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Biomedical subjects

R Watanabe

Publications and source records attributed to R Watanabe.

At least 145 records · Page 8Linked to original sources

[Early urachal carcinoma diagnosed by magnetic resonance imaging: a case report].

A case of an early urachal carcinoma is reported. A 46-year-old man was referred to our hospital because of urinary bladder tumor. Microhematuria had been detected by a medical health examination two months earlier. Gold punch biopsy under cystoscopy proved adenocarcinoma. Sagittal view in magnetic resonance imaging (MRI) clearly demonstrated a small tumor at the bladder dome. En bloc partial cystectomy and pelvic lymphadenectomy was performed under diagnosis of early urachal carcinoma. Microscopically, papillary adenocarcinoma like colon carcinoma was revealed, but the bladder wall and urachus were free from the infiltration of carcinoma cells and no pelvic lymph node metastasis was found. There has been no evidence of recurrence or metastasis 5 months after the operation.

Adenocarcinoma↗

Long-term follow-up of hemostatic molecular markers during remission induction therapy with all-trans retinoic acid for acute promyelocytic leukemia. Keio Hematology-Oncology Cooperative Study Group (KHOCS).

Hemostatic molecular markers were serially monitored in a prospective fashion during remission induction therapy with all-trans retinoic acid (ATRA) in sixteen patients with acute promyelocytic leukemia (APL). One patient with leukocytosis before treatment and three patients who later developed hyperleukocytosis also received chemotherapy with behenoyl Ara-C and daunorubicin. Plasma levels of E-fragment of fibrin and fibrinogen degradation product (FDP-E), FDP-D dimer (D-D), thrombin-antithrombin complex (TAT), and plasmin-alpha 2 plasmin inhibitor complex (PIC) were markedly elevated in all but one patient before treatment, and these parameters decreased to normal or near normal ranges in most patients within the first 7 days of treatment. Interestingly, we have found that these parameters were again elevated during the later course of ATRA therapy (after day +7) in eleven patients for various reasons including cytotoxic chemotherapy (3 cases), fever (5 cases; 2 cases with apparent infection, 3 cases without known etiology), Caesarean section (1 case), and no apparent etiology (2 cases). Three patients showed bleeding complications during re-elevation of molecular markers, but none developed thrombosis. Plasma elastase-alpha 1 proteinase inhibitor complex (E-alpha 1 PI) was markedly elevated in all patients at diagnosis and did not decrease significantly during ATRA therapy. Plasma tissue factor antigen was mildly elevated in one out of four patients studied, and thrombomodulin was elevated in two out of ten patients tested. These results confirmed the rapid normalization of coagulopathy during the early phase of remission induction therapy with ATRA but suggest that re-elevation of molecular markers occurs frequently during the later course of ATRA therapy.

Adolescent↗

[Steroid responsive chronic brainstem encephalitis featuring mental symptoms, abnormal eye movement and cerebellar ataxia].

A 53-year-old man presented with progressive ataxia two and a half years prior to admission. Initially he was treated in a local hospital for 4 months with a diagnosis of spinocerebellar degeneration. Subsequently he developed psychomotor excitement with hallucination and was admitted to a mental hospital for 7 months with a diagnosis of Wernicke's encephalopathy. After a year of partial remission, he presented with increasing difficulty in thinking and walking. On admission he developed mental agitation and excitement, ocular flutter and opsoclonus, and prominent cerebellar ataxia. A lymphocytic pleocytosis in the CSF and a high-intensity lesion in the superior cerebellar peduncle of the upper brainstem revealed on a T2-weighted MRI led to a diagnosis of brainstem encephalitis. Treatment with steroid (two series of 3 days of 1,000mg methylprednisolone DIV, followed by 60mg oral prednisolone) brought about a dramatic improvement in mental and ocular symptoms corresponding with the CSF findings. He was left with mild cerebellar ataxia and returned to work on a small dose of steroids. Differential diagnoses including Bickerstaff's encephalitis and pathomechanism were discussed.

Brain Stem↗

[Autobiographical memory loss following herpes encephalitis].

We report a patient with prominent autobiographical memory (ABM) impairment, and discussed possible mechanisms of her deficits. The patient was a 36-year-old woman who suffered from herpes simplex encephalitis in November 1994. Four months after the onset, the neuropsychological examination disclosed that her intelligence, attention, language and frontal lobe functions were normal. Moderate anterograde amnesia was evident for visual materials, and she showed difficulties in retrieving visual images. Deficits in verbal learning were minimal. In contrast, her retrograde amnesia (RA) was severe. Further analyses clarified that memory for public events and personal semantic memory were relatively well preserved whereas ABM was severely impaired with no evidence of temporal gradient. Her performance on the ABM questionnaire was even worse than that of alcoholic Korsakoff patients. Interestingly, however, deficits in memory for public events also emerged when questions were presented with pictures instead of ordinary verbal questionnaires. The results suggest that her principle deficits consisted in utilizing visual information of the past events. Her access to and manipulation of the past visual representation/images were impaired. Consequently, her deficits were almost exclusive to ABM because visual information is most crucial for ABM. This material specific ABM impairment demonstrated in the present patient could be differentiated from nonspecific retrograde amnesia observed in typical focal RA patients. MRI, SPECT and PET demonstrated that the present patient had lesions basically in the right hemisphere, specifically in the medical temporal area including the hippocampus.

Adult↗

PIG-A and PIG-H, which participate in glycosylphosphatidylinositol anchor biosynthesis, form a protein complex in the endoplasmic reticulum.

Many eukaryotic cell surface proteins are bound to the membrane via a glycosylphosphatidylinositol (GPI) anchor. Assembly of the GPI anchor precursor is a sequential addition of components to phosphatidylinositol (PI) in the endoplasmic reticulum (ER). The first step is the transfer of N-acetylglucosamine (GlcNAc) to PI from UDP-GlcNAc to generate GlcNAc-PI. This simple step, however, is regulated by at least three genes because in both mammals and yeasts, there are three mutants of different complementation classes. To clarify this complexity, we analyzed the products of two cloned human genes, PIG-A and PIG-H. Here we demonstrate 1) that PIG-A is an ER transmembrane protein with a large cytoplasmic domain that has homology to a bacterial GlcNAc transferase and a small lumenal domain; 2) that PIG-H is a cytoplasmically oriented, ER-associated protein; and 3) that they form a protein complex. We also show that part of the small lumenal domain of PIG-A plays an essential functional role in targeting itself to the rough ER. Taken together with the cytoplasmic orientation of GlcNAc-PI, these results indicated that PIG-A and PIG-H are subunits of the GPI GlcNAc transferase that transfers GlcNAc to PI on the cytoplasmic side of the ER.

Animals↗

PIG-C, one of the three human genes involved in the first step of glycosylphosphatidylinositol biosynthesis is a homologue of Saccharomyces cerevisiae GPI2.

Glycosylphosphatidylinositol (GPI) protein anchors are ubiquitous in eukaryotic cells. GPI anchors are synthesized in the endoplasmic reticulum by actions of ten or more gene products. The first step of the biosynthesis, the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine to phosphatidylinositol, is mediated by at least three genes in mammalian cells (PIG-A, PIG-H and PIG-C) and in yeast (GPI1, GPI2 and GPI3/SPT14/CWH6). PIG-A is homologous to GPI3/SPTI4/CWH6. However, PIG-H has no homology with GPI1 or GPI2. Here we cloned a human homologue of GPI2 and showed that it is PIG-C. PIG-C protein is a 297 amino-acid membrane protein in the endoplasmic reticulum that has 20% amino acid identity with GPI2. Since there are several human EST sequences that have homology to GPI1, our results suggest that four genes are involved in the first step of GPI anchor synthesis in mammalian cells.

Amino Acid Sequence↗

Loss of human E-cadherin (ECD) correlated with invasiveness of transitional cell cancer in the renal pelvis, ureter and urinary bladder.

Loss or decreased expression of E-cadherin (ECD), which forms an epithelial junction complex that includes several other proteins and triggers signal transduction, may contribute to tumor progression. In the present study, we examined 90 transitional cell cancers (TCCs), 47 urinary bladder cancers and 43 ureteral or renal pelvic cancers, as well as TCC and papilloma cell lines to determine whether they express ECD. We classified ECD expression into normo-expression (like normal epithelial), decreased and loss of ECD staining on TCCs (urinary bladder, renal pelvic or ureteral). We found that low-stage TCCs expressed normal ECD in 68%, decreased of ECD in 20% and loss of ECD in 12%, whereas high-stage TCCs expressed 29%, 41% and 30% of ECD staining, respectively (P < 0.01). Furthermore, grade 1 TCCs were all estimated to show normo-expression, grade 2 TCCS expressed normal ECD in 49%, decreased of ECD in 41% and loss of ECD in 10% grade 3 TCCs classified as 20%, 30% and 50%, respectively (P < 0.01). Staining for cultured cell lines showed positive membranous staining for ECD in a benign papilloma cell line, RT4 and a TCC cell line, HT1376, but not in a TCC cell line, T24. Reverse-transcription polymerase chain reaction showed the presence of ECD and alpha-catenin mRNA in RT4 and HT1376, and only alpha-catenin in T24. Thus, it is more likely that decrease or loss of ECD might contribute to the malignant character of tumor cells and result in tumor progression.

Adult↗

Morphometric analysis of the lumbosacral nerve roots and dorsal root ganglia by magnetic resonance imaging.

STUDY DESIGN: Lumbosacral nerve roots and dorsal root ganglia in relation to surrounding bony structures in normal subjects were investigated using magnetic resonance imaging. OBJECTIVES: This study determined the normal anatomic parameters of the lumbosacral nerve root and dorsal root ganglion, to which degenerative or pathologic changes may be compared. SUMMARY OF BACKGROUND DATA: In the previous literature, most authors have used various modalities in either cadavers or symptomatic patients to study the anatomic details of the lumbar nerve roots and dorsal root ganglia. The data in the literature are conflicting, mainly because of individual variations and different degrees of degenerative change in the spine. METHODS: Twenty male volunteers who had no back pain or radiculopathy underwent magnetic resonance imaging. Ages ranged from 22 to 38 years, with a mean of 30.4 years. T1-weighted coronal magnetic resonance images were taken from L1 to S1. Two hundred thirty-three nerve roots were examined, including 36 L1, 40 L2, 40 L3, 39 L4, 40 L5, and 38 S1. nerve roots Measurements were determined using a computer digitizer. RESULTS: The nerve root origin was at a more cephalad level for the caudad nerve roots, particularly the S1. The take-off angels acutely changed at L1 and S1. The length of the nerve roots increased progressively to a maximum at L5, and decreased at S1. The center of the dorsal root ganglion was positioned more cephalad at S1. The average dimension of the dorsal root ganglion gradually increased from L1 to S1. The most striking difference was in the S1 root, which takes off more cephalad, at a more vertical angle, and has the shortest length of any of the nerve roots. The S1 dorsal root ganglion was also unique in that it was the largest and more frequently located intraspinally. CONCLUSION: The anatomy of the lumbar nerve roots and dorsal root ganglia and their relations to bony structures have been better defined in this study. Because of its more medial location, S1 radiculopathy may involve both the nerve root and dorsal root ganglion as a result of either disc herniation or degenerative L5-S1 facet changes. The relatively larger dorsal root ganglia and the greater dorsal root ganglion/foramen height ratios in the lower lumbar region may explain the higher incidence of L5 or S1 radiculopathy, particularly given the propensity to disc degeneration and intervertebral foraminal narrowing in the lower lumbar region.

Adult↗

Tolerance to the anti-metastatic effect of lipopolysaccharide against liver metastasis in mice.

We describe the involvement of endotoxin tolerance in the refractoriness of its anti-metastatic effect against murine syngeneic tumors. Three i.v. administrations of LPS at intervals of 4 days after tumor inoculation inhibited liver metastasis of L5178Y-ML25 cells, whereas 3 consecutive i.v. administrations of LPS showed only a slight suppressive effect. Multiple i.v. administrations of LPS, synthetic lipid A, its synthetic derivative DT-5461, Staphylococcus aureus (S. aureus) BioParticles or Staphylococcal enterotoxin B (SEB) on days 1, 5 and 9 after tumor inoculation inhibited liver metastasis of T-lymphoma cells in normal mice. The anti-metastatic effects of LPS, synthetic lipid A or DT-5461 but not S. aureus BioParticles or SEB were diminished in mice injected with LPS at daily intervals for 7 days before tumor inoculation. Mice receiving 3 consecutive i.v. administrations of LPS at daily intervals exhibited suppression of LPS-induced production of endogenous tumor necrosis factor-alpha (TNF-alpha), tumoricidal activity of macrophages, and natural-killer (NK) activity of splenocytes when compared with those of normal mice. Macrophages from mice receiving consecutive daily i.v. administrations of LPS for 3 days showed reduction of LPS-induced tyrosine phosphorylation of several intracellular proteins, including p42(mapk) /ERK2 when compared with that of the cells obtained from normal mice. These data suggest that the LPS-induced anergic state of monocytes/macrophages plays a crucial role in endotoxin tolerance with respect to the metastasis of T lymphoma in the liver.

Animals↗

Expression of cutaneous fatty acid-binding protein and its mRNA in rat skin.

Cutaneous fatty acid-binding protein (C-FABP) has been purified from rat skin. Since there was little information about the role of C-FABP in the skin, we investigated the expression of C-FABP and its mRNA in normal rat skin using an immunohistochemical technique and in situ hybridization. In the epidermis, C-FABP mRNA was found to be expressed in basal cells and highly in prickle cells, while C-FABP itself was strongly expressed in the upper prickle and the granular cell layers. In sebaceous glands, both C-FABP and its mRNA were expressed in both peripheral and differentiating cells, although the expression of C-FABP mRNA gradually reduced during differentiation of sebocytes. Since epidermis and sebaceous glands are active sites of fatty acid synthesis, these results suggest that C-FABP may have important roles in the transport and synthesis of fatty acids.

Animals↗

Retroviral pseudo-virus carrying the envelope proteins of neurotropic Friend murine leukemia virus effectively transferred retroviral vector into glial cells.

We isolated the neurotropic Friend murine leukemia virus, FrC6 and its molecular clone A8, which proliferated in rat glial cell lines in vitro and in the rat brain in vivo. To investigate the contribution of viral envelope proteins to the neurotropism of A8 virus, the retroviral pseudo-virus carrying the envelope proteins of A8 virus and Moloney murine leukemia virus (MoMLV) was produced by transfecting the env gene of A8 virus (A8env) in the MoMLV based packaging cell, psi CRE. The phenotypically mixed pseudo-virus infected the rat glial cell lines as well as NIH 3T3 cells, whereas the psi CRE-produced pure pseudo-virus without A8env expression infected the glial cells at lower efficiency. Furthermore, the psi CRE cells with A8env expression produced pseudo-virus at a higher titer than normal psi CRE cells. The infectivity of the phenotypically mixed pseudo-virus to the glial cells was abolished by a neutralizing antibody against A8 virus, which did not reduce the ability of the psi CRE-produced pure pseudo-virus to infect NIH 3T3 cells. These results indicated that the envelope protein of A8 virus is assembled into the pseudo-viral particles and that it contributes to glial cell infection by the A8 virus.

3T3 Cells↗

Security implementation issues in Japan.

A survey was conducted in the year 1994 among medical school hospitals in Japan to know whether there are some written rules or regulations about the use of medical information, and whether they are well matched both to secure patient's privacy and to promote the adequate use of the information. A questionnaire was mailed to 80 medical school hospitals in Japan and 65 of them responded. Besides copies of rules, questioners were also requested for detailed investigation. Twenty nine hospitals responded to our request. The security implementation issues in Japan will be discussed using data thus obtained.

Computer Security↗

Multilocular thymic cysts associated with thymoma. A case report.

The association of multilocular thymic cysts (MTC) with thymoma is exceedingly rare, and the pathogenesis of this combination is controversial. We describe the case of a 42-year-old man with an anterior mediastinal mass found to contain MTC and thymoma. A multilocular cystic mass, measuring 13 x 6.5 x 2 cm, was found in the right lobe of the thymus, and contained a 4.7 x 2 cm thymoma in its center. Microscopic thymomas, lipomatously involuted remaining thymic tissue, and lymphoid follicles with germinal centers were found in the walls of MTC as well as in the left thymic lobe. Non-specific chronic inflammation was also present in the walls. In addition, microcysts, which were only found at the periphery of the thymoma and covered with epithelium, might have been formed secondarily by dilatation of the perivascular spaces and of Hassall's corpuscles. These findings suggest that a chronic inflammatory process was responsible for the early formation and enlargement of this patient's MTC, and that while the cavities of the MTC expanded to various degrees, the thymoma, which originated from one of the microscopic thymomas in the walls of MTC, increased in size, and grew to involve the remaining thymic tissue.

Adult↗

Low prevalence of activated protein C resistance and coagulation factor V Arg506 to Gln mutation among Japanese patients with various forms of thrombosis, and normal individuals.

Resistance to activated protein C (APC), recently reported to be the most prevalent inherited cause of thrombosis among Caucasians, is associated with a single point mutation in the coagulation factor V gene. We investigated the prevalence of APC resistance and the factor V gene mutation (R506Q) in 34 consecutive Japanese patients with venous thrombosis or pulmonary thromboembolism and 63 control subjects. Three of the 33 patients examined (9%) had an APC ratio below the 5th percentile of control values (2.27), but all were above 2.0. The factor V mutation (R506Q) was not detected in the 29 patients studied, including the 3 patients whose APC ratios were below 2.27, or in 53 controls. In a tissue factor-based factor V assay to detect APC resistance recently described by Le et al. (Blood 1995;85:1704-1711), all patients studied were found to be normal including the three with a low APC ratio. We conclude that APC resistance and factor V gene mutation are less prevalent in Japan than in several European countries.

Adult↗

Circulating endogenous thrombopoietin, interleukin-3, interleukin-6 and interleukin-11 levels in patients undergoing allogeneic bone marrow transplantation.

To elucidate the physiologic role of thrombopoietin (TPO) for hematologic reconstitution following allogeneic bone marrow transplantation (BMT), serum TPO levels as well as interleukin-3 (IL-3), IL-6 and IL-11 were serially measured in 55 samples from 3 patients who underwent allogeneic BMT using an enzyme-linked immunosorbent assay (ELISA). The TPO level was higher in the serum taken during marrow aplasia than in the pretransplant serum. The serum TPO levels and platelet counts showed a strong inverse relationship in all patients examined. We also sequentially measured endogenous serum TPO levels before and within 36 h after platelet transfusions. Endogenous serum TPO levels were inversely correlated with platelet mass following platelet transfusions. Serum levels of IL-3 had no apparent correlation with platelet counts and serum levels of IL-11 remained below the detection levels (31.3 pg/ml) in all samples. Serum levels of IL-6 were high during myeloaplasia and more upregulated in the febrile period. These findings support the view that TPO is the central regulator for megakaryopoiesis in vivo and the rationale for its clinical use after allogeneic BMT.

Adult↗

Identification of two missense mutations in the GIP receptor gene: a functional study and association analysis with NIDDM: no evidence of association with Japanese NIDDM subjects.

Gastric inhibitory polypeptide (GIP) potently stimulates insulin secretion from pancreatic islets in the presence of glucose as an incretin. Because the insulinotropic effect of GIP is reduced in NIDDM, it should be clarified whether defects in the GIP receptor gene contribute to the impaired insulin secretion in NIDDM. Using genomic DNA samples from Japanese NIDDM and non-NIDDM subjects, we have investigated the entire coding region of the GIP receptor gene by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP). We have identified two missense mutations, Gly198-->Cys (Gly198Cys) in exon 7 and Glu354-->Gln (Glu354Gln) in exon 12. Investigation of the function of GIP receptor with either of these mutations reveals a half-maximal stimulation value of GIP-induced cAMP response in Chinese hamster ovary cells expressing the GIP receptor with Gly198Cys of 6.3 +/- 1.2 x 10(-10) mol/l (n = 3), which was considerably higher than that of the normal GIP receptor, 9.4 +/- 3.8 x 10(-12) mol/l GIP (n = 3), whereas that of the GIP receptor with Glu354Gln was not significantly different from that of the normal GIP receptor. To assess the possible role of the GIP receptor gene in genetic susceptibility to NIDDM, we have examined the allelic frequencies of Gly198Cys and Glu354Gln in NIDDM and control subjects. Association studies show no relationship between NIDDM and either of the two mutations.

Alleles↗