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S Mitsunaga

Publications and source records attributed to S Mitsunaga.

At least 37 records · Page 2Linked to original sources
PubMed1997

[Surgical emergency induced by chest tumors].

Mechanisms and therapeutic procedures for emergencies induced by chest tumors are reviewed. 1) Carcinomatous pleuritis is the most frequently encountered situation for clinicians. At first, pleural effusion should be punctured for diagnosis and chest drainage should be performed consequently. Intrathoracic chemotherapy and pleurodasis (OK-432 is usually used) are then used if necessary. 2) Airway stenosis is the most critical state. Conventionally, violent incubation throughout the stenotic portion of the airway has been used with poor results. Recently, however, irradiation of Nd:YAG laser can be utilized, and the prognosis of the airway stenosis is much improved. Another effective procedure is the insertion of several kinds of airway stent. Silicon stents like T-tube, Dumon tube and Dynamic stent or metallic stents like EMS (Expandable Metallic Stent) are generally used. The advantages of EMS are easy installation and little disturbance of sputum excretion. The disadvantages of EMS are difficult removal and re-stenosis of the airway. On the other hand, silicon tubes are easy to be removed, re-insertion is possible and re-stenosis is rare, but the insertion should be performed under general anesthesia and sputum excretion may pose problems. A case of laser irradiation and two cases of stent insertion are presented. 3) Airway bleeding is also emergent. Bronchofiberscopic ethanol injection (BEI) is effective against continuous bleeding of the central airway. We performed BEI for 33 lung cancer cases, and the method was effective for all cases. 4) Cardiac tamponade, SVC syndrome, esophago-bronchial fistula, bronchial stump fistula are also important emergencies induced by chest tumors. Standard therapeutic procedures are explained for all oncology surgeons and physicians.

Bronchial Fistula↗
PubMed1997

Chemopreventive effect of difluoromethylornithine (DFMO) on mouse skin squamous cell carcinomas induced by benzo(a)pyrene.

The effect of the chemopreventive agent D,L-alpha-difluoromethylornithine (DFMO) on the incidence of skin squamous cell carcinoma was studied in SENCAR mice treated weekly with topical applications of benzo(a)pyrene (B(a)P) (0.15 mmol, 2 x /week) on the dorsal skin. Animals were randomized to receive either chow or chow supplemented with DFMO (1 g/1 kg) and studied at 10, 15, 20, 25, and 30 weeks of B(a)P treatment. Morphometric analyses at each timepoint evaluated the epidermal thickness (ET) and the number of epidermal nucleated layers (NL). The ET increased from 12-17 microns as early as 10 weeks after B(a)P treatment, reaching 22 microns at 20 weeks, and 27 microns at 25 weeks (130% increase). The NL also increased markedly. A relatively modest increase in ET was observed in animals treated with B(a)P and DFMO (16% at 15 weeks, 53% at 20 weeks, and 85% at 25 weeks) as compared to controls. The relative increase in NL showed a similar pattern. Although extensive epidermal hyperplasia was seen early, clear-cut focal premalignant lesions were not identifiable before week 20 of B(a)P treatment. At 20 weeks, the most frequently noted focal premalignant lesions in carcinogen-treated animals (without DFMO) were moderate dysplasias. At 25 and 30 weeks, a large increase was seen in the incidence of more advanced dysplastic lesions and invasive carcinomas. In the group treated with B(a)P and DFMO, a marked reduction in the number of carcinomas was observed at 25 and 30 weeks. At 25 weeks, DFMO reduced tumor yield from 5.8 to 3.2 carcinomas per mouse. At 30 weeks, the reduction was from 13.1 to 5.7 carcinomas per mouse (57% reduction). Collectively, these data emphasize the strong chemopreventive effect of DFMO against tumors in the mouse skin complete carcinogenesis model, as indicated by the reduction of overall skin tumor incidence and the decreased epidermal hyperplasia in DFMO-treated animals. Morphometrically defined increases in ET and NL can be used as early biomarkers of DFMO chemoprevention in mouse skin tumorigenesis.

Animals↗
PubMed1996

Evidence of involvement of cytotoxic antibodies directed against patients's HLA class II produced by transfused donor-derived B cells in post-transfusion graft-versus-host disease.

Post-transfusion graft-versus-host disease (PTGVHD) is one of the most severe side-effects of blood transfusion. To characterize the effector cells causing this disease, we cloned lymphocytes from a PTGVHD patient's peripheral blood. T-cell and B-cell clones were established, the origins of which were proven to be transfused donor lymphocytes. It was found that the B cells produced IgG that mediated complement-dependent cytotoxicity to the cells bearing the patient's HLA class II genotype. Our results suggest, for the first time, the involvement of B-cell-produced cytotoxic antibodies directed against patient's HLA class II in the pathogenesis of PTGVHD.

Antibodies↗
PubMed1996

Factors influencing survival following pulmonary resection for metastatic colorectal carcinoma.

The results of pulmonary resection and clinical factors relating to long-term survival were evaluated in 29 patients with histologically proven pulmonary metastasis from colorectal carcinoma. The patients were followed up from 4 months to 120 months, with an average of 43.7 months. Overall 5- and 10-year survival rates were 41% and 34% respectively. The 5- and 10-year survival rates in patients with metastatic nodules 30 cm or less in diameter were 77% and 58%, respectively, a significantly better result than in those with metastatic nodules over 30 mm in diameter. Survival in patients without nodal involvement was significantly better than that in patients with lymph node metastases. Multivariate analysis according to Cox proportional hazards model demonstrated that the size of the metastasis was an independent prognostic factor.

Adult↗
PubMed1995

Lack of concordant p53 mutations in some paired primary and metastatic mouse squamous cell carcinomas induced by chemical carcinogenesis.

We studied the frequency and pattern of p53 mutations in 16 mouse skin primary squamous carcinomas induced by chemical carcinogens and their 19 matched metastases. The molecular changes were analyzed by polymerase chain reaction-single-strand conformation polymorphism and subsequent direct sequencing analysis. Eleven mutations of the p53 gene were detected in a total of eight primary tumors, and 10 mutations were detected in nine metastases. Only four pairs had identical mutations in primary and paired metastatic tumors. Eight mutations in six pairs were detected in primary tumors but not in their metastases, and four mutations from three matched pairs were detected in metastases but not in primary tumors. The four pairs that contained the same mutations in both the primary and secondary tumors had lymph-node metastases, and all mutations occurred in exon 8. Conversely, five of six pairs with p53 mutations only in primary tumors had lung metastases, and only one of the mutations occurred in exon 8. None of the mutations found only in metastases were located in exon 8. These data indicate that p53 mutations are prevalent in lymph-node metastases and infrequent in lung metastases of mouse skin tumors and that primary tumors with exon 8 mutations may be more likely to metastasize to the lymph nodes.

Animals↗
PubMed1995

Family segregation analysis of inheritance of human minor histocompatibility antigen.

Disparities in minor histocompatibility antigens (mHAs) between HLA-identical donor and recipient pairs often cause graft-versus-host disease (GVHD) or graft rejection. Minor HAs are thought to be peptides that are associated with specific major histocompatibility complex (MHC) molecules and are presented to specific T cells. Despite the importance of mHAs in constructing a strong immunological barrier following tissue transplantation, little information on mHAs in humans is available. We have already reported establishment of the DR9-restricted mHA-specific CD4+ cytotoxic T cell (CTL) clone "A-6." To investigate the chromosomal localization of the gene encoding the mHA peptide recognized by clone A-6 in context with DR9, we performed a family segregation analysis. We concluded that the mHA-encoding gene was transmitted from parent(s) to some offspring.

B-Lymphocytes↗
PubMed1995

High-resolution HLA-DQB1 typing by combination of group-specific amplification and restriction fragment length polymorphism.

A reliable method for high-resolution HLA-DQB1 typing using the combination of group-specific amplification and RFLP analysis is described. Group-specific amplification was carried out for the alleles of two groups using the two primer pairs under the same PCR conditions. One group contains DQ5 and DQ6 specificities and the other DQ2, DQ3, and DQ4 specificities. Computer analysis on cleavage patterns for 19 alleles of the DQB1 gene showed that the 11 alleles of the former group could be distinguished with five restriction enzymes and the eight alleles of the latter group could be distinguished with four enzymes. We could reduce the number of restriction endonucleases required compared with the number used in previous studies because we selected appropriate restriction enzymes which had at least one recognition site in almost all DQB1 alleles as a form of internal control. Moreover, DQB1*0602 and 0603, which were indistinguishable using the previously reported PCR-RFLP methods, could be distinguished by the present method. The results of typing of 100 samples from Japanese individuals by this method showed no discrepancy with the results obtained by serologic methods. The calculated allele frequencies showed good agreement with those reported at the 11th International Histocompatibility Workshop.

Base Sequence↗
PubMed1995

Establishment of a T-cell line from lymphocytes presumably implicated in posttransfusion graft-versus-host disease.

Posttransfusion graft-versus-host disease (PTGVHD) is known to develop in immunocompetent patients exhibiting clinical symptoms such as erythroderma, fever, liver dysfunction, diarrhea and pancytopenia. It is speculated that transfused blood donors' lymphocytes might recognize the recipients' HLAs as alloantigens. The thus stimulated lymphocytes might proliferate, expand and finally attack the host's immune system or tissues. However, details regarding these expanded donor cells such as: (1) whether they represent one clone or more, (2) the composition of lymphocyte subsets, and (3) the target HLA antigens of recipients, are not clear, since T-cell lines derived from PTGVHD patients have not yet been obtained. The aim of this study is to characterize T-cells responsible for PTGVHD and to identify their target molecules. For that purpose, we attempted to establish T-cell lines derived from a PTGVHD patient. We show that the established T-cell line, proven to be derived from donor lymphocytes, showed a CD4+ phenotype and had cytotoxic activities. Furthermore, we describe that the target of the cytotoxic T-cell line (CTL) is an HLA-DRB1*0405-related molecule of the patient.

Base Sequence↗
PubMed1995

Multiplex ARMS-PCR-RFLP method for high-resolution typing of HLA-DRB1.

A reliable method for high-resolution HLA-DRB1 typing using the combination of group-specific amplification and RFLP analysis is described. Group-specific PCR amplification (multiplex ARMS-PCR) was carried out under the same conditions for all groups using seven different primer pairs divided into four groups: (1) DR1 and DR10; (2) DR2, DR7 and DR9; (3) DR3 DR5, DR6 and DR8, and (4) DR4. The subsequent polyacrylamide gel electrophoresis was used to determine the group(s) contained in each sample. DR1, DR2/7, DR3/5/6/8, DR4, DRB1*0901 and DRB1*1001 could be distinguished easily using this system. Computer analysis of the various restriction enzyme cleavage sites was carried out on 105 DRB1 allele sequences. It was shown that all DRB1 alleles, except for five allele pairs and some alleles possessing silent mutations, could be distinguished with commonly available restriction endonucleases. Computer analyses on the discrimination of the heterozygous and homozygous combinations were also carried out. Although some heterozygous combinations could no be distinguished with single digestion, double digestion using two restriction enzymes could distinguish most of such heterozygotes. The results of the typing of 100 Japanese individuals using this method showed good agreement with those obtained by other methods.

Alleles↗
PubMed1994

Higher frequency of alterations in the p16/CDKN2 gene in squamous cell carcinoma cell lines than in primary tumors of the head and neck.

Sixty-eight primary head and neck squamous cell carcinomas and nine head and neck squamous cell carcinoma cell lines were examined for mutations and homozygous deletions of the p16/CDKN2 gene. Homozygous deletions of the p16/CDKN2 gene were found in three lines, and a mutation was detected in another cell line. In contrast, none of the primary tumors showed homozygous deletions and 11 of 68 tumors had missense or nonsense base changes. Seven tumors contained somatic mutations. Five tumors, including one that also had a somatic mutation, had a probable polymorphism at codon 140 leading to an amino acid change from Ala to Thr. Three of these also contained an apparent polymorphism at codon 98, which did not lead to an amino acid change. The frequency of mutations and deletions detected differs markedly between cell lines (44%) and primary tumors (10%) suggesting that while p16/CDKN2 may play a role in tumorigenesis in some head and neck squamous cell carcinomas, inactivation of p16/CDKN2 probably occurs more frequently in cell lines as a result of adaptation to cell culture.

Base Sequence↗
PubMed1994

Sequence-specific interactions of a nuclear protein factor with the promoter region of a rice gene for alpha-amylase, RAmy3D.

The expression of a rice gene for alpha-amylase, RAmy3D, in suspension-cultured cells is induced at the transcriptional level by the deprivation of sugars. Binding of a nuclear protein from suspension-cultured rice cells to the promoter region of the RAmy3D gene was studied by gel-retardation and DNase I footprinting assays. Gel-retardation assays indicated that a 358-bp fragment of the promoter region interacted specifically with a protein factor from suspension-cultured cells. DNase I footprinting analysis allowed us to define three protein-binding regions. Each of these protein-binding sequences contained the GCCG G/C CG motif, which is specifically present in the promoter region of the sugar-regulated gene, RAmy3D, for rice alpha-amylase and not in that of the gibberellin-regulated RAmy1A gene. Subsequent cross-competition experiments using gel-retardation assay and synthetic oligonucleotides showed that the GCCG G/C CG motifs directly mediated the binding of a nuclear protein. These observations are discussed in relation to expression of the gene for alpha-amylase in suspension-cultured cells.

Base Sequence↗
PubMed1994

A simple method for detecting single base substitutions and its application to HLA-DPB1 typing.

We have developed a simple and reliable method, PCR-PHFA (polymerase chain reaction dependent preferential homoduplex formation assay), for detection of single base substitutions within PCR amplicons. This technique is based upon strand competition during hybridization between a double labeled amplicon, prepared from biotin and DNP labeled primers, and an unlabeled amplicon. Under the precisely controlled temperature gradient, the preferential formation of a homoduplex over a heteroduplex occurs. After annealing, the identical sequence of the double labeled and unlabeled amplicon resulted in a low population of regenerated double labeled dsDNA due to strand exchange between them. Even when the two differed by only a single base substitution, double labeled molecule was regenerated efficiently because of preferential homoduplex formation. The regenerated double labeled molecule was captured onto a streptavidin coated microtiter plate and quantified enzymatically with a chromogenic substrate. The technique has been successfully applied in HLA-DPB1 typing. Furthermore, we detected a mutated gene even in the presence of a large excess of the corresponding normal gene.

Base Sequence↗
PubMed1994

Alloreactive feature of HLA-DP-specific cytotoxic T-cell clone.

The alloreactive feature of CD4+ cytotoxic T-cell clone that could specifically lyse the cells bearing DPB1*0202 sequence was described. The clone was generated from a mixed culture of peripheral blood lymphocytes derived from siblings who were HLA-A, B, C, DR, and DQ identical by serological typing and whose DNA sequence of the second exon of DPB1 was one-allele mismatched by oligonucleotide typing (responder, PDB1*0201/0402; stimulator, DPB1*0202/0402). Specific cytotoxic activity of the clone was strictly limited against the cells bearing DPB1*0202 and was not able to lyse the other tested cells bearing DPB1*0201, 0301, 0401, 0501, 0601, 0901, 1301, and 1601. The cytotoxic activity of the clone was blocked by treatment of target cells with anti-DP monoclonal antibodies (B7/21). On the other hand, treatment of target cells with blocking agents of endogenous or exogenous antigen transport pathway (brefeldin A (BFA), endogenous; chloroquine, exogenous) had no effect on the cytotoxic activity of the clone. These results strongly favor the view that the DP epitopes recognized by the clone are conformational epitopes conferred by specific amino acids in hypervariable regions of the HLA-DP second DPB1 exon and the contribution of peptides in the HLA grooves to the conformational epitope motif is less likely.

Acyclovir↗
PubMed1994

Protection against natural killer cells by interferon-gamma treatment of K562 cells cannot be explained by augmented major histocompatibility complex class I expression.

Prior study has revealed that the expression of certain major histocompatibility complex (MHC) class I molecules on the membranes of normal or transformed cells can prevent natural killer (NK)-cell-mediated killing. This has been explained by either (1) the target interference model, or (2) the effector inhibition model. In both cases, MHC class I molecules are concerned but the precise mechanisms are still unclear. The erythroleukaemia K562 cell is known as a NK-sensitive target. This sensitivity has been explained mostly as being due to lack of MHC class I antigens on the K562 membrane. However, several recent studies have indicated that the expression of MHC class I antigens on the cell does not solely explain the protection against NK cells. To elucidate the mechanism of NK-cell-mediated killing, we investigated the killing profiles of the K562 cells by NK cells. Previous studies indicated that the NK-sensitive K562 cells can express some MHC class I antigens on their surface, and become protective against NK-cell killing after treatment with human interferon-gamma (hIFN-gamma). In the present study, we show that this resistance is not rendered by MHC class I expression, because addition of anti-MHC class I monoclonal antibodies (mAb) in the killing assay of hIFN-gamma-treated K562 cells, which express MHC class I antigens as the target, did not restore the sensitivity to NK cells. Moreover, we show that spontaneously occurring K562 clones which could not express MHC class I antigens even after hIFN-gamma treatment, could be protected after treatment with the cytokine. Taken together, these results strongly suggest that the susceptibility of K562 cells to NK cell killing is due to some elements distinct from those related to MHC class I antigens.

Antibodies, Monoclonal↗
PubMed1994

A study of the complications induced by conventional and disposable contact lenses.

We reviewed the charts of 23,068 patients (45,580 eyes) who were prescribed contact lenses in order to investigate the incidence of corneal complications in Japan. This population of patients included wearers of various types of conventional contact lenses as well as disposable extended wear lenses and daily disposable lenses. The rate of corneal complications and 95% confidence interval for each lens group were: polymethylmethacrylate (PMMA) lenses, 15.8% (358 of 2,267 eyes, 14.3-17.3%); rigid gas permeable lenses, 10.5% (3,191 of 30,459 eyes, 10.2-10.8%); acrylelastomer lenses, 7.2% (nine of 124 eyes, 2.7-11.7%); HEMA lenses 8.5% (534 of 6,261 eyes, 7.8-9.2%); high water content lenses, 4.0% (103 of 2,591 eyes, 3.6-4.4%); weekly disposable lenses, 4.9% (146 of 2,985 eyes, 4.1-5.7%); and daily disposable lenses, 2.5% (22 of 893 eyes, 1.5-3.5%). PMMA lenses had a significantly higher rate of corneal complications compared with other lenses, whereas the daily disposable lens had a significantly lower rate for the same. The majority of corneal complications for all types of lenses consisted of superficial punctate keratopathy, and there were no cases of corneal ulcers.

Adolescent↗
PubMed1992

Family study on HLA-DPB1 polymorphism: linkage analysis with HLA-DR/DQ and two "new" alleles.

An extensive family study on HLA-DPB1 was performed in 105 families living in northeastern Japan. In a linkage study between HLA-DPB1 and other HLA loci, five apparent recombinations between DPB1 and DR/DQ loci were observed. The recombination frequency (theta) with maximum probability was estimated to be 0.017 by the lod score method. DPB1 allele and haplotype frequencies in unrelated parents were determined by direct counting. The most common allele was DPB1*0501 with the frequency of 41.2% and the second was DPB1*0201 with 24.0%. Nine DPB1-DR and six DPB1-DQ haplotypes were in significant linkage disequilibrium. Seven kinds of extended haplotypes were observed to be over 1%, in which the most common haplotype A24-B52-DR15-DQ6-DPB1*0901 occurred at 6.0%. Moreover, we found two "new" DPB1 alleles in this study. The first one possesses a single base substitution from DPB1*0501 resulting in an amino acid change. The other is most likely to be formed by an intraexonic recombination between DPB1*0301 and DPB1*0501.

Alleles↗