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Biomedical subjects

M Baba

Publications and source records attributed to M Baba.

At least 703 records · Page 39Linked to original sources

Phosphonylmethoxyethyl purine derivatives, a new class of anti-human immunodeficiency virus agents.

A study of the structure-activity relationship of a series of newly synthesized phosphonylmethoxyalkyl purine and pyrimidine derivatives revealed that several adenine derivatives substituted at the N9 position by a 2-phosphonylmethoxyethyl (PME) group inhibited human immunodeficiency virus (HIV)-induced cytopathogenicity and HIV antigen expression in vitro at concentrations significantly below the toxicity threshold for the host cells. In terms of anti-HIV potency in MT-4 cells, the PME 2,6-diaminopurine derivative (50% effective dose [ED50], 1 microM) ranked first, followed by the PME adenine derivative (ED50, 2 microM [MT-4]) and the PME 2-monoaminopurine derivative (ED50, 45 microM). Antiretroviral activity was also demonstrated in ATH8 and H9 cells, which were de novo infected with HIV, and extended to C3H mouse fibroblasts infected with Moloney murine sarcoma virus. Unlike 2',3'-dideoxyadenosine, these compounds were not found to be degraded by deaminases derived from bovine intestine.

Adenine↗

Renal cytochrome P-450-related arachidonate metabolism in rabbit aortic coarctation.

Cells of the medullary segment of the thick ascending limb of Henle's loop (TALH) convert arachidonic acid (AA) via the cytochrome P-450 monooxygenase pathway to biologically active metabolites: P1, a vasorelaxant, and P2, an inhibitor of Na+-K+-ATPase activity. These AA metabolites may contribute to the renal vascular and metabolic adjustments in response to renal hypoperfusion and the attendant elevation of blood pressure produced by suprarenal aortic coarctation. On the eighth postoperative day, the blood pressures of hypertensive and sham-operated control rabbits were 105 (90-115) and 63 (60-64) mmHg (medians with semiquartile values), respectively (P less than 0.01). Formation of P1 and P2 was increased twofold in TALH cells obtained from hypertensive rabbits: 2.35 (1.79-4.83) and 1.28 (1.56-4.56) micrograms AA converted.mg protein-1.30 min-1 compared with sham-operated rabbits: 1.27 (1.03-1.53) and 0.64 (0.58-1.10) micrograms AA converted.mg protein-1.30 min-1 (P less than 0.05). The profile of biological activity of AA metabolites contained within P1 and P2 was unaffected by aortic coarctation. The cytochrome P-450 monooxygenase-derived AA metabolites may exert a defensive function to limit the degree of TALH cell injury in response to renal hypoperfusion and associated zonal anoxia by reducing energy-dependent Na+-K+-ATPase activity and affecting local vasodilatation.

Animals↗

Structural mechanics of the blowout fracture: numerical computer simulation of orbital deformation by the finite element method.

Blowout fractures most frequently involve the orbital floor. The contour of the orbit has been postulated as one of the factors responsible for this phenomenon, but only a few studies have been carried out. The present study was planned to determine the effect of the contour of the orbit when intraorbital pressure is raised to simulate the hydraulic mechanism of blowout fracture. The profile of the orbit was estimated from five dry human skulls, and the measurements were approximated to frame models. The deformation of these models by raised intraorbital pressure was calculated by computer simulation using the finite element method. In all of the orbital models, the deformation of the orbital floor was significantly greater than that of the roof. These findings verified that the orbital roof has a higher resistance than the floor against raised intraorbital pressure. We suspect that this resistance is due to the arched shape of the orbital roof, whereas the floor is rather flat.

Computer Simulation↗

Localization of keratin mRNA in human tracheobronchial epithelium and bronchogenic carcinomas by in situ hybridization.

An in situ hybridization technique was applied to detect expression of keratin mRNAs in xenotransplanted human tracheobronchial epithelium and lung carcinomas. Tissues from eight tracheas repopulated with cells from five different noncancerous donors and 15 squamous cell carcinomas were used. Using a K6 (56 kd) human keratin cDNA (KA-1) and a K14 (50 kd) cDNA (KB-2) as probes, radiolabeled by nick-translation with 3H-dATP/TTP, the specificity and significant differences in the levels of silver grains on various epithelial lesions in formalin-fixed, paraffin-embedded tissue sections were demonstrated. In situ hybridization with either KA-1 or KB-2 probe showed similar localization of silver grains in all histologic types in consecutive tissue sections. In xenotransplanted tracheobronchial epithelia, very few grains were seen over cells of simple, pseudostratified, or stratified epithelia two to three cell layers thick. Nonkeratinizing stratified hyperplastic epithelia of more than three cell layers showed uniform localization of numerous grains throughout the lesions. In contrast, epidermoid metaplasias exhibited a dense and localized pattern of grains on the basal and parabasal cell layers with a decrease in grain density toward the surface layers. Carcinoma cells from bronchogenic squamous cell carcinomas showed a higher density and more uniform localization of grains. Well-differentiated carcinoma cells contained more keratin mRNAs than moderately to poorly differentiated carcinoma cells. This evidence obtained with the KA-1 and KB-2 probes demonstrates the different localization patterns of keratin mRNAs in different epithelial lesions. In addition, the levels of mRNA expressed show a positive correlation with the degree of squamous differentiation. It was of particular interest that an ordered program of keratin mRNA expression proportional to the level of cellular differentiation was observed in epidermoid metaplasias. Both of these probes serve as keratinization markers of human tracheobronchial epithelial lesions.

Animals↗

[Postoperative sequential testing of cytotoxic activity against the autologous and allogeneic tumor cells in patients with primary lung resected cancer].

The objective of this study of 27 primary lung resected cancer patients was to evaluate sequentially the cytotoxic activity against autologous and allogeneic tumor cells during the postoperative period. In patients given a complete resection, the cytotoxic activity against the autologous tumor cells during the postoperative 1-2 weeks was significantly higher than during the postoperative 4-5 weeks (P less than 0.05, Student t test). In patients given an incomplete resection, however, no significant difference was demonstrated between the postoperative 1-2 weeks and during the postoperative 4-5 weeks. In contrast, the cytotoxic activity against the PC-3 cells or K562 cells during the postoperative 4-5 weeks tended to rise in comparison to those at the postoperative 1-2 weeks all patients in any cancer stage and whatever the amount of their lung resection. The phenotype of the effector cells which mediated the cytotoxic activity to the autologous tumor cells was the monoclonal antibody OKT 3(+), 8(+), 4(-) OKM 1(-) and the cells which were cytotoxic to the K562 cells had an OKT 3(-), 4(-), 8(-), OKM 1(+) phenotype. These results suggest that the effectors which mediate cytotoxic activity to the autologous tumor cells and to the K562 cells seems to be different and a concomitant immunity may exist in primary lung resected cancer patients.

Adenocarcinoma↗

[A case of complete remission following recurrent relapses 12 years after onset of acute myelocytic leukemia. Response to protocol including neocarzinostatin].

A 23-year-old male who had suffered recurrent relapses of acute myelocytic leukemia was treated with a protocol including neocarzinostatin (NCS) and complete remission was obtained. At the age of 11 years, he had complained of general fatigue and anemia, and was diagnosed as having AML because of the presence of leukemic cell infiltration in the bone marrow as well as peripheral blood. Auer bodies and a positive reaction to peroxidase were found. The last episode of relapse occurred at the age of 15 years, when he achieved complete remission following a trial protocol which included NCS. NCS seemed to be effective after it had been used intravenously for a short time. The patient has maintained complete remission for the past 7 years and has had no consolidation therapy in the last 3 years. For the last 18 months, he has been working in a market as a clerk 8 hours a day. NCS with a rapid infusion time seems to have effects on leukemic cells when it used with proteolytic enzyme. Neither skull radiation nor testicular biopsy were attempted. Results of CSF examination were within normal limits, but EEG and CT scan revealed the probability of early-stage leukoencephalopathy, although no significant clinical signs were observed. He had suffered an asthmatic attack before the onset of AML, but no further attack occurred until several months ago. In order to establish any relationship between these two diseases, further detailed analysis will be necessary.

Adult↗

[Clinicopathological studies of the recurrence of esophageal squamous cell cancer--with special reference to the mode of recurrence and operative procedure].

In 93 out of 201 patients (46%) with squamous cell carcinoma of the esophagus who underwent radical resection (excluding death within 30 days after operation), the site of recurrence could be identified by means of X-ray, CT, ultrasonography, and biopsy. Recurrence was found in 55% of 93 cases within 12 months after surgery and in 86% of 93 cases within 24 months. Of 93 patients with recurrences, lymph node recurrences were present in 44 cases, visceral recurrences in 32 cases, both lymph node and visceral recurrences in 11 cases and others in 6 cases. Neck and/or upper mediastinal lymph node recurrences were found in 10 out of 15 patients who had recurrences within 3 months after surgery. Careful examination should be made in the left recurrent nerve chain and extended lymph node resection of upper mediastinal region should be performed under the adequate indication. Esophageal squamous cell cancer has a tendency to recur in the lymph nodes initially, and visceral metastases may occur thereafter. The incidence of visceral recurrence increased remarkably, when neck and/or upper mediastinal lymph nodes were involved at the time of operation. Accordingly, both irradiation and chemotherapy should also be applied for improving the prognosis of esophageal carcinoma.

Aged↗