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Biomedical subjects

Y Koyanagi

Publications and source records attributed to Y Koyanagi.

At least 37 records · Page 2Linked to original sources

Is preventive resection of the extrahepatic bile duct necessary in cases of pancreaticobiliary maljunction without dilatation of the bile duct?

BACKGROUND: No consensus has been reached on whether preventive resection of the extrahepatic bile duct is necessary in cases of pancreaticobiliary maljunction (PBM) without dilatation of the extrahepatic bile duct (undilated type). METHODS: Sixty-eight patients with PBM underwent corrective surgery and several clinical characteristics and pathological findings including K-ras point mutation were evaluated. RESULTS: Unlike dilated bile duct, none of the patients with undilated type duct had clinical symptoms in early childhood. In patients with either cystic or spindle type duct, amylase levels in the bile duct were >10(4) U/l, whereas those in patients with undilated type duct were <10(4) U/l. Postoperative scintigraphy of the biliary system of undilated type revealed no evidence of cholestasis. After surgery, eight patients with undilated type duct, in whom the bile duct had been preserved, had no further clinical symptoms and no evidence of malignancy. Bile duct tissue specimens revealed no hyperplasia, dysplasia or cancerous lesions and they had no K-ras mutation in undilated type. CONCLUSION: The results showed that there was little bile stasis, injury to the mucosa was mild and less genetic changes could be seen in patients with undilated type duct. Therefore, in patients without dilatation of bile duct and advanced cancer, cholecystectomy alone is sufficient.

Adult↗

Conformational change of dimerization initiation site of HIV-1 genomic RNA by NCp7 or heat treatment.

Dimerization initiation site (DIS) of the human immunodeficiency virus type 1 (HIV-1) genome has been identified as a primary sequence that can form a stem-loop structure with a self-complementary sequence in the loop and a bulge in the stem. A DIS RNA fragment spontaneously forms a kissing dimer and is converted into an extended-duplex dimer by supplement of nucleocapsid protein NCp7. This two-step dimerization reaction can be also executed by a heat treatment instead of the binding proteins. However, it has not identified whether mechanisms of the conformational conversion by two different treatments are identical or not. In the present study, we used a series of DIS RNA oligonucleotides and the conformations of two extended-duplex dimers produced by the two different treatments were compared by the analysis of NMR spectra in the imino proton region. It was found that the effects of the two kinds of treatments are quite similar and the conformations of the two extended-duplex dimers are identical. These findings suggest that the conversion mechanisms DIS RNA by NCp7 and heat treatments are similar.

Base Sequence↗

Improved nonpenetrating trabeculectomy with trabeculotomy.

PURPOSE: To examine surgical effects and complications of improved nonpenetrating trabeculectomy with trabeculotomy in glaucoma patients. METHODS: Glaucoma patients in two medical institutions underwent nonpenetrating trabeculectomy with sinusotomy with or without trabeculotomy, and the results were compared retrospectively in the two groups by evaluation of final intraocular pressure, drug score, and occurrence of postsurgical complications. RESULTS: Of the 63 eyes of 51 patients in this study, 31 were treated with nonpenetrating trabeculectomy with sinusotomy without trabeculotomy and 32 eyes were treated with nonpenetrating trabeculectomy with sinusotomy and trabeculotomy. The mean follow-up period was 17.0 months. The clinical features in both groups were similar in terms of age, presurgical intraocular pressure (P = 0.96), and presurgical drug score. The eyes treated with nonpenetrating trabeculectomy with sinusotomy without trabeculotomy had significantly reduced intraocular pressures from 21.0 +/- 4.3 (mean +/- SD) to 15.8 +/- 6.3 mm Hg (P = 0.0003) and drug scores from 2.4 +/- 1.2 to 1.6 +/- 1.1 without postsurgical complications. The eyes treated with nonpenetrating trabeculectomy with sinusotomy and trabeculotomy had significantly reduced intraocular pressures from 22.3 +/- 7.5 to 12.5 +/- 2.3 mm Hg (P < 0.0001) and drug scores from 2.5 +/- 1.9 to 0.9 +/- 1.3 without postsurgical complications. Thus, the eyes treated with nonpenetrating trabeculectomy with sinusotomy and trabeculotomy had significantly lower intraocular pressures (P = 0.016) and drug scores than did those treated with nonpenetrating trabeculectomy with sinusotomy without trabeculotomy. CONCLUSION: The authors obtained satisfactory results in reducing intraocular pressure by the combination of nonpenetrating trabeculectomy, sinusotomy, and trabeculotomy.

Adult↗

OX40 stimulation by gp34/OX40 ligand enhances productive human immunodeficiency virus type 1 infection.

OX40 is a member of the tumor necrosis factor (TNF) receptor superfamily and known to be an important costimulatory molecule expressed on activated T cells. To investigate the role of costimulation of OX40 in human immunodeficiency virus type 1 (HIV-1) infection by its natural ligand, gp34, the OX40-transfected ACH-2 cell line, ACH-2/OX40, chronically infected with HIV-1, was cocultured with paraformaldehyde (PFA)-fixed gp34-transfected mouse cell line, SV-T2/gp34. The results showed that HIV-1 production was strongly induced. This was followed by apparent apoptosis, and both processes were specifically inhibited by the gp34-specific neutralizing monoclonal antibody 5A8. Endogenous TNF alpha (TNF-alpha) and TNF-beta production were not involved in the enhanced HIV-1 production. Furthermore, enhanced HIV-1 transcription in gp34-stimulated ACH-2/OX40 cells was dependent on the kappa B site of the HIV-1 long terminal repeat, and the OX40-gp34 interaction activated NF-kappa B consisting of p50 and p65 subunits. When primary activated CD4(+) T cells acutely infected with HIV-1(NL4-3) (CXCR4-using T-cell-line-tropic) were cocultured with PFA-fixed gp34(+) human T-cell leukemia virus type 1-bearing MT-2 cells or SV-T2/gp34 cells, HIV-1 production was also markedly enhanced. The enhancement was again significantly inhibited by 5A8. The present study first shows that OX40-gp34 interaction stimulates HIV-1 expression and suggests that OX40 triggering by gp34 may play an important role in enhancing HIV-1 production in both acutely and latently infected CD4(+) T cells in vivo.

Animals↗

Dye-staining stereomicroscopic examinations for fine mucosal structures of the gallbladder.

BACKGROUND: In order to diagnose an unsuspected gallbladder carcinoma and to examine whether a differential diagnosis could be made between cancer and noncancerous lesions during surgery, we evaluated the findings of fine structures of various types of gallbladder mucosa. METHODS: We used stereomicroscopy with a dye-contrast technique under water and measured the maximum blood vessel diameters of the gallbladder mucosa: normal gallbladder, chronic cholecystitis, and carcinoma. RESULTS: All normal gallbladders showed fine-reticular-type findings. In chronic cholecystitis, 5.8% of the specimens (n = 69) had fine reticular type, 87.0% had rough reticular type, and 7.2% had atrophic type. All the cases of adenomyomatosis (n = 16) showed rough reticular type. In eight specimens of pancreaticobiliary maljunction, 75% of them showed high reticular type, and the other 25% showed papillary type. The two adenoma specimens showed fine granular type. In five gallbladder carcinomas, the lattice-like pattern completely disappeared and showed rough granular type. The average of maximum vessel diameters in the gallbladder mucosa were 41.0 microm in normal gallbladders, 99.1 microm in patients with chronic cholecystitis, and 614.8 microm in patients with a carcinoma. There were significant differences among them (p < 0.05). CONCLUSION: This study showed that differential diagnosis between cancer and noncancerous lesion is possible by dye-staining mucosal pattern and measurement of maximum vessel diameters by stereoscopic examination.

Adenoma↗

[Recurrent breast cancer successfully treated with a weekly dose of paclitaxel--a case report].

The patient was a 46-year-old women who was treated for axillary lymph node recurrence of breast cancer by a variety of methods, including surgery, chemotherapy, and radiotherapy, but who experienced recurrences in the cervical and mediastinal lymph nodes and skin, and developed hydrothorax and ascites. Although the recurrent foci responded to 4 cycles of CAF chemotherapy, there was concern that the foci would become refractory or resistant to chemotherapy. The administration of paclitaxel was therefore initiated. The patient received a dose of paclitaxel once a week for 5 consecutive weeks followed by a 1-week recovery period (one cycle). After two cycles of the paclitaxel treatment, a marked shrinkage of the lymph nodes and complete resolution of the hydrothorax and ascites were observed. Even though the patient exhibited bone marrow suppression and G-CSF was administered twice for neutropenia, there were no adverse effects except mild alopecia, again suggesting the possibility that paclitaxel is effective chemotherapy for recurrent breast cancer.

Antineoplastic Agents, Phytogenic↗

[A case of advanced gastric cancer treated with neoadjuvant chemotherapy of low-dose CPT-11 + CDDP].

Side effects due to administration of anti-cancer drugs often cause the treatment to be abandoned or a decrease in the amount of anti-cancer drugs. Recently, the anti-tumor effects of "low-dose CPT-11", which can be administered at the outpatient clinic, are reported. We performed "low-dose CPT-11 + CDDP" as a neoadjuvant chemotherapy to a patient with advanced gastric cancer. CPT-11 and CDDP combination chemotherapy caused very few side effects, so we could continue the treatment and achieve anti-tumor effects. Consequently, surgery could be performed, but disseminated metastasis was found so that the surgery ended as a non-curative operation. However, it was considered that this method of "low-dose CPT-11 + CDDP" was very effective as the neoadjuvant chemotherapy in a patient with advanced gastric cancer.

Aged↗

[Experience of gamma-detecting probe for the survey of sentinel node in gastroesophageal malignancies].

Gamma-detecting probe NAVIGATOR GPS (Autosuture Japan) was evaluated by using of 99mTc. Linearlity of counting in radioactivity was fairly good, but the sensitivity of the prove is so low, that sentinel node (SN) should contain the 3.7 x 10(-3) MBq (0.1 microCi) of 99mTc or more for the most effective use of it. And the count rate of the gamma-detecting probe was influenced by the distance and angle from the 99mTc source variously. It is important for the operator to know such characteristics of the gamma-detecting probe in order to obtain the correct SN judging.

Esophageal Neoplasms↗

[A case of AFP producing early gastric cancer successfully treated with small dose CDDP and 5-FU (PF) therapy].

A case of AFP producing early gastric cancer successfully treated with a small dose of CDDP and 5-FU therapy administered intermittedly is reported with a review of the literature. A 63-year-old male was admitted to our hospital because of liver metastasis with a high level of serum AFP (185.8 ng/ml) three months after gastrectomy. Systemic chemotherapy was performed twice with a regimen of CDDP 20 mg and 5-FU 750 mg/day in 5 days. After hepatic arterial infusion chemotherapy (HAIC) was performed once, the patient obtained partial response according to CT scan and was discharged. After he underwent HAIC once as an outpatient, liver metastasis completely disappeared 5 months after surgery. He was administered oral 5-FU, 150 mg and Krestin 3.0 g/day and underwent HAIC with CDDP 20 mg and 5-FU 750 mg/day every 2 weeks. After serum AFP level was returned to the normal range 7 months after surgery; HAIC was performed every 4 weeks and continued until one year after surgery. One year and 11 months after surgery, serum AFP remains within the normal limit and there is no evidence of recurrence.

Adenocarcinoma↗

Pertussis toxin enhances human immunodeficiency virus type 1 replication.

Pertussis toxin (PTX) has been used as a reagent to identify involvement of the G protein-mediated signal transduction pathway. In this study, we found that PTX enhanced HIV-1 replication in acute infection systems at a high dose (1-10 microg/ml) in vitro. PTX treatment enhanced the infectivity of HIV-1-based pseudovirus enveloped with HIV-1 or amphotropic murine leukemia virus (A-MuLV), but not with vesicular stomatitis virus (VSV). This high dose of PTX treatment did not affect HIV-1 gene expression. These data suggested that the effect was virus envelope dependent and that PTX acted on an early stage of viral infection. Treatment with B-oligomer, a nonenzymatic subunit of PTX, mimicked this enhancing effect of PTX. However, desialylation of viral and cellular surface glycoproteins, which are receptors for B-oligomer, did not affect the augmentation induced by PTX. These results indicate that the enhancement of HIV-1 replication is mediated through an unknown biological function of B-oligomer.

CD4 Antigens↗

Transcriptional regulation of HIV-1 LTR during antigen-dependent activation of primary T cells by dendritic cells.

Numerous factors are known to bind human immunodeficiency virus (HIV) long terminal repeat (LTR) and activate viral transcription, but little is known as to how they function in naturally activated T cells and to what extent their binding is relevant to HIV replication in vivo. To characterize the HIV LTR-binding factors responsible for antigen-dependent activation of HIV, we examined replication of LTR mutant viruses in CD4+ T cells activated by different stimuli. NF-kappaB or Sp1 mutant virus replicated well in CD4+ T cells activated by phorbol ester and calcium ionophore. When they were activated by antigen-pulsed dendritic cells, the replication of the Sp1-deleted virus was severely impaired in CD45RA+, but not in CD45RO+ T cell subsets that dominantly produce interleukin-2 (IL-2). Stimulation via CD3/CD28 induced a high level of IL-2 production in both T cell subsets, but Sp1-deleted virus poorly replicated in CD45RA+ subset. The level of NF-kappaB and Sp1-binding factors did not differ between these subsets. Our results suggest that additional cofactors distinct from IL-2-inducing signaling molecules are important for LTR activation during antigen-dependent T cell activation.

Antigen Presentation↗

Nuclear accumulation of beta-catenin in intestinal-type gastric carcinoma: correlation with early tumor invasion.

Mutation of the adenomatous polyposis coli gene, which is known to be an early event in the carcinogenesis of intestinal-type gastric carcinoma, leads to accumulation of beta-catenin. In addition, beta-catenin has been found to activate down stream signaling molecules in the wingless/Wnt pathway. In this study, the clinical significance of nuclear accumulation of beta-catenin was evaluated in gastric carcinoma. Immunohistochemical staining showed nuclear localization in 16 (12%) of 139 (94 intestinal-type and 45 diffuse-type) gastric carcinomas, and all 16 lesions with nuclear staining were intestinal-type adenocarcinomas. Of the 16 cases, 15 were in the early clinical stage. In the remaining case, the lesion had invaded the subserosal layer and showed strong nuclear staining at the invasive front. In 14 of the 16 cases with nuclear localization, there were no abnormal mobility shifts detected using polymerase chain reaction-single strand conformational polymorphism analysis. This was confirmed using direct sequencing analysis, which revealed the wild-type sequence in the 12 cases tested. Nuclear accumulation of beta-catenin did not correlate with lymph node metastasis or 5-year survival. These findings suggest that high intranuclear levels of beta-catenin protein play an important role in early tumor growth and may function in initiation of invasive processes in intestinal-type gastric carcinoma.

Adenocarcinoma↗

Relation between K-ras codon 12 mutation and p53 protein overexpression in gallbladder cancer and biliary ductal epithelia in patients with pancreaticobiliary maljunction.

It is well known that the incidence of biliary cancer is higher in patients with pancreaticobiliary maljunction (PBM) than in individuals without PBM. However, the relationship between PBM and the carcinogenesis remains unclear. The purpose of the present study was to examine histopathologic changes in the mucosa of the gallbladder and bile duct in patients with PBM, and to investigate K-ras oncogene mutation and overexpression of p53 protein in the mucosa. We examined 47 surgical specimens of gallbladder and 36 surgical specimens of bile duct obtained from 48 patients with PBM. The 48 patients were divided into three age groups: group A (0-3 years), group B (4-39 years), and group C (40 years or more). Investigation of K-ras mutation and overexpression of p53 protein was performed using an enriched polymerase chain reaction (PCR) and enzyme-linked mini-sequence assay (ELMA), and by the streptavidin-biotin (SAB) method, using DO-7 antibodies, respectively. Hyperplastic changes in the gallbladder mucosa were observed in patients in the three groups. However, metaplastic or dysplastic changes were observed in the mucosa of only groups B and C. K-ras gene mutation in the gallbladder mucosa was found in 18.8% of the hyperplastic mucosae in group B and in 20% in group C. The mutation was found in 33.3% of lesions with metaplastic change associated with hyperplastic changes and in 25% of lesions with dysplastic changes in group C. No mutation was observed in the non-cancerous mucosae of gallbladders and bile ducts without congenital dilatation of the bile duct. Overexpression of p53 protein was observed only in carcinoma of the gallbladder; in seven of nine advanced carcinomas and in two of three carcinomas in situ. We concluded that the mucosal epithelia of the biliary system in patients with PBM showed a high frequency of gene mutations and the carcinogenesis appeared in involve a multistage process of mutation in the K-ras gene and the p53 suppressor gene.

Adolescent↗

Metachronous triple cancers of the sigmoid colon, stomach, and esophagus: report of a case.

We report herein an unusual case of metachronous triple cancers of the sigmoid colon, stomach, and esophagus. A 60-year-old man was initially admitted to our hospital for investigation of occult fecal blood. This was found to be caused by sigmoid colon cancer which was resected in July 1985 (T3, N0, M0; Stage II). A follow-up endoscopy performed in 1990 showed early gastric cancer, and a gastrectomy was performed in August 1990 (Tis, N0, M0; Stage 0). Another endoscopic examination performed as follow-up in 1993 revealed early cancer of the remnant stomach, and all the remnant stomach was surgically resected in March 1993 (Tis, N0, M0; Stage 0). He presented again in December 1996, complaining of discomfort in the chest which was found to be caused by cancer of the middle thoracic esophagus. Although surgery was considered necessary, the patient refused to undergo any further operations. Instead, radiation was administered from January 1997. An endoscopy after the completion of radiotherapy confirmed that the cancer had almost disappeared; however, it started to grow again from the beginning of 1998. He was hospitalized due to esophageal stenosis in April 1998, and died of carcinomatous cachexia in September of the same year.

Adenocarcinoma↗

Structural requirement for the two-step dimerization of human immunodeficiency virus type 1 genome.

Generation of RNA dimeric form of the human immunodeficiency virus type 1 (HIV-1) genome is crucial for viral replication. The dimerization initiation site (DIS) has been identified as a primary sequence that can form a stem-loop structure with a self-complementary sequence in the loop and a bulge in the stem. It has been reported that HIV-1 RNA fragments containing the DIS form two types of dimers, loose dimers and tight dimers. The loose dimers are spontaneously generated at the physiological temperature and converted into tight dimers by the addition of nucleocapsid protein NCp7. To know the biochemical process in this two-step dimerization reaction, we chemically synthesized a 39-mer RNA covering the entire DIS sequence and also a 23-mer RNA covering the self-complementary loop and its flanking stem within the DIS. Electrophoretic dimerization assays demonstrated that the 39-mer RNA reproduced the two-step dimerization process, whereas the 23-mer RNA immediately formed the tight dimer. Furthermore, deletion of the bulge from the 39-mer RNA prevented the NCp7-assisted tight-dimer formation. Therefore, the whole DIS sequence is necessary and sufficient for the two-step dimerization. Our data suggested that the bulge region regulates the stability of the stem and guides the DIS to the two-step dimerization process.

Capsid↗

Ultrasonographic diagnosis criteria using scoring for hypertrophic pyloric stenosis.

PURPOSE: For diagnosis of infantile hypertrophic pyloric stenosis (HPS), ultrasonography (US) is a useful and objective diagnostic method. In the current study, pyloric diameter, muscular thickness, and pyloric length were measured in normal infants (n = 26) and infants which is an adequate (n = 57). Each score was assigned to relevant measurements, and diagnostic criteria obtained with a scoring system were prepared using statistical skills by the probit analysis. METHODS: For scoring, points were given to relevant measurements in conformity with the probit analysis. Zero points were given to patients with no possibility of HPS, 1 point to those with less than 25% probability, 2 points to those with 25% or more but less than 50% probability, and 3 points to patients with 50% or more probability. Points were totaled, and analysis was performed. RESULTS: The composite score was evaluated by probit analysis, and cases with a composite score of 2 or less were all included in the normal group, whereas those with a composite score of 3 or more were all in the HPS group. Both groups could thereby be 100% identified. CONCLUSION: US was able to diagnose cases with overall score of 2 or less as normal and those with overall score of 3 or higher as having HPS. In addition, after the current diagnostic criteria were prepared, preoperative diagnoses were performed prospectively using them for vomiting neonates and infants, and all cases were correctly discriminated and diagnosed. These findings indicate our ultrasonographic diagnosis criteria are useful for diagnosing HPS.

Female↗

NMR analysis of intra- and inter-molecular stems in the dimerization initiation site of the HIV-1 genome.

Two positive-strand HIV-1 genomic RNAs form a dimer in virion particles through interaction of the dimerization initiation sites (DIS). The DIS RNA fragment spontaneously formed a "loose-dimer" and was converted into a "tight-dimer" by supplementation with nucleocapsid protein NCp7. This two-step dimerization reaction requires the whole DIS sequence [Takahashi et al. (2000) RNA 6, 96-102]. In the present study, we measured imino proton resonances to investigate the secondary structures of the two types of dimers in a 39-mer RNA covering the entire DIS (DIS39), including discrimination between intra- and inter-molecular base pairing. Both the presence and absence of inter-molecular NOE between (15)N-labeled and unlabeled DIS39 were unambiguously detected in an equimolar mixture of (15)N-labeled and unlabeled DIS39. The stem-bulge-stem structures in both dimers were confirmed and found to be very close to each other from clear superimposition of the NMR spectra in the two dimeric states. Nevertheless, the modes of base pairing in the stems of the loose- and tight-dimers were intra- and inter-molecular, respectively. Our results suggest a large structural alteration of genomic RNA occurs during virion maturation.

Dimerization↗