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Biomedical subjects

Y Haga

Publications and source records attributed to Y Haga.

At least 37 records · Page 2Linked to original sources
PubMed2000

Elastase activity enhances the adhesion of neutrophil and cancer cells to vascular endothelial cells.

BACKGROUND: Elastase activity in cancer cells has been reported to promote their metastasis. Hence, we analyzed the influence of elastase activity of cancer cells on their responsive adhesion to vascular endothelial cells. MATERIALS AND METHODS: Human pancreatic (S2-007, S2-013, S2-020, S2-028) and colonic (COLO205) cancer cell lines were used. S2-007, S2-013, and S2-020 possess high elastase activity, whereas S2-028 and COLO205 have low elastase activity. Adhesive reactions of these cancer cells and neutrophils to TNFalpha-activated HUVEC were analyzed. Bound cells onto HUVEC were counted after incubation for 10 min. The effects of suppression of elastase activity by ZD8321, a potent elastase inhibitor, and supplementation of human neutrophil elastase (NE) on the adhesive reactions were also analyzed. In addition, E-selectin expression on HUVEC and concentrations of soluble E-selectin in the medium were measured. RESULTS: Adhesion of cells with high intracellular elastase activity to TNFalpha-activated HUVEC was suppressed by ZD8321. On the other hand, adhesion of cells with low elastase activity was enhanced by exogenous NE. Expression of E-selectin, a key molecule in leukocyte-endothelial cell interaction, on HUVEC was increased by NE. Soluble E-selectin concentration in the medium increased after the adhesive reaction between neutrophils and HUVEC. This increase was thought to be due to the shedding of cell surface E-selectin. Such responses were inhibited by ZD8321. CONCLUSION: Elastase activity has a biological function of stimulating both the E-selectin expression on HUVEC and the resultant adhesive reaction of cancer cells with them. Inhibition of elastase activity is a potent strategy for controlling cancer metastasis.

Cell Adhesion↗
PubMed2000

Clear cell adenocarcinoma with endobronchial polypoid growth.

Clear cell adenocarcinoma of the lung is extremely rare. On radiography, a 45-year-old female with fever was found to have an abnormal shadow in the left lower lung field. Bronchoscopy revealed a polypoid tumor in the left bronchus. On biopsy, the tumor was determined to be adenocarcinoma. Preoperative examination found no tumors outside of the lung. The patient underwent left lower lobectomy with bronchial wedge resection. The tumor had completely obstructed and dilated the left lower bronchus, but had not invaded the tissue outside the bronchial wall. Microscopically, the cytoplasm of the tumor cells contained abundant glycogen, and the tumor had solid and glandular structures. The tumor was diagnosed as clear cell adenocarcinoma of the lung.

Adenocarcinoma, Clear Cell↗
PubMed2000

Tumor necrosis factor alpha acts on cultured human vascular endothelial cells to increase the adhesion of pancreatic cancer cells.

We studied the effect of tumor necrosis factor alpha (TNFalpha), one of the major inflammatory cytokines, on the adhesive reaction of pancreatic cancer cells to human umbilical vein endothelial cells (HUVECs) and on the hepatic metastasis of cancer cells in vivo. After TNFalpha stimulation, the expression of E-selectin, an adhesion molecule to neutrophils on HUVECs, increased. In addition, the adhesion of pancreatic cancer cells to HUVECs increased after TNFalpha stimulation, as was observed with neutrophils. The TNFalpha-induced adhesive response depended on the extent of sialyl Lewis(a) expression on cancer cells. The hepatic metastasis in vivo was often observed when cancer cells expressing a high amount of sialyl Lewis(a) were inoculated intrasplenically after increase in plasma TNFalpha concentration by lipopolysaccharide administration. Because sialyl Lewis(a) on cancer cells is a ligand for E-selectin on HUVECs, as sialyl Lewis(x) on neutrophils, TNFalpha upregulated the adhesive interaction between sialyl Lewis(a) on cancer cells and E-selectin on HUVECs. These results suggest that production of TNFalpha after surgical trauma may stimulate the hematogenic metastasis of cancer cells with a high sialyl Lewis(a) expression.

Animals↗
PubMed1999

Less-invasive surgery for gastric cancer prolongs survival in patients over 80 years of age.

This study was undertaken to determine the most appropriate form of surgery for elderly patients with gastric cancer in relation to postoperative complications and long-term survival. A total of 72 consecutive patients over 80 years of age who underwent partial or total gastrectomy were evaluated using an E-PASS scoring system. This system is comprised of a preoperative risk score (PRS), a surgical stress score (SSS), and a comprehensive risk score (CRS) determined by both the PRS and SSS. Patients with a CRS > or = 0.5 had significantly higher rates of morbidity and mortality at 45.0% and 20.0%, respectively, than those with CRS < or = 0.5, at 17.0% and 2.1%, respectively. A Cox regression analysis of long-term survival, including death from other causes, identified five significant prognostic factors, namely: stage, curability, SSS, CRS, and allogeneic blood transfusion. Among the patients without any apparent residual cancer, a significantly better survival was seen in those who underwent less invasive surgery (SSS < 0.25), those with a CRS < or = 0.5, and those who had not been given a blood transfusion. These results suggest that less invasive surgery not requiring a blood transfusion is advisable for patients over 80 years of age with gastric cancer. Furthermore, gastrectomy with a CRS > or = 0.5 may have a poor therapeutic effect on both early and long-term outcome.

Aged↗
PubMed1999

Estimation of Physiologic Ability and Surgical Stress (E-PASS) as a new prediction scoring system for postoperative morbidity and mortality following elective gastrointestinal surgery.

Overwhelming surgical stress exceeding a patient's reserve capacity causes a disruption of homeostasis, leading to various postoperative complications. This study was undertaken to develop a new scoring system, "E-PASS", standing for the Estimation of Physiologic Ability and Surgical Stress, that predicts the postsurgical risk by quantification of the patient's reserve and surgical stress. E-PASS comprises the preoperative risk score (PRS), the surgical stress score (SSS), and the comprehensive risk score (CRS) that is determined by both scores. These scores were computed by a multiple regression analysis conducted on 292 consecutive patients who underwent elective common gastrointestinal operations at one hospital between 1992 and 1995 (internal group). The usefulness of the scores was evaluated in 989 consecutive patients who underwent the same surgical procedures during the same period at another hospital (external group). The morbidity and mortality rates increased similarly in both groups as the CRS increased. A marked step-up of both rates was observed at a CRS > 1.0, reaching mortality rates of 20% in the internal subjects and 28.5% in the external subjects. These results suggest that the E-PASS scoring system is reproducible, and that it may be useful for surgical decision making. This system requires no special examinations and can be used in every hospital.

Aged↗
PubMed1999

Absence of Mycobacterium paratuberculosis DNA in intestinal tissues from Crohn's disease by nested polymerase chain reaction.

A role of Mycobacterium paratuberculosis in Crohn's disease has been suggested for many years. To determine whether Mycobacterium paratuberculosis has the potential to cause Crohn's disease, we investigated Crohn's disease tissues for the presence of Mycobacterium paratuberculosis, using highly sensitive nested polymerase chain reaction (PCR). DNA was extracted from samples of intestine obtained from 13 patients with Crohn's disease, 14 patients with ulcerative colitis, and 13 control patients without inflammatory bowel disease. Nested PCR was performed using primer pairs complementary to sequences in the insertion element IS900 gene of Mycobacterium paratuberculosis. No Mycobacterium paratuberclulosis-specific PCR product was detected in any of these specimens, although PCR products of the appropriate size were consistently obtained using control DNA template from Mycobacterium paratuberculosis. The results did not suggest that Mycobacterium paratuberculosis is involved in the pathogenesis of Crohn's disease.

Adolescent↗
PubMed1999

[Detection of early hilar lung cancers with fluorescence bronchoscopy].

The development of fluorescence bronchoscopy has made it possible to diagnose locally superficial hilar lung cancers such as carcinoma in situ, and in some cases atypical squamous metaplasia thought to be precancerous lesions. The selection of a treatment modality can be difficult for early hilar lung cancers due to problems associated with multiple lung carcinomas and the large number of heavy smokers afflicted. Many patients also have decreased pulmonary function. If carcinoma in situ and microinvasive carcinomas can be detected early, it may be possible to treat them radically with a less invasive method than surgery, such as endoscopic laser therapy. Centrally arising squamous cell carcinoma of the tracheobronchial tree, especially in heavy smokers, is thought to develop in multiple stages from squamous metaplasia, to atypical squamous metaplasia, followed by carcinoma in situ, and finally invasive cancer. However, it is hoped that preventive medicine for lung cancer will be established whereby patients with localized atypical squamous metaplasia detected by fluorescence bronchoscopy can be carefully monitored and motivated to stop smoking, and also administered chemopreventive agents.

Adult↗
PubMed1998

Multiple factors determine the selection of the ectodomain cleavage site of human cell surface macrophage colony-stimulating factor.

Human cell surface macrophage colony-stimulating factor (CSF-1256, M-CSF alpha) is converted to a soluble growth factor by a regulated proteolytic cleavage process at amino acid residues 157-159. We have previously shown that multiple factors specified by the juxtamembrane region determine the cleavage efficiency [Deng, P., Rettenmier, C. W., and Pattengale, P. K. (1996) J. Biol. Chem. 271, 16338-16343]. In the present paper, we studied the effect of various deletion, insertion, and substitution mutations at or near the cleavage site on both the number and size of cleaved CSF-1(256) products to identify the mechanisms by which the cleavage sites are selected. Deletion of regions 161-162 or 163-165, C-terminal to the cleavage site, as well as deletion of region 150-156, N-terminal to the cleavage site, each yielded a single cleavage product that was smaller than that derived from the wild type (WT). In these experiments cleavage apparently occurred at a specific distance from the transmembrane domain. Insertion of three additional residues between the normal cleavage site and the transmembrane domain yielded one major product that was the same size as the processed form of WT CSF-1(256). In this case the selection of the cleavage site was apparently determined by the amino acid sequence of the juxtamembrane region rather than by the distance from the transmembrane domain. Other amino acid substitutions at the cleavage site caused changes in cleavage site selection, providing additional evidence for the role of amino acid sequence in cleavage site selection. Finally, a comparison of cleavage site selection in the presence and absence of tunicamycin treatment showed that N-glycosylation of certain mutant forms of CSF-1(256) sterically interfered with protease accessibility, which in turn had an effect on the selection of the site used for cleavage. Taken together, these results indicate that cleavage site selection is determined by the amino acid sequence of the juxtamembrane region, the distance of the site from the transmembrane domain, and steric accessibility of the protease.

3T3 Cells↗
PubMed1998

Ischial hypoplasia, tibial hypoplasia and facial abnormalities: a new syndrome?

A child with facial abnormalities, short stature and a variety of skeletal alterations is reported. The facial abnormalities comprised low-set ears, short nose with a long philtrum, micrognathia and cleft palate. The skeletal alterations included ischial hypoplasia, malformations of the cervical spine, hypoplasia of the lesser trochanters, tibial hypoplasia with bowing of the lower legs, tibio-fibular diastasis with malformed distal tibial epiphyses, clubfeet and brachymesophalangy. The constellation of clinical and radiological findings in the present patient do not fit any known malformation syndrome.

Abnormalities, Multiple↗
PubMed1998

Angiotensin-Converting Enzyme Gene Polymorphism and Plasminogen Activator Inhibitor 1 Levels in Subjects with Cerebral Infarction.

It has been suggested that the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene is an independent risk factor for coronary artery disease, but its relation to cerebral infarction is still controversial. Plasminogen activator inhibitor 1 (PAI-1) is also a predictor of risk of atherothrombotic disease. In this study we investigated the association of the ACE gene polymorphism and plasma PAI-1 levels in subjects with cerebral infarction. We evaluated the genotype of the ACE gene in 26 subjects with and 28 subjects without a history of ischemic stroke. The ACE genotype was analyzed by the polymerase chain reaction. Plasma PAI-1 antigen levels were measured by ELISA. There were no differences in accepted risk factors between the groups with or without cerebral infarction. However, the frequency of the D allele was significantly higher in subjects with cerebral infarction (0.63) than in those without infarction (0.39) (chi(2) = 6.306, P = 0.012). The frequency of the DD genotype of the ACE gene was also significantly higher in subjects with than in those without cerebral infarction (DD: 46.2%, ID: 34.6%, II: 19.2% vs. DD: 14.3%, ID: 50.0%, II: 35.7%, chi(2) = 6.689, P = 0.035). Plasma PAI-1 levels were not significantly different between groups with and without cerebral infarction. There was no association between the ACE genotype and PAI-1 levels. The DD genotype of the ACE gene is associated with cerebral infarction, which is independent of plasma PAI-1 level.

Journal Article↗
PubMed1998

Healing of cimetidine-resistant Ménétrier's disease by eradication of Helicobacter pylori infection.

We report a case of Ménétrier's disease associated with hypoproteinemia who was successfully treated by eradication of Helicobacter pylori infection. A 26-year-old woman had diffuse giant gastric folds with proven protein leakage from the stomach. She received cimetidine, famotidine, and omeprazole for more than 3 months with little benefit. H. pylori infection was detected, and she was treated with clarithromycin (200 mg three times a day), lansoprazole (30 mg/day), and ecabet sodium (1.5 g twice a day) for 2 weeks. After starting the treatment, rapid increase of serum albumin and IgG levels were observed. The treatment resulted in eradication of H. pylori infection, and serum albumin and IgG levels returned to normal. Histologic specimens also showed the improvement of the irregularly elongated gastric pits with inflammatory infiltrates after the treatment. This case report suggests that eradication of H. pylori is recommended therapy for the immediate improvement of Ménétrier's disease associated with hypoproteinemia.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1997

Severe myoclonic epilepsy in infancy: evolution of seizures.

Changes in seizure type of severe myoclonic epilepsy (SME) in infancy were reviewed retrospectively in 14 patients (11 males and 3 females) who were followed-up to the age of 7 years or more. The observation period ranged from 5 to 16 years with a mean of 10 years. During the follow-up, three or four types of seizures were seen per patient, but the pattern of appearance and disappearance of each seizure type varied considerably among the patients. Tonic-clonic convulsion, either generalized or unilateral, was seen most consistently through the entire course, and it continued to the end of follow-up in 11 patients (79%). On the contrary, myoclonic seizure, complex partial seizure, and atypical absence often disappeared and reappeared repeatedly during the course. In SME, seizure symptoms varied widely among patients in comparison with other neurological symptoms, and the most consistent core seizure type was tonic-clonic convulsions.

Child↗
PubMed1997

Systemic inflammatory response syndrome and organ dysfunction following gastrointestinal surgery.

OBJECTIVES: Progression from systemic inflammatory response syndrome (SIRS) to sepsis, severe sepsis, and septic shock has been demonstrated in a variety of patients. However, the presence of SIRS alone was not helpful in predicting the development of multiple organ dysfunction syndrome (MODS) since SIRS includes many nonprogressive conditions. This study was conducted to investigate the clinical significance of SIRS in postoperative patients. DESIGN: Retrospective study. SETTING: The surgical department of a university hospital. PATIENTS: Two hundred ninety-two consecutive patients who received elective common gastrointestinal surgery (esophagectomy, pancreatoduodenectomy, hepatectomy, gastrectomy, colorectal resection, and laparoscopic cholecystectomy) between 1992 and 1995. INTERVENTIONS: Patients were analyzed for preoperative physiologic status, surgical stress parameters, and postoperative status of SIRS, complications, and end-organ dysfunction. MEASUREMENTS AND MAIN RESULTS: Duration of SIRS or positive criteria's number of SIRS after surgery significantly correlated with surgical stress parameters (blood loss/body weight and operation time) and peak serum C-reactive protein concentrations. SIRS that continued or reappeared after postoperative day 3 was an early sign of postoperative complications. SIRS continuing consecutively for 2 days after postoperative day 3 had a 70.6% positive predictive value and a 92.5% negative predictive value for postoperative complications. Septic complications and prolongation of SIRS were associated with MODS. Five of six patients who met the SIRS criteria for >30 days developed severe MODS, and three of them died. CONCLUSIONS: SIRS is a useful criterion for the recognition of postoperative complications and end-organ dysfunctions. Early recovery from SIRS may arrest the progression of organ dysfunction.

Aged↗
PubMed1997

A case retaining contact urticaria against egg white after gaining tolerance to ingestion.

A girl, 5.7 years old, gained tolerance to egg white ingestion in spite of high immunoglobulin E (IgE) antibody titers to egg white but retained contact urticaria against egg white. She developed atopic dermatitis on her face at 2 months of age and showed high IgE antibody titers to egg white and cow's milk. Accidental ingestion of egg products initiated immediate symptoms such as wheezing, urticaria, erythema and edema of the eyelids and conjunctiva three times. These symptoms were confirmed by challenge tests using boiled egg white at 3.9 years of age. She also reacted positively to a 20 min patch test on her volar arm with raw egg white. However, there were no reactions to the oral challenge test by boiled egg and freeze-dried egg white at 5.1 and 5.7 years of age, respectively. This non-responsiveness was confirmed by a double-blind, placebo-controlled food challenge using freeze-dried egg white. Nevertheless, she showed positive reactions to a 20 min patch test with freeze-dried egg white. Her IgE antibody titers to the egg white components including ovomucoid, ovalbumin, ovotransferrin and lysozyme as well as egg white were high from 2.9 to 5.7 years old. Her IgE antibody titers for the ovomucoid fragments digested by pepsin, chymotrypsin and trypsin were not lower than those of positive control subjects. The binding activity of IgE antibody to ovomucoid, however, decreased from 2.9 to 5.6 years as shown by radioallergosorbent test (RAST) inhibition assays. The IgE antibody showed weaker binding activity to pepsin- and chymotrypsin-digested ovomucoid that were filtered through cut-off 10,000 filter at the age of 2.1 and 5.7 years. We speculated that the maturation of secretion of digestive enzymes was involved in the mechanisms of the acquisition of tolerance to egg white ingestion in spite of the persistence of contact urticaria.

Antibody Affinity↗
PubMed1997

Protective efficacy of an affinity-purified hemolysin vaccine against experimental swine pleuropneumonia.

Protective efficacy of Actinobacillus pleuropneumoniae extracellular hemolytic toxins, RTX-toxin I (Apx I) and Apx II, was evaluated in pigs. The hemolysins were purified from culture supernatant of A. pleuropneumoniae strain HA-337, serotype 1 by immunoaffinity chromatography using a monoclonal antibody specific for Apx I or Apx II as ligand. Four pigs were vaccinated with the purified hemolysins absorbed on aluminum phosphate gel adjuvant. Four pigs of a control group were given placebo. Hemolysin-neutralizing antibodies were detected only in vaccinated group after booster injection. One of four control pigs died following an aerosol challenge with the homologous strain, and three surviving pigs developed serious clinical signs of pneumonia and had extensive lung lesions. In contrast, there was no mortality in vaccinated group. Only transient hyperthermia was observed in two vaccinated pigs after challenge. A necropsy, two vaccinated pigs had slight localized pulmonary lesions, though the remaining two had no lung lesions at all. These results indicate that the hemolysin vaccine made of Apx I and Apx II has good protective activity against swine pleuropneumonia caused by A. pleuropneumoniae serotype.

Actinobacillus Infections↗