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Biomedical subjects

Y Mishima

Publications and source records attributed to Y Mishima.

At least 73 records · Page 4Linked to original sources

Ampullary carcinoma in familial adenomatous polyposis: report of a case.

We report the case of a 48-year-old man with familial adenomatous polyposis (FAP) who was found to have ampullary carcinoma 6 years after undergoing total colectomy. The patient was examined periodically after colorectal surgery except for duodenoendoscopy because he had also previously undergone distal gastrectomy with gastrojejunal anastomosis for a duodenal ulcer at 27 years of age. An ampullary lesion was suspected on blood chemistry and detected by computed tomography scan and ultrasonography although the patient showed no clinical symptoms. A pancreatoduodenectomy was performed and the histological examination revealed well-differentiated adenocarcinoma with no metastasis to the regional lymphnodes. Long-term periodic surveillance of the upper gastrointestinal tract including the papilla of Vater is therefore important for FAP patients who have undergone prophylactic colectomy.

Adenocarcinoma↗

Chronological changes in bone mineral content following gastrectomy.

Recent advances in the modalities of quantitatively assessing bone mineral content have resulted in an increasing awareness of metabolic bone disease as a late complication following gastrectomy. In this study, 98 postgastrectomy patients were examined by quantitative computed tomography (QCT). The bone mineral density index (BMDI), defined as 100 x (measured bone mineral density divided by that of age- and sex-matched controls), was used to evaluate the actual effect of gastrectomy on bone disorders. The BMDI values following gastrectomy were 80.4 +/- 27.3, with no significant difference between men and women, or between total and distal gastrectomy. Moreover, no significant differences were observed between the BMDI values within 6 months, being 92.6 +/- 37.3, and those 6 months to 1 year post gastrectomy, being 79.6 +/- 31.2; however, a significant and sharp decrease to 70.5 +/- 36.0 was evident after 1-2 years. The regression coefficient of the BMDI measured within 2 years postoperatively was lower than that measured after 2 years. These findings suggest that the influence of gastrectomy on bone metabolism is induced within 2 years, after which the bone mineral content decreases in accordance with physiological nature. Thus, we conclude that the treatment for bone disease resulting from gastrectomy would only be effective if initiated within a short period after surgery.

Adult↗

The positive relationship between the expression of CD44 variant 6 and prognosis in colorectal cancer.

CD44 variant 6 (CD44 v6) is well known as a useful marker of tumor progression; however, its relationship to prognosis has not yet been elucidated. In this study, we investigated the expression of CD44 v6 in colorectal cancer to analyze its relationship to hepatic metastasis as well as to prognosis. Tumor tissues were obtained from 42 patients with colorectal cancer who underwent curative resection with follow-up periods ranging from 5.9 to 71.3 months. There were 21 patients (50%) whose tumors were positive for CD44 v6, with no significant difference between colon and rectal cancer. CD44 v6 staining was significantly related to Dukes' classification as well as to hepatic metastasis. The 5-year survival rate was significantly higher in patients with CD44 v6 negative cancer (84%) than in those with CD44 v6 positive cancer (31%). Thus, we concluded that CD44 v6 could be a reliable prognostic indicator, as well as a predictor of metastatic potential after curative surgery for colorectal cancer.

Biomarkers, Tumor↗

Extrinsic nervous control of retrograde giant contraction during vomiting in conscious dogs.

Neural mechanisms controlling retrograde giant contraction during vomiting were studied in six conscious dogs with implanted strain gauge force transducers. The small intestine was divided into proximal (P), middle (M), and distal (D) segments. These segments were transplanted on intact mesenteric neurovascular pedicles. In three dogs, M and D segments were interchanged (group A). In three dogs, P and M segments were interchanged (group B). Before transplantation, apomorphine-induced vomiting caused retrograde giant contractions, starting from the M segment and rapidly migrating to the stomach. However, in group A, even after recovery of interdigestive migrating contractions migration, retrograde giant contractions during vomiting always originated in the distally interchanged M segment and jumped to the P segment without migration to the D segment. In group B, the retrograde giant contraction always originated in the proximally interchanged M segment and successively occurred in the distally interchanged P segment. We conclude that origination and migration of retrograde giant contractions are extrinsically controlled. These motor events during vomiting are thought to be a specific motor function that does not exist in the lower small intestine, and retrograde giant contraction during vomiting may originate in the mid-small intestine.

Animals↗

Thromboangiitis obliterans (Buerger's disease)

Buerger disease is an chronic vasculitis mainly involving lower extremities. This disease is sometimes contrasted with Takayasu arteritis because both are speculated autoimmune mechanisms as an important factor in their etiology. Furthermore both are frequently encountered in Asian countries. However, patients with Takayasu arteritis were mostly young women in Japan and, on the contrary, patients with Buerger disease were mainly middle aged men. Recent HLA studies on Buerger disease are revealing the interesting results in comparison with those on Takayasu arteritis. The outline of Buerger disease will be described herein.

Adult↗

Formation of a triple-stranded DNA between d(GGA:TCC) repeats and d(GGA) repeat oligonucleotides.

Incubation of the 162-bp duplex containing d(GGA:TCC)11 repeats with d(GGA)11 and d(GGT)11 oligonucleotides, but not with d(TCC)11, gave a mobility-shifted band in polyacrylamide gel electrophoresis, suggestive of the triplex formation. The two conformers, however, showed difference in binding affinity and structure. The complex formed with d(GGT)11 exhibited patterns protected from DNase I digestion and from modifications with osmium tetroxide and dimethyl sulfate. The patterns were conformed to a proposed triplex model. In contrast, the complex with d(GGA)11 was sensitive to DNase I and to osmium tetroxide, which is reactive to pyrimidine bases of single-stranded DNA. These results suggest that the d(GGA:TCC)11 and d(GGA)11 triple-stranded complex forms a D-loop-like structure. By considering the ability of d(GGA)11 oligonucleotides to form a parallel homoduplex, the structure may be one in which the GGA-strand of the duplex pairs with d(GGA)11 in parallel, with the TCC-strand being looped out.

Alkylating Agents↗

Stimulation of pancreatic growth. Distal small bowel resection mediated by increased levels of cholecystokinin.

SUMMARY BACKGROUND DATA: Distal, but not proximal, resection of the small bowel induces growth of rat pancreas, but the mechanism of this phenomenon is poorly clarified. The release of cholecystokinin (CCK), a trophic hormone for the pancreas, is regulated by a negative-feedback control of bile salts. The ileum is a major site for reabsorption of bile salts. Thus, unsuppressed release of CCK due to deleted reabsorption of bile salts after distal small bowel resection may be a cause of pancreatic growth. In this study, the authors have examined whether pancreatic growth after distal small bowel resection was mediated by endogenous CCK and have determined whether the mechanism of this pancreatic growth required biosynthesis of polyamine. METHODS: Male Fischer 344 rats underwent 70% distal small bowel resection or transection of the ileum. Beginning 48 hours after surgery, CR1409 (a CCK-receptor antagonist) or saline was injected subcutaneously every 8 hours. All animals were pair-fed and killed 14 days after surgery. The pancreas from each rat was excised, weighed, and assayed for DNA, RNA, protein, and polyamine content. RESULTS: Distal small bowel resection increased pancreatic weight, DNA, RNA, and protein, as well as polyamine levels; all of these increases were significantly suppressed by CR1409. Postprandial release of CCK into the circulation was significantly increased after distal small bowel resection. CONCLUSIONS: Pancreatic growth after distal small bowel resection was associated with the stimulation of polyamine biosynthesis; growth appeared to be mediated by endogenous CCK.

Animals↗

Composition of mammalian eumelanins: analyses of DHICA-derived units in pigments from hair and melanoma cells.

The proportions in which two eumelanin monomers, namely 5,6-dihydroxyindole-2-carboxylic acid (DHICA) and 5,6-dihydroxyindole (DHI), compose the eumelanin polymer are believed to determine properties of the pigment including its color. These proportions are, however, not well elucidated for naturally occurring eumelanins, largely because of methodological difficulties. In this study we estimate the content of DHICA-derived units in mammalian eumelanins using a combination of two analytical techniques: 1) quantitation of DHICA-derived eumelanin by measuring the yield of pyrrole-2,3,5-tricarboxylic acid (PTCA index) and 2) spectrophotometrical quantitation of total (DHI + DHICA) eumelanin at 350 nm (A350 index). The ratio of PTCA/A350 measured for melanins synthesized from DHI and DHICA mixed in various molar proportions correlates well with the content of DHICA in synthetic polymers. Using this relationship as a standard curve we estimated the proportion of DHICA-derived units in mammalian eumelanins from hair and melanoma cells and found it to be much higher in rodent pigments (58.8%-98.3%; two species, mouse and hamster were examined) as compared to human eumelanins (19.2%-41.8%; one Caucasian and one Oriental individual were examined). No relationship between proportion of DHICA-derived units in eumelanin and hair color is found. The latter seems to be determined predominantly by the ratio of pheo- to eumelanin synthesis.

Animals↗

Mouse fibroblast expressing human tyrosinase with DHICA-oxidase activity produces predominantly pheomelanin deposit in lysosome.

The melanogenic gene-transfected cell system serves as a useful tool for the study of the symphonic relation between melanin synthesis and intracellular organelles such as melanosomes in melanocytes. We constructed melanin-producing mouse fibroblasts by transfection of human tyrosinase cDNA to investigate the intracellular changes caused by tyrosinase expression. DHICA-oxidase (5,6-dihydroxyindole-2-carboxylic acid oxidase) activity without TRP-1 (Tyrosinase Related Protein-1) expression in the cells suggested that human tyrosinase also possesses a DHICA-oxidase activities different from mouse tyrosinase. Electron microscopic observation indicated that melanin-deposit organelles have some lysosomal features. These properties of melanin-deposit organelles in tyrosinase expressing fibroblasts provide one evidence for the hypothesis that melanosome is the specialized lysosome in melanocytes.

Animals↗

[A case of nonresectable advanced gastric cancer responding to combined chemotherapy with 5'-DFUR, CDDP, and MMC].

A 39-year-old man was referred for epigastric fullness and a mass in the umbilical region. A giant mass was palpated in the epigastric region, while a mass 1 cm in diameter with a hemorrhagic tendency was felt in the umbilical region. Fluoroscopy of the upper gastrointestinal tract and gastroscopy revealed a Borrmann 3 tumor in the upper part of the gastric corpus. The tumor was found by CT scanning to be growing clearly across the wall of the stomach, and the invasion to the transverse colon was suspected by the enema. The tumor was unresectable because of the extensive tumor invasion of the abdominal wall. Therefore, the patient received 2 courses of combined chemotherapy with 5'-DFUR, CDDP, and MMC. As a result, the tumor in the epigastric region was reduced dramatically, and it became unpalpable 6 months after treatment. At the same time, the tumor in the umbilical region disappeared. Both CT scanning and upper gastrointestinal radiography disclosed tumor reduction, and sufficient oral ingestion became possible. The administration of 5'-DFUR has since been continued as maintenance therapy. Aside from transient anorexia and slight leukopenia, the patient developed no symptoms during the treatment period. At present. 2 years and 9 months after starting chemotherapy, the patient is in good health.

Adult↗

[The current status of arteriosclerosis obliterans in Japan].

In Japan, the number of patients suffering from arteriosclerosis obliterans has increased remarkably in recent years, especially among the aged population. This paper presents an overivew of the current status of vascular surgery for atherosclerotic occlusive disease and the outlook for the future. It is important that endovascular surgery be further evaluated as an alternative to conventional arterial reconstruction, however, its precise indications and limitations can only be discussed with the accumulation of experience. The history of vascular surgery is extensive and not limited to the development of new techniques and methods of surgery alone. Further development in many fields will surely lead to great possibility in the future.

Angioplasty, Balloon, Coronary↗

[Risk factor, natural history and prognosis of the patients with arteriosclerosis obliterans].

A sufficient understanding of the risk factor and the natural history of arteriosclerosis obliterans, ASO, is essential for selecting the optimal treatment for this condition. Hypercholesterolemia, hypertension and cigarette smoking have been identified as independent major risk factors of ASO, and diabetics, obesity, hypertrigriceridemia, low HDL-cholesterol level, aging, gender, etc, as minor factors. The patients with ASO often have multiple risk factors, synergistically accelerating the disease progression. Recent objective studies on natural history of claudicants have demonstrated a more morbid prognosis, especially in the patients with disabling claudication, than that outlined by previous historical studies. Mortality rates for ASO patients in long-term follow-up have revealed to be significantly higher than those observed in control groups. The causes of death are mostly arteriosclerotic vascular disease, particularly coronary artery and cerebrovascular diseases, which indicate the significance of the systemic evaluation in treating patients with ASO.

Arteriosclerosis Obliterans↗

An international comparison of characteristics of the sensation of nasal obstruction between Canadian and Japanese patients.

To determine differences in perception of nasal obstruction in Canadians and Japanese, we assessed subjective and objective nasal patency of 48 patients in Canada and 43 patients in Japan. Mean severity of the sensation of nasal obstruction in Canadian patients was significantly higher than in Japanese patients, while no significant differences in nasal resistances were found. Complaints of nasal obstruction in Canadian patients were directly concerned with nasal breathing, while Japanese patients complained of indirect matters, such as "unable to concentrate on job or study" or "nasal obstruction or nasal speech pointed out by other persons." The differences might be due to national characteristics.

Adult↗

Formation of a parallel-stranded DNA homoduplex by d(GGA) repeat oligonucleotides.

The GGA9-H molecules consisting of a double helical stretch followed by a single-stranded 3'-terminal overhang of nine GGA sequence repeats exhibited a gel mobility-shifted band in a concentration-dependent manner, suggestive of the intermolecular complex formation. The position of the shifted band in a gel was almost identical to that of the Y-shaped dimer marker of the same molecular weight that had the two double-helices at one side. This suggests that GGA9-H dimerizes in a parallel orientation without the formation of four-stranded hairpin structure. Since the GGA9-H homoduplex was stably formed at pH 4, 7 and 9, the formation does not require protonation or deprotonation of the N1 position of adenines. Neither does it require the N7 group of guanines responsible for Hoogsteen base pairing from the methylation interference and modification studies. Modification of the N7 group of guanines with dimethyl sulfate (DMS) did not inhibit the association and also the N7 group in the homoduplex was not protected from DMS. On the other hand, the GAA9-H having the G to A base substitution did not show such an association with either GGA9-H or GAA9-H. These results suggest that the homoduplex formation may be due to G.G base pairing through non-Hoogsteen hydrogen bonds.

Base Composition↗

Site-specific crosslinking of 4-thiouridine-modified human tRNA(3Lys) to reverse transcriptase from human immunodeficiency virus type I.

We have mapped specific RNA-protein contacts between human immunodeficiency virus (HIV) type I reverse transcriptase (RT) and its natural primer, human tRNA(3Lys), using a site-specific crosslinking strategy. Four different tRNA(3Lys) constructs with a single 32P-labeled 4-thiouridine (4-thioU) residue at positions -1, 16, 36 or 41 were synthesized. After incubation with RT followed by irradiation, crosslinks were localized to either the p66 or p51 subunit of RT by digestion with nuclease and SDS gel fractionation. 4-thioU at position -1 or 16 transferred label to the p66 subunit almost exclusively (> 90%), whereas position 36 labeled both p66 and p51 (3:1). Position 41 yielded no detectable crosslinks. The region of p66 contacted by position -1 of tRNA(3Lys) was localized to the 203 C-terminal amino acids of RT by CNBr cleavage, whereas a 127 amino acid-CNBr peptide (residues 230-357) from both p66 and p51 was labeled by position 36. Functionality of the 4-thioU-modified tRNA(3Lys)(-1) crosslinked to RT in the presence of an RNA but not a DNA template was demonstrated by the ability of the tRNA to be extended. These results localize the 5' half of the tRNA on the interface between the two RT subunits, closer to the RNase H domain than to the polymerase active site, in accord with previous suggestions. They argue further that a specific binding site for the 5' end of the primer tRNA(3Lys) may exist within the C-terminal portion of the p66 subunit, which could be important for the initiation of reverse transcription.

Base Sequence↗

High-performance liquid-chromatographic analysis of dopachrome and dihydroxyphenylalanine.

A high-performance liquid-chromatographic system for the determination of dopachrome and dihydroxy-phenylalanine (dopa) is described. The retention of dopa and dopachrome on C18 reversed-phase columns was investigated as a function of pH in the mobile phase, and as expected the capacity factors were found to be pH dependent. The chromatographic behavior is explained by the change in net charge and polarity of dopachrome and dopa when pH varies. Satisfactory separation of dopachrome and dopa was obtained. An advantage of the method is that the measurements of dopachrome stability and disappearance are uninfluenced by concomitant formation of melanochromes which, however, is the case when the disappearance is followed by measurement of the decrease in absorbance at 475 nm. The utility of the method is illustrated by following the disappearance of dopachrome as a measure of dopachrome tautomerase activity.

Animals↗

Correlation between the number of melanosomes, tyrosinase mRNA levels, and tyrosinase activity in cultured murine melanoma cells in response to various melanogenesis regulatory agents.

Tyrosinase is the rate limiting enzyme critically associated with melanin synthesis. The melanosomes are specialized membrane-bound organelles within melanocytic cells in which melanin polymers are ultimately deposited. To determine whether tyrosinase correlates with the number of melanosomes, we examined the relationship between tyrosinase activity, tyrosinase mRNA levels, and the number of melanosomes in B16 murine melanoma cells, using melanogenesis regulatory agents. 12-O-Tetradecanoylphorbol-13-acetate (TPA) or linoleic acid decreased tyrosinase activity, while dibutyryl cyclic adenosine monophosphate (dbcAMP) or palmitic acid increased it. The tyrosinase mRNA levels were not always correlated with tyrosinase activity, i.e., TPA down-regulated, dbcAMP upregulated, while linoleic acid or palmitic acid did not alter the message levels, indicating that fatty acid regulation of melanogenesis was due to post-transcriptional events. The number of melanosomes changed when agents which modulate the tyrosinase gene expression were added, since TPA decreased, dbcAMP increased, and linoleic acid or palmitic acid did not alter their number. These results suggest that the number of melanosomes changed in relation to tyrosinase mRNA level but not to tyrosinase activity in response to melanogenesis regulatory agents.

Animals↗