Biomedical subjects

T Kawaguchi

Publications and source records attributed to T Kawaguchi.

At least 109 records · Page 6Linked to original sources

PubMed2000

Two cases showing clonal progression with full evolution from aplastic anemia-paroxysmal nocturnal hemoglobinuria syndrome to myelodysplastic syndromes and leukemia.

We report 2 paroxysmal nocturnal hemoglobinuria (PNH) patients who were initially diagnosed with aplastic anemia and sequentially developed PNH, myelodysplastic syndromes (MDS), and leukemia. Flow cytometry and cytogenetic analysis showed the initial appearance and expansion of PNH clones, gradual replacement of PNH clones by MDS clones with monosomy 7, and then expansion of MDS clones or their subclones with additional chromosomal abnormalities. In relation to these developments, expression increased of the Wilms' tumor gene WT1, a marker for leukemic progression. These patients not only shared bone marrow failure but also might have harbored a hematopoietic environment favorable for the emergence of abnormal clones leading to leukemogenesis.

Adult↗

PubMed2000

[Autopsy case of adenoid cystic carcinoma of the trachea: endobronchial treatment improves quality of life].

A 67-year-old man presented with dyspnea on exertion. Bronchoscopic examination revealed a tumor arising from the middle portion of the trachea and extending to the right main bronchus. The pathological diagnosis was adenoid cystic carcinoma. Radiotherapy and subsequent endobronchial electrocautery were performed, and elicited a partial response. In the clinical course. Dumon and Ultraflex stents were placed in the trachea asynchronically. Brachytherapy and esophageal stent placement were also performed for tumor control in the trachea and esophagus. Autopsy revealed that the tumor had invaded the trachea and esophagus, and bacterial mediastinitis was also demonstrated. Because the tumor was successfully controlled during the following 4 years and 9 months, we concluded that endobronchial therapy such as stent placement or electrocautery is useful for maintaining good quality of life.

Aged↗

PubMed2000

[rCBF study with 123I-IMP SPECT of dural arteriovenous fistula].

It is important for dural arteriovenous fistula (DAVF) to evaluate venous ischemia in the brain related to venous hypertension, but only a few such studies have been performed. In this study, regional cerebral blood flow(rCBF) in DAVF was examined for venous ischemia by 123I-IMP SPECT. The subjects were eighteen patients with DAVF. Of the eighteen patients, nine had DAVF with low perfusion areas and venous ischemia. The factors affecting rCBF in DAVF are: 1) the presence of retrograde leptomeningeal venous drainage, 2) sinus occlusion, and 3) DAVF with high flow. The presence of retrograde leptomeningeal venous drainage was observed in nine patients, sinus occlusion in four patients, high flow in three patients. In two patients, pure leptomeningeal venous drainage was formed by patent sinus, and blood regurgitated from DAVF on the sinus wall to cortical vein. When DAVF was associated with LMVD, most patients had venous hypertension and concomitant venous congestion in the same areas due to reduced venous circulation, resulting in a decrease in rCBF and an increase in regional cerebral blood volume. These hemodynamics suggest venous ischemia in the brain. 123I-IMP SPECT was useful for evaluating rCBF and as a parameter of the treatment.

Adult↗

PubMed2000

[Establishment and identification of B cell lines with PNH phenotype].

OBJECTIVE: To establish B cell lines from patients with paroxysmal nocturnal haemoglobinuria (PNH) and normal controls. METHODS: B lymphoid cells prepared from PNH patients and normal controls were infected with EB virus. Phenotype of the immortal cells was analyzed by flow cytometry. The immunomagnetic beads were used to select CD(55)(-) and CD(59)(-) B lymphoid cells, which were cloned by limiting dilution. The clonality of the cloned cells was confirmed by testing the pattern of Ig rearrangements using polymerase chain reaction (PCR). RESULTS: From 2 PNH patients and 2 normal controls, CD(55)(-) and CD(59)(-) B lymphoblastoid cell lines were established which had PNH phenotype and normal phenotype, respectively. CONCLUSION: B lymphoid cell lines from PNH patients can be obtained by EB virus infection.

B-Lymphocytes↗

PubMed2000

The conserved tryptophan-arginine-tyrosine motif of a proteinaceous alpha-amylase inhibitor T-76 from Streptomyces nitrosporeus is important for inhibition of animal alpha-amylases but not for an alpha-amylase from Bacillus sp. no. 195.

Site-directed mutagenesis of Trp-16, Arg-17, and Tyr-18, which were thought to form a putative active site in proteinaceous alpha-amylase inhibitor T-76 from Streptomyces nitrosporeus for inhibition, was performed. The mutation at the site (W16A, R17A, and Y18A) resulted in a marked decrease in inhibitory activity against all animal alpha-amylases tested. Only the alpha-amylase from Bacillus sp. no. 195 (BAA) remained sensitive to all the constructed mutant inhibitors. A competition between T-76 mutants and the wild-type for porcine pancreatic alpha-amylase (PPA) suggest that the loss of inhibitory activity against PPA in mutant inhibitors was due to the decrease in their binding ability for PPA. T-76 formed a complex with BAA as well as PPA at the stoichiometric ratio of 1:1. A competition between BAA and the PPA/T-76 complex suggests that PPA and BAA might bind to the same region or regions close to each other on the T-76 molecule. These results indicate that the conserved Trp-Arg-Tyr motif of T-76 is involved in the interaction between T-76 and PPA while other amino acid residues seem to be important for the T-76/BAA interaction. Since the BAA-type alpha-amylase is the actual target of the inhibitors from microbes in comparison with animal alpha-amylases, BAA might be a better material than PPA to elucidate the "true" function of proteinaceous alpha-amylase inhibitors.

Journal Article↗

PubMed2000

Cloning and secretive expression of the gene encoding the proteinaceous alpha-amylase inhibitor paim from Streptomyces corchorusii.

A gene encoding the proteinaceous alpha-amylase inhibitor Paim was cloned and sequenced. Southern analysis and the amino acid sequence deduced from the cloned gene indicated that Paim isoforms were encoded in the same gene. When the gene was expressed in Escherichia coli and Streptomyces lividans, recombinant Paim inhibitors were produced in the periplasmic space and in the culture supernatant, respectively. The purified inhibitors had different N-terminal sequences from those of the authentic inhibitors.

Journal Article↗

PubMed1999

Prognostic Relevance of Tn Expression in Breast Cancer.

BACKGROUND: Abnormal glycosylation patterns have been recognized as a featureof carcinomaassociated mucins. The expression of the Tn antigen in breast cancer tissue was investigated to assess its prognostic relevance. METHODS: Formalin-fixed, paraffin-embedded materials from 219 patients with breast cancer were used. Immunohistochemical staining of the Tn antigen was retrospectively investigated and a lesion staining 10% or more was considered positive RESULTS: Tn antigen expression was present in 99 (45%) of 219 lesions. There were no correlations between Tn antigen expression and mean patient age, nodal status, estrogen receptor status, or menopausal status, but there was a slightly significant association between Tn and tumor size. Patients negative for the Tn antigen had a significantly better survival rate than those who were positive. Multivariate analysis also indicated that Tn expression correlated significantly with overall survival in addition to nodal status and tumor size. CONCLUSION: Tn expression was a significant prognostic factor in breast cancer, but the significance was lost on multivariate analysis. The biological implication of Tn expression in breast cancer needs further investigation.

Journal Article↗

PubMed1999

Recognition of Amphiphiles with Many Pendent Galactose Residues by Ricinus communis Agglutinin.

Amphiphiles which carry many pendent galactose residues as side chains were prepared by telomerization of 2-methacryloyloxyethyl beta-D-galactopyranoside (MEGal) or 3-(2-methacryloyl aminoethylthio)propyl D-galactopyranoside (MEPGal, alpha:beta = 3.9:1) using a lipophilic radical initiator. The galactose-carrying amphiphiles (DP (degree of polymerization) = 15) incorporated in liposomes were recognized by a lectin from Ricinus communis (RCA120), which was proven by the increase in turbidity of the liposome suspension after mixing with the lectin. The recognition was largely affected by the distance between the galactose residues and the polymer main chain, and the surface density of the amphiphile in the liposomes. The liposomes containing these galactolipids were not taken up by mouse peritoneal macrophages, probably due to a steric hindrance of polymer main chains from the uptake of D-galactose receptors on the macrophages. Copyright 1999 Academic Press.

Journal Article↗

PubMed1999

Different lobular distributions of altered hepatocyte tight junctions in rat models of intrahepatic and extrahepatic cholestasis.

Hepatocyte tight junctions (TJs), the only intercellular barrier between the sinusoidal and the canalicular spaces, play a key role in bile formation. Although hepatocyte TJs are impaired in cholestasis, attempts to localize the precise site of hepatocyte TJ damage by freeze-fracture electron microscopy have produced limited information. Recently, several TJ-associated proteins like ZO-1 and 7H6 have been identified and characterized. Immunolocalization of 7H6 appears to closely correlate with paracellular permeability. We used rat models of intrahepatic cholestasis by ethinyl estradiol (EE) treatment and extrahepatic cholestasis by bile duct ligation (BDL) to precisely determine the site of TJ damage. Alterations in hepatocyte TJs were assessed by double-immunolabeling for 7H6 and ZO-1 using a confocal laser scanning microscope. In control rats, immunostaining for 7H6 and ZO-1 colocalized to outline bile canaliculi in a continuous fashion. In contrast, 7H6 and ZO-1 immunostaining was more discontinuous, outlining the bile canaliculi after BDL. Immunostaining for 7H6, not ZO-1, decreased and predominantly appeared as discrete signals in the submembranous cytoplasm of periportal hepatocytes after BDL. After EE treatment, changes in immunostaining for 7H6 and ZO-1 were similar to those seen in periportal hepatocytes after BDL, but distributed more diffusely throughout the lobule. This study is the first to demonstrate that impairment of hepatocyte TJs occurs heterogenously in the liver lobule after BDL and suggests that BDL and EE treatments produce different lobular distributions of increased paracellular permeability.

Animals↗

PubMed1999

Expression of cyclooxygenase-2 in human hepatocellular carcinoma: relevance to tumor dedifferentiation.

Cyclooxygenase (COX) is a key enzyme in the synthesis of prostanoids. Two isoforms of this enzyme have been identified: COX-1 and COX-2. Recent studies have suggested that COX-2, but not COX-1, may play a role in colorectal tumorigenesis. In the present study, we investigated the expression of COX-2 as well as COX-1 in human hepatocellular carcinoma (HCC) tissues using immunohistochemistry and immunoblotting. Forty-four surgically resected HCC tissues with adjacent nontumorous livers (NTs), involving 17 cases of chronic viral hepatitis and 27 cases of cirrhosis, and 7 surgically resected, histologically normal liver tissues were used. The well-differentiated HCC expressed COX-2 more frequently and strongly than less-differentiated HCC or hepatocytes of NTs. Less-differentiated HCCs expressed less COX-2 than hepatocytes of NTs, which showed scattered, strong COX-2 expression. Histologically normal liver was weakly positive for COX-2. The expression of COX-1 was weaker than that of COX-2 in hepatic neoplastic and non-neoplastic parenchymal cells. An enhanced expression of COX-1 was not observed in well-differentiated HCCs. Immunoblotting also confirmed up-regulation of COX-2, but not COX-1, in well-differentiated HCCs. The present study is the first to demonstrate a high expression of COX-2 in well-differentiated HCC and a low expression in advanced HCC, in contrast to its continuous expression during colorectal carcinogenesis. These findings suggested that COX-2 may play a role in the early stages of hepatocarcinogenesis, but not in the advanced stages, and may consequently be related to HCC dedifferentiation.

Adult↗

PubMed1999

Effect of clot removal and surgical manipulation on regional cerebral blood flow and delayed vasospasm in early aneurysm surgery for subarachnoid hemorrhage.

BACKGROUND: Effect of clot removal and surgical manipulation on cerebral blood flow (CBF) and delayed vasospasm was studied in early aneurysm surgery for subarachnoid hemorrhage (SAH). METHODS: Thirty-two patients in this study fulfilled the following criteria: ruptured anterior communicating aneurysms, computed tomography (CT) within 2 days and unilateral pterional approach within 3 days after the ictus, bilaterally symmetrical clots without intracerebral hematoma, no postoperative complication, and CBF studies with single photon emission computed tomography (SPECT) with 123I-IMP. RESULTS: Postoperative regional hypoperfusion due to brain retraction was frequently recognized on 123I-IMP-SPECT without infarction. The regional CBF (rCBF) showed a continuous fall during the first 4 weeks after the ictus, followed by improvement. The rCBF in the vicinity of the surgical route was significantly lower, especially in the acute stage (Day 3-7). A significant association between decrease of cisternal blood after surgery and the degree of local vasospasm and local CBF values during spasm stage was observed in the interhemispheric cisterns, A2 and medial frontal cortex, but not in the sylvian fissure or insular cisterns, M1 or M2, and frontal watershed and temporal cortex. CONCLUSIONS: The present study provides evidence for the effectiveness of direct clot removal by early surgery for SAH on local vasospasm and CBF reduction. However, a potential improvement in local CBF with clot removal could be masked by brain retraction, which was demonstrated to affect rCBF adversely. Therefore, it is critical to perform brain retraction as gently as possible.

Adult↗

PubMed1999

The use of an external-internal shunt in the treatment of extracranial internal carotid artery saccular aneurysms: technical case report.

BACKGROUND: Extracranial internal carotid artery aneurysms (EICAA) are rare lesions. Resection and grafting is the preferred method of management. However, the details of shunt use in surgery for this type of aneurysm has been described in few articles. We describe an external-internal shunt with intra-aneurysmal trans-orifice insertion. CASE REPORT: A 55-year-old woman presented with a 5-year history of a progressively enlarging pulsatile neck mass. An examination revealed no neurological deficit. Right carotid angiogram showed a saccular EICAA involving the ICA distal to the bifurcation, with kinking of the internal carotid artery (ICA). The dome of the EICAA extended from the upper border of C4 to the midportion of C2 and the maximum diameter was 4 cm. RESULTS: Using the shunt technique, we successfully removed the aneurysm and reconstructed the ICA. The end-to-end anastomosis was easy because the shunt was involved only in the distal free end of the ICA, but not in the proximal free end of the ICA. CONCLUSION: This technique could be an option for the treatment of EICCA when a shunt is needed to maintain the cerebral circulation.

Anastomosis, Surgical↗

PubMed1999

Phaseolus vulgaris leukoagglutinating lectin-binding reactivity in human diffuse large B-cell lymphoma and its relevance to the patient's clinical outcome: lectin histochemistry and lectin blot analysis.

Many reports have suggested a strong correlation between certain lectin-binding patterns and biological behavior in various tumors. To clarify a relationship between lectin-binding reactivity and survival of patients with diffuse large B-cell lymphoma (B-DLCL), 57 cases with B-DLCL were analyzed by lectin histochemistry and lectin blot method with or without treatment of neuraminidase or acidic hydrolytic conditions. B-DLCL cases were grouped into three types based on the data on lectin-binding reactivity under neuraminidase-treated or untreated conditions: (i) Group A (non-reactive type); (ii) Group B (sialylated type); and (iii) Group C (non-sialylated type). Among various lectins, Phaseolus vulgaris-L (L-PHA) binding reactivity showed that the survival of patients with Group A + B or Group B was significantly shorter than that of patients with Group C. Lectin blot analysis revealed failure of L-PHA-binding to 32 kd and 29 kd glycoproteins, which may be attributable to the masking of L-PHA-binding sites by sialylation or the lack of L-PHA-binding sites, leading to the short survival of patients with B-DLCL. L-PHA-binding reactivity may be a useful marker for the evaluation of survival of patients with B-DLCL.

Adult↗

PubMed1999

Detection of hepatitis-C virus and hepatitis-C virus replication in hepatocellular carcinoma by in situ hybridization.

BACKGROUND: Although hepatitis C virus (HCV) is a major causative agent of hepatocellular carcinoma (HCC), the role of this virus in carcinogenesis is not fully understood. METHODS: We studied HCV infection and replication by detecting plus- and minus-strand HCV RNA by in situ hybridization (ISH) in surgically resected HCCs and adjacent non-cancerous tissue obtained from 15 anti-HCV antibody-positive patients with HCC. RESULTS: Plus-strand HCV RNA was found in 9 of 15 HCCs. Both plus- and minus-strand HCV RNA were detected in four of these nine patients. In non-cancerous tissues obtained adjacent to the HCC, plus-strand HCV RNA was found in 10 of 15 patients, whereas both plus- and minus-strand HCV RNA were detected in 7 of these 10 patients. The degree of staining by ISH did not correlate with the differentiation of the HCC, histologic classification of the non-cancerous tissue, serum HCV RNA levels, or serum transaminase levels. CONCLUSIONS: HCV can be found in and replicates in both hepatoma cells and in non-cancerous hepatocytes in anti-HCV antibody-positive patients with HCC. The direct effects of HCV viral gene products on normal hepatocytes in the development of HCC require additional study.

Aged↗

PubMed1999

A case of long-term survival with stage IV small cell lung cancer and early-stage central-type squamous cell lung cancer treated by photodynamic therapy.

The present report is on a 67-year-old man with stage IV small cell lung cancer and early-stage centrally located squamous cell cancer of the lung. He was diagnosed as small cell lung cancer with multiple metastasis to the ipsilateral lung and was found to have a central-type early-stage squamous cell cancer by bronchoscope. After obtaining a complete response to the small cell lung cancer with chemotherapy and radiotherapy, photodynamic therapy was applied to the squamous cell carcinoma, resulting in complete disappearance of the tumor. Recurrence of small cell cancer occurred at the ipsilateral lung and this patient died of small cell cancer 8 years after initiation of treatment. Post mortem examination confirmed complete disappearance of squamous cell cancer treated by photodynamic therapy. This is a rare case of long-term survival with stage IV small cell lung cancer and early-stage central-type squamous cell lung cancer successfully treated by photodynamic therapy.

Aged↗

PubMed1999

Multiple sites of proteolytic cleavage to release soluble forms of hepatocyte growth factor activator inhibitor type 1 from a transmembrane form.

Hepatocyte growth factor activator inhibitor type 1 (HAI-1) is a Kunitz-type serine protease inhibitor, which was identified as a potent inhibitor of hepatocyte growth factor (HGF) activator from the conditioned medium of a human carcinoma cell line. HGF activator is a blood coagulation factor XII-like serine protease that is responsible for proteolytic activation of the inactive single chain precursor of HGF in injured tissues. The predicted sequence of the primary translation product of HAI-1, which has a hydrophobic sequence in its COOH-terminal region, suggested that HAI-1 is first produced in a membrane-associated form. In this study, we identified a transmembrane form of HAI-1 integrated in the plasma membrane of cultured cells using a monoclonal antibody against HAI-1. We also identified several soluble forms of HAI-1 in the conditioned medium of the cells, indicating that multiple sites are present in the transmembrane form of HAI-1 at which proteolytic cleavage releases the extracellular domain. At least two proteases, one of which is a metalloprotease, appear to be responsible for the release. Further, the soluble forms of HAI-1 have different inhibitory activity against HGF activator. These findings suggest that proteolytic processing plays important roles in regulation of the inhibitory activity of HAI-1.

Base Sequence↗

PubMed1999

Reduction of the side effects of an antitumor agent, KRN5500, by incorporation of the drug into polymeric micelles.

For intravenous (i.v.) injection of a water-insoluble antitumor drug, KRN5500, we have successfully incorporated KRN5500 into polymeric micelles. In the present study, in vitro and in vivo anti-tumor activity against several human tumor cell lines and toxicity in mice of polymeric micelles incorporating KRN5500 (KRN/m) were evaluated in comparison with those of the prototype KRN5500. KRN/m was found to express similar antitumor activity to KRN5500 in the in vitro and in vivo systems. However, the vascular damage and liver focal necrosis observed with KRN5500 i.v. injection were not seen when KRN/m was administered i.v. Therefore, we expect that KRN/m will be superior to KRN5500 for clinical use and that the methodology of polymeric micelle drug carrier systems can be applied to other water-insoluble drugs.

Animals↗

PubMed1999

Preserved hypocapnic pial arteriolar constriction during hyperammonemia by glutamine synthetase inhibition.

Ammonia intoxication, which results in astrocytic edema and glutamine accumulation, blocks cerebral vasodilation during hypercapnia but not during hypoxia. Ammonia's effect on blood flow during hypocapnia is unclear, with some brain regions showing a paradoxical increase in flow. Here, we studied the responses to hypocapnia of pial arterioles not surrounded by astrocytic end feet to avoid mechanical compression by local edema. Blood flow was measured by microspheres in pentobarbital sodium-anesthetized rats equipped with closed cranial windows that permitted intravital microscopy. The normal pial arterial constriction in hypocapnia (12 +/- 1%; mean +/- SE) was blocked (2 +/- 1%) during a 6-h intravenous infusion of ammonium acetate, with some regions (cerebrum, midbrain) showing increased flow during hypocapnia. After pretreatment with methionine sulfoximine (MSO), which inhibits glutamine synthesis, the normal hypocapnic constrictor response was retained in pial arterioles (11 +/- 2%) during hyperammonemia. The increase in the calculated cerebrovascular resistance also was retained. An analog of MSO that does not block glutamine synthesis (buthionine sulfoximine) was ineffective in maintaining hypocapnic reactivity. In a sodium acetate-treated control group, MSO did not alter the pial arteriolar response. Normal vasoconstrictive ability was shown during ammonium infusion in response to U-46619, a thromboxane analog. We conclude that the inhibition of hypocapnic responsivity induced by ammonium is not due to paralysis of the pial arteriolar smooth muscle or to vascular compression by swollen astrocytes but is in some way due to glutamine metabolically produced from the ammonium.

Acetates↗