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Biomedical subjects

M Katsuno

Publications and source records attributed to M Katsuno.

At least 19 recordsLinked to original sources

Plasticity of fitness and diversification process during an experimental molecular evolution.

A simplified experimental evolution encompassing the essence of natural one was designed in an attempt to understand the involved mechanism. In our system, molecular evolution was observed through three serial cycles of consecutive random mutagenesis of the glutamine synthetase gene and chemostat culture of the transformed Escherichia coli cells containing the mutated genes. Selection pressure was imposed solely on the glutamine synthetase gene when varieties of mutant genes compete in an unstructured environment of the chemostat. The molecular phylogeny and population dynamics were deduced from the nucleotide sequences of the genes isolated from each of the chemostat runs. An initial mutant population in each cycle, comprised of diversified closely-related genes, ended up with several varieties of mutants in a state of coexistence. Competition between two mutant genes in the final population of the first cycle ascertained that the observed coexisting state is not an incidental event and that cellular interaction via environmental nutrients is a possible mechanism of coexistence. In addition, the mutant gene once extinct in the previous passage was found to have the capacity to reinvade and constitute the gene pool of the later cycle of molecular evolution. These results, including the kinetic characteristics of the purified wild-type and mutant glutamine synthetases in the phylogenetic tree, revealed that the enzyme activity had diverged, rather than optimized, to a fittest value during the course of evolution. Here, we proposed that the plasticity of gene fitness in consequence of cellular interaction via the environment is an essential mechanism governing molecular evolution.

Escherichia coli↗

[A case of familial hypokalemic periodic paralysis with hyperuricemia during paralytic attack and genetic analysis of the pedigree].

We reported a 13-year-old boy and his family with hypokalemic periodic paralysis. He showed marked hyperuricemia during his paralytic attack, although neither ischemic forearm exercise test nor bicycle-ergometer exercise test revealed myogenic hyperuricemia when he was free from paralysis. Genetic analysis was performed to the proband and his affected elder brother, mother, and, maternal grand mother. We found the Arg528His mutation of CACNL1A3 gene in all the patients examined. The severity of the attacks and the age of onset did not vary in the different generations, and male predominancy was not evident in this family.

Adolescent↗

Familial cluster of cutaneous Mycobacterium avium infection resulting from use of a circulating, constantly heated bath water system.

We describe familial cases of cutaneous infection caused by Mycobacterium avium. A 45-year-old father, his 14-year-old son and 11-year-old daughter, among five persons in a family, presented with a 2-month history of inflammatory subcutaneous nodules and ulcerations. Histology of skin biopsy specimens showed granulomatous inflammation, and mycobacterial colonies isolated from the skin of each patient were identified as M. avium by DNA hybridization analysis. The patients were all treated successfully with combined drug therapy consisting of rifampicin, isoniazid and clarithromycin. Their lesions were purely cutaneous M. avium infection, without any visceral involvement. Neither systemic disease nor immunological impairment was detected in the family. However, they all used a circulating, constantly heated bath water system. The bath water was continuously heated to about 40 degrees C without changing the water for a few months, and M. avium was isolated from the filter of the bath tub heating unit. It is considered that this unusual familial cluster of cutaneous M. avium infection in healthy persons may have resulted from the use of contaminated bath water.

Adolescent↗

T-stem cell leukemia/lymphoma with both myeloid lineage conversion and T-specific delta recombination.

We evaluated retrospectively the clinical and biological characteristics of six patients with CD7+ early T-acute lymphoblastic leukemia and lymphoma (T-ALL/LBL) originating from prothymocyte stage I (pro-T I) or II cells. Patients exhibited mediastinal mass (five of six) and lymphoadenopathy (five of six) but without leukocytosis and circulating blast cells (six of six). All patients achieved a complete remission. All but one had a relapse with a transformation to the mixed type (triphenotype--three cases, biphenotype-two cases) including myeloid features in three patients. The altered phenotypes were myeloperoxidase (MPO)+ (three of five), CD13+ (four of five), CD33+ (three of five) and CD19+ (three of five). The difference for MPO-positivity were observed between the bone marrow (BM)- and lymph node (LN)-blast cells (three of three). On cytogenetic analysis, there is no common abnormality in these patients. Immunomolecular analysis revealed T-cell lineage specific delta gene rearrangements [D delta 2-J delta 1 (five of six) and V delta 1-J delta 1 (one of six)] in all cases. Furthermore, D delta 2-J delta 1 occurred even in the cases with the pro-T I phenotype. Rearrangements of TCR beta, gamma or immunoglobulin heavy chain genes occurred in three patients. The same rearranged band(s) appeared at both diagnosis and relapse, indicating the same originality of the pro-T leukemic cell clone (three of three). We suggest that this type of CD7+ early T-ALL/LBL was transformed from a pro-T I or II cell, such as T-stem cell leukemia/lymphoma, which is a subtype of CD7+ stem cell leukemia as defined by Kurtzberg et al. This study reveals that pro-T I and II cells might be capable of myeloid, T- and B-lymphoid differentiation, and T-cell lineage specific TCR delta recombination occurs.

Adult↗

[Usefulness of on-line spirometry in bronchospasm occurring during anesthesia].

A 45-yr-old asthmatic male was undergoing urgent clipping of the cerebral aneurysm. On-line spirometry was performed by a Ultima produced by Datex Co., Ltd. Bronchospasm occurred just after the endotracheal intubation. Inspiratory airway pressure increased and ausculation of the chest revealed bilateral wheezing. On the screen of the ventilatory monitor, right- and downward shift of P-V loops was noted. Intravenous and inhalational bronchodilator therapy was started. Symptoms improved gradually and P-V loops were also normalized. This case demonstrates that the on-line spirometry is useful for estimating and recording the severity of the bronchospasm occurring during anesthesia.

Anesthesia, General↗

Expression of EVI1 and the Retinoblastoma genes in acute myelogenous leukemia with t(3;13)(q26;q13-14).

The EVI1 DNA-binding protein gene on chromosome 3q26 has been reported to be activated in some leukemia cells with alterations in 3q26. We present an acute myelogenous leukemia (AML) patient with a rare chromosomal translocation, t(3;13)(q26.2;q13-14). By reverse transcription-polymerase chain reaction, we detected active transcription of the EVI1 gene in the patient's leukemia cells. The retinoblastoma susceptibility (Rb) gene, a tumor-suppressor gene, is located at chromosome 13ql4 and is within the other translocation breakpoint in this patient. The expression of the Rb gene product was found to be substantially decreased in the patient's leukemia cells by Western blotting. Southern blot analysis, however, revealed no gross abnormalities of the Rb gene. Although it is unlikely that the Rb gene is directly involved in this translocation, the loss of the Rb gene product combined with the activation of the EVI1 gene may have led to the development of leukemia.

Asian People↗

Acute leukemias expressing p210-and p 190-type bcr/abl mRNAs: report of two cases and review of the literature.

We report two patients with acute leukemias who expressed two types of bcr/abl mRNA. The first case was an 8-year-old boy with acute mixed leukemia in whom the Ph1 chromosome and p210/p190 types of bcr/abl mRNAs were detected at diagnosis. The second case was a 39-year-old male with acute nonlymphocytic leukemia transformed from myelodysplastic syndrome (refractory anemia with excess of blasts). In the latter case, the p210-type mRNA appeared after leukemic transformation, and the p190-type transcript was detected only during the late stage when the Ph1 chromosome was first observed. The leukemias in these two patients were aggressive in their clinical courses. We conclude that the dual expression of p210 and p190 types of bcr/abl is a factor indicating a poor prognosis, and that, in some patients, p190-type bcr/abl may contribute to disease progression.

Acute Disease↗

[Usefulness of brachial artery pressure with forearm compression as arterial pressure monitoring after cardiopulmonary bypass].

The pressures in the radial and brachial artery in the same extremity were measured before and after cardiopulmonary bypass (CBP) in 18 patients. Brachial pressures were measured in two different ways, with and without forearm compression. The forearm compression was achieved by a swelled blood pressure cuff. There were no significant differences in these pressures before CBP. But the brachial pressures with the forearm compression were the highest among three kinds of pressures after CBP and there were significant differences between them. The aortic pressures during weaning from CBP were measured and compared with these pressures in 4 patients. The brachial pressures with the forearm compression were closest to aortic pressures. Therefore brachial pressure with forearm compression was recommended as a good pressure monitor when CPB was about to be finished. The patients were them divided into two groups. The patient is in the first group had less than 10 mmHg pressure difference between brachial pressure and radial pressure just after CPB. The patients in the second group had higher pressure in brachial than those in radial for over 10 mmHg just after CPB. There were no significant differences in duration in CPB, lowest rectal temperature, hematocrit and doses of catecholamines between the two groups.

Aged↗

Cyclophosphamide-induced tolerance in fully allogeneic heart transplantation in mice.

We have established a long-lasting heart allograft tolerance in H-2-incompatible combinations by intravenous injection of 10(8) allogeneic spleen cells followed by the administration of 200 mg/kg of cyclophosphamide (CP). When C57BL/10 mice (B10, H-2b) were primed iv with 1 x 10(8) viable spleen cells from naive BALB/c mice (H-2d) and treated ip with 200 mg/kg CP 2 days later, BALB/c heart allografts were lasting in the recipients for as long as 8 weeks. On the other hand, B10 mice receiving either allogeneic spleen cells or CP rejected the heart allograft within 10 days after transplantation. A direct approach assessing the donor-reactive T cells for frequency and reactivity showed that the donor-reactive T cells were partially deleted and the rest were rendered unresponsive. CP-induced tolerance may be applied for the induction of antigen-specific tolerance to allogeneic heart transplantation.

Animals↗

Late-appearing Philadelphia chromosome in a patient with acute nonlymphocytic leukaemia derived from myelodysplastic syndrome: detection of P210- and P190-type bcr/abl fusion gene transcripts at the leukaemic stage.

We describe a patient with acute nonlymphocytic leukaemia (ANLL) derived from myelodysplastic syndrome in whom the Philadelphia chromosome (Ph1) first emerged at the late stage of ANLL transformation. Cytogenetically, the Ph1 chromosome was not detected until the late stage of ANLL transformation, 14 months after the transformation following a 3-month history of refractory anaemia with excess of blasts. The cells with and without the Ph1 chromosome had a common abnormal chromosome, t(3;3) (q21;q26). The reverse transcription-polymerase chain reaction analysis showed no bcr/abl message at diagnosis. However, the mRNA encoding P210bcr/abl was detected in the early stage of ANLL transformation. Furthermore, the mRNAs encoding both P210bcr/abl and P190bcr/abl were detected in the late stage of ANLL transformation when the Ph1 chromosome was detected by cytogenetic analysis. These evidences support a multistep pathogenesis of leukaemias, and the products of bcr/abl fusion gene may influence the course of disease.

Adult↗

[A comparative study of imipenem/cilastatin sodium BID vs QID in the treatment of infections associated with hematopoietic disorders].

Using the envelope method, we allocated 125 patients with infections accompanied by hematopoietic disorders into two groups treated with imipenem/cilastatin sodium (IPM/CS) at a daily dose of 1 g/1 g b.i.d. (group BID) or 0.5 g/0.5 g q.i.d. (group QID), and obtained the following results. 1. In group BID, ANLL was observed in 25 patients; ALL in 6; and NHL in 12. In group QID, ANLL was observed in 27 patients; ALL in 7; and NHL in 13. 2. In group BID, efficacy rates were 54.5% (6/11) in sepsis, 63.0% (17/27) in fever of undetermined origin and 50.0% (4/8) in pneumonia, thus the overall efficacy was 61.8% (34/55). In group QID, efficacy rates were 66.7% (4/6) in sepsis, 76.0% (19/25) in fever of undetermined origin and 35.7% (5/14) in pneumonia, thus the over all was 61.1% (33/54). No significant difference in response rates were observed between the two groups. 3. Bacteriologically, 22 bacterial strains were isolated in group BID and 21 21 strains, in group QID. The eradication rates after treatment with IPM/CS was 100% in group BID and 66.7% in group QID. 4. Side effects were observed in 8 patients in group BID and 3 in group QID. Laboratory examination revealed abnormal values in 9 patients in group BID and 6 in group QID. However, all of the side effects disappeared after the suspension or discontinuation of IPM/CS. The efficacies of IPM/CS therapy for severe infections in patients with hematopoietic disease were similar between 1 g/1 g b.i.d. and 0.5 g/0.5 g q.i.d. groups.

Adult↗

CD7+ stem cell leukemia/lymphoma. Features of a subgroup without circulating blast cells.

Recent advances in immunology have clarified the cellular origin of hematopoietic neoplasms. Blast cells with a CD7+ CD4- CD8- phenotype are demonstrated to originate from malignant pluripotent hematopoietic stem cells. In this article, the authors describe three rare cases, designated as a lymphoma type of CD7+ stem cell leukemia/lymphoma, with clinical features described below. All three patients were admitted with non-Hodgkin lymphoma with a 2-month to 4-month history of lymphadenopathy. Histologic examination of lymph nodes showed lymphoblastic lymphoma (LBL) in all patients. Bone marrow blast cells had an immunophenotype consistent with CD7+ CD4- CD8- acute leukemia, although abnormal cells were not observed in the peripheral blood during the course of the disease. One patient had a recurrence in the bone marrow, with myeloperoxidase-positive blast cells expressing myeloid differentiation antigens. Chromosomal analysis detected a common abnormal karyotype initially and at relapse. Furthermore, the same T-cell receptor gene rearrangement was found initially and at relapse, suggesting that these blast cells originated from the same pluripotent leukemic clone. Additional studies on more patients are required to determine the clinical significance of this group, including the difference from CD7+ stem cell leukemia/lymphoma with circulating blast cells (leukemic type) or LBL.

Acute Disease↗

PML/RAR alpha fusion gene is expressed in both granuloid/macrophage and erythroid colonies in acute promyelocytic leukaemia.

Acute promyelocytic leukaemia (APL) associated with a t(15;17) translocation generates a PML/RAR alpha chimaeric gene which is transcribed as a fusion PML/RAR alpha mRNA. To clarify the pathophysiologic role of PML/RAR alpha in APL patients, we examined the expression of PML/RAR alpha in haemopoietic colonies in five patients with APL by reverse transcriptase polymerase chain reaction (RT-PCR) analysis. By the two-step RT-PCR method, we demonstrated that PML/RAR alpha positive clones were present in progenitor cells including both CFU-GM and BFU-E in two cases. This result suggests that the translocation of PML/RAR alpha occurred in a pluripotent stem cell in some APL patients. In four patients we detected two amplified cDNA fragments of 780 and 640 bp which presumably arose by alternative splicing of the PML gene. Interestingly, of CFU-GM and BFU-E colonies examined in four patients, there were three different types of colonies: those expressing only the 780 bp fragment, those expressing only the 640 bp fragment, and those expressing both fragments. This suggests that alternative splicing was clonally determined in each colony. We describe a useful RT-PCR technique for the study of gene expression in a limited number of haemopoietic precursor cells.

Adult↗

Targeted in vivo infection with a retroviral vector carrying the interleukin-3 (multi-CSF) gene leads to immortalization and leukemic transformation of primitive hematopoietic progenitor cells.

To measure the effect of endogenous IL-3 (Multi-CSF) expression on hematopoietic cells in vivo, we have infected several kinds of hematopoietic cell populations with retroviral vectors carrying the IL-3 gene (M3MuV) in vitro and injected the virus-producing cells into mice to "target" the virus to sites of hematopoiesis. Mast cell lines (Elut cells) or multipotent cell lines (FDC-Pmix) were infected with MPSV-based replication defective retroviral vectors carrying either the neomycin resistance gene alone (M3neoV) or the neomycin gene plus the IL-3 gene (M3MuV). These cell lines produced infective retroviral particles consisting of the replication defective vectors and helper virus constitutively produced by the target cell populations. Irradiated and non-irradiated virus-producing Elut cells and the virus-producing FDC-Pmix cells were transplanted into syngeneic mice to "target" virus infection to the sites of hemopoiesis. Control mice injected with M3neoV-producing cells did not develop a disease up to 6 months following transplantation, whereas mice injected with M3MuV-producing cells developed a myeloproliferative disease within 3 months. Hematopoietic cell lines were rescued from diseased and control mice. In all cases these cell lines were of host origin. Cell lines derived from control mice were of basophil/mast cell morphology only, and required IL-3 for their continued proliferation (similar to cell lines derived from uninfected animals), whereas the cell lines generated from spleen and bone marrow cells of host mice with myeloproliferative disease carried the M3MuV vector, were G418 resistant and IL-3 independent. The biologic properties of M3MuV infected host derived cell lines varied considerably. Some were multipotential and could be induced to differentiate in response to stromal cells and serum factors, others were more restricted to the granulocyte/macrophage lineage but were also differentiation inducible, and some were blocked in differentiation at the myeloblast/promyelocyte stage. We conclude that the injected donor cells acted as "infectious centers" to facilitate the infection of host hematopoietic cells with the M3MuV vector. Our results indicate that the "targeted" in vivo infection of primitive hematopoietic cells with M3MuV can initiate the immortalization and leukaemogenesis of multipotential and lineage restricted progenitor cells.

Animals↗

[Epidural opioids for post-operative pain control in pediatric patients with cerebral palsy].

The safety and efficacy of epidural opioids as postoperative analgesics for children with cerebral palsy were studied in 85 pediatric patients with cerebral palsy. The patients were 5 to 15 years of age and were undergoing elective orthopedic operations on the lower extremities. These patients were divided into four groups. All the patients received inhalational anesthesia combined with caudal anesthesia, while the patients in groups 2, 3, and 4 were given epidural morphine (40 micrograms.kg-1), buprenorphine (3 micrograms.kg-1), or butorphanol (30 micrograms.kg-1) at the end of operation, respectively. Number of patients who received analgesics more than 2 times within 24 hours after operation was larger in group 1 than in groups 2-4. Although groups 2-4 compared with group 1 were still sedated at 24 hours after the operation, there was no difference in degree of sedation among the groups 2-4. The epidural opioids did not increase the frequency of side effects such as nausea, vomiting etc. The authors conclude that epidural opioids achieve safe and useful postoperative pain control in children with cerebral palsy.

Adolescent↗

Carbohydrate structures of beta-core fragment of human chorionic gonadotropin isolated from a pregnant individual.

Highly purified beta-core fragment was obtained from urine of a pregnant woman with use of an immunoaffinity column. The amino acid sequence of beta-core fragment indicated that it is composed of two polypeptides linked by a disulfide bond. The two polypeptides correspond to the 6-40 and 55-92 portions of hCG beta-subunit. Both Asn13 and Asn30 residues were glycosylated. The N-linked sugar chains of beta-core fragment were quantitatively released as radioactive oligosaccharides by hydrazinolysis, followed by N-acetylation and NaB3H4 reduction. The radioactive oligosaccharides were fractionated by serial lectin column chromatography and Bio-Gel P-4 column chromatography, and their structures were investigated by sequential exoglycosidase digestion and periodate oxidation. The results indicated that they were a mixture of the four oligosaccharides: Man alpha 1----6(+/- Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(+/- Fuc alpha 1----6)GlcNAc. The structural characteristics of the sugar chains of beta-core fragment are quite different from those of the beta-subunit of hCG whose structures were typical biantennary sugar chains containing the Neu5Ac alpha 2----3Gal beta 1----4GlcNAc beta 1----2 group as their outer chains.

Amino Acid Sequence↗