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Biomedical subjects

K Sugano

Publications and source records attributed to K Sugano.

At least 91 records · Page 5Linked to original sources

[Genetic diagnosis for cancer--tumorigenesis and genetic alterations].

During malignant transformation, cancer cells acquire multiple genetic alterations that override the normal mechanisms controlling cellular proliferation. In brief, cancer is a disease of genetic abnormalities caused by hereditary and/or environmental factors. Genetic diagnosis for cancer can be divided into four categories: 1) pre-symptomatic diagnosis, 2) existence diagnosis, 3) property diagnosis-prognosis diagnosis and 4) genetic test for gene therapy. 1) For hereditary cancer families, pre-symptomatic diagnosis is available. Individuals with multiple cancers can be diagnosed by microsatellite instability(MSI) test using resected cancer tissues and by genotyping of mismatch repair enzymes. If the genotype abnormality is detected, the propositus can obtain early diagnosis and prevention of cancer, and genetic services of their siblings. 2) Using PCR technology, occult tumor cells can be detected from blood and other biological body fluids, as targets of chimeric transcripts and tissue-specific expressions. 3) Molecular properties of cancer cells are investigated for grading malignancy and therapeutic sensitivities. Using the molecular properties, prognosis of the patient can be estimated. 4) Following the genetic test results, the specific and superior gene therapy can be applied individually. Post-therapeutic monitoring is also available only by genetic test. After the genome project, the significance of single nucleotide polymorphisms(SNPs) related with cancer will be established, then tailor-made therapy and/or prevention will be applicable to individuals. The ultimate goal of genetic diagnosis would be the final priority to the phenotypic diagnosis.

Genetic Counseling↗

[Genetic counseling and clinical genetics services for cancer prone kindreds].

Gene testing elucidates the identification of heterozygous carrier for hereditary cancer and the needs for genetics services are increasing in cancer hospitals. Genetic services include educational explanation for the disease and Mendelian inheritance, risk assessment, orientation for gene testing, post-test counseling for cancer prevention and psychosocial issues, and support services. This review outlines how they are performed in the clinic of cancer hospital.

Female↗

DNA methylation analysis using bisulfite treatment and PCR-single-strand conformation polymorphism in colorectal cancer showing microsatellite instability.

The combination of bisulfite treatment and PCR-single-strand DNA conformation polymorphism (SSCP) analysis is proposed for quantitative methylation assay. We applied this procedure to the methylation analysis of the hMLH1 promoter region in colorectal cancer. An analysis of mixtures of known amounts of methylated and unmethylated DNA revealed a linear relation. Using a calibration curve, proportions of methylated DNA were calculated. The hMLH1 promoter region was highly methylated in about 80% of microsatellite instability (MSI) (+) colorectal cancers, but in none of the MSI(-) colorectal cancers. A significant correlation existed between hypermethylation of the hMLH1 promoter and MSI, as in previous reports. In conclusion, bisulfite-PCR-SSCP (BiPS) analysis could be applied to the rapid identification of methylation status in multiple samples, quantification of methylation differences, and detection of methylation heterogeneity in amplified DNA fragments.

Adaptor Proteins, Signal Transducing↗

A novel splicing mutation (894-9 G --> A) of the MEN1 gene responsible for multiple endocrine neoplasia type 1.

Germline MEN1 gene mutations are responsible for multiple endocrine neoplasia type 1 (MEN1), a dominantly inherited cancer syndrome. We identified a MEN1 germline mutation 894-9 G --> A in three MEN1 patients from two unrelated families. This mutation was not present in any of the 100 blood samples from normal volunteers. The wild type MEN1 sequence was lost in the patient's pancreatic tumor. Abnormal mRNA was identified in the tumor, which retained an intronic sequence indicating aberrant mRNA splicing at a newly created splicing acceptor site. These findings indicate that this nucleotide substitution is, though previously reported to be a polymorphism, a causative splicing mutation.

Adult↗

Laparoscopic cholecystectomy in gallstone patients with acute cholecystitis.

It remains controversial whether patients with gallstones with acute cholecystitis should be operated on early, or whether surgery should be delayed until the acute phase subsides. To help resolve this question, we retrospectively studied 109 patients with acute cholecystitis, 56 of whom underwent laparoscopic cholecystectomy after acute cholecystitis had subsided (delayed group) and 53 of whom underwent early laparoscopic cholecystectomy--within 7 days after admission (early group). On admission, the inflammatory findings in the two groups were very similar; however, at operation, the inflammatory findings were alleviated in the delayed group, while they remained unchanged in the early group. The mean operative time for the two groups was very similar. As for intraoperative complications, there was no conversion to laparotomy in either group, and there were no major complications in either group. The total hospital stay was 37.7 +/- 14.4 days for the delayed group and 12.7 +/- 2.0 days for the early group, showing a highly significant difference (P < 0.001). Early laparoscopic cholecystectomy seems to be better than delayed treatment for patients with gallstones with acute cholecystitis.

Acute Disease↗

The role of laparoscopic US and laparoscopic US-guided aspiration biopsy in the diagnosis of multicentric hepatocellular carcinoma.

BACKGROUND: Detection of small hepatocellular carcinomas has become possible with improvements in various diagnostic imaging techniques. However, intraoperative US can detect lesions not visualized by any preoperative imaging study in which case it is difficult to determine whether the lesion is a hepatocellular carcinoma. METHODS: Nodular lesions detected by laparoscopic US in 186 patients with hepatocellular carcinoma were examined and we evaluated the diagnostic ability of laparoscopic US to detect multicentric hepatocellular carcinoma. RESULTS: One hundred thirty-four new nodular lesions were detected by laparoscopic US in 64 (34.4%) of 186 patients. Aspiration biopsy under laparoscopic US guidance was performed on the 134 nodules, and 28 nodules in 23 (12.4%) of the 186 patients were histologically diagnosed as hepatocellular carcinoma. Of these 23 patients, 18 had been diagnosed with solitary hepatocellular carcinoma before laparoscopic US. One hundred six of the newly detected lesions were initially diagnosed as noncarcinomatous nodules, but the diagnosis of 10 of these lesions was changed to hepatocellular carcinoma during follow-up that was as long as 96 months. CONCLUSIONS: Laparoscopic US is useful in the initial diagnosis of hepatocellular carcinoma and impacts treatment selection by more accurately defining the presence of multicentric hepatocellular carcinomas.

Biopsy, Needle↗

Preoperative assessment of extrahepatic bile duct carcinoma using three-dimensional intraductal US.

BACKGROUND: We investigated the utility of a new imaging modality, three-dimensional intraductal ultrasonography (US), for staging bile duct cancer. METHODS: In eight patients with extrahepatic bile duct carcinoma, two- and three-dimensional intraductal US was used to assess tumor invasion of the right hepatic artery, portal vein, and pancreatic parenchyma before resection. The findings were correlated with histologic information from the resected specimen. RESULTS: Three-dimensional intraductal US enabled accurate assessment of tumor invasion of the right hepatic artery in 88% of cases, the portal vein in 100%, and pancreatic parenchyma in 100%. Two-dimensional intraductal US enabled accurate assessment of invasion of these structures in 88%, 88%, and 88% of cases. CONCLUSIONS: Three-dimensional intraductal US is useful in assessing tumor stage in bile duct carcinoma.

Aged↗

How many biopsies should be performed during percutaneous transhepatic cholangioscopy to diagnose biliary tract cancer?

BACKGROUND: The sensitivity of biopsy in the diagnosis of cholangiocarcinoma using percutaneous transhepatic cholangioscopy is not well defined. METHODS: Patients with a biliary tract malignancy (n = 52) underwent directed biopsy during percutaneous transhepatic cholangioscopy using a 1.8 mm diameter forceps. Histologic findings were correlated with endoscopic appearance. RESULTS: A diagnosis of carcinoma was made in all four patients with a tumor of the major duodenal papilla and in all 15 patients with a polypoid bile duct tumor with two biopsies from the mass. In 19 patients with stenotic bile duct cancer, a positive diagnosis was made in 95% of cases when three biopsies were taken from the margin of the stenotic area. When cholangioscopy showed a tortuous, dilated vessel (n = 10), the diagnosis of cancer was made with two biopsies taken from the margin of the stenosis. In 14 patients with metastatic bile duct cancer, the diagnosis was made in only 43% of cases when three biopsies were taken from the margin of the stenosis. When combined with results from the three biopsies taken from within the area of stenosis, the sensitivity for diagnosing pancreatic cancer improved from 20% to 60%. CONCLUSIONS: Directed cholangioscopic biopsies are highly sensitive for the diagnosis of cholangiocarcinoma but less sensitive for cancer metastatic to the bile duct. The numbers and locations of the biopsies required to make a diagnosis of carcinoma depend on the origin and cholangioscopic appearance of the tumor.

Adult↗

Two germline missense mutations at codons 804 and 806 of the RET proto-oncogene in the same allele in a patient with multiple endocrine neoplasia type 2B without codon 918 mutation.

Multiple endocrine neoplasia (MEN) type 2B is a clinically distinct entity among the autosomal dominant MEN 2 syndromes. Most patients with MEN 2B carry a germline mutation (M918T) of the RET proto-oncogene, while a few carry A883F. We examined a patient with MEN 2B, but without M918T or A883F, and her relatives. Here, we report the presence in this patient of 2 germline mutations, V804M and Y806C in the same allele. While the novel Y806C was inherited from her father, its carriers (her father and brother) was not affected by MEN 2. In contrast, V804M was a de novo mutation, that has been reported in patients with familial medullary thyroid carcinoma. Combinations of mutations of the RET proto-oncogene may cause oncogenic activities different from those of single mutations.

Base Sequence↗

Simultaneous colonisation of Helicobacter pylori with and without mutations in the 23S rRNA gene in patients with no history of clarithromycin exposure.

BACKGROUND: It was recently reported that A to G transition mutations at positions 2143 and 2144 in the 23S rRNA gene are associated with clarithromycin resistance in Helicobacter pylori. AIMS: To study the incidence and mechanism of development of clarithromycin resistance by analysing these mutations. SUBJECTS: Eighty two H pylori positive patients who had an endoscopic examination and no history of treatment with macrolide antibiotics. METHODS: Clarithromycin resistance was screened for by polymerase chain reaction-restriction fragment length polymorphism of the 23S rRNA gene coupled with antibiotic susceptibility testing. In clinical isolates with mutations or resistance, mutations in individual colonies were analysed by direct sequencing. RESULTS: Of the 79 amplicons (DNA fragments amplified by polymerase chain reaction), Alw26I and MboII digestion disclosed the mutation in four (5%) and one (1%) respectively. However, the Alw26I cleavage was incomplete in two of the four amplicons, as was the MboII cleavage. Individual colony analysis of the isolates with incomplete cleavage patterns showed the presence of both wild type and mutated strains in the 23S rRNA genes. CONCLUSIONS: Both clarithromycin sensitive and resistant strains colonised in some patients with no history of exposure to macrolides. The results suggest that resistant strains may not be formed but selected by clarithromycin administration.

Adult↗

Gastrin stimulates the growth of gastric pit with less-differentiated features.

Gastrin stimulates the growth of gastric mucosa by increasing mostly its glandular region but is not known to induce the growth of a pit region where its major constituent cells, gastric surface mucous (GSM) cells, turn over rapidly. To investigate the effect of gastrin on GSM cells, we generated hypergastrinemic mice by expressing a human gastrin transgene. We obtained a hypergastrinemic mouse line whose average serum gastrin level is 671 +/- 252 pg/ml (normal level <150 pg/ml). Gastrin-positive cells were found in the fundic mucosa. The gastric mucosa exhibited hypertrophic growth, which was characterized by an elongated pit with an active proliferative zone, but the glandular region containing parietal cells was normal or reduced in size. The GSM cells contained fewer mucous granules than those of control littermates and lost reactivity to the GSM cell-specific cholera toxin beta-subunit lectin. GSM cells along the foveolar region and many mucous neck cells became Alcian blue positive, suggesting the appearance of sialomucin in these cells. We suggest that gastrin stimulates the growth of the proliferative zone of gastric glands, which results in the elongation of the pit region whose GSM cells exhibit less-differentiated features.

Animals↗

[Antimicrobial resistance testing of H. pylori epsilometer test and disk diffusion test].

The resistance of Helicobacter pylori to antibiotics leaves great influence on treatment outcome. Routine antimicrobial susceptibility testing of H. pylori should be a simple, inexpensive and standardized method to be adopted. Agar and broth dilution techniques are difficult to perform and not practical. E-test and disk diffusion methods have the advantage of allowing the visualization of resistant subpopulations of bacteria within zones of inhibitions. We studied the susceptibility results of 246 H. pylori isolates against metronidazole and clarithromycin using E-test and disk diffusion test. The results of disk diffusion test were well correlated with these of E-test. Our results showed that disk method is cost effective and simple for the screening for antimicrobial resistance of H. pylori.

Clarithromycin↗

[Triple therapy regimens involving H2 blockaders for therapy of Helicobacter pylori infections].

Comparison of ranitidine and lansoprazole in short-term low-dose triple therapy for Helicobacter pylori infection. To evaluate the efficacy and safety of two 1-week low-dose triple-therapy drug regimens involving antisecretory drugs for Helicobacter pylori infection, 99 patients with H. pylori infection were treated with either lansoprazole (LPZ) or ranitidine (RNT) used together with clarithromycin (CAM) and metrinidazole (MTZ). The drug combination and administration periods in the PPI group were LPZ 30 mg, CAM 400 mg, MTZ 500 mg (LCM group). The ranitidine group received RNT 300 mg, CAM 400 mg, MTZ 500 mg (RCM group). The cure rate of H. pylori infection was 88% in the LCM group; 95% CI 79-97 and 92% in the RCM group; 95% CI 84-99.

2-Pyridinylmethylsulfinylbenzimidazoles↗

[Changes in the severity of atrophic gastritis after Helicobacter pylori eradication].

There is a diversity of opinions as to whether Helicobacter pylori eradication leads to the improvement or regression of atrophic gastritis and intestinal metaplasia (IM), which are considered precursor lesions of intestinal type gastric cancer. We have made a 1.5-yr follow-up study after H. pylori eradication, but no significant improvement of atrophy or IM has so far been found. Some other factors than H. pylori may also play an important part in the development and progress of atrophic gastritis. The discrepancy between our data and others may be caused in part by the different methods of assessment of the grade of atrophy and sampling of biopsies.

Follow-Up Studies↗

[A case of recurrent Guillain-Barré syndrome with myocarditis].

We report a 35-year-old man who recovered from an initial episode of Guillain-Barré syndrome (GBS) and had acute relapse after two years of asymptomatic interval. He had an acute muscle weakness with areflexia in his extremities following an upper respiratory tract infection in 1993. He was treated with plasma exchange and recovered completely within two months. Two years later he had a relapse of muscle weakness in the same distribution as the initial episode following the symptoms and signs of congestive heart failure. Biopsy of the heart muscle disclosed mild infiltration of lymphocytes with edema and fibrosis: the diagnosis of healing myocarditis was made. He underwent plasma exchange after the heart failure resolved and fully recovered neurologically within three months. The association of GBS and myocarditis is extremely rare. Moreover, there have been no reports describing recurrent GBS with myocarditis. Since GBS with myocarditis sometimes takes a fatal outcome, careful observation and treatment are mandatory.

Adult↗