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Biomedical subjects

M Maeda

Publications and source records attributed to M Maeda.

At least 1,135 records · Page 63Linked to original sources

Phase II trial of cis-diamminedichloroplatinum (cis-platinum), vincristine, and peplomycin for advanced squamous cell carcinoma.

Advanced squamous cell carcinoma of the head and neck, lung, esophagus, and uterine cervix is still a challenging cancer to the medical practice. We have treated 23 such patients with a combination of cis-platinum, vincristine, and peplomycin. Cis-platinum was given at a dose of 60 mg/m2 on day 1, and 1.0 mg/m2 of vincristine was given on day 3, followed 6 hours later by peplomycin 10 mg/day by continuous infusion iv or sc over the next 5 days. This combination was given every 3 weeks. The overall response rate was 71% for 17 evaluable patients, including one complete response. The median duration of response and survival was 2 and 5 months, respectively. Six other patients with esophageal and cervical carcinoma were treated with two cycles of this combination followed by radical radiation therapy or surgery. Five of them achieved significant response prior to radical treatment. Major side effects were nausea, vomiting, alopecia, and mild myelotoxicity, which were acceptable. This regimen, with a high response rate and acceptable toxicity, warrants further investigation.

Adult↗

Binding of Mg2+ to the beta subunit or F1 of H+-ATPase from Escherichia coli.

The bindings of Mg2+ to the F1 portion of Escherichia coli H+-ATPase and its isolated alpha and beta subunits were studied with 8-anilinonaphthalene-1-sulfonate (ANS). The fluorescence of ANS increased upon addition of F1 or its alpha subunit or beta subunit, as reported previously (M. Hirano, K. Takeda, H. Kanazawa, and M. Futai (1984) Biochemistry 23, 1652-1656). The fluorescence of ANS bound to F1 or its beta subunit increased significantly with further addition of Mg2+, whereas that of the alpha subunit increased only slightly. Ca2+ and Mn2+ had similar effects on the fluorescence of ANS with F1 and its beta subunit. The Mg2+-induced fluorescence enhancement (delta F) was high at an alkaline pH and was lowered by addition of ethylenediaminetetraacetic acid. Dicyclohexylcarbodiimide and azide had no effect on the delta F. Binding analysis showed that the concentration dependence of Mg2+ on the fluorescence enhancement of the beta subunit is similar to that of F1. These results suggest that both the beta subunit and F1 have binding sites for Mg2+ and that the delta F observed with F1 may be due to the binding of Mg2+ to the beta subunit.

Anilino Naphthalenesulfonates↗

Fc receptors of liver sinusoidal endothelium in normal rats and humans. A histologic study with soluble immune complexes.

Fc receptors for immunoglobulin G in the liver sinusoidal wall were studied in the normal rat and in humans by applying peroxidase-antiperoxidase immunoglobulin G complexes to the frozen sections. Fc receptors were found to exist continuously along the sinusoidal lining. The receptors showed no zonal distribution in the rat, and they were generally scarce near the central veins and portal areas in humans. To characterize the sinusoidal cells, carbon or latex was given intravenously and endogenous peroxidase was demonstrated for the rat, whereas factor VIII-related antigen and endogenous peroxidase were demonstrated for the humans. In the rat, Fc receptors were detected on Kupffer cells, which were characterized by an intense endogenous peroxidase activity and ingestion of latex or quantities of carbon. They were also detected on sinusoidal endothelial cells, which were characterized by undetectable peroxidase activity and no ingestion of latex nor of a small quantity of carbon. In humans, Fc receptors were also present on Kupffer cells as well as sinusoidal endothelial cells, as identified by endogenous peroxidase and factor VIII-related antigen, respectively.

Animals↗

Fluorescence and chemiluminescence enzyme immunoassays of 17 alpha-hydroxyprogesterone in dried blood spotted on filter paper.

Enzyme immunoassays for 17 alpha-hydroxyprogesterone (17-OHP) were developed. Horseradish peroxidase (HRP), glucose oxidase (GOD), invertase (INV) and glucose-6-phosphate dehydrogenase (G6PDH) were used as label enzymes. Double antibody coated beads or tubes were used for separating the bound and free fractions. Antisera used were prepared by using 4-carboxyethylthio-17-OHP and 3-carboxymethyl oxime-17-OHP-bovine serum albumin as immunogens. The bridge heterologous system was more sensitive than other site heterologous and homologous systems. The minimum amounts of 17-OHP detected were 0.25 and 1.0 pg/tube for fluorescence EIAs using HRP and GOD, and 0.1, 10 and 0.1 pg/tube for chemiluminescence EIAs using GOD, INV and G6PDH, respectively. The reproducibility and correlation with RIA were also studied. The present study demonstrates the feasibility of a neonatal screening for congenital adrenal hyperplasia.

17-alpha-Hydroxyprogesterone↗

Production and characterization of monoclonal antibodies to 17 alpha-hydroxyprogesterone.

Hybridoma clones producing antibodies to 17 alpha-hydroxyprogesterone (17-OHP) were established by using a 17-OHP-bovine serum albumin conjugate as an immunogen. Six representative IgG-class monoclonal antibodies of high affinity (10(8)-10(9) M-1) showed differential reactivities with several structurally related steroids. Two enzyme immunoassay (EIA) systems (fluorescence EIA and micro-EIA) for 17-OHP using OHP 4B2.2.3, which showed the lowest cross-reactivity with other steroids, were established. The micro-EIA system was shown to be applicable to the mass-screening of congenital adrenal hyperplasia.

17-alpha-Hydroxyprogesterone↗

Molecular biological studies on structure and mechanism of proton translocating ATPase (H+-ATPase, F0F1).

Recent results on ATPase, mainly from E. coli, obtained by biochemical and molecular biological approaches are reviewed, with special emphasis on results obtained in this laboratory. The advantages of using E. coli in studies of this important enzyme in oxidative phosphorylation are indicated: variant enzymes with specific amino acid replacements can be obtained and their functions and structures can be compared with those of the wild-type enzyme. Structural aspects of this complex enzyme are discussed, including the primary amino acid sequences and molecular assembly of subunits, and mechanistic aspects of the catalytic mechanism and proton translocation.

Amino Acid Sequence↗

Completely thrombosed giant aneurysm of the pericallosal artery: case report.

Patients with a giant intracranial aneurysm usually present as having an intracranial space-taking lesion, but no subarachnoid hemorrhage. The authors describe a 61-year-old man with a completely thrombosed giant aneurysm at the pericallosal artery. Computed tomography scan showed a large, round, mottled, high-density area in the paramedian frontal region that had ringlike enhancement with contrast media. On cerebral angiography it was demonstrated to be an avascular mass lesion. These findings led to an initial diagnosis of falx meningioma. However, final diagnosis at operation was completely thrombosed giant aneurysm. The literature is reviewed and the pathogenesis of intracranial thrombosed giant aneurysm, in regard to its growth and thrombus formation, is discussed.

Brain↗

Cell cycle specificity of tumor necrosis factor and its receptor.

Phase specificity in the TNF cytotoxic effect and the number of TNF binding receptors was investigated using L-M cells incubated synchronously from the S phase. TNF cytotoxicity was observed to occur at various levels during the cell cycle, with peak effect in the G2-M phase. Analysis with 125I-labeled TNF to determine the number of receptors binding TNF in the various cell phases shewed a phase specificity with the maximum number occurring in the G2-M phase, similar to the peak in cytotoxicity. The results suggest the existence of a cell cycle specificity in the cytotoxicity of TNF which is apparently related to changes in the number of receptors capable of binding TNF.

Animals↗

Alteration of lymphocyte functions by 8-methoxypsoralen and long-wave ultraviolet radiation. II. The effect of in vivo PUVA on IL-2 production.

Our previous studies demonstrated that psoralen plus long-wave ultraviolet radiation (PUVA) treatment inhibited certain T-lymphocyte functions, such as locomotive ability. To further analyze the effects of PUVA on T-lymphocyte function, we investigated the ability of mouse spleen cells to produce interleukin 2 (IL-2) after treatment of the mice in vivo with PUVA. Interleukin 2 production was impaired in cells from PUVA-treated mice compared with those from UVA-irradiated, 8-methoxypsoralen-treated, or normal mice. This impairment was not dose dependent, over the dose range of UVA (2-20 J/cm2) examined. Interleukin 2 production was markedly suppressed on day 3 after PUVA and returned to normal by day 7 after the treatment. Topical treatment of the mice with croton oil did not affect IL-2 production of their spleen cells. This result indicates that cutaneous inflammation per se may not be responsible for the suppressive effect of PUVA on IL-2 production. Addition of exogenous IL-1 did not reconstitute the decreased ability of spleen cells to produce IL-2 in vitro, indicating that PUVA affected primarily IL-2 producing cells. These suggest that impaired IL-2 production may account for some of the immune dysfunction observed in PUVA-treated animals.

Animals↗

Serial section analysis of the lesions in diffuse panbronchiolitis.

Diffuse panbronchiolitis (DPB) is clinically and pathologically an independent entity and should be discriminated from the usual bronchiolitis obliterans. The lesions of 20 cases of DPB were serially sectioned and reconstruction was made focusing on the region from the terminal to the respiratory bronchioles. Morphological changes in the region of the respiratory bronchioles were clearly understood and were classified into three types by the presence and the size of the intraluminal granulation tissue. The walls of the respiratory bronchioles were thickened with cell infiltration and granulation tissue in all foci (28 in total), and 26 foci showed intraluminal granulation tissue whereas only 2 foci did not exhibit intraluminal plugs. Xanthoma cells were mostly observed in the interstitial tissue of the alveolar ducts, sacs, and septal walls distal to the stenotic sites as well as in the alveolar spaces in the marked cases.

Adult↗

Responses of intracranial pressure (ICP) produced by stimulating the pressor area in the brainstem at various levels of blood pressure and ICP in cats.

An increase in intracranial pressure (ICP) was produced by stimulating brainstem pressor sites in cats anesthetized with alpha-chloralose. The ICP responses were augmented by lowering prestimulus BP and reduced by elevating prestimulus BP. In contrast, stimulus-induced pressor response of BP showed no consistent correlation to prestimulus BP. When the mean amplitude of stimulus-induced ICP responses at the control prestimulus ICP (within 18 mmHg) was plotted against the mean of the prestimulus BP levels for each site examined, the sites were classified into 2 groups by the regression line; sites generating a marked ICP response above the line and those generating a small ICP response on and under the line. The former sites were located in the paramedian region of the reticular formation including nuclei parvocellularis and gigantocellularis. The latter sites scattered throughout the brainstem pressor area. The ICP response at the former sites was markedly increased at an elevated prestimulus ICP. The peak ICP response at 30-50 mmHg of prestimulus ICP was 70-100 mmHg, similar to plateau waves. The ratio of ICP response size to BP response size was negatively correlated to prestimulus BP and the regression line was 2-5 times steeper at an elevated prestimulus ICP (18-60 mmHg) than at the control ICP. On the other hand, the negative relation between the response ratio and the BP for the latter sites produced no such change at the increased prestimulus ICP. These findings suggest that the ICP response is produced primarily by neurogenic intracranial vasodilation, which works most effectively at moderately decreased cerebral perfusion pressure. This mechanism may be involved in a series of events that results in plateau waves.

Animals↗

Freeze-fracture electron microscopic studies of age-related plasma membrane changes in Sporothrix schenckii.

Characteristics of the plasma membrane of Sporothrix scheckii cells as revealed by freeze-fracture techniques have been classified into eight types (Y1, Y2a, Y2b, Y3a, Y3b, Y4a, Y4b, and Y5) in yeastlike cells grown under the following two conditions: brain heart infusion agar medium at 27 degrees C, and brain heart infusion agar medium at 37 degrees C. Type Y1 cells are yeastlike cells having smooth plasma membranes without any invagination. Typical characteristics of the other types are as follows: type Y2a, smooth plasma membranes with few trenchlike invaginations; type Y2b, wavy plasma membranes with few oval or irregularly formed invaginations; type Y3a, plasma membranes with many randomly distributed trenchlike invaginations; type Y3b, plasma membranes with many cocoonlike or irregularly formed invaginations; type Y4a, plasma membranes with longer trenchlike invaginations; type Y4b, plasma membranes with irregularly formed, enlarged invaginations; and type Y5, smooth or wavy plasma membranes with aggregations of intramembranous particles and with many vacuoles between cell walls and plasma membranes or in the cytoplasm in some cells. By counting the proportion of each type of yeastlike cell under the two conditions and with different cultivation periods, it appears that plasma membrane types change as aging progresses in the following order: type Y1, Y2a, Y3a, Y4a, and Y5 in conidia and type Y1, Y2b, Y3b, Y4b, and Y5 in yeastlike vegetative cells. These observations provide us with an important advantage when studying the effects of antifungal agents on the plasma membrane of Sporothrix scheckii, as it is important to know the natural course of changes in membrane structure during aging.

Cell Membrane↗

Interleukin-2 receptor-inducing factor(s) in adult T cell leukemia.

The expression of the interleukin-2 receptor (IL-2-R) is regulated by transcriptional and post-transcriptional mechanisms. IL-2-R gene expression is induced by pharmacological agents including calcium ions, phorbol esters such as phorbol myristate acetate (PMA) and forskolin (FK), a direct activator of adenylate cyclase. HTLV-I(+) leukemic T cells and T cell lines from patients with adult T cell leukemia (ATL) continuously expressed IL-2-R without production of IL-2. However, there was no abnormality of the structural gene for IL-2-R in these cell lines as well as in fresh leukemic cells of ATL. We have detected that many HTLV-I(+) T4(+) T cell lines constitutively produce a non-IL-2 lymphokine named ATL-derived factor (ADF), which induced the expression of the high-affinity IL-2-R on a variety of cells including HTLV-I(+) T cells, myeloid leukemia cells and YT cells. IL-2-R-inducing agents such as ADF and FK were shown to induce elevation of the mRNA levels for IL-2-R through transcriptional enhancement of the IL-2-R gene. The possible involvement of IL-2-R-inducing cytokines in the physiological lymphocyte activation and the leukemogenesis in ATL and other T cell leukemias is discussed.

Antibodies, Monoclonal↗