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Biomedical subjects

T Osada

Publications and source records attributed to T Osada.

At least 73 records · Page 4Linked to original sources

Replacement of receptor cells in the hamster vomeronasal epithelium after nerve transection.

Chemoreceptor cells in the vomeronasal and olfactory epithelium are replaced following experimentally induced degeneration. This study analyzes quantitatively the time course and degree of vomeronasal receptor cell replacement. Unilateral transection of the vomeronasal nerves in adult hamster was used to induce a retrograde degeneration of receptor cells in the vomeronasal organ. Histological measurement of both number of receptor cells and epithelial thickness were made for recovery times from 0 to 60 days. After nerve transection, there was a gradual degeneration of receptor cells, the number decreasing to 50% of control by day 2 and 16% by day 6. During days 7-15 maximum receptor cell replacement was observed. Cell number increased rapidly and reached a peak on day 15. At recovery times of 40-60 days, cell number returned to the control level. Epithelial thickness, however, decreased to 60-70% during the degeneration period (days 4-6) and did not return to control levels. After 40-60 days epithelial thickness remained at 70% of control. These results demonstrate that vomeronasal receptor cells are replaced following degeneration, but epithelial thickness does not return to control levels. These findings suggest that the number of replacement cells is not limited by the reduced thickness of the epithelium, and that recovery mechanisms may function to restore an optimum number of receptor cells.

Animals↗

A neurotrophic pyrimidine compound, MS-818, enhances EGF-induced restoration of gastric epithelial wounds in vitro.

MS-818 is a novel synthetic pyrimidine compound that stimulates nerve regeneration and promotes synthesis of various growth factors and differentiation of astrocytes. Effects of MS-818 on gastric epithelial cells were assessed using a wound repair model with primary cultured gastric epithelial cells from rabbits. A round wound with a constant cell-free area was created and the process of restoration was monitored by measuring wound size every 12 h. Cell proliferation was monitored by sequential staining with BrdU. As previously reported, EGF (10 ng/ml) accelerated wound repair by promoting cell migration and proliferation. Although MS-818 alone had no effects, MS-818 (10-100 microM) enhanced EGF-induced acceleration of gastric epithelial restoration, including cell migration and proliferation. Although the detailed mechanism of action of this agent is still unclear, MS-818 might have favorable effects on in vivo gastric mucosal repair.

Animals↗

Polymerase chain reaction analysis of the Y chromosome long arm in azoospermic patients: lack of the Y chromosome recognition motif (YRRM1) gene.

We analyzed DNA from a patient with azoospermia whose Y chromosome was cytogenetically normal. A total of 16 loci on the Y chromosome long arm were examined: 15 loci between DYS7E and DYZ1, and the Y chromosome RNA recognition motif (YRRM1) locus, a candidate gene for the azoospermic factor AZF. We did not detect the YRRM1 gene in this patient. This finding supports the theory that YRRM1 is an essential gene for spermatogenesis.

Adult↗

Fixed drug eruption due to amlexanox.

A 23-year-old woman developed allergic rhinitis in 1993. Her doctor prescribed for her Solfa (amlexanox 25 mg) and Lysozymen 90 (lysozyme chloride 90 mg) tablets. She took the tablets occasionally, whenever she developed allergic rhinitis. She noticed a macular erythema of about 3.5 cm wide on her buttocks in 1994, about 1 year after the initial prescription. We conducted a series of tests with the tablets. On patch testing, the patient had a positive reaction to Solfa 50% pet. on the eruptive area, but no such reaction on the non-eruptive area. Furthermore, on patch testing, she had no reaction to Lysozymen 90, 50% pet. on either the eruptive or the non-eruptive area. We also used open application test with Solfa 50% pet. to confirm the cause of her erythema.

Adult↗

[Sick sinus syndrome after chemotherapy for malignant lymphoma with right atrial tumor at initial presentation].

A 56-year-old man was admitted complaining of throat discomfort and dyspnea. He was given a diagnosis of diffuse large B-cell lymphoma on the basis of findings from tumor biopsy specimens of his left pharynx. MRI tomograms and ultrasonic cardiograms revealed a right atrial tumor causing tricuspid stenosis. Although chemotherapy rendered the cardiac tumor indistinct on MRI and UCG images, gallium-67 scintigraphy still demonstrated abnormal cardiac uptake. After 6 courses of CHOP therapy, sick sinus syndrome with syncope suddenly developed in the patient. A cardiac pacemaker was immediately implanted, and radiotherapy was started. The patient's sinus rhythm returned to normal shortly afterward, and the gallium-67 uptake eventually disappeared. In this case gallium-67 scintigraphy was the only diagnostic procedure capable of detecting evidence of residual disease.

Antineoplastic Combined Chemotherapy Protocols↗

[The clinical significance of plasma tissue plasminogen activator (t-PA) levels in severe acute or fulminant hepatitis].

We studied the tissue plasminogen activator (t-PA) levels in the plasma of patients with acute hepatitis (AH), severe acute hepatitis (AHs) and fulminant hepatitis (FH). Plasma t-PA levels were measured consecutively on the first, third and seventh days of hospitalization. Plasma t-PA levels were markedly higher in AHs and FH than in AH (p < 0.05, p < 0.01, respectively) on the first day, but did not differ significantly between AHs and FH on this day. The t-PA levels decreased markedly on the third and seventh days in AHs (both p < 0.05), but did not change from the first day to the third and seventh days in FH. The t-PA levels on the third and seventh days were higher in FH than in AHs (both p < 0.05). There was a significant increase in the plasma t-PA level before an episode of encephalopathy in FH compared with levels in AHs. These observations suggest that t-PA level may be useful as a prognostic parameter in patients with acute hepatic injury.

Acute Disease↗

[Hypoplastic myelodysplastic syndrome progressing to acute myelocytic leukemia (M2) after treatment with G-CSF and immunosuppressants].

A 34-year-old woman was admitted to our hospital because of pancytopenia. She had been given a diagnosis of idiopathic thrombocytopenic purpura during her first pregnancy about 7 years earlier. The patient received a diagnosis of severe aplastic anemia (AA) and was treated with methylprednisolone, cyclosporin A, and granulocyte colony-stimulating factor (G-CSF), but no hematological improvement was observed. Six months later, myeloblasts appeared in the patient's peripheral blood, and she was given a diagnosis of acute myelocytic leukemia AML (FAB : M2). No chromosomal abnormalities were found. As some dyshematopoietic features had been observed in the bone marrow when the patient was first given a diagnosis of AA, it is conceivable that she already had hypoplastic myelodysplastic syndrome (MDS) then. She was treated according to the JALSG-AML92 protocol and achieved complete remission (CR). In this case, the long-term administration of G-CSF may have played an important role in the transformation of MDS into AML. It may be difficult to strictly distinguish AA from hypoplastic MDS with slight dysplastic features, as in this case, because we have no established criteria. Recently the incidence of MDS/AML in AA patients undergoing G-CSF treatment has become a concern. We should be careful about ruling out hypoplastic MDS when diagnosing a condition as AA, especially when therapy includes G-CSF. The patient is still in CR 26 months after intensive combination chemotherapy.

Adult↗

Rebamipide prevented delay of wound repair induced by hydrogen peroxide and suppressed apoptosis of gastric epithelial cells in vitro.

The effects of rebamipide on the restoration process of gastric epithelial wounds were assessed using an in vitro wound-healing model and hydrogen peroxide treatment. Rebamipide (10 or 100 microM) was added to a complete monolayer cell sheet after artificial wounding. The restoration process was analyzed sequentially by a time-lapse video system, and cell migration, proliferation, and apoptosis were assessed. Hydrogen peroxide (1 or 3 mM) inhibited restoration after wounding by suppressing cell migration and proliferation. It also induced epithelial cell apoptosis around the wound. The addition of rebamipide abolished the H2O2-induced retardation and prevented apoptosis. Rebamipide might act as a radical scavenger and have favorable effects on peptic ulcer diseases.

Alanine↗

Hepatic stellate cell contraction is inhibited by lipo-prostaglandin E1 in vitro.

Prostaglandin E1 (PGE1) has been reported to have, experimentally and clinically, a protective effect against liver damage. This effect may result from the relaxation of hepatic stellate cells, whose contraction induces vasoconstriction of hepatic sinusoids. However, prostaglandins are unstable and a new drug delivery system is necessary to administer a sufficient amount of prostaglandin to achieve a protective effect in the liver. The aim of the study is to investigate the effects of lipo-prostaglandin E1 (lipo-PGE1) which has a novel drug delivery system on the stellate cell contraction induced by endothelin-1 in vitro. Lipo-PGE1 inhibited endothelin-1-induced stellate cell contraction in concentrations of 10, 30 and 50 ng/mL. Therefore, lipo-PGE1 may show a cytoprotective effect in the liver through the relaxation of stellate cells and an increase in the hepatic sinusoidal blood flow.

Alprostadil↗

[Acute eosinophilic pneumonia with diffuse fine nodular shadows].

A 45-year-old man was admitted to our hospital because of high fever, dry cough, and respiratory distress. Chest roentgenograms and computed tomograms showed diffuse fine nodular shadows without any other interstitial or alveolar infiltrates. An examination of transbronchial lung biopsy specimens disclosed infiltration of eosinophils and lymphocytes in alveolar walls and perivascular areas. Bronchoalveolar lavage fluid revealed elevated total cell counts, mostly of eosinophils and lymphocytes. The patient was given a diagnosis of acute eosinophilic pneumonia (AEP), but his symptoms improved in a week without any medication. Although diffuse fine nodular shadows on x-ray films may sometimes be the only sign of AEP.

Acute Disease↗

Subcutaneous tissue distribution of vancomycin from a fibrin glue/Dacron graft carrier.

We investigated the tissue distribution of vancomycin (VCM) incorporated in fibrin glue (FG) in a rat model. One VCM-loaded FG Dacron graft (VCM-FG, VCM 0.6 mg/ graft) was implanted in the subcutaneous tissue of the anterior abdominal wall of each rat. VCM was injected intravenously at an equal dose (0.6 mg/rat) after implantation of one control graft (without VCM-FG). After the implantation and the iv injection of an equal dose of VCM (0.6 mg/rat), the tissue distribution of VCM for up to 24 h was determined through analysis of the implanted VCM-FG grafts, which released VCM over a 24 h period. The area under the VCM concentration-time curve (AUC) of the tissue was 89.58 micrograms.h/g after the implantation of the VCM-FG graft, and 7.40 micrograms.h/g after the iv injection of VCM, respectively. The targeting index of the tissue, defined as the ratio of AUC after the implantation of the VCM-FG graft to that after VCM iv injection, was 12.11. None of the six VCM-FG Dacron grafts after implantation became infected following inoculation with S. aureus ATCC 25923 (0.1 mL 10(8) CFU/mL). These results suggest that this VCM-FG Dacron graft delivery may be useful in preventing local infection by enhancing the delivery of VCM to the local areas of the implanted site in rats.

Animals↗

Quasispecies nature of hepatitis C virus and response to alpha interferon: significance as a predictor of direct response to interferon.

BACKGROUND/AIMS: We evaluated the significance of the quasispecies nature of HCV as a predictor of the response to alpha interferon therapy in patients with chronic hepatitis C. METHODS: Natural alpha interferon was administered in 62 patients for 24 weeks (daily for 2 weeks, then three times weekly for 22 weeks) and factors were analyzed that could affect the response. HCV subtype, HCV RNA concentrations and the number of HCV quasispecies were evaluated before treatment. HCV RNA concentrations were measured by branched DNA probe assay. The number of HCV quasispecies was measured by fluorescence single-strand conformation polymorphism analysis. RESULTS: The HCV RNA concentration (p < 0.0001), HCV subtype (p = 0.0076), and the number of HCV quasispecies (p = 0.0024) were significantly associated with a complete response. Multivariate analyses showed that the number of HCV quasispecies was an independent predictor of the disappearance of HCV RNA during the administration of alpha interferon, but did not predict a relapse after its completion. Pretreatment concentration of HCV RNA was the only factor that was related to a long-term disappearance of HCV RNA. CONCLUSIONS: The number of HCV quasispecies was significantly related to the response to alpha interferon early in its administration. The pretreatment concentration of HCV RNA was mainly related to a relapse following completion of treatment.

Adult↗

Increased ubiquitin immunoreactivity in hepatocellular carcinomas and precancerous lesions of the liver.

BACKGROUND/AIMS: Ubiquitin covalently attaches to abnormal and short-lived proteins, thus marking them for ATP-dependent proteolysis in eukaryotic cells. Increased ubiquitin immunoreactivity was recently observed immunohistochemically in human malignant tumors. To clarify the change in protein metabolism during hepatocarcinogenesis, we studied ubiquitin immunoreactivity in hepatocellular carcinomas (HCCs) and precancerous lesions using immunohistochemistry and immunoblot analysis. METHODS: A total of 72 HCCs (37 advanced, 19 early, 16 early-advanced (advanced HCC component in early HCC nodule) type HCCs) and 18 precancerous lesions (8 atypical adenomatous hyperplasias (AAHs), 10 adenomatous hyperplasias (AHs)) were studied immunohistochemically. Immunoblot analysis was also performed in advanced HCC and early HCC cases. RESULTS: Non-tumorous hepatocytes were either immunonegative or weakly stained in their nuclei. Advanced HCCs showed strong immunoreactivity in most cases, while early HCCs showed relatively weaker immunoreactivity. In 14 of 16 early-advanced type tumors, the inner portion of the nodules, which corresponds to advanced HCC, showed stronger immunoreactivity than the outer low-grade portion. In 8 of 8 AAHs and 7 of 10 AHs, positive but weak staining was found. Immunoblot analysis showed an increase in 42 kDa ubiquitinated protein(s) in 8 of 16 advanced HCC cases (50%) and in 1 of 6 early HCC cases (16.7%), as well as an increase in several other bands in tumor tissues. CONCLUSIONS: The intensity of ubiquitin staining appeared to increase in a stepwise manner from AH to advanced HCC, and the results suggest a possible correlation between changes in the ubiquitinated proteins and multistep hepatocarcinogenesis.

Adenoma↗

Patterns of recurrence after initial treatment in patients with small hepatocellular carcinoma.

To assess intrahepatic metastasis (IM) and multicentric occurrence (MO) after initial treatment of small hepatocellular carcinomas (HCC) < or = 2 cm in diameter, we performed clinical and pathological studies in 112 patients who underwent percutaneous ethanol injection therapy (PEIT) or hepatic resection for HCC from January 1985 to December 1994. Patients with intrahepatic recurrences were classified into two groups based on the type of recurrence: the IM group (n = 29, 50.9%) and the MO group (n = 28, 49.1%). Overall recurrence rates after initial treatment were 23.7% at 1 year, 64.5% at 3 years, and 76.1% at 5 years. In patients with IM, the majority of intrahepatic recurrences were observed within 3 years of initial treatment and the primary HCC lesions were closely related to the degree of tumor cell differentiation. Alternatively, intrahepatic recurrences occurred throughout the follow-up period in patients with MO, and the evidence of underlying liver disease (anti-HCV [antibody to hepatitis C virus] positive) and elevated serum alfa-fetoprotein (AFP) concentrations were closely associated with intrahepatic recurrence. Prognoses following additional treatment in MO group patients were superior to those in IM group patients. These results suggest that differentiation between IM and MO in patients with HCC is important for understanding the development and biological behavior of the tumor. That is, the early detection of intrahepatic recurrence and the institution of appropriate additional therapy (PEIT or hepatic resection) may prolong survival in patients with MO.

Adult↗

Immunoreaction at 43 kDa with anti-ubiquitin antibody in breast neoplasms.

Protein ubiquitination has been implicated in ATP-dependent protein turnover and normal cell proliferation. To investigate whether the ubiquitin-mediated system is functionally involved in the cancerous state, we examined changes in protein ubiquitination in 52 surgically resected primary breast tumors. Immunohistochemically, ubiquitin (Ub) was identified in the cytoplasm of cancer cells, which were stained more strongly than adjacent normal ductal epithelium. Corresponding immunoblot analysis of normal and neoplastic regions of human breast showed that the immunoreaction for Ub at about 43 kDa was increased in all of the tumors (100%), regardless of the clinical stage or histologic grade. This protein, which gave a single spot on two-dimensional gel electrophoresis, had partial amino acid sequences which were identical to those of actin family members. Our results suggest that ubiquitination of this 43-kDa protein may be involved in the carcinogenesis or biological characteristics of human breast neoplasms.

Amino Acid Sequence↗

Effects of CRH and LHRH on rat septo-hippocampal neurons.

Electrical activities of septum-diagonal band neurons (SD neurons) antidromically activated by electrical stimulation of the fimbria were recorded in urethane anesthetized male rats. The mean basal firing rate of antidromically identified SD neurons (2.3 Hz) was not different from that of unidentified ones (2.2 Hz). The mean latency of antidromic activation by the fimbria stimulation was 4.2 ms. Iontophoretically applied CRH and LHRH affected 60% and 40% of identified SD neurons, but only 19% and 13% of unidentified SD neurons, respectively. The ratio of response to no response to both peptides was significantly different in unidentified SD neurons from that in identified SD neurons. These results suggest that SD neurons mediate the effect of CRH and LHRH on hippocampal neurons.

Animals↗