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Biomedical subjects

K Tashiro

Publications and source records attributed to K Tashiro.

At least 217 records · Page 12Linked to original sources

Cloning of Xenopus Dr1 (TBP-binding repressor) and its expression in oocytes and early embryos.

With a final goal to study how TBP-binding repressor Dr1 regulates transcription in Xenopus early embryos, we cloned its cDNA from Xenopus liver cDNA library. The cDNA was 1,986 bp long, with the open reading frame coding for 175 amino acids, whose sequence was highly homologous to its human counterpart. Xenopus Dr1 mRNA was expressed from the earliest stage of oogenesis, inherited as maternal mRNA at a high level, but its level became low at and after the neurula stage where RNA synthetic activity is strongly activated. Dr1 mRNA occurred in larger amounts in the animal half than in the vegetal half in 8-cell stage embryos, and in neurula and tailbud stage embryos its distribution was slightly larger in the anterior part than in the posterior part. These data show that Dr1 mRNA is expressed in a temporally and spatially regulated manner, and its occurrence at higher levels in earlier stage embryos may be responsible for their low transcriptional activity.

Amino Acid Sequence↗

Immunohistochemical localization of D-aspartate in the rat pineal gland.

Specific polyclonal antibody was raised against D-aspartate (D-Asp) which had been conjugated to glutaraldehyde and was purified by affinity chromatography. Immunohistochemical staining of rat pineal gland with the antibody demonstrated the presence of D-Asp in the cytoplasm of pinealocytes, the predominant cell type in this gland. D-Asp immunoreactivity was more evident in the distal region than in the proximal region of the gland. Pinealocytes in the distal region are presumably involved in the synthesis and secretion of the pineal hormone, melatonin, and the results of staining may indicate some yet unknown role of D-Asp in the regulation of melatonin secretion.

Animals↗

Molecular cloning of a novel mouse aspartic protease-like protein that is expressed abundantly in the kidney.

By use of the signal sequence trap method, we isolated a cDNA encoding a novel aspartic protease-like protein from the mouse kidney, and termed it 'kidney-derived aspartic protease-like protein (KAP).' The protein, a 419-amino-acid polypeptide with a 16-amino-acid signal sequence, had 47% identity with mouse cathepsin D, and its overall structure was closely related to known aspartic proteases. Northern blot analysis revealed that KAP mRNA is expressed at the highest level in the kidney, at a moderate level in the lung, and at low levels in the spleen and adipose tissue. In situ hybridization analysis demonstrated that the mRNA is expressed abundantly in the proximal straight tubule and slightly, but significantly, in the proximal convoluted tubule in the kidney. This intra-renal distribution differs distinctly from those of previously reported proteases such as cathepsins B, D, and H.

Amino Acid Sequence↗

Clonal integration and expression of human T-cell lymphotropic virus type I in carriers detected by polymerase chain reaction and inverse PCR.

Adult T-cell leukemia (ATL) is a neoplasm of mature helper (CD4) T lymphocytes, and human T-cell lymphotropic virus type-I (HTLV-I) has been suggested to be the causative virus of ATL. HTLV-I integrates its proviruses into random sites in host chromosomal DNA. Clonal integration has been observed in patients with ATL, including smoldering, chronic, and acute states. However, random and/or polyclonal integration has only been reported in a few asymptomatic HTLV-I carriers. To clarify the clonality of HTLV-I-infected cells in carriers, we used an inverse polymerase chain reaction (IPCR), which is more sensitive than Southern blot analysis. We used the peripheral blood momonuclear cells (PBMC) from 16 asymptomatic carriers and the separated CD4-positive cells. No cases showed either a monoclonal or polyclonal integration of the HTLV-I provirus by Southern blot. But, using IPCR, 7 of 16 cases showed either mono- or oligoclonal integration. In addition, the populations of clonal provirus in the total PBMC were frequently different from those in the CD4-positive cells. Three cases showed expression of HTLV-I tax/rex mRNA in the total PBMC, but no such expression was found in CD4-positive cells. In this study, an unexpected frequency of clonal HTLV-I provirus DNA was observed in HTLV-I carriers. These findings indicate that the clonal but nonmalignant proliferation of HTLV-I-infected cells already occurs even in HTLV-I carriers, and therefore that some other step is necessary to induce malignant proliferation.

Adolescent↗

Terminal deoxynucleotidyl transferase staining of malignant lymphomas in paraffin sections: a useful method for the diagnosis of lymphoblastic lymphoma.

Terminal deoxynucleotidyl transferase (TdT) is a DNA polymerase located in the cell nucleus which catalyses the polymerization of deoxynucleotides at the 3'hydroxyl ends of oligo- or polydeoxynucleotide initiators without a template. TdT is known as a useful marker for the diagnosis of acute lymphoblastic leukaemia/lymphoma, but its detection usually requires fresh tissue specimens or cell suspensions, using either an enzyme analysis or immuno-fluorescence or -peroxidase staining. Until the recent development of the use of microwave-treated paraffin sections for immunoperoxidase staining, detection of TdT in paraffin sections required rather complicated processes. This new simple technique was applied to paraffin sections from the tumour tissue specimens of 16 patients with lymphoblastic lymphoma and of seven patients with non-endemic Burkitt's lymphoma, which is sometimes difficult to differentiate from lymphoblastic lymphoma because of their similar clinicopathological characteristics. In addition, as a control, ten cases each were examined of adult T-cell leukaemia/lymphoma (ATLL) and angioimmunoblastic lymphoma (AILD), which are both peripheral T-cell lymphomas. The tumour cells from 15 of the 16 (94 per cent) patients with lymphoblastic lymphoma were found to be TdT-positive. The specificity of the anti-TdT antibody used was confirmed by immunoblot and the specific 60 kD band was detected only in a specimen of lymphoblastic lymphoma. These results show that the immunostaining of TdT on paraffin-embedded sections is a useful method for differentiating lymphoblastic lymphoma from other lymphomas. This method is applicable to a routine diagnostic service.

Adolescent↗

Assignment of the possible HTLV receptor gene to chromosome 17q21-q23.

We have determined the HTLV (Human T-cell leukemia virus) receptor localization more precisely on the human chromosome 17. Based on the fact that HTLV infection induces syncytium formation of infected cells as a result of interaction between the viral envelope and viral receptor, we performed the sensitive biological assay using recombinant vaccinia expression system. Our results from the induced syncytium pattern of the somatic hybrid cell lines with different deletions indicated that the HTLV receptor gene may reside from q21 to q23 on the long arm of the human chromosome 17.

Animals↗

Dominantly inherited leukodystrophy showing cerebellar deficits and spastic paraparesis: a new entity?

We studied a dominant hereditary disorder showing progressive spastic paraparesis. The symptoms began in early childhood, with cerebellar deficits and mild mental deterioration, and the subsequent appearance of limb spasticity resulted in severe disability in the 3rd-4th decades of life. None of the patients were associated with any somatic abnormalities. Brain MRI showed diffuse white-matter involvement in all affected patients, but not in unaffected siblings. Although dominant, recessive, or X-linked leukodystrophies cause similar clinical features, our family did not show any known biochemical or gene deficits characteristic of these disorders. The clinical, radiological, and biochemical findings of this family are reported and suggest a possible novel genetic disorder.

Adult↗

Anti-nuclear antibodies and the optic-spinal form of multiple sclerosis.

We found anti-nuclear antibodies (ANA) (1:20 or higher) in sera from 11 of 16 patients with a diagnosis of the optic-spinal form of multiple sclerosis (OpS-MS) and 13 of 59 patients with other forms of MS (other MS), both rates being significant (P = 0.0004). Six of the OpS-MS patients had a high level of ANA (1:80 or higher), while levels were high in only three of the other MS patients, showing a significant difference (P = 0.0022). Titres of ANA were significantly higher in OpS-MS patients than in other MS patients (P < 0.0001). There was no relationship between the presence of ANA and age in OpS-MS patients, while patients with were older than those without high ANA levels among other MS patients. ANA-positive rate and titres were significantly higher in OpS-MS patients than in sex- and age-matched other MS patients. These results support the concept that OpS-MS constitutes a distinct subgroup among patients with a clinical diagnosis of MS and may indicate that systemic dysregulation of the inflammatory or immune response is more common in OpS-MS patients; the possible pathogenetic relevance of ANA-associated vasculopathy to some patients with a clinical diagnosis of OpS-MS should be considered.

Adult↗

Facial palsy in multiple sclerosis.

Facial palsy occurred in 21 (19.6%) of 107 Japanese patients with multiple sclerosis (MS) during a mean follow-up period of 4.3 years. We observed residual signs of facial palsy in five other patients in whom acute onset was confirmed from medical records. Facial palsy began on average 7.6 years after the onset of MS but in five patients (4.7%) was the first symptom of MS, preceding the next MS symptom by 0.5-3 years. Facial palsy was usually associated with other brainstem signs, while two patients showed only facial palsy 1 and 3 years after the onset of MS. Twenty-one (84.0%) of the 25 patients who underwent brain magnetic resonance imaging (MRI) showed brainstem lesions in the pontine tegmentum ipsilateral to the facial palsy. However, the two patients without other symptoms or signs had no apparent causal lesion on MRI, which suggests difficulty in differentiating idiopathic Bell's palsy from MS- associated facial palsy by MRI, although it has an excellent capacity to detect causal lesions of facial palsy associated with MS.

Adult↗

Identification of cell types producing RANTES, MIP-1 alpha and MIP-1 beta in rat experimental autoimmune encephalomyelitis by in situ hybridization.

The chemokines RANTES, macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta are members of the beta-family of chemokines and potent chemoattractants for lymphocytes and monocytes. To investigate the factors which regulate lymphocyte traffic in experimental autoimmune encephalomyelitis (EAE), we studied, by in situ hybridization analysis, the kinetics of mRNA expression and the potent cellular sources of RANTES, MIP-1 alpha and MIP-1 beta in the central nervous system (CNS) during the course of EAE. RANTES-positive cells appeared in the subarachnoid space and infiltrated the subpial region at around day 10, increased to a peak at days 12-13 and then decreased following the resolution of the acute phase of EAE, though elevated RANTES message expressions still remained on chronic subclinical stage. Most of RANTES positive cells were identified as T-lymphocytes located mainly around blood vessels, by combined studies of in situ hybridization and immunohistochemistry. The remainder of the RANTES-positive cells were astrocytes and macrophages/microglia. MIP-1 alpha and MIP-1 beta mRNA-positive cells appeared around day 10, increased further on days 12-13 and then gradually decreased. Most of the MIP-1 alpha- and MIP-1 beta-positive mononuclear cells were located around blood vessels. The kinetics of RANTES, MIP-1 alpha and MIP-1 beta expression paralleled those of the recruitment of infiltrating inflammatory cells and disease severity. Our observations support the possibility that chemokine production by T-cells, macrophages and astrocytes lead to the infiltration of inflammatory cells into the CNS parenchyma during the acute phase of EAE.

Animals↗

Malignant histiocytosis-like B-cell lymphoma, a distinct pathologic variant of intravascular lymphomatosis: a report of five cases and review of the literature.

Malignant histiocytosis (MH)-like B-cell lymphoma (BCL) is a neoplastic proliferation of large B cells clinically characterized by fever, hepatosplenomegaly, haemophagocytosis and abnormal laboratory data, without lymphadenopathy or skin lesions. Interestingly, most cases have been reported in Asian patients, and it is unclear whether MH-like BCL is biologically distinct from conventional large B-cell lymphomas. We report five Japanese patients with MH-like BCL. Biopsied specimens of bone marrow, liver and/or spleen showed infiltration of neoplastic B cells accompanied by haemophagocytosing histiocytes. Lymphoma cells were positive for CD19, CD20 and HLA-DR surface antigens, and negative for CD5 and CD10. In four cases elevated serum levels of interleukin (IL)-6 and the soluble IL-2 receptor isoform were noted, but not IL-1beta, IL-2 or tumour necrosis factor-alpha. Autopsies of two cases were pathologically diagnosed as intravascular lymphomatosis (IVL). Based on these observations, the current and nine previous cases reported as MH-like BCL in Japan were re-evaluated. They appear to form a peculiar variant of IVL, characterized by bone marrow involvement at presentation, haemophagocytic syndrome, and a rapidly aggressive clinical course, but rarely neurological complications or skin lesions. This variant may merit separate consideration because of the problems posed in the initial diagnosis and therapeutic approaches.

Aged↗

Two closely-related left-right asymmetrically expressed genes, lefty-1 and lefty-2: their distinct expression domains, chromosomal linkage and direct neuralizing activity in Xenopus embryos.

BACKGROUND: Vertebrates have numerous lateral asymmetries in the position of their organs, but the molecular basis for the determination of left-right (L-R) asymmetries remains largely unknown. TGFbeta-related genes such as lefty and nodal are L-R asymmetrically expressed in developing mouse embryos, and may be involved in L-R determination. RESULTS: We have identified two highly conserved genes, lefty-1 and lefty-2, in the mouse genome. These two genes are tightly linked on mouse chromosome 1. lefty-1 and lefty-2 are both expressed in a L-R asymmetric fashion in mouse embryos. However, the major expression domains of the two genes are different: lefty-1 expression is predominantly confied to the left side of ventral neural tube, whereas lefty-2 is strongly expressed in the lateral plate mesoderm on the left side. In embryos homozygous for the iv and inv mutation, which cause situs inversus, the expression sites of both genes are affected, either reversed or bilaterally, indicating that lefty-1 and lefty-2 are downstream of iv and inv. Although Lefty-1 and Lefty-2 prepro-proteins are not readily processed in cultured cells, BMP2-Lefty chimeric proteins can be processed to a secreted form. We have examined the activities of Lefty-1 and Lefty-2 in Xenopus embryos. In animal cap explants, Lefty-1 and Lefty-2 induce neural cells in the absence of mesoderm induction. The direct neuralizing activities of Lefty-1 and Lefty-2 thus seem remarkably similar to those of BMP antagonists such as noggin and chordin, suggesting that the action of Lefty-1 and Lefty-2 may be to locally antagonize BMP (bone morphogenic protein)-mediated signals in tissues positioned on the left side of the mouse embryos. CONCLUSION: There are two lefty genes in mice (lefty-1 and lefty-2), both of which are expressed in a L-R asymmetric fashion and are downstream of iv and inv. Lefty-1 and Lefty-2 possess direct neuralizing activity in Xenopus embryos, resembling the activities of BMP antagonists.

Amino Acid Sequence↗

Effects of surfactant proteins SP-B and SP-C on dynamic and static mechanics of immature lungs.

To investigate the effects of surfactant proteins B (SP-B) and C (SP-C) on lung mechanics, we compared tidal and static lung volumes of immature rabbits anesthetized with pentobarbital sodium and given reconstituted test surfactants (RTS). With a series of RTS having various SP-B concentrations (0-0.7%) but a fixed SP-C concentration (1.4%), both the tidal volume with 25-cmH2O insufflation pressure and the static volume deflated to 5-cmH2O airway pressure increased, significantly correlating with the SP-B concentration: the former increased from 6.5 to 26.0 ml/kg (mean), and the latter increased from 6.4 to 31.8 ml/kg. With another series of RTS having a fixed SP-B concentration (0.7%) but various SP-C concentrations (0-1.4%), the tidal volume increased from 5.1 to 24.8 ml/kg, significantly correlating with the SP-C concentration, whereas the static volume increased from 3.4 to 32.0 ml/kg, the ceiling value, in the presence of a minimal concentration of SP-C (0. 18%). In conclusion, certain doses of SP-B and SP-C were indispensable for optimizing dynamic lung mechanics; the static mechanics, however, required significantly less SP-C.

Animals↗

Nine-year follow-up study of bromocriptine monotherapy for Parkinson's disease.

A 9-year nationwide study of bromocriptine monotherapy and combination therapy with bromocriptine and levodopa in Parkinson's disease is reported. Eleven patients were on bromocriptine monotherapy, 35 patients were on combined treatment of bromocriptine and levodopa for a certain time during a 9-year period. Maintenance doses of bromocriptine at the end of the 9th year in the two groups were 11.1 mg/day in the monotherapy and 12.7 mg/day in the combination therapy group with levodopa. Changes in Hoehn and Yahr's grading between the time of trial start and the end of 108 months' treatment revealed that 5 of 11 cases in the monotherapy group remained in the same stages, the other 2 cases improved in condition from stage II to I, and another 4 deteriorated compared with pretreatment grade. On the other hand, 20 of 35 cases in the combination-therapy group reached more advanced stages, 3 patients moving to stage V. Four of them, however, improved, and 11 did not change at the end of 9 years of treatment. Although it is difficult to prove the neuroprotective effect of a dopamine receptor agonist, our long-term nation-wide collaborative studies will help us to answer the question of how bromocriptine works in pharmacokinetic aspects.

Aged↗

Nationwide multicenter prospective study on the long-term effects of bromocriptine for Parkinson's disease. Final report of a ten-year follow-up.

A 10-year nationwide multicenter prospective study on the long-term efficacy of bromocriptine for Parkinson's disease is reported. Six patients remained on bromocriptine monotherapy for 10 years, while 22 patients achieved good disease control with bromocriptine plus levodopa (added during the course of the study). In the 6 patients on bromocriptine alone, the disease remained in Hoehn and Yahr stage I or II for 10 years. In the other 22 patients on bromocriptine plus levodopa therapy, disease progression was very slow for 7-8 years. None of the 6 patients remaining on bromocriptine monotherapy experienced adverse reactions like the wearing-off phenomenon, dyskinesia, or the on-off phenomenon. Among the 22 patients who started levodopa therapy during the course of the study, these adverse reactions to levodopa were infrequent (10, 3, and 3 patients, respectively). Thus, early introduction and long continuation of bromocriptine therapy with restricted concomitant use of levodopa may have led to very slow disease progression and the suppression of adverse reactions. Although the patients who could be maintained long-term on bromocriptine monotherapy might represent a population who have very slowly progressive disease, their adequate disease control and the low incidence of adverse reactions in the patients who later started concomitant levodopa suggest that the unwanted effects of levodopa may be reduced by early and sustained treatment with bromocriptine. Introduction of bromocriptine monotherapy at an early stage of Parkinson's disease or with restricted use of additional levodopa therapy to bromocriptine when necessary may be a useful strategy for achieving adequate and sustained disease control.

Aged↗

A case of lupus nephritis showing good clinical course and apoptosis in glomerular cells detected by the nick end labeling method.

We report here an adult patient with lupus nephritis who had a good clinical course under long-term observation. Apoptotic bodies in the glomeruli were determined in serial renal biopsy specimens by the nick end labeling method. Apoptotic bodies in the proliferated glomerular cells were detected in the 3rd renal biopsy but not in the 2nd biopsy. The clinical activities of lupus nephritis fluctuated until the time of the 3rd renal biopsy. The 3rd renal biopsy was performed because of increased proteinuria and an increased amount of hyaline, granular and red blood cell casts, with impairment of renal function. The levels of proteinuria, creatinine clearance and serum complements were improved after the 3rd renal biopsy. It appears that apoptosis might control glomerular cell proliferation and also influence the clinical course of lupus nephritis.

Adult↗

Spinocerebellar ataxia type 1 and familial spontaneous pneumothorax.

We report two siblings with spinocerebellar ataxia type 1 (SCA1) who experienced frequent episodes of spontaneous pneumothorax. Radiologic findings indicated underlying degenerative changes in the lungs. This suggests a possible pathophysiologic relationship between SCA1 and familial occurrence of spontaneous pneumothorax.

Adult↗