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H Mochizuki

Publications and source records attributed to H Mochizuki.

At least 73 records · Page 4Linked to original sources
PubMed2001

Survival effects of pigment epithelium-derived factor expressed by a lentiviral vector in rat cerebellar granule cells.

We have previously shown that pigment epithelium-derived factor (PEDF) acts as a survival factor for cerebellar granule cells (CGCs), by blocking apoptotic death, and can also protect these cells against glutamate-induced neurotoxicity. In preparation for gene therapy studies, pseudotyped HIV-1-based lentiviral vectors containing the PEDF gene, as well as either green fluorescent protein or beta-galactosidase, were prepared. These bicistronic vectors are unique in that they express two genes efficiently under one promoter. Primary cell cultures of CGCs from postnatal day 8 rats were infected with the vectors encoding PEDF. RT-PCR demonstrated expression of mRNA and Western blot analysis confirmed that infected CGCs secrete PEDF protein to the medium. Assays for cell survival demonstrated that PEDF-infected cells were significantly more protected compared with mock-infected controls for 6-8 days in culture, as well as against induced apoptosis. The PEDF vectors expressing tat (trans-acting transcription factor) provided more protection than the tat(-) vectors. These results demonstrate that while the lentiviral vectors expressing PEDF are as neuroprotective as the protein itself for CGCs, the vectors have the advantage of providing long-lasting expression of PEDF protein, which will be more effective in in vivo studies. The present results suggest that this system may be useful for gene therapy for neurodegenerative disorders.

Animals↗
PubMed2001

Increased monocyte activation in elderly patients after surgical stress.

OBJECTIVE: To investigate age-related changes in the host response to surgical stress. The clinical course, serum interleukin-6 (IL-6) levels, monocyte production of tumor necrosis factor-alpha (TNF-alpha), and monocyte expression of CD11b/CD18 were used as markers of the systemic response. METHODS: Patients with gastric cancer, undergoing distal gastrectomy were divided into 2 groups: >75 years of age (elderly group) and < or =75 years of age (young group). Serum IL-6 levels, TNF-alpha production and CD11b/CD18 expression by monocytes, and the postoperative clinical course were compared between the 2 groups. RESULTS: TNF-alpha production by lipopolysaccharide-stimulated monocytes and CD11b/CD18 expression on monocytes after surgical stress were significantly higher in the elderly than in the young group. Moreover, serum IL-6 levels on the first postoperative day in the elderly group were significantly higher than those in the young group. The incidence and duration of systemic inflammatory response syndrome (SIRS) were significantly greater in the elderly than in the young group. CONCLUSIONS: The activation of monocytes and hypercytokinemia occur readily after surgical stress in the elderly and may therefore contribute to SIRS and increased susceptibility to postoperative complications.

Aged↗
PubMed2001

Analysis of the P3 promoter of the human parathyroid hormone (PTH)/PTH-related peptide receptor gene in pseudohypoparathyroidism type 1b.

Hypocalcemia and hyperphosphatemia caused by PTH resistance are the only discernible abnormalities in pseudohypoparathyroidism type 1b (PHP-1b). Because of the selective resistance toward PTH, inactivating mutations in its receptor, the PTH/PTH-related peptide receptor (PTHR1), were thought to be responsible for PHP-1b. However, gene abnormalities responsible for PHP-1b have not been identified in the coding region and well conserved promoters (P1 and P2) of the PTHR1 gene. The purpose of the present study was to analyze the structure of the P3 promoter, the main promoter of the human PTHR1 gene in kidney, in patients with PHP-1b. Southern analysis of genomic DNA from lymphoblastoid cell lines of eight nonfamilial patients with PHP-1b revealed neither gross rearrangements nor methylation abnormalities in the P3 promoter region of the PTHR1 gene. Sequencing revealed no abnormalities in the P3 promoter region, although one patient was homozygous for an (AAAG)n polymorphic variant. In conclusion, despite the selective resistance toward PTH in the kidney, which mainly uses the PTHR1 P3 promoter, PHP-1b in eight cases is not associated with structural abnormalities in this promoter. This study also indicates that inactivation of the P3 promoter is not achieved by methylation as tested in patients' genomic DNA from lymphoblastoid cell lines. The influence of alterations in the polymorphic A-rich repeat sequence on promoter activity warrants further study.

Adolescent↗
PubMed2001

Synthesis and evaluation of 1-arylsulfonyl-3-piperazinone derivatives as factor Xa inhibitor.

Intravascular clot formation is an important factor in a number of cardiovascular diseases. Therefore, the prevention of blood coagulation has become a major target for new therapeutic agents. One attractive approach is the inhibition of factor Xa (FXa), which is a key enzyme in coagulation cascade responsible for the generation of thrombin by limited proteolysis of its zymogen, prothrombin. We have investigated 1-arylsulfonyl-3-piperazinone derivatives, containing a 4-(piperidino)pyridine group in place of guanidino and/or amidino groups, and discovered compound M55113 (30a: 4-[(6-Chloro-2-naphthalenyl)sulfonyl]-1-[[1-(4-pyridinyl)-4-piperidinyl]methyl]piperazinone), as a potent inhibitor of FXa (IC50=0.06 microM) with high selectivity for FXa over trypsin and thrombin.

Anticoagulants↗
PubMed2001

Relationship between bronchial hyperresponsiveness and development of asthma in wheezy infants.

STUDY OBJECTIVES: To evaluate the relationship between bronchial hyperresponsiveness (BHR) in infants with wheezing and the subsequent development of asthma. INTERVENTION: Bronchial reactivity to inhaled methacholine (BRm) during the infantile period was studied using the transcutaneous partial pressure of oxygen (tcPO(2)) method. Children were followed long-term for the development of asthma. PATIENTS: Fourteen children with bronchiolitis (mean age, 0.7 years) and 48 with wheezy bronchitis (mean age, 2.3 years) were enrolled. For comparison, 40 children with asthma (mean age, 4.6 years) and 27 healthy control subjects without chronic respiratory disease (mean age, 2.7 years) were studied. MEASUREMENTS: Consecutive doses of methacholine were doubled until a 10% decrease in tcPO(2) from baseline was reached. The cumulative dose of methacholine (Dmin) at the inflection point of tcPO(2) (Dmin-PO(2)) was recorded. RESULTS: During > 10 years of follow-up, seven patients with bronchiolitis developed asthma and all patients in the higher BRm set developed asthma, compared with none in the lower BRm set. In the wheezy bronchitis group, Dmin-PO(2) values in the 32 patients who developed asthma were lower than those in patients who had not developed asthma (p < 0.001). CONCLUSIONS: We concluded that there is a tendency for infants with a clinical diagnosis of bronchiolitis or wheezy bronchitis and who show BHR in the infantile period to develop asthma. The presence of increased BHR after infantile respiratory diseases associated with wheezing may be a prelude to the development of childhood asthma.

Asthma↗
PubMed2001

Female gonadal development in XX patients with distal 9p monosomy.

OBJECTIVE: A sex determining gene(s) has been mapped to a approximately 700 kb region distal to the exons of DMRT1 on 9p. The aim of this study was to examine gonadal developmental status in XX patients hemizygous for the 9p sex determining region. DESIGN: Clinical and molecular studies were performed in an 8-year-old girl with 46,XX,del(9)(p22) (case 1) and in a 2-year-old girl with 46,XX,del(9)(p23) (case 2). METHODS: Ovarian function status was assessed by gonadotrophin-releasing hormone (GnRH) tests. Hemizygosity for the sex determining region was examined by fluorescence in situ hybridisation and microsatellite analyses for a total of 17 loci on distal 9p. RESULTS: GnRH tests indicated mild gonadotrophin hyper responses in both cases (case 1: follicle stimulating hormone 9.2-->22.7 IU/l, luteinising hormone 0.7 --> 16.6 IU/l; case 2: follicle stimulating hormone 7.6 --> 38.2 IU/l, luteinising hormone 0.6 --> 9.4 IU/l). Molecular studies showed hemizygosity for the 9p sex determining region in both cases. CONCLUSIONS: The results, in conjunction with previous reports describing sex development in XX and XY patients hemizygous for the 9p sex determining region, imply that haploinsufficiency of the 9p sex determining gene(s) primarily hinders the formation of the indifferent gonad, leading to a wide range of testicular or ovarian development.

Child↗
PubMed2001

Protection of mice from LPS-induced shock by CD14 antisense oligonucleotide.

CD14 is a pattern recognition receptor on myeloid cells and plays a pivotal role in an innate immune system that is responsible for Gram-negative and Gram-positive bacteria infection. Lipopolysaccharide (LPS), a cell wall component of Gram-negative bacteria, can induce production of a large quantity of proinflammatory cytokines into the circulation mediated by CD14-mediated macrophages and monocytes. These cytokines eventually cause septic shock. Several in vitro and in vivo studies have shown that suppression of a CD14 function by a CD14 antibody led to an inhibition of the production of proinflammatory cytokines such as TNF-alpha, IL-1 beta, and IL-8. In the present study, we found that CD14 antisense oligonucleotide (ODN) can prevent lethal LPS shock in D-galactosamine-sensitized mice. This ODN inhibited CD14 expression in a mouse macrophage cell line, RAW264.7, and suppressed production of TNF-alpha in LPS-stimulated RAW264.7 cells. Furthermore, we designed a consensus antisense ODN that could hybridize human and mouse CD14 RNA, and we evaluated its efficacy. The consensus antisense ODN rescued mice primed with Mycobacterium bovis bacillus Calmette-Guerin (BCG) from the LPS-induced lethal shock. In this model, the CD14 antisense ODN down-regulated LPS-elicited CD14 expression in the liver, resulting in a decrease in LPS-induced TNF-alpha production. These findings suggest that the CD14 antisense ODN is distributed in the liver and efficiently suppresses LPS-induced TNF-alpha production by reducing CD14 expression on Kupffer cells. This CD14 antisense ODN may be useful for the development of a therapeutic agent against sepsis and septic shock.

Animals↗
PubMed2001

Regression of both pituitary and ovarian cysts after administration of thyroid hormone in a case of primary hypothyroidism.

We report a 19-year-old woman who was diagnosed as polycystic ovary. Hypothyroidism with a markedly elevated TSH level and an enlarged pituitary gland on MRI were noted. The 123I uptake was decreased to 6.5%. After treatment with thyroid hormone, regression of the enlarged pituitary and the ovarian cysts was observed. In the present case, hypothyroidism was considered to have caused a reversible enlargement of the pituitary gland and concomitant polycystic ovary. We concluded that the polycystic ovary might have resulted from the effects of an excessive amount of TSH on immature ovaries.

Adult↗
PubMed2001

Nodular cutaneous amyloidosis and carpal tunnel syndrome due to the amyloidogenic transthyretin His 114 variant.

This is the second report of transthyretin (TTR) amyloidosis in a patient who had ATTR Tyr114His diagnosed by mass spectrometry and gene analysis. This case had some clinical features that differed from those of the first reported cases. The patient, 73-year-old man, complained of generalized cutaneous tubercula that had started at age 68. These tubercula gradually increased in size and became generalized. He felt a slight numbness in his extremities. Clinical and electrophysiological examinations revealed that he had bilateral carpal tunnel syndrome (CTS), whereas there was no clear evidence of sensory and/or motor polyneuropathy. Autonomic symptoms were not present. Biopsy studies revealed that both his tuberculum and his sural nerve contained TTR-related amyloid. In his sural nerve, amyloid deposits were observed mainly in the perineurium, not in the endoneurium, and there was no significant depletion of myelinated fibers. The features of this patient were clinically characterized by generalized cutaneous amyloid deposits and late-onset CTS with a lack of overt polyneuropathy and autonomic dysfunction. The unique clinical features in this case seemed to be consistent with the distribution of amyloid deposits.

Aged↗
PubMed2001

[An 84-year-old woman with progressive mental deterioration and abnormal behavior].

We report an 84-year-old woman with progressive mental deterioration. She was well until January 1994, when she was 80 years of the age. At that time she developed a delusional ideation, in that she stated that she would be killed by her fellow members of the society for elderly, in which she was belonging. At times, she closed the shutter of her house saying that a stranger was wandering outside of her house. In 1995, she could not identify the face of her son's wife. When she went out for shopping, she lost her way to the home. She prowled about in and out of her home. In 1996, she had to be admitted to a nursing home, where quarrelled with other patients and behaved violently. She was admitted to the neurology service of Hatsuishi Hospital on November 20th, 1997. Family history revealed that her mother was said to be demented. On admission, she was alert and behaved in a good manner. She was disoriented to the time and unable to do serial 7. Her memory was very poor. She did not show aphasia or apraxia. Cranial nerves appeared to be intact. She showed no weakness or muscle atrophy. Gait was normal for her age. Plastic rigidity was noted in four limbs more on the right side. No ataxia was noted. Deep tendon reflexes were exaggerated, however, no Babinski sign was noted. Sensory examination was intact. Her hospital course was characterized by the development of progressive gait disturbance, violent behaviour, and prowling around. On November 30th, 1998, she fell down and suffered from a fracture in the neck of her femur. Although replacement of the femur head was performed, she became unable to walk after this episode. Her mental functions deteriorated further. She developed pneumonia and expired on February 2, 1999. She was discussed in a neurological CPC and the chief discussant arrived at a conclusion that the patient probably had diffuse Lewy body disease, because of the combination of dementia and parkinsonism. Other possibilities discussed in the CPC included Pick's disease, frontotemporal dementia and parkinsonism, and Alzheimer's disease. Post-mortem examination revealed moderate atrophy in the frontal and temporal cortices. Microscopic examination showed atrophy and gliosis in the hippocampus. Many diffuse plaque and neuritic plaques were seen in the frontal cortex by methenamine silver staining. Neurofibrillary tangles were also found. The Meynert nucleus was preserved. The putamen and the substantia nigra were also intact. Pathologic diagnosis was consistent with Alzheimer's disease.

Aged↗
PubMed2001

[Clinical significance of detecting circulating cancer cells in patients with solid malignancies].

There have been several studies attempting to detect the existence of cancer cells in the peripheral blood of patients with solid malignancies. The use of RT-PCR assays for cytokeratin (CK), carcinoembryonic antigen (CEA), alpha-fetoproteins (AFP), prostate specific antigen (PSA) and prostate specific membrane antigen (PMSA) is likely to be practicable in the detection of circulating tumor cells from epithelial-derived malignancies. The positive rates varied widely among the studies attempting to detect circulating cancer cells in peripheral blood, even when the same targets were used, which may be explained by the sensitivity of the RT-PCR assays and the target genes used. Both false negative results and false positive results can be obtained with the RT-PCR assay system. Furthermore, cancer cells may be released from the primary cancer into the circulation intermittently rather than constantly, and the results may vary among the samples obtained at different time points. In this report, we review our recent studies and related studies by other researchers to show the advances and the problems in detecting circulating cancer cells in patients with solid malignancies. The clinical significance of detecting circulating cancer cells in peripheral blood remains to be determined.

Biomarkers, Tumor↗
PubMed2001

[Sentinel lymph node (SLN) in breast cancer: prediction of axillary metastasis confined to the SLN spares patients further axillary dissection].

Although regional control of the axilla in patients with breast cancer is important, axillary lymph node dissection (ALND) is performed mainly for staging purposes. The sentinel lymph node (SLN) that first receives lymphatic drainage from the tumor was investigated. After SLN identification, ALND or radiation therapy is performed in patients with SLN metastasis who are also likely to have non-SLN metastasis. However, it is important to select patients with SLN metastasis who may benefit from further axillary treatment. The size of the primary tumor and the size of its SLN metastasis are reported to be associated with the presence of non-SLN metastases. Patients in whom the SLN indicates less than 20% of nodes are involved have a low probability of non-SLN involvement and therefore can avoid further axillary treatment. Although large clinical trials are necessary for confirmation, it appear, that patients with axillary involvement confined to the SLN can be spread further ALND.

Axilla↗
PubMed2001

[Glutamine].

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Animals↗
PubMed2001

[Childhood asthma].

During the past two decades, childhood asthma around the world has become more common. Recent large epidemic studies in Japan and other countries have been demonstrated that the prevalence of asthma is higher in their previous studies, especially for childhood asthma. Other large studies have been indicated that the prevalence of asthma is higher in large cities. The effects on health of chronic exposure to allergens and aeropollutants have been much studied, also in relation to the increasing number of asthmatic patients. The combination of the genetic basis characteristic of asthma and indoor allergens like dust mite and atmospheric dusts to the increasing frequency of asthma has been emphasized, and recent Japanese lifestyles have been proposed as a possible factor. Therefore, these recent observations indicate the necessity of up-to-date strategies for therapy and for patient education against childhood asthma.

Adolescent↗