Biomedical subjects

S Oka

Publications and source records attributed to S Oka.

At least 55 records · Page 3Linked to original sources

PubMed2001

Increased concentrations of 14-3-3 epsilon, gamma and zeta isoforms in cerebrospinal fluid of AIDS patients with neuronal destruction.

BACKGROUND: 14-3-3 proteins are major evolutionarily conserved cytosolic proteins that regulate signal transduction, apoptosis and neurotransmitter synthesis. Five homologous 14-3-3 isoforms, beta, gamma, zeta, epsilon and eta, are reported in mammalian neurones. To elucidate the diagnostic value of 14-3-3 in cerebrospinal fluid (CSF), a highly specific antibody against each isoform and studies on the isoform patterns in patients with neuronal destruction are needed. METHODS: In this study, we raised isoform-specific antibodies against 14-3-3 proteins and established a semiquantitative method of identification of each isoform by Western immunoblotting. RESULTS: We found that three isoforms, 14-3-3 epsilon, gamma and zeta, appeared in the CSF of HIV patients with AIDS dementia complex or cytomegalovirus encephalitis, but not in AIDS patients without neurological symptoms or the non-HIV patients examined. The isoform patterns in AIDS patients were different from those reported in Creutzfeldt-Jakob disease and herpes simplex encephalitis, suggesting that the isoform patterns may facilitate the differential diagnosis. A high frequency of 14-3-3 in CSF was observed in seriously ill AIDS patients, particularly those with CD4 levels of less than 20 mm(3). CONCLUSION: These findings suggested that 14-3-3 proteins were released from destroyed neural cells and are useful real-time markers of the rate and amount of neural cell destruction in these patients.

14-3-3 Proteins↗

PubMed2001

Maternal serum triglyceride at 24--32 weeks' gestation and newborn weight in nondiabetic women with positive diabetic screens.

OBJECTIVE: To determine whether elevated midpregnancy maternal serum lipid levels predict newborn weight at term and the risk of large for gestational age (LGA) infants in women with positive diabetic screen but normal glucose tolerance test. METHODS: Japanese gravidas who had positive diabetic screens and normal 75-g oral glucose tolerance tests (GTT) at 24--32 weeks were enrolled. Subjects with complications, including diabetes, hypertension, or fetal anomalies were excluded, as were women with multifetal gestations. Fasting serum triglyceride, free fatty acids, and total cholesterol levels were measured at the time of GTT. We tested the association between maternal variables and birth weight by univariable analysis. We used multivariable analysis to test whether the association between fasting lipids and birth weight was independent of prepregnant maternal body mass index (BMI), maternal weight gain during pregnancy, and plasma glucose levels at GTT. We also used multiple logistic regression analysis to determine whether maternal hyperlipidemia, defined as more than the 75th percentile of each lipid, is a risk factor for having an LGA infant. RESULTS: We enrolled 146 subjects. Among measured maternal lipids, only triglyceride levels correlated with birth weight in univariable analysis (r = 0.22, P =.009). Birth weight also was correlated with prepregnant maternal BMI (r = 0.18, P =.04) and fasting plasma glucose levels (r = 0.17, P =.04). The association between maternal fasting triglyceride level and birth weight remained significant after adjusting for prepregnant BMI, maternal weight gain, fasting plasma glucose levels, fetal gender, and gestational age at birth (P =.01). Logistic regression analysis showed that fasting maternal hypertriglyceridemia (over 259 mg/dL) was the significant predictor of LGA infants, independent of prepregnant BMI, maternal weight gain, and maternal plasma glucose levels (odds ratio 11.6; 95% confidence interval 1.1, 122; P =.04). CONCLUSION: In women with positive diabetic screens but normal GTTs, fasting triglyceride levels at 24-32 weeks correlated positively with newborn weight at term, independent of maternal plasma glucose levels and obesity. Maternal fasting serum triglyceride levels in midpregnancy might be an independent predictor of fetal macrosomia in those women.

Adult↗

PubMed2001

A VEP study on visual processing of figural geometry.

The possibility of a link between medial axes (hereafter called symmetries) and figure salience has recently been proposed [Vision Res. 38 (1998) 2323; Vision Res. 38 (1998) 2429]. In this paper we investigated the characteristics of transient visual evoked potentials (VEPs) associated with stimulus figures designed to have different symmetries. Significant trends were observed for VEP components N1 (160-190 ms) and P2 (220-250 ms). N1 and P2 had shorter peak latencies for stimuli with greater symmetry peak amplitudes.

Adult↗

PubMed2001

New antimetastatic hypoxic cell radiosensitizers: design, synthesis, and biological activities of 2-nitroimidazole-acetamide, TX-1877, and its analogues.

We designed, based on the molecular orbital (MO) calculation, synthesized, and evaluated the biological activities of the new antimetastatic hypoxic cell radiosensitizer, 2-nitroimidazole-acetamide, TX-1877, and its analogues. Each analogue has an electron-affinic imidazole group, an acetamide group and a certain hydrophilic group to control its biological effect, toxicity, and pharmacokinetics. In in vitro radiosensitization assay, most TX-1877 analogues, which have an electron affinity (EA) of more than 0.9 eV and partition coefficient (P) of more than 0.021, showed satisfactory enhancement ratios (ER > 1.60) at doses of I mM. On the other hand, imidazole analogues, such as TX-1908 (EA = 0.67 eV), TX-1910 (EA = -0.34 eV) and TX-1931 (EA = -0.37 eV), which have low electron affinities, had an ER of 1.31 or less. TX-1877 and KIN-806 effectively inhibited tumor regrowth when administered with irradiation in vivo at a dose of 0.4 mg/g. Tumor lung metastasis was inhibited by treatment with either TX-1877 or KIN-806 without irradiation at a dose of 0.4 mg/g. TX-1877 reduced markedly the mean number of metastatic lung nodules in comparison with KIN-806. Moreover, TX-1877 and KIN-806 enhanced macrophage and helper T lymphocyte infiltration for 3 weeks after drug treatment. TX-1877 shows a high EA value and has the C2 of HOMO localizing on N-methylamide and the C2 of LUMO localizing on 2-nitroimidazole group. The MO data might be useful for designing a bifunctional hypoxic cell radiosensitizer. TX-1877 and its analogues are potential antimetastatic hypoxic cell radiosensitizers, which would improve the efficiency of radiotherapy and quality of life in cancer treatment.

Animals↗

PubMed2001

Risk factors influencing early and late mortality after total cavopulmonary connection.

OBJECTIVE: Among the later modifications of the Fontan type procedure, a significant alteration was introduced by de Leval and associates when they described the total cavopulmonary connection (TCPC). Although current results of TCPC have encouraged us to extend this procedure to high risk patients, risk factors influencing surgical outcome after TCPC have not been evaluated. We review our experiences with TCPC to identify which risk factors may have had a considerable impact on the outcome of patients undergoing TCPC and to clarify selection criteria of high-risk Fontan candidates for TCPC. PATIENTS AND METHODS: We retrospectively reviewed the medical and surgical records of all 76 patients who underwent TCPC between July 1988 and August 2000. A cross-sectional review of these patients was undertaken. RESULTS: There were eight early deaths and four late deaths. In a Fisher's exact test, the following variables were associated with an increased early mortality after TCPC: systemic ventricular morphology (right ventricle), ejection fraction of the systemic ventricle less than 60%, and prolonged cardiopulmonary bypass time (240 min or longer). The log-rank test demonstrated that heterotaxy syndrome, moderate to severe atrioventricular valve regurgitation, prolonged cardiopulmonary bypass time (240 min or longer), and prolonged aortic cross clamp time (70 min or longer) were associated with late mortality after TCPC. Six deaths occurred in eight (75%) patients who had six or more risk factors, whereas six deaths (9%) occurred in those who had five or fewer. CONCLUSIONS: Patients with complex cardiac anomalies who have six or more risk factors should be excluded from TCPC candidates.

Adolescent↗

PubMed2001

Linkage of sugar chains to a fragment peptide of FGF-5S by a chemoenzymatic strategy and changes in the rate of proteolytic hydrolysis.

Various O-linked and N-linked sugar chains were linked enzymatically to a fragment peptide (Leu-Ser-Gln(or Asn)-Val-His-Arg) of FGF-5S. First, galactose was linked with beta-(1-->3)-linkage to GalNAc-linked peptide by a transglycosylation using beta-galactosidase from Bacillus circulans (recombinant). Then sialic acid was linked with the aid of sialyltransferase from rat liver (recombinant) to give NeuAcalpha-(2-->3)-Galbeta-(1-->3)-GalNAc-linked hexapeptide. Further, a sialylated 2-chain biantennary sugar chain was linked by a transglycosylation using endo N-acetyl-beta-D-glucosaminidase from Mucor hiemalis (endo M, recombinant). The activity of DNA synthesis in a fibroblast cell line was increased by this glycosylation. The resistance of the obtained glycopeptides towards proteolytic hydrolysis by rat serum and by five proteases was compared with that of original peptide. The resistance was remarkably enhanced by the glycosylation.

Animals↗

PubMed2001

Discrimination of ameloblastomas from odontogenic keratocysts by cytokine levels and gelatinase species of the intracystic fluids.

In the present study, we measured the levels of the cytokines and gelatinase species in the fluids of ameloblastomas and odontogenic keratocysts, and showed that ameloblastomas can be distinguished from odontogenic keratocysts by the use of these biochemical data. We found that interleukin (IL)-1alpha and IL-1beta levels in the intracystic fluids of ameloblastomas were significantly lower than those in the fluids of odontogenic keratocysts, while IL-6 levels in the fluids of ameloblastomas were significantly higher than those in the fluids of odontogenic keratocysts. On the other hand, no significant differences in tumor necrosis factor (TNF)-alpha levels of the fluids were detected between ameloblastomas and odontogenic keratocysts. An immunohistochemical study revealed that the staining intensity of IL-1alpha, IL-1beta and TNF-alpha in the tumor cells of ameloblastomas was significantly weaker than that in the epithelial cells of odontogenic keratocysts, while the staining intensity of IL-6 in the tumor cells was significantly stronger than that in the epithelial cells of odontogenic keratocysts. Gelatin zymography of the fluids showed that only a small amount of pro-MMP-9 was detected in ameloblastomas, while both pro-MMP-9 and the active form of MMP-9 were detected in 8 of 10 cases of odontogenic keratocysts. Thus, ameloblastomas can be distinguished from odontogenic keratocysts by measuring IL-1alpha and IL-6 levels, and gelatinase species in the fluids.

Adult↗

PubMed2001

Mechanism of intramedullary high intensity area on T2-weighted magnetic resonance imaging in osteoid osteoma: a possible role of COX-2 expression.

To study the mechanism and pathophysiology of the development of intramedullary high intensity areas on T2-weighted magnetic resonance images (MRI) in cases of osteoid osteoma, we examined the expression of cyclooxygenase-2 (COX-2) in the nidus and surrounding bone tissues. In all six cases showing a marked intramedullary high intensity area adjacent to the nidus before surgery, neoplastic osteoblasts inside the nidus showed strong and diffuse COX-2 immunoreactivity. On the other hand, the osteoblasts rimming the surrounding reactive bone were COX-2 negative. In two cases examined by reverse transcription-polymerase chain reaction (RT-PCR), COX-2 mRNA was detected in abundance in the nidus. Histologically, vascular dilatation together with intramedullary edema was observed in all cases, which was probably reflected as a high intensity area on T2-weighted MRI. From our study, a high level of COX-2 expression in neoplastic osteoblasts in the nidus of osteoid osteomas may cause the secondary changes depicted by MRI.

Adolescent↗

PubMed2001

Alkaloids and flavonoids from peanut skins.

Separation of the water-soluble fraction of peanut skins led to the isolation of 8 flavonoids and two novel indole alkaloids. Two new flavonoid glycosides have been identified as isorhamnetin 3-O-[2-O-beta-glucopyranosyl-6-O-alpha-rhamnopyranosyl]- beta-glucopyranoside and 3',5,7-trihydroxyisoflavone-4'-methoxy-3'-O-beta-glucopyranoside. Two alkaloids are 2-methoxyl-3-(3-indolyl)-propionic acid and 2-hydroxyl-3-[3-(1-N-methyl)-indolyl]-propionic acid. These isolated flavonoids were evaluated for their free radical scavenging activity and protein glycation inhibitory effects.

Alkaloids↗

PubMed2001

Clinicopathologic features and endoscopic treatment of superficially spreading colorectal neoplasms larger than 20 mm.

BACKGROUND: A colorectal neoplasm that spreads superficially over the mucosa is known as a laterally spreading tumor. The clinicopathologic features of these large lesions and the efficacy and safety of endoscopic mucosal resection (EMR) were studied retrospectively. METHODS: Surgically or endoscopically resected laterally spreading tumors larger than 20 mm in diameter were studied. Lesions were divided into 2 macroscopic subtypes: F-type, composed of superficially spreading lesions with a flat and smooth surface, and G-type, composed of superficially spreading aggregates of nodules that form relatively flat, broad-based lesions with granulonodular and uneven surfaces. RESULTS: Thirty-three lesions were of the F-type and 87 the G-type. G-type (mean +/- SD, 35.3 +/- 11.4 mm) lesions were significantly larger (p < 0.01) than F-type (26.0 +/- 7.2 mm) lesions. F-type lesions had a significantly higher frequency of invasive cancer (27.2%) than G-types (10.3%)(p < 0.05). Of the 120 lesions, 81 (67.5%) were resected endoscopically. Patients with 78 of these lesions were followed postoperatively for 60.8 +/- 20.1 months. The rate of local recurrence of endoscopically treated tumors as determined at colonoscopy was 7.4% (6/78). These lesions were completely resected endoscopically. Distant metastases were not detected. Thirteen (16.0%) patients had local bleeding after EMR that was stopped endoscopically. Microperforation of the colonic wall as a result of EMR was diagnosed in 1 (1.2%) of 81 cases. CONCLUSIONS: Laterally spreading tumors larger than 20 mm, especially those of the G-type, have a low rate of invasion despite their relatively large size. The F-type lesion has a higher malignant potential than the G-type. EMR is an effective and safe treatment for the large laterally spreading tumor.

Adenoma↗

PubMed2001

Mixed lineage kinase LZK forms a functional signaling complex with JIP-1, a scaffold protein of the c-Jun NH(2)-terminal kinase pathway.

Leucine zipper-bearing kinase (LZK) is a novel member of the mixed lineage kinase (MLK) protein family, the cDNA of which was first cloned from a human brain cDNA library [Sakuma, H., Ikeda, A., Oka, S., Kozutsumi, Y., Zanetta, J.-P., and Kawasaki, T. (1997) J. Biol. Chem. 272, 28622-28629]. Several MLK family proteins have been proposed to function as MAP kinase kinase kinases in the c-Jun NH(2) terminal kinase (JNK)/stress-activated protein kinase (SAPK) pathway. In the present study, we demonstrated that, like other MLKs, LZK activated the JNK/SAPK pathway but not the ERK pathway. LZK directly phosphorylated and activated MKK7, one of the two MAPKKs in the JNK/SAPK pathway, to a comparable extent to a constitutive active form of MEKK1 (MEKK1DeltaN), suggesting a biological role of LZK as a MAPKKK in the JNK/SAPK pathway. Recent studies have revealed the essential roles of scaffold proteins in intracellular signaling pathways including MAP kinase pathways. JIP-1, one of the scaffold proteins, has been shown to be associated with MLKs, MKK7, and JNK [Whitmarsh, A.J., Cavanagh, J., Tournier, C., Yasuda, J., and Davis, R.J. (1998) Science 281, 1671-1674], suggesting the presence of a selective signaling pathway including LZK, MKK7, and JNK. Consistent with this hypothesis, we provided evidence that LZK is associated with the C-terminal region of JIP-1 through its kinase catalytic domain. In addition, LZK-induced JNK activation was markedly enhanced when LZK and JNK were co-expressed with JIP-1. These results constituted important clues for understanding the molecular mechanisms regulating the signaling specificities of various JNK activators under different cellular conditions.

Adaptor Proteins, Signal Transducing↗

PubMed2001

The time course of acquisition of ischemic tolerance and induction of heat shock protein 70 after a brief period of ischemia in the spinal cord in rabbits.

We examined the time course of development of ischemic tolerance in the spinal cord and sought its mechanism exploring the expression of heat shock protein 70 (HSP70). Spinal cord ischemia was produced in rabbits by occlusion of the abdominal aorta. In Experiment 1, neurologic and histopathologic outcome was evaluated 48 h after prolonged ischemia (20 min) that was given 2 days, 4 days, or 7 days after a short period of ischemia (ischemic pretreatment) sufficient to abolish postsynaptic component of spinal cord evoked potentials. Control animals were given prolonged ischemia 4 days after sham operation. In Experiment 2, HSP70 expression in motor neurons after pretreatment without exposure to prolonged ischemia was examined by immunohistochemical staining. Ischemic pretreatment 4 days (but not 2 days or 7 days) before 20 min ischemia exhibited protective effects against spinal cord injury. In the cytoplasm, HSP70 immunoreactivity was mildly increased after 2, 4, and 7 days of ischemic pretreatment. However, the incidence of nuclear HSP70 immunoreactivity 2 days, 4 days, and 7 days after ischemic pretreatment was 2 of 6 animals, 4 of 6 animals, and 1 of 6 animals, respectively (none in the control group). These results suggest that ischemic tolerance is apparent 4 days after ischemic pretreatment and that HSP70 immunoreactivity in the nucleus may provide some insight into the mechanisms of ischemic tolerance in the spinal cord.

Animals↗

PubMed2001

The addition of epinephrine to tetracaine injected intrathecally sustains an increase in glutamate concentrations in the cerebrospinal fluid and worsens neuronal injury.

UNLABELLED: We have reported that large concentrations of intrathecal tetracaine increase glutamate concentrations in the cerebrospinal fluid (CSF) and cause neuronal injury in the spinal cord. In this study, we investigated whether the addition of epinephrine to tetracaine modulates these events. New Zealand white rabbits were assigned into five groups (six rabbits in each group) and intrathecally received 0.3 mL of epinephrine 0.1 mg/mL in NaCl solution (control), 1% tetracaine dissolved in saline (1%T), 1% tetracaine with epinephrine (1%TE), 2% tetracaine (2%T), or 2% tetracaine with epinephrine (2%TE). Glutamate concentrations in the lumbar CSF were monitored by microdialysis. Neurologic and histopathologic assessments were performed 1 wk after the administration. Glutamate concentrations significantly increased in all four groups that received tetracaine, whereas no change was observed in the Control group. The addition of epinephrine to tetracaine sustained large concentrations of glutamate. Sensory and motor dysfunction was observed in the 1%TE, 2%T, and 2%TE groups, and the dysfunction tended to be progressively exacerbated in this order. Characteristic histologic changes in animals with sensory and motor dysfunction were vacuolation in the dorsal funiculus and chromatolytic damage of motor neurons. The vacuolation of the dorsal funiculus in the 1%TE group was significantly worse than in the 1%T group. These results suggest that the addition of epinephrine to tetracaine may increase its neurotoxicity, which may possibly be related to a sustained increase of glutamate concentrations in the CSF. IMPLICATIONS: Sustained increase of glutamate concentrations produced by the addition of epinephrine to intrathecal tetracaine can cause neuronal injury.

Anesthetics, Local↗

PubMed2001

[Evaluation of an anti-HIV-1/2 antibodies detection kit based on counting immunoassay].

A novel anti-HIV antibody detection kit, by which anti-HIV-1/2 antibodies were detected based on the counting immunoassay using an auto analyser (PAMIA-50), was evaluated. In an examination using 100 samples each of HIV-1 antibody positive and negative sera, either sensitivity and specificity was 100%. This kit was able to detect all antibodies tested including against HIV-1 subtype A to F, E/F, C/E, B/O, HIV-1 group O, and HIV-2. However, by one of the commercially available kits, one serum containing anti-subtype A antibody was missed. In other comparative studies with the conventional kits using various commercial available panel sera, the same results were obtained. This method was completed within 15 min and was able to examine many samples at one assay. Therefore, this kit is a useful and reliable one if hospitals or institutions had PAMIA-50 in their clinical laboratory.

Antibodies, Viral↗

PubMed2001

[A case of falciparum malaria successfully treated with intravenous artesunate].

The case was a 47-year-old Nigerian male who was thought to have contracted malaria in Nigeria and then manifested fever with chill, arthralgia and diarrhea in Japan. The blood test at International Medical Center of Japan revealed thrombocytopenia and anemia. Ring forms of 0.03% of his RBCs and ICT Malaria P.f/P.v test was also positive for Plasmodium falciparum. We prescribed mefloquine to him, but the number of the paresites in his peripheral blood did not decrease, and, in fact, they came to increase (maximum 6.66%) 20 hours after the drug treatment. As clinical condition of malaria were liable to change seriously, intravenous Artesunate (a qinghaosu derivative) was decided to be given additionally to the patient. Consequently the parasites disappeared in 20 hours from his blood but a low grade fever still continued possibly because of cholecystitis. At the same time of Artesunate treatment, hemoglobinuria started and anemia worsened partly because of his G-6-PD deficiency. All pending problems were improved by the time he left Japan and those parasites were finally found to be susceptible for mefloquine by the in vitro susceptibility test. This is the first reported case of falciparum malaria successfully treated with intravenous Artesunate in Japan.

Antimalarials↗

PubMed2001

Rapid and simple phenotypic assay for drug susceptibility of human immunodeficiency virus type 1 using CCR5-expressing HeLa/CD4(+) cell clone 1-10 (MAGIC-5).

We describe a rapid and simple novel phenotypic assay for drug susceptibility of human immunodeficiency virus type-1 (HIV-1) using a CCR5-expressing HeLa/CD4(+) cell clone 1-10 (MAGIC-5). MAGIC-5 cells produced large amounts of HIV-1 in culture supernatants, which enabled us to perform the phenotypic resistance assay. Determination of HIV-1 susceptibility to various protease inhibitors (PI) and nucleoside reverse transcriptase inhibitors was completed within 15 days in T-cell-tropic (X4) and macrophage-tropic (R5) viruses using fresh plasma samples containing at least 10(4) copies/ml. The nucleotide sequence of the envelope V3 region of HIV-1 in plasma was almost identical to that of the virus isolated by MAGIC-5 cells, suggesting a lack of selection bias in our assay. The assay variability was confined to within five-fold in all drugs examined. Accordingly, we used a 10-fold increase in the 50% inhibitory concentration as the cutoff value for viral resistance in the present assay. HIV-1 resistant to lamivudine, which was not detected by conventional genotypic assays, was isolated. In HIV-1 with PI-associated primary amino acid substitutions, our assay showed that drug resistance profiles correlated well with previously reported genotypic-assay data. Furthermore, our assay provided comprehensive results regarding PI resistance in the presence of multiple mutations. The novel assay successfully quantified the level of resistance of clinical HIV-1 isolates to a battery of anti-HIV drugs, indicating its clinical usefulness, particularly in patients who failed to respond to antiretroviral chemotherapy.

Amino Acid Sequence↗

PubMed2001

Augmentation of human immunodeficiency virus type 1 subtype E (CRF01_AE) multiple-drug resistance by insertion of a foreign 11-amino-acid fragment into the reverse transcriptase.

A human immunodeficiency virus type 1 (HIV-1) subtype E (CRF01_AE) variant (99JP-NH3-II) possessing an in-frame 33-nucleotide insertion mutation in the beta3-beta4 loop coding region of the reverse transcriptase (RT) gene was isolated from a patient who had not responded to nucleoside analogue RT inhibitors. This virus exhibited an extremely high level of multiple nucleoside analog resistance (MNR). Neighbor-joining tree analysis of the pol sequences indicated that the 99JP-NH3-II variant had originated from the swarm of drug-sensitive predecessors in the patient. Population-based sequence analyses of 82 independently cloned RT segments from the patient suggested that the variants with the insertion, three or four 3'-azido-3'-deoxythymidine resistance mutations, and a T69I mutation in combination had strong selective advantages during chemotherapy. Consistently, in vitro mutagenesis of a drug-sensitive predecessor virus clone demonstrated that this mutation set functions cooperatively to confer a high level of MNR without deleterious effects on viral replication capability. Homology modeling of the parental RT and its MNR mutant showed that extension of the beta3-beta4 loop by an insertion caused reductions in the distances between the loop and the other subdomains, narrowing the template-primer binding cleft and deoxynucleoside triphosphate-binding pocket in a highly flexible manner. The origin of the insert is elusive, as every effort to find a homologue has been unsuccessful. Taken together, these data suggest that (i) HIV-1 tolerates in vivo insertions as long as 33 nucleotides into the highly conserved enzyme gene to survive multiple anti-HIV-1 inhibitors and (ii) the insertion mutation augments multiple-drug resistance, possibly by reducing the biochemical inaccuracy of substrate-enzyme interactions in the active center.

Adult↗

PubMed2001

Clinicopathological findings in patients with gastric adenocarcinoma with familial aggregation.

BACKGROUND/AIMS: The clinicopathological characteristics of gastric cancer (GC) with a positive family history of site-specific GC have not been well discussed. The aim of this study was to estimate the risk of familial aggregation of GC in a hospital-based case-control study and to analyze the clinicopathological characteristics of GC with familial aggregation of GC. METHODS: Our series was comprised of 926 histologically confirmed patients with GC (588 males and 338 females) and 2,052 non-cancer outpatients between 1985 and 1996. The odds ratios (ORs), as estimators of relative risks, together with the corresponding 95% confidence intervals (CIs) for a family history of GC and for a family history of other cancers were calculated. Moreover, the clinicopathological findings of patients with GC who had a GC family history were compared with those of patients with GC who had no GC family history. RESULTS: A positive family history of GC was associated with a statistically significant increase in the risk of GC (OR = 2.15; 95% CI = 1.77-2.63), while no association was observed between the risk of GC and a family history of other cancers (OR = 1.11; 95% CI = 0.91-1.36). The incidence of a multifocal occurrence of GCs was higher in patients with a family history of GC (19.4%) than in patients without a family history of GC (12%, p = 0.005). The risk (OR) of occurrence of multiple cancers in the stomach in patients who had a family history of GC was 1.77 (95% CI = 1.19-2.64). CONCLUSIONS: Our results suggest that a family history of GC seemed to be a risk factor for the development of GC. Further, a family history of GC was found to be associated with a multifocal occurrence of GC.

Adenocarcinoma↗