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Biomedical subjects

S Baba

Publications and source records attributed to S Baba.

At least 37 records · Page 2Linked to original sources
PubMed2000

[Hereditary tumor syndrome: of its concept and classification].

With the cloning of cancer-predisposing genes many responsible genes have been identified from hereditary tumor syndrome over the past 10 years. Cancer is a genetic disease, arising from accumulation of mutations that promote clonal selection of cells and tumor progression. An individual who carries a mutant allele of an inherited cancer gene has a variable cancer risk. The proteins encoded by inherited cancer genes have been implicated in diverse cellular function, including proliferation, differentiation, apoptosis, and maintenance of genomic integrity. Concept and classification of hereditary tumor syndrome are discussed from genetic aspect.

Alleles↗
PubMed2000

[Rapidly progressed secondary amyloidosis in a patient with Still's disease with gamma-allele in his SAA 1 gene].

A fifteen-year-old boy was admitted to our hospital because of lower abdominal pain, watery diarrhea and mucobloody stool. Two years before admission, he was diagnosed to have Still's disease presenting with polyarthritis, sore throat, remittent fever and typical skin rash. He had been treated with non-steroidal anti-inflammatory agents, oral prednisolone and low-dose methotrexate. Although he was almost free of symptoms during the next two years, serum C-reactive protein (CRP) levels continued to be elevated moderately. He began to complain of lower abdominal pain and loose stool in May 1997 and came down with mucous-bloody diarrhea in June. Laboratory data on admission showed an elevated level of serum CRP (13.9 mg/dl). The biopsy of the stomach, ileum, sigmoid colon and rectum revealed the deposition of amyloid protein of AA type, which confirmed the diagnosis of secondary amyloidosis. The dose of prednisolone was increased and dimethyl sulfoxide per os or rectum was instituted, which improved his gastro-intestinal symptoms to some extent. However, fever, arthritis and diarrhea recurred along with tapered prednisolone dosage. In addition to gastro-intestinal symptoms, arrhythmia and proteinuria appeared. These symptoms were considered to reflect general deposition of amyloid in his body. He is now on immunosuppressive agent and high-dose prednisolone. Several studies report the higher frequency of gamma-allele of SAA 1 gene in the cases of rheumatoid arthritis with AA-amyloidosis than in those without. In the patient presented here, molecular biological analysis revealed that his SAA 1 gene was composed of beta- and gamma-allele. The presence of gamma-allele in his SAA 1 gene might be one of the factors that predisposed him for generalized deposition of amyloid protein in such a short period of time.

Adolescent↗
PubMed2000

Colorectal cancer: how does it start? How does it metastasize?

Colorectal carcinogenesis is a multistep process with an apparently orderly progression from benign tissue to invasive malignancy and metastases. Yet at the genome level, a considerably more chaotic situation exists, with order arising through the process of natural selection in the midst of genomic instability. Major pathways for colorectal carcinogenesis begin with suppressor loss or acquisition of a mutator phenotype, but there are other pathways known and yet to be described. These pathways result in the natural selection of cells with unstable genomes leading to malignancy and metastases.

Animals↗
PubMed1999

Alcohol consumption and all-cause and cancer mortality among middle-aged Japanese men: seven-year follow-up of the JPHC study Cohort I. Japan Public Health Center.

To examine the association between alcohol consumption and mortality in Japan, where mortality and lifestyle differ substantially from Western countries, a population-based prospective study was conducted in four public health center areas as part of the Japan Public Health Center-based prospective study on cancer and cardiovascular disease (JPHC). After excluding subjects with self-reported serious diseases at baseline, 19,231 men aged 40-59 years who reported their alcohol intake were followed from 1990 through 1996, and 548 deaths were documented. The association between all-cause mortality and alcohol consumption was J-shaped. The lowest risk was observed for men who consumed 1-149 g/week (relative risk (RR) = 0.64, 95% confidence interval (CI) 0.46, 0.88), while the highest risk was seen for men who consumed > or =450 g/week (RR = 1.32, 95% CI 1.00, 1.74), after adjustment for possible confounders. The association did not change after excluding deaths that occurred in the first 2 years of follow-up. However, the association was modified by smoking, and beneficial effects of moderate drinking were largely limited to nonsmokers. The risk of cancer death showed a similar trend, but increased more in heavy drinkers. The background characteristics of moderate drinkers were healthier than either nondrinkers or heavy drinkers. The authors conclude that moderate alcohol consumption was associated with the lowest risks of all-cause and cancer mortality, especially among nonsmokers.

Adult↗
PubMed1999

Human prostacyclin synthase gene and hypertension : the Suita Study.

BACKGROUND: Prostacyclin (prostaglandin I(2)) is a strong vasodilator that inhibits the growth of vascular smooth muscle cells and is also the most potent endogenous inhibitor of platelet aggregation. Therefore, it has been considered to play an important roles in cardiovascular disease. On the basis of the hypothesis that variations of the prostacyclin synthase gene may also play an important role in human cardiovascular disease, we performed a screening for variations in the human prostacyclin synthase gene. METHODS AND RESULTS: We have detected a repeat polymorphism in the promoter region of the human prostacyclin synthase gene. The number of 9-bp (CCGCCAGCC) repeats in the promoter region, which encodes a tandem repeat of Sp1 transcriptional binding sites, varied between 3 and 7 in Japanese subjects. Luciferase reporter analysis indicated that the alleles of 3 and 4 repeats (R3 and R4, respectively) had less promoter activity in cultured human umbilical vein endothelial cells. We then investigated the possible association of this repeat polymorphism with blood pressure in a large population-based sample (the Suita Study), which consisted of 4971 Japanese participants. Multivariate models indicated that participants with the R3R3, R3R4, or R4R4 genotype (SS genotype, n=80) had significantly higher systolic pressure (P=0.0133) and pulse pressure (P=0.0005). The odds ratio of hypertension (140/90 mm Hg) for the SS genotype was 1.942 (95% confidence interval 3.20 to 1.19, P=0.0084). CONCLUSIONS: Repeat polymorphism of the human prostacyclin synthase gene seems to be a risk factor for higher pulse pressure and is consequently a risk factor for systolic hypertension in the Japanese population.

Adult↗
PubMed1999

Parathyroid hormone-related protein is an independent prognostic factor for renal cell carcinoma.

BACKGROUND: Parathyroid hormone-related protein (PTHrP) has been shown to be the principal cause of humoral hypercalcemia associated with renal cell carcinoma (RCC). Recent studies have demonstrated that the amino-terminal region of PTHrP has growth factor-like activities, suggesting it may play a role in the development of RCC. In this study, expression of the carboxy-terminal region of PTHrP was assessed immunohistochemically and its significance in predicting the prognosis of RCC was studied. METHODS: Forty radical nephrectomy specimens were immunostained with a murine monoclonal antibody (9H7) against the carboxy-terminal region (amino acids 109-141) of PTHrP using the streptavidin-peroxidase enzyme conjugate method. Staining intensity was evaluated semiquantitatively and compared with clinicopathologic features of the corresponding RCC. RESULTS: Immunoreactivity to 9H7 was observed to be localized to the cytosol of tumor cells at various staining intensities. There were 30 cases (75.0%) with strong staining and 10 cases (25.0%) in which staining was weak or nonexistent. Staining intensity showed no significant correlation with gender, tumor greatest dimension, stage, or grade. Tumors of the clear cell type expressed PTHrP to a significantly greater extent than tumors of the granular cell type. Tumor recurrence was significantly greater in the weakly stained or unstained group compared with the strongly stained group (P = 0.035). Multivariate analysis indicated that PTHrP expression and tumor stage were equally significant prognostic indicators in RCCs measuring <10 cm in greatest dimension. CONCLUSIONS: Evident PTHrP(109-141) expression is present in the majority of RCCs. The results of the current study indicate PTHrP(109-141) may be a possible marker of cellular differentiation and may be useful for predicting recurrence free survival in RCC patients after radical nephrectomy.

Adult↗
PubMed1999

Predominant germ-line mutation of the hMSH2 gene in Japanese hereditary non-polyposis colorectal cancer kindreds.

By means of PCR-SSCP and direct sequencing, we detected 12 germ-line mutations of hMSH2 or hMLH1 in 37 Japanese hereditary non-polyposis colorectal cancer (HNPCC) kindreds, of whom 15 satisfied the Amsterdam and 22 the Japanese criteria. The germ-line mutation detection rate of hMSH2 was much higher than that of hMLH1 (11/37 vs. 1/37). The total mutation detection rate of hMSH2 and hMLH1 in the Amsterdam criteria group was significantly higher than that in the Japanese criteria group (9/15 vs. 3/22). Furthermore, the mean age of the HNPCC patients in the mutation-positive group was lower than that in the mutation-negative one; the rates of both vertical transmission and multiplicity of tumors in the mutation-positive group were higher than those in the mutation-negative one. In addition, the number of patients with microsatellite instability-positive cancers in the mutation-positive group was higher than that in the mutation-negative one. Our results suggest firstly that the hMSH2 gene plays a much more important role than hMLH1 in the carcinogenesis of Japanese HNPCC patients, secondly that the rate of hMSH2 and hMLH1 mutations is high in the kindreds satisfying the Amsterdam criteria and thirdly that both the clinical phenotypes (early onset, vertical transmission and multiplicity of tumors) and the microsatellite instability status are important for the genetic screening of HNPCC.

Colorectal Neoplasms, Hereditary Nonpolyposis↗
PubMed1999

Observations of prostate specific antigen doubling time in Japanese patients with nonmetastatic prostate carcinoma.

BACKGROUND: To understand better the natural history and biology of prostate carcinoma occurring in Japanese patients, the authors attempted to define changes with time in prostate specific antigen (PSA) measurements in 48 men with clinically resectable T1-T3 nonmetastatic disease. METHODS: The authors analyzed PSA changes prospectively in prostate carcinoma patients who were managed by watchful waiting. PSA doubling time was calculated by linear regression. These values and their distribution were compared with clinical parameters and with published series of prostate carcinoma patients. RESULTS: The mean age of the 48 patients at the time of diagnosis was 74.2 years. The median follow-up from the time of diagnosis was 24.0 months. The median PSA doubling time was 35.7 months. In 27.1% of patients, there was no increase in the PSA level over the observation period. A rapid rise in PSA (doubling time of <2 years) was observed in 29.2% of patients. These results in Japanese patients are virtually the same as those reported in Western countries. There was no statistically significant relation between calculated PSA doubling time and clinical disease stage, tumor grade, PSA level at the time of diagnosis, probability of extraprostatic disease, patient age at diagnosis, or prostate volume (P > 0.05). CONCLUSIONS: Prostate carcinoma may not differ significantly by race once it becomes clinically manifest. The magnitude of positive changes in PSA over a given period of observation may not be helpful in determining the need for therapy. The previously reported incidence of clinically insignificant prostate carcinoma, which primarily was based on pathologic findings in surgical specimens, may have been an underestimation.

Aged↗
PubMed1999

Complete genome sequence of an aerobic hyper-thermophilic crenarchaeon, Aeropyrum pernix K1.

The complete sequence of the genome of an aerobic hyper-thermophilic crenarchaeon, Aeropyrum pernix K1, which optimally grows at 95 degrees C, has been determined by the whole genome shotgun method with some modifications. The entire length of the genome was 1,669,695 bp. The authenticity of the entire sequence was supported by restriction analysis of long PCR products, which were directly amplified from the genomic DNA. As the potential protein-coding regions, a total of 2,694 open reading frames (ORFs) were assigned. By similarity search against public databases, 633 (23.5%) of the ORFs were related to genes with putative function and 523 (19.4%) to the sequences registered but with unknown function. All the genes in the TCA cycle except for that of alpha-ketoglutarate dehydrogenase were included, and instead of the alpha-ketoglutarate dehydrogenase gene, the genes coding for the two subunits of 2-oxoacid:ferredoxin oxidoreductase were identified. The remaining 1,538 ORFs (57.1%) did not show any significant similarity to the sequences in the databases. Sequence comparison among the assigned ORFs suggested that a considerable member of ORFs were generated by sequence duplication. The RNA genes identified were a single 16S-23S rRNA operon, two 5S rRNA genes and 47 tRNA genes including 14 genes with intron structures. All the assigned ORFs and RNA coding regions occupied 89.12% of the whole genome. The data presented in this paper are available on the internet homepage (http://www.mild.nite.go.jp).

Archaea↗
PubMed1999

Contribution of endothelin-1 to microcirculatory impairment in total hepatic ischemia and reperfusion injury.

BACKGROUND: Endothelin (ET)-1 may have a role in hepatic polymorphonuclear leukocyte infiltration as well as microcirculatory disturbance during hepatic ischemia-reperfusion (HIR) injury. This study was conducted to investigate the influence of ET-1 on the hepatic microcirculation after total HIR and to evaluate the effect of a nonselective ET receptor antagonist under these conditions. METHODS: Male rats pretreated with either normal saline (NS group) or TAK-044, a nonselective ET receptor antagonist (TAK group), were subjected to 120 min of total hepatic ischemia with extracorporeal portosystemic shunting. RESULTS: Plasma ET-1 levels increased significantly from 1 to 6 hr after reperfusion in the NS group when compared with the nonischemic control. In the early phase of reperfusion, the NS group showed significantly narrower sinusoids, lower hepatic tissue blood flow, a lower hepatic tissue oxy-hemoglobin concentration, and more hepatic neutrophil infiltration than the TAK group (P<0.05). Pretreatment with TAK-044 improved hepatic microcirculatory derangement, and resulted in significantly better 7-day survival (61.5%) with more bile production after reperfusion when compared with the NS group (P<0.01). CONCLUSIONS: The present study demonstrated that ET-1 is involved in the development of HIR injury by causing deterioration of the hepatic microcirculation. A nonselective ET receptor antagonist successfully ameliorated HIR injury through improvement of hepatic oxygenation and of the microcirculation along with reduced hepatic neutrophil infiltration.

Alanine Transaminase↗
PubMed1999

Participation of platelet-activating factor in the lipopolysaccharide-induced liver injury in partially hepatectomized rats.

Platelet-activating factor (PAF) has been shown to be an important mediator in the pathogenesis of lipopolysaccharide (LPS)-induced liver injury in regenerating rat livers. Both LPS and PAF activate nuclear factor-kappa B (NF-kappaB), a key transcription factor for tumor necrosis factor-alpha (TNF-alpha) and cytokine-induced neutrophil chemoattractant (CINC). The aim of this study is to investigate how PAF participates in the LPS-induced and NF-kappaB-mediated regulation of TNF-alpha and CINC in regenerating rat livers. LPS (1.5 mg/kg) was intravenously administered into 70% hepatectomized rats and sham-operated rats 48 hours postoperatively. LPS administration caused a high mortality rate, scattered necrosis in the liver with infiltration of CINC-positive neutrophils, and a continuous CINC messenger RNA up-regulation and activation of NF-kappaB in the liver only in hepatectomized rats. These phenomena were all effectively prevented by pretreatment and posttreatment with a PAF receptor antagonist, TCV-309. Hepatectomized rats showed NF-kappaB staining in hepatocytes, Kupffer cells, and neutrophils around necrosis 4 hours after the LPS injection, representing the activation of this factor in these cells. Based on these results, we propose that PAF contributes to continuous CINC up-regulation and NF-kappaB activation via accumulation and activation of neutrophils, and thereby is involved in LPS-induced liver injury in regenerating rat livers.

Alanine Transaminase↗
PubMed1999

Acute portal hypertension increases ileal vulnerability to platelet-activating factor in rats.

BACKGROUND: Patients with portal hypertension can easily develop sepsis of enteric origin after suffering severe trauma and hemorrhagic shock. Platelet-activating factor (PAF) is one of the key mediators of such stress. The aim of this study was to investigate whether portal hypertension increases the vulnerability of the ileum to PAF. MATERIALS AND METHODS: Seven days after surgery, PAF (1.5 microg/kg) was intravenously injected into portal stenosis (PS) rats and sham-operated rats. The levels of tumor necrosis factor-alpha (TNF-alpha), cytokine-induced neutrophil chemoattractant (CINC), and endotoxin in portal plasma were determined. The levels of PAF receptor (PAFR), TNF-alpha, and CINC mRNA in the ileum were also investigated. RESULTS: After PAF administration, PS rats showed (1) significantly higher portal plasma levels of TNF-alpha, CINC, and endotoxin; (2) higher histological damage scores in the ileum; (3) more infiltrating neutrophils in the ileum; and (4) a significantly higher mortality rate than sham-operated rats (P < 0.01). However, PAFR mRNA levels were similar in the two groups. The CINC mRNA level in the ileum of PS rats was increased from 1 to 4 h after PAF administration, while that of the sham-operated rats was transiently increased at 1 h. CONCLUSIONS: Portal hypertension increases the vulnerability of the ileum to PAF. These findings suggest that conditions which causes PAF production may be dangerous in patients with portal hypertension.

Acute Disease↗
PubMed1999

Suspected hereditary nonpolyposis colorectal cancer: International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer (ICG-HNPCC) criteria and results of genetic diagnosis.

PURPOSE: The aim of this study was to determine the frequency of mutations in the mismatch repair genes in families suspected of having hereditary nonpolyposis colorectal cancer. METHODS: We devised two criteria for families suspected of having hereditary nonpolyposis colorectal cancer (Criteria I and II). Criteria I consist of at least two first-degree relatives affected with colorectal cancer with at least one of the following: development of multiple colorectal tumors including adenomatous polyp, at least one colorectal cancer case diagnosed before the age of 50, and occurrence of a hereditary nonpolyposis colorectal cancer extracolonic cancer (endometrium, urinary tract, small intestine, stomach, hepatobiliary system, or ovary) in family members. Criteria II consist of one colorectal cancer patient with at least one of the following: early age of onset (<40 years); endometrial, urinary tract, or small intestine cancer in the index patient or a sibling (one aged <50 years); and two siblings with other integral hereditary nonpolyposis colorectal cancer extracolonic cancers (one aged <50 years). A questionnaire was mailed to members of the International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer to determine the mutation detection rate in mismatch repair genes from the families fulfilling these criteria. For comparison the mutation detection rate for families fulfilling the Amsterdam hereditary nonpolyposis colorectal cancer criteria in each institution was also obtained. RESULTS: Data were obtained from eight different institutions (in 7 different countries). In a total of 123 patients from 123 families (67 families fulfilling Criteria I and 56 families fulfilling Criteria II), genetic testing for germline mismatch repair gene variants was performed. Germline mutations of the hMLH1 or hMSH2 genes were identified in 24 families (20 percent). Of these, the mutation detection rate for families fulfilling Criteria I was 28 percent (19/67). The mutation detection rate for families fulfilling Criteria II was 9 percent (5/56). In these eight institutions, the overall mutation detection rate for families fulfilling the Amsterdam hereditary nonpolyposis colorectal cancer criteria was 50 percent (77/154). CONCLUSION: The Criteria I for suspected hereditary nonpolyposis colorectal cancer have the advantages that they can be applied to nuclear families and they can include extracolonic cancers. The results of this study suggest that families fulfilling Criteria I should be offered genetic testing. The relatively low mutation detection rate in those families fulfilling Criteria II suggests that, using current techniques, genetic testing in these families is not practical.

Age of Onset↗
PubMed1999

Double cancer of the gallbladder and common bile duct associated with an anomalous pancreaticobiliary ductal junction without a choledochal cyst: report of a case.

We report herein the case of a 37-year-old woman found to have double cancer of the gallbladder and common bile duct associated with an anomalous pancreaticobiliary ductal junction (APBDJ) without a choledochal cyst (CC). Abdominal ultrasonography showed an isoechoic mass in the gallbladder, and percutaneous transhepatic biliary drainage tubography revealed incomplete obstruction in the upper portion of the common bile duct and APBDJ. The patient underwent cholecystectomy, partial hepatic resection, pancreatoduodenectomy, and portal vein reconstruction. Pathological examination of the tumors from the gallbladder and bile duct revealed papillary carcinoma and poorly differentiated adenocarcinoma, respectively, and direct continuity was not observed between the tumors. A review of the literature on six cases of multiple primary carcinoma of the biliary tract associated with APBDJ without CC is presented following this case report. Double cancer of the biliary tract was found synchronously in five patients and metachronously in one. Gallbladder cancer showed subserosal invasion in four patients, while bile duct cancer invaded the pancreas in one patient and reached the serosa in two patients. Considering the potential for cancer to arise in the biliary tract and the difficulties associated with monitoring it, cholecystectomy and resection of the extrahepatic common bile duct may be the most appropriate treatment for patients with an APBDJ without a CC.

Adenocarcinoma↗
PubMed1999

Management of incidentally discovered adrenal masses.

The incidental discovery of adrenal masses in radiologic imaging studies is becoming increasingly common. Herein we present our experience with 59 cases of incidentally discovered and surgically removed adrenal masses. Of 59 adrenal incidentalomas, 15 cases were hypersecretory tumors, including 11 pheochromocytomas; only 3 were adrenocortical carcinomas. The prevalence of incidentally discovered adrenal masses and their differential diagnosis and management are discussed in a review of the literature.

Adrenal Gland Neoplasms↗