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Biomedical subjects

M Kikuchi

Publications and source records attributed to M Kikuchi.

At least 487 records · Page 27Linked to original sources
PubMed1995

Adult T-cell leukemia/lymphoma with two distinct clones in the peripheral blood and lymph node.

A case of adult T-cell leukemia/lymphoma (ATL) with two different clones in the peripheral blood and lymph nodes is reported here. When cellular DNA from the lymph node was digested with EcoRI, one band larger than 9 Kb was detected. Digestion of the cellular DNA with PstI resulted in one clear band in addition to three internal fragments. In contrast, when cellular DNA from malignant peripheral blood lymphocytes (PBL) was digested with the same endonucleases, distinct bands at positions different from those observed in the lymph node were detected, indicating two separate malignant clones in the patient. Monoclonality of the tumor cells was shown by T-cell receptor-beta (TCR-beta) gene rearrangement in both PBL and lymph node. Furthermore, there was a difference in the surface phenotype between tumor cells taken from peripheral blood (CD4+, CD8-) and lymph node (CD4+, CD8+). These findings suggest the presence of two different ATL clones in PBL and lymph node in a single patient simultaneously, which is distinguishable by the integration pattern of human T-cell leukemia virus type I (HTLV-I) proviral DNA.

Aged↗
PubMed1995

Mitochondrial diabetes mellitus--glucose-induced signaling defects and beta-cell loss.

Japanese diabetic patients whose mothers were also diabetic were screened, using peripheral leukocytes, for an A to G transition at nucleotide pair 3243 of the mitochondrial gene, a tRNA(Leu)(UUR) mutation. This mutation was identified in four pedigrees from among 300 unrelated patients. Diabetes mellitus cosegretated with the mutation, except in 1 young subject, and was maternally inherited. Long-term follow-up revealed that the underlying disorder in affected members is a progressive impairment of insulin secretion. In accord with this finding, this mutation was found to be highly prevalent in a subset of diabetes mellitus called slowly progressive IDDM; the mutation was identified in 3 of 27 Japanese patients enrolled in the prospective study of islet cell antibody (ICA)-positive, initially non-insulin-dependent diabetic patients, who are very likely to become insulin dependent in several years. The histologic characteristics of slowly progressive IDDM include loss, though incomplete, of pancreatic beta-cells. Mitochondrial gene defects in beta-cells could therefore cause glucose-induced signaling defects as well as beta-cell loss, which explains the wide range of diabetic phenotypes, from NIDDM phenotype to IDDM, in patients with this mitochondrial gene mutation.

Adolescent↗
PubMed1995

A megakaryocyte analysis of the bone marrow in patients with myelodysplastic syndrome, myeloproliferative disorder and allied disorders.

A morphometric analysis was performed on aspirate clots of bone marrow to identify the presence of atypical megakaryocytes after immunohistological staining with a monoclonal antibody against Factor VIII. This study included cases of myelodysplastic syndrome (MDS), myeloproliferative disorder (MPD), aplastic anaemia (AA), idiopathic thrombocytopenic purpura (ITP), chronic myelogenous leukaemia (CML), and control cases free from any haematological disease. Quantitative and qualitative abnormalities of megakaryocytes were assessed using an image analyser and a personal computer to perform a morphometric analysis of the number (per mm2), arrangement (microns), nuclear size (microns2), cell size (microns2), nuclear size/cell size (N/C) ratio, and nuclear contour index (NCI). Micromononuclear megakaryocytes were detected in MDS, while in MPD, large over-mature magakaryocytes were observed to increase in number. In AA, the megakaryocytes decreased dramatically in number without showing any morphological abnormality. In CML, the megakaryocytes also increased without any remarkable morphological abnormality. In ITP, only the NCI increased. The above results show that MDS is characterized by the presence of atypical micromegakaryocytes, while MPD is characterized by atypical large over-mature megakaryocytes.

Antibodies, Monoclonal↗
PubMed1995

Circulating catecholamine and glucose concentrations in Japanese toads (Bufo japonicus) during the breeding season.

We investigated the relationship between catecholamine neurohormones and glucose during seasonal reproductive activity in Japanese toads (Bufo japonicus). Field studies found that plasma epinephrine concentration increased as toads migrated to their breeding ponds, where amplexus most frequently took place. Blood glucose concentration also increased as toads arrived at the ponds, even though these animals did not eat during the breeding season, and there was a positive correlation between epinephrine and glucose levels. Blood glucose concentration was higher in amplectic than in solitary males, whereas this relationship did not occur in females. For both males and females, plasma epinephrine concentration was elevated during amplexus. The plasma concentration of norepinephrine was lower than that of epinephrine and did not correlate with either the proximity of the animal to the breeding ponds or the blood glucose concentration. Laboratory experiments showed that systemic injection of [Trp7,Leu8]gonadotropin-releasing hormone (sGnRH) increased plasma epinephrine to levels characteristic of amplectic feral toads. These results suggest that a physiological role of GnRH-like peptides may be to stimulate epinephrine secretion and consequently to increase glucose production in toads under the starvation conditions associated with the breeding migration.

Animals↗
PubMed1995

Portal and peripheral endotoxins in patients with esophageal varices undergoing surgery.

Under the hypothesis that portal endotoxemia, which has been considered evidence of endogenous endotoxemia, is actually a false-positive reaction of the Limulus test, the conventional method of determination, Toxicolor (TOX) and a new endotoxin-specific method, Endospecy (ES) were investigated, whereby portal endotoxemia was reexamined. Peripheral and portal blood samples were collected from 12 patients at various intervals during surgery for esophageal varices, and then evaluated by TOX and ES, the normal values of which are under 60.0 pg/ml and under 9.8 pg/ml, respectively. The mean peripheral and portal endotoxin (Et) levels by TOX were 23.1 pg/ml and 38.9 pg/ml, 1.5 h after the start of surgery, which continued to increase thereafter, the corresponding levels being 48.1 pg/ml and 58.7 pg/ml 8 h after the start of surgery, respectively. The portal Et levels were significantly higher by ES, indicating portal endotoxemia, the mean peripheral and portal Et levels being 6.9 pg/ml, and 6.5 pg/ml, 1.5 h after the start of surgery, these levels showing changes within a similar range. The levels determined by the conventional TOX method increased with time, to a portal Et level of 5.0 pg/ml 8 h after the start of surgery, whereas those determined by ES changed within the same range suggesting that the onset of portal endotoxemia primarily involves the G-factors and that endogenous endotoxemia does not occur.

Blood Specimen Collection↗
PubMed1995

Primary tubular adenocarcinoma arising in the duodenal limb of reconstructed gastroduodenostomy for signet-ring cell carcinoma of the stomach.

Adenocarcinoma of the small intestine is uncommon. Due to this paucity and the lack of specificity of symptoms, patients are usually seen late in the course of their illness, when curative therapy, mainly represented by extensive surgical resection, is unlikely. The authors report a case of primary well-differentiated tubular adenocarcinoma (T4N0M0) arising in the duodenal limb of a reconstructed Billroth I gastroduodenostomy, 9 years after a distal gastrectomy for signet-ring cell carcinoma of the stomach (T4N0M0). Evidence for excluding the possibility of a recurrence of the primary gastric cancer was based on the different histologic pattern, the long disease-free interval, and other features of the second neoplasm. Relatively early diagnosis of the neoplasm, followed by curative surgical therapy was made possible by the early onset of the obstructive symptoms and the favorable anatomical location of the tumor.

Adenocarcinoma↗
PubMed1995

Immunofluorescence study of immune complexes in polymyalgia rheumatica.

Two elderly patients with polymyalgia rheumatica (PMR), one with and the other without temporal arteritis (TA), are presented. Immunofluorescence study of muscle biopsy specimens showed IgG, IgA, and fibrinogen deposits in the perifascicular area in the perimysium. This finding suggests that immune complexes play a role in the pathogenesis of this condition and that the pathophysiology of PMR involves an interstitial inflammatory process.

Angiography↗
PubMed1995

Abnormal arachidonate distribution in low-density lipoprotein and thoracic aorta in hyperinsulinemia.

The mechanism by which hyperinsulinemia promotes atherogenesis is unknown. The effects of hyperinsulinemia on risk factors for atherosclerosis were investigated by subcutaneously injecting rats daily with an insulin-zinc suspension (20 U/kg) for 12 weeks. After this period, body mass and food consumption did not differ significantly between control and insulin-treated animals. Daily insulin injection significantly increased urinary excretion of epinephrine and decreased urinary excretion of norepinephrine and dopamine, but had no significant effect on blood pressure or heart rate. Although insulin decreased plasma triglyceride concentration by 44% (P < .01), the triglyceride to protein ratio in plasma low-density lipoprotein (LDL) was increased by 34% (P < .05) in insulin-treated rats; the cholesterol to protein and triglyceride to protein ratios remained unaffected, indicating a change in the quality of the LDL particle. Insulin also increased the percentage of arachidonic acid (20:4) in LDL triglycerides by 37% (P < .05). In contrast, cholesteryl esters and triglycerides in the thoracic aorta were significantly increased (49% and 91%, respectively) by insulin treatment. Insulin increased the percentage of monounsaturated fatty acids and decreased the percentage of n-6 fatty acids, including arachidonate, in aortic triglycerides. Insulin also increased the percentage of palmitoleic acid (16:1) and decreased the percentages of saturated fatty acids and n-6 fatty acids in aortic cholesteryl esters. These results indicate that insulin induced deposition of cholesteryl esters and triglycerides, especially those containing monounsaturated fatty acids, and abnormal arachidonate distribution in LDL and tissues. The data further suggest that the development of atherosclerosis in response to hyperinsulinemia may be associated with arachidonate-rich triglycerides in LDL.

Animals↗
PubMed1995

CD30-positive anaplastic large cell lymphoma in a human T-cell lymphotropic virus-I endemic area.

Clinicopathological and cytogenetic studies were performed on specimens from 43 patients with CD30-positive anaplastic large cell lymphoma (ALCL). All patients were born and lived in a human T-cell lymphotropic virus (HTLV)-I endemic area. Twenty-one patients (48.8%) had serum anti-HTLV-I antibody suggesting the presence of adult T-cell leukemia/lymphoma (ATL). Seventeen of them showed a clonal integration of complete HTLV-I proviral DNA by the Southern blot hybridization method in materials obtained by biopsy. Their ages ranged from 37 to 81 years (median, 67.0), and they frequently presented with lymphadenopathy (82.4%) and extranodal tumors with (76.5%) as well as with rare leukemic changes (5.9%). Immunohistologically the lymphoma cells in 15 ATL patients showed a T-cell phenotype. In only one patient (5.9%) was there an expression of epithelial membrane antigen (EMA) in most of the lymphoma cells. Cytogenetically aberration of chromosome band 5q35 was not found in seven patients with HTLV-I proviral DNA. The overall median length of survival was 11.9 months for the patients with HTLV-I proviral DNA, indicating a worse prognosis compared with that of the age-matched patients with negative anti-HTLV-I antibody (P < .01). The specimens of the patients with HTLV-I proviral DNA had unique clinicopathological and cytogenetic features. These findings suggested that T-cell ALCL with HTLV-I proviral DNA should be considered to represent the lymphoma type of ATL.

Adult↗
PubMed1995

Angiocentric immunoproliferative lesions of the skin show lobular panniculitis and are mainly disorders of large granular lymphocytes.

Eleven patients with angiocentric immunoproliferative lesion (AIL) of the skin were studied. Histologically, three patients were grouped into AIL grade II (AIL-II), whereas eight showed angiocentric lymphoma (AIL-III). All the patients' specimens exhibited lobular panniculitis. Infiltrating atypical lymphocytes in nine patients possessed electron-dense membrane bound granules in electron microscopy. Phenotypically, the lymphoid cells in the AIL-II patients were positive for CD3 epsilon; two of these showed a positive reaction to CD2, CD7, and CD8, but lacked natural killer-associated (NKa) antigens CD16, CD56, and CD57. In six AIL-III patients, lymphoma cells were positive for CD2 in all patients, CD56 in five, CD3 epsilon in four, CD7 in four, interleukin-2 beta receptor in four, a pore-forming protein in four, and CD30 in three patients. The remaining two AIL-III patients had B-cell lymphoma. By the Southern blot analysis, three patients with AIL-III showed a rearranged T-cell-receptor beta-gene or a deletion of its germline. The preceding results in nine of 11 patients suggest that abnormal or neoplastic large granular lymphocytes with the characteristics of T and NK cells have an important role in producing the angiocentric/angiodestructive features and lobular panniculitis. Clinically, all three patients with AIL-II and four with AIL-III showed liver dysfunction, cytopenia, and abnormal coagulopathy during the clinical course. Five patients with AIL-III died within 8 months. The histological grading of AIL, patients' age, and limited clinical stage of the disease seem to correlate with response to the treatment and prognosis.

Adolescent↗
PubMed1995

Anti-inflammatory effects and specificity of L-156,602: comparison of effects on concanavalin A and zymosan-induced footpad edema, and contact sensitivity response.

We investigated the in vivo selective anti-inflammatory effect of L-156,602, which was first identified as a preferential delayed-type hypersensitivity-suppressant in our screening program and first reported to be a C5a antagonist. The agent most profoundly suppressed footpad edema 4 h after elicitation by concanavalin A (con A) and also caused a significantly impaired response after a further 20 h. Footpad edema induced by either serotonin, carrageenan or zymosan was not much influenced by the agent. Although the dominant cell population that migrated in response to con A and zymosan 4 h after elicitation was neutrophils, L-156,602 specifically prevented the con-A-induced migration of neutrophils, suggesting a distinct mechanism of neutrophil recruitment between con A and zymosan-induced inflammation. The agent also reduced the contact-sensitivity response, especially in host mice sensitized with a moderate dose of picryl chloride and almost completely suppressed the infiltration of mononuclear leukocytes and neutrophils into the site of inflammation. These selective effects of L-156,602 on inflammatory reactions appeared to be not merely via C5a antagonism.

Animals↗
PubMed1995

Application of in situ hybridization with a novel phenytoin-labeled probe to conventional formalin-fixed, paraffin-embedded tissue sections.

Non-isotopic in situ hybridization with a novel phenytoin (PHE)-labeled probe was developed. The mixture of cloned cytomegalovirus (CMV) DNA fragments was labeled by random primer technique using PHE-11(spacer)-dUTP, instead of dTTP. The tissue sections were treated with 0.2 N HCl and with proteinase K (1 microgram/ml), and then heated at 70 degrees C in the presence of 50 or 75% formamide. The sections were hybridized with PHE-labeled probe at 37 degrees C overnight. The hybridization signal was visualized by alkaline phosphatase-5-bromo-4-chloro-3-indolyl phosphate (BCIP)/4-nitroblue tetazolium (NBT) system. Strong hybridization signals were detected in sections of the small intestine and the placenta, even when denatured in the presence of 50% formamide. In the case of small intestine, CMV DNA was also detected in the endothelial cells of the mucosa where apparent infected cell was not observed histologically. In the sections of the submaxillary gland, the lung, the adrenal gland and the ovary, hybridization signal was not detected when denatured in the presence of 50% formamide, but detected after denaturation with 75% formamide. Thus, in situ hybridization with the novel PHE-labeled probe is applicable to conventional formalin-fixed, paraffin-embedded tissue sections.

Adrenal Glands↗
PubMed1995

Antiviral activity of 9-[[(ethoxyhydroxyphosphinyl)-methoxy]methoxy] guanine against cytomegalovirus and herpes simplex virus.

An isosteric analog of 9-[2-(phosphonomethoxy)ethyl]guanine (PMEG), 9-[[(ethoxyhydroxyphosphinyl)methoxy]methoxy]guanine (SKI 1008), was evaluated for its in vitro antiviral activity against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), murine cytomegalovirus (MCMV), and human cytomegalovirus (HCMV), and its in vivo antiviral efficacy against MCMV in mice. The in vitro anti-HSV activity of SKI 1008 was much lower than that of acyclovir, even though SKI 1008 showed similar antiviral activity against thymidine kinase positive (TK+) and thymidine kinase negative (TK-) strains. Like ganciclovir and PMEG, SKI 1008 selectively inhibited plaque formation of MCMV; the 50% effective concentration (EC50) and the 50% cytotoxic concentration (CC50) of SKI 1008, ganciclovir, and PMEG being 0.51 and 600, 1.65 and 461, and 0.06 and 12.1 micrograms/ml, respectively. The in vitro EC50 value of SKI 1008 against HCMV was comparable to that of ganciclovir (0.24 vs 0.16 microgram/ml) and was 12-fold higher than that of PMEG in a plaque reduction assay, but the therapeutic indices (the ratios of CC50 to EC50) of SKI 1008 and ganciclovir were higher than that of PMEG. The in vivo antiviral efficacy of SKI 1008 in MCMV-infected normal BALB/c and severe combined immunodeficiency (SCID) mice was lower than that of ganciclovir in terms of mortality and mean survival time.

Acyclovir↗
PubMed1995

Improved treatment results of non-Hodgkin's lymphoma in children: a report from the Children's Cancer and Leukemia Study Group of Japan.

From 1985 to 1989, 69 patients with non-Hodgkin's lymphoma (NHL) were treated by members of the Children's Cancer and Leukemia Study Group of Japan with a protocol consisting of vincristine, prednisolone, cyclophosphamide, doxorubicin, high-dose methotrexate (HD-MTX), mercaptopurine and cytarabine; central nervous system (CNS) prophylaxis with intrathecal MTX and hydrocortisone (NHL855). The 4-year event-free survival (EFS) was 78% (S.E., 10%) for patients with localized disease (n = 18) and 38% (S.E., 7%) for those with advanced disease (n = 51). Among the patients with advanced disease, those with non-lymphoblastic lymphoma tended to have a better 4-year EFS than those with lymphoblastic lymphoma (52% vs. 25%). Based on these findings, we initiated a new protocol NHL890 in which patients were assigned to two different chemotherapies according to the histology. Non-lymphoblastic subtype was treated almost identically to NHL855 while asparaginase and VP-16 were newly added in the consolidation-maintenance phase in advanced-stage lymphoblastic lymphoma. Sixty-seven patients with advanced disease were assessable. The overall 4-year EFS for advanced disease improved to 69% (S.E., 6%). A significant improvement was gained in the lymphoblastic lymphoma with a 4-year EFS of 56% (S.E., 11%) as compared with 25% (S.E., 9%) in the preceding study (P < 0.05). These findings suggest the importance of histology in the treatment of advanced-stage non-Hodgkin's lymphoma in childhood.

Adolescent↗
PubMed1995

Demonstration of Epstein-Barr virus genomes, using polymerase chain reaction in situ hybridization in paraffin-embedded lymphoid tissues.

We used the polymerase chain reaction (PCR) in situ hybridization (ISH) (PCR-ISH) on sections of malignant lymphoma and nonspecific lymphadenitis to detect small amounts of Epstein-Barr virus (EBV), a DNA virus of the herpes virus family. We first surveyed the EBV DNA by Southern blot analysis and PCR, and then compared results of the two PCR/ISH methodologies with the results of simplified/sensitive ISH for the positive cases. The target of the simplified in situ (DNA-ISH) was a few copies of EBV DNA per cell, and the target of the sensitive in situ (RNA-ISH) was as many as 10(7) copies of EBV RNA per cell. When EBV DNA was detected by Southern blot, DNA-ISH, RNA-ISH and PCR-ISH all revealed EBV genomes. When PCR revealed only amplified EBV DNA, DNA-ISH showed no EBV genomes, but PCR-ISH and RNA-ISH showed EBV genomes in a few cells. When PCR showed no detectable amplified EBV DNA, all of DNA-ISH, RNA-ISH and PCR-ISH showed no genomes. These findings indicate that PCR-ISH consistently detected a few copies of the EBV virions. The PCR-ISH was as sensitive as RNA-ISH. The RNA-ISH could not detect virus if RNA was not expressed, but the PCR-ISH could detect virus without such expression. The ability to detect a single copy of a specific gene in situ has many advantages and multiple applications in molecular biology, pathology, and cell biology.

Base Sequence↗
PubMed1995

Limited TCR V beta usage of infiltrating T cells in synovial tissues from patients with HTLV-I associated arthropathy.

Human T cell lymphotropic virus type-I (HTLV-I) is the etiologic agent of adult T cell leukemia/lymphoma and recently has also been suggested to be involved in chronic arthritis. The synovia of patients with rheumatoid arthritis (RA) contains activated T lymphocytes, with a restricted expression of T cell receptor (TCR) variable (V) beta gene segments. To characterize the T-cell populations of RA among HTLV-I carriers and noncarriers, we performed the immunohistochemical staining of CD4 and CDB, as well as a reverse transcription polymerase chain reaction (RT-PCR) to estimate the proportion of TCR beta RNA containing any particular V elements on the synovial specimens. In all but one HTLV-I carrier, the proviral DNA and/or RNA expression of HTLV-I was detected in the synovium. The CD4-positive cells proliferated markedly in the HTLV-I carriers compared with the noncarriers. In contrast to mononuclear cells in the peripheral blood, synovial T cells expressed only a few V beta transcripts, and no definite difference was observed between the carriers and the noncarriers. These results suggest that a common major antigen associated with the pathogenesis of RA may thus selectively interact with the V beta component of the TCR. Using RT-PCR, we studied the expression of the recombination-activating gene-1 (RAG-1), which was used in the V(D)J recombination of immunoglobulin and TCR genes. In all cases, RAG-1 was transcripted. The results supported the possibility that the extrathymic development of the selected TCR V beta T cells occurred in the synovia.

Adult↗
PubMed1995

Moyamoya disease in three siblings--follow-up study with magnetic resonance angiography (MRA).

Three siblings with moyamoya disease including identical twins are reported. Although the younger of identical twins had no neurological problems, CT and MRI detected cerebral infarctions and cerebral angiography showed the typical features of moyamoya disease. All three cases underwent encephalo-duro-arterio-synangiosis (EDAS), and serial magnetic resonance angiography (MRA) showed that the distal portions of the middle cerebral artery (MCA) were well perfused through surgically created anastomoses. There were no findings of disease progression. MRA might play an important role in follow-up studies of moyamoya disease.

Brain↗