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Biomedical subjects

M Baba

Publications and source records attributed to M Baba.

At least 145 records · Page 8Linked to original sources

Novel sulfated polymers as highly potent and selective inhibitors of human immunodeficiency virus replication and giant cell formation.

Novel synthetic sulfated polymers, namely, sulfated polyvinyl alcohol (PVAS) and sulfated copolymers of acrylic acid with vinyl alcohol (PAVAS), proved to be potent and selective inhibitors of human immunodeficiency virus type 1 (HIV-1) and HIV-2 in vitro. The compounds completely inhibited HIV-1-induced cytopathogenicity in MT-4 cells and HIV-1 antigen expression in CEM cells at a concentration of 0.8 micrograms/ml. They were equally effective against HIV-2 replication. In addition, and in contrast to azidothymidine, PAVAS and PVAS suppressed HIV-1-induced giant cell (syncytium) formation, a process that may account for the depletion of T4 lymphocytes in patients with acquired immunodeficiency syndrome. PAVAS and PVAS completely blocked giant cell formation at a concentration of 4 micrograms/ml, whereas for dextran sulfate a concentration of 100 micrograms/ml was required to achieve complete inhibition of giant cell formation. As has been demonstrated previously for the sulfated polysaccharides, the mechanism of action of PAVAS and PVAS resides in the inhibition of virus adsorption to the cells.

Acrylic Resins

Anti-human immunodeficiency virus type 1 activities and pharmacokinetics of novel 6-substituted acyclouridine derivatives.

The novel 6-substituted acyclouridine derivatives 1-[(2-hydroxyethoxy)methyl]-6-phenylthiothymine (HEPT), 1-[(2-hydroxyethoxy)methyl]-6-(3-methylphenylthio)thymine (HEPT-M), 6-cyclohexylthio-1-[(2-hydroxyethoxy) methyl]thymine (HEPT-H), and 1-[(2-hydroxyethoxy)methyl]-6-phenylthio-2- thiothymine (HEPT-S) have proved to be potent and selective inhibitors of human immunodeficiency virus type 1 (HIV-1) replication in a variety of cell systems, including peripheral blood lymphocytes. They are not inhibitory to the replication of HIV-2. HEPT-S emerged as the most active congener, with a 50% inhibitory concentration of 1.6 microM for HIV-1 (human T-cell lymphotropic virus type IIIB) in MT-4 cells. We also examined the pharmacokinetics of the compounds following oral administration to rats. The pharmacokinetic profile varied considerably from one compound to another. The highest concentration in plasma (7.4 micrograms/ml, or 22.8 microM) was achieved by HEPT-S within 30 min after administration of an oral dose of 20 mg/kg of body weight. HEPT-S can be considered a promising candidate for the treatment of HIV-1 infections.

Animals

[The influence of anticancer agents at various stages to induce LAK cell on its cytotoxicity and cell yield. Examination in vitro].

To establish the combination of chemotherapy with adoptive immunotherapy (AIT), using lymphokine activated killer cells (LAK) and/or interleukin-2 (IL-2), author examined the following: 1) Pretreatment with anticancer agents for peripheral blood mononuclear cells (PBMC) and its effect on LAK cell cytotoxicity and cell yield. 2) The addition of anticancer agents in the induction phase to LAK cell and its effect on LAK cell cytotoxicity and cell yield. 3) Pretreatment with anticancer agents to induced LAK cell and its effect on LAK cell cytotoxicity and cell yield. 4) The cytotoxicity of LAK cell against tumor cells treated with anticancer agents. Our experiment has shown that when we take peripheral blood mononuclear cells (PBMC) to induce LAK cells, there is no influence on its LAK cell yield or its cytotoxicity after being harvested as LAK cells, even if there is a maximum concentration of anticancer agents, but in the case of the LAK cell induction phase VDS, CDDP, ADM and MMC have a significant effect on LAK cell yield and on cytotoxicity of LAK cell after being harvested as LAK cells. And it has also been shown that, if there is a maximum concentration of anticancer agents, it has an effect on the induced LAK cell cytotoxicity and on the LAK cell yield after being recultured with IL-2. On the other hand, LAK cell cytotoxicity makes no difference to tumor cells whether they are treated or not with anticancer agents. These results suggest that we can take peripheral blood mononuclear cells to induce LAK cells unrelated to the administration of anticancer agents, and that if we use a combination of chemotherapy with adoptive immunotherapy (IL-2 administration and/or LAK cell adaptation), we should start with the administration of anticancer agents and then administer IL-2 and/or transfer LAK cells after the concentration of anticancer agents decreased under 1/10 of maximum concentration in the blood level of our conventionally clinical use.

Antineoplastic Agents

Ovalbumin-specific induction of IL2 responsiveness in lymphocytes from patients with hen egg allergy and its regulation by the culture supernatant of normal lymphocytes.

Interleukin 2 (IL2) responsiveness of ovalbumin (OVA)-stimulated lymphocytes from patients with hen-egg allergy was studied. The number of viable cells of 5-day cultured lymphocytes stimulated with OVA was increased by an additional three days incubation with recombinant IL2. This phenomenon was not observed when the lymphocytes of patients allergic to OVA but not to Dermatophagoides farinae extract antigen (Df) were stimulated with Df. Normal lymphocytes stimulated with OVA expressed Tac antigen (low affinity IL2 receptor) but, in contrast to those from the allergic patients, did not absorb nor respond to IL2. The induction of OVA-specific IL2 responsiveness in patient lymphocytes was markedly suppressed on the addition of culture supernatant from OVA-stimulated normal T cells, but Df-specific IL2 responsiveness of the lymphocytes from Df-sensitized patients with bronchial asthma was not suppressed by the same supernatant. The supernatant of lymphocytes from allergic patients did not show such suppressive effect. The patient lymphocytes whose IL2 responsiveness was suppressed with the supernatant from normal lymphocytes still expressed Tac antigen. These observations suggest that the culture supernatant of normal T lymphocytes stimulated with OVA contained an antigen-specific factor suppressing the induction of IL2 responsiveness of OVA-stimulated patient lymphocytes. The production of such a suppressive factor was impaired in the patient, and further, the factor may have inhibited the triggering signal of IL2 receptors having absorbed IL2. The existence of some allogeneic barrier between the factor(s) and patient lymphocytes was suggested, since the supernatant from OVA-stimulated normal T cells did not necessarily suppress the response of all patients tested.

Absorption

Establishment of a bioassay to determine serum levels of dextran sulfate and pentosan polysulfate, two potent inhibitors of human immunodeficiency virus.

Dextran sulfate and pentosan polysulfate are two promising candidate anti-acquired immune deficiency syndrome (AIDS) drugs that have already been the subject of initial clinical trials in patients with AIDS. There is at present no reliable assay method to monitor blood drug levels in humans following the administration of either drug. We have now developed a sensitive bioassay system based on the inhibitory activity of the compounds against human immunodeficiency virus type 2 (HIV-2) in MT-4 cells. This method permits the detection in (rabbit) serum samples of dextran sulfate and pentosan polysulfate concentrations as low as 3.0 and 0.5 micrograms/ml, respectively. Pharmacokinetic studies with dextran sulfate and pentosan polysulfate in rabbits indicated that the half-life of these compounds after intravenous bolus injection is approximately 1 h 24 min.

Acquired Immunodeficiency Syndrome

Sulfated polysaccharides as potent inhibitors of HIV-induced syncytium formation: a new strategy towards AIDS chemotherapy.

Multinucleated giant cell (syncytium) formation induced by the interaction between the gp120 glycoprotein expressed on the surface of cells infected with human immunodeficiency virus type (HIV-1) and the CD4 receptor of uninfected CD4-positive (CD4+) cells may play an important role in the depletion of T4 lymphocytes in acquired immune deficiency syndrome (AIDS) patients. Using a double fluorescence cell-staining technique and analysis of the cells by the fluorescence-activated cell sorter (FACS), we have demonstrated that giant cell formation between persistently HIV-1-infected HUT-78 cells and uninfected MOLT-4 cells results in a selective destruction of the uninfected CD4+ MOLT-4 cells. Apparently, bystander CD4+ cells may serve as targets for the killing effect of the HIV-1-infected cells, and this killing effect is preceded by fusion between the target (uninfected) and aggressor (infected) cells. Pentosan polysulfate, dextran sulfate, and various other sulfated polysaccharides, but not heparin, have proved to inhibit this cell fusion process and hence protect the target CD4+ cells against destruction by the killer HIV-1-infected cells. Azidothymidine does not interfere with this process. Assuming that fusion between HIV-infected and uninfected CD4+ cells is a crucial event in the pathogenesis of AIDs, any compounds that specifically interfere with this process may be therapeutically advantageous in the treatment of this disease.

Acquired Immunodeficiency Syndrome

[Suppressive effect of Saibokuto on Dermatophagoides farinae (Df) antigen-induced IL2 responsiveness of lymphocytes from asthmatic children].

The effect of Saibokuto on induction of antigen specific IL2 responsiveness was studied. Saibokuto suppressed the induction of IL2 responsiveness induced by Dermatophagoides farinae (Df) antigen in peripheral blood mononuclear cells from patients with bronchial asthma. Saibokuto-pretreated adherent cells failed to present Df antigen to non-adherent responding T cells for induction of their IL2 responsiveness. The same dose of Saibokuto had no impact on non-adherent cells. Saibokuto also suppressed the induced IL2 responsiveness of lymphocytes from the same patients on stimulation wit PPD, but not with Con A. These combined data suggests that Saibokuto has a weak immunosuppressive effect on Df induced IL2 responsiveness of lymphocytes from asthmatic children. Effect of Saibokuto on induction of antigen specific IL2 responsiveness was studied. Saibokuto suppressed the induction of IL2 responsiveness induced by Dermatophagoides farinae (Df) antigen in peripheral blood mononuclear cells from patients with bronchial asthma. Saibokuto-pretreated adherent cells failed to present Df antigen to non-adherent responding T cell for induction of their IL2 responsiveness. Non-adherent cells had no impact by the same dose of Saibokuto. Saibokuto also suppressed the induced IL2 responsiveness of lymphocytes from the same patient on stimulation with PPD, but not Con A. These combined data suggest that Saibokuto has a weak immunosuppressive effect on Df induced IL2 responsiveness of lymphocytes from asthmatic children. Effect of Saibokuto on induction of antigen specific IL2 responsiveness was studied. Saibokuto suppressed the induction of IL2 responsiveness induced by Dermatophagoides farinae (Df) antigen in peripheral blood mononuclear cells from patients with bronchial asthma. Saibokuto-pretreated adherent cells failed to present Df antigen to non-adherent responding T cell for induction of their IL2 responsiveness. Non-adherent cells had no impact by the same dose of Saibokuto. Saibokuto also suppressed the induced IL2 responsiveness of lymphocytes from the same patient on stimulation with PPD, but not Con A. These combined data suggest that Saibokuto has a weak immunosuppressive effect on Df induced IL2 responsiveness of lymphocytes from asthmatic children.

Animals

Synthesis of novel 6-substituted acyclouridine derivatives and their anti-HIV-1 activity.

To improve the anti-HIV activity of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT), a variety of its analogues were synthesized. Introduction of SR group to the C-6 position was carried out based on LDA lithiation followed by the reaction of aryl- or alkyl disulfide. An addition-elimination reaction of a 6-phenylsulfinyl derivative was used for synthesizing the analogues having OR or NHR group at the C-6 position. The C-5 modified derivatives were synthesized mainly based on LTMP lithiation of a 6-phenylthio derivative. Modification at the 2- or 4-position was also carried out. Some compounds prepared in the present study showed higher activity than HEPT.

Antiviral Agents

[Some characteristics of orthodontic treatment in high mandibular cases].

Maxillary protrusion cases with a high mandibular plane angle have some clinical difficulties. In such cases, each cephalometric plane spreads out with large angles and masticatory muscles are weak. Due to these morphological and functional abnormalities, anchorage loss as well as elongation of anchor teeth is easily caused and retrusion of the mandible is hard to be improved. Maxillary protrusion cases with a high mandibular plane angle were reestimated through a consideration of how natural anchorage is established by occlusal force. The first case showed a high mandibular plane and occlusal plane angles. Cervical head gear and class II elastics were used for a short period of time, which caused elongations of 6/6 and the opening of the mandibular plane angle by 3 degrees. The lateral profile, however, did not worsen since the mandibular ramus had a fair growth. The second case showed no opening of the mandibular plane angle as the result of an unusual extraction of 4/6. There was, however, no skeletal improvement because of an adult case. The third case showed the opening of the mandibular plane angle from the effect of the cervial head gear besides a weak muscular force, although the initial record revealed no high angles in cephalometric data. It may be suggested that cephalometric data are not enough to estimate function of orthodontic cases.

Adolescent

[Anti-CD45R antibody-treated normal lymphocytes respond to interleukin 2 (IL2) after stimulation by allergens].

Interleukin 2 (IL2) responsiveness was specifically induced by Dermatophagoides farinae (Df) antigen in Df-sensitized lymphocytes from asthmatic children, but not in normal lymphocytes. Df-induced IL2 responsiveness was also observed in normal lymphocytes pretreated (Day 0) with anti-CD45R antibody, which recognize suppressor inducer subset among CD4+ T cells. However anti-CD45R antibody was no longer effective when the lymphocytes were cultured for more than one day with the antigen, suggesting its effect in the initial phase of the reaction. The intensity of the response induced in normal lymphocytes by the anti-CD45R was comparable to that of the patients sensitized to the nominal antigen. The response of the patients was no longer augmented by the anti-CD45R antibody. Taken together, these data suggest that even normal lymphocytes have potentiality to elicit Df-induced IL2 responsiveness and it is probably derepressed by inhibiting suppressor inducer subset with the anti-CD45R antibody. Also suggested is a defective suppressor inducer activity in the lymphocytes which may lead to hyperreactivity to allergens in asthmatic children.

Allergens

[Present status and problems of surgical treatment of non-small cell lung cancer].

Surgical treatment and combined chemotherapy of non-small cell lung cancers during the last 10 years were analyzed. Overall 5 year survival rate of non-small cell lung cancer was 37% and those in stages I, II, IIIA and IIIB were 59%, 33%, 21% and 12%, respectively. Poor outcome in IIIA cases depended strongly on surgical respectability, however, adenocarcinoma cases depended more on the T factor and squamous cell carcinoma depended more on the N factor. IIIA cases, even though resected curatively, showed 10-20% local recurrence, indicating the importance of further improvement of the surgical procedure. In the cases with absolutely non-curative resection tumor remained in mediastinal lymph nodes or organs adjacent to the mediastinum, indicating the necessity of extended combined resection including contralateral mediastinal lymph nodes or organs adjacent to the mediastinum for better results of surgical treatment. Preoperative chemotherapy for the suppression of local recurrence and distant metastasis was significant only in very limited circumstances.

Adenocarcinoma

[Successful ATG and bolus methylprednisolone therapy towards severe aplastic anemia with splenomegaly].

A 22-year-old female patient with severe aplastic anemia was treated by ATG.bolus methylprednisolone therapy. After the therapy, anemia and thrombocytopenia began to recover within a month. The frequency of blood transfusion decreased thereafter. Since anemia due to splenomegaly was certified, bolus methylprednisolone therapy was performed in good response. Suppressor T-cells towards hemopoiesis were confirmed in this case, and hemopoietic potential was augmented by ATG.bolus methylprednisolone therapy. In spite of discontinuation of any therapy in 1986, she is being in good health more than five years.

Adult

[Significance of superior vena cava reconstruction with EPTFE grafts in the surgical treatment of superior and anterior mediastinal invasive malignant tumors].

The objective of this study is to demonstrate the significance of superior vena cava (SVC) reconstruction in the surgical treatment of superior and anterior mediastinal invasive malignant tumors, by using a total of 48 cases consisting of 36 invasive thymomas, 3 thymic cancers, 3 carcinoids, 2 germ cell tumors, 2 malignant lymphomas, 1 intrathoracic thyroid cancer and 1 malignant melanoma. In 22 of 48 cases there was only mediastinal pleural invasion or tumor capsule invasion, on the other hand, 26 cases had high ratios of invasion to adjacent organs, including lung, pericardium, great veins and the phrenic nerve. Sixteen of 26 cases had invasion to 1-2 adjacent organs, but 10 had 3-6 organ invasion. Among 12 cases invading SVC or brachiocephalic veins, 9 cases during the last 7 years underwent SVC resection and reconstruction with EPTFE grafts. The patency was good in the grafts with external ring support and no SVC symptoms were observed in all cases postoperatively. The longest patent and functional graft is 40 months postoperative. No statistically significant difference were demonstrated in the survivals between cases with SVC reconstruction and those with resections of other adjacent organs, furthermore, remarkable difference of survival was demonstrated in SVC reconstructed cases with complete resection and incomplete resection. The survivals in cases with combined resection of 1-2 adjacent organs was statistically significantly better than those with combined resection of 3-6 adjacent organs (p less than 0.05, Cox-Mantel test).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[A case of Pryce's type I intralobar pulmonary sequestration diagnosed by noninvasive techniques].

The patient was a female who came to our hospital with a chief complaint of hemoptysis. Radiography of the chest demonstrated a funicular shadow, and CT of the chest also revealed a similar shadow in contact with the thoracic aorta enhanced by the contrast material. Pulmonary arteriography and aortography showed that the left S8, S9 and S10 areas were supplied by abnormal blood vessels bifurcating from the thoracic aorta, rather than the pulmonary artery. This finding was supported by scintigraphy of the pulmonary blood flow and pulmonary RI angiography. Since bronchography revealed no obvious abnormality in the bronchial system, the diagnosis of Pryce's type I intralobar pulmonary sequestration was established, and left lower lobectomy was carried out. While the evidence of abnormal blood vessels is important for the definitive diagnosis of pulmonary sequestration, concurrent image processing of the results of scintigraphy of the pulmonary blood flow and pulmonary RI angiography permits noninvasive demonstration of the fact that the sequestral pulmonary tissue is regulated by the systemic circulatory system, rather than the pulmonary circulatory system and thus is a useful technique.

Adult

[The relationship between respiratory threshold to acetylcholine and prognosis for asthma].

Forty nine asthmatic children were studied to clarify the relationship between the respiratory threshold of acetylcholine (RT-Ach) and the prognosis for asthma. In those patients who had asthmatic attacks fewer than 60 days in the last year, there was a statistically significant relationship between RT-Ach and the number of the days of asthmatic attacks over the 6 and 12 month periods following the inhalation test. In the younger group (5-11 years old), there was a statistically significant relationship between RT-Ach and the number of the days of asthmatic attacks over the 6 and 12 month periods following the inhalation test. However, in the elder group (12-15 years old), no such relationship was recognized. In the elder group, the obstructive index, one of the indices of flow-volume curve, had a statistically significant correlation with the number of asthmatic attacks over the 6 and 12 month periods following the inhalation test. However in the younger group, no such relationship was recognized.

Acetylcholine

[A case of solitary thalamic abscess treated by sterotactic aspiration].

The Solitary thalamic abscess appears to be uncommon, 17 cases have been reported since 1973. We successfully treated a case of thalamic abscess associated with diabetes mellitus by sterotactic aspiration with external drainage. A 55 years old man presented right hemiparesis. A computed tomographic (CT) scan revealed solitary thalamic low density lesion with ringed contrast enhancement. We started the administration of antibiotics, but on the 9th day he became drowsy and his eyes were deviated downward and inward. CT scan on the 10th day showed the edema had been spread to the tectum. We aspirated purulent fluid material with confidence by sterotactic operation. We considered the mid brain tectum to be responsible for the downward and medial deviation of the eyes, because it appeared only when the edema and abscess were spread to that area, and disappeared after aspiration of the abscess with subsidence of the edema.

Abscess

[Myelofibrosis with marked subcapsular bleeding of the spleen--a case report].

A 22-year old male was admitted to Ashikaga Red Cross Hospital because of the progressing abdominal distension in May 1988. The physical examinations disclosed marked hepato-splenomegaly, lymphadenopathy and cachexic state. In the laboratory examinations, anemia, leukocytosis with left shift of nuclei and severe inflammatory reactions were found. Bone marrow aspirations were dry taps, and the biopsy showed myelofibrotic changes. Abdominal computed tomography and ultrasonography revealed a marked hepatomegaly and a giant splenomegaly with subcapsular hematoma. Philadelphia chromosome was negative and neutrophilic alkaline phosphatase score was slightly high. A little amount of peritoneal effusions was obtained and yielded S. aureus. A diagnosis of myelofibrosis with subcapsular hematoma due to spontaneous rupture of spleen and peritonitis of unknown cause was made. Operative indication was considered, but his family did not agree with it. Then conservative therapies for general conditions, those are, administrations of antibiotics and diuretics, and blood transfusions were taken. On the enlarged spleen, total irradiation was done. After the therapies, his spleen got smaller and hematoma was going to be absorbed. A rare case of myelofibrosis with splenic hematoma is reported and the conservative therapies were effective to this case.

Adult

Highly specific inhibition of human immunodeficiency virus type 1 by a novel 6-substituted acyclouridine derivative.

A novel 6-substituted acyclouridine derivative, 1-[(2-hydroxy-ethoxy) methyl]-6-phenylthiothymine (HEPT), has proved to be a potent and selective inhibitor of human immunodeficiency virus type 1 (HIV-1) in vitro. HEPT inhibits HIV-1 replication in various T4 cell cultures as well as peripheral blood lymphocytes and macrophages. The 50% antiviral effective concentration for HIV-1 (HTLV-IIIB) in MT-4 cells is 7.0 microM, while the 50% cytotoxic concentration for mock-infected MT-4 cells is 740 microM. Although HEPT is inhibitory to various strains of HIV-1, it has no effect on the replication of other retroviruses including HIV type 2. In contrast with the dideoxynucleoside (i.e. azidothymidine) 5'-triphosphates, the triphosphate of HEPT does not interact with HIV-1 reverse transcriptase. The mechanism of action of HEPT remains subject of further study.

Antiviral Agents