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Biomedical subjects

K Shimokata

Publications and source records attributed to K Shimokata.

At least 253 records · Page 14Linked to original sources

[Cisplatin, peplomycin, mitomycin C, and vincristine combination chemotherapy of non-small cell carcinoma of the lung].

Twenty patients with unresectable non-small cell lung cancer were treated with a combination chemotherapy of cisplatin (30 mg/body i.v., days 1-5), peplomycin (5 or 8 mg/body continuous infusion, days 1-5), mitomycin C (4 mg/body i.v., day 1), and vincristine (2 mg/body i.v., day 1), of 15 patients evaluable for response (9 with squamous cell carcinoma, 2 with adenocarcinoma, nd 4 with large cell carcinoma), the overall response rate was 46.7% with 7 partial responses. The median survival period for responders. Toxicity included hair loss, nausea and/or vomiting, mild to moderate myelosuppression, nephrotoxicity, and pulmonary toxicity, all of which was manageable. This four-drug combination chemotherapy is concluded to be effective for non-small cell lung cancer.

Adenocarcinoma↗

Detection of cellular receptors for Sendai virus in mouse tissue sections.

We have established a method for detecting virus receptors in the tissue sections and have been able to clarify the distribution of cellular receptors for Sendai virus in various mouse organs, including trachea, esophagus, large intestine and cerebrum. The virus receptors were detected in ciliated cells of the trachea, as to be expected for a pneumotropic virus. The lamina propria and connective tissue of the mouse esophagus and large intestine, immediately under the epithelium, contained an abundance at virus receptors, but very few were detected in the epithelium of these organs. In mouse cerebrum, the cells lining the ventricles had a large number of virus receptors.

Animals↗

Comparative studies on the distribution mode of orthomyxo-virus and paramyxo-virus receptor possessing cells in mice and birds.

Many experimental studies have shown that orthomyxo- and para-myxoviruses may be pneumotropic, but not enterotropic in mammals. On the other hand, these viruses are both pneumotropic and enterotropic in avian species. We have devised a new method for detecting virus receptor possessing cells (VRPC) in tissue sections. VRPC could be detected in the cells lining the airways of both mice and birds. The mode of distribution of VRPC in mouse digestive system differed remarkedly from that in avian digestive system. VRPC were not found in the epithelium of mouse digestive systems whereas the epithelium of bird digestive system were abundant in VRPC. When the large intestines from mice or duck undergoing laparotomy and inoculated directly into intestine with influenza virus were examined, viral antigen was detected in the epithelial cell of duck colon, but not in mouse intestines. From the study utilizing the new method, it could be concluded that the distribution mode of VRPC is one of the most important factors determining the virus tissue specificity.

Animals↗

Gamma interferon production in allogeneic stimulation: antigenicity that is sufficient to cause interferon production.

Spleen cells obtained from allogeneic cell-primed mice produced immune interferon when cocultivated with the antigenic cells. The purpose of this study was to clarify the antigenic determinants for immune interferon production in this allogeneic stimulation system. An incompatibility at the K end alone or at the D end alone of the H-2 complex was sufficient for immune interferon induction. No interferon production was observed in the combinations between strains of mice that differ for the non-H-2 regions, including the M locus. Immune interferon-producing cells (IIPC), induced by difference of the H-2K or H-2D regions, recognized the specificities controlled by the H-2K or H-2D regions, respectively; namely, there was no cross-reaction between the two regions. The difference between H-2d and H-2b did not cause interferon production in the combinations of which non-H-2 regions were very similar to each other. IIPC were not induced in the combination, but when IIPC were properly induced in B6 spleen cells, the IIPC could recognize the specificities controlled by the H-2d region (B10D2) and produced immune interferon.

Animals↗

Local cellular immunity in tuberculous pleurisy.

The characteristics and function of lymphocytes in both pleural exudate and peripheral blood in 18 patients with tuberculous pleurisy were studied. The pleural fluid of 13 of 16 patients with tuberculous pleurisy had more T-lymphocytes than the peripheral blood. The difference between them was significant by the t test (p less than 0.05). When lymphocytes in peripheral blood were cocultured with purified protein derivative (PPD), lymphocytes from only 4 of 18 patients produced immune interferon on the fifth day. The titer was only 4 or 8 units/ml. On the contrary, lymphocytes in pleural fluid from 17 of 18 patients reacted to PPD and produced immune interferon on the fifth day, and titers were much higher (more than 128 units/ml) than those of lymphocytes in peripheral blood. When the relationship between the interferon titer produced by lymphocytes in pleural effusion and tuberculin skin reaction was investigated, the group with the stronger skin reactions showed a significantly higher interferon production (p less than 0.05). In conclusion, exudative-sensitized lymphocytes in morbid sites reacted to the specific antigen more effectively and produced titers of lymphokines than circulating lymphocytes.

Adult↗

Measurement of surface temperature in lung cancer.

We measured the surface temperature of the tumors in 27 patients with primary lung cancer, using a flexible bronchofiberscope and a thermometer made from chromel-constantan. The thermometer was inserted into the aspiration channel of the bronchofiberscope, and temperature was studied under bronchofiberscopic located in the central portion of the lung were higher than those of the carina of the trachea (P less than 0.01), truncus superior (P less than 0.01), or truncus inferior (P less than 0.05), and almost equal to those of the peripheral lung. Thus, lung cancer showed a significantly higher surface temperature. When 67Ga scintigraphy was performed in 22 patients with lung cancer, the temperature of the high-uptake group was higher than that of the low-uptake group.

Adenocarcinoma↗

[Clinical studies of cefoxitin for the treatment of respiratory tract infections (author's transl)].

A total of 42 patients who were suffering from respiratory tract infections were treated with cefoxitin, and the following results were obtained. 1. Out of 32 patients clinically evaluated, excellent or good responses were observed in 30 patients (94%). 2. Presumed causative organisms were isolated in 14 patients. The organisms were eradicated in 11 patients and the eradication rate was 79% (11/14). The number of the organisms decreased or unchanged in 1 patient each. In other 1 patient the pathogenic agent was replaced with other agents during the course of treatment. 3. As for the side effects, skin eruption was observed in 3 patients. One patient received drugs other than cefoxitin concomitantly that might have caused the eruption. Another patient had an allergic history to many antibiotics. In 4 patients slight elevations of S-GOT and S-GPT were observed but improved soon after the completion of cefoxitin treatment. In 1 patient an elevation of serum creatinine was observed but this was not attributed to the administration of cefoxitin. 4. From the results stated above, cefoxitin is considered to be a safe and effective antibiotic which can be one of the first-choice antibiotics for the treatment of respiratory tract infections.

Adolescent↗

Plaque formation by human-origin parainfluenza type 2 virus in established cell lines.

Two strains of parainfluenza type 2 virus formed well-defined plaques in cultures of Vero cells, an established line of African green monkey kidney cells. In the absence of trypsin, satisfactory plaques were formed by the Toshiba strain of virus. When trypsin was added in the overlay medium of Vero cell monolayers, another strain (62-M786) of virus produced plaques. The Toshiba strain was also able to make plaques in HeLa, BHK, and LLC-MK2 (an established line of monkey kidney) cells without trypsin, but not in mouse L cells. The sensitivity of plaque assay was about equal to that of the hemadsorption method.

Animals↗

Natural interferon-producing cells in mice.

When mouse lymphoid cells derived from untreated C57BL/6 mice were cocultivated in liquid cultures with L-cell monolayers for 3 h, overlaid with soft agar, and then further incubated for 12 h, protected foci of L cells against vesicular stomatitis virus infection were formed. Many strains of mice have been found to have the protected focus-forming cells on the L-cell monolayers. The formation of the protected foci was completely suppressed by addition of cycloheximide into soft agar. When anti-interferon (type I) antiserum was added to soft agar, there was a decrease in focus counts of about 80%. These experimental results indicated that the formation of protected foci by untreated mouse lymphoid cells was mediated for the most part by type I interferon that was produced without addition of special inducer. We have designated these focus-forming cells as natural interferon-producing cells (NIPC). NIPC belong to the glass-adherent fraction, and Thy-1 antigen, immunoglobulin, and Ia antigen could not be detected on the surface of the NIPC. NIPC were detected in congenitally athymic nude mice. These findings suggest that NIPC belong to the Ia-negative macrophages. Mouse lymphoid cells obtained from germfree mice could form the protected foci on L-cell monolayers and could produce interferon without the addition of a special inducer. NIPC are considered to be a cellular background for spontaneous interferon production.

Animals↗

Mechanism of immune interferon production in vitro: interaction between immune interferon-producing cells and antigenic cells.

Various processes of in vitro immune interferon production by sensitized spleen cells stimulated with allogeneic cells were investigated. When L cells, an interferon-inducing antigen, were fixed with methyl alcohol or paraformaldehyde, the ability to induce immune interferon disappeared. In this immune interferon production system, the majority of sensitized spleen cells adhered to target cells within 1 h of cocultivation. Adherence of immune interferon-producing cells to target cells was observed only when L cell-sensitized spleen cells were cocultured with L cells or with mouse embryo cells derived from C3H mice. Fixation of antigenic cells with methyl alcohol or paraformaldehyde significantly reduced cell adherence. When L cells alone or sensitized spleen cells alone were pretreated separately with cytochalasin D, neither cell type could bind to partner cells. Specific adherence did not take place at 4 degrees C, nor in the presence of dinitrophenol or sodium azide. Continuous protein synthesis in both cells was not required for immune cell adherence. Divalent cations, Ca2+ or Mg2+, were required for this immune specific adherence to take place. However, once stable adherence was established, treatment with cytochalasin D, ethylenediaminetetraacetic acid, or sodium azide, or simple reduction of temperature, did not disrupt the binding. Interaction between immune interferon-producing cells and antigenic cells can be subdivided into two phases according to the requirement for divalent cations: (i) lymphocytes and antigenic cells interact transiently, and divalent cations are required to maintain the binding; (ii) lymphocytes and antigenic cells form a stable interaction, and deprivation of divalent cations does not disrupt the binding. Colchicine showed an inhibitory effect in the period after cell-to-cell adherence. Colchicine did not inhibit the release of interferon. On the other hand, vinblastine, another antimicrotubule agent inhibited the secretion of immune interferon. Since interferon synthesis was not stopped immediately after addition of cycloheximide, continued protein synthesis of sensitized spleen cells was not required for interferon secretion. The present study showed that adherence of immune interferon-producing cells to antigenic cells was a complex phenomenon involving a series of successive events.

Animals↗

Characterization of altered BHK cells resistant to HVJ (Sendai virus) infection.

An altered baby hamster kidney cell culture which resists the c.p.e. of HVJ (haemagglutinating virus of Japan - the Sendai strain of parainfluenza I virus) has been obtained and characterized. These cells, designated BHK-R, were originally obtained by prolonged cultivation of cells surviving HVJ infection; they have been subcultured in the presence of HVJ. No infectious virus was recovered from BHK-R cells and no evidence for the presence of HVJ antigens in the cells was demonstrated by immunofluorescent staining. When BHK-R cells were inoculated with HVJ the growth of challenge virus was suppressed and no obvious cytopathic changes were detected, while these cells normally supported the replication of mumps, influenza, Newcastle disease, vesicular stomatitis or Sindbis viruses. BHK-R cells became susceptible to HVJ infection after serial subculture in growth medium free of HVJ. It was suggested that sialic acid residues present in the surface of BHK-R cell membranes and responsible for adsorption of HVJ were split off by the action of neuraminidase of virus particles, resulting in inhibition of the attachment of challenge virus of HVJ.

Adsorption↗

Influence of trypsin on the infectivity and biological properties or parainfluenza type 2 type 2 (croup-associated) virus in Vero cells.

A comparative study on the infectivity and biological activities of parainfluenza virus type 2 revealed that one strain (Toshiba) showed c.p.e. with cell fusion and produced plaques in Vero cells, an established line of African green monkey kidney cells. Another strain (62-M786) of this virus, however, showed minimum c.p.e. and produced almost no plaques in Vero cells, although c.p.e. appeared and plaques were observed following addition of trypsin. The infectivity titre of the latter strain, estimated by 50% tissue culture infectious doses (TCID50), was increased 10 times and plaque counts more than 6400 times by addition of an adequate concentration of trypsin; however, trypsin did not affect the infectivity of the former strain. Trypsin also increased the haemolytic activity of strain 62-M786 but not that of the Toshiba strain. These results show that the two isolates of parainfluenza virus type 2 were affected very differently by trypsin as regards infectivity, cell fusion and haemolytic activity.

Animals↗

Enumeration of immune interferon-producing cells induced by allogeneic stimulation.

We succeeded in enumerating interferon-producing cells induced by allogeneic stimulation, and proved that they were indeed T lymphocytes. The peak level of these cells in spleen was attained on day 5 after immunication, was maintained for about 2 days, and declined thereafter. Titers of interferon produced in vitro by sensitized spleen cells were maximum on day 7. This suggests that the maturation of immune interferon-producing cells follows cell proliferation after antigen stimulation.

Animals↗