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Biomedical subjects

K Kurosu

Publications and source records attributed to K Kurosu.

At least 19 recordsLinked to original sources

Feasibility of combination chemotherapy with cisplatin and etoposide for haemodialysis patients with lung cancer.

Cancer chemotherapy for haemodialysis patients has never been established. To elucidate the feasibility of cisplatin-based combination chemotherapy for haemodialysis patients with lung cancer, a dose escalation study was conducted. Five haemodialysis patients with lung cancer were treated with cisplatin and etoposide. A starting dose of 40 mg m(-2) of cisplatin on day 1 and 50 mg m(-2) of etoposide on days 1, 3 and 5 were administered as the first course for the first patient. Membrane haemodialysis was regularly performed three times a week and soon after the completion of therapy. By monitoring toxicity and pharmacokinetics data, the dose was escalated course by course and patient by patient. Dose escalation was completed for the first two patients resulting in full-dose chemotherapy consisting of 80 mg m(-2) of cisplatin on day 1 and 100 mg m(-2) of etoposide on days 1, 3 and 5. Multiple courses of the full-dose chemotherapy were administered to the other three patients. Toxicity was manageable and tolerable for all. Pharmacokinetics data were comparable to those from patients with normal renal function, except for potential long-lasting higher levels of free platinum in the renal insufficiency group. In conclusion, this standard-dose combination chemotherapy was feasible even for haemodialysis patients.

Aged↗

Hepatic histopathologic range compared with virological studies of hepatitis viruses among autopsy cases in Tokyo.

Few reports exist comparing virological studies on hepatitis viruses with histopathological studies of autopsy cases other than those of liver clinics. Relations between hepatitis virus-related markers and hepatic histopathology were studied in 1044 autopsy cases (779 men and 265 women) at the Medical Examiner's Office, Tokyo. Heart blood was obtained at the autopsy, and the sera were submitted for virus-marker detection of HBV, HCV, and HGV/GBV-C. Hematoxylin and eosin-stained paraffin sections were used for histological assessment. Histopathologically, 463 cases were determined as so-called normal liver; among them 440 cases (95.0%) were negative for all hepatitis virus-related markers, but HBV-DNA was positive in 13 cases, three cases were positive for HCV-RNA (indicating a healthy carrier rate of HCV-RNA of 4.1%), and seven cases were positive for HGV/GBV-C RNA. The incidence of these three virus-related markers was low in cases with fatty liver and micronodular cirrhosis, but in cases with chronic hepatitis, macronodular cirrhosis and hepatocellular carcinoma, the incidence of HBV-DNA and HCV-RNA increased with advancing disease. A positive rate of anti-HBs or anti-HBc (HBV-Ab) or both was found between 30 and 50% in all histopathological groups, and no noticeable relations between the positive rate and microscopical changes were detected. The presence of HGV/GBV-C RNA seemed to be unrelated to hepatic inflammation or generalized inflammatory changes or both occurring together. The decadal age incidence of the virus-related markers and their incidence in various hepatic diseases are also reported.

Journal Article↗

Direct-antiglobulin-test-negative immune haemolytic anaemia and thrombocytopenia in a patient with Hodgkin's disease.

A case of direct-antiglobulin-test (DAT)-negative auto-immune haemolytic anaemia (AIHA) and immune thrombocytopenia (ITP) associated with Hodgkin's disease (HD) is reported. A 52-year-old male was admitted with anaemia, thrombocytopenia, and lymphadenopathy. The patient was DAT negative, although he exhibited the clinical features of warm-type AIHA and elevated levels of red-blood-cell-associated IgG (RBC-IgG). The serum level of platelet-associated IgG (PA-IgG) was markedly increased. A biopsy specimen of the inguinal lymph nodes showed HD of mixed cellularity. Marked improvement of subjective symptoms, normalization of haematological values and a decrease in the level of both RBC- and PA-IgG were observed after the start of combination chemotherapy for HD. Although the association of HD, ITP, and/or AIHA has been infrequently reported, the measurement of RBC-IgG is recommended in cases of HD with anaemia even though DAT is negative, since HD is known to be associated with various protean immunological abnormalities.

Anemia, Hemolytic↗

Liver weight of adult Japanese, especially recent weight values.

Cases of 445 adult Japanese autopsies of the Tokyo Metropolitan Medical Examiner's Office were used in this study. They were either negative for all hepatitis virus-related markers examined or had little or no histopathological hepatic changes. The maximum liver weight was observed in the fifth decade in both sexes, and after the fifth decade the liver weight decreased markedly with increasing age. The sexual difference in the liver weight was most predominant in the third to fifth decades, but the sexual difference was not marked in the older age groups. The highest liver weight to body weight ratio was observed in the fifth decade of both sexes, and a total decadal pattern of the ratio was similar to a parabola. An interesting finding was that the male liver weights in the third to fifth decades considerably increased in recent years, but the female liver weights in the third decade were almost the same despite the difference in investigation period. We suggest the data of this study may be a standard for Japanese people.

Journal Article↗

Aberrant expression of immunoglobulin heavy chain genes in Epstein-Barr virus-negative, human immunodeficiency virus-related lymphoid interstitial pneumonia.

The two-step polymerase chain reaction (PCR) and sequencing analysis was used to analyze the immunoglobulin heavy chain variable (Ig V(H)) genes of open-chest biopsy or autopsy samples from five patients with Epstein-Barr virus-negative human immunodeficiency virus (HIV)-related lymphoid interstitial pneumonia (LIP), and the results were compared with those for Ig V(H) genes from five HIV-negative LIP patients. The findings of this study are consistent with the different immunological situations of HIV-related and HIV-negative LIP. (a) The Ig V(H)3 subgroup was underexpressed in three of five cases of HIV-related LIP. In contrast, none of the HIV-negative cases showed this abnormality. Because the Ig V(H)3 subgroup encodes the largest portion of Ig V(H) genes, a depletion of B cells expressing Ig V(H)3 genes reflects a major alteration in the B-cell compartment. (b) All HIV-related LIP cases demonstrated two or three oligoclonal populations. HIV-negative cases showed minor monoclonal or polyclonal populations, but not oligoclonal ones. These oligoclonal populations suggest the coexistence of several occult clonal B-cell populations in HIV-related LIP. (c) Some oligoclonal clones in HIV-related LIP showed mutated framework regions not demonstrated in HIV-negative clones. This degree of variation exceeds the usual mutation rate for frameworks, suggesting a role for framework residues in antigen binding. (d) The frequency of D-D fusions of minor oligoclonal clones (HIV-related LIP) is higher than that of minor monoclonal clones (HIV-negative LIP). Such D-D fusions may enhance the probability of expression of antibodies capable of binding HIV glycoproteins.

Adult↗

CDR3 sequences of MALT lymphoma show homology with those of autoreactive B-cell lines.

We have examined the CDR3 sequence and adjacent regions of immunoglobulin genes from B-cell lymphoma of mucosa-associated lymphoid tissue (MALT). Twenty-nine sequences (15 sequences from 13 low-grade MALT lymphomas, marginal zone B-cell lymphomas; 7 sequences from 6 high-grade MALT lymphomas; 7 sequences from 7 diffuse large cell lymphomas) were obtained after cloning of the polymerase chain reaction-amplified segments. In the low-grade MALT, high-grade MALT and diffuse large cell lymphomas, the mean length of the CDR3 region was 47.6+/-10.31 (range 21 to 60), 38.71+/-10.37 (range 27 to 57) and 40.86+/-3.34 (range 39 to 48) nucleotides, respectively. The length of the CDR3 region was significantly greater in the low-grade MALT lymphoma group than in the other two groups. CDR3 sequences in lymphoma cell clones of 14 cases showed 60 to 81% homology with autoantibody-associated lymphocyte clones including rheumatoid factor. The incidences of these autoantibody-associated lymphocyte clones were higher in the high-grade MALT (4/6) and diffuse large lymphomas (5/7) than in the low-grade MALT lymphoma (5/13). Cases with more than 70% homology at the nucleotide level were found to have 71 to 82% homology with autoantibodies at the protein level in the low-grade MALT lymphomas (2/13), and 67% homology in the high-grade MALT lymphomas (2/7). These results indicate that MALT lymphomas may be derived from the malignant transformation of autoreactive B-cells.

Amino Acid Sequence↗

Type I interferon induces inhibitory 16-kD CCAAT/ enhancer binding protein (C/EBP)beta, repressing the HIV-1 long terminal repeat in macrophages: pulmonary tuberculosis alters C/EBP expression, enhancing HIV-1 replication.

We have previously observed that HIV-1 replication is suppressed in uninflamed lung and increased during tuberculosis. In vitro THP-1 cell-derived macrophages inhibited HIV-1 replication after infection with Mycobacterium tuberculosis. Suppression of HIV-1 replication was associated with inhibition of the HIV-1 long terminal repeat (LTR) and induction of ISGF-3, a type I interferon (IFN)-specific transcription factor. Repression of the HIV-1 LTR required intact CCAAT/enhancer binding protein (C/EBP) sites. THP-1 cell-derived macrophages infected with M. tuberculosis, lipopolysaccharide, or IFN-beta induced the 16-kD inhibitory C/EBPbeta isoform and coincidentally repressed HIV-1 LTR transcription. C/EBPbeta was the predominant C/EBP family member produced in THP-1 macrophages during HIV-1 LTR repression. In vivo, alveolar macrophages from uninflamed lung strongly expressed inhibitory 16-kD C/EBPbeta, but pulmonary tuberculosis abolished inhibitory C/EBPbeta expression and induced a novel C/EBP DNA binding protein. Therefore, in vitro, proinflammatory stimulation produces an IFN response inhibiting viral replication by induction of a C/EBPbeta transcriptional repressor. THP-1 cell-derived macrophages stimulated with type I IFN are similar to alveolar macrophages in the uninflamed lung in vivo. In contrast, the cellular immune response in active pulmonary tuberculosis disrupts this innate immunity, switching C/EBP expression and allowing high level viral replication.

Base Sequence↗

Low-grade pulmonary mucosa-associated lymphoid tissue lymphoma with or without intraclonal variation.

We examined the immunoglobulin heavy chain variable (Ig VH) region genes of 11 low-grade pulmonary mucosa-associated lymphoid tissue (MALT) lymphomas by a two-step polymerase chain reaction (PCR) and sequencing analysis. We observed frequent somatic mutations with the positive selective pressure of the rearranged Ig VH genes in all cases, indicative of postgerminal center cell origin. Eight cases demonstrated intraclonal variations (hypermutation with intraclonal variation type), but the other cases showed only one major clone without intraclonal heterogeneity (hypermutation without intraclonal variation type). The former might reflect the reentry of marginal zone B cells into a germinal center environment leading to further mutations. The latter might be no longer susceptible to hypermutation mechanisms and seemed to be stable. Four cases used Ig VH genes (hv3019b9, VH26, and VH4.21), which are frequently found in a variety of autoantibodies, such as cold agglutinins, rheumatoid factors, and anti-DNA antibodies.

Adult↗

A particular characteristic of IgH complementarity-determining region 3 suggests autoreactive B-cell origin of primary gastric B-cell lymphomas.

To clarify the origin of tumor cells and the possible role of antigen in the pathogenesis of mucosa-associated lymphoid tissue (MALT) lymphoma, we analyzed the third complementarity determining region of IgH gene in nine primary gastric B-cell lymphomas by PCR. The presence of vacA gene of Helicobacter pylori was also determined. These cases were diagnosed histopathologically as three low (extranodal marginal zone B-cell lymphoma)- and three high-grade MALT lymphomas and three diffuse large-cell lymphomas without evidence of MALT lymphoma. All cases showed a monoclonally rearranged JH band. A single dominant clone was detected by sequencing the IgH CDR3 regions in eight cases. In the remaining cases. In the remaining case, two major sequences were identified. Complementarity-determining region 3 (CDR3) sequences in lymphoma cell clones of seven cases showed 61% to 81% homology with autoantibody-associated lymphocyte clones including rheumatoid factor. The N-D-N region in the low-grade MALT lymphoma group was significantly longer than in the high-grade lymphoma groups. Although vacA gene of H. pylori was detected in five of nine cases, all lymphoma cell clones showed no association with foreign antigen. These results indicate that autoantigen may be responsible for the clonal selection of lymphoma cells, and thus autoimmunity may play a role in the pathogenesis of primary gastric B-cell lymphomas.

Adult↗

Alleviation of monocrotaline-induced pulmonary hypertension by antibodies to monocyte chemotactic and activating factor/monocyte chemoattractant protein-1.

Administration of monocrotaline (MCT) causes pulmonary vascular lesions consisting of monocyte/macrophage infiltration in the early phase and medial thickening in pulmonary arteries and arterioles associated with pulmonary hypertension (PH) in the later phase. However, the molecular mechanism of monocyte/macrophage infiltration and its roles remain elusive. Herein, we have evaluated the role of a potent monocyte chemotactic and activating chemokine/monocyte chemoattractant protein-1 (MCAF/MCP-1) in MCT-induced PH in rats. A single injection of MCT induced PH at Day 21, as evidenced by increases in the ratio of right ventricular to left ventricular and septum weights (RV/LV+S) and right ventricular systolic pressure (RVSP). A significant increase in macrophage number in lungs started at Day 14, reaching a maximum at Day 21. MCAF/MCP-1 levels in bronchoalveolar lavage fluids were elevated significantly at Day 14 and remained high until Day 28, whereas plasma MCAF/MCP-1 levels increased at Day 7, returning to normal levels by Day 21. Immunoreactive MCAF/MCP-1 proteins were mainly detected in macrophages in alveoli and in perivascular regions of pulmonary arterioles and venules. Intravenous administration of anti-MCAF/MCP-1 antibodies with MCT significantly decreased macrophage infiltration and eventually reduced the increases in RV/LV+S and RVSP, as well as medial thickening of pulmonary arterioles. Thus, MCAF/MCP-1 is essentially involved in MCT-induced PH by recruiting and activating macrophages.

Animals↗

[A case of marginal zone B-cell lymphoma].

A 60-year-old woman had an abnormal shadow in the right lower lung field on chest roentgenogram. Transbronchial lung biopsy revealed findings consistent with malignant lymphoma, and a right middle lobectomy was performed. Pathological findings showed that tumor cells had infiltrated the epithelium, forming so-called lymphoepithelial lesions. Flow cytometric analysis of the resected specimen revealed that B-cell associated antigens (CD 19, 20) were expressed, and that the tumor cells were CD 5-, CD 10-. A marked increase in the number of lymphocytes with an IgM kappa component suggested monoclonal origin for the tumor cells in the resected specimen. Southern blot analysis showed clonal rearrangement of the heavy chain of the immunoglobulin gene. A diagnosis of malignant lymphoma of bronchus-associated lymphoid tissue was made. This tumor was defined according to the revised European. American classification of lymphoid neoplasms as a marginal zone B-cell lymphoma.

Antigens, CD19↗

Third complementarity-determining-region sequence analysis of lymphocytic interstitial pneumonia: most cases demonstrate a minor monoclonal population hidden among normal lymphocyte clones.

We analyzed the third complementarity-determining region (CDR3) of the immunoglobulin heavy chain (IgH) gene in five patients with lymphoid interstitial pneumonia (LIP) through a two-step polymerase chain reaction (PCR) and sequencing analysis. By sequencing analysis of the PCR products, morphologic LIP could be divided into two groups: a polyclonal type and a minor monoclonal type. Because of their high frequencies, minor monoclonal clones seemed to be neoplastic clones hidden in normally reactive lymphocyte clones. Consequently, only the polyclonal type might have represented true LIP. Sequencing of the PCR products from open-chest biopsy and transbronchial lung biopsy (TBLB) specimens obtained 8 yr later in one patient with minor monoclonal type LIP confirmed this possibility. In true LIP, six of 20 lymphocyte clones showed 67 to 86% homology with lymphocyte clones derived from fetal tissue. In three of these six clones, the D-region (N-D-N) lengths were very short, whereas four clones showed a high homology with autoreactive lymphocytes (rheumatoid factor, anti-DNA antibody, and G6-positive lymphocytes). Since rheumatoid factors, anti-DNA antibodies, and G6 are autoreactive antibodies, immature B cells stimulated by autoantigens might play some role in the pathogenesis of true LIP.

Adult↗

Reappraisal of the relationship between immunoglobulin heavy chain gene rearrangement and Epstein-Barr virus infection in Reed-Sternberg cells of Hodgkin's disease.

We investigated 44 cases of Hodgkin's disease for Epstein-Barr virus genome with EBER-1 in situ hybridization. Twenty of 44 (45.5%) were positive for EBV. Simultaneously, immunoglobulin gene rearrangements were assessed in 32 of these 44 cases with PCR on DNA extracted from Reed-Sternberg cell (RS-cell) -rich areas microdissected from paraffin sections. Clonally rearranged immunoglobulin (IgH) gene was observed in 15 cases (46.9%). EBV-negative cases showed more frequent IgH rearrangement than EBV-positive cases (10 and 5 cases, respectively). In 9 cases, the RS cells were CD20-positive immunohistochemically and these were all EBV negative and the IgH gene was rearranged in all except one. These findings may suggest that EBV infection has occurred before the immunoglobulin gene rearrangement or that EBV infection has influenced the rearrangement of the immunoglobulin gene. The results may also hint towards the obscure B-cell nature of the RS cells.

Adolescent↗

Monoclonality of B-cell lineage in primary pulmonary lymphoma demonstrated by immunoglobulin heavy chain gene sequence analysis of histologically non-definitive transbronchial biopsy specimens.

Immunoglobulin heavy chain (IgH) gene rearrangements were amplified in transbronchial lung biopsy (TBLB) specimens taken from five patients with primary lymphoma of the lung in whom the diagnosis was established by surgical specimens. By histopathological analysis of TBLB specimens, only two of the five cases were diagnosed as lymphoma, the other three cases being classified as equivocal due mainly to low levels of cellular atypia and to artefactual distortion. All five TBLB specimens, as well as the subsequent surgical specimens, showed a sharp monoclonal band of IgH gene rearrangement on electrophoresis of polymerase chain reaction (PCR) products. By contrast, three surgical biopsy specimens from cases of lymphoid interstitial pneumonia (LIP) showed smear polyclonal bands. No clonal rearrangements were detected in six non-neoplastic controls, including five cases of chronic bronchitis and one of sarcoidosis. The PCR products of three of the lymphoma cases were sequenced from both TBLB and surgical specimens. In all three cases, there was dominant expression of a particular rearrangement, assumed to be tumour-derived. In each case, the major clones derived from the TBLB and the surgical specimen were identical. In both lymphoma and LIP cases, more frequent usages of JH4 and JH6 were evident. The diagnosis of lymphoma can be confirmed on TBLB specimens by use of this technique.

Adult↗

A study of the sedative effect of home-administered oral diazepam for the dental treatment of children.

This study investigated the effects of oral diazepam administered at home to fearful child patients prior to dental treatment. Twenty-five healthy, uncooperative children, mean age 3 years 8 months (+/- 1 year 3 months), requiring at least three visits for the treatment of dental caries, were studied. Each child's behaviour was assessed during three treatment sessions: (i) control, with no diazepam or placebo; (ii) with diazepam; and (iii) with a placebo. Each child acted as his/her own control, being initially assigned to the control session. Subsequently each was randomly assigned to receive either diazepam or placebo for the second session and the other for the third session. The diazepam and placebo were administered by the parents at home approximately 60 minutes before treatment. Each patient's behaviour was assessed on a scale of 1 (definitely positive) to 4 (definitely negative) by two calibrated examiners who were blind to the medications given and independent of the treatment. Vital signs were monitored at 5-minute intervals. Behaviour was significantly better with diazepam than with the placebo or with neither. No significant differences were observed between the placebo and control sessions. At no time were any adverse effects noted, such as vomiting or respiratory depression. It was concluded that oral administration of 0.3 mg/kg diazepam at home by the parent is an effective and safe technique for preoperative sedation of fearful child patients.

Administration, Oral↗

Third complementarity determining region sequence analysis of low-grade bronchus-associated lymphoid tissue lymphoma: genotypic analysis reveals heterogeneity in maturation.

It has recently been suggested that autoimmunity may play a role in the pathogenesis of low-grade mucosa-associated lymphoid tissue lymphomas, but precise genotypic analysis of antigen binding sites of low-grade bronchus-associated lymphoid tissue (BALT) lymphomas has not been reported. We analyzed the third complementarity determining region (CDR3) in eight cases of low-grade BALT lymphoma by 2-step PCR and sequencing analysis. All cases showed a distinct monoclonal band (about 100 base pairs) on electrophoresis. In seven cases, a single major CDR3 sequence was identified with five to nine clones among 10 vector clones being identical; and in the remaining case, two major sequences were obtained, with four clones among nine vector clones being identical. Findings suggestive of the autoimmunity of low-grade BALT lymphoma were obtained: (1) VHDJH rearrangements in seven of the eight lymphoma cell clones were potentially functional; (2) genotypically, two lymphoma cell clones showed 60 to 74% homology with G6 positive lymphocyte clones; and (3) five lymphoma cell clones showed 61 to 71 % homology with lymphocyte clones derived from fetal liver or cord blood. In one case, the N-D-N length of the neoplastic clone was very short and lacked N nucleotides at the D-JH junction. Therefore, our study demonstrates genotypic heterogeneity in maturation in low-grade BALT lymphoma.

Adult↗

Glucose retention on the surfaces of primary teeth in 3- and 4-yr-old children.

Glucose retention was determined in 38 kindergarten children ages 3-4 yr. The children rinsed their mouths with 10 ml of a 0.5 mol/l glucose solution for 15 s and then spat out. Three minutes after they put the solution in their mouths, a small paper-point was used to collect samples of saliva from the labial and buccal surfaces of the maxillary and mandibular primary teeth. The concentration of glucose in the small amount of saliva collected was measured with an immobilized enzyme system. Glucose retention was highest on the maxillary central primary incisor, second highest on the maxillary first primary molar and third highest on the maxillary lateral primary incisor. An intermediate value was seen on the maxillary and mandibular second primary molars, the mandibular first primary molar and the maxillary primary canine. A lower value was observed on the mandibular primary canine and the lowest on the mandibular incisors. It was concluded that there were site differences in glucose retention on primary teeth of 3- and 4-yr-old children.

Analysis of Variance↗