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Biomedical subjects

K Yamazaki

Publications and source records attributed to K Yamazaki.

At least 163 records · Page 9Linked to original sources
PubMed2000

Anastomotic complications after bronchoplastic procedures for nonsmall cell lung cancer.

BACKGROUND: Anastomotic complications associated with bronchoplastic procedures cannot be completely avoided despite the improvements made in surgical techniques and suture materials. Thus, the present study attempted to clearly define the significant factors influencing anastomotic complications. METHODS: Between 1978 and 1998, 47 patients with primary nonsmall cell lung cancer underwent bronchoplastic procedures. The incidences of anastomotic complications were calculated according to each of the following clinical factors: primary site, age, pathologic type, pT factor, pN factor, pulmonary arterioplasty, surgical procedure, suture material, coverage of the anastomotic line, positive resection margin, and preoperative chemotherapy. The results were analyzed using univariate and multiple logistic regression analysis. RESULTS: Anastomotic complications occurred in 8 patients. Four had anastomotic dehiscence and 4 had stenosis. Of these 8 patients, the resection margin was diagnosed as being positive in 6 patients. Three showed metastasis of the most distal mediastinal lymph node whereas the others had a residual tumor at the bronchial resection margin. According to multiple logistic regression analysis, only pN factor (p = 0.04) and positive resection margin (p = 0.02) had a significant influence on the complications. CONCLUSIONS: Thus, pN2 patients, especially those with metastasis of the most distal mediastinal lymph node and patients with a residual tumor at the bronchial resection margin, have a significantly higher risk of anastomotic complications.

Adult↗
PubMed2000

Direct IFNluence of interferon-gamma on proliferation and cell-surface antigen expression of non-small cell lung cancer cells.

In order to clarify the anti-tumor activity of IFN-gamma, we investigated the direct IFNluence of IFN-gamma on both the growth and cell-surface antigen expression of tumor cells. In the present study, four human lung cancer cell lines were used; two squamous cell lines (QG-56, QG-95) and two adenocarcinoma cell lines (PC-9, PC-12). In all four tumor cell lines, mutations were detected in exon 7 of the p53 gene by a PCR-FSSCP analysis. The proliferation of QG-56 or QG-95 was inhibited by IFN-gamma in a dose-dependent manner with about 70% inhibition at 1000 JRU/ml while that of PC-9 was slightly inhibited with maximally 25% inhibition at 1000 JRU/ml. The growth of PC-12 was not inhibited at all. In QG-56, QG-95 and PC-9, the fraction of cells in G1 phase increased while the fractions of cells in both S and G2/M phases decreased after exposure to IFN-gamma (200 JRU/ml) for 72 h. The growth inhibition by long-term exposure to IFN-gamma was irreversible in QG-56. After culture in the presence of IFN-gamma (200 JRU/ml) for 14-16 days, tumor cells were examined for expression of various antigens, including HLA-class I, HLA-class II, and CEA. In all cell lines but PC-12, 100% of cells expressed HLA-class I after incubation with IFN-gamma. Both HLA-class II and CEA were also induced in those cell lines. The proportion of HLA-class II-positive cells or that of CEA-positive cells varied among the cell lines. Of the three antigens, the degree of HLA-class II expression paralleled that of growth inhibition by IFN-gamma treatment. These results suggested that in various function of IFN-gamma against tumor cells, the anti-proliferative effect might be closely linked with the induction of HLA-class II probably through a similar posttranscriptional process, independent of the function of p53 gene.

Antigens, Surface↗
PubMed2000

Fatal cardiovascular injuries to the unbelted occupant associated with airbag deployment: two case-reports.

We present two forensic autopsy cases of unbelted occupants associated with the airbag deployment in motor vehicle collisions. Both victims suffered from cardiovascular injuries which were the cause of death. Case 1: A 50-year-old man sustained a contusion on the left anterior chest with rib fractures and laceration of the intrapericardial inferior vena cava, the right ventricle, and the right pleuropericardium. Case 2: A 40-year-old man sustained multiple rib fractures, sternal fracture, and the rupture of the right ventricle. Autopsies and vehicle examinations revealed that both victims' chest seemed to strike the steering wheel through the deployed airbag. Therefore, we determined that the source of blunt impact force is the steering wheel through the airbag rather than airbag deployment only. In light of these two cases, we learned that the steering wheel should be considered as the blunt impact force inducing cardiovascular injuries even in cases in which the airbag has been deployed.

Journal Article↗
PubMed2000

Characterization of 5'-flanking region of human aggrecanase-1 (ADAMTS4) gene.

Aggrecanase-1, also known as ADAMTS4 (a disintegrin and metalloproteinase with thrombospondin motifs 4), cleaves at the Glu373-Ala374 site of aggrecan, thereby indicating aggrecan degradation. It is thought that ADAMTS4 plays a pivotal role in inflammatory joint diseases and cartilage degradation. To elucidate the mechanisms of regulation of ADAMTS4 gene expression, we cloned the 5'-flanking region of the human ADAMTS4 gene and characterized its promoter activity by means of reporter assay using porcine chondrocytes and NIH3T3 cells. Reporter gene analysis using deletion variants suggested that the region between -383 and +10 relative to the tentative transcription start site is necessary for full promoter activity; this region contains one Sp1 and three AP2 sites. In addition, the segment between -726 and -384 appears to contain silencer element(s). A complete deletion mutant of the nuclear factor I (NFI) binding site at -441 to -429 resulted in recovery of the promoter activity in chondrocytes, but not in NIH3T3 cells. Thus, the NFI site is involved in negative regulation of the human ADAMTS4 promoter activity in chondrocytes.

3T3 Cells↗
PubMed2000

Early mutation of precore (A1896) region prior to core promoter region mutation leads to decrease of HBV replication and remission of hepatic inflammation.

To evaluate the relationship between mutations and clinical courses, we investigated precore (preC) and core promoter (CP) mutations and serum HBV DNA levels in HBe-antibody-positive HBV carriers. Fifty-six asymptomatic carriers (ASC), 29 patients with chronic hepatitis who showed normal ALT levels for more than two years (CH-ASC), 31 patients with chronic hepatitis (CH), and 32 patients with hepatocellular carcinoma (HCC) were studied. Almost all patients (99.2%) had mutations in either CP or preC. Mutation only in preC (A1896) was present in 52.2% with ASC, 25.0% with CH-ASC, 16.1% with CH, and 8.0% with HCC, and was significantly higher in ASC (P < 0.01). The patients with only preC mutation showed low HBV DNA levels in each clinical stage. The mutation of preC (A1896) prior to the mutation of CP might control the replication of HBV, which leads to the remission of hepatitis.

Adult↗
PubMed2000

Clonal accumulation of T cells bearing V beta 6 T-cell receptor in chronic inflammatory periodontal disease.

Our previous study demonstrated that among the various T-cell receptor V beta gene segments, T-cell receptor V beta 6 gene-bearing T cells are predominant in periodontitis lesions. To explore the clonality of T cells expressing V beta 6 T-cell receptor, which is determined by the heterogeneity of the complementarity-determining region 3(CDR3), V beta 6-C beta polymerase chain reaction products derived from gingival tissue and peripheral blood of periodontitis patients were analyzed by single-strand conformation polymorphism and nucleotide sequence. Both techniques provided quite similar results in terms of the number of accumulated clones in which clonal accumulation of T-cell receptor V beta 6-bearing T cells was found in most periodontitis lesions but not in peripheral blood. From the analysis of deduced amino acid sequences, a possible conserved amino acid residue in the CDR3 region of the periodontitis lesion-derived sequences was found in most patients. This conserved amino acid motif however, was not identified. Furthermore, skewed J beta gene segment usage was observed for expanded clones from periodontitis lesions. Our results suggest that T cells infiltrating periodontitis lesions are responding to a restricted number of antigens or epitopes.

Adult↗
PubMed2000

Primary large-cell neuroendocrine carcinoma of the parotid gland: immunohistochemical and molecular analysis of two cases.

Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is a newly proposed clinicopathologic entity; a few cases of LCNEC have been reported in other sites, such as the uterine cervix and the thymus. In the salivary glands, LCNEC is extremely rare and is not recognized as a specific entity in the World Health Organization classification. We retrospectively reviewed from our files 1675 cases of surgically resected primary parotid gland tumors and found 2 cases of LCNEC that fulfilled the criteria of pulmonary LCNEC. These cases occurred in 72- and 73-year-old men who had short histories of enlarging parotid gland tumors. The tumors were composed of large cells that exhibited organoid, solid, trabecular, and rosette-like growth patterns with a high mitotic rate and a conspicuous tendency for necrosis. The tumor cells were polygonal and characterized by a moderate nuclear:cytoplasmic ratio, coarse chromatin, and conspicuous nucleoli. Immunohistochemical examination revealed that the tumor cells were positive for six general neuroendocrine markers, cytokeratin, p53, bcl-2, epidermal growth factor receptor, and cyclin D1. Markedly reduced expressions of p21Waf1 and p27Kip1 were also noticed. The Ki-67 labeling index was more than 50% in both cases. One case showed loss of heterozygosity at TP53 accompanied by a p53 gene point mutation. Loss of heterozygosity at chromosome 9p21 was detected in both cases; one was accompanied by a p16 gene silent point mutation. Both patients died of the disease, with recurrence 5 months and 4 years after surgery, respectively. These findings indicate that LCNEC is a rare but distinct salivary gland tumor with highly aggressive biologic behavior. Multiple alterations of cell cycle regulators and tumor suppressor genes may play an important role in presenting the biologic characteristics of this rare parotid gland tumor.

Aged↗
PubMed2000

Elevated CTLA-4 expression on CD4 T cells from periodontitis patients stimulated with Porphyromonas gingivalis outer membrane antigen.

To characterize the T cell response to Porphyromonas gingivalis, we examined the expression of costimulatory molecules on T cells derived from adult periodontitis patients with high serum antibody titre to P. gingivalis. The expression of CD28, CTLA-4, CD40 ligand (CD40L) on CD4+ T cells was analysed by flow cytometry. IL-10 and transforming growth factor-beta (TGF-beta) mRNA expression were determined by reverse transcription-polymerase chain reaction (RT-PCR) and subsequent image analysis. Peripheral blood mononuclear cells (PBMC) derived from periodontitis patients showed higher proliferative responses to P. gingivalis outer membrane (OM) than those from healthy controls (P < 0.05). The percentage of CTLA-4+ cells within CD4+ T cells of patients was significantly higher than that of healthy controls after P. gingivalis OM stimulation (33.0% versus 11.9%, P < 0.01). There was no significant difference in the percentages of CD28+ cells and CD40L+ cells, and the percentage of CD40L+ cells was low in both groups even after stimulation. Stimulation of PBMC with P. gingivalis OM induced significantly higher IL-10 mRNA expression in periodontitis patients than in healthy controls (P < 0.05). The level of TGF-beta mRNA expression of patients tended to be higher than that of healthy controls, but there was no significant difference. To elucidate the functional role of CTLA-4, we further investigated the secondary proliferative response to P. gingivalis OM. Interestingly, P. gingivalis OM stimulation did not enhance antigen-specific secondary response. Anti-CTLA-4 MoAb had no effect on proliferation in the presence of P. gingivalis OM. CTLA-4Ig suppressed the proliferative response significantly (P < 0.01). These results suggest that T cell responses to P. gingivalis OM may be regulated by CTLA-4 that is expressed at the late phase of T cell activation, and, in part, immunosuppressive cytokines. Taken together, CTLA-4 may play a crucial role in the pathogenesis of chronic inflammatory periodontal disease.

Abatacept↗
PubMed2000

Selective expansion of T cells in gingival lesions of patients with chronic inflammatory periodontal disease.

Chronic inflammatory periodontal diseases are characterized by a cellular infiltrate and are similar in many respects to other chronic inflammatory diseases. While periodontopathic bacteria have been recognized as the principal causative agent and the immune response to these bacteria is thought to be responsible for the tissue destruction, the full aetiological spectrum is still incompletely understood. In addition to many cell types such as polymorphonuclear leucocytes and macrophages, T cells have been implicated in pathogenesis and are considered to have regulatory roles in progression of the disease. Based on our recent studies demonstrating biased expression of several Vbeta families in periodontitis tissues, the aim of this study was to characterize further the T cells relevant to the disease process by reverse transcription-polymerase chain reaction-single-strand conformation polymorphism (RT-PCR-SSCP) and subsequent nucleotide sequence analysis of complementarity-determining region 3 (CDR3) of the TCR beta-chain. In spite of the likely involvement of numerous bacteria, the present study has clearly shown the oligoclonality of infiltrating T cells in periodontitis lesions in contrast to low clonality of peripheral blood T cells as evidenced by the appearance of distinct bands in gingival tissue samples and smear pattern of peripheral blood on SSCP gels. These were confirmed by the DNA sequencing of the CDR3 of Vbeta16 of selected samples. The analysis of deduced amino acid sequences demonstrated amino acid motifs in the CDR3 region of the periodontitis lesion-derived sequences from each patient. The results indicate that gingival tissue-infiltrating T cells recognizing a limited number of antigens or epitopes are involved in the disease process.

Adult↗
PubMed2000

Elevated humoral immune response to heat shock protein 60 (hsp60) family in periodontitis patients.

The presence of antibodies to the 60-kD human and Porphyromonas gingivalis GroEL hsp60 in the sera and inflamed gingival tissues of periodontitis patients was examined. In order to obtain the antigens, recombinant plasmids carrying human hsp60 and P. gingivalis GroEL genes were constructed and expressed as histidine-tagged recombinant proteins. Immunoreactivities of these proteins were confirmed by MoAbs specific to mammalian hsp60 and cross-reactive with both mammalian and bacterial hsp60. Western blot analysis clearly demonstrated that the number of periodontitis patients showing a positive response to P. gingivalis GroEL was higher than the number of periodontally healthy subjects. Furthermore, anti-P. gingivalis GroEL antibody was detected in all samples of gingival tissue extracts. For human hsp60, a higher frequency of seropositivity was found in the periodontitis patients than in the healthy subjects. In addition, the periodontitis patients demonstrated stronger reactivity compared with the healthy subjects. Quantitative analysis of serum antibodies by ELISA also demonstrated that the levels of antibodies in the sera of patients were significantly higher than those of control subjects. In the gingival tissue extracts, seven out of 10 patients demonstrated a positive response to human hsp60 and tso of these demonstrated strong positivity. Affinity-purified serum antibodies to human hsp60 and P. gingivalis GroEL from selected patients reacted with P. gingivalis GroEL and human hsp60, respectively, suggesting cross-reactivity of antibodies. These results suggest that molecular mimicry between GroEL of the periodontopathic bacterium P. gingivalis and autologous human hsp60 may play some role in immune mechanisms in periodontitis.

Adult↗
PubMed2000

Update: the clinical importance of acetaminophen hepatotoxicity in non-alcoholic and alcoholic subjects.

Acetaminophen (paracetamol) is one of the most commonly used over-the-counter medications. Taken in doses greater than 150 mg/kg/day (>10 g), it usually causes acute liver failure. The authors review mainly the management of acetaminophen toxicity in both users and nonusers of alcohol. Chronic alcoholics are a special subgroup, who risk serious toxicity when taking acetaminophen, even in therapeutic doses. The acetaminophen-alcohol interaction is complex, because acute and chronic ethanol have opposite effects. This review also considers physiological and clinical changes, as well as the diagnosis and treatment of acetaminophen poisoning.

Acetaminophen↗
PubMed2000

Effects of bright light pre-exposure on sleep onset process.

This study investigated the effects on the sleep onset process of enhanced cerebral cortex activity caused by bright light pre-exposure. Seven healthy young adults were exposed for 40 min before sleep onset, 2500 lx of bright light and 10 lx of dim light. Other factors that affect sleep onset (e.g. circadian phase) were experimentally controlled. Five stages of hypnagogic electroencephalogram (EEG) were scored. The latency of each EEG stage was longer at bright light than at dim light conditions, suggesting that activation of brain activity by bright light pre-exposure strongly regulates the sleep onset process.

Adult↗
PubMed2000

Rod-type transducin alpha-subunit mediates a phototransduction pathway in the chicken pineal gland.

The chicken pineal gland is a photosensitive neuroendocrine organ producing melatonin in circadian clock-regulated and light-sensitive manners. To understand the relationship between the photoreceptive molecule pinopsin and the light-dependent melatonin suppression that is sensitive to pertussis toxin treatment, we have searched for pertussis toxin-sensitive G protein alpha-subunits expressed in the chicken pineal gland. Here we report the cDNA cloning of the pineal transducin alpha-subunit (Gtalpha), which is highly homologous to human retinal rod cell-specific Gt(1)alpha. Concurrent cDNA cloning of chicken retinal Gt(1)alpha and Gt(2)alpha (rod and cone cell-specific alpha-subunits of transducin, respectively) revealed that the chicken pineal Gtalpha is identical to the retinal Gt(1)alpha. Double-immunostaining analysis of the chicken pineal sections localized Gt(1)alpha-immunoreactivity in the rudimentary outer segments of both follicular and parafollicular pinealocytes that were immunopositive to anti-pinopsin antibody. To examine whether pineal Gt(1)alpha is involved in the pineal phototransduction pathway, trypsin protection assay was applied for detecting the conversion of GDP-bound Gt(1)alpha into the guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS)-bound form in the pineal membrane homogenate. It was clearly demonstrated that the pineal Gt(1)alpha is activated in a light-dependent manner in the presence of GTPgammaS. These data together suggest strongly that pineal Gt(1)alpha mediates the phototransduction pathway triggered by pinopsin in the chicken pinealocytes.

Amino Acid Sequence↗
PubMed2000

Continuously maintaining positive flow avoids endocardial suction of a rotary blood pump with left ventricular bypass.

This study showed the usefulness of maintaining positive pump flow to avoid endocardial suction and as an assist bypass. Three calves were implanted with centrifugal pumps. Hemodynamics and pump parameters were measured at varying pump speeds (from 1,100 to 2,300 rpm). In each test pump, speed was adjusted to create 3 hemodynamic states: both positive and negative flow (PNF), positive and zero flow (PZF), and continuously positive flow (CPF). The pump flow volume was determined during systole (Vs) and diastole (Vd). Vs in PNF was 29.6 ml and was not significantly different from Vs in PZF (p > 0.15). Vd in PNF was significantly different from Vd in PZF (p < 0.05). All bypass rates of PNF were over 30% of pulmonary flow. All PZF bypass rates were between the PNF rate and the CPF rate. These data showed that PZF satisfied the minimum requirement of assist flow and was under 100% bypass. Thus, PZF may avoid endocardial suction.

Analysis of Variance↗
PubMed2000

Successful repair of tracheal defect using gelatin-resorcin-formaldehyde-glue-reinforced fascia patch.

We describe the case of a 63-year-old female who underwent repair of a membranous tracheal defect. The tracheal perforation occurred after subtotal esophageal resection, and was associated with empyema due to esophago-gastric anastomotic leakage. We employed a fascia patch reinforced with Gelatin Resorcin- Formaldehyde/Glutaraldehyde glue for the repair, as pedicle muscular flaps were not available due to thoracotomy and a pericardial patch was inadequate because of the empyema. Our method was uncomplicated and provided a satisfactory result.

Drug Combinations↗
PubMed2000

Somatic mutations of the multiple endocrine neoplasia type 1 (MEN1) gene in patients with sporadic, nonfamilial primary hyperparathyroidism.

BACKGROUND: Multiple endocrine neoplasia type 1 (MEN 1) is a syndrome with tumors of many endocrine tissues. Germline MEN1 gene mutations were found in most patients with familial or sporadic MEN 1. Recently, somatic MEN1 gene mutations were also detected in sporadic non-MEN 1 endocrine tumors. METHODS: We used direct sequence analysis to investigate MEN1 gene mutations in 30 parathyroid tumors obtained from 30 patients with sporadic, nonfamilial primary hyperparathyroidism. RESULTS: Four patients had somatic mutations of the MEN1 gene, comprising 1 small insertion (1091insAGC), one missense mutation (G42S), and 2 non-sense mutations (E388X, R460X). Identical missense and non-sense mutations were found in patients with familial and non-familial MEN 1. There were no differences between clinical features of patients with and without MEN1 gene mutations. CONCLUSIONS: The incidence of somatic MEN1 gene mutations (13.3%) in Japanese patients with sporadic, nonfamilial primary hyperparathyroidism is almost equal to those of such patients in the United States and Sweden. Occasionally, the MEN1 gene mutation sites in sporadic parathyroid tumors are identical to those reported in tumors from patients with familial or sporadic MEN 1.

DNA↗
PubMed2000

High accumulation of plasminogen and tissue plasminogen activator at the flow surface of mural fibrin in the human arterial system.

PURPOSE: We assessed the fibrinolytic activity of the organized mural thrombus lining of aneurysms and prosthetic grafts. METHODS: Between May 1995 and April 1998, the full-thickness mural thrombi of aneurysms and the pseudointima lining of vascular grafts were obtained from 12 patients, ranging from 55 to 78 years in age, who underwent elective surgery. These included five aortic arch aneurysms, four abdominal aortic aneurysms, and three patent synthetic vascular grafts. The specimens were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE)/immunoblot and immunohistochemistry for human plasmin/plasminogen, tissue plasminogen activator (tPA), and fibrin degradation product (D-dimer). RESULTS: In the SDS-PAGE/immunoblot, 25- and 27-kd bands appeared specifically in experimental fibrin plates after limited digestion by plasmin and were also recognized in the mural thrombi. The presence of bands at 25 and 27 kd, which were most prominent in sections near the flow surface layer, was consistent with the hypothesis that the mural fibrin was digested by the endogenous plasmin. Apparent immunoreactivity was found at the flow surface of the masses at a thickness of 10 to 400 micrometer suggesting the presence of a plasminogen and tPA-rich layer, with D-dimer as a consequential product of fibrinolysis. CONCLUSION: The hypothesis that fibrin surfaces in the arterial system acquire fibrinolytic activity because of digestion by circulating endogenous plasmin was confirmed; this may contribute to the antithrombogenicity of these flow surfaces.

Aged↗