Biomedical subjects

S Kishimoto

Publications and source records attributed to S Kishimoto.

At least 109 records · Page 6Linked to original sources

PubMed1996

Interleukin-12 activates human gamma delta T cells: synergistic effect of tumor necrosis factor-alpha.

gammadelta T cell populations are known to expand in response to intracellular bacterial infectious agents regardless of previous priming. We have shown previously that soluble factor(s) produced by Mycobacterium-stimulated monocytes activate cord blood gammadelta T cells to proliferate. In this study, we investigated whether cytokines produced by monocytes are responsible for gammadelta T cell activation in vitro: interleukin (IL)-1beta, IL-6, IL-8, IL-12, tumor necrosis factor (TNF)-alpha and granulocyte/macrophage colony-stimulating factor were examined. Recombinant human IL-12 stimulated gammadelta T cells, but not alphabeta T cells in peripheral blood mononuclear cells, to express CD25 on their surfaces, and to expand in number in vitro. IL-12-primed gammadelta T cell numbers increased to a greater extent in the culture to which exogenous IL-2 (5 U/ml) was added. Anti-TNF-alpha monoclonal antibody inhibited IL-12-induced up-regulation of CD25 on gammadelta T cells, suggesting that endogenous TNF-alpha may play a role in IL-12-induced activation of gammadelta T cells. Recombinant TNF-alpha synergistically augmented IL-12-induced activation of gammadelta T cells. Furthermore, IL-12 up-regulated TNF receptors on gammadelta T cells in vitro: TNF-alpha binding to its receptor induced CD25 expression on the gammadelta T cells in an autocrine or paracrine fashion, or perhaps both. It also became evident that both IL-12 and TNF-alpha were produced by mycobacterial lysate-stimulated monocytes. Taken together, these results suggest that upon confrontation with mycobacterial organisms, gammadelta T cells can be quickly and antigen-nonspecifically activated by soluble factors including IL-12 and TNF-alpha, both of which are produced by mononuclear phagocytes in response to mycobacterial organisms.

Adult↗

PubMed1996

Therapeutic effect of egualen sodium (KT1-32), a new antiulcer agent, on chronic gastritis induced by sodium taurocholate in rats.

We investigated the therapeutic effects of egualen sodium (KT1-32), a new antiulcer agent, on chronic erosive and atrophic gastritis induced by 5 months' administration of sodium taurocholate (TCA; 5 mM) in rats. The chronic gastritis was manifested by mucosal surface injuries (erosions), reduced mucosal thickness, reduction of the number of parietal cells, infiltration of inflammatory cells, and proliferation of collagenous fiber. Egualen sodium, (10-100 mg/kg, t.i.d.) administered orally to the rats for 2 weeks after the withdrawal of TCA, dose-dependently and significantly decreased the total length of erosions. The indicators of atrophic gastritis, i.e., reduced mucosal thickness and reduction in the number of parietal cells, were improved dose-dependently by the administration of this agent. Egualen sodium also reduced the inflammatory cell infiltration and the proliferation of collagenous fiber in the gastric mucosa in a dose-dependent manner. The reduced staining of neutral gastric mucus was improved by a high dose (100 mg/kg) of egualen sodium. The therapeutic effects of egualen sodium on experimental gastritis were superior to those of sofalcone and sodium guaiazulene 3-sulfonate. These results suggest that egualen sodium may be a promising agent for the treatment of erosive and atrophic gastritis.

Administration, Oral↗

PubMed1996

Detection of apoptosis by in situ labeling in pilomatricoma.

Pilomatricoma is a benign epidermal appendage tumor with differentiation toward hair cortex cells. It is composed of varying percentages of basophilic cells, shadow cells, and transitional cells. Transitional cells seem to be apoptotic cells as evidenced by their morphological and ultrastructural characteristics. We investigated apoptosis in ten specimens of pilomatricoma by the transferase-mediated dUTP-biotin nick end labeling (TUNEL) technique. TUNEL-positive structures were detected in both transitional cell and amorphous debris zones, but not in either basophilic cell or shadow cell zones. In the transitional cell zone, apoptotic cells were found either in groups or bands, while in the amorphous debris zone, apoptotic bodies of varying sizes were seen diffusely. These findings indicate that transitional cells, due to the fact that they are dying cells, may not differentiate into the shadow cells. This view is supported by the facts that the transition of basophilic cells into the shadow cells is abrupt in some areas and that tumor cells, with or without ultrastructural characteristics of apoptosis, are found in the transitional cell zone. Furthermore, ultrastructural nuclear changes in shadow cells are different from those seen in apoptosis. Therefore, we propose that the name of transitional cells should be changed to "condensed cells." Although it has been conventionally though that basophilic cells in pilomatricoma differentiate directly and/or via transitional cells into shadow cells, we demonstrate that basophilic cells undergo two different processes. The first is differentiation directly into shadow cells, an the second is passage, via "condensed cells" (transitional cells), into the amorphous debris that results from tumor kinetics.

Apoptosis↗

PubMed1996

Enhanced expression of platelet-activating factor receptor on human eosinophils by interleukin-3, interleukin-5 and granulocyte-macrophage colony-stimulating factor.

The effects of interleukin-3 (IL-3), IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) on the surface expression of platelet-activating factor (PAF) receptor on eosinophils was examined using a PAF receptor binding assay. Specific binding of [3H]WEB 2086, a specific ligand for PAF receptor, to peripheral blood eosinophils obtained from healthy individuals was significantly increased when the cells were cultured with IL-3, IL-5, or GM-CSF for 12 h, compared with untreated cells. The PAF-induced increase in intracellular calcium ion concentration in eosinophils was markedly augmented by exposure to IL-5 for 12 h. These results suggest that these cytokines modulate the responsiveness of eosinophils to PAF through enhancement of PAF receptor expression on the cell surface.

Calcium↗

PubMed1996

[Locoregional injection of OK-432/fibrinogen/thrombin for unresectable metastatic liver tumors].

We performed the locoregional injection of OK-432/fibrinogen/thrombin to unresectable hepatic tumors metastasized from colorectal cancers, which were hardly controlled by arterial infusion chemotherapy. CEA was markedly decreased following this treatment, although abdominal CT did not show a significant reduction of tumor mass. This immuno-injection therapy may be a choice of treatment for metastatic liver tumors, refractory to treatment by conventional chemotherapy.

Antineoplastic Agents↗

PubMed1996

[A patient with HCC successfully treated by ethanol injection therapy with etoposide].

A patient with hepatocellular carcinoma (HCC) who underwent successfully percutaneous ethanol injection therapy (PEIT) with etoposide was reported. A 72-year-old Japanese man with positive HCV-Ab developed multiple tumors of HCC. He underwent transcatheter arterial embolization (TAE) four times and PEIT three times, but the growth of tumors (particularly, S8) could not be controlled by these modalities. Then, the mixture of etoposide (20 mg), ethanol (8.5 ml) and lipiodol (1.5 ml) was injected into S6 tumors. Consistent with the normalization of serum AFP level, CT scan revealed the marked remaining lipiodol in these tumors. PEIT with etoposide is the treatment of choice in patients with HCC refractory to treatment by conventional TAE or PEIT.

Aged↗

PubMed1996

[A patient with hepatocellular carcinoma originating from the caudate lobe, who underwent hepatectomy following microwave coagulation therapy].

Hepatocellular carcinoma (HCC) originating from the caudate lobe is rare (about 2%), and prognosis is poor due to difficulties in early diagnosis, transarterial chemoembolization (TAE), and surgical resection. Distant metastasis is also likely to develop. To prevent metastasis during surgical manipulations, we performed microwave coagulation therapy before caudate lobectomy in one patient. Although the efficacy of this procedure remains to be elucidated, the multidisciplinary treatment described in this study is essential for the improvement of prognosis in patients with HCC developing from caudate lobe.

Carcinoma, Hepatocellular↗

PubMed1996

[A patient with pancreatic acinar cell carcinoma, effectively treated by the infusion chemotherapy through hepatic artery using 5-FU, CDDP and MMC].

Chemotherapy for pancreatic acinar cell carcinoma has not been well studied. We report herein one patient, in whom arterial chemotherapy with 5-FU, CDDP and MMC was extremely effective. He underwent distal pancreatectomy associated with partial resection of transverse colon. Hepatic recurrence was detected by MRI 8 months after the surgery. 5-FU (250 mg/day), CDDP (20 mg/day), and MMC (10 mg) was injected through a catheter introduced into the proper hepatic artery. His tumor became hardly detectable by MRI, and he was discharged about 1 month after admission. 5-FU (250 mg) and CDDP (20 mg) were injected every two weeks, and recurrence was not observed for 5 months.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1996

[A patient with unresectable cancer of pancreas head, effectively treated by a local injection of the mixture of OK-432, fibrinogen and thrombin].

The effective treatment of unresectable pancreatic cancer remains to be elucidated. We report herein a patient who underwent a local injection of a mixture of OK-432, fibrinogen and thrombin. Tumor size and tumor markers significantly decreased following this procedure. Local injection therapy with OK-432, fibrinogen and thrombin may be a promising treatment for unresectable pancreatic cancer.

Adenocarcinoma↗

PubMed1995

Platelet-activating factor and its structural analogues in the earthworm Eisenia foetida.

The earthworm Eisenia foetida was shown to contain large amounts of ether-containing phospholipids such as alkylacylglycerophosphocholine (61.3% of choline glycerophospholipids) and alkenylacylglycerophosphoethanolamine (66.0% of ethanolamine glycerophospholipids). We also found a substantial amount of ether-containing PAF-like lipid in this animal, its level being increased after the animal is injured. We showed evidence that this PAF-like lipid consists of PAF and PAF analogues containing short chain fatty acids other than acetic acid. Notably, a propionic acid-containing species but not PAF itself, is the most predominant species in this animal. We also confirmed that the earthworms contain enzyme activities involved in the synthesis of PAF and short chain fatty acid-containing PAF analogues. Interestingly, the acetyltransferase activity in earthworms is resistant to high concentrations of the substrate lysophospholipid. Thus, both the structure of the PAF-like lipid and the properties of the enzymes involved in the PAF-like lipid metabolism in the earthworms are somewhat different from those in mammalian tissues.

Acetyltransferases↗

PubMed1995

Expression of human platelet-activating factor receptor gene in EoL-1 cells following butyrate-induced differentiation.

Platelet-activating factor (PAF) is a potent lipid mediator of allergic inflammation through its interaction with eosinophils. Expression of the PAF receptor is modulated by many agents, including those responsible for cell differentiation. We report here that differentiation of a human eosinophilic leukaemia cell line, EoL-1, by sodium n-butyrate is associated with induction of PAF receptor gene expression, as indicated by: PAF receptor mRNA accumulation; increases in the binding of [3H]WEB 2086, a PAF antagonist; analysis of cell-surface expression of PAF receptor protein using a monoclonal anti-(PAF receptor) antibody; and augmentation of PAF-induced increase in the intracellular concentration of calcium. Using cDNA cloning, the receptor expressed in EoL-1 cells was identified as 'Transcript 1', one of two transcripts which was previously reported from human genomic analysis (Mutoh, Bito, Minami, Nakamura, Honda, Izumi, Nakata, Kurachi, Terano and Shimizu (1993) FEBS Lett. 322, 129-134). The PAF-induced calcium response and phosphoinositide turnover were decreased by pertussis toxin (PTX) treatment, suggesting that these signals are coupled largely with PTX-sensitive G-protein(s) in EoL-1 cells. These systems may provide a useful experimental model with which to investigate the relationship between eosinophilic differentiation and PAF receptor induction, and the role of eosinophils in allergic responses.

Amino Acid Sequence↗

PubMed1995

Digital subtraction high-frame-rate echocardiography in detecting delayed onset of regional left ventricular relaxation in ischemic heart disease.

BACKGROUND: Because left ventricular (LV) diastolic function is impaired before systolic function in patients with ischemic heart disease and because ischemic heart disease is constituted of regional rather than global abnormalities of the left ventricle, measures of LV regional diastolic dysfunction, if possible, should provide the most sensitive assessment of the coronary involved region. The objectives of this study are to clarify whether high-frame-rate two-dimensional echocardiography, combined with digital subtraction image processing, may be used to visualize regional LV relaxation abnormalities in patients with ischemic heart disease and to clarify whether this technique provides a measure for the noninvasive assessment of the coronary involved region. METHOD AND RESULTS: In 30 normal subjects and 59 patients with ischemic heart disease, two-dimensional echocardiograms obtained at a rate of 60 frames per second were provided on line for digital subtraction analysis, with which digitized images were continuously subtracted on a frame-by-frame basis. The subtracted images were analyzed to determine the onset of the segmental outward motion of the LV wall in early diastole in each of 16 segments per subject. Regional relaxation index, defined as the interval from the second heart sound to the onset of outward wall motion, was significantly prolonged in the coronary involved segments compared with the normal segments (36.3 +/- 18.0 versus 101.2 +/- 34.0 ms, P < .01). The prolongation in the regional relaxation index was observed even in the coronary involved segments without reduction in systolic wall motion. When a cutoff level of 50.0 ms was used, coronary involved segments could be distinguished from normal or border segments with a sensitivity of 92% and a specificity of 81%. CONCLUSIONS: Digital subtraction high-frame-rate echocardiography may be used to visualize regional LV relaxation abnormalities in patients with ischemic heart disease. The time interval from the second heart sound to the onset of the segmental outward motion of the LV wall (regional relaxation index) obtained with this technique provides a noninvasive and accurate measure for assessing coronary involved regions.

Adult↗

PubMed1995

Statistical survey from 1982 to 1991 of 49 patients with malignant melanocytic tumors.

We investigated the clinical characteristics and outcome of 49 patients with malignant melanoma: 17 with acral lentiginous melanoma; 14 with nodular melanoma, six with superficial spreading melanoma, one with lentigo maligna melanoma, eight with melanoma in situ, one with malignant blue nevus, and two with melanoma of unknown origin. Of the 41 patients without melanoma in situ, 34.1% were in stage I, 17.1% in stage II, and 48.8% in stage III. No patients had reached stage IV. All patients with stage I, II, and III melanoma were treated with wide resection, lymph node dissection including prophylactic dissection, and combination chemotherapy with dacarbazine, nimustine hydrochloride, and vincristine (DAV) with or without Interferon-beta. The statistical analysis revealed that tumor thickness and level of invasion were factors significantly associated with outcome. A gradual increase in the number of new cases of melanoma was seen each year of the registration period (1982-1991); there was an approximately 4-fold increase during this decade over the previous decade. The majority of the primary lesions (80.5%) were located on the upper or lower extremities, the pT4 tumor thickness subgroup was the most frequent (39.0% of all melanomas), and invasion level IV was the most common (42.5%). About half (51.2%) of the melanoma patients were stage I or II; this group had a 5-year survival rate of 100%. The stage III patients had a 5-year survival rate of only 54.2% (p < 0.05).

Adolescent↗

PubMed1995

A case of sarcoidosis which relapsed twice after successive parturitions.

A 30-year-old Japanese woman relapsed into sarcoidosis after two successive parturitions. The cutaneous lesions consisted of scar sarcoidosis, papular type, nodular type, and subcutaneous nodules with histologically typical "naked tubercles". Hypergammaglobulinemia, elevation of both serum angiotensin converting enzyme and lysozyme levels, and bilateral hilar lymphadenopathy were found in the acute and subacute stages, and spontaneously returned to normal levels 16 months after the onset. Our case suggests that parturition may trigger the onset of sarcoidosis.

Acute Disease↗

PubMed1995

Microcirculatory segments identified with monoclonal antibody against alpha-smooth muscle actin: comparison between Kimura's disease and angiolymphoid hyperplasia with eosinophilia.

Microcirculatory systems, which can be divided into several segments, have crucial physiological functions. We investigated whether monoclonal antibody against alpha-smooth muscle actin (alpha SMA) was useful for the identification of microcirculatory segments, according to the structure of their periendothelial cells, in two pathological cutaneous conditions. We examined skin specimens from patients with Kimura's disease and with angiolymphoid hyperplasia with eosinophilia, since little information is available on microvascular segments in these conditions. Immunostaining for alpha SMA revealed the morphological characteristics of the periendothelial cells clearly enough to identify five segments in the proliferative microvessels of Kimura's disease and angiolymphoid hyperplasia with eosinophilia. In Kimura's disease, postcapillary venules were predominant, while each vascular segment in angiolymphoid hyperplasia with eosinophilia was uniform. Vessels without periendothelial cells were detected to a greater extent in angiolymphoid hyperplasia with eosinophilia than in Kimura's disease. The antibody against alpha SMA appeared to be useful in the observation of periendothelial cells for the identification of vascular segments in pathological cutaneous conditions.

Actins↗

PubMed1995

Dual-isotope SPECT of skull-base invasion of head and neck tumors.

UNLABELLED: Skull-base invasions of head and neck tumors were examined by simultaneous bone and tumor dual-isotope SPECT (S-SPECT) with 99mTc-hydroxy-methylene-diphosphonate (99mTc-HMDP) and 201Tl-chloride. The effectiveness and reliability of tumor diagnosis by this method was the primary interest in this study. METHODS: Before S-SPECT imaging, a phantom experiment using dried skull-bone specimens was performed to establish anatomical details of the skull base with the SPECT camera. Radionuclide crosstalk, window widths and control patients were also examined prior to S-SPECT imaging. Twenty patients with suspected tumor invasion of the skull base underwent S-SPECT. RESULTS: Preliminary experiments revealed that crosstalk effects could be disregarded with adequate window width and routine administrative doses of the radionuclides. S-SPECT detected bone destruction and the extent of tumor invasion for all 12 patients in whom skull-base involvement was diagnosed by CT or MRI. For the three patients in whom CT or MRI revealed no tumor invasion, the S-SPECT images did not show any abnormal accumulation in similar regions. In the remaining five patients without CT and MRI confirmation of skull-base invasion, the S-SPECT findings showed skull-base abnormalities in three. Tumor invasion was confirmed surgically or by clinical follow-up. The remaining two patients had negative S-SPECT images. CONCLUSION: S-SPECT is an effective and reliable diagnostic technique for detecting tumor invasion in the complex bony regions of the skull base.

Adult↗

PubMed1995

Immunohistochemical study of p53 expression in cancer tissues from patients undergoing radiation therapy.

Immunostaining using p53 monoclonal antibodies (p53(Ab-3) recognizes mutant type and p53(Ab-6) the wild type of p53 protein) was performed on frozen sections of biopsy specimens obtained before and during preoperative radiotherapy from 23 patients with head and neck squamous cell carcinoma. The positive staining rates of p53(Ab-3) before radiotherapy and at radiation doses of 4Gy, 10Gy and 20Gy were 30.0%, 38.9%, 25.0% and 6.25%, and those of p53(Ab-6) 10.5%, 11.8%, 5.0% and 0% respectively. The relationship between the immunohistochemical findings and antitumor effect at radiation dose of 20Gy was examined on the correspondent haematoxylin-eosin sections. In patients whose p53(Ab-3) stainings were positive at any doses of radiotherapy, the antitumor effect at the cumulative dose of 20Gy waas either remarkable or effective. Moreover, the frequency of the expression of mutant type p53 protein tended to increase in rather radiosensitive tumors. As for wild type p53 protein, there was no remarkable relationship between the staining of p53(Ab-6) and the antitumor effect.

Adult↗

PubMed1995

[A case of unresectable gastric cancer responding to combined therapy with intraperitoneal cisplatinum administration and continuous intravenous infusion of 5-fluorouracil].

A 41-year-old woman diagnosed as gastric cancer with peritoneal dissemination was admitted for operation. Exploratory laparotomy was done and a reservoir was implanted with intraperitoneal catheter. At the operation, CDDP (100 mg) was administered intraperitoneally. Four days after the operation, continuous intravenous infusion of 5-FU (250 mg) was carried out. CDDP was administered every four weeks for 6 times and 5-FU continuously for 194 days. Grade 2 toxicity (nausea, vomiting) was noted without myelosuppression and renal disturbance. The general condition of the patient was fairly improved. PS (performance status) improved from Grade 3 to Grade 1. Combined therapy with repeated intraperitoneal CDDP administration and continuous intravenous infusion of 5-FU is effective and safe for gastric cancer with peritoneal dissemination based on biochemical modulation.

Adult↗