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Biomedical subjects

K Ohtsuka

Publications and source records attributed to K Ohtsuka.

At least 127 records · Page 7Linked to original sources

Acromegaly associated with Chiari-I malformation and polycystic ovary syndrome.

We report a 19-year-old female case of acromegaly associated with Chiari-I malformation and polycystic ovary syndrome. She also had syringomyelia and thoracic scoliosis. Although the association of acromegaly and Chiari-I malformation was by chance, exaggerated secretion of growth hormone may have aggravated the scoliosis. The incidence of polycystic ovary in acromegalic patients remains to be elucidated. However, elevation of plasma insulin and insulin-like growth factor, that is usually observed in patients with acromegaly, could stimulate androgen production in the ovaries. The patient was successfully treated with transsphenoidal adenomectomy for pituitary tumor and correction surgery for thoracic scoliosis.

Acromegaly↗

Binding of benanomicin A to fungal cells in reference to its fungicidal action.

An antifungal antibiotic, benanomicin A, binds in the presence of Ca2+ to susceptible fungi and some bacteria, but not to antibiotic-resistant bacteria and mammalian cells. With the susceptible yeast Saccharomyces cerevisiae, benanomicin A binds similarly to whole cells and to protoplasts. Studies using benanomicin A and three structurally related derivatives suggested that a carboxylic acid in the D-alanine moiety and a sugar moiety in the benanomicin A molecule are essential for both binding and antifungal activities against growing S. cerevisiae. An amino substituent on the sugar moiety can be replaced with a hydroxyl group without the loss of activities. Benanomicin A binds to various yeast mannans which differ in glycosidic linkages. These results indicate that binding of benanomicin A to the mannan portion of fungal cells is essential for exertion of the antifungal activity.

Anthracyclines↗

Descending projections from the cortical accommodation area in the cat.

PURPOSE: Results in previous studies indicated that the lateral suprasylvian (LS) area, the cortical area surrounding the middle suprasylvian sulcus (Mss) of the cat, has important roles in the control of accommodation. The current study was conducted to investigate descending projections from the accommodation-related area in the LS area to the brainstem. METHODS: Wheat germ agglutinin-horseradish peroxydase (WGA-HRP) was injected into the accommodation-related area in the pretectum or in the rostral superior colliculus (SC) of the cat. These regions are thought to be involved in the control of accommodation based on results of previous studies. The authors investigated locations of retrogradely labeled cells in the LS area. In addition, the authors compared amplitudes of accommodative responses evoked by stimulation of the LS area before and after neuronal activities in the rostral SC were inhibited by the injection of muscimol (gamma-aminobutyric acid agonist) into the accommodation-related area in the rostral SC. RESULTS: After injections of WGA-HRP into the accommodation-related area in the rostral SC, retrogradely labeled cells were observed in the lower part of the medial bank of the Mss, which corresponded to the accommodation-related area in the LS area. Conversely, after injections of WGA-HRP into the accommodation-related area in the pretectum, retrogradely labeled cells were seen in the upper part of the medial bank of the Mss, which did not correspond to the accommodation-related area in the LS area. Accommodation responses evoked by stimulation of the LS area were abolished by the injection of muscimol into the accommodation-related area in the rostral SC. CONCLUSIONS: These findings suggest that accommodation-related signals from the LS area mainly project to the rostral SC, but not to the pretectum.

Accommodation, Ocular↗

[Examination of the courses of the arteries in the axillary region. II. The course of the axillary artery in the case of Adachi's C-type brachial plexus].

Müller (1904) stated that the axillary artery in the case of Adachi's C-type brachial plexus (AxC) might be derived from the 9th segmental artery. Yamada (1967) named a type of the subscapular artery (Sbs) "the superficial subscapular artery" which arose from the normal axillary artery (Ax), crossed over the medial cord of the brachial plexus and then gave off the lateral thoracic artery (TL). He considered that it might be derived from TL and develop to form AxC by compensating the less developed normal Ax. We reexamined the courses of Sbs and Ax and distinguished three types (S-, I-, and P-type) of Sbs according to their origin and course. Then we stated that the mechanism of formation of Sbs variations could be explained by the combination between the three stem parts and the common peripheral arterial network (Sbs system) (Aizawa et al. 1995). Therefore, the purpose of this study was to justify the validity of Müller (1904) and Yamada (1967) and to clarify the origin of AxC by applying the concept of Sbs system. The materials were 15 cases of AxC and 7 cases of incomplete AxC (AxC). The results were as follows. 1) The course of AxC was divided into four parts. 2) Two types of AxC were discerned according to the course against the nerve bundle communicating from the medial cord to the radial nerve (FM-R). They are the type-1 AxC which does not pass between the FM-R and the radial nerve, and the type-2 AxC which dose pass between them. 3) The first part included the branching points of the thoracoacromial artery in all cases and the superior superficial brachial artery (BSS) in 8 cases. The BSS passed between C7 and C8 of the roots of Ansa pectoralis (50%) in about the same manner as BSS from the normal axillary artery (Ax). On the other hand, the point where Ax or AxC penetrated the ventral stratum of the brachial plexus was examined in 156 cases. The data except those of the AxC cases displayed a symmetrical distribution having a sharp peak in C7-C8 (79.5%) and were not compatible with the incidence of AxC penetrating lower than Th1 (7.7%). Therefore, it was difficult to conclude that the first part of AxC was derived from the 9th segmental artery. 4) The second part crossed over the medial cord and gave off TL in almost all the cases. Therefore, this part was considered to include the S-point where the S-type Sbs system (Yamada's superficial subscapular artery) arose and to be derived from TL. 5) From the S-point, while the S-type Sbs system immediately ran down to the deep region of the axilla, AxC traversed the axilla passing in front of the thoracodorsal nerve to reach the point where AxC was sandwiched between the ventral and the dorsal stratum of the brachial plexus. Therefore, the following course from the S-point of AxC (the third part) was different from that of the S-type Sbs system. From the third part of AxC, the I-type Sbs system arose in 15 cases, and both the subscapular branch (RS: *) and the branch to the coracobrachial muscle (CB) were often given off. They were the same branches as those which arose from the I-point of normal Ax, and type-2 AxC passed between FM-R and the radial nerve in this part. Therefore, it was considered that the third part included the I-point of the normal Ax and, moreover, AxC recovered the normal course of Ax at the I-point. 6) The fourth part of AxC included the P-point where the P-type Sbs system branched off from AxC in 7 cases. The course of the fourth part of AxC had exactly the same course as that of normal Ax. 7) It was elucidated that the first part, the distal half of the third part, and the fourth part of AxC were exactly the same as normal Ax, the second part was derived from TL, and the proximal half of the third part from the S-point to the I-point was unique in AxC. Recently, however, the reverse course of the unique part of AxC has appeared as the deep lateral thoracic artery (TLp) (Aizawa et al. 1995) in rare cases. 8) In co

Axillary Artery↗

[Isolation rate of Pseudomonas aeruginosa from surgical infections and their susceptibilities].

Pseudomonas aeruginosa isolated from surgical infections during the period from July 1982 to June 1995 were investigated in a multicenter study involving 19 hospitals in Japan, and the following results were obtained. 1. Though the isolation rate of P. aeruginosa was not high from primary infections, it was more frequently isolated from postoperative infections throughout the study period. Enterococcus spp., P. aeruginosa and Staphylococcus aureus including MRSA were predominant among postoperative infections. From the postoperative cases that had previous antibiotic treatment, Enterococcus spp., MRSA and P. aeruginosa were more predominantly isolated than from those without previous treatments with antibiotics. 2. Cefozopran, ceftazidime, cefsulodin, aztreonam, carumonam, gentamicin, amikacin and ofloxacin had strong activities against P. aeruginosa. We recognize recently that antibiotic-resistant strains of P. aeruginosa against imipenem and ofloxacin have been increasing year by year.

Anti-Bacterial Agents↗

Percutaneous lumbar nucleotomy.

We performed 66 percutaneous lumbar nucleotomies (PLN) in 63 patients from October 1984 to March 1990. The patients (42 male patients, 21 female patients) ranged in age from 13 to 73 years (average, 36.8 years). Postoperative observation ranged from 6 months to 5 years and 11 months (average, 2.0 years). Pre- and postoperative discograms were reviewed. Fifty-one patients (79.7%) were judged to have successful results: They were able to return to gainful employment and to their preinjury level of activity. Six patients (9.4%) were judged to have unsuccessful results, and they required more radical surgical procedures. PLN was not effective for the patients with extremely severe positive SLR or agonizing leg pain.

Adolescent↗

[Bacteria isolated from surgical infections and its susceptibilities to antimicrobial agents. Special references to bacteria isolated between July 1994 and June 1995].

Isolated bacteria from infections in general surgery during the period from July 1994 to June 1995 were investigated by a multicenter study in Japan, and the following results were obtained. One hundred and fifty-three strains were isolated from primary infections, and 143 strains were isolated from postoperative infections. From primary infections, both anaerobic Gram-positive and-negative bacteria were predominant, and from postoperative infections, aerobic Gram-positive bacteria were predominant. Among aerobic Gram-positive bacteria, the isolation rate of Enterococcus faecalis was highest, followed by that of Staphylococcus aureus from both types of infections. Among anaerobic Gram-positive bacteria, the isolation rate of Streptococcus intermedius was highest from primary infections, but from postoperative infections anaerobic Gram-positive bacteria was uncommon. Among aerobic Gram-negative bacteria, Escherichia coli was most predominantly isolated from primary infections, followed by Klebsiella pneumoniae and Pseudomonas aeruginosa in this order. From postoperative infections, P. aeruginosa was most predominantly isolated, followed by Serratia marcescens and E. coli. Among anaerobic Gram-negative bacteria, the isolation rate of Bacteroides fragilis group was the highest from both types of infections. We have noticed that resistant strains against imipenem and ofloxacin were increasing among P. aeruginosa and resistant strains against cefazolin were increasing among E. coli. MICs of cefazolin against four out of 30 strains of E. coli were higher than 100 micrograms/ml, and MICs of imipenem was higher than 50 micrograms/ml against 5 out of 22 strains of P. aeruginosa.

Anti-Bacterial Agents↗

Inhibitory effect of plasma FKBP12 on immunosuppressive activity of FK506.

To evaluate the roles of extracellular FKBP12, we examined the effect of extracellular FKBP12 on the immunosuppressive activity of FK506 in vitro and clinically. The ability of FK506 to suppress phytohemagglutinin-induced proliferative response of human peripheral blood mononuclear cells was inhibited in the presence of recombinant FKBP12 dose-dependently. We measured plasma levels of FKBP12 using a newly developed enzyme-linked immunosorbent assay system in 34 patients receiving FK506 after liver transplantation. In 7 patients with acute cellular rejection, plasma FKBP12 increased significantly at the onset of rejection compared with 1 week before onset (P < 0.05) and further increased to or remained at more than 250 ng/ml 1 week after onset. In 22 of 27 patients without acute cellular rejection, plasma FKBP12 was less than 70 ng/ml during the 4 weeks after transplantation. In the other 5 of 27 patients without acute cellular rejection, plasma FKBP12 exceeded 250 ng/ml. Rapid increase of plasma FKBP12 was observed in only one of these 5 patients, at the onset of high fever due to a liver abscess. There was no significant difference in whole blood trough levels of FK506 between the patients with or without acute cellular rejection. These results suggest that the rapid increase in plasma levels of FKBP12 may contribute to the occurrence and progress of acute cellular rejection probably by inhibiting the immunosuppressive activity of FK506.

Adolescent↗

Relationships between intermediate TCR cells and NK1.1+ T cells in various immune organs. NK1.1+ T cells are present within a population of intermediate TCR cells.

Experiments to date have revealed a population of T cells that carry intermediate (int) levels of TCR (or CD3) and express IL-2R beta-chain (IL-2R beta) in mouse liver. Such int TCR cells also reside in other immune organs, although in low numbers. On the other hand, NK1.1+ T cells with int TCR do reside in the thymus and other peripheral organs. To determine the relationship of two types of cells, we characterized int CD3 cells and NK1.1+ T cells throughout the organs in terms of the phenotype, V beta repertoire, and morphology. Although both IL-2R beta+ T cells and NK1.1+ T cells are classified as int CD3 cells, NK1.1+ T cells are present within int CD3 cells. The majority of int CD3 cells in the liver and thymus were NK1.1+, whereas the minority of such cells in the spleen, lymph nodes, and bone marrow were NK1.1+. Among int CD3 cells, double-negative (DN) CD4-8- cells and/or CD4+ were abundant in NK1.1+ subset, whereas CD8+ cells were generally abundant in NK1.1- subset. Self-reactive V beta+ clones estimated by the M1s system were distributed to both NK1.1+ and NK1.1- subsets. High CD3 cells in the thymus and other organs contained neither DN cells nor forbidden clones. Int CD3 cells had the morphology of granular or agranular lymphocytes carrying perforin. Among int CD3 cells, NK1.1+ subset had a higher level of perforin-positive cells than NK1.1- subset. These results clearly demonstrate the relationship between int TCR cells and NK1.1+ T cells in various organs.

Animals↗

Evidence for extrathymic generation of intermediate T cell receptor cells in the liver revealed in thymectomized, irradiated mice subjected to bone marrow transplantation.

In addition to the major intrathymic pathway of T cell differentiation, extrathymic pathways of such differentiation have been shown to exist in the liver and intestine. In particular, hepatic T cells of T cell receptors or CD3 of intermediate levels (i.e., intermediate T cell receptor cells) always contain self-reactive clones and sometimes appear at other sites, including the target tissues in autoimmune diseases and the tumor sites in malignancies. To prove their extrathymic origin and self reactivity, in this study we used thymectomized, irradiated (B6 x C3H/He) F1 mice subjected to transplantation of bone marrow cells of B6 mice. It was clearly demonstrated that all T cells generated under athymic conditions in the peripheral immune organs are intermediate CD3 cells. In the case of nonthymectomized irradiated mice, not only intermediate CD3 cells but also high CD3 cells were generated. Phenotypic characterization showed that newly generated intermediate CD3 cells were unique (e.g., interleukin 2 receptor alpha-/beta+ and CD44+ L-selectin-) and were, therefore, distinguishable from thymus-derived T cells. The precursor cells of intermediate CD3 cells in the bone marrow were Thy-1+ CD3-. The extrathymic generation of intermediate CD3 cells was confirmed in other combinations of bone marrow transplantation, C3H --> C3H and B10.Thy1.1 --> B6.Thy1.2. The generated intermediate CD3 cells in the liver contained high levels of self-reactive clones estimated by anti-V beta monoclonal antibodies in conjunction with the endogenous superantigen minor lymphocyte-stimulating system, especially the combination of B6 --> (B6 x C3H/He) (graft-versus-host-situation).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Transcriptional inhibition of insulin by FK506 and possible involvement of FK506 binding protein-12 in pancreatic beta-cell.

FK506 (tacrolimus) is a strong immunosuppressant: it has been approved as a drug for liver transplantation in Japan, the United States, and the United Kingdom. One of its main adverse effects is hyperglycemia. Thus, in this study, we investigated the mechanism and the reversibility of the hyperglycemia caused by FK506. FK506 did not affect the glucose uptake by insulin into rat strio-muscle cell line, but suppressed insulin production in rat insulinoma cells. Two-week oral administration of FK506 at 10 mg/kg/day suppressed insulin production time-dependently at the transcriptional step in pancreatic beta-cells, while glucagon content in pancreatic alpha-cells was not affected. When FK506 administration was stopped in these rats, insulin mRNA transcription and insulin production returned to normal. This recovery indicates that the adverse effect of FK506 on the pancreas is reversible. A high content of FK506 binding protein-12 (FKBP-12) in the pancreatic beta-cells was confirmed by immunostaining with anti-human FKBP-12 mAb, but the content was less in the pancreatic alpha-cells and almost negligible in the acinar cells. In contrast, a high content of calcineurin in the pancreatic alpha-cells was confirmed by using anti-calcineurin polyclonal antibody, but this content was less in the pancreatic beta-cells and not found in the acinar cells. Thus, as in the case with NF-AT in T cells, these findings point to the reduction of unidentified nuclear factors for insulin mRNA transcription caused by the binding of FK506 to FKBP-12 and a subsequent inhibition of calcineurin in the beta-cells.

Animals↗

Interaction between hsp70 and hsp40, eukaryotic homologues of DnaK and DnaJ, in human cells expressing mutant-type p53.

We have recently identified a novel 40-kDa heatshock protein hsp40 as a mammalian homologue of bacterial DnaJ protein. Here we demonstrate the physical interaction between hsp70 (DnaK homologue) and hsp40 in human cells as determined by immunoprecipitation methods. Co-immunoprecipitation of hsp70 with hsp40 was dependent on the presence of ATP or unfolded protein (reduced carboxymethylated alpha-lactalbumin). A mutant type of tumor suppressor gene product, mtp53, was co-immunoprecipitated not only with hsp70 but also with hsp40. These results suggest the existence of a hsp70(DnaK)/hsp40(DnaJ) chaperone system in mammalian cells.

Escherichia coli Proteins↗

Supportive cellular elements for hepatic T cell differentiation: T cells expressing intermediate levels of the T cell receptor are cytotoxic against syngeneic hepatoma, and are lost after hepatocyte damage.

Extrathymic T cells exist in the liver and are often seen in close contact with Kupffer cells in the hepatic sinusoids. Since selective depletion of Kupffer cells has become possible by using liposome-encapsulated clodronate, it was investigated whether elimination of Kupffer cells influences the level of extrathymic T cells in the liver. Extrathymic T cells were identified as interleukin-2 receptor beta-chain (IL-2R beta) intermediate TCR (TCRint) cells by two-color staining for CD3 or T cell receptor (TCR) and IL-2R beta. The elimination of Kupffer cells did not significantly affect levels of TCRint cells up to 7 days after treatment. We then examined monocyte colony stimulating factor (M-CSF)-deficient op/op mice (low levels of Kupffer cells). Extrathymic T cells both in the liver and spleen of these mice were detected at a level comparable to that of control mice. Since extrathymic T cells in the liver are sometimes located in the parenchymal space, the relationship between extrathymic T cells and hepatocytes was then examined. Electron microscopy revealed that some hepatic T cells adhered directly to hepatocytes. When hepatocytes were damaged by a single injection of CCl4, hepatocyte death and subsequent hepatic fibrosis were induced. Beginning 3 days after injection, CD3int cells, but not other type of cells, decreased prominently. Purified CD3int cells, as well as whole lymphocytes in the liver, were cytotoxic against syngeneic hepatoma. In parallel with the above-mentioned hepatic damage, the cytotoxic activity of lymphocytes against such targets was impaired in the liver. These results suggest that extra-thymic generation of TCRint cells and their acquisition of cytotoxic function are relatively independent of Kupffer cells, but are dependent on hepatocytes.

Animals↗

Unique order of the lymphocyte subset induction in the liver and intestine of mice during Listeria monocytogenes infection.

We investigated how NK cells, extrathymic T cells, and thymus-derived T cells are activated in mice during infection with an intracellular pathogen, Listeria (L.) monocytogenes. Although macrophages and granulocytes are known to be involved in the elimination of this pathogen in an early phase of infection, it was still controversial what type of lymphocytes are induced as effectors in subsequent phases. When mice were ip injected with 1 x 10(3) L. monocytogenes (a sublethal dose), a prominent increase in the number of mononuclear cells in the liver and spleen was induced. Phenotypic analysis revealed that serial induction of lymphocyte subsets, NK cells-->extrathymic T cells-->thymus-derived T cells, occurred in these organs. Extrathymic T cells were estimated to have intermediate CD3 and a high level of IL-2 receptor beta-chain on the surface (i.e., intermediate CD3 cells). These mice became free from infection after 2 weeks. In the case of oral administration, 1 x 10(3) L. monocytogenes increased the number of cells in the liver and the number of intraepithelial and lamina propria lymphocytes in the intestine. Phenotypic analysis also showed a sequential induction of lymphocyte subsets in the liver and the induction of extrathymic T cells in the intestine. Preelimination of intermediate TCR cells and NK cells by in vivo treatment with anti-LFA-1 mAb made mice susceptible to an ip injected sublethal dose of L. monocytogenes. These results reveal a unique order of lymphocyte induction during listerial infection and indicate that extrathymic T cells might be one of the important cells in achieving resistance against L. monocytogenes.

Animals↗

Adhesion molecules on intermediate TCR cells. II. Hepatoprotective effects of hyaluronic acid on acute liver injury.

The liver is a major organ wherein extrathymic T cells and NK cells exist in mice. Due to their unique properties, i.e., extrathymic T cells are TCR (or CD3)-intermediate+ IL-2R beta+ (herein termed intermediate TCR cells) and NK cells are TCR(-)IL-2R beta+, they are easily distinguished from the other lymphocyte subsets by using mAbs in conjunction with immunofluorescence tests. They were recently found to express a higher level of CD44 antigen, which is a ligand for hyaluronic acid, than that of another T cell subset (i.e., thymus-derived T cells or bright TCR cells). Since an intravenous administration of hyaluronic acid was also found to reduce the number of intermediate TCR cells and NK cells in the liver, we examined whether hyaluronic acid had a hepatoprotective effect on acute liver injury. Such injury was induced by LPS injection in mice pretreated with Propionibacterium acnes 1 week earlier. When a single dose of hyaluronic acid was given to these mice 12 hr before LPS injection, a prominent hepatoprotective effect was observed in terms of decreases of mortality (up to 50%), lymphocyte infiltration of the liver, serum transaminase levels, and tissue damage. At this time, liver mononuclear cells isolated from the treated mice showed decreased levels of cytokine production such as TNF and IL-1. These results reveal that intermediate TCR cells and NK cells in the liver actually adhere the sinusoid walls by means of an interaction of CD44 molecules and hyaluronic acid even in the case of acute liver injury. It suggests a possible therapeutic effect of the administration of hyaluronic acid in acute liver injury by eliminating the effector cells and cytokine-producing cells from the liver.

Adjuvants, Immunologic↗

Intermediate TCR cells with self-reactive clones are effector cells which induce syngeneic graft-versus-host disease in mice.

It has been established that, even after syngeneic bone marrow transplantation, animals treated with immunosuppressive drugs may suffer from graft-versus-host disease, showing autoimmune-like symptoms. Although the major effector cells are known to be T-cell subsets, detailed characterization of such T cells remains to be investigated. In the present study, we characterized them, especially as to whether they are thymus-derived T cells or extrathymic T cells, and how self-reactive clones were distributed among the above T-cell subsets. BALB/c mice (Mls-1b2a) were irradiated (9 Gy), subjected to bone marrow transplantation, and then treated with cyclosporin A (CsA) for 6 weeks. From 2 weeks after the cessation of CsA, these mice displayed signs of GVH disease. The major target organs included the liver and colon. Two-color staining for CD3 and IL-2R beta was applied to identify CD3-IL-2R beta+ NK cells, CD3-intermediate +IL-2R beta+ cells (i.e., intermediate CD3 or TCR cells of extrathymic origin) and CD3-high+IL-2R beta- cells (i.e., high CD3 cells of thymic origin). It was demonstrated that the major expanding lymphocytes were intermediate TCR cells and that self-reactive clones (V beta 3+ and V beta 11+ cells in this strain of mice) were confined to this population. Interestingly, these self-reactive clones had ability to respond to immobilized anti-V beta 3 and anti-V beta 11 mAbs. Liver MNC in mice with GVH disease which contained the highest proportion of intermediate TCR cells were able to mediate the adoptive transfer of GVH disease to other irradiated (6.5 Gy) mice. Intermediate TCR cells also showed potent cytotoxic activity against syngeneic leukemia cells. These results suggest that intermediate TCR cells are the major effector cells for the induction of syngeneic GVH disease.

Animals↗