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Biomedical subjects

H Goto

Publications and source records attributed to H Goto.

At least 145 records · Page 8Linked to original sources

Simultaneous macroamylasemia and macrolipasemia in a patient with systemic lupus erythematosus in remission.

We report the fourth case of simultaneous macroamylasemia and macrolipasemia. A 39-year-old woman had been treated for systemic lupus erythematosus from 1982 to 1993. She was found to have an unexplained increase in serum amylase and lipase activities since 1996. Immunoprecipitation assay showed that amylase was bound to IgA2-kappa and IgA1-kappa (IgA2 > IgA1), whereas lipase was bound to IgA1-kappa. During a follow-up period up to December 1999, the patient did not develop any additional autoimmune or lymphoproliferative disorders. In the situation of atypical clinical features associated with hyperamylasemia and hyperlipasemia, the possibility of macroenzymes should be considered.

Adult↗

Idiopathic myelofibrosis developing isolated granulocytic sarcoma with der (1;7)(q10; p10) after splenectomy and finally transforming to acute myelogenous leukemia.

A 47-year-old female with idiopathic myelofibrosis developed isolated granulocytic sarcoma with der (1; 7)(q10; p10) after splenectomy, followed by acute myelogenous leukemia. The patient had myelofibrosis since 22 years of age, received splenectomy at 47 years, and developed isolated submandibular granulocytic sarcoma, 8 months later. Although the initial tumor disappeared after irradiation, recurrent tumors selectively appeared in the areas of operative scars. She subsequently developed blastic transformation with der (1; 7)(q10; p10), and the blasts were refractory to different chemotherapy. This case is very rare in the following aspects: the onset of myelofibrosis occurred at a relatively young age; isolated granulocytic sarcoma after splenectomy preceded the transformation to acute leukemia; and the subcutaneous tumors developed in areas of operative scars.

Chromosomes, Human, Pair 1↗

[Two cases of orbital non-Hodgkin's lymphoma presenting with hemophagocytic syndrome].

We report 2 cases of orbital non-Hodgkin's lymphoma (NHL) with hemophagocytic syndrome (HPS). Patient 1 was a 64-year-old man with a diagnosis of peripheral T-cell lymphoma originating in the right orbita (clinical stage: IV B). Epstein-Barr virus DNA was demonstrated in tissue specimens by polymerase chain reaction. Laboratory findings on admission were WBC: 4,700/microliter, Hb: 12.1 g/dl, Plt: 14.6 x 10(4)/microliter, LDH: 951 IU/l, sIL-2R: 2,553 IU/ml, and ferritin: 5998.1 ng/ml. Patient 2 was a 73-year-old man with a diagnosis of diffuse large B-cell lymphoma originating in the right orbita (Clinical stage: IV B). Laboratory findings on admission were WBC: 9,100/microliter, Hb: 7.7 g/dl, Plt: 15.4 x 10(4)/microliter, LDH: 1,043 IU/l, sIL-2R: 10,090 IU/ml, and ferritin: 2079.3 ng/ml. Both patients had high-grade fever and extremely high serum cytokine levels. Bone marrow aspiration disclosed many histiocytes with hemophagocytosis. In both cases, combined chemotherapy was transiently effective, but patient 1 died of relapse of HPS and patient 2 of cerebral bleeding. Orbital non-Hodgkin's lymphoma with HPS is rare. These cases were interesting in terms of the relationship between HPS and the primary site of lymphoma.

Aged↗

[An elderly patient with myelodysplastic syndrome successfully treated with combination of granulocyte-colony stimulating factor and continuous-drip infusion of low-dose cytarabine and etoposide].

A 73-year-old man was given a diagnosis of myelodysplastic syndrome in October 1997. He was treated with red blood cell transfusion and granulocyte-colony stimulating factor (G-CSF). In February 1998, he was admitted due to progression of pancytopenia. Bone marrow aspiration revealed refractory anemia with excess of blasts in transformation. The patient was treated with continuous-drip infusion of low-dose cytarabine and etoposide with G-CSF (AVG therapy). Complete remission (CR) was obtained after 2 courses of AVG therapy. Non-hematologic adverse effects were mild enough to be tolerated. CR has been maintained for 16 months with 1 course of consolidation therapy and 3 courses of intensification therapy using the AVG regimen.

Aged↗

[Anesthetic management of a patient with a huge ovarian tumor].

We managed a patient with a huge ovarian tumor (15 kg). The patient was a 50-year-old woman and could not take the supine position because of the tumor causing respiratory embarrassment. An epidural catheter was inserted 3 cm cephalad via the Th 11-12 interspace in the right lateral position. Three milliliters of 1% mepivacaine was injected epidurally for test dose and produced hypesthesia of Th 9-12 five min after the injection. Additional 3 ml of 1% mepivacaine was injected epidurally, which widened the hypesthesia to Th 5-L 2. Intra-arterial pressure was monitored continuously. Under epidural anesthesia without sedation, 11,000 ml of fluid was suctioned slowly from the cyst in 20 min, during which time remarkable hemodynamic derangement did not occur. The patient was turned into the supine position and the trachea was intubated. Laparotomy was performed under general anesthesia. During the surgery, respiratory and hemodynamic conditions were stable. On the following day, chest radiography demonstrated an abnormal shadow in the lower lobe of the right lung. It disappeared the next day without any treatment. Anesthetic management of patients with huge abdominal tumor is also discussed.

Adenocarcinoma, Clear Cell↗

[Clinical statistics on patients and operations during a 20-year period (1978-1997) at Department of Urology, Jikei University School of Medicine].

A statistical analysis was made of diseases, patients, and operations at our department in the four affiliated hospitals of Jikei University School of Medicine from 1978 through 1997. Our findings were as follows. Newly diagnosed urogenital malignancies, except testicular tumors, have been increasing in the last two decades among both outpatients and inpatients. Urogenital infections, including tuberculosis, have gradually been decreasing in the last two decades. The treatment of urinary stone diseases was markedly altered by the induction of extracorponeal shock wave lithotripsy.

Female Urogenital Diseases↗

[Usefulness of dynamic MR mammography for diagnosis of axillary lymph node status in breast cancer patient].

A retrospective study was performed to evaluate whether dynamic MR imaging is useful for the diagnosis of axillary lymph node metastases from breast cancer. Thirty-five patients with breast cancer were scanned and 147 lymph nodes were detected and compared with pathological nodal status. The parameters were the long axis dimension, the short axis dimension, the long-to-short axis (L/S) ratio, the shape, the contrast enhancement ratio (CER), the CER of lymph node-to-primary tumor (L/P) ratio. All parameters had significant differences between metastatic and normal nodes and there was a positive correlation between the CER of primary breast tumors and metastatic nodes. Multivariate analysis identified three parameters: the shape, the CER (1st phase), the L/P ratio (1st phase). ROC analysis revealed the shape and CER are superior in diagnostic performance to L/P ratio. If the shape and CER (1st phase) 60% and above are employed as criteria, the sensitivity, the specificity, the accuracy and the positive and negative predictive value were 86.0%, 78.4%, 81.0%, 67.2% and 91.6%, respectively. This method gives us useful information about the evaluation of axillary lymph node status preoperatively.

Adult↗

Clinical experience of a vacuum-assisted nonroller extra-corporeal circulation system.

We designed a nonroller extra-corporeal circulation system (NRECC) to minimize space requirements and to improve the safety and ease of cardiopulmonary bypass. The NRECC includes a circuit, a centrifugal pump, and a vacuum regulator. The vacuum regulator has five channels, each of which can control negative pressure independently. Negative pressure is applied to suctions, a vent, and a venous reservoir. Auto Vent-SV and one-way valves were placed between the suctions/vent and the reservoir. The total space required for the NRECC with a heat exchanger was 0.49 m2, which is much smaller than that of our current roller pump system. The maximum volume through the suction/vent was 2.5 L/min at -100 mmHg measured in a simulated system. We used the NRECC for six CABG cases and compared results with those of five CABG cases managed by traditional roller pump extra-corporeal circulation (RECC). The two systems were compared in terms of set-up time and stability/accuracy of the suction/vent. The set-up time of the NRECC (5.3 +/- 1.9 min) was significantly shorter than that of RECC (29 +/- 3.4 min) (p < .01). Stable and accurate blood flow were achieved with the NRECC operating between -15 mmHg and -25 mmHg. In conclusion, NRECC can run a bypass easily and safely and has the benefit of reducing space requirements and shortening set-up time.

Cardiopulmonary Bypass↗

Lymphoid blast crisis during interferon-alpha therapy in a patient with chronic myelogenous leukemia in myeloid blast crisis.

A 47-year-old woman was admitted to the hospital on March 13, 1998, because of general malaise and fever. It was determined that she had chronic myelogenous leukemia (CML) in myeloid blast crisis. Hydroxyurea was started initially, and the blasts completely disappeared from peripheral blood on day 9 of therapy. Interferon (IFN)-alpha was subsequently started, but lymphoblasts newly appeared on day 13 of administration. Treatment with adriamycin, vincristine, and prednisolone (AdVP) was immediately started, which rapidly reduced the lymphoblasts. However, the myeloblasts again began to gradually increase. Subsequent examinations showed the combined presence of myeloblasts and lymphoblasts in the marrow and peripheral blood. The ratio between myeloblasts and lymphoblasts depended on the treatment (IFN-alpha or AdVP). The patient died from respiratory failure on November 16, 1998. This patient may have had an underlying bipotential blastic clone that evolved differently in response to IFN-alpha or AdVP. In some CML patients, IFN-alpha may induce lymphoid blast crisis.

Blast Crisis↗

[Role of level-1 trauma and critical care centers in treatment of acute poisoning].

In the summer of 1998, the so-called Wakayama currty poisoning case occurred, and subsequently additional murders took place in which the accusred used sodium aziede and thallium to posison their victims. When the poison victims were admitted to hospital, food poisoning was mistakenly diagnosed. Due to serious concerns that such misdiagnoses might recur, the Japanese Ministry of Health and Welfare equipped 10 level-1 trauma and critical care centers and 66 critical care centers nationwide with high-performance liquid chromotographs, ion chromatographs, gas chromatographs, fluorescence X-ray analyzers, and high-frequency plasma mass spectrometers. This equipment will allow the detection of most types of industial and other chemicals as well as most therapeutic drugs. This report describes the current status of poison analysis systems and the role of level-1 trauma and critical care centers in cases of poisoning.

Critical Care↗

Application of the Cre recombinase/loxP system further enhances antitumor effects in cell type-specific gene therapy against carcinoembryonic antigen-producing cancer.

A considerable number of studies of cancer have shown that the cell type-specific promoter is an effective tool for selective expression of foreign genes in tumor cells. However, few reports have demonstrated significant in vivo antitumor effects using this strategy thus far, possibly because the low activity of such a promoter results in insufficient expression of genes in cancer cells as well as in insignificant antitumor effects, even when the cells are infected by highly efficient gene transfer methods. To overcome this problem, we used the Cre/loxP system for the cell type-specific gene therapy against carcinoembryonic antigen (CEA)-producing cancer. We constructed a pair of recombinant Ads. One expresses the Cre recombinase (Cre) gene under the control of the CEA promoter (Ad.CEA-Cre). The other contains the herpes simplex virus thymidine kinase (HSV-TK) gene separated from the strong CAG promoter by insertion of the neomycin resistance (neo) gene (Ad.lox-TK). The HSV-TK gene of the latter Ad is designed to be activated through excisional deletion of the neo gene by Cre enzyme released from the former one only when CEA-producing cells are infected simultaneously with these Ads. Coinfection by these Ads rendered a human CEA-producing cancer cell line 8.4-fold more sensitive to ganciclovir (GCV) compared with infection by Ad.CEA-TK alone, the HSV-TK gene of which is directly regulated by the CEA promoter. On the other hand, coinfection with these Ads did not significantly change the GCV sensitivity of non-CEA-producing cells. Intratumoral injection of Ad.CEA-Cre combined with Ad.lox-TK followed by GCV treatment almost completely eradicated CEA-producing tumors established in the subcutis of athymic mice, whereas intratumoral injection of Ad.CEA-TK with GCV administration at most retarded the growth of inoculated tumors. These results suggest distinct advantages of the Cre/loxP system applied in the conventional cell type-specific gene therapy against cancer.

Adenocarcinoma↗

Identification of a novel phosphorylation site on histone H3 coupled with mitotic chromosome condensation.

Histone H3 (H3) phosphorylation at Ser(10) occurs during mitosis in eukaryotes and was recently shown to play an important role in chromosome condensation in Tetrahymena. When producing monoclonal antibodies that recognize glial fibrillary acidic protein phosphorylation at Thr(7), we obtained some monoclonal antibodies that cross-reacted with early mitotic chromosomes. They reacted with 15-kDa phosphoprotein specifically in mitotic cell lysate. With microsequencing, this phosphoprotein was proved to be H3. Mutational analysis revealed that they recognized H3 Ser(28) phosphorylation. Then we produced a monoclonal antibody, HTA28, using a phosphopeptide corresponding to phosphorylated H3 Ser(28). This antibody specifically recognized the phosphorylation of H3 Ser(28) but not that of glial fibrillary acidic protein Thr(7). Immunocytochemical studies with HTA28 revealed that Ser(28) phosphorylation occurred in chromosomes predominantly during early mitosis and coincided with the initiation of mitotic chromosome condensation. Biochemical analyses using (32)P-labeled mitotic cells also confirmed that H3 is phosphorylated at Ser(28) during early mitosis. In addition, we found that H3 is phosphorylated at Ser(28) as well as Ser(10) when premature chromosome condensation was induced in tsBN2 cells. These observations suggest that H3 phosphorylation at Ser(28), together with Ser(10), is a conserved event and is likely to be involved in mitotic chromosome condensation.

Amino Acid Sequence↗

Cell cycle regulation of human CDC6 protein. Intracellular localization, interaction with the human mcm complex, and CDC2 kinase-mediated hyperphosphorylation.

The binding of mammalian MCM complexes to chromatin is cell cycle-regulated and under CDC2 kinase negative control. Here, we investigated the properties of mammalian CDC6 protein, a candidate regulator of MCM. The levels of CDC6 were relatively constant during the HeLa cell cycle. In asynchronous cells, CDC6 was mainly detected in the nuclei with immunostaining, but some CDC6 was not extractable with nonionic detergent. In contrast to the chromatin-bound MCM, this fraction of CDC6 was resistant to DNase I treatment, suggesting that it binds to the detergent- and nuclease-resistant nuclear structure. In S phase cells, CDC6 became detectable in the cytoplasm with immunostaining; however, the level of the bound CDC6 was unchanged. In G(2)/M phase cells, the level of the bound CDC6 was still maintained, which was hyperphosphorylated by CDC2 kinase. These data suggest that some CDC6 protein is associated with the specific nuclear structure throughout the cell cycle and that major binding sites on chromatin differ between MCM and CDC6. However, co-immunoprecipitation assays with chemical cross-linking indicated that a small part of the chromatin-bound MCM is present close to the bound CDC6.

Cell Cycle↗

Generation of influenza A viruses entirely from cloned cDNAs.

We describe a new reverse-genetics system that allows one to efficiently generate influenza A viruses entirely from cloned cDNAs. Human embryonic kidney cells (293T) were transfected with eight plasmids, each encoding a viral RNA of the A/WSN/33 (H1N1) or A/PR/8/34 (H1N1) virus, flanked by the human RNA polymerase I promoter and the mouse RNA polymerase I terminator-together with plasmids encoding viral nucleoprotein and the PB2, PB1, and PA viral polymerases. This strategy yielded >1 x 10(3) plaque-forming units (pfu) of virus per ml of supernatant at 48 hr posttransfection. The addition of plasmids expressing all of the remaining viral structural proteins led to a substantial increase in virus production, 3 x 10(4)-5 x 10(7) pfu/ml. We also used reverse genetics to generate a reassortant virus containing the PB1 gene of the A/PR/8/34 virus, with all other genes representing A/WSN/33. Additional viruses produced by this method had mutations in the PA gene or possessed a foreign epitope in the head of the neuraminidase protein. This efficient system, which does not require helper virus infection, should be useful in viral mutagenesis studies and in the production of vaccines and gene therapy vectors.

Animals↗

Specific accumulation of Rho-associated kinase at the cleavage furrow during cytokinesis: cleavage furrow-specific phosphorylation of intermediate filaments.

The small GTPase Rho and one of its targets, Rho-associated kinase (Rho-kinase), are implicated in a wide spectrum of cellular functions, including cytoskeletal rearrangements, transcriptional activation and smooth muscle contraction. Since Rho also plays an essential role in cytokinesis, Rho-kinase may possibly mediate some biological aspects of cytokinesis. Here, using a series of monoclonal antibodies that can specifically recognize distinct phosphorylated sites on glial fibrillary acidic protein (GFAP) and vimentin, phosphorylation sites by Rho-kinase in vitro were revealed to be identical to in vivo phosphorylation sites on these intermediate filament (IF) proteins at the cleavage furrow in dividing cells. We then found, by preparing two types of anti-Rho-kinase antibodies, that Rho-kinase accumulated highly and circumferentially at the cleavage furrow in various cell lines. This subcellular distribution during cytokinesis was very similar to that of ezrin/radixin/moesin (ERM) proteins and Ser19-phosphorylated myosin light chain. These results raise the possibility that Rho-kinase might be involved in the formation of the contractile ring by modulating these F-actin-binding proteins during cytokinesis and in the phosphorylation and regulation of IF proteins at the cleavage furrow.

Cell Division↗