Biomedical subjects

J Iwata

Publications and source records attributed to J Iwata.

At least 19 recordsLinked to original sources

PubMed2002

Quantitative local cerebral blood flow change after cerebrospinal fluid removal in patients with normal pressure hydrocephalus measured by a double injection method with N-isopropyl-p-[(123)I] iodoamphetamine.

The efficacy of cerebrospinal fluid (CSF) shunting surgery for normal pressure hydrocephalus (NPH) is difficult to predict. The CSF removal test is useful but quantification of the results is difficult. A method to quantitatively measure cerebral blood flow (CBF) by single photon emission computed tomography twice within 30 min after double injection of N-isopropyl-p-[(123)I] iodoamphetamine using a background subtraction method to correct for the temporal profile was utilized in tandem with CSF removal via a lumbar spinal tube in 22 patients of NPH to produce maps of baseline CBF and quantitative CBF change after CSF removal. All 22 patients with NPH underwent ventriculoperitoneal shunting surgery and were divided into two groups according to improvement in clinical symptoms and signs (responder group, N=15; nonresponder group, N=7). Baseline clinical characteristics and baseline CBF values were not significantly different between the two groups. Regional and whole brain CBF changes in the responder group (range 98-105%, whole brain 101+/-39%) were significantly higher than those in the nonresponder group (range 41-48%, whole brain 46+/-40%) (P<0.01). Discrimination analysis showed that an increase of more than 80% in CBF after CSF removal was predictive of response to shunt surgery with 77% accuracy. This new quantitative CSF removal test could be useful for selecting good candidates for CSF shunting surgery among patients with NPH.

Aged↗

PubMed2001

Expression of SMARCF1, a truncated form of SWI1, in neuroblastoma.

Previously we cloned and mapped a B120 gene to human chromosome 1p35-36.1 where possible suppressor genes for various neuroendocrine tumors including neuroblastoma have been mapped. Very recently, B120 was identified as a truncated form of p270, a putative human counterpart of SWI1. In the present study, expression of the B120 gene product was immunohistochemically investigated in 23 neuroblastomas. We also examined B120 expression in neural stem cells in developing brain and intact adrenal medulla. Four of 23 neuroblastomas strongly expressed B120 gene product in both cytoplasm and nucleus. The other neuroblastomas expressed B120 gene product in the nucleus; however, the intensity of staining was much weaker and equivalent to that in developing human brain stem cells in the subventricular region. B120 gene product was less strongly expressed in intact adrenal medulla. Subsequently, we performed loss of heterozygosity studies on 19 neuroblastomas using the polymorphic markers D1S195 and D1S511 located near the B120 gene. Loss of heterozygosity was observed in three of 19 tumors that abundantly expressed B120 protein. Furthermore, neuroblastoma cells were transfected with B120 expression vector. These transfected neuroblastoma cells adhered to each other and aggregated. Differential display experiments followed by reverse transcriptase-polymerase chain reaction and Northern blot analysis were performed and three molecules with altered expression in B120-transfected neuroblastoma cells were identified. One of three genes seemed to be a proliferation-related and cell cycle-related nucleolar protein, p120, encoding gene. We further characterized the genomic structure of B120. B120 appeared to be encoded by 17 exons in more than 20-kbp genomic DNA. The present findings contribute to understanding of the B120 gene, a truncated form of human SWII1, an approved term for which is SMARCF1, in normal cells and neuroblastomas.

Base Sequence↗

PubMed2001

Effects of genotype matching of feline major histocompatibility complex (FLA) class II DRB on skin-allograft transplantation in cats.

In order to confirm the effects of matching of expressed feline major histocompatibility complex (FLA) class II DRB genotype on transplantation immunity in cats, skin-allogeneic transplantation was carried out between cats, in which DRB genes expressed were genotyped by the RT-PCR-RFLP method using group-specific primers. Duration until grafts were rejected was 14.63 +/- 1.69 days (mean +/- standard deviation) in the pairs that had the same type of subgroups, 7.25 +/- 0.71 days in the pairs that had one different type of subgroup and 6.88 +/- 0.35 days in the pairs that had two different types of subgroups. The duration of graft survival in the pairs with the same type of subgroups was significantly longer (P<0.01) than those in the pairs with different types. Although FLA components involved in transplantation immunity should not only be DRB genes, it was suggested that the expressed FLA-DRB genotype might associate with feline transplantation immunity, and that typing and matching of expressed FLA-DRB genes might be one of the important factors in the control of feline transplantation immunity.

Animals↗

PubMed2001

Adjunctive osteopathic manipulative treatment in women with depression: a pilot study.

The authors assessed the impact of osteopathic manipulative treatment (OMT) as an adjunct to standard psychiatric treatment of women with depression. Premenopausal women with newly diagnosed depression were randomly assigned to either control (osteopathic structural examination only; n = 9) or treatment group (OMT; n = 8). Both groups received conventional therapy consisting of the antidepressant paroxetine (Paxil) hydrochloride plus weekly psychotherapy for 8 weeks. Attending psychiatrists and psychologists were blinded to group assignments. No significant differences existed between groups for age or severity of disease. After 8 weeks, 100% of the OMT treatment group and 33% of the control group tested normal by psychometric evaluation. No significant differences or trends were observed between groups in levels of cytokine production (IL-1, IL-10, IL-2, IL-4, and IL-6) or in levels of anti-HSV-1, anti-HSV-2, and anti-EBV antibody. There was no pattern to the osteopathic manipulative structural dysfunctions recorded. The findings of this pilot study indicate that OMT may be a useful adjunctive treatment for alleviating depression in women.

Adult↗

PubMed2000

A giant cell angiofibroma involving 6q.

Giant cell angiofibroma, a recently proposed new clinicopathological entity, arises exclusively in the orbit in adults and histologically exhibits features intermediate between those of giant cell fibroblastoma and solitary fibrous tumor. In a typical case of giant cell angiofibroma, abnormalities of chromosome 6 with a common pattern involving 6q13 were detected together with various other chromosomal aberrations. To our knowledge, this is the first reported case of giant cell angiofibroma demonstrating chromosomal abnormalities.

Angiofibroma↗

PubMed2000

Overexpression of cyclin D1 in nonmelanocytic skin cancer.

Although the overexpression of cyclin D1 has been believed to play important roles in neoplastic transformation of some tumors, little is known about the function of cyclin D1 protein in carcinogenesis in human skin. A total of 307 patients with nonmelanocytic skin cancer, being 46 with Bowen's disease (BOD), 134 with squamous cell carcinoma (SCC) and 127 with basal cell carcinoma (BCC), were investigated immunohistochemically using monoclonal antibody to cyclin D1 by the LSAB method, to assess the expression of cyclin D1 in skin cancer including its precursors. The positive rates of cyclin D1 immunostaining in BOD, SCC and BCC were 63.0%, 69.4% and 54.3%, respectively. The positive rates in dysplasia adjoining BOD, SCC and BCC were 43.6%, 67.9% and 59.8%, respectively. In morphologically normal skin, however, only 2 cases, 1 of SCC and 1 of BCC, exhibited positive staining. These findings suggested that overexpression of cyclin D1 is an early event in dysplastic lesions of skin. Overexpression of cyclin D1 was related to sun exposure, especially in dysplasia of SCC. The score for cyclin D1 expression in dysplasia of BCC was correlated with age. Expression of cyclin D1 markedly increased from normal skin through dysplasia to BOD, but was not significantly related to the degree of SCC differentiation. These findings demonstrate that the effect of cyclin D1 overexpression is restricted to proliferation of cells, so that they gain a growth advantage, but their differentiation is not increased. Comparison with the results for p53 protein expression in these tumors, a significant correlation with cyclin D1 expression was found in dysplasia in BOD and SCC, and in patients with BCC who were less than 74 years old. These findings suggested the hypothesis that prior aberrant p53 expression may affect or regulate the overexpression of cyclin D1.

Adult↗

PubMed2000

Multinucleated giant cells in submucosal layer of human urinary bladder: an immunohistochemical and electron microscopic study.

Multinucleated giant cells (MGC) detected in the submucosal layer of human urinary bladder mainly associated with transitional cell carcinoma were examined immunohistochemically and ultrastructurally. The cases examined totaled 29, namely 14 cases with transitional cell carcinoma and another 15 cases mostly with malignancy in other organs. Histologically, MGC were smooth, irregular or dendritic in shape, and tended to increase in number in the vicinity of cancer or marked inflammation. They were consistently positive for not only vimentin, but also MB-2, and CD34, and were mostly positive for proliferating cell nuclear antigen (PCNA), but not MIB-1 (Ki-67) and HLA-DRalpha antigens. On occasion, antibodies to alpha-smooth muscle actin (alpha-SMA), muscle actin (M-actin), CD68 (KP-1) and alpha subunit of S-100 protein also yielded positive reactions. Interestingly, aggregated short bulbous processes were ultrastructurally observed on their surface in parts. These findings suggested that MGC in the submucosal layer of human urinary bladder were MB-2 and CD34-positive multipotential mesenchymal cells with no mitotic activity expressing fibroblastic (vimentin), myofibroblastic (alpha-SMA), or histiocytic (CD68) markers mostly in the vicinity of malignancy, and that these MGC were formed by fusion of mononuclear cells expressing identical markers with those of MGC. Further investigations are needed to clarify the exact function of MGC in human urinary bladder.

Adult↗

PubMed2000

Design syntheses and mitochondrial complex I inhibitory activity of novel acetogenin mimics.

Some natural acetogenins are the most potent inhibitors of mitochondrial complex I. These compounds are characterized by two functional units [i.e. hydroxylated tetrahydrofuran (THF) and alpha, beta-unsaturated gamma-lactone ring moieties] separated by a long alkyl spacer. To elucidate which structural factors of acetogenins, including their active conformation, are crucial for the potent inhibitory activity we synthesized a novel bis-acetogenin and its analogues possessing two gamma-lactone rings connected to bis-THF rings by flexible alkyl spacers. The inhibitory potency of the bis-acetogenin with bovine heart mitochondrial complex I was identical to that of bullatacin, one of the most potent natural acetogenins. This result indicated that one molecule of the bis-acetogenin does not work as two reactive inhibitors, suggesting that a gamma-lactone and the THF ring moieties act in a cooperative manner on the enzyme. In support of this, either of the two ring moieties synthesized individually showed no or very weak inhibitory effects. Moreover, combined use of the two ring moieties at various molar ratios exhibited no synergistic enhancement of the inhibitory potency. These observations indicate that both functional units work efficiently only when they are directly linked by a flexible alkyl spacer. Therefore, some specific conformation of the spacer must be important for optimal positioning of the two units in the enzyme. Furthermore, the alpha,beta-unsaturated gamma-lactone, the 4-OH group in the spacer region, the long alkyl tail attached to the THF unit and the stereochemistry surrounding the hydroxylated bis-THF rings were not crucial for the activity, although these are the most common structural features of natural acetogenins. The present study provided useful guiding principles not only for simplification of complicated acetogenin structure, but also for further wide structural modifications of these molecules.

Animals↗

PubMed2000

Immunohistochemical detection of cytokeratin and epithelial membrane antigen in leiomyosarcoma: a systematic study of 100 cases.

Although 'aberrant' expression of the epithelial markers, cytokeratin (CK) and epithelial membrane antigen (EMA), in leiomyosarcoma has been described previously, there has not been a study of this phenomenon with clinicopathological correlation in a large series of lesions at different anatomical sites. We investigated systematically the immunohistochemical reactivity for CK and EMA in 100 cases of leiomyosarcoma. CK and EMA were positive in 38% and 44% of the cases, respectively. Although staining was usually focal, extensive immunoreactivity was observed in 11% with CK and 6% with EMA. There was no correlation between immunoreactivity for CK and EMA in leiomyosarcomas and non-neoplastic smooth muscle at the same location. Immunoreactivity for CK and EMA was not correlated with the location, age, sex, histological grade, or histological features, except for more frequent EMA positivity in vascular and uterine tumors than in soft tissue cases. These results indicate that CK and/or EMA-positive leiomyosarcomas do not have distinctive clinicopathological features differing from those of negative cases. However, the considerable frequency of immunoreactivity for these epithelial markers in leiomyosarcoma, occasionally with diffuse and strong immunopositivity, should be recognized as a potentially serious diagnostic pitfall in the differential diagnosis of other malignant spindle cell neoplasms.

Abdominal Neoplasms↗

PubMed2000

Lipidized fibrous histiocytoma: clinicopathologic analysis of 22 cases.

We report the clinicopathologic analysis of 23 tumors from 22 patients with lipidized fibrous histiocytoma (FH), which has been an underrecognized variant of cutaneous FH. The 16 men and 6 women patients (male/female ratio, 2.7:1) ranged in age from 21 to 82 years (median, 50 years). The location of the tumor was concentrated strikingly in the lower limb, especially around the ankle, hence the alternative informal designation of "ankle-type" FH. The tumors showed relatively large size compared with those of conventional FH, ranging up to 8 cm in greatest dimension (median, 2.5 cm), and tended to be polypoid and yellowish in color. Hyperlipidemia was only a rare and perhaps incidental association in two cases. Histologically, lipidized FH was characterized by accumulation of numerous foam cells, smaller numbers of siderophages, and stromal hyalinization typically appearing "wiry," keloidlike, or osteoidlike, although focal features of ordinary FH almost always coexisted and were identified as a focal storiform or curlicue pattern of spindle tumor cells, epidermal hyperplasia, and peripheral "entrapped" dermal collagen. Although follow-up data are limited, the prognosis appears to be good with no recurrence, even after incomplete excision. These clinicopathologic features highlight lipidized FH as a distinctive variant, which can be distinguished from ordinary or other variants of FH, as well as from other foam cell-rich cutaneous lesions, especially xanthoma.

Adult↗

PubMed2000

Genotyping of feline MHC (FLA) class II DRB by PCR-RFLP method using group-specific primers.

For genotyping of feline major histocompatibility complex (FLA) class II DRB, the polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method using group-specific primers was tried. Sixty-six DRB genes were classified into 8 groups according to differences in the first 5' amino acid sequences. The group-specific primers were designed as forward ones, which were specific for 5' base sequences of genes in each group. Three to 7 appropriate restricted enzymes were selected by computer analysis for RFLP typing of the genes divided into each group. In 6 out of 9 cats, the results of DRB typed by direct sequence method agreed with results of the PCR-RFLP method using group-specific primers. In the other 3 cats, the number of genes amplified by group-specific primers was I or 2 more than those detected by direct sequence method. The direct sequence method in 9 cats identified 5 new FLA-DRB genes. The PCR-RFLP method using group-specific primers could divide 66 genes into 37 genes and 10 subgroups from the RFLP pattern. One to 6 genes in each cat, and a total of 203 genes and subgroups were detected in 68 domestic cats. The genes detected might be biased to the subgroup G1-1a (28.8%), DRB*0501 (10.3%), G1-2a (9.4%) and G6b (7.4%). The PCR-RFLP method using group-specific primers may be useful in typing FLA class II DRB.

Animals↗

PubMed1999

Vibrational modes of ubiquinone in cytochrome bo(3) from Escherichia coli identified by Fourier transform infrared difference spectroscopy and specific (13)C labeling.

In this study we present the infrared spectroscopic characterization of the bound ubiquinone in cytochrome bo(3) from Escherichia coli. Electrochemically induced Fourier transform infrared (FTIR) difference spectra of DeltaUbiA (an oxidase devoid of bound ubiquinone) and DeltaUbiA reconstituted with ubiquinone 2 and with isotopically labeled ubiquinone 2, where (13)C was introduced either at the 1- or at the 4-position of the ring (C=O groups), have been obtained. The vibrational modes of the quinone bound to the discussed high-affinity binding site (Q(H)) are compared to those from the synthetic quinones in solution, leading to the assignment of the C=O modes to a split signal at 1658/1668 cm(-)(1), with both carbonyls similarly contributing. The FTIR spectra of DeltaUbiA reconstituted with the labeled quinones indicate an essentially symmetrical and weak hydrogen bonding of the two C=O groups from the neutral quinone with the protein and distinct conformations of the 2- and 3-methoxy groups. Perturbations of the vibrational modes of the 5-methyl side groups are discussed for a signal at 1452 cm(-)(1). Only negligible shifts of the aromatic ring modes can be reported for the reduced and the protonated form of the quinone. Alterations of the protein upon quinone binding are reflected in the electrochemically induced FTIR difference spectra. In particular, difference signals at 1640-1633 cm(-)(1) and 1700-1670 cm(-)(1) indicate variations of beta-sheet secondary structure elements and loops, bands at 1706 and 1678 cm(-)(1) are tentatively attributed to individual amino acids, and a difference signal a 1540 cm(-)(1) is discussed to reflect an influence on C=C modes of the porphyrin ring or on deprotonated propionate groups of the hemes. Further tentative assignments are presented and discussed. The (13)C labeling experiments allow the assignment of the vibrational modes of a bound ubiquinone 8 in the electrochemically induced FTIR difference spectra of wild-type bo(3).

Binding Sites↗

PubMed1999

Origin of selective inhibition of mitochondrial complex I by pyridinium-type inhibitor MP-24.

Positively charged pyridiniums are unique inhibitors to probe the structural and functional properties of the ubiquinone reduction site of bovine heart mitochondrial complex I. In this study, we synthesized a series of neutral as well as pyridinium analogues of MP-24 (N-methyl-4-[2-methyl-2-(p-tert-butylbenzyl)propyl]pyridinium), a selective inhibitor of one of the two proposed binding sites of these pyridinium-type inhibitors of complex I (H. Miyoshi et al., J. Biol. Chem. 273 (1998) 17368-17374), to elucidate the origin of its selectivity. Inhibitory potencies of all neutral and pyridinium analogues with tetraphenylboron (TPB(-)), which forms an ion-pair with pyridiniums, were comparable, although the degrees of selective inhibition by pyridiniums without TPB(-) were entirely different. In contrast to MP-24, the dose-response curves of nonselective pyridiniums and all neutral analogues were not affected by incubation conditions. These results strongly suggested that the process of the inhibitor passage to the binding sites is responsible for the selective inhibition.

Animals↗

PubMed1999

A new human synovial sarcoma cell line, HS-SY-3, with a truncated form of hybrid SYT/SSX1 gene.

Recent cytogenetical and molecular studies have indicated that synovial sarcoma harbors a t(X;18)(p11.2;q11.2) translocation, resulting in the formation of a hybrid SYT/SSX (SSX1 or SSX2) gene. We newly established a human cell line, HS-SY-3, from a synovial sarcoma. HS-SY-3 cells were shown to harbor the pathognomonic t(X;18)(p11.2;q11.2) translocation by chromosome analysis but not to exhibit the classical hybrid SYT/SSX transcripts induced by this translocation, using RT-PCR. To determine the reason for this discrepancy, we analyzed cDNA from HS-SY-3 cells, as well as the original sarcoma tissue by the rapid amplification of cDNA 3' end assay, and found that the chimaeric cDNA was 240 bp shorter than the previously established SYT/SSX1 cDNA due to truncation of the 3' side of SSX1. The HS-SY-3 cells should be useful for future functional studies of the SYT/SSX chimeric gene.

Aged↗

PubMed1999

Endometrial stromal sarcoma with clonal complex chromosome abnormalities. Report of a case and review of the literature.

Only eleven endometrial stromal sarcomas (ESS) with clonal chromosomal abnormalities have been reported in the literature. Of these, four have been reported to harbor the t(7;17) translocation. We report here an additional ESS that exhibited clonal complex chromosome abnormalities not described earlier: 38,XX,-1,del(1)(q11),-2,add(2)(p13),-3,der(4)add(4)(p12)psu dic(4;14)(q35;q11.2), add(6)(p21.3),add(7)(q22),del(7)(p11.2p13),-8,-9,add(9)(q34),- 10,add(10)(q24),-11,-11,ins(12;?) (q13;?),-14,-14,-15,ins(15;?)(q22;?),add(16)(q22),add(17)(q11.2),- 18,der(18)t(7;18)(q11.2;p11.2),-19, add(20)(p13),add(21)(p11.2),-22,add(22)(p11.2),+6mar in metaphase cells from primary short-term culture.

Adult↗

PubMed1999

Further characterization of the human clear cell sarcoma cell line HS-MM demonstrating a specific t(12;22)(q13;q12) translocation and hybrid EWS/ATF-1 transcript.

Only a small number of clear cell sarcoma (CCS) cell lines have been reported, including the cell line HS-MM. In the present study, this cell line, maintained for more than 4 years since establishment, was further characterized by cytogenetic studies, fluorescence in situ hybridization (FISH) analysis, and reverse transcriptase-polymerase chain reaction (RT-PCR). HS-MM cells both in vitro and in vivo exhibited pseudodiploid karyotypes with the specific t(12;22)(q13;q12) translocation. The translocation between chromosomes 12 and 22 was confirmed by FISH analysis and the hybrid EWS/ATF-1 transcript induced by this translocation was detected by RT-PCR. The HS-MM cell line will be useful for further studies of CCS.

Chromosome Aberrations↗

PubMed1999

Sun-exposure- and aging-dependent p53 protein accumulation results in growth advantage for tumour cells in carcinogenesis of nonmelanocytic skin cancer.

Three hundred and sixteen patients with nonmelanocytic skin cancer, including 46 cases of Bowen's disease (BOD), 134 cases of squamous cell carcinoma (SCC), and 136 cases of basal cell carcinoma (BCC), were examined immunohistochemically using monoclonal antibody DO-7 to assess p53 protein accumulation related to sun exposure and ageing, and growth and differentiation of skin cancer and its precursors. The rates of p53 immunostaining of BOD, SCC and BCC were 80.4%, 76.1% and 70.6%, respectively. p53-positive cells were present not only in cancer nests, but also in dysplastic and even morphologically normal epidermis adjoining cancers. Sun exposure was statistically correlated with the p53 immunostaining scores in morphologically normal epidermis of the three skin cancers and in cancer nests of SCC and BCC. The positivity and score of p53 protein often differed significantly among the three types of cancer, especially in regions of dysplasia. Interestingly, differentiation of SCC was correlated with individual p53 scores for dysplasia and cancer nests, especially for dysplasia. BOD, as the precursor of SCC, demonstrated the strongest p53 expression. Furthermore, 12.3% cases with p53 negative cancer nests showed p53-positive reaction in dysplasia and in morphologically normal epidermis. It seems that the accumulation of p53 protein plays a part in precancerous lesions and in the genesis of more highly differentiated types of skin cancer and affects mainly the growth of tumour cells rather than their differentiation. For BCC, however, age was significantly related to p53 expression. Our findings suggest that overexpression of p53 in normal skin and cancer nests of SCC and BCC is significantly related to sun exposure, that the expression of p53 in BCC is an age-dependent process, and that the early accumulation of p53 protein may be a useful predictor for the detection of nonmelanocytic skin cancer.

Adult↗

PubMed1999

Overexpression of c-Met protein in human thyroid tumors correlated with lymph node metastasis and clinicopathologic stage.

To examine the expression of c-Met protein in thyroid tumors and the correlation of c-MET protein expression with lymph node metastasis (LNM) and pathological stage, 111 papillary thyroid carcinomas (PTC), including 44 with synchronous LNM, and 117 follicular adenomas (FA) were immunohistochemically examined using dewaxed sections of formalin-fixed, paraffin-embedded tissues. Immunohistochemical results were confirmed by Western blot analysis. For PTC, positive immunostaining was observed in 107 of 111 (96.4%) cases and was diffusely present in either cytoplasm and nucleus, or only cytoplasm or only nucleus of cancer cells at varying intensities. Staining tended to be stronger in the periphery of cancer cell nests. Positive reaction was also found in 44 of 117 (37.6%) cases of FA. However, the extent and intensity of c-Met immunostaining in FA were far less than those in PTC (p < 0.0001). Forty-four PTC cases (39.6%) exhibited LNM, and the extent and intensity of c-Met expression were significantly correlated with both LNM (p < 0.0001) and pathological stage (p < 0.0001). No significant correlation of c-Met expression with age, sex or tumor size was found. Our findings suggest that PTC expresses c-Met protein much more strongly and intensively than does FA, and that strong and intense overexpression of c-Met protein may be an indicator of the presence of lymph node metastasis and advanced pathological stage of papillary thyroid carcinoma.

Blotting, Western↗