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Biomedical subjects

T Murase

Publications and source records attributed to T Murase.

At least 253 records · Page 14Linked to original sources

Islet amyloid polypeptide (IAPP) gene analysis in a Japanese diabetic with marked islet amyloid deposition.

Islet amyloid polypeptide (IAPP) is a major constituent of pancreatic amyloid deposits in many patients with non-insulin-dependent diabetes mellitus (NIDDM). We analyzed the IAPP gene in a Japanese diabetic with marked islet amyloid deposition. Pancreatic specimens were obtained from an 87-year-old NIDDM patient who had had diabetes for 37 years. All islets (100/100) in his pancreas had IAPP-positive amyloid deposition, and 70% of the area of the islet was replaced by amyloid. We amplified the coding regions as well as the upstream region of the IAPP gene by polymerase chain reaction (PCR). The products of PCR were sequenced, and the sequences of the coding regions were identical to the Caucasian ones. However, the nucleotides of two positions of 5'-upstream and one position of intron 2 were different from the Caucasian data: the upstream region of the IAPP gene in the patient had cytosine substituted for thymine at -259, and had two alleles including cytosine and adenine at -229, respectively. The nucleotide of position 539, that is guanine, was deleted. A possible difference in the IAPP promoting region between the Japanese and Caucasian population was suggested.

Aged↗

Regulation of proliferation by vasopressin in aortic smooth muscle cells: function of protein kinase C.

AIM: To investigate the effect of arginine vasopressin-stimulated prostaglandin synthesis and the activation of protein kinase C on DNA synthesis in rat aortic smooth muscle cells. METHODS: The effects of arginine vasopressin on the release of arachidonic acid and the synthesis of prostaglandin (PG) E2 and prostacyclin (PGI2) were determined. The effects of 12-o-tetradecanoylphorbol-13-acetate (TPA), a protein kinase C-activating phorbol ester, and of 1-oleoyl-2-acetylglycerol, a specific activator of protein kinase C, were evaluated in cultured rat aortic smooth muscle cells. The effects of arginine vasopressin and prostaglandins on the progression from the late G1 to the S phase of the cell cycle were evaluated by measuring the DNA synthesis, and the effects of TPA on them were evaluated. RESULTS: Arginine vasopressin dose-dependently stimulated arachidonic acid release. TPA and 1-oleoyl-2-acetylglycerol dose-dependently increased the vasopressin-induced arachidonic acid release. Vasopressin stimulated the synthesis of both PGE2 and PGI2. TPA increased the vasopressin-stimulated prostaglandin synthesis as well as the arachidonic acid release. Vasopressin, added at the G0/G1 phase of the cell cycle, stimulated DNA synthesis of aortic smooth muscle cells. Exogenous PGE2 and PGI2 inhibited the DNA synthesis and showed maximum inhibition when added at the late G1 phase. TPA alone, added at the late G1 phase, reduced the DNA synthesis stimulated by vasopressin at the G0/G1 phase to about 45%, but vasopressin alone, added at the late G1 phase, had little effect. However, with TPA pretreatment, vasopressin significantly suppressed the DNA synthesis by about 70%. Staurosporine, a protein kinase C inhibitor, reduced the suppression by TPA alone or by vasopressin with TPA pretreatment almost to the control level. Indomethacin, a cyclo-oxygenase inhibitor, reduced the suppression by vasopressin with TPA pretreatment almost to the level of TPA alone. CONCLUSIONS: These results suggest that arginine vasopressin has a suppressive effect on DNA synthesis in rat aortic smooth muscle cells by inhibiting progression from the late G1 into the S phase of the cell cycle through the synthesis of PGE2 and PGI2, and that protein kinase C acts as an amplifier of this mechanism.

Animals↗

[Aztreonam or gentamicin combined with piperacillin as empiric antibiotic therapy during neutropenia of patients with hematologic diseases].

Fourty-two febrile episodes of 32 patients with hematologic disease during neutropenia were treated with two randomly assigned antibiotic combinations of either piperacillin plus gentamicin or piperacillin plus aztreonam. Eleven of the 22 febrile episodes treated with piperacillin plus gentamicin and 12 of the 20 febrile episodes treated with piperacillin plus aztreonam responded. Addition of cefamandole to non-responders improved the outcome in 2 of the 16 febrile episodes. Mean nadir leucocyte count, age, sex, and underlying disease were not significantly different in both groups. Side effects were tolerable in both groups, although 1 patient treated with piperacillin plus gentamicin showed severe renal impairment. Piperacillin plus aztreonam is as effective as piperacillin plus gentamicin as an empiric antibiotic combination in the treatment of febrile episodes with hematologic disease during neutropenia.

Adolescent↗

[Pelvic floor muscle training as treatment of stress incontinence. The effectiveness of vaginal cones].

Pelvic floor muscle training is the mainstream of the non-operative treatment for female stress urinary incontinence. However, in order to make this method effective, it is mandatory to learn how to correctly contract pelvic floor muscles. Thirty adult women suffering from mild stress incontinence were instructed to train their pelvic muscles using vaginal cones. They retained cones of increasing weight in the vagina by contracting pelvic floor for 15 minutes twice a day. Twenty-seven of 30 (90%) patients could complete the training in five weeks. Both incidence and degree of incontinence decreased significantly after the training. The subjective improvement rate (incontinence cured or decreased by 50%) was 70%. The cone weights which they could hold over one minute and the voluntary pelvic floor contractions measured with the perineometer increased significantly, which indicated strengthening of pelvic floor muscles. Vaginal cones have a shape similar to tampons and are accepted by Japanese women with little psychological resistance. This device helps the patients to understand how to contract pelvic floor muscles and to motivate them to continue training, thus contributing for the treatment of stress incontinence.

Adult↗

Detection of three separate DNA polymorphisms in the human lipoprotein lipase gene by gene amplification and restriction endonuclease digestion.

A rapid detection method was developed for DNA polymorphisms in the human lipoprotein lipase (LPL) gene. The examined polymorphisms include an A-C transversion in the 5'-region of intron 3, a T-G transversion that occurs within a Hind III site of intron 8, and the previously described C-T transition that causes a Pvu II polymorphism in intron 6. Gene fragments encompassing each polymorphic site were amplified by the polymerase chain reaction (PCR) and digested with an appropriate restriction enzyme whose recognition site was either naturally affected by the polymorphism or artificially created with a mismatched PCR-primer. According to the digestion profiles, genotypes were unambiguously distinguished. With this method, respective allelic frequencies were determined for 50 or 70 normal subjects. The procedure will facilitate LPL genotyping in the large population.

Base Sequence↗

[Determination of ER-D5 (estrogen receptor related antigen) in prostatic cancer and its significance].

The existence of an estrogen receptor and various other sex steroid receptors has been confirmed in prostatic cancer. However, the action mechanism of hormone therapy and relationship between the disappearance of hormone response, which is observed in the recurrence of prostatic cancer, and various sex steroid receptors have yet to be identified. The use of monoclonal antibody ERICA is known as a method of detecting the estrogen receptor in the immuno-histological chemistry method. However, this monoclonal antibody is difficult to use on paraffin sections. Therefore, using monoclonal antibody D5, which allows ER-D5 detection of the estrogen receptor related antigen on paraffin sections, we investigated whether or not estrogen receptors are present in the prostatic cancer preparation and studied the survival rate of prostatic cancer as well as relationship with recurrence. Positive ER-D5 results were obtained in 37 of 93 prostatic cancer cases (39.8%) and in all 20 prostatic hypertrophy cases (100%). ER-D5 tended to be more densely stained in prostatic hypertrophy than in prostatic cancer. The survival rate was obviously higher in the ER-D5 positive prostatic cancer cases than in ER-D5 negative cases for a certain period of time after the start of treatment. Despite differences in the histo-differentiation degree and clinical stage of prostatic cancer, the ER-D5 positive percentage did not change and remained between 35% and 45%. In cases where another prostatic cancer preparation was taken because of recurrence of prostatic cancer, there were no ER-D5 positive cases at the time of recurrence.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

[Studies of human bone marrow stromal cells--effects of antimetabolites on the growing dynamics of human bone marrow cells and their support of hemopoietic cells].

The effects of antimetabolites on the growing dynamics of human bone marrow stromal cells and their support of hemopoietic cells were tested by using a modified version of Dexter's culture system. Cytosine arabinoside (ara-C) was found to suppress neither the growing dynamics nor the supportability. On the other hand, methotrexate (MTX) suppressed the supportiveness, even though it hardly suppressed the growing dynamics. The recognition of injury to marrow cells could be of potential importance in cancer chemotherapy. Our in vitro evidence may provide clinical insights for cancer chemotherapy including prolonged marrow suppression or pretreatment of bone marrow transplantation.

Adult↗

[A randomized study of pirarubicin (THP) versus adriamycin (ADM) for intravesical instillation therapy against superficial bladder cancer].

To determine the antitumor action by intravesical instillation prior to transurethral resection TUR, a randomized study on pirarubicin (THP) versus adriamycin (ADM) was performed for superficial, papillary and initially detected bladder cancers with participation of 21 Urological Clinics in 3 Tokai Prefectures. The instillation dose of 500 micrograms/ml was given 3 times per week for 3 weeks in both THP (n = 33) and ADM (n = 30) groups. The complete and partial response rates were 56.3% in THP group and 26.7% in ADM group. THP instillation was more effective against multiple tumors than a single tumor, stage Ta than T1 and grade G1 than G2 and G3. However, these findings were not statistically significant. Untoward effects were mainly bladder irritability and its frequency was 60.6% in the THP group and 23.3% in the ADM group. Contracted bladder was found in 2 of the 33 patients in the THP group and 2 of the 30 patients in the ADM group. The antitumor effect of a half dose of THP was equivalent to that of one dose of ADM, and the THP group showed a twofold higher frequency of side effects. Therefore, a clinical trial should be made comparing the effect of 500 micrograms/ml of THP and that of 1,000 micrograms/ml of ADM.

Administration, Intravesical↗

[Mitoxantrone and conventional-dose cytosine arabinoside for relapsed and refractory acute leukemia].

Fourteen patients with relapsed or refractory acute leukemia received combination chemotherapy of mitoxantrone 6 mg/m2/day intravenously for three to six days and cytosine arabinoside 60 mg/m2/day intravenously over 24 hours continuously for five to ten days. Complete remission was attained in six patients (42.9%) and partial response in two patients (14.3%). Six patients (42.9%) had resistant disease, and four patients (28.6%) died during the myelosuppressive phase. Of the patients achieving complete remission, four relapsed and other two continued complete remission up to 27.3 months. Median remission duration was approximately 10.6 months. No significant difference was found with regard to the efficacy of our regimen between AML and ALL. Hematological toxicity was no more severe than the prior cumulative chemotherapy. Major non-hematologic side effects were nausea and vomiting (71.4%), stomatitis (64.3%) and liver dysfunction (57.1%), which were moderate and manageable, while no cardiotoxicity was observed in any patient. In conclusion, the combination chemotherapy of mitoxantrone and conventional dose cytosine arabinoside is an effective salvage therapy in relapsed or refractory acute leukemia, and our regimen has possible utility as first-line chemotherapy in de novo acute leukemia also.

Acute Disease↗

Lymphangioma of the upper extremity.

Lymphangioma of the upper extremity is rare; its treatment is unstandardized. We reviewed five female and one male patient with cavernous lymphangioma of the hand and forearm. Each of them underwent at least one surgical procedure. Five patients had satisfactory results with cosmesis and hand function. Satisfactory results are expected in those treated initially in early childhood, as most lymphangiomas tend to increase gradually in size and infiltrate previously uninvolved normal tissues.

Arm↗

Occurrence of multiple aberrantly spliced mRNAs upon a donor splice site mutation that causes familial lipoprotein lipase deficiency.

A donor splice site mutation was found in the lipoprotein lipase (LPL) gene of a patient with familial LPL deficiency. The mutation, a G----A substitution, occurred at the first nucleotide of intron 2. Northern blot analysis of total RNA from the patient showed strikingly low levels of LPL-specific mRNAs. Using the polymerase chain reaction, the LPL mRNA splicing was analyzed in detail. The results demonstrated that no normal splicing occurred at the authentic splice site; rather a cryptic splice site 18 bases upstream from the mutation site was preferentially utilized. Although the resulting alteration in mRNA was a minute in-frame 18-base deletion, the amount of the abnormal transcript was only 1/12 that of the normal. In addition to this major cryptic splice site, we also identified multiple minor sites which were utilized at extremely lower efficiencies. Unexpectedly, one of these minor sites was also used as an alternative splice site in the normal subject at a comparably low efficiency. The sequences of these minor cryptic sites possessed many of the characteristics common to those of other normal splice sites, indicating that even such minor sites should have also been selected according to the general rules for splice site selection. These results demonstrate that upon mutation, a broad spectrum of cryptic splice sites is activated in vivo at the sites' respective efficiencies.

Adult↗

Differential phenotypic expression by three mutant alleles in familial lecithin:cholesterol acyltransferase deficiency.

Familial deficiency of lecithin:cholesterol acyltransferase (LCAT) is an autosomal recessive disorder characterised by abnormalities of all plasma lipoprotein classes and by abnormal deposition of unesterified cholesterol in tissues. To elucidate the molecular basis of the disease, the LCAT genes of three unrelated Japanese patients were amplified by means of the polymerase chain reaction. Direct sequencing of the amplified fragments covering all exons and junctions showed that the patients are homozygotes for separate gene mutations. In one patient a 3 bp insertion, which should cause a substantial change in the enzyme structure, was found in exon 4; he had near absence of LCAT mass and activity. Two separate missense mutations were identified in exon 6 of the other two patients, who produced functionally defective enzymes that differed widely in specific activity. The replacement of asparagine228 with positively charged lysine completely abolished enzyme activity, whereas the other, conservative, aminoacid substitution (methionine293----isoleucine) gave rise to a partially defective enzyme. These results show that distinct mutations cause differences in plasma LCAT activity and LCAT mass, ultimately leading to differential phenotypic expression of familial LCAT deficiency.

Adult↗

Centrally administered galanin inhibits osmotically stimulated arginine vasopressin release in conscious rats.

The effect of centrally administered galanin on arginine vasopressin (AVP) release was investigated in conscious rats. Intracerebroventricular injection of porcine galanin suppressed hypertonic saline-induced increase in plasma AVP in a dose-dependent manner (12.5-100 pmol/rat) at 10 min after the injection. Pretreatment with subcutaneous injection of naloxone (1 mg/100 g b.wt.) partially blocked the galanin-induced effect on plasma AVP. These results suggest that central galanin inhibits osmotically stimulated AVP release and endogenous opioids are, at least in part, involved in the mechanism.

Animals↗

Hereditary high-potassium erythrocytes with high Na, K-ATPase activity in Japanese shiba dogs.

The sodium (Na) and potassium (K) concentrations and Na, K-ATPase activity were examined in erythrocytes from 24 Japanese shiba dogs and 79 dogs of 24 other breeds. Eleven of the shibas had erythrocytes with high K and low Na concentrations, together with high Na, K-ATPase activity (HK RBCs), while red cells from the remaining shibas and all of the other breeds examined showed low K and high Na concentrations, with no enzyme activity (LK RBCs). The concentration of reduced glutathione in HK RBCs was about five times that in LK RBCs. All the findings from HK shibas were in good agreement with those from HK mongrel dogs found in Japan previously. Since the shiba is a Japanese breed of dog, the results of the present study strongly suggest that the gene for HK RBCs may be inherent in dogs indigenous to Japan, particularly in shiba dogs.

Animals↗

Benign mixed mesenchymal tumor of the spermatic cord.

We report a case of benign mixed mesenchymal tumor consisting of spindle cells and an area involving osseous elements. Immunohistochemical investigation revealed the spindle tumor cells to express vimentin and the alpha-subunit of S100 protein, but no staining for other specific antigens. The findings thus suggest that the spindle tumor cells are undifferentiated in nature and derived from mesenchyma, the osseous component being interpreted as evidence of a specific differentiation.

Antigens, Neoplasm↗

Heterogeneous mutations in the human lipoprotein lipase gene in patients with familial lipoprotein lipase deficiency.

The DNA sequences were determined for the lipoprotein lipase (LPL) gene from five unrelated Japanese patients with familial LPL deficiency. The results demonstrated that all five patients are homozygotes for distinct point mutations dispersed throughout the LPL gene. Patient 1 has a G-to-A transition at the first nucleotide of intron 2, which abolishes normal splicing. Patient 2 has a nonsense mutation in exon 3 (Tyr61----Stop) and patient 3 in exon 8 (Trp382----Stop). The latter mutation emphasizes the importance of the carboxy-terminal portion of the enzyme in the expression of LPL activity. Missense mutations were identified in patient 4 (Asp204----Glu) and patient 5 (Arg243----His) in the strictly conserved amino acids. Expression study of both mutant genes in COS-1 cells produced inactive enzymes, establishing the functional significance of the two mis-sense mutations. In these patients, postheparin plasma LPL mass was either virtually absent (patients 1 and 2) or significantly decreased (patients 3-5). To detect these mutations more easily, we developed a rapid diagnostic test for each mutation. We also determined the DNA haplotypes for patients and confirmed the occurrence of multiple mutations on the chromosomes with an identical haplotype. These results demonstrate that familial LPL deficiency is a heterogeneous genetic disease caused by a wide variety of gene mutations.

Adolescent↗

Cryoglobulinemia in a horse.

Cryoglobulin was isolated from a horse which had glomerulo-nephritis and a history of swelling and skin ulcers of the limbs in the winter. The isolated cryoglobulin showed a single peak on a gel permeation chromatography column with an apparent molecular mass (Mr) of 180,000 which could be divided into two gamma bands by cellulose acetate electrophoresis. Immunoelectrophoretic analysis revealed that the cryoglobulin formed two precipitation lines with anti-horse IgG. Spur formation was observed when the cryoglobulin and the IgG purified from a normal healthy horse were cross-reacted with anti-horse IgG on a double diffusion gel. In addition, sodium dodecyl sulfate-polyacrylamide gel electrophoresis under the reduced conditions showed that the isolated cryoglobulin consisted of two doublets of polypeptides with Mr values of 52,000 and 50,000, and 31,000, and 30,000, corresponding to the heavy chain and the light chain of the horse IgG molecules, respectively. These results suggest that the isolated cryoglobulin might consist of two different IgG molecules, and that the manifestations such as foot swelling with skin ulcers and renal failures were all induced by the cryoglobulin in the serum.

Animals↗