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Biomedical subjects

S Kishimoto

Publications and source records attributed to S Kishimoto.

At least 253 records · Page 14Linked to original sources
PubMed1989

Cutaneous metastasis from hepatocellular carcinoma resembling granuloma teleangiectaticum.

We reported a case of cutaneous metastasis originated from hepatocellular carcinoma, which appeared as a nodule resembling granuloma teleangiectaticum. The nodule, which was composed of tumor cells and intervening capillaries, showed characteristics similar to those of primary hepatocellular carcinoma. On immunohistochemical staining, the tumor cells were positive not only for AFP (alpha-fetoprotein), but also for CEA (carcinoembryonic antigen), which is negative in most cases of primary hepatocellular carcinoma. We discussed this case with a review of previous reports of skin metastasis from liver carcinoma.

Carcinoma, Hepatocellular↗
PubMed1989

Synergy of Nocardia rubra cell wall skeleton and interleukin 2 in the in vivo induction of murine lymphokine-activated killer cell activity.

Combination of an ip injection of Nocardia rubra cell wall skeleton (N-CWS) and 3 daily sc injections of human recombinant interleukin 2 (rIL 2) into C3H/HeN mice resulted not only in a significant increase in the number of peritoneal cells (PC) but also in a potent induction of their lymphokine-activated killer (LAK) activity, compared with results obtained with N-CWS or rIL 2 alone. The augmented LAK activity of PC was mediated by nonadherent, nonphagocytic, Thy-1.2+(-)- and asialo GM1+ cells. Nonadherent PC induced by an ip injection of N-CWS bound more 125I-labeled rIL 2 than did normal, nonadherent PC, and generated high LAK activity when cultured overnight with rIL 2. In contrast, normal, nonadherent PC responded only weakly to the overnight stimulation with rIL 2. The phenotype of N-CWS-induced PC with an elevated IL 2 responsiveness was Thy-1.2+(-)-, Lyt-1.1-, Lyt-2.1- and asialo GM1+, suggesting that the N-CWS-stimulated LAK precursors were derived mainly from the NK cell lineage. However, mature T cells may also be involved in this mechanism, because N-CWS failed to augment the IL 2 responsiveness of nonadherent PC in BALB/c nu/nu mice. Treatment of C57BL/6N mice bearing solid Lewis lung carcinoma (3LL) tumors with an intratumoral injection of N-CWS followed by 6 daily sc injections of rIL 2 resulted in the apparent suppression of tumor growth, while N-CWS or rIL 2 alone produced no such suppression. These results suggest that N-CWS augments the antitumor effect of rIL 2 by accumulating LAK precursors and elevating their responsiveness to rIL 2 at the injection site.

Adjuvants, Immunologic↗
PubMed1989

Augmentation of murine lymphokine-activated killer cell induction by a factor produced by Nocardia rubra cell wall skeleton-stimulated T cells.

Four-hour exposure of C3H/HeN mouse spleen cells to Nocardia rubra cell wall skeleton (N-CWS) before 4-day culture with a suboptimal dose of human recombinant interleukin 2 (rIL 2) augmented the induction of lymphokine-activated killer (LAK) cell activity, whereas the treatment with N-CWS alone induced no cytotoxicity. In accordance with this, the IL 2 binding activity of spleen cells was augmented by combined stimulation with N-CWS and rIL 2. The augmented cytotoxicity was mediated by Thy-1.2+, Lyt-1.1-, Lyt-2.1- and asialo GM1+ cells. Cell cultures in diffusion chambers revealed that N-CWS-treated spleen cells produced a LAK cell induction-helper factor (LAK-helper factor, LHF) when cultured with rIL 2. The LHF production required Thy-1.2+, Lyt-1.1+, Lyt-2.1+ and asialo GM1- cells, and the coexistence of unstimulated accessory cells was also essential for the LHF production. Cells responding to both LHF and rIL 2 to generate LAK activity were Thy-1.2-, Lyt-1.1-, Lyt-2.1- and asialo GM1+. The culture fluid of spleen cells stimulated with both N-CWS and rIL 2 contained no tumor necrosis factor (TNF) activity, and the additional stimulation with N-CWS caused no production of either IL 2 or interferon (IFN). Murine recombinant interleukin 1 alpha (Mu-rIL 1 alpha) could not replace the augmentative effect of N-CWS on LAK cell induction. These results suggest that in the presence of rIL 2, N-CWS stimulates murine T cells to produce LHF that is probably distinct from IL 1, IL 2, TNF and IFN.

Adjuvants, Immunologic↗
PubMed1989

Enzyme-immunoassay for estrogen receptors in human pituitary adenomas.

We have performed an enzyme-immunoassay for estrogen receptor on 56 human pituitary adenomas and compared the results with a single point estradiol binding assay. There was a significant positive correlation between the two assays of cytoplasmic estrogen receptor (r = 0.960). Normal human pituitaries (N = 2) had an estrogen receptor concentration of 17 fmol/mg protein by enzyme-immunoassay. Of 14 prolactinomas, 6 (43%) contained estrogen receptor with a concentration of 33.5 +/- 7.4 (mean +/- SEM) fmol/mg protein. Six of 11 (55%) macroprolactinomas were estrogen receptor-positive, whereas all 3 microprolactinomas were estrogen receptor-negative. Only one (13%) of 8 GH- and PRL-secreting adenomas, and 3 of 6 (50%) gonadotropin-secreting adenomas were estrogen receptor-positive; the latter had a concentration of 13.5 +/- 1.6 fmol/mg protein. Estrogen receptor was not detected in 21 pure GH-secreting adenomas and 7 nonsecreting adenomas. These results demonstrate the precise frequency of estrogen receptor in various human pituitary adenomas, since enzyme-immunoassay as well as single point estradiol binding assay could detect estrogen receptor even in small specimens. Enzyme-immunoassay is suitable for evaluation of estrogen receptor status in human pituitary adenomas.

Adenoma↗
PubMed1989

Infrequent utilization of the immunoglobulin heavy chain variable region(s) identical or closely related to that of MOPC315 myeloma protein in the functional V region formation in B-precursor cell lines.

We raised anti-VH315 antibodies by immunization of rabbits with VH315 fragments, the variable portions of the immunoglobulin heavy chains of MOPC315 myeloma protein. Inhibition radioimmunoassay using various immunoglobulins as inhibitors showed that the anti-VH315 antibodies specifically reacted with the variable portions of the heavy chains of MOPC315 myeloma protein. When the variable region (VH) gene of the heavy chains was cloned and sequenced from the cells producing the heavy chains detected by the anti-VH315 antibodies, the VH gene was closely related (82% homology at amino acid level) to the VH gene of MOPC315. When we examined the frequency with which the variable region(s) detected by the anti-VH315 antibodies were expressed in eight Ignull Abelson virus-transformed cell lines (DJ/DJ or VDJ-/DJ), which were able to generate functional V regions during culture, only one cell line, AT8-1, produced a small number of intracytoplasmic mu-positive cells (VH315+ cells) stained by the anti-VH315 antibodies. The percentage of the total number of the VH315+ cells to the total number of intracytoplasmic mu-positive cells was 0.91% in AT8-1. In the remaining seven cell lines, no VH315+ cells were detected. In the present study we estimate, for the first time at the individual cell level, the frequency of the utilization of the heavy chain variable region(s) identical or closely related to that of MOPC315 in the functional V region formation during early B-cell development.

Amino Acid Sequence↗
PubMed1989

Occlusion of small hepatic veins associated with systemic lupus erythematosus with the lupus anticoagulant and anti-cardiolipin antibody.

We report the case of a woman with lupus anticoagulant-positive systemic lupus erythematosus who developed small hepatic vein occlusion. Since the age of 34, she had been known to have hepatomegaly. A definitive diagnosis of systematic lupus erythematosus was made eight years later. Histological evaluation of the liver biopsy specimen was not fully diagnostic of prominent hepatomegaly during this period. Occlusion of the small hepatic veins was confirmed by hepatic venography, but the lumen of the large hepatic veins showed a smooth appearance. The lupus anticoagulant and anti-cardiolipin antibody were both positive. Since a high incidence of thromboembolic diseases in patients with the lupus anticoagulant or anti-cardiolipin antibody has been reported, the presence of this type of anticoagulant may provide an explanation for hypercoagulability and subsequent development of hepatic vein thrombosis in this patient. This is the first report of a patient with systemic lupus erythematosus who developed an occlusion of small hepatic veins attributable to the lupus anticoagulant and anticardiolipin antibody. This case suggested that a systematic search for hepatic vein occlusion should be made in patients with systemic lupus erythematosus who have developed inexplicable hepatomegaly, especially in those with positive tests for the lupus anticoagulant and/or anti-cardiolipin antibody.

Adult↗
PubMed1989

[Intra-arterial injection of cisplatin suspension in Lipiodol (LPS) in the treatment of hepatocellular carcinoma].

Cisplatin suspension in Lipiodol (LPS) was prepared for the treatment of hepatocellular carcinoma by intra-hepatic arterial injection. In a rabbit liver cancer model, concentrations of cisplatin in tumor were more than 20 times higher than those in a nontumorous part of the liver at 5 min after LPS injection into the hepatic artery. Cisplatin at high concentrations was detected at 7 days after injection. The concentrations in other organs were lower except in the gall-bladder. In clinical trials for 71 patients with hepatocellular carcinoma, partial response was observed in 33 cases (46.5%) and minor response in 20 cases (28.2%). The survival rate was 77% at 6 month and 55% at one year. Although fever, nausea, vomiting and epigastralgia were observed as side effects, these were temporary. Acute gastroduodenal mucosal lesions, cholecystitis, pancreatitis, delayed jaundice and hepatic encephalopathy were observed as complications and super selective cannulation was necessary for their prevention.

Animals↗
PubMed1989

Nuclear phosphotyrosyl-protein with DNA-binding ability in peripheral blood mononuclear cells from systemic lupus erythematosus patients.

This study examined the phosphorylation of cytoplasmic and nuclear proteins in peripheral blood mononuclear cells (PBMC) of systemic lupus erythematosus (SLE) patients. The cytoplasmic and nuclear protein kinase activity in PBMC from SLE patients was at least five-fold higher than that of normal healthy subjects. PBMC of SLE patients produced different nuclear endogenous substrates on phosphorylation and also displayed distinct protein kinase activity. Nuclear phosphoproteins, with human PBMC DNA-binding ability, of 38 kD and 70 kD were detected from both SLE patients and normal healthy subjects, while the 40 kD phosphoprotein, with tyrosine as the main phosphorylation residue, was found only in SLE patients. Other nuclear phosphoproteins, and most of the detected cytoplasmic phosphoproteins, were present in higher levels in both normal PBMC with mitogen stimulation, such as PHA, and SLE PBMC. The expression level of the 40 kD nuclear phosphotyrosyl-protein showed a positive correlation with the clinical disease activity of SLE. These results suggest that PBMC from SLE patients had distinct tyrosine protein kinase (TPK) activity and/or a different endogenous substrate of nuclear DNA-binding proteins in tyrosine phosphorylation. The possible significance of tyrosine phosphorylation in PBMC of SLE patients in the pathogenesis, and its clinical meaning, are discussed.

DNA↗
PubMed1989

Pharmacological study of a traditional Chinese medicine: effect of bezoar bovis on the irregular beating pattern of cultured mouse myocardial cells.

The water-extract from "Bezoar bovis", a drug used in Chinese traditional medicine, was examined for its ability to alter the beating pattern of spontaneously contracting cultured embryonic mouse myocardial cells following changes in extracellular calcium (Ca2+). Incubation of the cells with medium containing low Ca2+ concentration (0.4 mM) caused the number of beating cells and beating rate to decrease and the number of arrhythmic cells to increase. By contrast, the number of beating cells decreased while beating rate and the number of arrhythmic cells increased at high Ca2+ (20 mM). Addition of Bezoar bovis extract to the medium attenuated the response to varying Ca2+ concentration. One of the major constituents of Bezoar bovis extract, taurine, was effective in protecting against the abnormal beating pattern induced by high Ca2+. Since beta-alanine, an inhibitor of taurine transport, antagonized the protective effects of both Bezoar bovis and taurine, it is likely that the effect of Bezoar bovis is partially mediated by taurine.

Alanine↗
PubMed1989

No correlation between locations of bcr breakpoints and clinical states in Ph1-positive CML patients.

The majority of patients with chronic myelogenous leukemia (CML) have a characteristic reciprocal translocation between chromosome 9 and 22, resulting in the Philadelphia (Ph1) chromosome. During this translocation, the c-abl oncogene on chromosome 9 is transferred to the Ph1 chromosome and linked to a breakpoint cluster region (bcr), which is part of a large bcr gene. This phenomenon results in the formation of a bcr-c-abl fusion gene, which is transcribed into an 8.5 kb chimeric mRNA encoding a 210 kd bcr-c-abl fusion protein. The fusion protein has tyrosine kinase activity implicated in the pathogenesis of CML. The breakpoint near the c-abl locus on chromosome 9 can occur within a large area. In contrast, the breakpoints on chromosome 22 cluster within the bcr region of 5.8 kb. A chronic phase lasts for an average of 2 to 3 years; and, subsequently, most patients enter blast crisis. In the present study, we examined 15 Ph1-positive CML patients (eight in chronic phase, one in accelerated phase, and six in blast crises) as to whether the identifiable difference in the locations of the bcr breakpoints exist between CML patients in chronic phase and those in blast crisis. In seven of eight CML patients in chronic phase, in one in accelerated phase, and in four out of six CML patients in blast crisis, the bcr breakpoints clustered in the 3' portion of the bcr. Thus, we could not find out the correlation between the locations of the bcr breakpoints and the clinical stage of the CML patients. This might imply that blastic transformation in Ph1-positive CML was caused by other mechanisms than the transition of the bcr breakpoints.

Blast Crisis↗
PubMed1989

Changes in inducible nuclear factors with specific binding ability to c-myc gene fragments in peripheral blood mononuclear cells from systemic lupus erythematosus patients.

Using a gel retardation assay, we found new nuclear proteins of peripheral blood mononuclear cells (PBMC) from systemic lupus erythematosus (SLE) patients specifically binding to c-myc gene fragments. A different pattern could be detected between SLE patients and healthy controls for the c-myc exon I fragment, but both groups had similar patterns for the c-myc 5'-upper region fragment. For the c-myc exon I fragment, one DNA-protein complex was induced only in SLE patients and the other DNA-protein complex was amplified in SLE and normal PBMC with mitogen stimulation. It is suggested that abnormal c-myc protooncogene transcription in PBMC from SLE patients could be related to differences in nuclear specific binding proteins. These differences apparently play a key role in abnormal lymphocyte function in changes in gene regulation.

DNA↗
PubMed1989

C-myc gene binding factors in peripheral blood mononuclear cells from patients with systemic lupus erythematosus (SLE).

We characterized the nuclear proteins with specific binding ability against c-myc gene by gel-shift assay in cell extracts of peripheral blood mononuclear cells (PBMC) from SLE patients and SLE-prone mice with use of distinct c-myc fragments. With the fragment named Fmyc in our experiments, two kinds of complexes which we call C1 and C2 respectively were found in PBMC from SLE patients and SLE-prone mice. The C1 was shown to be inducible in PBMC from healthy persons without nascent protein synthesis after lectin binding to the cell and found to be elevated in the SLE patients and in all of the established cell lines we examined. The C2 seemed to be peculiar to SLE subjects. The binding site of the C1 factor (C1F) and C2 factor (C2F) which forms C1 and C2 respectively with Fmyc appeared to be common and were found to reside at 51 kbp sequence (from XhoI to Sau3A) of exon I of c-myc gene. Interestingly, XhoI site of the binding site was highly demethylated in PBMC of SLE patients as compared with healthy persons. The roles of these binding factors for the pathogenesis of SLE are discussed.

DNA-Binding Proteins↗
PubMed1989

[Basic studies on optimal intra-arterial infusion rate of cisplatin].

The relationship between platinum concentration in tissues, free CDDP concentration in plasma and infusion rate was investigated in order to determine the optimal intra-arterial infusion rate of CDDP for chemotherapy of cervical carcinoma. Platinum concentrations in uterus were in the same level in the intravenous infusion groups independent of the infusion rate. In the intra-arterial infusion groups, platinum concentrations in the uterus increased as the infusion rate decreased from 24 to 0.8 mg/hr, although Cmax and AUC were decreased. Platinum concentrations in the ovary supplied by another artery were not influenced by the intra-arterial infusion rate. It is suggested that uptake of CDDP in the targeted tissues can be increased by control of intra-arterial infusion rate.

Animals↗
PubMed1989

[The characteristic changes of immune function with aging].

It is well-known that the most prominent age-related immunological abnormalities were reduced immune response against foreign antigens and increased auto-antibody production against intrinsic antigens. To explain these immunological abnormalities, we examined the various functions of human lymphocytes from aged and young groups at cellular, molecular and genetic levels. The results indicate: The first, T cells from the aged showed significantly reduced proliferative response not only to specific antigen TAP but also to mitogen PHA or combined stimulation of PMA and ionomycin. The second, the number of IL-2 receptor, particularly high affinity ones, on aged T cells were significantly reduced in the aged after TAP and PHA stimulation. The third, the ability to express Tac (p55) and p70/75 of IL-2R and to internalize the rIL-2 bound to the receptor were reduced in aged T cells. The fourth, although the ability to proliferate in response to SAC stimulation was two folds less in the aged B cells than that in the young ones, the capacity to differentiate into IgG and IgA class ISC after the combined stimulation with SAC and partially purified BCDF were rather increased on the basis of the number of viable cells recovered. The fifth, the amount of IL-2 activity produced by aged T cells was ten fold less than that by young ones, but the amount of BCDF activity produced by aged T cells was three folds higher than that by young ones after PHA stimulation. An inverse correlation between IL-2 activity and BCDF activity was found when the both activities were determined in the same sample. The sixth, the combined stimulation with PMA and ionomycin could induce proliferative response to highly purified T cells, T cell subsets and B cells. The degree of age-related decline of the proliferative response of CD-8 positive T cells was most significant, that of CD-4 positive ones was next and that of B cells was least. The seventh, although the maximum of c-myc mRNA level was attained at 2 hr after the stimulation and similar amount between the both age groups, the amount of mRNA at 8 or 24 hr was rather higher in the aged T cells than in the young ones. The reduction of the degradation rate of c-myc mRNA seemed to be the cause. We found no difference of the maximum amount and kinetics of c-myb mRNA between both age groups in T cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1988

Age-related changes of heat shock protein gene transcription in human peripheral blood mononuclear cells.

In this study, we show the age-related retardation of heat shock 70 kD protein (hsp 70) gene transcription in peripheral blood mononuclear cells (PBMC). The amount of maximum transcription of the hsp 70 gene is decreased in PBMC from aged subjects, compared with PBMC from young control subjects. It might mean that the ability for homeostasis against heat shock stress decreases in PBMC from aged subjects. Our observation might be at least correlative and consistent with the age-related change of a possible essential function in PBMC.

Actins↗