeated twice, with an interval of 75 min, during early (2.5 hr) and late (26.5 hr) nonlethal endotoxicosis induced by Salmonella enteritidis endotoxin (ETX) at 10 micrograms/kg i.v. In comparison with saline controls, glucose tolerance was dramatically increased in early endotoxicosis; however, it was restored to near normal in late endotoxicosis. Augmentation of tolerance by repeated IVGTTs i.e. the Staub-Traugott effect, occurred in the saline control groups; however, it was absent in both early and late endotoxicosis. The elevations of plasma insulin (IRI) in response to the glucose loads were exaggerated vs. controls in both early and late endotoxicosis; however, the hyperinsulinemias were not significantly diminished by repeated IVGTTs in any group. These results indicate loss of the Staub-Traugott effect in endotoxicosis that is 1) independent of augmented insulin secretory responses to a repeated glucose challenge and 2) dependent on some adaptive cellular mechanisms to repeated glucose loads which were impaired in nonlethal endotoxicosis.

Animals↗

[Antitumor activity of HO-221, a derivative of benzoylphenylurea against human cancer xenografts in nude mice].

HO-221, a derivative of benzoylphenylurea, is a newly developed anticancer drug which was found to show an excellent antitumor effect against transplantable murine tumors by the novel mechanism of action. This study was designed to evaluate the antitumor effect of HO-221 and to establish the optimum regimen, using seven human gastrointestinal and breast cancers xenografted in nude mice. Better antitumor effect of HO-221 by oral administration was observed when it was suspended in larger volume of the vehicle. Moreover, the effect increased by the multiple intermittent administration compared to the single treatment. Best antitumor effect was observed by oral administration of 75 mg/kg (0.1 ml/10 g mouse body weight) repeated twice weekly for a total of eight times or 300 mg/kg (0.2 ml/10 g mouse body weight) repeated once weekly for a total of four times. The antitumor effects of these two regimens were approximately equal except against H-31, the former regimen being more effective. When the tumor growth inhibition rate (IR) over 58% was rated as "effective", the above two regimens were equally effective against 4 of 7 cancers, H-111, H-154, H-143 and H-31. While HO-221 was not effective to a gastric cancer line, H-81, which was most susceptible to the variety of existing anticancer agents, but effective to another gastric cancer line, H-111, which was relatively resistant to conventional cytocidal agents. From the aspect of chemosensitivity spectrum, this drug revealed a rather different pattern compared to other antimetabolites. Although oral administration volume is limited in small animal model, enhancing its antitumor effect may be possible in clinical application by contriving the method of administration. HO-221 is, thus, considered to be a promising drug for further study.

Administration, Oral↗

[Combination chemotherapy of HO-221, a derivative of benzoylphenylurea with various anticancer agents against human cancer xenografts in nude mice].

Antitumor effect of HO-221, a derivative of benzoylphenylurea, has been previously studied against seven human cancer xenografts in nude mice established and maintained in our laboratory. In this study, the effect of combination chemotherapy was examined with six of the above seven human cancer cell lines. These consisted of four gastric cancers (H-55, H-111, H-81 and H-154), one breast cancer (H-31) and one pancreatic cancer (H-48). HO-221 was used in combination with one of the following widely used anticancer drugs; mitomycin (MMC), adriamycin (ADM), CDDP, VP-16 and 5-fluorouracil (5-FU). When the tumor growth inhibition rate (IR) by combination of two drugs (at 1/2 MTD for each drug) exceeded both of IR obtained separately with single drug at 1/2 MTD, the combination regimen was rated as showing an additive effect. When IR by combination of two drugs at the same dose level exceeded both of IR obtained separately by MTD of each single drug, the regimen was rated as showing a synergistic effect. Histological changes and side-effects were also taken into consideration for the evaluation of the drug. Combination of HO-221 and MMC produced an additive effect against H-55 and H-111, a synergistic effect against H-81. In the treatment of H-31 which was highly susceptible to these drugs, a remarkable effect was shown in both IR and cellular changes even by combination using 1/2 MTD and 1/4 MTD doses. Combination with ADM at 1/2 MTD for both produced an additive effect against H-111 and H-48. Combination at MTD produced a marked antitumor effect against H-111 and a strikingly remarkable combination effect was confirmed. Combination with CDDP produced an additive effect against H-81 and a synergistic effect against H-154. Moreover, the weight loss by this combination regimen was far less than that by single administration of CDDP at MTD. An additive effect was demonstrated by combination with VP-16. Combination with 5-FU produced minimal combination effect. HO-221 was thus found to have a high antitumor effect by combination with various anticancer agents that are at present widely used clinically. HO-221 is expected to be a promising anticancer drug in its clinical application.

Animals↗

[Treatment of endoscopic laser therapy for obstruction due to granulation at the anastomosis site after right sleeve lobectomy].

A case treated with endoscopic laser therapy for obstruction due to granulation at the anastomosis site after sleeve lobectomy was reported. A 57-year-old male was admitted to our hospital with complaint of dyspnea four months after right sleeve upper lobectomy for long cancer. Chest roentgenogram showed complete atelectasis of the right lung and bronchoscopy revealed obstruction at the anastomotic site. The biopsy of the site showed granulation tissue. Pulmonary angiography immediately after bronchography yielded 3 to 4 mm obstruction in length and no particular vascular communication between the obstruction site and pulmonary vessel. Nd-YAG Laser irradiation of 774 Joules gave complete reopening. Good patency has been maintained one month since the laser therapy. It is important to recognized bronchus peripheral to the obstructive site and to identify the correlation between the anastomotic site and vascular system preoperatively. Pulmonary angiography combined with bronchography examination could be very useful to obtain these information.

Anastomosis, Surgical↗

[Time-course of the concentration of cefotiam in human extra-vascular pulmonary tissue].

The concentration of cefotiam in the blood and in blood-free, extra-vascular pulmonary tissue (lung tissue) was determined and its transition into the lung tissue was observed. One gram of cefotiam was injected intravenously into 27 lobectomized cases of bronchogenic carcinoma at 30 (n = 8), 60 (n = 6), 120 (n = 7) and 180 minutes (n = 6) before thoracotomy. Informed consent was obtained from these patients before the study. Lung samples were collected from the resected lobe immediately after thoracotomy, and the blood samples were also collected. Drug concentrations of the lung and blood specimens were determined. The blood volume of the lung sample was determined according to the gravimetric method with hemoglobin as an index. The drug concentration in the lung tissue was determined by the difference of the concentration between blood and lung. The time-courses of lung tissue drug concentration and blood drug concentration were compared. The lung tissue drug concentration reached a peak at 30 minutes after intravenous injection and thereafter decreased gradually, reaching equilibrium at about 50% of the blood concentration. Thirty minutes after intravenous injection, the lung tissue drug concentration was higher than the blood concentration, suggesting a higher rate of transition of the drug from the blood to the lung tissue than vice versa.

Biological Availability↗

[A case of pulmonary nocardiosis with squamous cell carcinoma].

A 61-year-old man was admitted to our hospital with cough, bloody sputum, and chest pain. Bronchoscopy showed a tumor in the truncus intermedius which biopsy and brushing cytology revealed to be squamous cell carcinoma. Also, bronchial washings grew only N. asteroides. Treatment with minocycline and trimethoprimsulfamethoxazole (TMP/SMX) over one month resulted in some improvement in pulmonary symptoms and resolution of the infiltrates in the right lower field. Then, right pneumonectomy was performed. N. asteroides was isolated from the resected tumor. Aggressive bacteriological examinations should be utilized when the possibility of pulmonary nocardiosis is considered.

Carcinoma, Squamous Cell↗

Ultraweak photoemission from dark-adapted leaves and isolated chloroplasts.

Dark-adapted isolated spinach chloroplasts and leaves, unlike sub-chloroplast fractions, are capable of emitting ultraweak light spontaneously (50-125 counts/s per cm2). The emission of leaves is due to two processes with activation energies of 97 and 25 kJ/mol while in isolated chloroplasts, it is the result of a single process (98 kJ/mol), as indicated by the Arrhenius plots of the intensity. Emission spectra demonstrate that the terminal step of these reactions is the excitation of chlorophyll in both samples. We suggest that the additional component in the ultraweak light emission of leaves may be related to mitochondria.

Chlorophyll↗

The first observation of O2- generation in in situ lungs of rats treated with drugs to induce experimental acute respiratory distress syndrome.

To investigate O2- generation in in situ lungs of rats treated with drugs to induce experimental acute respiratory distress syndrome, phorbol myristate acetate (PMA) or endotoxin were injected into rats, who had been continuously infused with 2(methyl-6-[p-methoxyphenyl]-3,7-dihydroimidazo[1,2-alpha]pyraz in-3-one (MCLA) and the chemiluminescence in in situ lung was detected by a sensitive photon counter. In PMA-treated rats, two phases of chemiluminescence over non-specific chemiluminescence were observed. The first phase luminescence was sensitive to Cu-Zn superoxide dismutase, while the second phase chemiluminescence was less sensitive to Cu-Zn superoxide dismutase. Similar chemiluminescence was detected in the rats treated with endotoxin instead of PMA, but not in neutropenic rats.

Animals↗

Threshold and stability results for an age-structured epidemic model.

We study a mathematical model for an epidemic spreading in an age-structured population with age-dependent transmission coefficient. We formulate the model as an abstract Cauchy problem on a Banach space and show the existence and uniqueness of solutions. Next we derive some conditions which guarantee the existence and uniqueness for non-trivial steady states of the model. Finally the local and global stability for the steady states are examined.

Age Factors↗

Effects of iron and desferrioxamine on Rhizopus infection.

To investigate the association among iron, desferrioxamine, and a Rhizopus infection, the influence of iron and/or desferrioxamine on experimental mucormycosis in mice was examined. All mice pretreated with iron, desferrioxamine, or a combination of iron and desferrioxamine died within 5 days after the inoculation of R. oryzae. In the mice fungal lesions were observed in the brain which resembled human cerebral mucormycosis. By contrast, the mortality in the control mice with R. oryzae was 20% through the 3-week experimental period. Therefore, it was demonstrated that iron as well as desferrioxamine administration markedly promotes the growth of R. oryzae. The increased susceptibility to R. oryzae was considered to be due to increased serum iron in the animals pretreated with iron only; however, pretreatment with desferrioxamine did not affect the amount of serum ion. Thus, the data suggest that desferrioxamine acts as a siderophore to R. oryzae and exerts an adverse effect on mucormycosis. This study has shown that the presence of iron and desferrioxamine enhances the virulence and pathogenicity of R. oryzae by serving as a growth factor.

Animals↗

A tubular bioreactor for high density cultivation of microorganisms.

By simulating the functions of the animal intestine, the authors have developed a novel tubular bioreactor (TBR) which is capable of containing both the reaction and separation of products in a single system. This reactor consisted of inorganic ultra filtration membrane modules in the primary part of the system, a heat exchanger and a recycling pump. The operation characteristics of the TBR were studied by cultivating Lactobacillus casei at a laboratory scale. The cell density obtained was up to 10 times higher than the density obtained by using the conventional jar fermentor. Furthermore, 40 g l-1 of cell mass was obtained in only 14 hours with 20 l of fresh medium when the dilution rate was increased according to the cellular growth. Afterwards, the cultivation time and the volume of fresh medium were reduced to 44% and 74%, respectively, of the values in the cultivation operation at constant dilution rate.

Bacteriological Techniques↗

[Cytotoxicity of lymphocytes sensitized by autologous tumor cells in vitro, against autologous lung cancer cell lines].

In order to obtain killer lymphocytes that would have a strong cytotoxicity against autologous tumor cells, we conducted a cytotoxic assay of effector cells cultured from human peripheral blood lymphocytes (PBL) using 10 cultured lung cancer cell lines as target cells. We present this result. (1) Lymphocytes obtained by 17 days mixed lymphocyte tumor cell culture (MLTC: Fresh PBL from lung cancer patients was mixed with irradiated autologous tumor cells in a medium, and cultured for 3 days. Irradiated allogeneic lymphocytes were then added, and cultured for 14 days) were cytotoxic against 4 of the 10 autologous lung cancer cell lines. (2) Lymphocytes obtained by 14 days MLTC and 3 more days culture in a medium containing interleukin 2 were cytotoxic against all 10 of the autologous lung cancer cell lines. These lymphocytes proliferated to 4.13 times of the original cell number, and their surface marker was OKT3+. These killer lymphocytes are expected to be effective in adoptive immunotherapy as effector cells.

Adult↗

Augmentation of superoxide generation in phagocytosing murine peritoneal macrophages by dietary restriction.

The effects of dietary restriction on the generation of superoxide anion (O2-) in phagocytosing mouse peritoneal macrophages (MPs) were investigated. MPs obtained from diet-restricted mice generated larger amount of O2- during phagocytosis of opsonized zymosan than those from unrestricted mice. This augmentation of the O2- generation was not inhibited by the protein kinase C (PKC) inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7). However, the augmentation was clearly disappeared when the calmodulin (CaM) antagonist N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) was added. These results strongly suggest that the augmentation of O2- generation in phagocytosing MPs by dietary restriction is due to the increased activity of CaM in the MPs, and that PKC is not involved in the augmentation. It is thought that one of the major factors for the reduced incidence of tumor and infection in diet-restricted animals is the augmentation of O2- generation in MPs.

Animals↗

Effects of intraperitoneally administered dietary fibers on superoxide generation from peritoneal exudate macrophages in mice.

To clarify whether edible polysaccharides (dietary fibers) have a host defense stimulating activity, the effects of intraperitoneally administered dietary fiber on the generation of microbicidal superoxide anion (O2-) in mouse peritoneal exudate macrophages (MP) were investigated. MP obtained from mice injected cellulose or pectin generated larger amount of O2- when stimulated by 12-o-tetradecanoylphorbol-13-acetate (TPA) or during phagocytosis of opsonized zymosan than those from mice injected proteose peptone, a widely used elicitor for MP. Especially, generated O2- from cellulose-elicited MP was as strikingly large as that from MP elicited by lentinan, a strong antitumor polysaccharide, when stimulated by TPA. Yeast mannan had no effect on O2(-)-generation. These results suggest the possibility that cellulose and pectin may act as host defense stimulators. The augmentation by cellulose or pectin of O2(-)-generation during phagocytosis was not inhibited by the calmodulin (CaM) antagonist N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7). However, the augmentation was completely disappeared when the protein kinase C (PKC) inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7) was added. These results strongly suggest that the augmentation of O2(-)-generation in phagocytosing MP by cellulose or pectin might be due to the increased activity of PKC in the MP, and that CaM may not be involved in the augmentation.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

[A useful combination chemotherapy of cisplatin and etoposide in mediastinal yolk sac tumor].

A 28-year-old male was referred to our hospital because of chest pain and dry cough. Chest x-ray film revealed a tumor mass in the anterior mediastinum indicating invasion into the chest wall and upper lobe of right lung. No tumor was found in the testis. Serum level of alpha-fetoprotein (AFP) was 6,400 ng/ml. Percutaneous biopsy of the tumor suggested yolk sac tumor. The patient was treated with a combination chemotherapy schedule including 30 mg of cisplatin (CDDP) i.v. on Days 1, 2, 3, 4, and 5 and 150 mg of etoposide on Days 1, 2, and 3 as one course therapy. Two courses were employed. Partial response was achieved followed by successful resection of the tumor. This case indicated that a combination chemotherapy CDDP and etoposide combined with surgery could play an active role increasing long-term survival rates in mediastinal yolk sac tumors.

Adult↗