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Biomedical subjects

S Imamura

Publications and source records attributed to S Imamura.

At least 55 records · Page 3Linked to original sources
PubMed1999

Peripheral blood stem cell collection and transplantation using the Haemonetics Multi Component System.

AIM: To assess clinical usefulness of an intermittent-flow blood cell separator in peripheral blood stem cell (PBSC) collection and transplantation. RESULTS: The Haemonetics Multi Component System (Multi) was used to collect PBSC (52 aphereses in 17 patients). The mean processing blood volume and the mean PBSC yield were 7407 ml and 2.16 x 10(6) CD34+ cells/kg, respectively. When CD34+ cells exceeded 0.3% of the peripheral WBC, more than 2.0 x 10(6) CD34+ cells/kg could be collected by a single apheresis. Eight patients underwent PBSC transplantation after high-dose chemotherapy. Hematopoietic recovery was achieved in a median period of 10 days. CONCLUSIONS: (1) A single-arm, light-weight machine has sufficient capability to collect PBSC. (2) The percentage of CD34+ cells in the peripheral WBC is a good predictor of the CD34+ cell yield of the collection.

Adult↗
PubMed1999

The role of oxidative DNA damage in human arsenic carcinogenesis: detection of 8-hydroxy-2'-deoxyguanosine in arsenic-related Bowen's disease.

Arsenic is widely distributed in nature in the form of either metalloids or chemical compounds, which cause a variety of pathologic conditions including cutaneous and visceral malignancies. Recently, reactive oxygen species have been hypothesized to be one of the causes of arsenic-induced carcinogenesis. 8-Hydroxy-2'-deoxyguanosine is one of the major reactive oxygen species-induced DNA base-modified products that is widely accepted as a sensitive marker of oxidative DNA damage. We studied the presence of 8-hydroxy-2'-deoxyguanosine by immunohistochemistry using N45.1 monoclonal antibody in 28 cases of arsenic-related skin neoplasms and arsenic keratosis as well as in 11 cases of arsenic-unrelated Bowen's diseases. The frequency of 8-hydroxy-2'-deoxyguanosine positive cases was significantly higher in arsenic-related skin neoplasms (22 of 28; 78%) than in arsenic-unrelated Bowen's disease (one of 11; 9%) (p < 0.001 by chi2 test). 8-Hydroxy-2'-deoxyguanosine was also detected in normal tissue adjacent to the arsenic-related Bowen's disease lesions. Furthermore, arsenic was detected by neutron activation analysis in the deparaffined skin tumor samples of arsenic-related disease (four of five; 80%), whereas arsenic was not detected in control samples. Our results strongly suggest the involvement of reactive oxygen species in arsenic-induced human skin cancer. Key word: neutron activation analysis.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1999

Unique expression patterns of myosin heavy chain genes in the ductus arteriosus and uterus of rabbits.

In smooth muscle tissue, two smooth muscle myosin heavy chain (MHC) isoforms (SM1, SM2) and two non-muscle MHC isoforms (NMA, NMB) have been identified. The purpose of our study was to clarify whether smooth muscle MHC mRNA expression reflects the physiological and functional state of the muscle. We studied the expression pattern of MHC mRNAs, using the S1-nuclease mapping procedure, in functionally and morphologically changeable organs; the ductus arteriosus (DA) during development (25 and 29 days of gestation, and from 3-day-old neonates) and uteri from virgin, day-10 pregnant (P10) and day-29 pregnant (P29) rabbits. The results demonstrated that SM2 expression was greater in the fetal DA than in the fetal aortic and pulmonary arteries, but that it decreased significantly following closure of DA. In the gravid uterus, SM1 expression was significantly (P<0.05) strong compared to other MHC mRNAs from virgin to P10 rabbits. During pregnancy, NMB expression showed a tendency to increase until P10, and after P10, SM2 expression increased dramatically and NMB expression decreased to give almost a mirror image of the SM2 expression. Smooth muscle type (SM1, SM2) was significantly (P<0.05) strong compared to non-muscle type expression (NMA, NMB) at P29. These data suggest that smooth muscle MHC mRNA, especially SM2 expression reflects the physiological and functional state of the smooth muscle.

Animals↗
PubMed1999

Effects of Sho-seiryu-to on experimental allergic rhinitis in guinea pigs.

The effects of Sho-seiryu-to, an antiallergic Kampo medicine, on experimental allergic rhinitis were investigated in actively sensitized guinea pigs. The number of sneezes and scratches by the animals after a topical antigen challenge was significantly inhibited by pretreatment with Sho-seiryu-to (1000 mg/kg per os p.o.). The antigen-induced eosinophil infiltration in the nasal mucosa was significantly inhibited by Sho-seiryu-to (1000 mg/kg p.o.). Sho-seiryu-to (100 mg/kg p.o.) also reduced the increase in dye leakage to the nasal cavity induced by the antigen challenge and the antigen-induced decrease in volume of the nasal cavity was inhibited. Moreover, Sho-seiryu-to (1000 mg/kg p.o.) suppressed the volume change in the nasal cavity induced by leukotriene D4. These results demonstrate that Sho-seiryu-to inhibits experimental allergic rhinitis in guinea pigs, confirming that the agent may be beneficial for the treatment of allergic rhinitis.

Animals↗
PubMed1998

The two functional keratin 6 genes of mouse are differentially regulated and evolved independently from their human orthologs.

The type II keratin 6 (K6) features a complex expression pattern, with a constitutive component in a subset of stratified epithelia and an inducible component following injury and other types of acute challenges. Multiple genes encoding highly related K6 isoforms have been described for human and bovine, a unique feature among mammalian keratin genes. Here we report on the cloning and characterization of two functional genes and their cDNAs encoding the K6 isoforms in mouse and two related pseudogenes. A systematic comparison of the mouse and human K6 genes suggests that they evolved independently after these species diverged. The mK6alpha and mK6beta genes are organized in tandem with the same transcriptional orientation in the mouse genome. Similar to the human isoforms, the coding sequences for mK6alpha and mK6beta isoforms show approximately 95% identity. The two mouse K6 genes are differentially regulated at the mRNA level in several stratified epithelia. The mK6alpha isoform mRNA clearly predominates in intact trunk skin of adult mice, where it is restricted to the outer root sheath of hair follicles. Both mRNAs are induced in epidermis and proximal hair follicles as early as 1 h following acute injury or topical application of phorbol esters and subsequently increase to a comparable extent but with different kinetics. These novel findings have important implications for the evolution, regulation, and function of K6 genes in mammalian species.

Amino Acid Sequence↗
PubMed1998

Kainic acid-induced perirhinal cortical seizures in rats.

Seizures induced in rats by kainic acid microinjection into the perirhinal cortex were studied electrophysiologically and behaviorally and compared with known features of seizures following kainic acid injection into the amygdala. Unlike amygdalar seizures, perirhinal cortical seizures did not generalize to become limbic seizures but rather spread to sensorimotor cortex to become manifest as motor seizures. Perirhinal cortical seizures also required larger kainic acid doses for provocation and were briefer.

Amygdala↗
PubMed1998

A de novo missense mutation (R1623Q) of the SCN5A gene in a Japanese girl with sporadic long QT sydrome. Mutations in brief no. 140. Online.

Two missense mutations and a nine-nucleotide deletion of the cardiac sodium channel (SCN5A) gene have been shown to cause long QT syndrome (LQTS) in several familial cases. We identified a novel missense mutation (R1623Q) of the SCN5A gene in a Japanese girl with sporadic LQTS. We used polymerase chain reaction, single-strand conformation polymorphism analysis and DNA sequence analysis to identify a mutation of the SCN5A gene in the patient. A single nucleotide substitution of guanine to adenine, in codon 1612, changed the coding sense of the SCN5A from arginine to glutamine (R1623Q) in the S4 segment of domain IV which is a highly conserved region of the SCN5A. This mutation was not identified in the unaffected biological parents and brother of the patient, and 100 normal, unrelated individuals. This finding is the first evidence of a de nova mutation in SCN5A associated with LQTS.

Amino Acid Substitution↗
PubMed1998

Monocyte-derived dendritic cells have a phenotype comparable to that of dermal dendritic cells and display ultrastructural granules distinct from Birbeck granules.

Most monocyte-derived dendritic cells (DC) display CD1a, like Langerhans cells (LC) and some dermal DC, but their relationship with these skin DC remains unclear. To address this issue, we studied the expression of different antigens characteristic of skin DC and of monocyte/macrophages in CD1a+ and CD1a- monocyte-derived DC. Their phenotype indicated that they may be related to dermal DC rather than to LC, i.e., they were all CD11b-positive, and 72% were Factor XIIIa-positive, but they did not express E-cadherin nor VLA-6. It is interesting that CD1a+ and CD1a-cells showed intracytoplasmic granules that were different from LC Birbeck granules. These phenotypical and ultrastructural features are comparable to those of CD14-derived DC obtained from cord blood precursors [C. Caux et al. J. Exp. Med. 184, 695-706]. These results show a close relationship between these two in vitro models, which are both related to dermal DC.

Antigens, CD↗
PubMed1998

Mutations of p16 and p15 tumor suppressor genes and replication errors contribute independently to the pathogenesis of sporadic malignant melanoma.

Mutations of p16 and p15 suppressor oncogenes and the replication errors in six microsatellite loci in sporadic malignant melanomas were analyzed. Four (9.1%) homozygous deletions of both p16 and p15 genes and one point mutation (2.3%) in the p15 gene were detected among 44 primary melanoma samples. One mutation in each of the p16 and p15 genes was observed in ten metastatic lesions. Eight (18.2%) replication errors were detected in three microsatellite loci in the primary melanoma samples, but no replication error was detected in the metastatic samples. None of the samples showed the alteration of p16/p15 genes and the replication errors concomitantly. These results suggest that (1) the homozygous deletions of p16/p15 genes and the replication errors may occur in rather early stages of melanoma tumorigenesis, while the p16/p15 gene mutation may occur in later stages, and (2) the p16 and p15 gene mutations in sporadic malignant melanomas might not be induced by the defect in mismatch repair, implying that p16 as well as p15 gene alterations may play an important role in the pathogenesis of sporadic malignant melanomas.

Adenine Nucleotides↗
PubMed1998

Molecular and clinical study of 183 patients with conotruncal anomaly face syndrome.

To investigate molecular and clinical aspects of conotruncal anomaly face (CAF), we studied the correlation between deletion size and phenotype and the mode of inheritance in 183 conotruncal anomaly face syndrome (CAFS) patients. Hemizygosity for a region of 22ql1.2 was found in 180 (98%) of the patients with CAFS by fluorescence in situ hybridization (FISH) using the N25(D22S75) DiGeorge critical region (DGCR) probe. No hemizygosity was found in three (2%) of the patients with CAFS by FISH using nine DiGeorge critical region probes and a SD1OP1 probe (DGA II locus). None of these three patients had mental retardation and just one had nasal intonation, which was observed in almost all of the 180 CAFS patients who carried deletions (mental retardation, 92%; nasal voice, 88%). Nineteen of 143 families (13%) had familial CAFS and 16 affected parents (84%) were mothers. Although only two of the affected parents had cardiovascular anomalies, the deletion size in the 16 affected parents and their affected family members, who were studied by FISH analysis, was the same. It indicates that extragenic factors may play a role in the genesis of phenotypic variability, especially in patients with cardiovascular anomalies. No familial cases were found among CAFS patients with absent thymus/DiGeorge anomaly (DGA). Also, in all 18 CAFS patients with completely absent thymus/DGA and all 6 CAFS patients with schizophrenia, it was revealed that the deletion was longer distally. A study of the origin of the deletion using microsatellite analyses in 48 de novo patients showed that in 65% of CAFS patients it was maternal, while in 64% of DGA patients it was paternal. The findings of this study indicated that CAF was almost always associated with the deletion of 22ql1.2. As well as the major features of the syndrome, other notable extracardiac anomalies were found to be susceptibility to infection, schizophrenia, atrophy or dysmorphism of the brain, thrombocytopenia, short stature, facial palsy, anal atresia, and mild limb abnormalities.

Adolescent↗
PubMed1998

Idarubicin and idarubicinol are less affected by topoisomerase II-related multidrug resistance than is daunorubicin.

We investigated the cytotoxicity and cellular pharmacology of idarubicin (IDA), idarubicinol (IDAol) and daunorubicin (DNR) in K562/VP-H2 cells, which show topoisomerase II-related multidrug resistance but do not overexpress P-glycoprotein. K562/VP-H2 cells were less resistant to IDA and IDAol than to DNR. There was no significant difference in the accumulation of each drug between K562 and K562/VP-H2 cells. The cleavage of DNA induced by each drug was decreased in K562/VP-H2 cells, however, the decrease in cleavage in K562/VP-H2 cells was less with IDA and IDAol than with DNR. These results suggest that IDA and IDAol have more cytotoxic potency than DNR in topoisomerase II-related multidrug-resistant leukemia cells.

Antineoplastic Agents↗
PubMed1998

Psychosomatic aspects of patients complaining of dizziness or vertigo with orthostatic dysregulation.

Eighty-five patients (26 males and 59 females) with orthostatic dysregulation who visited our clinic complaining of dizziness or vertigo between December, 1990 and August, 1996 were analyzed using the Japanese Edition Cornell Medical Index-Health Questionnaire and the Yatabe-Guilford Personality Test. The condition of OD was most commonly noted in 29 patients (34.1%) with dizziness or vertigo of indeterminate etiology, followed by in 14 (16.5%) with Meniere's disease, in ten (11.8%) with hypotension and CNS disorder each, and in 22 (25.9%) with other disorders. The percentage classed as Type III (possible neurotic) or Type IV (probable neurotic), was 46.1% in males and 47.4% in females. The percentage classed as Type B or Type E, suggestive of emotional or psychological disturbance, was 38.5% in males and 37.3% in females. There was good correlation between the Japanese Edition Cornell Medical Index-Health Questionnaire and the Yatabe-Guilford Personality Test results as to psychosomatic aspects. We conclude that, in the treatment of patients with orthostatic dysregulation, it is necessary to consider both physical and psychological aspects of the condition.

Adult↗
PubMed1998

Analysis of mechanisms of epidermal proliferation induced by intracutaneous injection of cholera toxin by the use of site-specifically mutated cholera toxins.

Intracutaneous injection of cholera toxin (CT) into rabbits increases vascular permeability and induces epidermal proliferation. To understand the mechanisms of these effects on the skin, we evaluated the involvement of the ADP-ribosyltransferase activity of the A subunit of CT and receptor-binding interactions between GM1-ganglioside and the B subunit of CT. We constructed two mutant CTs, E112K and W88K, by site-directed mutagenesis. Mutant CT-E112K, in which glutamic acid at position 112 (E112) of the A subunit of CT was replaced by lysine, has been shown to have lost its biological activity on Chinese hamster ovary (CHO) cells because of its abolished ADP-ribosyltransferase activity. Mutant CT-W88K, in which tryptophan at position 88 (W88) of the B subunit of CT was replaced by lysine, has been shown to have lost its binding ability to GM1-ganglioside. Intracutaneous injection of these mutant CTs evoked less vascular permeability and less epidermal proliferation than recombinant wild-type CT. These results suggest that: (1) the ADP-ribosyltransferase activity carried by E112 of the A subunit of CT; and (2) the binding ability to GM1-ganglioside via W88 of the B subunit of CT are essential for these effects of CT on the skin.

Animals↗
PubMed1998

Further characterization of a new in vitro angiogenesis model under serum free culture conditions; suppression of endothelial cell differentiation by serum.

We studied the regulation of the extracellular matrix in the recently established murine vascular endothelial cell clones, F-2 or F-2C. F-2 cells constitutively show a cobblestone growth pattern under serum supplemented culture conditions, whereas F-2C cells undergo spontaneous histodifferentiation to form tubular structures in chemically defined media. We reported that the tubulogenesis induced by F-2C might relate to the heavy deposition of a 'basement membrane analog' as a subendothelial matrix (SEM). We further characterized the regulation of extracellular matrix (ECM) metabolism in these cell clones, in terms of gelatinase expression, ECM degradation and the effects of serum. F-2C cells in culture medium containing 1% serum did not undergo tubulogenesis but presented cobblestone growth. Zymography analysis showed that both F-2 and F-2C cells express two gelatinase (72 and 92 kDa). However, F-2 cells mainly expressed the former and faintly the latter, whereas F-2C mainly expressed the latter. Proteolysis studies showed that the spent media conditioned by F-2C cells partially cleaved type IV collagen and completely degraded type V collagen. The cleavage of type V collagen was suppressed by the addition of serum, whereas that of type IV collagen was not. The proteolysis of laminin and fibronectin by the conditioned medium was not observed. Serum-supplemented F-2 or F-2C cultures markedly suppressed SEM deposition. These results indicated that F-2C cells under serum free culture conditions not only present a simple and useful in vitro model with which to study the dynamic processes of proteolysis and ECM metabolism during the sequential phases of angiogenesis, but is also useful for analyzing the serum effects on angiogenesis (AG).

Animals↗