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Biomedical subjects

Y Uchida

Publications and source records attributed to Y Uchida.

At least 145 records · Page 8Linked to original sources

Multiple gastric carcinomas 21 years after gastrojejunostomy without gastrectomy. Report of a case.

We report a case of gastric carcinoma after gastrojejunostomy (GJ-stomy) without gastrectomy. Multiple gastric carcinomas were discovered 21 years after GJ-stomy without gastrectomy which had been performed for treatment of pyloric stenosis due to severe gastric ulcer. Multiple gastric carcinomas were found in the stomach, or the esophagocardiac junction, and in the corpus and anastomotic lesion of the GJ-stomy. Under the light microscope, intestinal metaplasia was detected in the antral mucosa and the area around the anastomosis. In immunohistochemical analysis, p53-specific antibodies gave a positive reaction in every gastric carcinoma and in the noncancerous gastric glands around the carcinoma at the anastomosis and in the corpus. Cells positive for immunostaining with Ki-67-specific antibodies were more numerous in all gastric carcinomas and in the area around the anastomotic lesion than in the normal gastric mucosa. Hsp70-specific antibodies reacted with cells in the noncancerous glands around the carcinoma in the anastomotic area. Mucosal injury and the potential for carcinogenesis due to exposure to gastroduodenal reflux are discussed. The results of this study suggest that similar cases with gastroduodenal reflux should be followed carefully.

Adenocarcinoma↗

Infection and inflammation induce LDL oxidation in vivo.

Epidemiological studies have shown an increased incidence of coronary artery disease in patients with chronic infections and inflammatory disorders. Because oxidative modification of lipoproteins plays a major role in atherosclerosis, the present study was designed to test the hypothesis that the host response to infection and inflammation induces lipoprotein oxidation in vivo. Lipoprotein oxidation was measured in 3 distinct models of infection and inflammation. Syrian hamsters were injected with bacterial lipopolysaccharide (LPS), zymosan, or turpentine to mimic acute infection, acute systemic inflammation, and acute localized inflammation, respectively. Levels of oxidized fatty acids in serum and lipoprotein fractions were measured by determining levels of conjugated dienes, thiobarbituric acid-reactive substances, and lipid hydroperoxides. Our results demonstrate a significant increase in conjugated dienes and thiobarbituric acid-reactive substances in serum in all 3 models. Moreover, LPS and zymosan produced a 4-fold to 6-fold increase in conjugated diene and lipid hydroperoxide levels in LDL fraction. LPS also produced a 17-fold increase in LDL content of lysophosphatidylcholine that is formed during the oxidative modification of LDL. Finally, LDL isolated from animals treated with LPS was significantly more susceptible to ex vivo oxidation with copper than LDL isolated from saline-treated animals, and a 3-fold decrease occurred in the lag phase of oxidation. These results demonstrate that the host response to infection and inflammation increases oxidized lipids in serum and induces LDL oxidation in vivo. Increased LDL oxidation during infection and inflammation may promote atherogenesis and could be a mechanism for increased incidence of coronary artery disease in patients with chronic infections and inflammatory disorders.

Animals↗

Pneumoconiosis-related lung cancers: preferential occurrence from diffuse interstitial fibrosis-type pneumoconiosis.

It has been reported that patients with pneumoconiosis occasionally have a diffuse interstitial fibrosis (DIF) that resembles interstitial pneumonia, but little is known about the relation between pneumoconiosis-associated DIF and the risk of lung cancer. In the present study, we evaluated the incidence of DIF by chest CT and its contribution to lung cancer in 563 patients with nonasbestos pneumoconiosis. Fifty-five (10%) of the 563 patients had DIF. Pneumoconiosis with DIF had an exceedingly high concurrence of lung cancers when compared with pneumoconiosis without DIF (29 [53%] of 55 versus 78 [15%] of 508, p < 0.001). Squamous cell carcinomas (SCCs) of the lung from pneumoconiosis with DIF exclusively comprised peripheral-types, as compared with SCCs from pneumoconiosis without DIF (13 [100%] of 13 versus 33 [72%] of 46, p = 0.03). In addition, lung cancers arose frequently from the area of DIF in pneumoconiosis with DIF (20 [74%] of 27). Furthermore, our pathologic examination revealed that dysplasias from pneumoconiosis with DIF were significantly more frequently observed in peripheral bronchioli than were dysplasias from pneumoconiosis without DIF (11 [69%] of 16 versus 20 [30%] of 66, p = 0.01). p53 expression evaluated by immunohistochemistry was frequently observed in dysplasias from pneumoconiosis with DIF, although it was not significantly different compared with that in dysplasias from pneumoconiosis without DIF (5 [50%] of 10 versus 12 [38%] of 32). Taken together, these results may suggest a positive causal relationship between pneumoconiosis and peripheral-type SCCs of the lung, and further indicate a pivotal role of diffuse fibrosis for the excess incidence of lung cancers, especially peripheral-type SCCs, in DIF-type pneumoconiosis.

Aged↗

Dislocation of E-cadherin in the airway epithelium during an antigen-induced asthmatic response.

The airway epithelium plays a critical role in asthma. E-cadherin, located on the basolateral side of the epithelial cells, forms adherent junctions. To investigate the role of E-cadherin on the regulation of permeability of molecules and fluid in asthmatic responses, we observed the dynamics of E-cadherin after an immunochallenge against guinea pigs. Immunohistochemical studies revealed that E-cadherin was expressed on the lateral sides of epithelial cells before the immunochallenge and after immediate airway responses (IAR). However, E-cadherin immunoreactivities decreased from the basolateral region in late airway responses (LAR) 6 h after the challenge. Simultaneously, soluble E-cadherin immunoreactivities were detected in lavage fluid only in LAR, suggesting that E-cadherin is partly cleaved and released into the lumen in LAR. Airway permeability, which was examined by penetration of horseradish peroxidase from the airway side into the epithelium, increased in both IAR and LAR. These results suggest that E-cadherin detachment from the lateral side of the epithelial cells increased airway permeability in LAR but not IAR. We conclude that an antigen challenge causes an opening of adherent junctions as well as increases airway permeability in LAR. This mechanism would participate in airflow limitation during attacks and the increase of airway permeability and hyperresponsiveness in asthmatics.

Animals↗

Autoantibody responses to cardiolipin and DNA in infancy: association with lymphocytic panniculitis.

We report an infant with anticardiolipin (aCL) antibodies who presented with erythematous nodular skin lesions and elevated liver enzyme levels. The cutaneous manifestation was histologically lymphocytic lobular panniculitis with vasculitic and hemorrhagic changes. The infant also had low levels of anti-double stranded DNA (dsDNA) and anti-single stranded DNA (ssDNA) antibodies. There were no detectable antibodies to small nuclear ribonucleoproteins including Ro/SSA and La/SSB. His mother was consistently seronegative for any of these antibodies. Without corticosteroid therapy, cutaneous lesions resolved and anticardiolipin antibodies, but not anti-dsDNA and ssDNA antibodies, normalized within 16 months after the onset of the disease. Our patient demonstrated an uncommon presentation of aCL related cutaneous manifestation, the presentation with panniculitis being only the third such patient reported in the literature. Of great interest was the appearance of aCL antibodies and skin lesions during very early infancy.

Adult↗

Molecular analysis of maleate cis-trans isomerase from thermophilic bacteria.

Several strains of thermophilic bacteria containing maleate cis-trans isomerase were isolated from soil samples and identified as Bacillus stearothermophilus, Bacillus circulans, Bacillus brevis, and Deleya halophila. The maleate cis-trans isomerase was purified and characterized from one of the isolated strains, B. stearothermophilus MI-102. The purified enzyme of strain MI-102 showed higher thermal stability than the enzyme of a mesophile, Alcaligenes faecalis IFO13111. The seven maleate cis-trans isomerase genes (maiA) of thermophile were cloned and sequenced. B. stearothemophilus MI-102 MaiA has 67% amino acid identity with A. faecalis MaiA. All eight amino acid sequences of maiA gene products had significant conserved regions containing cysteine residues, which were previously suggested to be involved in an active site of the enzyme. To probe the catalytic mechanism, three cysteine residues in the conserved regions of A. faecalis MaiA were replaced with serine by site-directed mutagenesis. The results suggest that Cys80 and Cys198 play important roles in the enzyme activity.

Alcaligenes↗

Local antithrombotic therapy using a novel porous balloon catheter.

The efficacy of local treatment of thrombosis with low-dose antithrombotic drugs (heparin: 30 U/kg, or argatroban: 0.02 mg/kg) was investigated using a novel porous balloon catheter. This novel balloon catheter can deliver drug into arterial walls without causing vascular trauma. Thrombus formation was significantly inhibited in balloon-injured and locally-treated iliac arteries compared with control balloon-injured arteries in 12 dogs. In the systemic high-dose delivery group (ten times as high as the low dose), thrombus formation in injured arteries was significantly less than that of controls in 7 dogs. Low-dose systemic delivery was not effective at inhibiting this thrombus formation. Thus, local treatment with an antithrombotic drug using this novel porous balloon catheter can prevent thrombosis without influencing systemic coagulability.

Angioscopy↗

The effects of age on hearing and middle ear function.

Audiometric test results from 933 community dwelling males and females were presented to obtain the norm for each generation after middle age. Three aspects were adopted in this analysis; the cross-sectional aging transition of pure tone thresholds, the comparison in the self-perceived hearing difficulty among generations and the evaluation of middle ear function using multifrequency tympanometry. Subjects were divided into four age groups; 40s, 50s, 60s and 70s. There were statistically significant differences in pure tone thresholds between almost any two age groups at each frequency in both genders, especially at higher frequencies. The pure tone thresholds were also discussed in regard to gender difference and laterality. A contradiction between self-perceived hearing difficulty and auditory accuracy was observed in the elderly generation. Analysis of tympanometric measurements was performed on static admittance at 226 Hz, tympanometric peak pressure at 226 Hz and resonance frequency of the middle ear. These variables did not show any systematic aging change. However, it was considered they represented the reference values of each generation.

Acoustic Impedance Tests↗

[Clinical management of esophageal achalasia].

In this report, we describe the clinical management of esophageal achalasia in Japan. Both balloon dilation and surgical myotomy or myectomy with antireflux procedures are accepted as the standard treatment for esophageal achalasia. In most patients balloon dilation is attempted first. If that is not sufficiently effective, they than undergo surgery. The most important point in treatment is not to repeat the dilation procedure more than twice, because patients who do not respond significantly to the first two dilation procedures are unlikely to improve after subsequent ones. Recently, many physicians and surgeons in Western countries have investigated the effects of botulinum toxin in patients with esophageal achalasia. If the safety of this treatment is confirmed in the near future, it will become a new treatment option for esophageal achalasia.

Catheterization↗

[Reflux esophagitis with hiatal sliding hernia].

Hiatal sliding hernia is often found in aged patient and some of them contribute to the development of reflux esophagitis. We described the etiology of gastroesophageal reflux disease(GERD) briefly and mentioned the relationship between hiatal hernia and reflux esophagitis. The old patients suffers from GERD are accompanying hiatal hernia at the high rate. Our successful results of laparoscopic Nissen's operation were reported shortly. Furthermore, we reviewed the reflux esophagitis after distal gastrectomy as most important complication after surgery. We emphasize that we should not hesitate to perform the surgical treatment to the patients suffering from GERD with hiatal hernia or after gastrectomy because it is safe and bring them the better Q.O.L. after treatment.

Aged↗

[Day surgery for breast cancer].

In Japan, day surgery for breast cancer usually means partial mastectomy without axillary dissection for small carcinoma under local anesthesia in the outpatient clinic. If histopathological examination of the specimens by serial section reveals that the cancer is noninvasive and completely resected with negative surgical margins, no additional surgery under general anesthesia is needed, and the patient does not require hospitalization. We call this procedure "probe lumpectomy". From 1991 to 1998, 169 patients underwent probe lumpectomy in our institution, and there were no major complications. Of these 169 patients, 64 did not require hospitalization. Ipsilateral breast cancer was observed in two patients, and these tumors were diagnosed not as recurrence but as second primary cancers. No distant metastases were observed. As sentinel node biopsy, which is not always easy under local anesthesia, becomes more common, the indications for day surgery or short-stay surgery will expand. As breast cancer is a malignant disease, informed consent and careful follow-up are needed if the treatment is completed only in the outpatient clinic.

Ambulatory Surgical Procedures↗

Epidermal sphingomyelins are precursors for selected stratum corneum ceramides.

Epidermal ceramides (Cer) comprise a heterogeneous family of seven species, including two unique omega-hydroxylated Cer, that are key components of the stratum corneum (SC) intercellular lamellar membranes responsible for the epidermal permeability barrier. Although both glucosylceramide (GlcCer) and the phospho-sphingolipid sphingomyelin (SM) are potential precursors of SC Cer, based on reported chemical structures of epidermal GlcCer and SC Cer, it is assumed that all major subfractions of SC Cer are generated from lamellar body-derived GlcCer. Yet, we and others have shown that SM-derived Cer are required for normal barrier homeostasis. Moreover, two pools of SM, one from plasma membrane, the other from lamellar body-derived contents, are potentially available for Cer production. To clarify the role of SM as a potential precursor of bulk or specific SC Cer, we compared Cer moieties in epidermal SM, Cer generated from epidermal SM by sphingomyelinase treatment, Cer within SC, and Cer that persist in Gaucher SC, where GlcCer cannot generate Cer due to an absence of beta-glucocerebrosidase. Using gas chromatography-mass spectrometry, fast atom bombardment-mass spectrometry, and nuclear magnetic resonance for Cer characterization, epidermal SM comprise three major subfractions with distinctive amide-linked (N-acyl) fatty acid (FA) compositions: that is, either long-chain FA (SM-1; C(22;-26)), short-chain FA (SM-2; primarily C(16)), and short-chain alpha-hydroxy FA (SM-3; C(16;-18)). In contrast, only trace quantities of omega-hydroxy FA were present. For each SM subfraction, the sphingoid base was either sphingosine or sphinganine, but phytosphingosine was not detected. Comparison of these SM with corresponding sphingomyelinase-generated epidermal Cer and SC Cer revealed that the Cer moieties of SM-1 and SM-3 are equivalent to Cer 2 (NS) and Cer 5 (AS), respectively. Moreover, both Cer 2 and Cer 5 occurred in Gaucher SC, whereas other Cer subfractions did not occur. These results indicate that two epidermal SM, that is, SM-1 and SM-3, are important precursors of two corresponding Cer in mammalian SC, that is, Cer 2 and Cer 5, but other Cer species, including the omega-hydroxy Cer species, do not derive from SM.

Animals↗

[Outcomes of home anti-cancer chemotherapy--estimation of hepatic arterial infusion chemotherapy for patients with multiple liver metastases].

A total of 18 patients (13: colon cancer, 5: gastric cancer) with multiple liver metastases (H3) underwent hepatic arterial infusion chemotherapy (HAI) using an implanted arterial port with portable syringe pumps in our outpatient clinic. Clinical perspective: overall response rate was 22.2% (CR: 1 case, PR: 3 cases (1 case: hepatectomy after HAI), NC: 12 cases, PD: 2 cases), however, 7 of 12 cases of NC were long NC (more than 6 months). No major complications with HAI were experienced. Patient Perspective: After HAI in our outpatient clinic, the 50% survival was 341 days, 50% hospital free days were 319 days and home stay rate was 92.9%. Societal Perspective: cost and hospital stay days were significantly reduced. Home anti-cancer chemotherapy using HAI for gastrointestinal cancer patients with multiple liver metastases was safe and efficient from the viewpoint of medical outcomes.

Aged↗

Regulation of phosphorylation level and distribution of PTP36, a putative protein tyrosine phosphatase, by cell-substrate adhesion.

Recently we have cloned a putative protein tyrosine phosphatase, PTP36/PTPD2/pez, which possesses a domain homologous to the N-terminal half of band 4.1 protein. In mouse fibroblasts adhered to substrates, PTP36 was phosphorylated on serine residues. PTP36 was found to make complexes with serine/threonine kinase(s), which phosphorylated PTP36 in vitro. PTP36 was dephosphorylated rapidly when the cell-substrate adhesion was disrupted and it was phosphorylated again along with the reattachment of the cells to fibronectin. Rephosphorylation of PTP36 seemed to depend on actin polymerization since it was inhibited by cytochalasin D. The cell detachment also induced the translocation of PTP36 into the membrane-associated cytoskeletal fraction. Staurosporine and ML-9, which inhibited the phosphorylation of PTP36 in vivo, induced the translocation of PTP36 too. On the contrary, when the dephosphorylation of PTP36 was inhibited by okadaic acid, no translocation of PTP36 was induced by the cell detachment. These results demonstrate that the cell-substrate adhesion and cell spreading regulates the intracellular localization of PTP36 most likely through its phosphorylation and therefore, PTP36 may play important roles in the signal transduction pathway of cell-adhesion.

Animals↗

Regulation of glycosphingolipid metabolism in liver during the acute phase response.

The host response to infection is associated with multiple alterations in lipid and lipoprotein metabolism. We have shown recently that endotoxin (lipopolysaccharide (LPS)) and cytokines enhance hepatic sphingolipid synthesis, increase the activity and mRNA levels of serine palmitoyltransferase, the first committed step in sphingolipid synthesis, and increase the content of sphingomyelin, ceramide, and glucosylceramide (GlcCer) in circulating lipoproteins in Syrian hamsters. Since the LPS-induced increase in GlcCer content of lipoproteins was far greater than that of ceramide or sphingomyelin, we have now examined the effect of LPS and cytokines on glycosphingolipid metabolism. LPS markedly increased the mRNA level of hepatic GlcCer synthase, the enzyme that catalyzes the first glycosylation step of glycosphingolipid synthesis. The LPS-induced increase in GlcCer synthase mRNA levels was seen within 2 h, sustained for 8 h, and declined to base line by 24 h. LPS-induced increase in GlcCer synthase mRNA was partly accounted for by an increase in its transcription rate. LPS produced a 3-4-fold increase in hepatic GlcCer synthase activity and significantly increased the content of GlcCer (the immediate product of GlcCer synthase reaction) as well as ceramide trihexoside and ganglioside GM3 (products distal to the GlcCer synthase step) in the liver. Moreover, both tumor necrosis factor-alpha and interleukin-1beta, cytokines that mediate many of the metabolic effects of LPS, increased hepatic GlcCer synthase mRNA levels in vivo as well as in HepG2 cells in vitro, suggesting that these cytokines can directly stimulate glycosphingolipid metabolism. These results indicate that LPS and cytokines up-regulate glycosphingolipid metabolism in vivo and in vitro. An increase in GlcCer synthase mRNA levels and activity leads to the increase in hepatic GlcCer content and may account for the increased GlcCer content in circulating lipoproteins during the acute phase response.

Acute-Phase Reaction↗