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Biomedical subjects

S Abe

Publications and source records attributed to S Abe.

At least 37 records · Page 2Linked to original sources
PubMed2004

Heat sensitivity of a SARS-associated coronavirus introduced into plasma products.

BACKGROUND AND OBJECTIVES: Various measures to inactivate/remove viruses have been implemented for manufacturing plasma-derived products. Here, we examined the heat inactivation ability of an agent of the severe acute respiratory syndrome (SARS), SARS coronavirus (CoV). MATERIALS AND METHODS: The Frankfurt-1 strain of SARS-CoV was incorporated in manufacturing processes of several products by using samples collected immediately before liquid heat treatment at 60 degrees C. RESULTS: SARS-CoV was easily inactivated by this treatment for 60 min in all in-process samples. However, the different composition of the tested samples affected the heat sensitivity of the virus strain: the infectivity of the virus in Antithrombin III preparation still remained after heating for 30 min at 60 degrees C. CONCLUSION: If by rare chance SARS-CoV contaminates source plasma, there should be no or only minor risk of this virus infection, due to sufficient inactivation by the 60 degrees C 10 h liquid heating step, although we must pay attention to the composition used for blood product preparation.

Blood↗
PubMed2004

Reduction of bleomycin induced lung fibrosis by candesartan cilexetil, an angiotensin II type 1 receptor antagonist.

BACKGROUND: Signalling of angiotensin II via angiotensin II type 1 receptor (AT1) promotes cardiac and renal fibrosis, but its role in lung fibrosis is little understood. Using a rat bleomycin (BLM) induced model of pulmonary fibrosis, we examined the expression of AT1 in the lung and the effect of an AT1 antagonist on pulmonary fibrosis. METHODS: Adult male Sprague-Dawley rats were given 0.3 mg/kg BLM intratracheally. Two days earlier they had received 10 mg/kg/day of the AT1 antagonist candesartan cilexetil mixed in the drinking water. AT1 expression in the lungs was examined by immunohistochemistry and immunoblot methods. The effect of the AT1 antagonist on pulmonary fibrosis was studied by analysis of bronchoalveolar lavage (BAL) fluid, histopathology, and hydroxyproline assay. RESULTS: Immunohistochemical studies showed overexpression of AT1 in inflammatory immune cells, alveolar type II cells, and fibroblasts. A quantitative assay for AT1 showed that AT1 expression was significantly upregulated in cells from BAL fluid after day 3 and in the lung homogenates after day 21. Candesartan cilexetil significantly inhibited the increase in total protein and albumin, as well as the increase in total cells and neutrophils in BAL fluid. On day 21 candesartan cilexetil also ameliorated morphological changes and an increased amount of hydroxyproline in lung homogenates. In addition, BLM increased the expression of transforming growth factor (TGF)-beta1 in BAL fluid on day 7; this increase was significantly reduced by candesartan cilexetil. CONCLUSION: AT1 expression is upregulated in fibrotic lungs. Angiotensin II promotes lung fibrosis via AT1 and, presumably, in part via TGF-beta1.

Albumins↗
PubMed2004

Thrombin induces collagen gel contraction partially through PAR1 activation and PKC-epsilon.

The ability of fibroblasts to contract three-dimensional collagen gels has been used as an in vitro model of the tissue contraction which characterises both normal repair and fibrosis. Among its actions, thrombin can activate the protease-activated receptor (PAR)1 and, thereby, stimulate inflammation and repair. The current study evaluated whether thrombin could stimulate fibroblast-mediated collagen gel contraction by activating PAR1 and whether its downstream signalling depends on protein kinase C (PKC)-epsilon. Human foetal lung fibroblasts (HFL-1) were cultured in three-dimensional collagen gels and the area of the gels was measured by image analyser. Both thrombin and TFLLR, a selective PAR1 agonist, stimulated collagen gel contraction mediated by HFL-1. After RNA interference-mediated PAR1 knockdown in HFL-1, both thrombin and the PAR1 agonist-induced gel contraction were partially inhibited (by 22.4+/-2.2% and 17.6+/-5.6%, respectively). The gel contraction stimulated by thrombin was also reduced by a nonspecific PKC inhibitor and a calcium-independent PKC-epsilon inhibitor. Both thrombin and TFLLR significantly increased PKC-epsilon activity, and this effect was blocked by PAR1 knockdown. Thrombin stimulates collagen gel contraction at least partially through activation of protease-activated receptor 1 and protein kinase C-epsilon, and may contribute to tissue remodelling in inflammatory airway and lung diseases.

Analysis of Variance↗
PubMed2004

[Strategy for surgical treatment for small peripheral carcinoma of the lung especially on systemic nodal dissection].

The diagnosis of small-sized (< or = 2 cm) non-small cell lung cancer (NSCLC) has increased with the development of computed tomography (CT), whereas unexpected extensive mediastinal involvement has been occasionally detected in such a small-sized lung cancer. We retrospectively analyzed the clinicopathological features to determinate the predictors for lymph node involvement in patients with a small-sized adenocarcinoma. One hundred and eighty one patients who underwent pulmonary resection and systematic nodal dissection for a peripheral small-sized adeno-carcinoma were reviewed. Of these, 24 patients (13.3%) had lymph node involvement. These patients were divided into 2 groups according to the existence of lymph node involvement, and the predictors for lymph node involvement were determined using univariate analysis and multivariate regression analysis. Univariate analysis revealed GGOR (ground glass opacity area/tumor area at the level of the greatest dimension of the lesion on chest computer tomography) > or = 25% (p = 0.0137) and pleural lavage fluid involvement (p = 0.0467) as predictors for lymph node involvement. No patients had lymph node involvement if their GGOR was higher than 50%. Multivariate regression analysis revealed GGOR > or = 25% (p = 0.0274), pleural tags on the lesion on chest CT (p = 0.0138) and pleural lavage fluid involvement (p = 0.0415) as predictors. We recommend performing systemic nodal dissection even if small peripheral adeno-carcinoma's maximal diameter is 20 mm or less. Systemic nodal dissection is unnecessary if the patients' GGOR > or = 50% or they do not have pleural tags or pleural lavage fluid involvement.

Aged↗
PubMed2003

Phase II study of cisplatin, ifosfamide, and irinotecan with rhG-CSF support in patients with stage IIIb and IV non-small-cell lung cancer.

A phase II study of cisplatin, ifosfamide, and irinotecan with recombinant human granulocyte colony stimulating factor (rhG-CSF) support was conducted in previously untreated patients with stage IIIB or IV non-small-cell lung cancer (NSCLC). Between June 1998 and August 2001, 50 patients were registered in this phase II study. Cisplatin (20 mg m(-2)) and ifosfamide (1.5 g m(-2)) were administered on days 1-4 and irinotecan (60 mg m(-2)) was given on days 1, 8, and 15, respectively. This regimen was repeated every 4 weeks. rhG-CSF was administered subcutaneously at a dose of 50 microg m(-2) on days 5-18 except on the days of irinotecan treatment. In total, 49 patients were assessable for toxicity and response and 50 for survival. In all, 33, patients (67.3%; 95% confidence interval 57.4-77.2%) achieved an objective response. The median response duration was 192 days and the median time to progression for 49 patients was 170 days. The median survival time was 540 days with 1- and 2-year survival rates of 63.5 and 30.7%, respectively. Grade 3 or 4 neutropenia and thrombocytopenia developed in 63.3 and 38.8% of the patients, respectively. In conclusion, the combination of cisplatin, ifosfamide, and irinotecan with rhG-CSF support was highly effective for the treatment of stage IIIB or IV NSCLC with acceptable toxicities.

Adenocarcinoma↗
PubMed2003

A new mouse model for Down syndrome.

Trisomy 21 (Ts21) is the most common live-born human aneuploidy and results in a constellation of features known as Down syndrome (DS). Ts21 is a frequent cause of congenital heart defects and the leading genetic cause of mental retardation. Although overexpression of a gene(s) or gene cluster on human chromosome 21 (Chr 21) or the genome imbalance by Ts21 has been suggested to play a key role in bringing about the diverse DS phenotypes, little is known about the molecular mechanisms underlying the various phenotypes associated with DS. Four approaches have been used to model DS to investigate the gene dosage effects of an extra copy of Chr 21 on various phenotypes; 1) Transgenic mice overexpressing a single gene from Chr 21, 2) YAC/BAC/PAC transgenic mice containing a single gene or genes on Chr 21, 3) Mice with intact/partial trisomy 16, a region with homology to human Chr 21 and 4) Human Chr 21 transchromosomal (Tc) mice. Here we review our new model system for the study of DS using the Tc technology, including the biological effects of an additional Chr 21 in vivo and in vitro.

Animals↗
PubMed2003

Increased circulating interleukin-12 (IL-12) p40 in pulmonary sarcoidosis.

In sarcoidosis, a T helper 1 (Th1) response is an essential event and the up-regulation of interleukin-12 (IL-12) has been detected in affected disease sites. In order to investigate the clinical usefulness of circulating IL-12, we measured the serum concentrations of IL-12 by ELISA and performed immunohistochemistry using specific MoAbs for IL-12 in the lungs and scalene lymph nodes of patients with sarcoidosis. The serum concentration of IL-12 p40 was detectable in all 45 patients with pulmonary sarcoidosis and 18 normal controls, whereas that of IL-12 p70 was undetectable. The serum concentrations of IL-12 p40 in pulmonary sarcoidosis were significantly higher than those of the normal controls, especially in cases with abnormal intrathoracic findings detected by chest roentogenogram. The serum concentrations of interferon-gamma (IFN-gamma) also increased compared with those of normal controls and there was a significant positive correlation between the serum concentrations of IL-12 p40 and IFN-gamma. Furthermore, serum angiotensin-converting enzyme (ACE) and lysozyme, which are known to be useful markers for disease activity in sarcoidosis, correlated well with the serum concentrations of IL-12 p40. The positive 67Ga scan group (for lung field) had significantly elevated serum IL-12 p40 levels compared with those of the negative group. No bioactivity of IL-12 p70 was detected in three sarcoid cases sera by using the IL-12 responsive cell line. Finally, the immunohistochemical approach revealed that IL-12 p40 was expressed in the epithelioid cells and macrophages of sarcoid lungs and lymph nodes. We concluded that the production of IL-12 p40 was far greater in the sera and we have demonstrated this to be a useful clinical marker for disease activity and the Th1 response in pulmonary sarcoidosis.

Analysis of Variance↗
PubMed2003

Myosin heavy chain isoforms of the murine masseter muscle during pre- and post-natal development.

Masticatory muscles that are derived from the branchial arches express different compositions of myosin heavy chain (MHC) isoforms during the transitional phase from suckling to mastication. To clarify the developmental changes of murine masseter muscle, the composition of MHC isoforms was examined using immunohistochemical staining and competitive reverse transcription PCR. We found that MHC1 was expressed transiently in the pre and post-natal stages. In the compositional change of isoforms, the embryonic type MHCp was expressed consistently, whereas the adult isoforms increased with the developmental process. In particular, a significant change was observed between embryonic days 14 and 16, a stage when murine facial development is conspicuous. This suggests that the development of murine masseter muscle is closely associated with facial development.

Aging↗
PubMed2003

Transplanted BM and BM side population cells contribute progeny to the lung and liver in irradiated mice.

BACKGROUND: BM cells have been shown to give rise to progeny of various cell lineages, including cells in lung and liver. This investigation evaluated whether purified BM mononuclear cells and side population (SP) cells that have hematopoietic stem-cell activity also had this property; whether a TBI preparative regimen was necessary for engraftment; and where BM-derived cells were engrafted. METHODS: Either 1-3 million BM mononuclear cells or 2000 BM SP cells from transgenic enhanced green fluorescent protein-expressing (EGFP) mice were transplanted i.v. to unirradiated or 7-9.5 Gy irradiated recipients. RESULTS: Flow cytometric analysis showed that lung cells (mean 45%, range 4-70%) and liver cells (mean 4%, range 0.4-8.3%) from irradiated, but not unirradiated recipients, were EGFP donor-derived. Similar results were obtained transplanting BM mononuclear cells or SP cells. Morphologically, donor-derived cells in the lung were primarily monocytes and macrophages. Additionally, lung fibroblasts and Type I, but not Type II, alveolar cells and rare cells in the bronchial epithelium were donor BM derived. In the liver, Kupffer cells, inflammatory cells and small clusters of hepatocytes, but not bile duct cells, were donor-derived. DISCUSSION: BM mononuclear and SP cells generated progeny in some compartments of the lung and liver, but only in TBI recipients. Stem cells in BM can contribute to repair of tissue injury in some compartments, but not to the same extent in the lung and liver.

Animals↗
PubMed2003

Origins and frequencies of SLC26A4 (PDS) mutations in east and south Asians: global implications for the epidemiology of deafness.

Recessive mutations of SLC26A4 (PDS) are a common cause of Pendred syndrome and non-syndromic deafness in western populations. Although south and east Asia contain nearly one half of the global population, the origins and frequencies of SLC26A4 mutations in these regions are unknown. We PCR amplified and sequenced seven exons of SLC26A4 to detect selected mutations in 274 deaf probands from Korea, China, and Mongolia. A total of nine different mutations of SLC26A4 were detected among 15 (5.5%) of the 274 probands. Five mutations were novel and the other four had seldom, if ever, been identified outside east Asia. To identify mutations in south Asians, 212 Pakistani and 106 Indian families with three or more affected offspring of consanguineous matings were analysed for cosegregation of recessive deafness with short tandem repeat markers linked to SLC26A4. All 21 SLC26A4 exons were PCR amplified and sequenced in families segregating SLC26A4 linked deafness. Eleven mutant alleles of SLC26A4 were identified among 17 (5.4%) of the 318 families, and all 11 alleles were novel. SLC26A4 linked haplotypes on chromosomes with recurrent mutations were consistent with founder effects. Our observation of a diverse allelic series unique to each ethnic group indicates that mutational events at SLC26A4 are common and account for approximately 5% of recessive deafness in south Asians and other populations.

Asia, Southeastern↗
PubMed2002

Preoperative cisplatin for initial treatment of limb osteosarcoma: its local effect and impact on prognosis.

PURPOSE: The significance of preoperative cisplatin (CDDP) as a single agent has not been assessed in terms of its effect on prognosis. The purpose of this multi-institution study was to assess the local effect of preoperative CDDP as a single agent as well as its impact on the prognosis of limb osteosarcoma. PATIENTS AND METHODS: The study group comprised 44 patients with stage IIB limb osteosarcoma who were treated with single-agent CDDP as initial preoperative chemotherapy. Two to five courses of CDDP (mean 2.4 courses) were administered intravenously and/or intraarterially as an initial preoperative treatment. The mean dose of CDDP was 3.0 mg/kg (2.5-3.4 mg/kg). The effect of the treatment was evaluated clinically and histologically. RESULTS: The clinical and histological response rates to preoperative CDDP were 56.8% and 47.6%, respectively. The survival rate was 59.1% among all patients in the study, 64.0% among those with a grade III or IV clinical response, and 52.6% among those with a grade I or II clinical response, with no significant differences between the groups. The survival rate was 70% among patients with a grade III or IV histological response, and 54.5% among those with a grade I or II histological response, with no statistical differences between the groups. CONCLUSIONS: We consider that CDDP is a useful chemotherapeutic agent for preoperative induction therapy for osteosarcoma because of the excellent local effect observed. Good responders to preoperative CDDP showed a better survival rate, but a correlation between the local response to CDDP and the survival rate was not demonstrated statistically. Systemic multidrug chemotherapy should follow preoperative CDDP to diminish the microscopic foci of metastatic disease.

Adolescent↗
PubMed2002

Organochlorine pesticides and polychlorinated biphenyl residues in foodstuffs and human tissues from china: status of contamination, historical trend, and human dietary exposure.

Concentrations of persistent organochlorine pesticides such as DDTs, hexachlorocyclohexanes (HCHs), chlordane compounds (CHLs), hexachlorobenzene (HCB), and polychlorinated biphenyls (PCBs), were determined in a wide variety of foodstuffs and human tissues collected from Shanghai and its vicinity in China in 2000-2001. Among the organochlorines analyzed, DDT and its metabolites were prominent compounds in most of the foodstuffs. In particular, mussels contained noticeable residues of DDTs (34,000 ng/g lipid weight), which are one to three orders greater than those reported levels in bivalves from other Asian countries. Concentrations of HCHs, CHLs, HCB, and PCBs in foodstuffs were generally low, suggesting small amounts of inputs into the environment. Temporal trends examined by comparing the results of previous studies of organochlorine levels in Chinese foodstuffs in 1970s and 1992 revealed a greater amounts of declines of DDTs and HCHs residues and the average daily intakes during the past 30 years. In contrast, very high concentrations of DDTs and HCHs were detected in human tissues from Shanghai, with the maximum values as high as 19,000 ng/g lipid weight (mean: 7,600 ng/g) and 17,000 ng/g (mean: 7,400 ng/g), respectively. Considering that foodstuffs are a main source of human exposure to contaminants, the greater concentrations of DDTs and HCHs in Chinese people might be due to past extensive usage of these compounds as agricultural pesticides. Continuous monitoring and epidemiological studies of organochlorine pesticides in humans are warranted in China. To our knowledge, this is the first report to present the residue levels of persistent organochlorine pesticides and PCBs in human tissues of China.

Aged↗
PubMed2002

Effects of alcohol intake on ambulatory blood pressure, heart rate, and heart rate variability in Japanese men with different ALDH2 genotypes.

The effects of alcohol intake on haemodynamics and heart rate variability were investigated with relation to genotypes of aldehyde dehydrogenase 2 (ALDH2), which were determined in 33 male Japanese volunteers (mean +/- s.e., 35.7 +/- 1.4 years) using the PCR-RFLP method. On the alcohol intake day, they consumed 660 ml of beer containing 33 ml of ethanol (0.3-0.5 g/kg of body weight) from 18.00 to 18.30. On the control day, they ingested the same amount of non-alcoholic beer. Ambulatory blood pressure, heart rate, and ECG R-R intervals were measured during a 24-h period with a portable recorder. A power spectral analysis of R-R intervals was performed to obtain the low-frequency (LF) and high-frequency (HF) components. Sixteen subjects were homozygotes for the normal ALDH gene (active ALDH2), only one was a homozygote for the mutant ALDH2 gene (inactive ALDH2), and the remaining 16 were heterozygotes (inactive ALDH2). Alcohol intake did not change 24-h average blood pressure (BP) either in the active ALDH2 group or in the inactive ALDH2 group. However, during the time interval from 18.30 to 0.00, alcohol intake significantly decreased diastolic BP in the active ALDH2 group and both systolic and diastolic BPs in the inactive ALDH2 group. In the active ALDH2 group, alcohol intake did not change heart rate, while in the inactive ALDH2 group, alcohol intake significantly increased 24-h average heart rate by 5.3 +/- 1.6 beats per minute (P < 0.01). In the active ALDH2 group, neither the LF nor the HF component was changed by alcohol intake, while in the inactive ALDH2 group, both the LF and the HF components were significantly decreased during the time interval from 18.30 to 0.00. These results demonstrate for the first time that ALDH2 genotypes modify the effects of intake of a small amount of alcohol on haemodynamics and heart rate variability in Japanese men.

Adult↗
PubMed2002

Characteristics of myofibres in the masseter muscle of mice during postnatal growth period.

Functional maturation of muscles is related to the constitutional proportion of muscle protein isoforms during development and growth. Although the mouse masseter muscle (MS) is classified as a fast limb muscle, its functions are different from those of a limb muscle. This study investigated the differentiation of myosin heavy chain (MHC) isoforms during the postnatal development periods in mouse MS and mouse tibialis anterior (TA), which is a fast limb muscle. Many anti-MHC slow-type-positive fibres were observed in neonatal MS and TA; these fibres decreased during development. Adult MS was composed of anti-MHC fast-type-positive fibres. MHC isoforms in MS were composed of MHC-2a and MHC-2d soon after birth. MHC-2b was expressed, but MHC-2a was not seen after 21 days. Expression of MHC-2b agreed with the weaning period, that is 2-3 weeks after birth. This fact suggested that the transformation from suckling to mastication changed the MHC isoforms during this period. In this study, the expressions of MHC-2b agree with the weaning period.

Aging↗
PubMed2002

[Anomalous systemic arterial supply to normal basal segment of the left lower lobe; report of a case].

A 28-year-old male was referred to our hospital because of hemoptysis. A chest X-ray revealed an increase of vascular marking in the left lower field and a partial defect in the lateral line of the descending thoracic aorta. An aortogram and pulmonary arteriogram showed a large artery arising from the descending thoracic aorta and supplying the left basal segment, which had no normal pulmonary arteries. A bronchoscopy showed no abnormal findings in the bronchial tree. A clinical diagnosis of systemic arterial supply to the basal segment of the left lower lung was made, and a left lower lobectomy and closure of the anomalous systemic artery by video-assisted thoracic surgery (VATS) were successfully performed. Vascular marking of the visceral pleura of left lower basal segment was observed and the anomalous arterial pressure was 84 mmHg, as high as systemic arterial pressure, during the procedure. The histopathological examination revealed normal alveolar structure, and sclerosis and hypertrophy of pulmonary arteries of the lesion (Heath-Edwards V, which means irreversible vascular changes due to pulmonary hypertension). The patient had an uneventful postoperative course and was discharged on postoperative day 8. The VATS procedure is a more useful and less invasive method for cases of systemic arterial supply to the basal segment of the left lower lung than an open thoracotomy.

Adult↗
PubMed2001

Lack of contact transmission of recombinant Marek's disease virus type 1 expressing the fusion protein of Newcastle disease virus.

To clarify the level of excretion of a recombinant Marek's disease virus type 1 (rMDV1) that confers good protection in chickens against both Marek's and Newcastle diseases, even in the presence of maternal antibodies, contact transmission tests were conducted. Naïve chickens kept in the same cage or room with chickens inoculated with rMDV1 did not produce antibodies against MDV1 or the fusion protein of Newcastle disease virus. Moreover, the rMDV1 was not isolated from the dander of chickens inoculated with rMDV1. Even under the stressful conditions of forced molting and a high temperature environment, rMDV1 was not isolated from the dander of inoculated birds. The viral DNA, however, was detected from the dander of chickens inoculated with rMDV1 as well as a commercial vaccine. These findings indicate that dander from chickens inoculated with rMDV1 includes viral DNA, but does not contain infectious virus.

Animals↗