Biomedical subjects

H Onodera

Publications and source records attributed to H Onodera.

At least 91 records · Page 5Linked to original sources

PubMed1998

Complement activation as a cause of transient hypotension during plasmapheresis.

Hypotension is one of the most common adverse effect of plasmapheresis (PP) and often is attributed to hypovolemia due to extracorporeal circulation and the vasovagal reflex. Complements are activated during PP, and the activated complements are strong anaphylatoxins and potent vasodilators. Therefore, we studied the relationship between the transient hypotension and the plasma levels of activated complements during and after PP in 8 sessions of 7 patients using the Plasmafro OP-08 as a plasma separator. Five of the patients underwent immunoadsorption PP using the IM-TR 350 or IM-PH 350 as the adsorption column. The other underwent double filtration PP using the Evaflux 4A as a second filter. In 4 of 8 sessions, patients experienced transient hypotension with significantly elevated plasma levels of activated complements C3a and C5a. In contrast, patients without hypotension showed no increases in C3a and C5a values during PP. In this report, we emphasize the critical role of activated complements for hypotension during PP.

Adolescent↗

PubMed1998

Induction of squamous cell carcinomas in the salivary glands of rats by potassium iodide.

In a 2-year carcinogenicity study of potassium iodide (KI) in F344/DuCrj rats, squamous cell carcinomas (SCCs) were observed in the salivary glands of 4/40 males and 3/40 females receiving 1000 ppm KI in the drinking water. Ductular proliferation with lobular atrophy was observed at high incidence in the submandibular glands of the high-dose animals, and squamous metaplasia was frequently evident within the proliferative ductules and the larger interlobular ducts. A transition from metaplasia to SCC was apparent. The results suggest that squamous metaplasia in proliferative ductules, occurring secondarily to lobular impairment induced by KI, may develop into SCCs via a non-genotoxic, proliferation-dependent mechanism.

Administration, Oral↗

PubMed1998

A new device for selective removal of CD4+ T cells.

To control antigen (Ag)-specific immune cells is important in the treatment of autoimmune diseases. In particular, a direct solution may be obtained by controlling the CD4+ cell function that controls the immune response of autoimmune T cells. Thus, a technique to selectively remove CD4+ cells has been developed, based on the consideration that the immune system may possibly be modified by selectively removing the CD4+ cells by means of extracorporeal circulation. The currently developed device to selectively remove CD4+ cells uses a material made of nonwoven fabric with monoclonal antibodies immobilized on the surface. With this device, removal of only CD4+ cells from human mononuclear cells suspension can be accomplished. Moreover, CD4+ cells can be specifically removed from peripheral whole blood by direct perfusion. This review outlines a series of procedures for selective cell removal and the results of our research.

Animals↗

PubMed1998

Preventive effects of Shichimotsu-koka-to on renal lesions in stroke-prone spontaneously hypertensive rats.

Shichimotsu-koka-to (SKT) has been prescribed to treat patients with essential and renal hypertension. We investigated the effects of SKT on renal lesions in stroke-prone spontaneously hypertensive rats (SHRSPs). SHRSPs were given an extract of SKT by mixing it with drinking water, from 8 through 29 weeks of age, so that the average intake of SKT extract was about 1.5 g/kg/d. At 29 weeks of age, the kidneys of SHRSPs exhibited proliferative arteritis characterized by the proliferation of smooth muscle cells in the interlobular arteries, dilation and degeneration of renal tubules, infiltration of inflammatory cells and hemorrhage, with partial swelling or necrotizing of glomeruli. In particular, arteritis and periarteritis were noted. The treatment of SHRSPs with SKT ameliorated this morphological damage in the kidney and significantly decreased urea nitrogen in the serum. Treatment with SKT also strongly decreased the xanthine oxidase (XOD) activity and significantly increased the superoxide dismutase (SOD) activity in the kidney of SHRSPs; consequently, these values became close to those in normotensive Wistar Kyoto rats (WKYs). These results indicate that treatment with SKT ameliorated the histopathological damage and change in activity of enzymes related to free radicals in the kidney of SHRSPs, which may be important mechanisms for SKT for protecting SHRSPs from renal dysfunction.

Animals↗

PubMed1998

Expression of inducible nitric oxide synthase and inflammatory cytokines in alveolar macrophages of ARDS following sepsis.

STUDY OBJECTIVE: The objective of this study was to evaluate the role of inducible nitric oxide synthase (iNOS) and proinflammatory cytokines in alveolar macrophages (AMs) in the pathogenesis of ARDS following sepsis. SETTING: ICU in a university hospital. DESIGN: Prospective exploratory, open-labeled study was carried out. PATIENTS: A total of 24 patients were investigated: 8 patients diagnosed as having ARDS following sepsis (ARDS group); 8 patients under general anesthesia in the operating room whose lung functions were normal (control group); and 8 patients who were intubated and artificially ventilated for 1 week in the ICU whose lung functions were not deteriorated without fulfilling the ARDS criteria and whose general state fulfilled the sepsis criteria (long-term ventilation group, or LTV group). MEASUREMENTS AND RESULTS: The expression of iNOS, interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and interleukin-8 (IL-8) in AMs obtained from BAL fluid (BALF) was determined by the immunofluorescent technique. We observed the significant expression of iNOS, IL-6, and IL-8 only in the ARDS group. Meanwhile, NOx (the sum of NO2- + NO3-) was elevated in the BALF supernatant, and IL-6 and IL-8 levels in both the BALF supernatant and the serum were also elevated in the ARDS group. No significant expressions were detected in the control and the LTV group. CONCLUSIONS: The result that iNOS was detected only in ARDS patients following sepsis suggests that iNOS together with proinflammatory cytokines produced by AMs might play a pivotal role in the pathogenesis of acute lung injury and be useful for monitoring disorders in the lung in such conditions.

Adult↗

PubMed1998

Immunohistochemical studies of TSH-producing cells in the pituitary and expression of growth factors in thyroidal proliferative lesions in rats treated with thiourea and excess vitamin A.

Changes of TSH-producing cells in the pituitary and thyroid expression of the growth factors, transforming growth factor alpha (TGF alpha) and epidermal growth factor receptor (EGFR), as well as cyclin D1, were investigated immunohistochemically in order to clarify their contribution to the enhancing effects of excess vitamin A (VA) on thyroidal carcinogenesis induced by thiourea (TU). Male rats were allocated to 4 groups, control, TU, VA, and TU + VA, respectively, receiving no treatment, water containing 0.2% TU, diet containing 0.1% VA, and both for 10 or 19 weeks after a single s.c. injection of DHPN (2800 mg/kg) for initiation. Immunohistochemistry using antibodies against TSH demonstrated enlargement of TSH-producing cells in the TU + VA group as compared to the TU group, supporting our conclusion that enhanced TSH stimulation is mainly responsible for promoting the effects of excess VA. Since the expression of TGF alpha, EGFR, and cyclin D1 in thyroid proliferative lesions did not exhibit any differences between the TU and TU + VA groups in the present study, these factors are unlikely to participate in VA enhancement of carcinogenesis.

Animals↗

PubMed1998

[A case of systemic lupus erythematosus complicated with marked intestinal edema and paralytic ileus].

A 43-years-old female was admitted to our hospital because of facial erythema and photosensitivity in 1983 and was diagnosed as systemic lupus erythematosus (SLE). She was treated with betamethazone 2.5 mg/day as an outpatient. Abdominal pain and diarrhea were developed in September, 1995. So she was admitted to our hospital and diagnosed as having paralytic ileus. Ultrasonography showed marked intestinal edema. Forbidden oral intake and given antibiotics, she was satisfactorily improved in a few days, but the symptoms got worse soon. We forbid oral intake again. We performed a pulse therapy with 1 g of methylprednisolone and increased a dose of betamethasone 2.5 to 4.0 mg/day, but the symptoms were not improved. Since October 6th, serum creatinine level (s-CRE) increased to 8.1 mg/dl at October, 20th. We suspected the worsening of SLE nephropathy or drug-induced nephropathy, so we stopped a medication of pravastatin and used 50 mg/day of azathioprine. Moreover, we did a pulse therapy of methylprednisolone and a plasmapheresis. By these treatments, s-CRE level returned to normal range and paralytic ileus was completely improved. The cause of hypercreatininemia was suspected to be rhabdomyolysis due to pravastatin. The main cause of paralytic ileus with intestinal edema was suspected to be vascular disturbance of superior mesenteric arteries. We consider that pulse therapy and plasmapheresis are useful for a patient of SLE with marked intestinal edema and paralytic ileus.

Adult↗

PubMed1998

[Implication of VEGF and MMPs in hepatic metastasis of human colon cancer].

This article describes the significance of mRNA expression of VEGF, MMP-2, MMP-9, and MT1-MMP in human colorectal cancer metastases, particularly hepatic metastases. The levels of gene expression were quantified by Northern blot hybridization in tumor and nontumor tissues obtained from 66 primary cases. Significantly higher levels of expression of VEGF mRNA were observed in patients with synchronous hepatic metastases (n = 15) and/or lymph node metastases than in those without. Patients with synchronous hepatic metastases had significantly higher levels of mRNA expression of all MMP genes than in those without, and no apparent correlation was seen between MMP mRNA expression and other clinicopathologic variables. Also in a study including 4 cases of metachronous hepatic metastases after surgery. VEGF, MMP-9, and MT1-MMP mRNA expression were significantly higher in patients with hepatic metastases than in those without, indicating that these are predictable markers for hepatic metastases. Immunohistochemical examination revealed that VEGF and MT1-MMP were localized mainly in cancer cells, whereas MMP-2 and MMP-9 were distributed throughout stromal cells such as fibroblasts and leukocytes in tumor tissues.

Collagenases↗

PubMed1997

Primary central nervous system leukemia with a novel chromosomal translocation.

A case of central nervous system (CNS) leukemia with normal bone marrow, associated with a novel chromosomal abnormality, is described. A 58 year-old woman complained of hearing disturbance, severe headache and vomiting, and showed signs of meningeal irritation, as well as papilledema and bilateral dysacusis. Immature atypical cells were found in the cerebrospinal fluid (CSF) with elevated pressure, pleocytosis, increased protein and decreased glucose levels. She was diagnosed as having neoplastic meningitis. In spite of intensive investigations, including bone marrow puncture, malignancies were not found in organs other than intra-cranial site. The symptoms and CSF findings were temporarily improved with chemotherapy and irradiation, but she relapsed into neoplastic meningitis. The anaplastic cells in CSF were positive with CD45 by immunocytochemistry, and were positive by peroxidase staining. Thus, the anaplastic cells were considered to be myelocytic leukemic cells. Chromosomal analysis showed that these leukemic cells had a novel chromosomal abnormality: 46XX, 4q+, 10q-, 16q-. There has been no report of leukemic meningitis without bone marrow abnormalities. It is possible that this peculiar abnormal chromosome is related to the primary infiltration of the central nervous system. With this novel chromosomal abnormality, this case is important for considering the mechanism of primary leukemic meningitis.

Central Nervous System Diseases↗

PubMed1997

New therapeutic possibility of blocking cytokine-induced neutrophil chemoattractant on transient ischemic brain damage in rats.

Earlier we indicated that neutrophilic invasion into cerebral parenchyma is an important step in rat cerebral ischemia-reperfusion injury and the production of chemotactic factors, cytokine-induced neutrophil chemoattractant (CINC) precede the neutrophilic invasion. The aim of the present study was to evaluate the role of CINC production and the therapeutic possibility of blocking CINC activity in the transient ischemic brain damage in rats. Focal transient ischemia was produced by intraluminal occlusion of the right middle cerebral artery for 60 min. An enzyme immunoassay was used to measure the brain concentration of CINC and myeloperoxidase activity in ischemic areas was measured as a marker of neutrophilic accumulation. An immunohistochemical staining technique was used to detect the immunopositive cells for anti-CINC antibody. Further, application of anti-CINC antibody or anti-neutrophil antibody to rats was used to evaluate the role of CINC production. In ischemic areas, CINC production was detected and peaked 12 h after reperfusion, which followed 60 min of ischemia. Intraperitoneal injection of anti-neutrophil antibody 24 h before and immediately after reperfusion significantly reduced the brain water content and partially reduced the CINC production in ischemic areas. Further, immunohistochemical staining showed that anti-CINC antibody was found on the endothelial surface of venules and on parts of neutrophils that had invaded the ischemic area 6 to 24 h after reperfusion. Also, treatment with anti-CINC antibody reduced ischemic edema formation 24 h after reperfusion and the size of infarction areas 7 days after reperfusion. It thus appears that CINC, mainly produced by endothelium activated by factors released from neutrophils, plays an important role in ischemic brain damage. Furthermore, the blocking of CINC activity with antibody suggests an immuno-therapeutic approach to the treatment of stroke patients.

Animals↗

PubMed1997

Indefinite islet allograft survival in mice after a short course of treatment with anti-CD45 monoclonal antibodies.

BACKGROUND: Although islet cell transplantation is considered an ideal form of endocrine replacement for type I diabetes, clinical application in humans is still not feasible. New immunosuppressive strategies are clearly needed to control inexorable rejection. CD45 is a family of transmembrane protein tyrosine phosphatases critically involved in the regulation of lymphocyte activation signals. Anti-CD45RB monoclonal antibody can prevent rejection of murine renal allografts. METHODS: Here, we examine the consequences of targeting CD45 in murine islet cell transplantation. Diabetic mice recipients received islet allografts under the kidney capsule and were divided into seven groups. Recipients received no treatment (controls) or anti-CD45RB monoclonal antibody (mAb; MB23G2 or C363.16A) at different dosages and treatment intervals. RESULTS: All untreated control animals lost islet function, becoming hyperglycemic within 10-17 days after transplantation. Animals treated with either anti-CD45RB mAb showed a significant prolongation of islet allograft survival when compared with controls. Anti-CD45RB MB23G2 at 100 microg/day, given on days -1, 0, and 5 was particularly effective, inducing indefinite islet allograft survival in 60% of recipients. CONCLUSIONS: These results indicate that anti-CD45 mAbs are potent immunomodulatory agents, able to sustain indefinite islet allograft function after a short treatment course in the highly immunogenic model of islet transplantation.

Animals↗

PubMed1997

New saxitoxin analogues from the freshwater filamentous cyanobacterium Lyngbya wollei.

Along with decarbamoylsaxitoxin and decarbamoylgonyautoxin-2 and -3, six new saxitoxin analogues were isolated from the freshwater mat-forming filamentous cyanobacterium Lyngbya wollei collected from Guntersville Reservoir on the Tennessee River in Alabama. Their structures were determined by electrospray ionization mass spectrometry and several NMR techniques. Five of the toxins contain an acetyl moiety attached to the side chain, which is the first report of these saxitoxin analogues. In three of the toxins a hydrated ketone at C-12 was reduced to alpha-alcohol. The presence of acetate in the side chain resulted in a sevenfold to 17-fold times decrease in mouse toxicity compared to their carbamoyl counterparts, while the reduction at C-12 resulted in a complete loss of mouse toxicity.

Animals↗

PubMed1997

Small intestinal cancer with extensive lymph node metastases showing complete remission by methotrexate/5-fluorouracil sequential therapy: report of a case.

A case of poorly differentiated adenocarcinoma of the small bowel with extensive lymph node metastases is herein presented, which responded to methotrexate/5-fluorouracil (MTX/5-FU) sequential therapy. The lymph node metastases disappeared completely after 10 months of treatment. After recurrence, combination therapy with radiation, hyperthermia, and cisplatinum were also effective in reducing the degree of nodal swelling while still allowing the patient to maintain her accustomed lifestyle for a prolonged period of time. Further multi-institutional studies are still needed, however, to fully assess this new therapeutic regimen for small bowel cancers.

Adenocarcinoma↗

PubMed1997

UDP-GT involvement in the enhancement of cell proliferation in thyroid follicular cell proliferative lesions in rats treated with thiourea and vitamin A.

The mechanisms underlying enhanced cell proliferation in thyroid proliferative lesions of rats simultaneously treated with large amounts of vitamin A (VA) and thiourea (TU) were investigated. Male F344 animals were initiated with N-bis(2-hydroxypropyl)nitrosamine (2800 mg/kg body weight, single s.c. injection). Starting 1 week later, groups received water containing 0.2% TU (TU group), diet containing 0.1% VA (VA group), both 0.2% TU and 0.1% VA (TU + VA group) or tap water/basal diet without supplement (control group) for 10 weeks. The serum levels of triiodothyronine (T3) and thyroxine (T4) were decreased and the thyroid stimulating hormone (TSH) levels were elevated in the TU and TU + VA groups, with the degree of change being significantly greater in the combined treatment group. The induction of P450 isoenzymes by TU was not enhanced by VA supplementation, but uridine diphosphate glucuronosyltransferase (UDP-GT) activity in the liver was significantly increased in the TU + VA group compared to the TU group. Thyroid weights were increased in both the TU and TU + VA groups, this being more pronounced with VA supplementation. Thyroid follicular cell hyperplasias and neoplasias were induced to similar extents in both TU treated groups, but their cell proliferation appeared to be increased by the VA supplementation. The results of the present study suggest that enhanced cell proliferation is due to increased TSH stimulation, resulting from the decrease in serum T3/T4 levels brought about by induction of liver UDP-GT activity with the combined action of TU + VA as well as inhibition by TU of thyroid hormone synthesis in the thyroid.

Animals↗

PubMed1997

Detection of colorectal carcinoma cells in circulating peripheral blood by reverse transcription-polymerase chain reaction targeting cytokeratin-20 mRNA.

For the detection of circulating colorectal carcinoma cells, we investigated the presence of cytokeratin 20 (CK 20) mRNA in the peripheral blood of colorectal carcinoma patients. Application of our published technique resulted in analysis by reverse transcription followed by three-step nested polymerase chain reaction. This analysis could detect a single Colo 205 colon cancer cell mixed with 1 ml of blood. Our system also successfully detected the presence of CK 20 mRNA in actual patients' peripheral blood samples. Our highly sensitive and specific system for the detection of CK-20 mRNA from patients' peripheral blood thus seems to be useful for screening for circulating colorectal carcinoma cells.

Adult↗

PubMed1997

Confirmation of anatoxin-a(s), in the cyanobacterium Anabaena lemmermannii, as the cause of bird kills in Danish lakes.

Cyanobacterial blooms were implicated in bird kills at lakes in Denmark in July 1993 and June-July 1994. These blooms were dominated by Anabaena lemmermannii and were shown to contain a neurotoxin with anticholinesterase activity. In this study, the toxin was isolated by mouse lethality guided column chromatographies from the field sample collected at Lake Knud sø in 1993. Various spectroscopic data indicated that the toxin was anatoxin-a(s), an irreversible anticholinesterase, first reported in Anabaena flos-aquae. Chemical detection of the same toxin in cultured A. lemmermannii also confirmed this species as the cause of the deaths of the wild birds.

Anabaena↗

PubMed1997

Expression of corticotropin-releasing factor (CRF) in peritoneum and pericardium in the rat embryo by in situ hybridization histochemistry.

Corticotropin releasing factor (CRF) mRNA expression in the thorax and abdomen was studied by in situ hybridization in rat tissue sections obtained from embryonic day 12 (E12) to E16. On E12 no signal was observed in any region. On E13 the first signals were detected particularly in serous membranes such as pericardium and peritoneum. By E14, the signal was strong in these membranes. On E15 the signal markedly diminished, and on E16 no signal was evident in serous membranes. This stage-specific expression of CRF mRNA in developing pericardium and peritoneum suggests that this peptide acts in pericardial and peritoneal development.

Animals↗

PubMed1997

Lack of carcinogenicity of cyanoguanidine in F344 rats.

The carcinogenicity of cyanoguanidine, a compound used in the production of melamine, guanidine salts and guanamine derivatives, was examined in male and female Fischer 344 rats fed CRF-1 pulverized diets containing 0, 2.5 and 5% cyanoguanidine for up to 2 yr. The rats were randomly allocated to three groups, each consisting of 50 males and 50 females. The mean body weight gains in both sexes of the 5% group and in females of the 2.5% group were significantly lower than the control values after wk 1 of treatment. No other signs of toxicity were seen in any of the rats throughout the treatment period. Histopathologically, various tumours developed in all groups, including the control group, but these were all similar to those known to occur spontaneously in this strain of rats, and no toxicologically significant increase was found for any lesion type in the treated groups. On the basis of these results, it is concluded that cyanoguanidine exerts no carcinogenic potential in F344 rats when administered for up to 2 yr under the conditions of the present study.

Administration, Oral↗