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Biomedical subjects

M Kikuchi

Publications and source records attributed to M Kikuchi.

At least 559 records · Page 31Linked to original sources

Genetic changes in atypical hyperplasia and lymphoma with angioimmunoblastic lymphadenopathy and dysproteinaemia in the same patients.

The transition between atypical hyperplasia and lymphoma with angioimmunoblastic lymphadenopathy and dysproteinaemia (AILD) was studied in serial lymph node biopsy specimens from five patients using DNA analysis with Southern blot analysis, polymerase chain reaction, chromosomal analysis, and immunophenotyping. The chromosomal analysis showed additional abnormalities as the disease progressed to those present initially, and immunological staining showed a corresponding increase in the numbers of CD4- and Ki67-positive cells. In the first biopsy from each patient a diagnosis of atypical hyperplasia with AILD was made and lymphoma excluding by the finding of only a few atypical lymphoid cells and the preservation of follicles with germinal centres. DNA analysis of lymph nodes at this stage showed either germ lines or oligoclonal rearrangements of the T-cell receptor (TCR) and immunoglobulin heavy chain genes. In the final biopsy, when a diagnosis of lymphoma with AILD was made, either a monoclonal rearrangement of the TCR was observed or one of the rearranged bands had increased in density. These results suggest selective proliferation of a clone of abnormal cells may account for the progression of atypical hyperplasia to lymphoma with AILD.

Base Sequence↗

Analysis of adhesion molecules in Ki-1 anaplastic large-cell lymphoma.

We analysed the expression of adhesion molecules on lymphoma cells in 13 patients with Ki-1 (CD30)-positive anaplastic large-cell lymphoma (Ki-1 ALCL; lymph nodes in 6, extranodal tumours in 6, and both lymph nodes and bone in 1). Very late activation antigen (VLA)-alpha 4 (CD49d) and Hermes lymph node homing receptor (CD44) were constantly expressed in all specimens, and intercellular adhesion molecule-1 (ICAM-1; CD54) was frequently expressed in 10 of the 14 specimens. The expressions of lymphocyte function-associated antigen-1 alpha (LFA-1 alpha; CD11a) and VLA-alpha 5 (CD49e) occurred in 5 of 14 and 4 of 14 specimens, respectively. The expression of VLA-alpha 2 (CD49b), endothelial leukocyte adhesion molecule-1, neural cell adhesion molecule (CD56) and E cadherin were always lacking. VLA-alpha 6 (CD49f) was absent in all but one specimen. The expression of VLA-alpha 5 on Ki-1 ALCL was high in subcutis-cutis but absent in lymph nodes. Furthermore, in one case, LFA-1 alpha was detected in the primary lymph node, but was absent in a metastatic bone lesion. These results suggest that the expression of ICAM-1 is partially responsible for aleukemic behaviour in Ki-1 ALCL and, moreover, that the Ki-1 ALCL cells modify their expression of adhesion molecules at each of the involved organs.

Adolescent↗

Early malignant histiocytosis of the intestine: an autopsy report.

A 63-year-old man with malignant histiocytosis of the intestine died 3 days after gastrectomy for early gastric adenocarcinoma. Malignant histiocytosis of the intestine was unexpectedly found at autopsy. The intestine was thickened with mucosal erosions. Histologically, a few atypical large histiocyte-like cells were found in focal aggregates in the mucosa. These large cells expressed the T-cell antigen and monoclonality was demonstrated by the polymerase chain reaction showing variable-joining segment rearrangement in the T-cell receptor delta-chain gene. Malignant histiocytosis of the intestine was thus diagnosed.

Base Sequence↗

Expression of human T-cell leukaemia virus type I and associated antigens, and interleukin-2 and receptor in lymph nodes of adult T-cell leukaemia/lymphoma.

To examine the relationship between the expression of human T-cell leukaemia virus type (HTLV-I) mRNA and associated antigens and clinicopathological features, we studied 31 lymph nodes of patients with adult T-cell leukaemia/lymphoma (ATLL) and related diseases, using in situ hybridization and immunohistochemistry. We classified the patients into four types on the basis of their clinicopathological features (HTLV-I associated lymphadenitis, incipient ATLL, ATLL with complete HTLV-I provirus, and ATLL with defective HTLV-I provirus. The expression of HTLV-I mRNA was detected in all 3 patients with incipient ATLL, in 5 of 10 patients with defective-provirus ATLL, in 5 of 11 patients with complete-provirus ATLL, and 3 of 7 with HTLV-I associated lymphadenitis, but the amounts were very small; approximately 1 in 10000-200000 lymph node cells express the viral genomes. This suggests that expression of viral genomes may not be important for immortalization, but it is important that to note the capacity for HTLV-I infection is preserved in each group of non-neoplastic and neoplastic states. HTLV-I mRNA was detected only in lymphocytes and/or lymphoma cells, but the HTLV-I associated antigens (env, gag and pX) were found in histiocytes and endothelial cells, as well as in lymphocytes and/or lymphoma cells. Anti-interleukin 2 receptor (IL-2R) antibody reacted with the giant cells of incipient ATLL and with the transformed lymphocytes and immunoblast-like cells of the HTLV-I-associated lymphadenitis but not with the lymphocytes in the background. Of the typical ATLL, IL-2R was found in both lymphoma cells and giant cells. IL-2 was rarely detected.

Adult↗

Angiocentric lymphoma with granulomatous panniculitis in the skin expressing natural killer cell and large granular T-cell phenotypes.

We investigated three patients suffering from angiocentric lymphoma with granulomatous panniculitis in the skin. All three patients presented with multiple purple subcutaneous nodules. Immunohistologically, the lymphoma cells in all three patients expressed CD2 (T-11), CD56 (neural cell adhesion molecule), and Mik-beta 1 (interleukin-2 beta receptor). CD3s (CD3, Leu-4)-positive lymphoma cells were found in two patients. A pore-forming protein (perforin) was detected in the lymphoma cells of all three patients. Perforin-possessing lymphoid cells were focally scattered in 2 of 15 patients with CD56-negative cutaneous lymphomas who served as controls. By the Southern blot method, one patient showed a rearranged T-cell receptor (TcR)beta gene in the biopsied specimen, and the other two patients had germ-line configurations of TcRs and immunoglobulin heavy chain genes. One patient had serum anti-human T-cell lymphotropic virus (HTLV)-I antibody, but showed no integration of its proviral DNA. Ultrastructurally, membrane-bound azurophilic granules were detected in the atypical lymphoid cells of all three patients. Angiocentric lymphoma with panniculitis in three patients showed the characteristics of natural killer and large granular T-cells. The histological features might be due to the characteristics of the neoplastic cells with azurophilic granules and perforin.

Aged↗

Cervical spinal cord injury associated with ossification of the posterior longitudinal ligament.

Among 231 patients with cervical injuries treated over 12 years, 15 had cervical spinal cord injury associated with ossification of the posterior longitudinal ligament. All of them were male and most had injuries due to a relatively weak external force. Four of them underwent surgery. There was little difference in improvement of paralysis between the conservatively and the surgically treated group.

Aged↗

Development of a transcutaneous blood-constituent monitoring method using a suction effusion fluid collection technique and an ion-sensitive field-effect transistor glucose sensor.

The paper describes a method for the transcutaneous monitoring of blood constituents. It combines the use of a suction effusion fluid (SEF) collecting technique with a silicon on sapphire/ion-sensitive field-effect transistor (SOS/ISFET) biosensor. SEF is directly collected by a weak evacuation through skin from which the stratum corneum has been removed. An SEF collecting cell with a stainless-steel mesh at the bottom is kept in a weak vacuum condition, and SEF is sucked up through the mesh and deposited in a reservoir above. An ISFET glucose sensor is able to detect glucose concentrations in very small SEF samples through the use of two small ISFETs and an immobilised enzyme membrane. The reliability of transcutaneously obtained SEF was first confirmed in an experiment using rabbits. A clinical analyser was used to determine levels of glucose, urea nitrogen and creatinine in SEF obtained transcutaneously; these results are compared with results obtained by the same analyser directly from sera. The ISFET glucose sensor was successfully tested on human subjects for the monitoring of blood glucose levels. During these tests, glucose level changes in the SEF followed actual blood glucose level changes with a slight time delay. Results suggest the feasibility of non-invasive, transcutaneous monitoring of low molecular weight substances in the blood without the use of ordinary blood sampling.

Animals↗

Mitochondrial diabetes mellitus: prevalence and clinical characterization of diabetes due to mitochondrial tRNA(Leu(UUR)) gene mutation in Japanese patients.

Mutations in the mitochondrial gene were recently identified in a large pedigree of diabetes mellitus and deafness. As the mitochondrial gene is materially inherited, Japanese diabetic patients whose mothers were also diabetic were screened, using peripheral leucocytes, 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 who were screened. Diabetes co-segregated with the mutation, except in one young subject, and was maternally inherited. The apparent onset of disease occurred between 11 and 68 years of age. Some of the affected members developed hearing impairment and congestive heart failure due to cardiomyopathy, though generally long after the onset of diabetes, and these patients had therefore not been diagnosed as having a specific form of diabetes. The duration of sulphonyl-urea treatment was not more than 8 years in these pedigrees and affected members were prone to progression to insulin-requiring diabetes. Thus, these patients were secondary sulphonylurea failures. Long-term follow-up revealed that the underlying disorder in affected members is a progressive impairment of insulin secretion. Some were initially diagnosed as having IDDM based on an apparent acute onset in youth and the clinical severity of their diabetes. Others were regarded as having MODY with an aggressive course. The mitochondrial gene mutation or diabetes is not transmitted to all offspring of the affected mothers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Self-reported prevalence of non-insulin-dependent diabetes mellitus in the 1st (Issei) and 2nd (Nisei) generation of Japanese-Brazilians over 40 years of age.

The immigration of Japanese people to Brazil began in 1908 with two major waves, from 1925 to 1940 and from 1952 to the 1960s. Brazil has the largest population (about 1,288,000) of Japanese origin outside Japan with varying age groups. A mortality study revealed that diabetes as an underlying cause of death was higher in the first-generation Japanese than in Japan (3.4 vs. 1.9 per 100,000 for men, and 7.2 vs. 1.9 for women). The self-reported prevalences of known diabetes in subjects aged 40 years or older were obtained by questionnaires from three sources. In six Japanese cultural associations in Säo Paulo city, the prevalences were 9.7% and 6.9% for the first generation (mean age 61.5 years) and for the second generation (mean age 40.0 years), respectively. Age-adjusted prevalences, according to the Brazilian population in the 1980 national census, were 6.9% and 8.1% for the first and second generations. According to a study carried out as a part of a socioeconomic census of the Japanese population in Brazil, the prevalences of diabetes were 7.4% and 5.2%, and the age-adjusted prevalences were 5.3% and 5.8% in the first and second generations, respectively. Another study carried out for employees of a bank, owned by Japanese-Brazilian community members, revealed crude prevalences of diabetes in the first and second generations of 7.1% and 4.2%, and age-adjusted prevalences of 7.3% and 8.2%, respectively. These data indicate an increased prevalence of diabetes in this population compared to Japan, suggesting the importance of environmental factors in the pathogenesis of diabetes.

Adult↗

Diabetic retinopathy and control of diabetes with special reference to blood glucose levels.

Data concerning diabetic retinopathy were collected prospectively in the Diabetes Clinic of the Third Department of Internal Medicine, University of Tokyo, from the beginning of the Clinic in 1957 until 1985. These data are analyzed here. The prevalence and severity of the retinopathy at the initial visit was strongly related to the duration of diabetes before examination. Pretreatment fasting blood glucose levels were also significantly related. During follow-up, the incidence of retinopathy was most strongly influenced by the degree of control of blood glucose, followed by other factors like blood pressure, age at diagnosis, etc. The effectiveness of sulfonylurea on retinopathy was not inferior to insulin so long as good control was obtained. It was deduced from the analysis of the chain of events that dot hemorrhage is the initial component of diabetic retinopathy, followed by hard exudate, blot hemorrhage, soft exudate and proliferative retinopathy. A six-year fluorescein angiography follow-up of well-controlled non-insulin dependent cases with mild retinopathy showed that microaneurysms disappear rapidly during the first year and more slowly thereafter. The avascular areas once formed seem to progress despite the degree of control exerted here. The other Japanese results are discussed.

Blood Glucose↗

The enhancement of the extracellular carboxyl-terminal domain of human growth hormone receptor on growth hormone dependent responses of 3T3-F442A cells.

We have expressed the carboxyl-terminal domain (C domain) of the cytokine receptor homologous (CRH) region of human growth hormone receptor (hGHR) as a protein fused with maltose binding protein (MBP) in E. coli. Following proteolytic cleavage by restriction protease factor Xa, the C domain was purified to homogeneity as a monomeric form. The purified C domain appears to be folded properly judged by NMR spectrum and the far-UV circular dichroism (CD) spectrum. The C domain did not exhibit ligand binding activity. However, the C domain enhanced the human growth hormone (hGH) dependent differentiation of preadipose 3T3-F442A cells into adipose cells and the phosphorylation of a 34 kDa membrane protein.

Adipocytes↗

Clonality of benign lymphoid hyperplasia in orbit and conjunctiva.

In order to thoroughly characterize the clonal population of lymphoid hyperplasia of the orbit and conjunctiva, we investigated six cases which were histologically proven to be benign lymphoid hyperplasia. We analyzed the clonal rearrangements of the antigen receptors and bcl-2 gene, Epstein-Barr virus (EBV), and human T-cell leukemia virus type 1 (HTLV-I) by Southern blot and/or polymerase chain reaction (PCR), and performed in situ hybridization for mRNA of kappa and lambda immunoglobulin. Five cases showed rearrangements of immunoglobulin heavy chain gene (JH) and/or light chain gene (J kappa), and the monoclonal V-J recombination of JH in PCR. However, the rearranged bands were much more faint than was the germ-line band. We considered the monoclonal population of B cells small. Two of the five cases recurred locally after four and nine years respectively. Because benign lymphoid hyperplasias frequently contain an occult monoclonal B-cell population, a follow-up should be conducted. The remaining case in our investigation showed a rearrangement of the T-cell-receptor gene and proviral DNA of HTLV-I, and it showed rapid progress to adult T-cell leukemia after the biopsy. EBV and bcl-2 gene rearrangements were not observed in any of the six cases we studied.

Adult↗

Monoclonal B cells and restricted oligoclonal T cells in T-cell-rich B-cell lymphoma.

Immunophenotyping of lymphoma using paraffin-embedded lymphoid tissue is useful in identifying the large neoplastic B cells in T-cell-rich B-cell lymphoma (TRBL), but does not succeed in deciding clonality. We studied six cases to determine the clonal population of B and T cells of TRBL. Immunohistochemistry on frozen and paraffin-embedded material showed that the cellular population in all six cases consisted mainly of T cells; fewer than ten percent of the cells stained as B cells. However, in all cases, monoclonality of the immunoglobulin was helpful for diagnosing the B-cell neoplasia. Southern blot-yielded genetic analysis showed monoclonality of B cells in three cases, but no evidence of clonality in the T cells. Moreover, gene monoclonality has been detected in all cases examined by polymerase chain reaction, using the primers for the V and J regions of the immunoglobulin heavy chain gene. For T cells, the D and J regions of the T-cell receptor (TCR) beta chain showed the same patterns of oligoclonal bands in all cells, and the V and J regions of the TCR gamma chain showed the same bands in all. The expression of TCR V beta families was polyclonal but restricted.

Aged↗

Tissue inhibitor of metalloproteinases (TIMP-1) produced by granulosa and oviduct cells enhances in vitro development of bovine embryo.

Embryogenesis-stimulating activity (ESA) was found in serum-free conditioned media (CM) of bovine cumulus/granulosa cells (BGC) and bovine oviductal epithelial cells (BOEC). The CM of BGC (BGC-CM) contained two molecular species of ESA, one with a low molecular weight (M(r) 30,000) and another with a high molecular weight (M(r) 80,000); but only the activity with low molecular weight was detected in CM of BOEC by gel-permeation chromatography. The smaller ESA (embryogenin-1) in BGC-CM was purified to homogeneity, as a common activity in both CM by a combination of gel-permeation chromatography, ion-exchange chromatography, and reverse-phase HPLC. Embryogenin-1 has a molecular weight of 31,100 (reduced) and has been identified as a bovine tissue inhibitor of metalloproteinase-1 by NH2-terminal amino acid sequence analysis. Western blot analysis, anti-proteinase activities against metalloproteinases, and the nucleotide sequence of cDNA isolated from a lambda gt11 cDNA library of the bovine ovary by a polyclonal antibody against embryogenin-1. These data suggest that the tissue inhibitor of metalloproteinase-1 produced by BGC and BOEC is a major ESA for in vitro development of bovine embryos.

Amino Acid Sequence↗

Purification and molecular cloning of bovine oviduct-specific glycoprotein.

A specific 85-97-kDa (95-kDa) glycoprotein was found in bovine oviductal tissue and fluid during the follicular phase. In this study, a 95-kDa bovine oviductal glycoprotein (95-kDa BOGP) was purified by wheat germ agglutinin affinity and Mono-Q ion-exchange column chromatography. The first 29 NH2-terminal amino acid residues were determined by gas-phase microsequencing. A cDNA expression library prepared from poly(A)+ RNA isolated from bovine oviducts was screened with a monoclonal antibody to 95-kDa BOGP. A single positive clone containing a approximately 2-kb cDNA insert was isolated. The coding region contained 1612 bp translating to 537 amino acids. The derived amino acid sequence contained a partial signal sequence of 18 amino acids followed by 29 amino acids that were identical to the NH2-terminal amino acids determined by protein sequencing of purified 95-kDa BOGP. The amino acid sequence predicted a mature protein of 519 amino acids (57,684 daltons) containing one potential N-linked glycosylation site and five cysteines. Northern blot hybridization with a digoxigenin-labeled probe indicated that a single message of approximately 2.5 kb was present in oviductal RNA, and this message was detected in significantly greater amounts in oviductal RNA during the follicular phase than during the luteal phase. The amino acid sequence of a portion of 95-kDa BOGP was highly homologous (71% identity) to that of a baboon oviduct-specific glycoprotein.

Amino Acid Sequence↗

Susceptibility to neonatal streptozotocin-induced diabetes in spontaneously hypertensive rats.

We studied the difference in the susceptibility to neonatal streptozotocin (STZ) diabetes between spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). Two-day-old female SHR and WKY were injected intraperitoneally with 75.0 mg/kg of STZ or vehicle for control. Hyperglycemia developed in both strains at 4 days of age, but SHR were more hyperglycemic. Overt hyperglycemia developed in SHR with aging after a partial recovery from initial hyperglycemia at 10 days of age, whereas WKY did not develop significant hyperglycemia except shortly after STZ treatment. Percentage of insulin-positive B cells in total islet cells and pancreatic immunoreactive insulin (IRI) content were measured at 4 days, 10 days, 4 weeks, and 12 weeks of age. B cells per islet and pancreatic IRI content were significantly reduced in STZ-treated groups as compared with control in both SHR and WKY at 4 days of age, but later they increased significantly with aging in both strains. However, the reduction in pancreatic IRI content relative to control was significantly greater in SHR than in WKY from 4 days (-94.5 +/- 3.5%, -84.1 +/- 4.8%; p < 0.01) to 12 weeks (-97.1 +/- 2.1%, -28.0 +/- 2.5%; p < 0.05), and the reduction in B cells per islet was also greater in SHR at 4 weeks of age. These results indicated that the initial destruction of pancreatic B cells induced by STZ was greater, and the following regeneration was less in SHR than in WKY. The association of the susceptibility to neonatal STZ diabetes with the development of genetic hypertension in SHR remained to be elucidated.

Animals↗