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T Kinjo

Publications and source records attributed to T Kinjo.

At least 37 records · Page 2Linked to original sources

Rhabdoid tumour of the lung is a dedifferentiated phenotype of pulmonary adenocarcinoma.

AIMS: Primary rhabdoid tumour of the lung is rare, and histological and biological characteristics have not been fully documented. We describe three cases of primary lung rhabdoid tumour, all associated with adenocarcinoma, and investigate the histological features and biological characteristics. METHODS AND RESULTS: Three cases were obtained from a total 902 cases of surgically removed primary lung tumours between 1986 and 1998. The rhabdoid cells were found to occupy about 50-90% of each tumour. All of the tumours had nonrhabdoid adenocarcinoma foci in the centre of the tumours. Transition between the adenocarcinomatous and rhabdoid components was demonstrated. Detailed immunohistochemical studies were carried out. The epithelial markers, cytokeratins and epithelial membrane antigen (EMA), were strongly expressed in rhabdoid and adenocarcinomatous components. Furthermore, surfactant apoprotein A was positive in both components in one case, but myoglobin, MyoD and HHF35 were not expressed. Vimentin was strongly and diffusely stained in all cases. The neuroendocrine markers, chromogranin A (all cases), neuron-specific antigen (NSE) (two cases) and CD56 (one case) were occasionally positive in only a small number of the rhabdoid tumour cells. GM-CSF was positively stained in one case, and the dedifferentiated characteristics of the rhabdoid cells was suggested. Proliferative cell nuclear antigen (PCNA) was strongly demonstrated in the rhabdoid tumour cells (all cases). To gain better understanding the highly proliferative characteristics of the tumours, p53 gene (exons 5-8) mutation was examined by DNA sequencing analysis; mutation of the p53 DNA was not detected. Overexpression of p53 protein was also not demonstrated in all cases. HPV6 was demonstrated in one case by PCR method and also non-isotopic in-situ hybridization (NISH). Two cases died in a short period of time (3 years and 4 months, respectively). CONCLUSION: The rhabdoid cells in these three cases were considered to represent the dedifferentiated components of the accompanying adenocarcinoma. Dedifferentiated characteristics (neuroendocrine markers, GM-CSF, vimentin, and the aggressive behaviour) were evident.

Adenocarcinoma↗

Mapping of epitopes and structural analysis of antigenic sites in the nucleoprotein of rabies virus.

Linear epitopes on the rabies virus nucleoprotein (N) recognized by six MAbs raised against antigenic sites I (MAbs 6-4, 12-2 and 13-27) and IV (MAbs 6-9, 7-12 and 8-1) were investigated. Based on our previous studies on sites I and IV, 24 consecutively overlapping octapeptides and N- and C-terminal-deleted mutant N proteins were prepared. Results showed that all three site I epitopes studied and two site IV epitopes (for MAbs 8-1 and 6-9) mapped to aa 358-367, and that the other site IV epitope of MAb 7-12 mapped to aa 375-383. Tests using chimeric and truncated proteins showed that MAb 8-1 also requires the N-terminal sequence of the N protein to recognize its binding region more efficiently. Immunofluorescence studies demonstrated that all three site I-specific MAbs and one site IV-specific MAb (7-12) stained the N antigen that was diffusely distributed in the whole cytoplasm; the other two site IV-specific MAbs (6-9 and 8-1) detected only the N antigen in the cytoplasmic inclusion bodies (CIB). An antigenic site II-specific MAb (6-17) also detected CIB-associated N antigen alone. Furthermore, the level of diffuse N antigens decreased after treatment of infected cells with cycloheximide. These results suggest that epitopes at site I are expressed on the immature form of the N protein, but epitope structures of site IV MAbs 6-9 and 8-1 are created and/or exposed only after maturation of the N protein.

Amino Acid Sequence↗

Recent striking changes in histological differentiation and rate of human papillomavirus infection in squamous cell carcinoma of the lung in Okinawa, a subtropical island in southern Japan.

AIMS: The incidence of lung cancer in Okinawa has been the highest in Japan since 1975, and squamous cell carcinoma (SCC), especially the well differentiated form, is the most prevalent form in Okinawa, although well differentiated SCC is relatively rare in mainland Japan. Furthermore, a high proportion of SCC of the lung in Okinawa was positive for human papillomavirus (HPV). In this study, we report recent striking changes in histological features and in the incidence of HPV infection. METHODS: In Okinawa between 1986 and 1998, 1109 surgically resected lung tumours were examined histopathologically. In addition, human papillomavirus infection was detected by the polymerase chain reaction and Southern blot analysis in SCC cases reported in 1993 and 1995-8. Non-isotopic in situ hybridisation of HPV DNA was also carried out. RESULTS: Up until 1994 SCC, especially the well differentiated form, was the most prevalent type of tumour. However, since 1995 the number of such cases has diminished steadily, accompanied by a slight rise in the incidence of adenocarcinoma. Although most present and past patients are heavy smokers, the incidence of SCC, especially the well differentiated form, continues to decrease steadily. Furthermore, in 1993, HPV was detected in 79% of all cases, and was particularly prevalent in the well differentiated form, but the rate fell to 68% in 1995, 35% in 1996, 23% in 1997, and 24% in 1998. The age distribution of patients, the male to female ratio, and the number of tumours overexpressing p53 protein did not change significantly over the study period, and thus did not correlate with changes in the differentiation of SCC. CONCLUSIONS: The decreasing incidence of viral infection correlates strongly with the falling numbers of SCC cases, especially well differentiated cases. These findings suggest that HPV might be involved in the development of SCC of the lung, affecting the histological differentiation of SCC in particular, at least in Okinawa, a subtropical island in southern Japan.

Adenocarcinoma↗

Brain metastasis of epithelioid sarcoma--case report.

A 20-year-old-female first presented with an epithelioid sarcoma of the right thumb, and the right thumb was amputated. Five years later, a metastasis was found in the right lower lung and a partial lobectomy was performed. Three years later, computed tomography showed a metastatic brain tumor in the left frontal lobe, which was removed surgically. Adjuvant radiotherapy and chemotherapy were given after all operations. Histological examination showed all resected tumors were epithelioid sarcoma. She has maintained a good activity of daily living level as an outpatient for 2 years, although subcutaneous metastases and bronchial lymph node metastases have been observed. Such intensive treatment of slowly growing tumors often prolongs survival time, even in patients with multiple metastases.

Activities of Daily Living↗

[Alpha-herpesvirus infection in the central nervous system].

Herpes simplex virus type 1 (HSV1) encephalitis is commonly observed, but HSV1 myelitis is rare. On the other hand, HSV2 is common etiologic agent for ascending necrotizing myelitis associated with diabetes mellitus, malignant tumors, AIDS and immunocompromised hosts. It is suggested that latent infection of the virus of root ganglia or primary infected virus is possibly followed by spread of infection to the central nervous system, particularly in immunocompromised patients. In this report, pathological findings and clinical symptoms of our recent encephalitis and myelitis cases infected with HSV2 and HSV1 are described.

Alphaherpesvirinae↗

Sequence analysis of a total of three megabases of DNA in two regions of chromosome 8p.

Large-scale sequencing of genomic regions and in silico gene trapping together represent a highly efficient and powerful approach for identifying novel genes. We performed megabase-level sequence analyses of two genomic regions on human chromosome 8p (8p11.2 and 8p22-->p21.3), after covering those segments with sequence-ready contigs composed of 74 cosmids, 14 BACs, and three PAC clones. We determined continuous nucleotide sequences of 1,856,753 bases on 8p11.2 and 1,210,381 bases on 8p22-->p21.3 by combining the shotgun and primer-walking methods. In silico gene trapping identified four novel genes in the 8p11.2 region and, in the 8p22-->p21.3 region, six known genes (PRLTS, PCM1, MTAMR7, HCAT2, HFREP-1 and PHP) and three novel genes. The distribution of Alu and LINE1 repetitive elements and the densities of predicted exons were different in each region, and Alu-rich portions contained more exonic sequences than LINE1-rich areas.

Amino Acid Sequence↗

Sequence analysis of an 800-kb genomic DNA region on chromosome 8q21 that contains the Nijmegen breakage syndrome gene, NBS1.

An 800-kb region on chromosome 8q21, which complements the phenotype of cells from Nijmegen breakage syndrome patients, is a candidate for the locus of the underlying gene, termed NBS1. The sequence of this 800-kb region of DNA indicated that the size of this segment is 755,832 bp with an additional 36-kb gap. From this region, we identified four genes including NBS1, a gene coding for a 27-kDa vitamin D-dependent calcium-binding protein (27-kDa calbindin), the mitochondrial 2,4-dienoyl-CoA reductase gene, and a novel gene, C8orf1/hT41. All four genes were aligned in a 250-kb centromeric portion of the region, and no gene was found in the remaining telomeric portion containing 500 kb. The genomic organization of the C8orf1/hT41 and NBS1 genes has been analyzed using the computer programs GRAIL 2 and GENSCAN. They predicted and successfully found more than 93% of the exons, even a small 54-bp exon, indicating that one or more exons in any gene can be identified by these programs. GENSCAN was more efficient at locating the four genes than GRAIL 2 and identified 15 of the 16 exons of the NBS1 gene. This 800-kb region contained repetitive sequences, including 179 copies of the Alu sequence (1 copy/4.2 kb), 123 copies of the L1 sequence (1 copy/6.1 kb), 107 copies of the LTR sequence (1 copy/7.1 kb), and 63 copies of the MER sequence (1 copy/12 kb). There was a slight but not significant difference in the repetitive content of the gene-rich region and the remaining noncoding region. Our results indicate that computer-assisted methods are useful and powerful for identifying exons of both known and novel genes.

Abnormalities, Multiple↗

Alteration of mRNA levels of delta-aminolevulinic acid synthase, ferrochelatase and heme oxygenase-1 in griseofulvin induced protoporphyria mice.

Human erythropoietic protoporphyria (EPP) is an inherited disorder of porphyrin metabolism and its experimental murine model can be produced by treatment with griseofulvin (GF). We investigated the alteration of mRNA expression in ferrochelatase (FeC), delta-aminolevulinic acid synthase (ALAS) and heme oxygenase-1 (HO-1) in liver, skin and peripheral blood cells of GF-treated mice. In liver, ALAS mRNA was enhanced dramatically by GF administration, in accord with thesis that the expression of ALAS is regulated by feedback mechanism. The expression of HO-1 mRNA increased most rapidly and drastically in liver, however its mechanism of regulation may be different from that of ALAS mRNA. The level of FeC mRNA in liver was less affected with GF treatment. Our results indicate that the inhibition of FeC by GF administration might occur primarily at post-transcriptional level. Similar effects were observed in the ALAS and HO-1 mRNA expression in peripheral blood cells, 2-fold increase in the ALAS mRNA and increase from undetectable level to detectable level in the HO-1 mRNA. In skin of GF-treated mice, average increases of 1.3-fold in the ALAS mRNA and 1.6-fold in the HO-1 mRNA were statistically insignificant. The FeC mRNA level was not altered in peripheral blood or in skin of GF-treated mice. The present study indicates that the molecular analysis is practicable in skin and peripheral blood. In further study, this model could contribute to investigate the pathogenesis of clinical manifestation including possibly cutaneous changes in EPP.

5-Aminolevulinate Synthetase↗

Coxsackievirus B4 myocarditis in an orangutan.

A 37-year-old female orangutan died at the zoological garden. Autopsy examination demonstrated severe coxsackievirus B4 myocarditis immunohistochemically as a cause of the death. Apoptosis of the cardiac muscle cells was observed using the TdT-mediated dUTP-biotin nick endo labeling method and was considered to play a role in the myocarditis. Congestion of the liver and both lungs due to cardiac failure was also observed. Coxsackievirus infection is found frequently in the Okinawan human population. The present orangutan's infection might have come from visitors who were allowed to go near the orangutan. Malignant tumors, severe suppurative infections, and intestinal parasite infections were not observed. Epstein-Barr virus DNA was detected in lymph nodes, but there was no Burkitt's lymphoma.

Animals↗

[A case of TSH-secreting pituitary adenoma associated with an unruptured aneurysm: successful treatment by two-stage operation and gamma-knife].

We report a successfully treated case of invasive TSH-secreting pituitary adenoma associated with an unruptured internal carotid artery aneurysm by two-stage operation and gamma-knife radiosurgery. A 64-year-old woman was admitted to our department with a 3-year history of general fatigue and 1-year history of anxiety, palpitation and hyperhydrosis. Endocrinological examination revealed hyperthyroidism with elevated TSH, GH and somatomedin C. Magnetic resonance images demonstrated a tumor in the sella turcica which extended into the left cavernous sinus, furthermore, indicated aneurysm-like flow void at the ventral part of the left internal carotid artery. The aneurysm was confirmed by conventional angiography. Neck clipping of the aneurysm was performed through pterional approach as the first operation. One month later, at the second operation, the pituitary adenoma except for cavernous sinus portion was resected via the transsphenoidal approach. Immunohistological examination revealed positive for TSH and GH. Gamma-knife radiosurgery with a central dose of 33.3 Gy and peripheral dose of 17 Gy was carried out for residual tumor at the cavernous sinus under both MRI and CT guidance. Posttreatment course was uneventful with normalization of thyroid function at 16 months after gamma-knife. Two-stage operation and gamma-knife radiosurgery is effective for TSH-secreting adenoma extending into the cavernous sinus associated with an unruptured aneurysm.

Adenoma↗

Extensive intra-alveolar haemorrhage caused by disseminated strongyloidiasis.

We describe here four cases of disseminated strongyloidiasis. In Okinawa, it has been reported that about 10% of the residents are infected with Strongyloides stercoralis, but disseminated cases are rare. Detailed histopathological examination revealed that the present four cases could clearly be separated into two groups, two acute cases and two subacute cases. The acute cases died rapidly due to extensive diffuse intra-alveolar haemorrhage in both lungs. However, there were no inflammatory infiltrates, abscesses or granulomas in the lungs. Worms were demonstrated in the alveolar spaces. No extensive bleeding was observed in any organs except the lungs. The acute cases could be diagnosed as severe diffuse intra-alveolar haemorrhage syndrome, but deposition of immune complex (parasite antigen and immunoglobulins) and complement C3c was not demonstrated in the alveolar wall and small vessels of the lung. The subacute cases exhibited no such extensive haemorrhage, but scattered microabscesses were found with sepsis. During the migration of the worms from the colon, enteric bacteria entered the circulation in the two subacute cases. The acute cases received steroid therapy before the dissemination of the worms, but the two subacute cases did not. Steroids might have influenced the Strongyloides stercoralis dissemination and/or the course of the disease.

Adult↗

Organochlorine pesticides and polychlorinated biphenyl congeners in wild terrestrial mammals and birds from Chubu region, Japan: interspecies comparison of the residue levels and compositions.

In order to understand the residue levels of organochlorine compounds (OCs) and their accumulation patterns in wildlife inhabiting Chubu region, Japan, the concentrations of polychlorinated biphenyls (PCBs), hexachlorocyclohexane isomers (HCHs), DDT compounds (DDTs) and hexachlorobenzene (HCB) were measured in 8 species of terrestrial mammals and 10 species of birds. In view of feeding habits, the contamination levels of OCs were found to be higher in omnivorous mammals than in herbivorous ones, and in fish-eating ones and raptores than in omnivorous birds. In fox and dog, PCB-180 (2, 2', 3, 4, 4', 5, 5'-heptachlorobiphenyl) was the most dominant PCB congener, while in the other species PCB-153 (2, 2', 4, 4', 5, 5'-hexachlorobiphenyl) was the most persistent. The ratios of lower chlorinated PCB congeners (tri- to tetra-) to total PCBs were larger in fish-eating birds than in the other birds. The results indicate that the compositions of PCB congeners would reflect the differences of feeding habits and xenobiotic metabolizing systems among each species.

Animals↗

Antigenic and functional analyses of glycoprotein of rabies virus using monoclonal antibodies.

Thirty-five monoclonal antibodies (MAbs) against glycoprotein (G protein) of the RC-HL strain of the rabies virus have been established. Using these MAbs, two antigenic sites (I and II) were delineated on the G protein of the RC-HL strain in a competitive binding assay. Of these, 34 MAbs recognized the epitopes on site II. Site II was further categorized into 10 subsites according to their patterns in a competitive binding assay. Each site II-specific MAb showed 5 to 23 nonreciprocal competitions. The reactivities of 35 MAbs to rabies and rabies-related viruses in an indirect immunofluorescent antibody test showed that six MAbs in group A binded to rabies and rabies-related viruses and eight MAbs in group E reacted only with rabies viruses, considering that the former represent the genus-specific of Lyssavirus and the latter are rabies virus-specific. From biological assays, 28 of the 35 MAbs showed neutralization activity, 31 showed hemagglutination inhibition (HI) activity, and 18 showed immunolysis (IL) activity. The MAbs recognizing neutralization epitopes fell into at least three groups: those exhibiting both HI and IL activity, those showing only HI activity, and those showing neither HI nor IL activity. All IL epitopes overlap with HA epitopes. Five of the nine MAbs which reacted with the antigen treated by sodium dodecyl sulfate in ELISA were not reduced, or reduced only slightly, in the titer. None of the MAbs reacted with 2-mercaptoethanol-treated antigen. Only one MAb that recognized site I reacted with the denatured G protein in a Western blotting assay, indicating that its epitope is linear. These results suggest that almost all of the epitopes on the G protein of the rabies virus are conformation-dependent and the G protein forms a complicated antigenic structure.

Antibodies, Monoclonal↗

Serological surveillance of Lyme borreliosis in wild Japanese serows (Capricornis crispus).

Through serological surveillance of wild animals by enzyme linked immunosorbent assay with protein G (PG-ELISA), we obtained epidemiological data on Lyme borreliosis in Japanese wild animals. In this study, we carried out serological surveillance for Lyme borreliosis in wild Japanese serows (Capricornis crispus). Forty-six of 200 (23%) serum samples were positive, indicating that Lyme borreliosis is prevalent in wild Japanese serows. This positive rate was relatively higher than that of other animals and was similar/identical to that in other important hosts worldwide. Our results suggest that Japanese serows may be one of the important hosts of Lyme borreliosis in the central mountainous and forested areas of Japan.

Animals↗

[Transsphenoidal surgery and gamma-knife radiosurgery for a treatment of recurrent craniopharyngioma with moyamoya vessels].

A recurrent craniopharyngioma associated with moyamoya vessels was successfully treated by partial removal of the tumor via the transsphenoidal approach followed by gamma-knife radiosurgery. This 19-year-old man was first treated by partial tumor removal and radiotherapy (54Gy) at the age of 6 years. Growth hormone and human chorionic gonadotropin were given from the ages of 13 to 18 years. At ag 17 years, follow-up magnetic resonance imaging (MRI) revealed regrowth of the tumor. At the age of 19 years, he was readmitted for treatment of the enlarging remnant tumor. Neurological examination revealed bilateral blindness. MRI showed marked suprasellar, sphenoidal and bilateral cavernous sinus extension of the tumor. Angiography revealed stenosis of the right internal carotid artery and the M1 and A1 segments of the right cerebral arteries, as well as occlusion of the C3 segment of the left internal carotid artery. There were vault and ethmoidal moyamoya vessels. The patient underwent tumor removal via the transsphenoidal approach, instead of craniotomy, to avoid injury to the transdural anastomosis. The intrasellar solid tumor was partially removed. The tumor was then irradiated by the gamma knife. MRI 15 months after the treatment showed marked reduction of the tumor. The pathogenesis of the moyamoya phenomenon and the choice of the treatment in this patient are discussed.

Adult↗

A virus-neutralizing epitope on the glycoprotein of rabies virus that contains Trp251 is a linear epitope.

We have established a hybridoma producing monoclonal antibody (MAb) against a linear epitope of glycoprotein (G protein) of the RC-HL strain of rabies virus. This MAb15-13 showed almost the same neutralizing activity to all of five rabies fixed strains, including RC-HL, and reacted to the denatured G protein in western blot analysis. To characterize and map this linear epitope, an antigenic variant NR15-13 was selected from RC-HL strain in the presence of neutralizing MAb15-13. The variant reacted with MAb15-13 in an immunofluorescent antibody test but was not neutralized by the antibody and the antibody did not bind to the variant G protein in a Western blot analysis. The variant NR15-13 had an amino acid substitution at position 251 of the G protein, where tryptophan of the parental RC-HL strain was replaced by arginine. Site-directed mutagenesis analysis using the expression system in simian COS7 cells revealed that a single amino acid substitution at 251-tryptophan by arginine on the G protein of the parental RC-HL strain abolished the antigenicity of the epitope for MAb15-13 in western blot analysis, and the replacement of 251-arginine by tryptophan recovered the activity. These results strongly suggest that tryptophan at position 251 on the G protein is essential for construction of the linear epitope against MAb15-13.

Animals↗

Experimental myelitis caused by herpes simplex virus type 2 in C57BL/6N and BALB/cN mice.

Intraperitoneal and intracranial inoculation of herpes simplex virus type 2 (HSV 2) into BALB/cN and C57BL/6N mice was carried out to induce experimental myelitis. The myelitis was clearly observed in C57BL/6N mice following intraperitoneal inoculation. Within 24 hours before death, the mice showed urinary and rectal incontinence and paraplegia of the hind legs. Randomly distributed, severe necrosis was demonstrated in the spinal cord, mainly at the lower cord. In BALB/cN mice the clinical symptoms were not clearly observed, as the mice died shortly after their onset. Although spinal cord necrosis was more prominent in C57BL/6N mice than BALB/cN mice, brain necrosis was only found in the latter, and not in the former. Both strains of mouse showed marked nuclear pyknosis of the nerve cells and slight nuclear pyknosis of the astrocytes in the brain where HSV 2 antigen was demonstrated immunohistochemically. The antigen was also detected in the necrotic spinal cord. In contrast, intracranial inoculation of the virus into both strains did not cause myelitis. Spinal cord necrosis was not demonstrated and virus DNA was not detected, by PCR, in spinal cord samples. In the brain, however, the virus was demonstrated by both PCR and immunohistochemistry.

Animals↗