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Biomedical subjects

S Sumi

Publications and source records attributed to S Sumi.

At least 73 records · Page 4Linked to original sources

[A case of gastric cancer with decreased dihydropyrimidine dehydrogenase activity].

We analyzed the pyrimidine metabolite in the urine of a patient with severe mucositis and hand and foot syndrome, who was administered 5-fluorouracil for recurrence of gastric cancer. From our analysis, it was suggested that the patient had decreased dihydropyrimidine dehydrogenase activity. Dihydropyrimidine dehydrogenase activity is usually measured in peripheral blood mononuclear cells, but this time it was estimated from the analysis of uracil, dihydrouracil, thymine, and dihydrothymine in the urine. We concluded that urinary analysis of the pyrimidine metabolism is effective as screening for the prediction and prevention of 5-fluorouracil toxicity.

Adenocarcinoma↗

Identification of novel mutations in the dihydropyrimidine dehydrogenase gene in a Japanese patient with 5-fluorouracil toxicity.

5-Fluorouracil (5-FU) is used widely in the treatment of several common neoplasms. Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme in the catabolism of 5-FU. Several recent studies have described a pharmacogenetic disorder in which cancer patients with decreased DPD activity develop life-threatening toxicity following exposure to 5-FU. We reported recently the first Japanese case of decreased DPD activity accompanied by severe 5-FU toxicity. The present study describes the results of molecular analysis of this patient and her family, in which three novel mutations (Arg21Gln, Val335Leu, and Glu386Ter) of the gene coding for DPD were identified. We also revealed that Arg21Gln and Glu386Ter are on the same allele and that Val335Leu is on the other allele, on the basis of analysis of the family genome. Expression analysis in Escherichia coli showed that Val335Leu and Glu386Ter led to mutant DPD protein with significant loss of enzymatic activity and no activity, respectively. The Arg21Gln mutation, however, resulted in no decrease in enzymatic activity compared with the wild type. The present data represent the first molecular genetic analysis of DPD deficiency accompanied by severe 5-FU toxicity in a Japanese patient.

Antimetabolites, Antineoplastic↗

Serum concentration of type I collagen metabolites as a quantitative marker of bone metastases in patients with prostate carcinoma.

BACKGROUND: Bone scans, widely used for the detection of bone metastases from prostate carcinoma, can neither quantitate metastatic lesions nor detect osteolytic lesions. METHODS: Serum concentrations of the carboxyterminal propeptide of Type I procollagen (PICP), the carboxyterminal pyridinoline cross-linked telopeptide of Type I collagen (ICTP), and prostate specific antigen (PSA) were measured by radioimmunoassays in 48 patients with benign prostatic hyperplasia (BPH), 25 patients with prostate carcinoma (PCA) without bone metastases, and 36 patients with PCA and bone metastases. RESULTS: Serum concentrations of PICP were significantly higher in patients with PCA with bone metastases than in patients with BPH or PCA without bone metastases. No significant differences were observed between patients with BPH and those with PCA without bone metastases. Serum ICTP concentrations were significantly higher in patients with PCA than in patients with BPH regardless of the presence or absence of bone metastases. Serum concentrations of PICP, ICTP, and PSA correlated significantly with Soloway's grading system for bone scans. The serum concentrations of PICP and ICTP in patients without bone metastases showed a significant downward trend in response to antiandrogen therapy. CONCLUSIONS: These observations suggest that the serum concentrations of PICP and ICTP are quantitative markers of bone metastases from PCA when followed serially in individual patients.

Age Factors↗

Serial lectin affinity chromatography with concavalin A and wheat germ agglutinin demonstrates altered asparagine-linked sugar-chain structures of prostatic acid phosphatase in human prostate carcinoma.

Differences between human prostate carcinoma (PCA, five cases) and benign prostatic hyperplasia (BPH, five cases) in asparagine-linked (Asn) sugar-chain structure of prostatic acid phosphatase (PAP) were investigated using lectin affinity chromatography with concanavalin A (Con A) and wheat germ agglutinin (WGA). PAP activities were significantly decreased in PCA-derived PAP, while no significant differences between the two PAP preparations were observed in the enzymatic properties (Michaelis-Menten value, optimal pH, thermal stability, and inhibition study). In these PAP preparations, all activities were found only in the fractions which bound strongly to the Con A column and were undetectable in the Con A unbound fractions and in the fractions which bound weakly to the Con A column. The relative amounts of PAP which bound strongly to the Con A column but passed through the WGA column, were significantly greater in BPH-derived PAP than in PCA-derived PAP. In contrast, the relative amounts of PAP which bound strongly to the Con A column and bound to the WGA column, were significantly greater in PCA-derived PAP than in BPH-derived PAP. The findings suggest that Asn-linked sugar-chain structures are altered during oncogenesis in human prostate and also suggest that studies of qualitative differences of sugar-chain structures of PAP might lead to a useful diagnostic tool for PCA.

Acid Phosphatase↗

Experimental investigation of the role of the splenic vein in gastric venous obstruction after pylorus-preserving pancreatoduodenectomy in the dog.

CONCLUSION: This study showed that the splenic vein (SV) plays a major role in maintaining gastric blood flow after ligature of peripyloric vessels in the dog. Therefore, SV preservation or alternative venous drainage may be recommended to maintain sufficient gastric blood flow in pylorus-preserving pancreatoduodenectomy (PPPD). BACKGROUND: In PPPD, we often encounter the problem of gastric venous drainage obstruction, if the splenic-portal vein confluence needs to be resected. This study investigated significance of venous drainage via the left gastric and splenic veins in gastric tissue blood flow. METHODS: In seven mongrel dogs, gastric tissue blood flow was measured by both laser Doppler flowmetry (LDF) in the antrum and hydrogen gas clearance (HGC) in the antrum and body. Blood flow was measured after the following treatments: 1. No treatment; 2. Duodenal transection; 3. Ligature of the right gastric and gastroepiploic arteries and veins; 4. Transient obstruction of the left gastric vein (LGV); 5. Transient obstruction of the SV with the LGV open; and 6. Obstruction of both the LGV and the SV. RESULTS: As judged by LDF, treatments 2, 3, and 4 did not decrease blood flow, but treatments 5 and 6 significantly decreased it compared with both treatments 1 and 3. By HGC, changes in the antrum and the body were parallel. Duodenal transection did not, but treatments 3 and 4 did decrease blood flow compared with no treatment. Obstruction of the left gastric vein did not, but treatments 5 and 6 did significantly decrease it compared with treatment 3.

Animals↗

Nucleotide sequences of the 3' terminal region of onion yellow dwarf virus isolates from Allium plants in Japan.

The 2032 nucleotide sequence of the 3' terminal region of onion yellow dwarf virus (OYDV) isolated from Allium wakegi, bearing the genes for viral coat protein (CP) and a truncated RNA-dependent RNA polymerase, has been determined. Respective homologies of the nucleotide sequence in the corresponding region and the deduced amino acid sequence of CP with the equivalents of leek yellow stripe virus (LYSV) from garlic were 68.0 and 59.3%. Variation in the nucleotide sequence is concentrated in the boundary region between the putative RNA-dependent RNA polymerase gene and the CP gene as well as in the 3' noncoding region. These sequence divergencies, including the deletion of 79 nucleotides, resulted both in alterations to the amino acid sequence and the absence of 28 amino acid residues in the amino terminal region of OYDV CP in comparison with LYSV CP. In addition, the length of the 3' noncoding sequence of OYDV was one-third that of LYSV. Comparison of the 3' terminal 1197 nucleotides sequence of OYDV with sequences of the respective cDNAs cloned by RT-PCR directly from the total RNA of infected Allium plants that included two varieties of A. fistulosum, "Wakenegi" and "Shimonita-negi", and A. chinense, showed 90.7% overall identities, even though they have long been cultivated in locally restricted area in Japan. These findings appear to suggest that a single strain of OYDV invaded Japanese Allium plants long ago and spread throughout them.

Allium↗

Focal liver masses: characterization with diffusion-weighted echo-planar MR imaging.

PURPOSE: To evaluate diffusion-weighted echo-planar magnetic resonance (MR) imaging for improving the specificity of characterization of liver tumors. MATERIALS AND METHODS: Diffusion-weighted echo-planar imaging was performed with a 1.5-T whole-body imager with use of a body phased-array coil in 51 patients with 59 hepatic masses (41 malignant tumors, nine hemangiomas, and nine cysts). Apparent diffusion coefficient (ADC) values were obtained with two motion-probing gradients (b = 30 and 1,200 sec/mm2) during each of the breath-hold periods, and an ADC map was constructed. The T2 was derived from spin-echo echo-planar images with echo times of 47 and 99 msec. RESULTS: The ADC value of malignant masses (1.04 x 10(-3) mm2/sec) was significantly lower (P < .01) than that of benign masses (hemangiomas [1.95 x 10(-3) mm2/sec] and cysts [3.05 x 10(-3) mm2/sec]), although the T2s showed considerable overlap. A small amount of overlap in ADC values occurred among malignant tumors, hemangiomas, and cysts. ADC values of two cystic masses from ovarian carcinomas were within the range of those of hemangiomas. CONCLUSION: These preliminary results indicate that diffusion-weighted MR imaging can be useful in characterizing focal liver masses. With the exception of cystic metastatic tumors, the technique may be especially useful in tumors that appear markedly hyperintense on T2-weighted images due to a long T2.

Adult↗

Study of the structure of struvite stones with scanning electron microscopy and energy-dispersive X-ray microanalysis.

Topographic features of eight struvite calculi were investigated with scanning electron microscopy (SEM) equipped with energy-dispersive X-ray microanalysis (EDX). Perpendicularly cracked fragments showed concentric laminations composed of compact and loosely packed strata alternately. Magnesium and phosphorus were detected in the compact strata with their characteristic dispersive X-ray spectra. There existed numerous spherular crystals with smooth or porous surfaces and scattered penta- or hexa-hedral coffin-lid shaped crystals in the loosely packed strata. The former crystals showed the dispersive X-ray spectra of calcium and phosphorus, and were estimated to be calcium phosphate (CaP). The latter ones were presumed to be magnesium ammonium phosphate (MAP) with EDX. The surfaces of the fragments were cracked like eggshells and displayed numerous CaP crystals and scattered MAP crystals in most cases, while in only 1 case some faces of pieces demonstrated wavy MAP phases, sundry areas which were rimmed with aggregated CaP spherulites. The mean molar ratios of Mg/P and Ca/P in each case were 0.88-1.03 and 1.25-1.52, respectively. Though EDX was inadequate to determine the accurate chemical formula of CaP and MAP crystals by detecting their molar ratios of Ca/P and Mg/P with EDX, SEM/EDX is useful to observe these urolith crystals and to surmise them to be CaP or MAP crystals by detecting their atomic elements with EDX.

Adult↗

Serum levels of the carboxy-terminal propeptide of type I procollagen and the pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen as markers of bone metastases in patients with prostate carcinoma.

OBJECTIVES: To evaluate serum levels of the carboxy-terminal propeptide of type I procollagen (PICP) and the pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (ICTP) as possible markers of bone metastases in patients with prostate carcinoma (PCA) patients. METHODS: Levels of PICP and ICTP were measured by radioimmunoassay of serum from 29 patients with benign prostatic hyperplasia (BPH), 17 patients with PCA without bone metastases and 29 patients with PCA and bone metastases. RESULTS: Serum levels of PICP in patients with PCA and bone metastases (mean +/- SD 304.3 +/- 365.9 ng/ml) were significantly higher than those in patients with BPH (95.6 +/- 27.1 ng/ml) and in patients with PCA without bone metastases (111.1 +/- 44.6 ng/ml). No significant difference was observed between the BPH and the PCA without bone metastases groups. Serum levels of ICTP were significantly higher in the PCA with (10.4 +/- 10.3 ng/ml) and without bone metastases groups (7.7 +/- 6.0 ng/ml) than in the BPH group (3.7 +/- 2.0 ng/ml). There was no significant difference between the PCA groups with and without bone metastases. CONCLUSION: Serum PICP levels correlate well with results of bone scans, while serum ICTP levels increase in patients with PCA regardless of the presence of bone metastases.

Adenocarcinoma↗

In vitro and clinical studies of image acquisition in breath-hold MR cholangiopancreatography: single-shot projection technique versus multislice technique.

OBJECTIVE: This study was undertaken to compare the in vitro and clinical value of two-dimensional multislice breath-hold MR cholangiopancreatography (MRCP) with a single-shot projection technique using a half-Fourier acquisition single-shot turbo spin-echo sequence. SUBJECTS AND METHODS: We examined 108 patients with pancreaticobiliary diseases, using breath-hold MRCP and a half-Fourier acquisition single-shot turbo spin-echo sequence on a 1.5-T MR unit with a body phased-array coil. Two data acquisition techniques were employed: multislice acquisition postprocessed by maximum intensity projection (MIP) (multislice technique) and single-shot projection with a thick slice (projection technique). In the multislice technique, nine contiguous slices were obtained with a thickness of 5 mm (acquisition time. 18 sec). In the projection technique, a single slice was obtained with a thickness of 30, 50, or 70 mm (acquisition time. 2 sec). Contrast-to-noise ratio (CNR) between the common bile duct and the liver as well as detectability of normal structures and diseases were compared for these two acquisition techniques. In the multislice technique, source images were also evaluated. ERCP or percutaneous transhepatic cholangiography images were used as the gold standard. RESULTS: Most of the pancreatic duct and common bile duct was revealed on 54% and 100% of the projection images, respectively, and on 35% and 98% of the MIP images, respectively, CNR was significantly higher with the multislice technique than with the projection technique (p < .01). With the projection technique, CNR decreased as slice thickness increased. Dilatation and occlusion of the pancreaticobiliary tree were equally well revealed by the two imaging techniques. However, abnormalities in the periampullary region and anomalies in the pancreaticobiliary tree were more clearly seen on projection images than on MIP images (p < .05). Stones in the common bile duct, gallbladder, or intrahepatic bile duct were best seen on source images acquired by the multislice technique (83% sensitivity). CONCLUSION: Because of the absence of misregistration and the speed of image acquisition, breath-hold single-shot MRCP using the projection technique with a slice thickness of 30 or 50 mm consistently revealed the pancreaticobiliary tree and periampullary region with an acceptable CNR. Stones in the bile duct were best seen on the source images acquired by the MIP technique.

Biliary Tract Diseases↗

Molecular cloning of the human UMP synthase gene and characterization of point mutations in two hereditary orotic aciduria families.

Uridine monophosphate (UMP) synthase is a bifunctional enzyme catalyzing the last two steps of de novo pyrimidine biosynthesis, orotate phosphoribosyltransferase (OPRT) and orotidine-5'-monophosphate decarboxylase (ODC). Loss of either enzymatic activity results in hereditary orotic aciduria, a rare autosomal recessive disorder characterized by retarded growth, anemia, and excessive urinary excretion of orotic acid. We have isolated the UMP synthase chromosomal gene from a lambdaEMBL-3 human genomic library and report a single-copy gene spanning approximately 15 kb. The UMP synthase genomic structure encodes six exons ranging in size from 115 bp to 672 bp, and all splicing junctions adhere to the canonical GT/AG rule. Cognate promoter elements implicated in glucocorticoid- and cAMP-mediated regulation as well as in liver-, myeloid-, and lymphocyte-specific expression are located within the 5' flanking sequence. Molecular investigation of UMP synthase deficiency in a Japanese orotic aciduria patient revealed mutations R96G (A-to-G transition; nt 286) and G429R (G-to-C transversion; nt 1285) in one allele and V109G (T-to-G transversion; nt 326) in the other allele. Expression of human UMP synthase cDNAs containing these mutations in pyrimidine auxotrophic Escherichia coli and in recombinant baculovirus-infected Sf21 cells demonstrates impaired activity presumably associated with the urinary orotic acid substrate accumulations observed in vivo. We further establish the identity of two polymorphisms, G213A (v = .26) and 440Gpoly (v = .27) located in exons 3 and 6, respectively, which did not significantly compromise either OPRT or ODC function.

Adult↗

[A case of concurrent bilateral adrenocortical adenoma causing Cushing's syndrome].

A 43-year-old woman presented with obesity and lumbago. Endocrinological examinations revealed normal plasma cortisol levels and a suppressed serum adrenocorticotropic hormone (ACTH) level. On venous sampling, markedly elevated plasma cortisol levels were observed for bilateral adrenal veins (243 and 62.3 micrograms/dl on the right and left sides, respectively). Although the computed tomogram revealed bilaterally enlarged adrenal glands, 131I-adosterol scintigram showed a strong uptake only on the right side. Right adrenalectomy successfully relieved Cushing's syndrome. Pathological diagnosis was adrenocortical adenoma, 3.5 cm in diameter. Cushing's syndrome recurred in 9 years. At that time, she underwent left subtotal adrenalectomy including a 3-cm adrenocortical adenoma. Postoperative convalescence has been uneventful with oral steroid supplementation. All 14 previously reported cases of bilateral adrenocortical adenoma (BAA) causing Cushing's syndrome as well as the present case were concurrent and dominant in females of reproductive age. This suggests that some cofactors other than ACTH, such as estrogen, contribute to the pathogenesis of BAA.

Adenoma↗

Relationship of epidermal growth factor binding capacity to histopathologic features and prognosis in human renal cell carcinoma.

We studied the association between epidermal growth factor (EGF) binding capacity and histopathologic features or prognosis in human renal cell carcinoma (RCC) by Scatchard analysis in 67 patients. EGF binding capacity was significantly greater in metastatic than in nonmetastatic tumors, and in nuclear grade 3 than nuclear grade 1 tumors. Multivariate analysis revealed that tumor stage, nuclear grade, EGF binding capacity, and tumor size significantly correlated with overall survival. These results suggest that EGF binding may be an important determinant of prognosis in patients with RCC.

Adult↗