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Biomedical subjects

I Hirata

Publications and source records attributed to I Hirata.

At least 55 records · Page 3Linked to original sources

A role for granulocyte and monocyte apheresis in the treatment of rheumatoid arthritis.

Rheumatoid arthritis (RA) is an inflammatory condition, the etiology of which is not well understood. Recent reports indicate a major role of granulocytes in the pathogenesis of RA; arthritic joints are infiltrated with phagocytic leukocytes, granulocytes, and monocytes/macrophages, and it is believed that these cells, by releasing degradative proteinases, cytokines, and reactive oxygen species, contribute to joint destruction. Hence, the apheresis of granulocytes and monocytes may benefit patients with RA. Granulocyte and monocyte apheresis was carried out in 143 patients with RA using an apheresis column (G-1) packed with 220 g cellulose acetate beads, which selectively adsorb granulocytes and monocytes. Patients received 1 or 2 apheresis sessions, each of 1 h duration per week over a 4 week period at a flow rate of 30 ml/min. Apheresis significantly reduced swollen and tender joint counts and the duration of morning stiffness, and it increased grip strength, together with suppression of tumor necrosis factor-alpha and interleukin-1beta production by peripheral blood monocytes. It is concluded that this alternative treatment induces a kind of immunomodulation.

Adult↗

[Increased IL-2 and sIL-2R in sera of infants with HTLV-I infection from mother].

In our laboratory, children born to women are known to be infected with Human T-cell Leukemia Virus type-1 (HTLV-I) have been followed using, detect of gene by PCR and antibody by Western Blot Assay (WB) and Immunofluorescence Assay (IFA) test from 1990 through 1996. Four children out of 123 delivery cases have been confirmed to be infected with HTLV-I. We analyzed the correlation between the concentration of cytokines (IL-2, sIL-2R, IFN-gamma) and HTLV-I infection. IL-2 and sIL-2R in sera increased after HTLV-I infection. There was no correlation between the concentration of IFN-gamma and HTLV-I infection. These result suggested that detection of IL-2 and sIL-2R might be the marker of HTLV-I infection.

Biomarkers↗

Bile acids inhibit tumour necrosis factor alpha-induced interleukin-8 production in human colon epithelial cells.

To clarify the regulatory mechanism of the production of various inflammatory mediators by intestinal epithelial cells, the effect of bile acids (tauroursodeoxycholate, TUDC; taurochenodeoxycholate, TCDC; and taurocholate, TC) on the cytokine-induced production of interleukin (IL)-8 in a human colon epithelial cell line (HT-29) was examined. HT-29 cells were incubated for 24 h in a culture medium containing tumour necrosis factor alpha (TNF alpha; 1 ng/mL) and/or interleukin (IL)-1beta (1 ng/mL) in the presence or absence of bile acids. The IL-8 concentration in the medium was measured by an enzyme-linked immunosorbent assay. The binding assay of TNF alpha was performed using [125I]-TNF alpha (100 pmol/L). Interleukin-8 production during incubation with TNF alpha was markedly reduced in the presence of 0.5 and 1 mmol/LTUDC, 0.5 and 1 mmol/LTCDC and 0.5 and 1 mmol/LTC, by 56, 85, 86, 91, 37 and 70%, respectively. The IL-8 production during incubation with IL-1beta was not significantly reduced in the presence of these bile acids. The specific binding of TNF alpha to cells was inhibited 33, 47, and 14% by 1 mmol/LTUDC, TCDC and TC, respectively. These findings suggest that bile acids inhibit TNF alpha-induced IL-8 production by the colonic cells. The suppression may be partly due to inhibition of TNF alpha binding to the cells by bile acids.

Bile Acids and Salts↗

Cyclosporine A inhibits interleukin-8 production in a human colon epithelial cell line (HT-29).

Intestinal epithelial cells produce various inflammatory mediators. However, the way in which immunosuppressive agents influence the production of these mediators by intestinal epithelial cells is not understood. The effects of cyclosporine A (CsA), tacrolimus (FK506), and dexamethasone (DEX) on cytokine-induced production of interleukin (IL)-8 in a human colonic cancer cell line (HT-29) were examined. HT-29 cells were stimulated with either IL-1 beta or tumor necrosis factor alpha (TNF alpha) together with CsA, FK506, or DEX. The presence of IL-8 protein was detected by enzyme-linked immunosorbent assay, and the expression of IL-8 messenger RNA (mRNA) by reversetranscription polymerase chain reaction. CsA (1, 5, and 10ng/ml) significantly reduced IL-1 beta-induced IL-8 production (by 32%, 41%, and 48%, respectively), and reduced TNF alpha-induced IL-8 production (by 21%, 42%, and 50%, respectively). FK506 or DEX had no effect on IL-1 beta- or TNF alpha-induced IL-8 production. The expression of IL-8 mRNA was also inhibited by CsA. These findings suggest that CsA may influence the production of inflammatory mediators in colonic cells in a different manner from FK506 and DEX.

Cell Count↗

Granulocytapheresis in the treatment of patients with rheumatoid arthritis.

The G-1 column is an extracorporeal type granulocytapheresis device packed with 220 g cellulose acetate beads to which granulocytes and monocytes specifically adhere. A total of 59 rheumatoid arthritis patients with elevated granulocyte counts from 4 hospitals in Japan received 2 apheresis sessions of 1 h duration/week for a total of 8 times over a period of 4 weeks. About 55% of the leukocytes which entered the G-1 column were adsorbed onto the beads: 95% were granulocytes, 3.5% monocytes, and 0.4% lymphocytes. Clinical and efficacy assessments showed improvements in swollen joints (p < 0.01), tender joints (p < 0.001), the active joint score (p < 0.001), duration of morning stiffness (p < 0.01), and grip strength (p < 0.001). In good responders, the improvements were observed for up to 12 weeks following the last apheresis. Exacerbation was noted in 2 patients. It is suggested that the efficacy of the G-1 column is attributable to the removal or suppression of hyperactive leukocytes and inflammatory cytokines, inducing a kind of immunomodulation.

Adsorption↗

[A case of recurrent advanced colon cancer treated with CPT-11 for second-line chemotherapy].

A 59-year old male patient had been operated on for sigmoid colon cancer in July, 1990. Operative findings were, P0, H0, S1, N (-), Stage I, and histological findings were ss, ly 2, v0, n (-). In July 1994, the CEA level elevated, and be was diagnoted as having para-aortic LN swelling and stenosis of anastomosis of colon. He was admitted for treatment of recurrent colon cancer. Initially, he was treated with continuous injection of 5-FU, low-dose CDDP and Leucovorin. His CEA level decreased and para-aortic LN diminished in size. But, in December 1995, the CEA level and para-aortic LN relapsed. 5-FU, CDDP and Leucovorin were administered, but the CEA level became more and more elevated. This regimen was not considered responsible for drug resistance. CPT-11 was administered at 60 mg/week 6 times, and 80 mg/week 3 times. The side effects disappeared, LN sightly diminished in size, and the CEA level decreased. Judging by the anticancer effect without severe side effect, we found CPT-11 a useful drug for second-line chemotherapy.

Antineoplastic Agents, Phytogenic↗

[A case of aneurysm of the descending thoracic aorta associated with Behçet's disease].

A 66-year-old male with Behçet's disease admitted again with hemoptysis. He underwent the resection and direct closure of descending aortic aneurysm 3 years ago, followed without the use of steroid. Chest CT scanning demonstrated a recurrent aneurysm of the descending aorta which was could not be detected on the previous CT only 23 days before. In the current operation, we performed resection, direct closure and wrapping of the aneurysm. The pathological examination showed a true aneurysm of Behçet's disease. The patient is free from recurrence for 17 months since the operation under steroid therapy.

Aged↗

Determination of L-buthionin (SR)-sulfoximine, gamma-glutamylcysteine synthetase inhibitor in rat plasma with HPLC after prelabeling with dansyl chloride.

L-(SR)-Buthionin sulfoximine (L-(SR)-BSO) is a potent and specific inhibitor of gamma-glutamylcysteine synthetase, which catalyzes the first reaction of glutathione biosynthesis. A selective, sensitive, and simple high-performance liquid chromatographic method was developed for the determination of L-(SR)-BSO in rat plasma. After the compound was labeled with dansyl chloride (Dns-Cl) under optimal conditions, it was separated in a Zolbax-ODS column with a mobile phase that consisted of 0.01M phosphate buffer, methanol, and acetonitrile (8:1:3, v/v). The compound was detected with a fluorescence detector at an excitation wavelength of 335 nm and an emission wavelength of 525 nm using a xenon lamp. The coefficients of variation (DV) from the interassay in the low and high concentrations (10 and 500 micrograms/mL of L-(SR)-BSO in rat plasma) were 2.5 and 4.8%, respectively. The CVs from the intra-assay in the low and high concentrations were 3.2 and 5.6%, respectively. The minimum concentration of L-(SR)-BSO that could be determined was 10 micrograms/mL when 100-microL serum samples were used. The detection limit was 50 ng per injection volume. This method enables pharmacokinetic and pharmacodynamic studies in rats.

Animals↗

Argyrophilic nucleolar organizer regions in colorectal malignancy: application of typing by their density.

Colorectal neoplasms obtained at colonoscopy were examined by argyrophilic nucleolar organizer region (AgNOR) staining to evaluate the usefulness of AgNOR as a discriminant for malignancy. AgNOR dots were divided into two kinds: 'structures' (larger and less-densely stained) corresponding to the nucleolus, and 'units' (smaller and densely stained) presumed to be true AgNOR within the structure. The number of structures per nucleus did not differ between the adenoma and carcinoma groups, whereas the number of units per nucleus showed a significant difference. However there were several cases showing an overlap between the adenoma and carcinoma groups, leading to a difficulty in deciding whether any given case was benign or malignant. Three types of AgNOR patterns were categorized based on the ratio of units to structure. Type I was defined as the unit being indistinguishable from the structure, Type II as each structure having one to five units, and Type III as at least one structure having six or more units, irrespective of total number of units per nucleus. The colorectal lesions in which more than half of the neoplastic cells showed Type III coincided well with carcinomas histologically diagnosed, with the exception of adenomas with severe atypia. Labeling index of proliferating cell nuclear antigen (PCNA LI) differed between the adenoma and carcinoma groups with a considerable extent of overlap, and correlated to some extent with the AgNOR values. These results showed that the AgNOR staining was useful for determining malignancy and its usefulness appeared superior to PCNA LI.

Adenoma↗

Fecal lactoferrin as a marker for disease activity in inflammatory bowel disease: comparison with other neutrophil-derived proteins.

OBJECTIVES: 1) To investigate which neutrophil-derived proteins in feces most accurately reflect disease activity in inflammatory bowel disease. 2) To examine the extracellular release of these proteins by activated neutrophils and their stability in feces by in vitro study. METHODS: We studied 41 patients (91 samples) with ulcerative colitis (UC), 34 patients (105 samples) with Crohn's disease (CD), and 25 control subjects. Fecal levels of lactoferrin (Lf), polymorphonuclear neutrophil elastase (PMN-E), myeloperoxidase (MPO), and lysozyme (Lys) were measured by ELISA. We also measured fecal hemoglobin (Hb) and alpha 1-antitrypsin (alpha 1-AT), useful markers of disease activity in UC and CD, respectively. For the in vitro study, blood samples were stimulated with phorbol myristate acetate or latex beads. For the assessment of stability, homogenized stool samples were stored at 4 degrees C, 25 degrees C, and 37 degrees C for various periods. RESULTS: 1) Fecal Lf, PMN-E, MPO, and Lys concentrations were significantly increased in the active phase of the disease compared to the inactive phase in both UC and CD. 2) Fecal Lf, PMN-E, MPO, and Lys concentrations correlated significantly with fecal Hb concentration in UC, whereas fecal Lf, PMN-E, and MPO concentrations correlated significantly with alpha 1-AT concentration in CD. In UC, fecal Lf, PMN-E, MPO, and Lys concentrations were high in 15, 9, 14, and 14 samples, respectively, of 25 samples with normal Hb concentration. In CD, fecal Lf, PMN-E, and MPO concentrations were high in 19, 10, and 16 samples, respectively, of 30 samples with normal alpha 1-AT concentration. 3) The extracellular release of Lf was the most efficient and this molecule was the most stable in feces. CONCLUSIONS: Both our clinical and our in vitro studies suggested that Lf is the most suitable of these proteins to use as neutrophil-derived fecal marker of inflammation for clinical application.

Adult↗

[A case of psittacosis with psychiatric symptoms, abnormal EEG, and abnormal SPECT].

A 40-year-old woman was admitted to our hospital with disorientation, delusional idea, and sensory disturbance of lower face after having a fever and cough for 5 days. A chest X-ray examination revealed an infiltration in the left lower lobe field. Psittacosis was diagnosed because the serum antibody titer against chlamydia psittaci was elevated. Electroencephalogram showed right temporal lobe spikes. SPECT showed decreased accumulation of 99mTc-HMPAO in the right frontal and temporal lobe. Computed tomography scan of the brain was normal. This patient was diagnosed as ornithsis Encephalitis.

Adult↗

Effects of interferon-gamma on cell differentiation and cytokine production of a human monoblast cell line, U937.

The U937 cell, a human monoblast cell line, has been used as a model to study the function of human monocytes. We investigated the effects of interferon-gamma (IFN-gamma) on superoxide anion (O2-) production, cell surface antigens, and cytokine production of U937 cells. IFN-gamma treatment enhanced O2- production of fMLP or PMA-stimulated U937 cells. IFN-gamma increased the ratio of CD23 and CD11b positive cells. The fluorescence intensity of CD14 and CD25 was enhanced by IFN-gamma treatment. U937 cells produced IL-1 alpha, IL-1 beta, IL-6, and TNF-alpha by lipopolysaccharide (LPS) stimulation. IFN-gamma treatment enhanced TNF-alpha production, but decreased IL-6 production. These results suggest that IFN-gamma differentiates U937 cells to monocyte-like cells and it regulates the production systems of IL-6 and TNF-alpha separately in U937 cells.

Antigens↗

Transferrin is not involved in initial uptake process of iron in rat duodenal mucosa. Ultrastructural study by x-ray energy spectrometry.

The role of transferrin in iron absorption by the duodenal mucosa in rats with iron deficiency and controls was evaluated immunohistochemically. Ferric iron was administered to each rat using a metallic gastric tube. Transferrin was stained by an immunoperoxidase method and iron with Prussian blue in the same duodenal sections and observed by light microscopy. The localization of transferrin differed from that of ferric iron both in rats with iron deficiency and in controls. In iron-deficient rats, transferrin was weakly stained after iron administration but was strongly stained after saline administration. In contrast, in controls, transferrin was weakly stained after saline administration but was strongly stained after iron administration. By electron microscopy, x-ray energy spectrometric analysis of the transferrin-positive areas showed no iron peak. In iron-deficient rats, accumulation of electron-dense transferrin-negative microgranules was observed in some of the duodenal columnar epithelium. X-ray energy spectrometric analysis of this area revealed iron, indicating iron absorption. These results suggest that mucosal transferrin does not act as a shuttle protein in iron absorption via the rat duodenal columnar epithelium, and the function of this protein may be to inform the absorptive cells of the iron status of the body as observed in other organs.

Animals↗

Intestinal protein loss and bleeding assessed by fecal hemoglobin, transferrin, albumin, and alpha-1-antitrypsin levels in patients with colorectal diseases.

Four fecal proteins (hemoglobin, transferrin, albumin, and alpha 1-antitrypsin) were measured by enzyme-linked immunosorbent assay (ELISA) in patients with colorectal diseases. Levels of all 4 proteins were significantly increased in patients with colonic cancer and ulcerative colitis (UC) compared to levels in control subjects, while fecal alpha 1-antitrypsin was particularly elevated in colonic Crohn's disease (CD). That is, the fecal protein pattern of CD was distinct from those of colonic polyps, colonic cancer, and UC. To investigate whether levels of these fecal proteins reflect disease activity in UC and CD, comparative evaluation of fecal proteins in the active and inactive phases was performed. In UC, differences in the fecal concentrations of all 4 proteins were significant between the active and inactive phases of the disease. In CD, however, the difference in alpha 1-antitrypsin concentration was significant. Our results suggest that measurements of these 4 fecal proteins would be useful in the screening of colorectal diseases. In addition, these markers can also be used as indicators of disease activity in inflammatory bowel diseases.

Adult↗

[Clinical result of left ventricular free wall rupture resulting from acute myocardial infarction].

We have treated 10 patients of left ventricular free wall rupture (LVFWR) resulting from acute myocardial infarction (AMI) in our intensive care unit (ICU) from Oct. 1984 to Dec. 1993. Nine of 10 patients underwent surgical repair, however, one patient was treated with pericardocentetesis in ICU and fibrin-glue was infused into the pericardial space (fibrin-glue therapy:FG therapy). The survival rate of surgical repair was only 33% (3/9), especially that was only 17% (1/6) when cardiopulmonary bypass (CPB) was required. One patient (49-year-old, male) suffered from cardiogenic shock following AMI in the posterior wall was performed coronary angioplasty (PTCA) in emergency and IABP support was required. Fourth day after PTCA, a sudden hemodynamical collapse had occurred on this patient due to cardiac tamponade. This patient was treated with pericardiocentetesis in ICU and FG therapy was performed, because all surgical teams were occupied in their operations. After FG therapy hemodynamical stability was obtained, the patient was survived and discharged at 2 months after LVFWR. In conclusion, the surgical result of LVFWR is still not good, especially when CPB was utilized. FG therapy was successful in one patient, suggesting FG therapy can be an alternative therapy for LVFWR when surgical team is not available.

Aged↗