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Biomedical subjects

J Fujimoto

Publications and source records attributed to J Fujimoto.

At least 253 records · Page 14Linked to original sources

brt, a mouse gene encoding a novel receptor-type protein-tyrosine kinase, is preferentially expressed in the brain.

Using polymerase chain reaction (PCR)-mediated cloning procedure, we have isolated a novel gene encoding protein-tyrosine kinase from fetal mouse brain. This gene, named brt (from brain tyrosine kinase), had an open reading frame that encoded 856 amino acids. The deduced amino acid sequence revealed that the gene product had all the hallmarks of a receptor-type protein-tyrosine kinase. The brt protein showed significant homology to the axl/ufo protein that has an oncogenic potential. Northern blot analysis showed that brt was expressed preferentially in the brain of both embryo and adult. Thus, brt is a new member of the subfamily of receptor-type protein-tyrosine kinases and is suggested to play important roles in development and functions in the central nervous system.

Amino Acid Sequence↗

[Malignant lymphoma with various neuropsychological symptoms].

A case of malignant lymphoma presented with various neuropsychological symptoms which made it difficult to achieve the diagnosis and therapy. A 9-year-old boy was referred to our hospital with complaints of psychological symptoms, impairment of consciousness and generalized convulsive seizures. A lumbar puncture revealed infiltration of numerous blasts which were positive for immature B cell markers. CT scan showed a mass in the right ethmoidal sinus, but no space occupying lesion in the brain. The tumor cells in the right ethmoidal sinus had the same phenotypes as those in the CSF. Thus a diagnosis of non-Hodgkin's lymphoma, developing in the right ethmoidal sinus and infiltrating into the central nervous system, was established. The blast cells in the liquor and the tumor of the right ethmoidal sinus disappeared after induction of systemic chemotherapy, irradiation and intrathecal chemotherapy. However, intracranial bleeding occurred during the chemotherapy. He died of respiratory failure 10 months after the start of treatment.

Child↗

Hyperphosphorylation of a novel 80 kDa protein-tyrosine kinase similar to Ltk in a human Ki-1 lymphoma cell line, AMS3.

Ki-1 lymphoma is a subtype of human malignant lymphoma characterized by the expression of CD30 (Ki-1) and a peculiar morphology. It is occasionally accompanied by a unique reciprocal chromosomal translocation t(2;5)(p23;q35). A Ki-1 lymphoma cell line, AMS3, was established by maintaining biopsied tumor cells in SCID (severe combined immunodeficiency) mice. To investigate abnormalities of the signal transduction in Ki-1 lymphomas, AMS3 lysate was immunoprecipitated with anti-phosphotyrosine monoclonal antibody, 25.2G4, and the immunoprecipitates were subjected to kinase assay and immuno-blotting with 25.2G4. A unique phosphotyrosine-containing protein of MW 80,000, designated p80, was found only in AMS3 cells and not in other cell lines or mononuclear cells from healthy donors. Subsequent amino acid sequence analysis of its tryptic digests showed that p80 was a hitherto undescribed tyrosine phosphoprotein similar to Ltk (leukocyte tyrosine kinase). Furthermore, physical interaction of p80 with CD30 was suggested from immunoprecipitation experiments with AMS3 lysates.

Animals↗

Combined determination of N-myc oncogene amplification and DNA ploidy in neuroblastoma. Complementary prognostic indicators.

BACKGROUND: N-myc gene amplification is a well-established prognostic indicator in neuroblastoma. Flow cytometric analysis of nuclear DNA content has shown that an abnormal nuclear DNA content in neuroblastoma is associated with a better prognosis. Because some patients with N-myc unamplified tumors have a poor prognosis, factors other than N-myc amplification may play a role in determining the clinical behavior of neuroblastoma. In the current study, the authors correlated N-myc gene amplification and flow cytometric nuclear DNA content with respect to prognosis. METHODS: Forty-one patients with neuroblastoma, including 15 screened patients, served as subjects. The copy number of the N-myc gene was determined by Southern blot analysis. DNA ploidy analysis was done on nuclei isolated from formalin-fixed, paraffin-embedded blocks. RESULTS: Of 40 specimens of neuroblastoma, 7 involved tumors containing amplification of the N-myc gene and 33 did not; 13 specimens showed DNA diploidy, and 27 showed DNA aneuploidy (including 4 with DNA tetraploidy). The Kaplan-Meier survival analysis indicated a significantly better prognosis in patients with unamplified N-myc tumors compared with those with N-myc amplified tumors (87.3% versus 28.6%, P < 0.05) and in patients with DNA aneuploid tumors compared with those with DNA diploid tumors (96.3% versus 43.0%, P < 0.001). The difference in the survival of the two extreme combinations, (e.g., 25 with N-myc unamplified and DNA aneuploidy [4 tetraploidy] versus 5 with N-myc amplified and DNA diploidy) was more significant (96.0% versus 20.0%, P < 0.001) than any other combination. CONCLUSION: Evaluations of N-myc gene amplification and DNA ploidy are complementary, and the combined determination of these two factors may be one of the most powerful prognostic indicators in neuroblastoma.

Child, Preschool↗

Efficacy of autotransfusion in hepatectomy for hepatocellular carcinoma.

PURPOSE: Although autotransfusion is used in a wide variety of surgical procedures, it is largely unexplored for use in oncologic operations. This study evaluates the impact of autotransfusion in hepatectomy for hepatocellular carcinoma. PATIENTS AND METHODS: Fifty-four patients with hepatocellular carcinoma underwent hepatectomy by receiving autologous blood transfusion (group 1). Fifty patients receiving homologous blood without any autologous blood were matched for comparison (group 2). RESULTS: No statistical differences were found between group 1 and group 2 patients in cumulative recurrence rates (62.8% vs 67.3%, respectively) or cumulative survival rates (61.9% vs 52.8%). Autologous transfusion reduced the mean volume of homologous blood used (814 mL vs 3466 mL). The mean postoperative hemoglobin level, platelet count, prothrombin time, and partial thromboplastin time were comparable between groups. CONCLUSIONS: Autotransfusion is a safe and effective procedure in patients with hepatocellular carcinoma undergoing hepatectomy.

Aged↗

Hypofibrinogenemia in a girl with Langerhans cell histiocytosis during etoposide and prednisolone therapy.

A case of a girl with Langerhans cell histiocytosis who had hypofibrinogenemia during etoposide (VP-16) and prednisolone therapy is described. A patient on a three times per week schedule of 100 mg/m2 etoposide in combination with 40 mg/m2 of prednisolone every day had hypofibrinogenemia of 90 mg/dL after 12 doses of etoposide. Hypofibrinogenemia improved after discontinuing the course of etoposide. The clinical course suggested that the combination of etoposide with prednisolone caused this side-effect. Although the exact mechanism of toxicity of etoposide with prednisolone remains unknown, it is possible that the side-effect might be due to reduced production of fibrinogen in the liver. Careful monitoring of fibrinogen is mandatory in patients receiving etoposide and prednisolone.

Afibrinogenemia↗

Estrogen and androgen receptors in aorta of the rabbit and regulation by estrogen and androgen.

This study was designed to investigate the sexual and/or regional dimorphism of the effects of estrogens and androgens on the aorta. Estrogen, estradiol-17 beta (E2) and estriol (E3), or androgen, dihydrotestosterone (DHT) and testosterone (T), binding levels, and of effects of E2 and T on their levels were determined in aortas of the male and female rabbits. Priming with E2 affected estrogen binding levels of the male aorta, but the physiological condition with E2 plus T induced the levels of E2 and E3 receptors in the female aorta. DHT receptor level in the male was increased with E2 alone or with T, while a rise in T binding level was seen in the male and female primed with E2 and T. These findings suggest that there is a sexual and/or regional dimorphism in the actions of estrogen and androgen on their receptor synthesis in the aorta.

Androgens↗

Clinical significance of TAL1 gene alteration in childhood T-cell acute lymphoblastic leukemia and lymphoma.

The TAL1 gene is altered as a consequence of t(1;14)(p32;q11) found in T-cell acute lymphoblastic leukemia (ALL) and shows site specific recombination (tald rearrangement). We investigated TAL1 gene alterations in 39 children with T-cell ALL, in 32 with B-precursor ALL, in three with ALL with myeloid-associated antigen, and in 18 with T-non-Hodgkin's lymphoma (T-NHL). tald rearrangement was found in nine of 39 T-cell ALL patients using Southern blot analysis with a TAL1 gene probe. Polymerase chain reaction (PCR) products predicted from the sequences of the corresponding tald alleles were shown in all of these patients. In contrast, no rearranged band was observed in other kinds of leukemia or in T-NHL patients. All of these patients with tald rearrangement had CD1- CD2+ CD4- CD7+ CD10- pheno-type. Of these, seven were classified as stage I thymic differentiation, and eight have survived for three to 59 months remission. Four of seven patients investigated had normal karyotypes, which has been reported to be associated with a good prognosis in T-cell ALL. We conclude that tald rearrangement is restricted to T-cell ALL, for which it provides a useful clonal marker. Such patients with this rearrangement may constitute a subgroup of T-cell ALL with a good prognosis.

Adolescent↗

[Hepatic resection under liver surface or perfusion cooling together with hepatoprotective agents of PGE1 and urinastatin].

The techniques and results of nine patients who underwent hepatic resections with surface and/or in situ perfusion cooling with hepatoprotective agents of PGE1 and Ulinastatin are described. Eight hepatocellular carcinomas associating chronic liver disease and one hemangioma are included in this report. Complete vascular exclusion technique with the centrifugal blood pump driven veno-venous bypass was employed on the three patients with giant liver tumors. The bypass technique with liver cooling made it possible to carry out otherwise impossible and risky resections, particularly in case with neoplastic involvement of the inferior vena cava. The other patients were subjected to segmentectomy of the right lobe under hemihepatic surface cooling or in situ hypothermic perfusion by chilled Lactate Ringer for vascular arrested right lobe. Liver tissue temperature dropped down to 19 degrees C to 26 degrees C during cooling. Postoperative physiologic changes were minimal irrespective of prolonged continuous vascular interruption of the cirrhotic liver for up to 60 min. There was no mortality and major morbidity in the present series. Liver cooling can be an useful hepatoprotective method for the cirrhotic liver in the hepatic resection with vascular occlusion.

Aged↗

Dynamics of normal and injured human liver regeneration after hepatectomy as assessed on the basis of computed tomography and liver function.

We compared liver volume and function kinetics after partial hepatectomy according to extent of resection and severity of coexisting liver disease in 57 adults with uneventful postoperative courses. Liver volume and massiveness of resection, or resection rate, were estimated on computed tomography. Patients were categorized into three groups on the basis of reaction rate: small (< 30%), medium (30%-50%) and large (> 50%). The regenerative patterns of normal livers in the medium and large groups consisted of three phases: a rapid increase during the first month, some decrease in the second month and a final, slower increase. This contrasted with the pattern of injured livers with chronic hepatitis or cirrhosis, which generally showed a phase of less rapid, gradual increase. The regeneration rate (volume gain, cm3/day) during the first month was found to be proportional to resection rate in the presence or absence of liver disease. Normal livers regenerated at least twice as rapidly as injured livers in patients with comparable resection rates. Normal livers reached plateau levels within 1 to 2 mo regardless of the massiveness of resection, whereas regeneration took 3 to 5 mo in injured livers. Liver function (albumin, bilirubin) recovered concomitantly with liver volume in the medium group, whereas in the large group they generally returned to their initial values behind volume restoration, particularly in cirrhotic patients. In conclusion, human liver regeneration is strongly influenced by the massiveness of the resection and presence of coexisting liver disease. However, we found that some cirrhotic livers can regenerate, albeit more slowly and less completely, as long as the extent of hepatectomy remains within safe functional limits.

Adult↗

[Adverse effect of prolonged formalin fixation on DNA ploidy in paraffin-embedded tissue].

From retrospective analysis of 174 formalin fixed, paraffin-embedded, HCC tissue samples, the possible correlation was investigated between the CV determined by FCM and the duration of formalin fixation. An adverse effect of prolonged formalin fixation on CV and fluorescence intensity in liver tissue was investigated prospectively in samples from 4 patients.

DNA, Neoplasm↗

Do the tumor cells of hepatocellular carcinomas dislodge into the portal venous stream during hepatic resection?

BACKGROUND: The current study was undertaken to investigate whether or not tumor cells are dislodged into the portal venous stream during hepatic resection for hepatocellular carcinomas. METHODS: A catheter was placed using echo guidance into the portal branch through the mesenteric vein in 31 patients. Cytologic examinations were done on multiple blood samples at various operative stages. RESULTS: Tumor cells were recovered in 7 of 31 patients in whom the tumor sizes were more than 5 cm and portal invasions were found microscopically and/or macroscopically. By contrast, the remaining 24 tumors were less than 5 cm in size and showed negative portal invasions. Recovery of the tumor cells was found, not during the earlier operative stage of mobilization or rotation of the hepatic lobe, but during the later stages of hilar dissection or hepatic parenchymal dissection. CONCLUSIONS: The portal pedicles should be divided before hepatic dissection in segmentectomy and lobectomy to lessen the chance of dissemination of intravasated tumor cells.

Adult↗

Regulation by thyrotropin-releasing hormone (TRH) of TRH receptor mRNA degradation in rat pituitary GH3 cells.

In rat pituitary GH3 cells, thyrotropin-releasing hormone (TRH) down-regulates TRH receptor (TRH-R) mRNA (Fujimoto, J., Straub, R.E., and Gershengorn, M.C. (1991) Mol. Endocrinol. 5, 1527-1532), at least in part, by stimulating its degradation (Fujimoto, J., Narayanan, C.S., Benjamin, J.E., Heinflink, M., and Gershengorn, M.C. (1992) Endocrinology 130, 1879-1884). Here we show that TRH regulates RNase activity in GH3 cells and that specific mRNA sequences are needed for in vivo regulation of TRH-R mRNA by TRH. TRH affected RNase activity in a biphasic manner with rapid stimulation (by 10 min) followed by a decrease to a rate slower than in control lysates within 6 h. This time course paralleled the effects of TRH on degradation of TRH-R mRNA in vivo. The regulated RNase activity was in a polysome-free fraction of the lysates and was not specific for TRH-R RNA. A truncated form of TRH-R RNA that was missing the entire 3'-untranslated region (TRHR-R5) was more stable than full-length TRH-R RNA (TRHR-WT). In contrast to TRHR-WT mRNA, TRHR-R5 mRNA and TRHR-D9 mRNA, which was missing the 143 nucleotides 5' of the poly(A) tail, were not down-regulated by TRH in stably transfected GH3 cells as their rates of degradation were not increased. These data show that TRH regulates RNase activity in GH3 cells, that the 3'-untranslated region bestows decreased stability on TRH-R mRNA and that the 3' end of the mRNA is necessary for regulation by TRH of TRH-R mRNA degradation. We present an hypothesis that explains specific regulation of TRH-R mRNA degradation by TRH in GH3 pituitary cells.

Animals↗

Immunohistological analysis of tumour infiltrating lymphocytes in seminoma using monoclonal antibodies.

Immunological characterization of tumour infiltrating lymphocytes (TIL) by immunohistological techniques was carried out in 20 cases of stage I seminoma. Routine pathological examination of these surgical specimens showed typical seminoma in 20 cases. Eighteen cases showed obvious TIL and immunohistological staining on frozen specimens was performed in 12. TIL in seminomas were predominantly T-cells but B-cells were also identified. T-cells were distributed diffusely with predominance of the CD8+ phenotype judged semiquantitatively. In contrast to the distribution of T-cells, B-cells tended to accumulate and occasionally formed lymphoid follicles. In such follicles the phenotypic pattern of B-cell antigens was comparable with secondary lymphoid follicles in lymphoid organs. There is an immunologically complex response to seminoma by the host with a predominant infiltration of cytotoxic/suppressor T-cells and functional maturation of B-cells.

Adult↗

O6-methylguanine-DNA methyltransferase activity in human tumors.

The distribution of O6-methylguanine-DNA methyltransferase (MGMT) activity in extracts of tumors from 74 patients was measured. The results demonstrated that there was considerable variation of MGMT activity in different human tumor tissues as well as in different individuals. The mean values (X +/- SD, pmol/mg of protein) in breast cancer, stomach cancer, small cell lung cancer, non-small cell lung cancer, renal cell carcinoma, esophageal carcinoma, brain tumors, colon carcinoma and malignant melanoma were 1.071 +/- 0.374 (9), 0.515 +/- 0.107 (5), 0.509 +/- 0.251 (5), 0.461 +/- 0.227 (24), 0.329 +/- 0.246 (5), 0.273 +/- 0.376 (5), 0.244 +/- 0.175 (14), 0.242 +/- 0.308 (5) and 0.201 +/- 0.161 (2) respectively. It was notable that six samples (1/24 non-small cell lung cancer, 3/5 esophageal carcinoma, 1/14 brain tumors and 1/5 colon carcinoma) did not have any detectable level of MGMT activity. Activity of glutamine pyruvic transaminase (GPT) was also measured in the same extracts used for the assay of MGMT activity. The activity of GPT in these samples with undetectable level of MGMT activity was similar to those with significant MGMT activity. These results further strengthen the assumption that a certain fraction of human tumors are Mer-.

Adult↗

Expression pattern of SR alpha promoter in human embryonal carcinoma and transgenic tissues in mice.

Human embryonal carcinoma is thought to be a counterpart of mouse embryonal carcinoma, which has provided useful information for studying early molecular events in murine embryogenesis. A major practical problem in the use of human embryonal carcinoma for molecular pathological studies is the lack of an efficient expression system for foreign genes. The SR alpha promoter is a fusion promoter containing the SV 40 early promoter and the R segment and part of the U5 sequence of the long terminal repeat derived from human T-cell leukemia virus type I. We analyzed the expression pattern of the SR alpha promoter in human and mouse embryonal carcinoma lines and transgenic mouse tissues. Efficient and stable expression was detected in all cell lines tested, and tissues from all mice of four independent transgenic lines carrying the SR alpha-CAT vector showed a detectable level of CAT expression. These data suggest that the SR alpha promoter is useful for studies of both human embryonal carcinoma and transgenic mouse tissue. Using this expression system, we are now able to label human embryonal carcinomas with various genes, for example beta galactosidase, and follow their fate at the single-cell level in nude mice, where xenotransplanted human embryonal carcinoma expresses differentiation capability.

Animals↗