In previous transfection analyses using the chloramphenicol acetyltransferase reporter gene system, we determined that linker substitution (LS) mutations between -201 and -130 (relative to the transcription start site) of the human immunodeficiency virus type 1 long terminal repeat (LTR) caused moderate decreases in LTR transcriptional activity in a T-cell line (S. L. Zeichner, J. Y. H. Kim, and J. C. Alwine, J. Virol. 65:2436-2444, 1991). In order to confirm the significance of this region in the context of viral replication, we constructed several of these LS mutations (-201 to -184, -183 to -166, -165 to -148, and -148 to -130) in proviruses and prepared viral stocks by cocultivation of transfected RD cells with CEMx174 cells. In addition, two mutations between -93 and -76 and between -75 and -58 were utilized, since they affect the nuclear factor kappa B (NF-kappa B)- and Sp1-binding sites and were expected to diminish viral replication. Our results suggest that while transfection analyses offer an adequate approximation of the effects of the LS mutations, the analysis of viral replication using a mutant viral stock presents a more accurate picture, which is sometimes at variance with the transfection results. Three mutants (-201/-184 NXS, -165/-148 NXS, and -147/-130 NXS) had effects on viral replication that were much more severe than the effects predicted from their performance in transfection analyses, and the effects of two LS mutations (-201/-184 NXS and -183/-166 NXS) were not predicted by their effects in transfection. In addition, we observed cell type-specific permissiveness to replication of some mutant viruses. In the cell types tested, the LS mutations indicated an apparent requirement not only for the intact NF-kappa B and SP1-binding sites but also for several regions between -201 and -130 not previously associated with viral infectivity.
In mouse tooth development, the roots of the first lower molar develop after crown formation to form 2 cylindrical roots by post-natal day 5. This study compared the morphogenesis and cellular events of the mesial-root-forming (MRF) and bifurcation-forming (BF) regions, located in the mesial and center of the first lower molar, to better define the developmental mechanisms involved in multi-rooted tooth formation. We found that the mesenchyme in the MRF showed relatively higher proliferation than the bifurcation region. This suggested that spatially regulated mesenchymal proliferation is required for creating cylindrical root structure. The mechanism may involve the mesenchyme forming a physical barrier to epithelial invagination of Hertwig’s epithelial root sheath. To test these ideas, we cultured roots in the presence of pharmacological inhibitors of microtubule and actin polymerization, nocodazole and cytochalasin-D. Cytochalasin D also inhibits proliferation in epithelium and mesenchyme. Both drugs resulted in altered morphological changes in the tooth root structures. In particular, the nocodazole- and cytochalasin-D-treated specimens showed a loss of root diameter and formation of a single-root, respectively. Immunolocalization and three-dimensional reconstruction results confirmed these mesenchymal cellular events, with higher proliferation in MRF in multi-rooted tooth formation.
tooth development; molar; tooth root; odontogenesis; cell proliferation; histochemistry
The aim of this study was to evaluate the relationships between the severity of appendicitis as depicted on CT and blood inflammatory markers of serum white blood cell (WBC) count and C-reactive protein (CRP).
CT images in 128 patients (109 surgically proven and 19 with clinically excluded appendicitis) were retrospectively reviewed. Two radiologists by consensus evaluated and scored (using a 0, 1 or 2 point scale) severities based on CT-determined appendiceal diameters, appendiceal wall changes, caecal changes, periappendiceal inflammatory stranding and phlegmon or abscess formation. We investigated whether CT findings were significantly related to elevated WBC counts or CRP levels and performed the correlations of WBC counts and CRP levels with CT severity scores. Patients were also subjectively classified using four grades from normal (Grade I) to perforated appendicitis (Grade IV) on the basis of CT findings to evaluate differences in WBC counts and CRP levels between grades.
Only appendiceal wall changes and the phlegmon or abscess formation were related to elevated WBC counts and CRP levels, respectively (p<0.05). CT severity scores were found to be more strongly correlated with CRP levels (r = 0.669) than with WBC counts (r = 0.222). On the basis of CT grades, the WBC counts in Grade I were significantly lower than in other grades (p<0.001), whereas CRP levels in Grade IV were significantly higher than in other grades (p<0.001).
CRP levels were found to correlate with CT-determined acute appendicitis severity and could be a useful predictor for perforated appendicitis, whereas WBC counts might be useful to detect early acute appendicitis.
A total of 33 carnation cultivars cultured in Korea were screened for resistance to the southern root-knot nematode, Meloidogyne incognita. Carnations were tested by either inoculating with 5,000 eggs or by transplanting into a mixture of bedding medium and soil infested with an average of 435 second-stage juveniles/300 cm³ soil. Cultivars, Desio, Castelaro, Kappa, Rara, Izu Pink, Target, and Antalia were highly resistant to M. incognita. Twelve cultivars were moderately resistant, and the remaining 14 cultivars were susceptible. These results were similar to those obtained when the cultivars were subjected to field populations of the condition on a carnation farm.
carnation; Dianthus caryophyllus; Korea; Meloidogyne incognita; resistance; root-knot nematode
This experiment was carried out to investigate effects of onion extract on growth performance, meat quality and blood profiles of White mini broilers. Total of 600 one-d-old male White mini broiler chicks were divided into four groups and fed control diets (non-medicated commercial diet or antibiotics medicated) or experimental diets (non-medicated diets containing 0.3% or 0.5% onion extract) for 5 wks. The final body weight (BW) and weight gain of the group fed non-medicated control diet were lower than those of medicated control group (p<0.01). The chicks fed diet with 0.3% or 0.5% onion extract showed a similar BW to that of medicated control group. The relative weight of various organs, such as liver, spleen, bursa of Fabricius, abdominal fat, and the activities of serum enzymes were not affected by dietary treatments. There were no significant differences in meat color among groups. Whereas, groups fed diets containing onion extract had slightly lower cooking loss and higher shear force value, but not significantly. The concentrations of serum free cholesterol and triacylglycerol in groups fed diet containing onion extract were significantly decreased compared with those of controls (p<0.01). In conclusion, the onion extracts exerted a growth-promoting effect when added in White mini broiler diets, reflecting potential alternative substances to replace antibiotics.
Onion Extract; Growth Performance; Serum Cholesterol; Blood Profiles; White Mini Broilers
To assess the properties of adrenal lesions with and without known primary cancer and investigate predictors for differential diagnosis between benign and malignant adrenal enlargement.
This retrospective study used fluorine-18 fludeoxyglucose positron emission tomography (PET)/CT in 325 patients with adrenal lesions (229 with known primary cancer and 96 without primary cancer). Age, sex, the presence of right and left masses, nodules or hyperplasia, unenhanced attenuation, maximum standardised uptake value (SUVmax) ratio, and the presence of metastasis in other body parts and locations of the primary cancer were assessed. Univariate and multivariate analyses were used to assess variables associated with risk of adrenal metastasis.
Patients with adrenal metastasis vs those without had a higher frequency of primary lung cancer (52.3% vs 30.7%) but a lower frequency of gastrointestinal cancer (7.9% vs 16.6%). The frequency of other abnormalities, including adenoma and hyperplasia, was similar between patients with and without known primary cancer. A higher proportion of patients with adrenal metastasis regardless of primary cancer site were younger, had a nodule or a mass, had an unenhanced attenuation of >10 HU, had an SUVmax ratio of >2.5, and had metastasis in other body parts. Analysis found independent associations of age, unenhanced attenuation of >10 HU, SUVmax ratio of >2.5 and the presence of metastasis in other body parts with adrenal metastasis. The combination of the four variables was strongly associated with adrenal metastasis.
PET/CT was useful in characterising adrenal lesions as benign or malignant and helpful in identifying adrenal metastasis and cancer severity.
Advances in knowledge:
PET/CT can help in the differential diagnosis between benign and malignant adrenal enlargement.
We fabricated and characterized the material with Mn (10 at.%: atomic percent) doped In3Sb1Te2 (MIST) using co-sputtering and synchrotron radiation, respectively. The MIST thin film showed phase-changes at 97 and 320°C, with sheet resistances of ~10 kΩsq (amorphous), ~0.2 kΩsq (first phase-change), and ~10 Ωsq (second phase-change). MIST did not exhibit any chemical separation or increased structural instability during either phase-change, as determined with high-resolution x-ray photoelectron spectroscopy. Chemical state changes were only depended for In without concomitant changes of Sb and Te. Apparently, doped Mn atoms can be induced with movement of only In atoms.
p53 is a key regulator of cell growth and death by controlling cell cycle progression and apoptosis under conditions of stress such as DNA damage or oncogenic stimulation. As these processes are critical for cell function and inhibition of tumor development, p53 regulatory pathways are strictly monitored in cells. Recently, it was recognized that nucleolar proteins, including nucleophosmin/B23, ribosomal protein L11, and alternate reading frame (ARF), form the nucleolus-ARF-murine double minute 2 (MDM2) axis in p53 regulatory pathways, which increases p53 stability by suppressing the activity of MDM2. In this work, we show that nucleolar protein glioma tumor-suppressor candidate region gene 2 (GLTSCR2) translocates to the nucleoplasm under ribosomal stress, where it interacts with and stabilizes p53 and inhibits cell cycle progression without the involvement of the major upstream p53 regulator, ARF. Furthermore, ectopic expression of GLTSCR2 significantly suppressed growth of cancer cells in a xenograft animal model via p53-dependent pathway. Our data identify GLTSCR2 as a new member of the nucleolus–nucleoplasmic axis for p53 regulation. ARF-independent direct regulation of p53 by GLTSCR2 may be a key mechanism and therapeutic target for cell death or growth inhibition when nucleolus-ARF-p53 pathways are inactivated by genetic or epigenetic modifications of ARF, which are the second most common types of genetic change observed in human cancers.
GLTSCR2; p53; tumor suppressor; nucleolus
Salivary duct carcinoma (SDC) is a rare malignancy of high-grade pathological type. We evaluated clinical outcomes and prognostic factors in 35 patients with SDC treated post-operatively with adjuvant radiation.
We retrospectively assessed overall survival, locoregional control and disease-free survival in 35 patients with SDC of the major salivary glands who underwent surgery and were subsequently treated with radiotherapy. The evaluated prognostic factors included gender, age, symptom duration, tumour site, tumour size, TNM classification, and the following pathological features: perineural invasion, lymphovascular invasion, extraparenchymal invasion and resection-margin status.
Of the 35 patients, 30 (85.7%) were male. Median age at initial diagnosis was 62 years (range 38–75 years). The parotid gland was the main site affected in 22 patients (62.9%). 18 patients (51.5%) had pathological T3/T4 tumours, and 26 (74.3%) showed pathological nodal involvement. Actuarial 5-year locoregional control, disease-free survival and overall survival rates were 63.3%, 47.4% and 55.1%, respectively. The cause-specific death rate was 31.4% (n=11). Pathological nodal involvement was correlated with distant metastasis (p=0.011). Lymphovascular invasion was significantly prognostic for distant metastasis-free survival (p=0.049), locoregional control (p=0.012) and overall survival (p=0.003) in a Cox proportional hazard model, whereas perineural invasion was only significantly prognostic for overall survival (p=0.005).
Surgery and post-operative radiotherapy were effective for locoregional control. Lymphovascular invasion and perineural invasion were significant prognostic factors in patients with SDC.
This study was carried out to determine the effects of tomato powder (TP) on cooked pork patties during storage at 10±1°C in the dark. The total phenolic and flavonoid contents of TP extract were 26.22 mg gallic acid/100 g and 3.52 mg quercetin/100 g, respectively. The extract of TP showed a potential antioxidant activity in the DPPH radical-scavenging assay (EC50 = 16.76 μg/mL). Pork patties were manufactured with 0.25% (T1), 0.5% (T2), 0.75% (T3) and 1.0% (T4) TP in a basic formula (C). The pH and volatile basic nitrogen (VBN) values of T2, T3 and T4 patties were lower (p<0.05) than the C patties during storage. Increased concentration of TP in meat patties decreased (p<0.05) the 2-thiobarbituric acid reactive substances (TBARS) and total plate count (TPC) values at d 7 of storage. Tomato treated-patties had lower (p<0.05) values for lightness (L*), but higher (p<0.05) values for redness (a*) and yellowness (b*) at d 3 and 7 of storage compared with the C. In the case of sensory evaluation, the scores of colour, flavour and overall acceptability of T3 and T4 patties were higher (p<0.05) than those of the C patty after 3 or 7 days of storage.
Tomato Powder; Natural Antioxidant; Pork Patties; Antioxidant Activity; Sensory Evaluation
The aim of this study was to determine the differences in CT findings of miliary tuberculosis in patients with and without HIV infection. Two radiologists reviewed retrospectively the CT findings of 15 HIV-seropositive and 14 HIV-seronegative patients with miliary tuberculosis. The decisions on the findings were reached by consensus. Statistical analysis was performed using the χ2 test, Mann–Whitney U-test and Fisher's exact test. All of the HIV-seropositive and -seronegative patients had small nodules and micronodules distributed randomly throughout both lungs. HIV-seropositive patients had a higher prevalence of interlobular septal thickening (p = 0.017), necrotic lymph nodes (p = 0.005) and extrathoracic involvement (p = 0.040). The seropositive patients had a lower prevalence of large nodules (p = 0.031). In conclusion, recognition of the differences in the radiological findings between HIV-seropositive and -seronegative patients may help in the establishment of an earlier diagnosis of immune status in patients with miliary tuberculosis.
The aim of this study was to investigate the incidence of intraocular pressure (IOP) elevation after resident-performed cataract surgery and to determine variables, which influence postoperative day 1 (POD1) IOP.
In all, 1111 consecutive cataract surgeries performed only by training residents between 1 July 2001 and 30 June 2006 were included. Elevated IOP was defined as ≥23 mm Hg. Surgeries were classified according to the presence of POD1-IOP elevation. Fisher's exact test and Student t-test were used to compare both groups. Multivariate analyses using generalized estimating equations were performed to investigate predictor variables associated with POD1-IOP elevation.
The average preoperative IOP was 16.0±3.2 mm Hg and the average POD1-IOP was 19.3±7.1 mm Hg, reflecting a significant increase in IOP (P<0.001, paired t-test). The incidence of POD1-IOP elevation ≥23 mm Hg was 22.0% (244/1111). Presence of glaucoma and ocular hypertension, higher preoperative IOP, and longer axial length were frequently encountered variables in the POD1-IOP elevation group (all P<0.05). Using a multivariate analysis, presence of glaucoma (P=0.004, OR=2.38; 95% confidence interval (95% CI)=1.31–4.30), presence of ocular hypertension (P=0.003, OR=6.09; 95% CI=1.81–20.47), higher preoperative IOP (P<0.001, OR=3.73; 95% CI=1.92–7.25), and longer axial length (P=0.01, OR=1.15; 95% CI=1.03–1.29) were significant predictive factors for POD1-IOP elevation.
IOP elevation on the first postoperative day following resident-performed cataract surgery occurred frequently (22.0%). Increased early postoperative IOP was associated with presence of glaucoma and ocular hypertension, higher preoperative IOP, and longer axial length.
intraocular pressure; postoperative day 1; cataract surgery; resident-performed cataract surgery
This study was conducted to determine how the isolation method of the porcine preantral follicles influenced the following follicular growth in vitro. Mechanical and enzymatical isolations were used for retrieving the follicles from prepubertal porcine ovaries, and in vitro-growth of the follicles and the expression of folliculogenesis-related genes were subsequently monitored. The enzymatic retrieval with collagenase treatment returned more follicles than the mechanical retrieval, while the percentage of morphologically normal follicles was higher with mechanical retrieval than with enzymatic retrieval. After 4 days of culture, mechanically retrieved, preantral follicles yielded more follicles with normal morphology than enzymatically retrieved follicles, which resulted in improved follicular growth. The mRNA expression of FSHR, LHR Cx43, DNMT1 and FGFR2 genes was significantly higher after culture of the follicles retrieved mechanically. These results suggest that mechanical isolation is a better method of isolating porcine preantral follicles that will develop into competent oocytes in in vitro culture.
Porcine; Preantral Follicle; Enzymatic Retrieval; Mechanical Retrieval; In vitro Culture; Follicular Growth
Presently, co-culture of human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) with BV2 microglia under amyloid-β42 (Aβ42) exposure induced a reduction of Aβ42 in the medium as well as an overexpression of the Aβ-degrading enzyme neprilysin (NEP) in microglia. Cytokine array examinations of co-cultured media revealed elevated release of soluble intracellular adhesion molecule-1 (sICAM-1) from hUCB-MSCs. Administration of human recombinant ICAM-1 in BV2 cells and wild-type mice brains induced NEP expression in time- and dose-dependent manners. In co-culturing with BV2 cells under Aβ42 exposure, knockdown of ICAM-1 expression on hUCB-MSCs by small interfering RNA (siRNA) abolished the induction of NEP in BV2 cells as well as reduction of added Aβ42 in the co-cultured media. By contrast, siRNA-mediated inhibition of the sICAM-1 receptor, lymphocyte function-associated antigen-1 (LFA-1), on BV2 cells reduced NEP expression by ICAM-1 exposure. When hUCB-MSCs were transplanted into the hippocampus of a 10-month-old transgenic mouse model of Alzheimer's disease for 10, 20, or 40 days, NEP expression was increased in the mice brains. Moreover, Aβ42 plaques in the hippocampus and other regions were decreased by active migration of hUCB-MSCs toward Aβ deposits. These data suggest that hUCB-MSC-derived sICAM-1 decreases Aβ plaques by inducing NEP expression in microglia through the sICAM-1/LFA-1 signaling pathway.
hUCB-MSC; amyloid-β; Alzheimer's disease; intracellular adhesion molecule-1; paracrine and neprilysin
FTO harbours the strongest known obesity-susceptibility locus in Europeans. While there is growing evidence for a role for FTO in obesity risk in Asians, its association with type 2 diabetes, independently of BMI, remains inconsistent. To test whether there is an association of the FTO locus with obesity and type 2 diabetes, we conducted a meta-analysis of 32 populations including 96,551 East and South Asians.
All studies published on the association between FTO-rs9939609 (or proxy [r2 > 0.98]) and BMI, obesity or type 2 diabetes in East or South Asians were invited. Each study group analysed their data according to a standardised analysis plan. Association with type 2 diabetes was also adjusted for BMI. Random-effects meta-analyses were performed to pool all effect sizes.
The FTO-rs9939609 minor allele increased risk of obesity by 1.25-fold/allele (p = 9.0 × 10−19), overweight by 1.13-fold/allele (p = 1.0 × 10−11) and type 2 diabetes by 1.15-fold/allele (p = 5.5 × 10−8). The association with type 2 diabetes was attenuated after adjustment for BMI (OR 1.10-fold/allele, p = 6.6 × 10−5). The FTO-rs9939609 minor allele increased BMI by 0.26 kg/m2 per allele (p = 2.8 × 10−17), WHR by 0.003/allele (p = 1.2 × 10−6), and body fat percentage by 0.31%/allele (p = 0.0005). Associations were similar using dominant models. While the minor allele is less common in East Asians (12–20%) than South Asians (30–33%), the effect of FTO variation on obesity-related traits and type 2 diabetes was similar in the two populations.
FTO is associated with increased risk of obesity and type 2 diabetes, with effect sizes similar in East and South Asians and similar to those observed in Europeans. Furthermore, FTO is also associated with type 2 diabetes independently of BMI.
Electronic supplementary material
The online version of this article (doi:10.1007/s00125-011-2370-7) contains peer-reviewed but unedited supplementary material, which is available to authorised users.
Asians; FTO; Meta-analysis; Obesity; Type 2 diabetes
Images in cardiology
Stathmin1 is a microtubule-regulating protein that has an important role in the assembly and disassembly of the mitotic spindle. The roles of stathmin1 in carcinogenesis of various cancers, including prostate and breast cancer, have been explored. However, its expression and roles in gastric cancer have not yet been described.
Stathmin1 expression in paraffin-embedded tissue sections from 226 patients was analysed by immunohistochemistry. Roles of stathmin1 were studied using a specific small interfering RNA (siRNA).
The expression of stathmin1 was positively correlated with lymph node metastasis, TNM stages and vascular invasion, and negatively with recurrence-free survival, in the diffuse type of gastric cancer. The median recurrence-free survival in patients with a negative and positive expression of stathmin1 was 17.0 and 7.0 months, respectively (P=0.009). When the expression of stathmin1 was knocked down using siRNA, the proliferation, migration and invasion of poorly differentiated gastric cancer cells in vitro were significantly inhibited. Moreover, stathmin1 siRNA transfection significantly slowed the growth of xenografts in nude mice.
These results suggest that stathmin1 can be a good prognostic factor for recurrence-free survival rate and is a therapeutic target in diffuse-type gastric cancer.
stathmin1; gastric cancer; proliferation; migration
We investigated the change in activity of the sympathetic nervous system (SNS) in high-sucrose diet (HSD)-induced obese rats compared with controls. Power spectral analyses of R-R interval variability were performed to obtain the low frequency (LF, 0.04-0.699 Hz) and high frequency (HF, 0.7-3.0 Hz) powers. The percents of fat mass to body weight (%F/BW) and fat to muscle ratios (F/M) were significantly increased in HSD-fed rats. Plasma glucose, leptin, and triglyceride concentrations in rats fed with HSD were significantly increased. LF in normalized units (LFn), which represents both sympathetic and parasympathetic activities, was significantly increased whereas HF in normalized unit (HFn), which represents parasympathetic activity, was significantly decreased in HSD-fed rats. LF/HF, which represents sympathetic activity, was significantly increased in HSD-fed rats and was correlated with leptin (r=0.549, p<0.023), %F/BW (r=0.513, p<0.035), F/M (r=0.536, p<0.038), and triglyceride (r=0.497, p<0.042). When adjusted for leptin concentrations, however, LF/HF of HSD-fed rats was significantly decreased. In conclusion, HSD-induced obese rats showed increased LF/HF, which was significantly decreased by adjustment for leptin concentrations. We suggest that stimulating effect of leptin on SNS is reduced, which might play a role in induction of obesity by HSD.
To know the effects of nicotinamide (NCT) treatment for 5 weeks at the early age on insulitis and development of diabetes in non-obese diabetic (NOD) mice, this experiment was performed. Ten ICR (Institute of Cancer Research) and 15 female NOD mice at 4 weeks of age were used. Mice were assigned to ICR and NOD groups, and NOD mice were randomly divided to control and NCT-treated groups. NCT was administered to mice orally as a solution and in a dose of 500 mg/kg body weight a day from the age of 4 to 8 weeks. Diabetes onset was 18 weeks of age in control group, and 22 weeks of age in NCT-treated group. Cumulative incidences of diabetes at 25 weeks of age in control and NCT-treated NOD mice were 63 and 29%, respectively. Insulitis occurred in all NOD mice. Incidence of insulitis in total islets was decreased by NCT treatment in diabetic NOD mice, but intensity of insulitis was not improved by NCT treatment. Blood glucose level was increased markedly, and plasma insulin level was decreased by diabetes development in NOD mice. Plasma triglycerides and total cholesterol levels were increased in diabetic mice than in non-diabetic mice. In conclusion, these results suggest that NCT treatment for 5 weeks at the early age in NOD mice inhibits development of diabetes and insulitis in diabetic NOD mice.
Focusing on prevention of HIV will not prevent the deaths of the millions already infected. The international community must adopt a strategy that links treatment and prevention
A cross-sectional study evaluated the prevalence of and the risk factors for hepatitis C and B viruses among 700 adults above the age of 40 years in a rural area of South Korea. Seropositivity for hepatitis C virus antibody (11.0%, 95% confidence interval: 8.7–13.6) was higher than that for hepatitis B surface antigen (4.4%, 95% confidence interval: 3.0–6.2). Anti-hepatitis C virus seropositivity was associated with a history of repeated acupuncture (odds ratio=2.1, 95% confidence interval: 1.1–4.0), and blood transfusion (odds ratio=5.5, 95% confidence interval: 1.6–19.3) before 1992 when hepatitis C virus screening in blood donors became mandatory. Hepatitis C virus 2a was the most prevalent genotype, followed by 1b. Hepatitis C virus risk attributable to acupuncture was 38% (9% for men and 55% for women). Safer acupuncture practice has become a priority for hepatitis C virus prevention in South Korea.
British Journal of Cancer (2002) 87, 314–318. doi:10.1038/sj.bjc.6600436 www.bjcancer.com
© 2002 Cancer Research UK
hepatitis C virus; hepatitis B virus; acupuncture; blood transfusion; South Korea
The purpose of the present study was to determine whether chronic high-fat diet (HF) induces insulin resistance independently of obesity. We randomly divided 40 rats into two groups and fed them either with a HF or with a high-carbohydrate diet (HC) for 8 weeks. Whole body glucose disappearance rate (Rd) was measured using a euglycemic hyperinsulinemic clamp. Firstly, we defined whether insulin resistance by HF was associated with obesity. Plasma glucose and triglyceride concentrations were significantly increased in HF. Rd was decreased (10.6+/-0.2 vs. 9.1+/-0.2 mg/kg/min in HC and HF, respectively) and the hepatic glucose output rate (HGO) was increased in HF (2.2+/-0.3 vs. 4.5+/-0.2 mg/kg/min in HC and HF, respectively). Rd was significantly correlated with %VF (p<0.01). These results implicate that visceral obesity is associated with insulin resistance induced by HF. In addition, to define whether dietary fat induces insulin resistance regardless of visceral obesity, we compared Rd and HGO between groups 1) after matching %VF in both groups and 2) using an ANCOVA to adjust for %VF. After matching %VF, Rd in HF was significantly decreased by 14% (p<0.001) and HGO was significantly increased by 110% (p<0.001). Furthermore, statistical analyses using an ANCOVA also showed Rd for HF was significantly decreased even after adjusting %VF. In conclusion, we suggest that dietary fat per se could induce insulin resistance in rats fed with chronic HF independently of obesity.
To assess the value of DNA ploidy, flow cytometric analysis was performed on unfixed fresh materials obtained from 86 patients with gastric cancer who underwent stomach resection. We evaluated the DNA content of gastric carcinoma cells from four different sites and compared it with Ki-67 proliferating activity, and other pathologic parameters. The incidence of aneuploid and diploid was similar (48.8% vs. 51.1%). Early gastric carcinoma showed a higher rate of the diploid pattern (75%) compared to that of advanced gastric carcinoma (47.3%). DNA diploidy was noted increasingly in diffuse-type tumors according to Lauren, in signet ring cell type tumor according to WHO classification and in poorly differentiated tumors (p<0.05). Well and moderately differentiated carcinomas revealed the aneuploid pattern more frequently than poorly differentiated tumors. The aneuploidy was associated with high S phase fraction and high proliferative index. Aneuploidy was noted in the mucosa adjacent to the tumor (26%), in the close normal-looking mucosa (7%) and in the remote normal-looking mucosa (3%). This result suggest the possible role of field cancerization in the development of gastric adenocarcinoma.