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Biomedical subjects

A Harada

Publications and source records attributed to A Harada.

At least 109 records · Page 6Linked to original sources
PubMed1998

Association of a polymorphism of the transforming growth factor-beta1 gene with genetic susceptibility to osteoporosis in postmenopausal Japanese women.

Transforming growth factor-beta (TGF-beta) is both abundant in bone and an important regulator of bone metabolism. A T-->C transition at nucleotide 29 in the signal sequence region of the TGF-beta1 gene results in a Leu-->Pro substitution at amino acid position 10. The possible association of this polymorphism with bone mass and the prevalence of osteoporosis has now been investigated in a total of 287 postmenopausal women from two regions (Obu City, Aichi Prefecture, and Sanda City, Hyogo Prefecture) of Japan. A significant association of TGF-beta1 genotype with bone mass was detected in both populations; bone mineral density (BMD) at the lumbar spine was greater in individuals with the CC genotype than in those with the TT or TC genotype. The frequency of vertebral fractures was significantly lower in individuals with the CC genotype than in those with the TC or TT genotypes. For each region, multivariable logistic regression analysis revealed that the frequency of the T allele was significantly higher in subjects with osteoporosis than in controls. Also, the serum concentration of TGF-beta1 in individuals with the CC genotype was significantly higher than that in age-matched subjects with the TC or TT genotype in osteoporotic or osteopenic as well as healthy control groups. These results suggest that the T/C polymorphism of the TGF-beta1 gene is one of the genetic determinants of bone mass and that the T allele is an independent risk factor for the genetic susceptibility to osteoporosis in postmenopausal Japanese women. Thus, analysis of the TGF-beta1 genotype may be useful in the prevention and management of osteoporosis.

Adult↗
PubMed1998

Effect on the femur of a new hip fracture preventive system using dropped-weight impact testing.

To reduce hip fractures during falls, we devised a new hip fracture preventive system to attenuate impact on the greater trochanteric region and studied the effects of the system on the femur. Twelve coupled, embalmed, cadaveric femora were used. Right femora were fractured without protection as a control and compared with left femora covered by the protection system, which consisted of a silicone gel pad or the silicone gel pad combined with a resin cover. The impact of a fall was simulated by mounting a femur in the horizontal plane and dropping an 8.4 kg mass on its greater trochanteric region. The impact load and time were measured using a load cell within the mass. The maximum strain during impact at the inferior side of the femoral neck was determined from an attached strain gauge. Trochanteric fractures were produced in 18 of the 24 femora (75%). The mean impact load for a drop height of 25 cm was reduced from 3117 N to 2176 N by silicone gel (p < 0.01) and to 1681 N by the addition of the resin cover (p < 0.01). The mean maximum strain was similarly reduced from 2276 microvarepsilon to 1872 microvarepsilon (p = 0.15) and to a mean 1559 microvarepsilon (p < 0. 05). The mean impact time was prolonged from 13 ms to 20 ms (p < 0. 01) and 22 ms (p < 0.01), respectively. The effect of the cover became more conspicuous as height increased. We concluded that the silicone gel pad provided effective impact attenuation, and the addition of the rigid cover was even more effective for impact reduction. This system was thought to be clinically useful in preventing hip fractures.

Absorptiometry, Photon↗
PubMed1998

[The switching time of propofol syringes for the propofol specific pump is dependent on the familiarity of pumps].

The switching time of syringes during propofol anesthesia was investigated among various anesthesiologists. One hundred and thirty times of exchanges were observed in the early 82 propofol anesthesia cases using a propofol specific syringe pump STC-525 X (Terumo, Japan) since the introduction of propofol in our hospital. The anesthesiologists were divided into three groups: group A; the board certified anesthesiologists with more than one month experience of propofol anesthesia, group B; the board certificed anesthesiologists with less than one month experience, group C: the trainee. There were no cases of intraoperative recall case. The median times of switching syringes were 14 seconds, 26 seconds, 56 seconds in the group A, group B, group C, respectively. Group A is significantly quicker than the other groups. This indicates that switching time is dependent on the experience with propofol and syringe pumps. We conclude that not only trainees but also expert anesthesiologists should be accustomed to switching syringes in order to avoid intraoperative awareness.

Anesthesiology↗
PubMed1997

Induction of dendritic cell differentiation by granulocyte-macrophage colony-stimulating factor, stem cell factor, and tumor necrosis factor alpha in vitro from lineage phenotypes-negative c-kit+ murine hematopoietic progenitor cells.

To elucidate the capacity of murine early hematopoietic progenitor cells (HPCs) to differentiate into dendritic cells (DCs), lineage phenotypes (Lin)-c-kit+ HPCs were highly purified from either wild-type or tumor necrosis factor (TNF) receptor p55 (TNF-Rp55)-deficient mice. Upon culture with granulocyte-macrophage colony-stimulating factor (GM-CSF) and stem cell factor (SCF) for 14 days, wild-type mouse Lin-c-kit+ HPCs did not exhibit characteristic features of DC such as sheet-like projections and veil processes. Moreover, these cells expressed a marginal level of DC markers such as DEC-205, CD86, and barely supported allogenic MLR. However, the addition of mouse TNFalpha generated a large number of cells with typical DC morphology, expression of high levels of Ia, DEC-205, CD86, and function of stimulating allogenic MLR. Moreover, a proportion of these mature DCs and thymic DCs expressed Thy-1 mRNA as well as Thy-1 antigen, whereas freshly isolated splenic DCs did not. These results suggested that DCs generated in our culture system phenotypically resemble thymic ones. In contrast, mouse TNFalpha failed to induce TNF-Rp55-deficient mice-derived Lin-c-kit+ HPCs to generate DCs with characteristic morphology, immunophenotype, and accessory function for T cells under the same culture conditions, suggesting a crucial role of TNF-Rp55 in TNFalpha-mediated DC differentiation from HPCs. Interestingly, human TNFalpha, which can bind to mouse TNF-Rp55 but not TNF-Rp75, was incapable to augment DC generation from wild-type mouse Lin-c-kit+ HPCs. Collectively, these results suggest that TNFalpha has a pivotal role in DC generation from murine early HPCs in collaboration with GM-CSF and SCF through the interaction of TNF-Rp55 and TNF-Rp75.

Animals↗
PubMed1997

Structural characterization of mouse monoclonal antibody 13-1 against a porphyrin derivative: identification of a disulfide bond in CDR-H3 of Mab 13-1.

The amino acid sequence of a mouse monoclonal antibody Mab13-1, a catalytic antibody against TCPP (meso-tetrakis(4-carboxyphenyl)porphyrin), was confirmed by mass spectrometric (MS) peptide mapping. The amino-terminal sequence of the heavy chain was established by MS/MS analysis of the isolated N-terminal peptide. The presence of a unique disulfide bond between Cys93H and Cys102H was identified by MS peptide mapping and sequence analysis of an S-S containing peptide. Positions of other disulfide bonds were identified to be conserved. The non-conserved disulfide bridge was found to be resistant as other intra-chain disulfide bonds against reduction under non-denaturing condition, and to be buried inside the molecule. This extra disulfide bond is expected to support antigen-binding by restricting the flexibility of CDR-H3 loop, and it might be favorable for the recognition of a plane antigen, a porphyrin derivative.

Amino Acid Sequence↗
PubMed1997

Delayed development of nervous system in mice homozygous for disrupted microtubule-associated protein 1B (MAP1B) gene.

Microtubule-associated protein 1B (MAP1B), one of the microtubule-associated proteins (MAPs), is a major component of the neuronal cytoskeleton. It is expressed at high levels in immature neurons during growth of their axons, which indicates that it plays a crucial role in neuronal morphogenesis and neurite extension. To better define the role of MAP1B in vivo, we have used gene targeting to disrupt the murine MAP1B gene. Heterozygotes of our MAP1B disruption exhibit no overt abnormalities in their development and behavior, while homozygotes showed a slightly decreased brain weight and delayed nervous system development. Our data indicate that while MAP1B is not essential for survival, it is essential for normal time course development of the murine nervous system. These conclusions are very different from those of a previous MAP1B gene-targeting study (Edelmann, W., M. Zervas, P. Costello, L. Roback, I. Fischer, A. Hammarback, N. Cowan, P. Davis, B. Wainer, and R. Kucherlapati. 1996. Proc. Natl. Acad. Sci. USA. 93: 1270-1275). In this previous effort, homozygotes died before reaching 8-d embryos, while heterozygotes showed severely abnormal phenotypes in their nervous systems. Because the gene targeting event in these mice produced a gene encoding a 571-amino acid truncated product of MAP1B, it seems likely that the phenotypes seen arise from the truncated MAP1B product acting in a dominant-negative fashion, rather than a loss of MAP1B function.

Animals↗
PubMed1997

Prevention of adenocarcinoma colon 26-induced cachexia by interleukin 10 gene transfer.

A s.c. injection of a mouse colon adenocarcinoma cell line, colon 26 clone 20, induced cachexia, as evidenced by progressive weight loss and severe hypoglycemia. Several lines of evidence indicate that a pro-inflammatory cytokine, interleukin 6 (IL-6), plays a major role, albeit partially, in the establishment of cachexia in this model. Because IL-10 can potentially inhibit the production of pro-inflammatory cytokines including IL-6, we evaluated the effects of IL-10 gene transfer on the establishment of cachexia. IL-6 transcript was detected at tumor sites of mice inoculated with parental or control vector transfectant cells, and serum IL-6 levels were markedly increased in these mice. The injection of parental cells into IL-6-deficient mice induced cachexia with elevated serum IL-6 levels comparable to wild-type mice, indicating that tumor cells are a major source of IL-6. The inoculation of IL-10-transfectant cells kept IL-10 mRNA expression at tumor sites and induced the elevation in serum IL-10 levels without affecting the growth rates of colon 26 cells both in vitro and in vivo. However, the implantation with IL-10-transfectant cells reduced the expression of IL-6 mRNA at the tumor sites and the elevation in serum IL-6 levels. Concomitantly, mice inoculated with IL-10-transfectant cells did not exhibit progressive weight loss, a reduction in food intake, or severe hypoglycemia, which was observed in mice inoculated with parental or control vector-transfectant cells. Collectively, these results suggest that IL-10 gene transfer prevented the occurrence of cachexia with a concomitant inhibition of IL-6 production at the tumor sites.

Animals↗
PubMed1997

Effect of electrochemically deposited apatite coating on bonding of bone to the HA-G-Ti composite and titanium.

The surfaces of hydroxyapatite-glass-titanium (HA-G-Ti) functionally gradient composite and titanium bars were treated with electrochemical apatite deposition, and a cathodic current was applied at 62 degrees C in a solution containing calcium and phosphate ions. Specimens with and without the electrochemical surface treatment were implanted in the femurs of Japanese white rabbits. The rabbits were sacrificed at 3, 6, and 9 weeks after implantation, and the bonding strengths of bone to these specimens were determined by a pull-out method. At 3 and 6 weeks after implantation the specimens with the electrochemical surface treatment showed larger values for the Weibull modulus and characteristic strengths than those of untreated specimens, whereas there was no remarkable difference in the results at 9 weeks. Especially the pull-out strengths of surface-treated specimens were significantly larger than the untreated ones at 3 weeks after implantation. Scanning electron microscopy and Fourier transform infrared absorption spectroscopy of the specimen surface after implantation demonstrated that formation of new bone was enhanced by the electrochemical surface treatment. It can be concluded that the electrochemical surface treatment undoubtedly contributes to the early stage fixation between bone and implant.

Animals↗
PubMed1997

Pivotal role of interleukin-8 in the acute respiratory distress syndrome and cerebral reperfusion injury.

Neutrophil recruitment is one of the hallmarks of acute inflammation. A potent neutrophil chemotactic and activating factor, interleukin-8 (IL-8), has been demonstrated to be elevated in body fluids in various human diseases and experimental animal models. Recent investigations on animal disease models using blocking antibodies to IL-8 have revealed the essential involvement of IL-8 in acute inflammation. We previously reported that the administration of a neutralizing antibody against IL-8 prevented the neutrophil infiltration and neutrophil-mediated tissue injury in several animal studies. In addition, we have recently demonstrated that anti-IL-8 treatment is also effective in prevention of two models that are very relevant to clinical situations: cerebral reperfusion injury and endotoxemia-induced acute respiratory distress syndrome-like lung injury. These results further support the hypothesis that IL-8 has a pivotal role and is a novel target for therapeutic intervention in neutrophil-mediated injury.

Animals↗
PubMed1997

Potentially multicentric hepatocellular carcinoma: clinicopathologic characteristics and postoperative prognosis.

When multiple hepatic tumors are present, it is sometimes difficult to distinguish between metastatic and multicentric hepatocellular carcinoma (HCC). To identify the important clinicopathologic features of multicentric HCC, we evaluated the clinical characteristics of patients with multicentric HCC and examined the usefulness of surgical treatment in those patients. A total of 99 patients with multiple HCCs were classified into one of the following two groups according to whether their tumors were multicentric or metastatic: Group MO consisted of 18 patients with tumors thought to have developed synchronously from multicentric origins. Group IM consisted of 64 patients with intrahepatic metastases. In this study 18% of the patients with multiple HCCs were thought to have presented with multicentric tumors. This study revealed that synchronous multicentric HCCs often affected multiple segments of the liver and responded relatively well to partial hepatectomy of individual tumor-affected areas. To appropriately treat potentially multicentric HCC, it is important to understand the histopathologic characteristics of multicentric HCC and diagnose during preoperative and intraoperative ultra-sonography, so surgical treatment may be useful.

Carcinoma, Hepatocellular↗
PubMed1997

Hepatic resection for hepatocellular carcinoma.

BACKGROUND: The significance of pTNM staging of hepatocellular carcinoma (HCC) as a prognostic factor after hepatic resection was evaluated. PATIENTS AND METHODS: The prognoses were analyzed in 262 patients treated with hepatic resection for HCC. RESULTS: As a whole, the pTNM stages correlated well with the survival rates. The survival rates of stage I and II patients were significantly higher than those of stages III and IV. However, there was no significant difference in survivals between stage I and II, and between stage III and IV-A. The survival rates of the patients treated with segmentectomy or lobectomy in stages I and II were significantly higher than those with subsegmentectomy or smaller resection. Multivariate analysis revealed that tumor size greater than 2 cm, multiple gross tumors, surgical margin less than 1 cm, and Child C classification were independently significant factors of poor survival. CONCLUSIONS: The results of hepatic resection for HCC should be stratified by pTNM staging and by Child classification of hepatic function before comparison.

Adult↗
PubMed1997

Effect of thromboxane A2 antagonists on bronchial hyperresponsiveness induced immediately after interleukin-8 inhalation in guinea-pigs.

1. Although repeated intranasal administration of interleukin-8 (IL-8) causes bronchial hyperresponsiveness (BHR) mediated via thromboxane A2 (TXA2) and airway neutrophil accumulation in guinea-pigs, the acute effect of inhaled IL-8 is unclear. We performed this study to clarify the acute effect of IL-8 on bronchial responsiveness and the role of TXA2. 2. The effects of inhaled IL-8 on bronchial responsiveness and of the TXA2 antagonists, S-1452 (0.01 and 0.1 mg kg-1) and ONO-NT-126 (1.0 or 10 micrograms kg-1), on IL-8-induced BHR were examined by use of a modified Konzett-Rössler method in guinea-pigs. 3. Inhaled IL-8 at 100 ng ml-1, which failed to induce significant changes in Pao (pressure at the airway opening), enhanced an increase in Pao induced by subsequent inhalations of ascending doses (50-200 micrograms ml-1) of methacholine and histamine, suggesting the potentiating effect of IL-8 on bronchial responsiveness. No significant leukocyte infiltration was observed histologically sixteen minutes after the IL-8 inhalation. Both S-1452 and ONO-NT-126 reduced the IL-8-induced BHR. 4. In conclusion, IL-8 rapidly causes BHR via TXA2 release in guinea-pigs.

Administration, Inhalation↗
PubMed1997

Lymph node metastasis in carcinoma of the body and tail of the pancreas.

BACKGROUND: There have been no precise reports concerning lymph node metastatic involvement in carcinoma of the body and tail of the pancreas. METHODS: Histopathological examination of lymph node involvement in 30 specimens obtained from patients who underwent pancreatic resection and wide dissection of lymph nodes, including para-aortic lymph nodes, for carcinoma of the body and tail of the pancreas was performed. RESULTS: Fourteen of 30 patients had lymph node involvement. The highest incidence of lymph node involvement was around the splenic artery (five of 30 patients), aorta (four of 30) and coeliac trunk (four of 30). No significant difference in survival rate between the lymph node-negative group and the lymph node-positive group was observed, but all patients in the positive group died within 2 years after surgery, and four patients with para-aortic lymph node involvement died from recurrence within 10 months after surgery. Survival rates were significantly worse in patients with histopathological extrapancreatic nerve plexus invasion, retropancreatic tissue invasion, tumour diameter more than 4 cm, histological portal system vein wall invasion and carcinoma invasion of the surgical margins. CONCLUSION: Although aggressive extended surgery including para-aortic node dissection has been performed, the postoperative survival rate is still low in patients with carcinoma of the body and tail of the pancreas. The high incidence of liver metastasis after surgery is a prime cause of the poor outcome, and effective therapy for postoperative liver recurrence requires evaluation.

Adult↗
PubMed1997

Sudden death in chronic dialysis patients.

METHODS: Causes of sudden death were investigated in 113 chronic dialysis patients who died during the 10-year period from July 1979 to January 1989; postmortem examination was performed on 93 of the cases (autopsy rate; 82.3%). Sudden death was regarded as death 24 h after the onset of acute illness in patients without any restriction in their daily activities. There were 35 sudden death cases out of the 93 autopsied chronic dialysis patients. We analysed the causes of sudden death for all chronic dialysis patients and for those who died suddenly. RESULTS: The mean age of the 93 cases was 61.4 +/- 10.5 years (+/-SD). Stroke was the most frequent cause of death (24 cases, 25.8%) in the 93 autopsied cases. This was followed by cardiac disease in 18 (19.4%), infectious disease in 16 (17.2%), malignancy in 14 (15.1%), and dissecting aortic aneurysm in 5 (5.4%). The mean age of the 35 sudden death cases was 60.9 +/- 10.9 years. Of the 35 sudden death cases in chronic dialysis patients, dissecting aortic aneurysm was the most common cause of sudden death (5 cases, 14.3%), followed by cerebral haemorrhage in three (8.6%), acute subdural haematoma in three (8.6%), acute myocardial infarction in two (5.7%), cerebral infarction in two (5.7%), and subarachnoidal haemorrhage in one (2.9%). CONCLUSIONS: Dissecting aortic aneurysm, leading frequently to stroke as a cause of sudden death in chronic dialysis patients, at least in Japan, should be carefully differentiated from other cardiac diseases in chronic dialysis patients, such as severe atherosclerosis.

Adult↗
PubMed1997

Peritoneal washing cytology combined with immunocytochemical staining and detecting mutant K-ras in pancreatic cancer: comparison of the sensitivity and availability of various methods.

Peritoneal metastases are the second most common site of involvement, following the liver, in pancreatic cancer. Thus, we performed peritoneal washing cytology at laparotomy to diagnose accurately the intraperitoneal spread of carcinoma cells to determine the appropriate therapy. Peritoneal washings were collected at laparotomy from 20 Japanese pancreatic carcinoma patients at Nagoya University Hospital between April 1993 and December 1994. From centrifuged deposits, we examined the cytology by three methods as follows. The first method was conventional cytology, including May-Grünwald and Giemsa, Papanicolaou, periodic acid-Schiff, and Alcian blue. The second method was immunocytochemical staining, using antibodies to carbohydrate antigen (CA19-9) and carcinoembryonic antigen. After extracting DNA from the remaining pellet, we studied the last method, detecting K-ras point mutation, by two-step polymerase chain reaction and restriction fragment length polymorphism analysis. In two cases, peritoneal metastases were macroscopically recognized, and the results of all three methods were positive. In the two other cases, where peritoneal dissemination was not macroscopically recognized, the judgments of conventional cytological study and detecting K-ras point mutation were negative. However, a few malignant cells were found by the immunocytochemical staining method. Judging from their clinical course, the positively stained cells were suggestive of malignancy. At present, the immunocytochemical staining method is the most sensitive of these three methods in peritoneal washing cytology. However, preserving DNA is suitable for repeated examination, and a modified method can be applied. If the sensitivity increases, the method of detecting K-ras has the potential to become the standard for peritoneal washing cytology in pancreatic cancer.

Adult↗
PubMed1997

Neutrophil behavior in pancreas and liver and the role of nitric oxide in rat acute pancreatitis.

The behavior of neutrophils in a rat acute pancreatitis model was observed in the pancreas and liver using fluorescence microscopy with an image analyzing system after labeling with a specific fluorescent reagent. Nonviable cells of both organs were also labeled and quantified. The role of nitric oxide in neutrophil accumulation and organ damage was estimated by administering a relatively selective inhibitor of constitutive nitric oxide synthase, N-nitro-L-arginine (L-NNA). The animal model of acute pancreatitis was induced by cerulein injection (80 mg/kg). Two groups were created, one given and the other not given L-NNA (2.5 mg/kg) prior to the induction of pancreatitis. The number of accumulated neutrophils in the pancreas and liver increased in a time-dependent manner. There was a close relation between the distribution of the neutrophils and inviable acinar cells or hepatocytes. When pretreated with L-NNA, the numbers of accumulated neutrophils and nonviable cells increased significantly in the pancreas. In the liver, a more pronounced accumulation of neutrophils was observed after treatment with L-NNA. Although hepatocyte injury was mild despite the neutrophil accumulation in the control, such injury was marked in the group treated with L-NNA. This suggests that neutrophils serve an important role in exacerbating acute pancreatitis and that nitric oxide provides a defense mechanism against neutrophil accumulation in pancreas and liver.

Acute Disease↗