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Background Ezrin, ERK, STAT3, and AKT are proteins that are overexpressed in various types of cancer, although their expressions in tongue cancer has received less focus. This study aimed to address associations between the expression levels of these proteins and with characteristics of the tumor and patient survival. Methods We performed immunohistochemical staining of ezrin, ERK, STAT3, and AKT in tumors from patients with tongue carcinoma in situ (CIS, n = 17) and tongue squamous cell carcinoma (SCC, n = 46). Statistical differences between the SCC versus the CIS cohorts were estimated by calculations of bivariate odds ratios of low versus high expression of the proteins. Fisher's exact tests were used to appraise interassociations between the proteins, as well as expression levels versus patient and tumor characteristics. Survival based on Kaplan–Meier statistics in combination log‐rank tests were used to address potential effects of the patient and tumor characteristics versus 5‐year survival rate. Results The relative high: low expression of all four proteins in the two cohorts differed, and particularly ERK was markedly overexpressed in the SCC versus the CIS cohort (odds ratio = 45.3, p

Aim:Prevention of medication-related osteonecrosis of the jaw (MRONJ) in patients with osteoporosis requires the cooperation of physicians and dentists. We investigated the knowledge, experience, and behaviour related to medical and dental cooperation for MRONJ prevention in patients with osteoporosis between physicians and dentists practising in the Shiga prefecture., Materials and methods:We conducted a cross-sectional study to investigate the cooperation between practising physicians and dentists for preventing osteonecrosis of the jaw (ONJ) in patients with osteoporosis using 2 separate questionnaires from July 28, 2018, to February 3, 2019, in Shiga prefecture, Japan., Results:Of 461 dentists who were sent the questionnaires at their dental clinics, 307 (67%) responded via fax. Of 846 physicians who were sent the questionnaire at their clinics, 378 (45%) responded via fax. Of these, 268 (32%) were finally analysed because 110 (13%) physicians had never treated patients with osteoporosis; 50% dentists and 24% physicians were familiar with the MRONJ position paper in Japan, and 39% dentists and 9% physicians had encountered MRONJ in their clinical practice. A total of 30% physicians had requested oral health care by a dentist before administering bone-modifying agents (BMA) therapy. The knowledge and experience of MRONJ differed between doctors and dentists., Conclusion:The behaviour of doctors and dentists was insufficient to enable medical and dental cooperation for the prevention of MRONJ in patients with osteoporosis. The lack of cooperation between physicians and dentists during osteoporosis treatment in the Shiga prefecture in Japan is documented in this study.

Detecting the origin of the primary cancer that metastasizes in the oral cavity in patients with multiple primary cancers is challenging because of its rarity and complexity. We present an unusual case of an 86‐year‐old women with a maxillary gingival tumor that was histologically proven to be adenocarcinoma; she had been diagnosed with rectal and lung adenocarcinoma. A multidisciplinary approach involving complementary molecular analysis of KRAS gene mutation helped in the diagnosis of metastatic gingival tumor from rectal cancer.

Microbiota has been thought to be one of important environmental factors for obesity or Type 2 diabetes mellitus. Among oral microbe, Porphyromonas gingivalis, Treponema denticola and Tannellera forsythia are known as risk factors, so called red complex, for periodontitis. Red complex could also be a risk factor for obesity. However, recent study indicated that obesity was not improved by periodontal therapy. Thus, we performed a cross sectional study to reveal the association of oral microbe with body mass index in a healthy population. Healthy individuals were randomly recruited. The infections of oral microbe were identified by Taqman polymerase chain reaction. The relationships between number of red complex and body mass index or waist circumference were analyzed. Two hundred and twenty-two apparently healthy Japanese were enrolled. BMI and waist circumference as well as age, periodontitis, number of brushing teeth were significantly associated with the number of red complex after adjusting covariance. The effect size of body mass index or waist circumference was 0.023 (p = 0.028) or 0.024 (p = 0.024), respectively. Body mass index and waist circumference were independently associated with the number of red complex among apparently healthy Japanese. The current observation implies the possibility that oral microbe was associated with obesity in healthy population.

Objective:To investigate dental appearance and cephalometric features, using a sample of orthognathic and/or orthodontic patients. A special interest was to identify the relationship of the Dental Aesthetic Index (DAI) with anteroposterior basal bone discrepancy (APBBD) and cephalometric indicators.Materials and Methods:A full sample of 159 patients in two Japanese hospitals was used. Each patient was assessed with a preorthodontic dental cast and cephalometric radiography.Results:Malocclusion with APBBD was more prevalent among high DAI subjects (P = .034, OR = 1.04, 95% CI: 1.00–1.08), Class III malocclusion patients (P = .048, OR = 2.32, 95% CI: 1.01–5.34) and male patients (P = .008, OR = 2.96, 95% CI: 1.33–6.61). Participants scoring 88 points (the highest score in this sample) of the DAI had 16.84 times the risk of APBBD of those who scored 17 points (the lowest score in this sample). Patients with APBBD presented with a greater adjusted ANB angle (t = −8.10, P < .001) and a larger adjusted A-B/NF appraisal (t = −9.65, P < .001). The SNA angle (P < .001), the SNB angle (P = .002), the adjusted ANB angle (P = .001), and the adjusted A-B/NF appraisal (P = .035) were associated with DAI scores in cubic regression models.Conclusion:This study has demonstrated a relationship between the DAI and APBBD. Feasibility of using the adjusted ANB angle and the adjusted A-B/NF appraisal to assess severity of APBBD has been confirmed. The DAI may provide a supportive method to evaluate orthognathic needs. Future investigations are indicated.

Aspiration pneumonia is defined as lung injury caused by the contents of the oral cavity, pharynges, and gaster accidentally entering the airway. It is divided broadly into three categories: chemical injury, aspiration of particulate food matter, and injury by pathogenic bacteria. Aspiration pneumonia during general anesthesia is very rare, occurring in only 0.01-0.03% of cases. The process of lung injury by chemical pneumonitis is divided into two phases: direct chemical injury and secondary inflammation reaction in the lung tissue. In severe cases, excess inflammation reaction in the lung tissue leads to a systemic inflammatory response syndrome and causes acute respiratory distress syndrome. We report a case of aspiration pneumonia of gastric juice occurring upon induction of general anesthesia for orthognathic surgery in a 23-year-old male. Immediate treatment in the intensive care unit resulted in satisfactory progress. We confirmed later that he had an esophageal hiatal hernia. It is important to prevent perioperative complications and consider measures for aspiration pneumonia.

To determine whether the presence of periodontitis (PD) and Porphyromonas gingivalis (Pg) in the subgingival biofilm associates with the development of rheumatoid arthritis (RA) in treatment naïve preclinical stage of arthritis patients., 歯周病と関節リウマチ発症との相関を示す. 京都大学プレスリリース. 2015-04-21.

Background: In patients with inflammatory bowel diseases, T-cell activation driven by microflora has been implicated as a mechanism causing clonal expansion and infiltration of CD4 + T cells in colonic lamina propria (LP). We explored a regulatory mechanism preventing infiltration of CD4 + T cells specific to a microbe-associated antigen in the gut. Methods: SCID mice were reconstituted with CD4 + T cells specific to ovalbumin (OVA) and were orally administered with Escherichia coli engineered to produce OVA. Results: OVA-specific CD4 + T cells (KJ1-26 + ) were recruited to colonic LP in an Ag-dependent manner, which was inhibited by adoptive transfer of naturally occurring CD4 + CD25 + T (Treg) cells. KJ1-26 + T cells and Treg cells are localized preferentially to the colonic follicles that contain dendritic cells. In mice given Treg cells, LP CD4 + T cells showed a decrease in proliferative and interferon γ response and an increase in transforming growth factor p 1 response to OVA stimulation. Treg cells inhibited both antigenic activation of effector CD4 + T cells and class II/CD80/CD86 up-regulation of dendritic cells. Conclusion: Treg cells suppress recruitment of CD4 + T cells specific to a microbe-associated antigen to LP, which was associated with colocalization of effector CD4 + T cells and Treg cells in colonic follicles.

1. In the present study we investigated the difference in the distribution of selected cardiovascular disease risk factors among three middle-aged Tanzanian populations with different lifestyles. 2. The prevalence of hypertension and overweight was higher in urban areas than in rural areas. Plasma leptin concentration was also highest in urban areas. Based on these results, we speculated that overweight in the urban population may be partly due to adiposity. 3. Resting energy expenditure was lower in urban areas than in other areas for both genders. These findings suggest that the high prevalence of overweight in the urban population may be partly due to low physical activity levels.

Ags administered orally at a high dose are absorbed in immunogenic forms and perfuse the liver, which raises a question regarding the relevance of hepatic lymphocyte activation to the systemic hyporesponsiveness against the ingested Ag. Oral administration of 100 mg of OVA to the mice led to massive cell death of OVA-specific (KJ1-26+) CD4+ T cells by Fas-Fas ligand (FasL)-mediated apoptosis in the liver, which was associated with the emergence of hepatic KJ1-26+CD4+ T cells expressing FasL. Hepatic CD4+ T cells in OVA-fed mice secreted large amounts of IL-4, IL-10, and TGF-β1 upon restimulation in vitro and inhibited T cell proliferation. Adoptive transfer of these hepatic CD4+ T cells to naive mice and subsequent antigenic challenge led to suppression of T cell proliferation as well as IgG Ab responses to OVA; this effect was mostly abrogated by a blocking Ab to FasL. i.p. administration of an Ag at a high dose also generated hepatic CD4+FasL+ T cells with similar cytokine profile as T cells activated by oral administration of Ags at a high dose. Finally, we did not see an increase in FasL+ cells in the hepatic CD4+Vβ8+ T cell subset of MRL/lpr/lpr mice given staphylococcal enterotoxin B, indicating the requirement for Fas-mediated signals. These hepatic CD4+FasL+ regulatory cells may explain the tolerogenic property of the liver and play roles in systemic hyporesponsiveness induced by an Ag administered at a high dose.

Trigeminal neuralgia is associated with various symptoms. Its causes are also diverse, including oral infection, tumorous lesions, and vascular compression of nerves. Trigeminal neuralgia with intracranial disease is rarely encountered in daily medical practice.We describe our experience with trigeminal neuralgia caused by intracranial disease. This case was diagnosed by early head CT scan and improved after cerebral nerve surgery.

20歳未満の舌癌患者はまれであることことから, どの治療法を選択するかについての統一した見解が得られていないのが実情であり, その選択に際しても術後の機能障害などの配慮が必要である。また若年者であることから病名の告知やインフォームドコンセントなど, 家族の協力が必要となってくる。今回, 18歳男子高校生の若年者舌癌の症例を経験したのでその概要を報告する。症例は18歳男子高校生, 1998年3月14日右側舌縁部接触痛を主訴に当科受診。右側舌縁部に境界明瞭で表面不整な硬結を伴った15×10mmの腫瘤・潰瘍性病変を認めた。初診時に生検を施行し, 中分化型扁平上皮癌 (TINOMO) の診断を得た。若年者であることから治療後の機能障害を考慮し, かつ根治的治療を目的に外科療法 (右側舌部分切除術) と術前・術後化学療法 (シスプラチン, ペプロマイシン) を1クール施行した。術後化学療法による軽度の副作用を一過性に認めたが, 局所は舌尖が保存できたことから著明な舌の機能障害は認めなかったため経過観察となった。約1年後, 頚部リンパ節転移を認めたために右側全頚部郭清術を施行した。術後17か月, 全身・局所ともに良好で経過観察中である。なお, 若年者であり, また両親の希望もあって告知をせずにいたが, 加療期間が長期に渡るにつれて病態とそれに対する治療への相違に困惑し, 精神的に不安定になった。告知せずに加療を続けて行けるように努めたが, 患者本人の治療への理解を得られず, 加療途中に両親から本人へ癌告知をせざるを得なくなるという不測の事態が生じ, あらためて若年者癌での病名の告知やインフォームドコンセントの難しさを痛感した。

Objective: The use of electronic medical record (EMR) data is necessary to improve clinical research efficiency. However, it is not easy to identify patients who meet research eligibility criteria and collect the necessary information from EMRs because the data collection process must integrate various techniques, including the development of a data warehouse and translation of eligibility criteria into computable criteria. This research aimed to demonstrate an electronic medical records retrieval system (ERS) and an example of a hospital-based cohort study that identified both patients and exposure with an ERS. We also evaluated the feasibility and usefulness of the method. Design: The system was developed and evaluated. Participants: In total, 800 000 cases of clinical information stored in EMRs at our hospital were used. Primary and secondary outcome measures: The feasibility and usefulness of the ERS, the method to convert text from eligible criteria to computable criteria, and a confirmation method to increase research data accuracy. Results: To comprehensively and efficiently collect information from patients participating in clinical research, we developed an ERS. To create the ERS database, we designed a multidimensional data model optimised for patient identification. We also devised practical methods to translate narrative eligibility criteria into computable parameters. We applied the system to an actual hospital-based cohort study performed at our hospital and converted the test results into computable criteria. Based on this information, we identified eligible patients and extracted data necessary for confirmation by our investigators and for statistical analyses with our ERS. Conclusions: We propose a pragmatic methodology to identify patients from EMRs who meet clinical research eligibility criteria. Our ERS allowed for the efficient collection of information on the eligibility of a given patient, reduced the labour required from the investigators and improved the reliability of the results. ARTICLE SUMMARY

Oral bisphosphonates (BPs) represent the first line of prevention and treatment for osteoporosis. However, several studies have reported osteonecrosis of the jaw (ONJ), also known as osteomyelitis of the jaw (OMJ), as a side effect of these drugs. Although absolute risk is suggested to be low, information to date on the relative risk or attributable risk has in fact been limited. Here, we estimated risk of oral BPs for OMJ in osteoporosis patients taking oral BPs compared with other osteoporosis drugs. Using an electronic medical records retrieval system and manual confirmation of OMJ, we conducted a retrospective cohort study of patients taking medications for osteoporosis at Kyoto University Hospital between November 2000 and October 2010. To evaluate relative risks of oral BPs for OMJ, logistic regression analysis was performed and odds ratios (ORs) and 95% confidence interval (CIs) were estimated. In addition, sensitivity analyses were performed according to hierarchical diagnosis. A total of 4129 patients (59.6%) were prescribed BPs while 2794 (40.3%) received other osteoporosis drugs. Absolute risk for OMJ was estimated to range from 0.46% to 0.99% (95% CIs: 0.25-0.66 to 0.69-1.2) among patients receiving oral BPs and 0.071% to 0.17% (95% CIs: 0-0.17 to 0.022-0.33) among patients receiving other osteoporosis drugs. The attributable risks of oral BPs for OMJ were estimated to range from 0.38% to 0.81% (95% CIs: 0.38-0.39 to 0.80-0.81). ORs (95% CIs) adjusted for confounding factors were 5.0 (1.9-12.9) to 6.0 (1.3-26.1) for confirmed cases only. In terms of absolute and attributable risks, the risk of oral BPs for OMJ is considered to be less than 1% in patients with osteoporosis. However, oral BPs may increase the risk of OMJ compared with patients treated with other osteoporosis medications and the risk of side effects should be kept in mind.

This study estimated the cumulative incidence and risk ratio for osteonecrosis of the jaw (ONJ) after tooth extraction in patients with and without administration of bisphosphonates (BP) and identified potential risk factors for bisphosphonate-induced osteonecrosis of the jaw (BIONJ). A cohort study was conducted in all patients undergoing tooth extraction at a university hospital in Japan from April 2006 to June 2009. Of 3216 patients, 126 had BP administration, of whom 5 (3.9%, 95% confidence interval (CI): 1.2-9.2) developed ONJ, versus 1 (0.032%, 95% CI: 0.00081-0.18) among 3090 patients without BP administration. BP administration was associated with the development of ONJ after tooth extraction, with an unadjusted risk ratio of 122.6 (95% CI: 14.4-1041.8). When stratified by age and route of BP administration, the risk ratio for ONJ patients aged 65 years or older with intravenous BP administration compared to those without was 200.2 (95% CI: 23.8-1679.4, P

The purpose of this cross-sectional study was to investigate the association of periodontitis and/or tooth loss with hypertension by excluding the common confounders. Eighty-one Tanzanian women who were aged 46–58 years, nonsmokers, nonalcoholic drinkers, and on no medication underwent clinical examination. Multiple-regression analysis showed that the severity of periodontitis was significantly correlated with increased systolic blood pressure and diastolic blood pressure. Simple-regression analysis indicated that the severity of periodontitis was inversely correlated with 24-hour urinary excretion of potassium (r=-0.579,P=0.0004) and also inversely with the frequency of intakes of green vegetables (r=-0.232,P=0.031) and fruits (r=-0.217,P=0.0043). Low-potassium intake in the diet mostly accompanied by low dietary fiber intake increases BP as well as periodontal inflammation. Potassium intake may be an important factor linking periodontitis and hypertension in middle-aged nonsmoking and nonalcoholic women on no medication, although chronic inflammation such as periodontitis may cause hypertension through a more direct mechanism.

Background and Aim: Dysregulated immune responses in the gut to luminal antigens can cause inflammatory bowel diseases (IBD). The roles played by dietary antigens in the pathogenesis or prevention of IBD are poorly understood. Soybean isoflavones are digested in large amounts and have many biological activities. The aim of this study was to determine whether isoflavones in aglycon and bioavailable forms have any effect on gut immunity and protect the host from tissue damage in a mouse model of colitis. Methods: We administered daidzein-rich isoflavone aglycones (DRIA) to mice for 1 week and then treated them with 2% dextran sodium sulfate (DSS) in drinking water for 4 days to induce colitis. The effect of DRIA was evaluated by examining the histopathology of the colon, body weight changes, and functional analysis of mesenteric lymph node cells (MLN). Results: DRIA inhibited interleukin (IL)-6 and IL-8 production by Toll-like receptor (TLR)2, and TLR4-stimulated monocytes in a dose-dependent manner. The mice administered DRIA had less inflammation and tissue damage in the colon than the control mice. This protective effect of DRIA was associated with a decrease in interferon-γ, IL-6, and IL-12p40 secretion, and an increase in IL-10secretion and low cell-activation status of antigen-presenting cells (APC) in MLN. Conclusion: Ingested DRIA can downregulate the functions of APC and inhibit DSS colitis.

Colonization of Helicobacter pylori in the stomach leads to chronic gastritis with massive infiltration by Th1 cells. To assess a role played by those T cells in the remodeling of gastric epithelium, we activated gastric T cells utilizing mice with CD4 T cells bearing transgenic TCR with or without deficiency in either IL-4 or IFN-γ or IL-12. Mice developed gastritis upon injection of an antigen into gastric mucosa. While neutrophil infiltration occurred even with a control antigen, infiltration by transgenic T cells was dependent on the specific antigen. The numbers of epithelial cells undergoing apoptosis and regeneration were increased in the mice with infiltrating T cells producing IFN-γ and the alignment of those cells in the glands was markedly dysregulated. In contrast, mice deficient in Th1 response showed no increase in cell division and apoptosis of epithelial cells. Thus, Th1 type T cells infiltrating into gastric mucosa play an independent role in controlling turnover of epithelial cells.

Administration of an antigen (Ag) per oral route leads to apoptosis of Ag-specific CD4(+) T cells and to development of Th2 cells expressing Fas ligand (FasL) in the liver. We determined whether presentation of an ingested Ag in the liver alone was enough to select these FasL(+)Th2 cells and explored how this selection was achieved in the liver. Ovalbumin (OVA) administered orally was colocalized with class II(+) cells in the periportal and parenchymal area of the liver. On coculture with naive OVA-specific CD4(+) T cells, hepatic CD11c(+) cells from mice fed OVA generated Ag-specific Th2 cells. This was achieved by apoptosis of CD4(+) T cells, decrease of interleukin 12 (IL-12) secretion, and increase of IL-18 secretion by the CD11c(+) cells. Addition of IL-12 to this coculture prevented apoptosis of the CD4(+) T cells, which was associated with up-modulation of IL-2 receptor beta chain expression. Administration of IL-12 to mice fed OVA prevented apoptosis of OVA-specific CD4(+) T cells in the liver. Moreover, adoptive transfer of hepatic CD11c(+) cells from mice fed OVA together with OVA-specific CD4(+) T cells led to development of Th2 cells as well as apoptosis of the transferred CD4(+) T cells in the lymph nodes of the recipient mice on immunization with OVA. In conclusion, presentation of an ingested Ag by hepatic CD11c(+) cells selects Th2 cells resistant to apoptosis in the liver, which is mediated in part by down-regulation of IL-12 secretion by the former cells.

To assess the relationship between dietary factors and cardiovascular (CVD) risk factors in middle-aged men and women, in urban, rural and pastoral settings in Tanzania.Cross-sectional epidemiological study designed according to the protocol of the World Health Organisation (WHO) Cardiovascular Diseases and Alimentary Comparison (CARDIAC) study.Three centres in Tanzania, namely Dar es Salaam (urban), Handeni (rural) and Monduli (pastoral population).The subjects, aged 47-57 years, were recruited randomly from administrative lists available from each centre.Blood pressure (BP) was measured using a centrally calibrated automatic BP machine (Khi machine). Dietary history of the participants was obtained using a standard questionnaire designed on the basis of a seven-day recall system. Height, weight, serum total cholesterol (TC) and high-density lipoprotein cholesterol (HDLC), haemoglobin A1c, sodium, potassium and magnesium were measured.The prevalence of hypertension (BPor = 140/90 mmHg or antihypertensive drug use), obesity (body mass index (BMI)or = 30 kg/m2) and hypercholesterolaemia (TC5.2 mmol/l) were lowest in the rural area. Consumption of green vegetables, milk, coconut milk, meat, and fish varied significantly between the three areas. Important determinants for BP among men were BMI (p0.001), and salt intake (p0.05). Among women, TC (p0.05), age (p0.05), BMI (p0.001) and coconut milk consumption (p0.001) were important BP determinants. Salt intake was positively associated with systolic BP (SBP) and diastolic BP (DBP) in men but not among women (both SBP and DBP p0.05 respectively). Dietary determinants of serum TC were meat, fish and green vegetable consumption.Differences in dietary habits contributed significantly to the urban-rural-pastoral variations in CVD risk pattern in Tanzania.

Background: Although T-cell responses to food antigens are normally inhibited either by deletion, active suppression, or both of antigen-specific T cells, T helper cells for IgE response to a food antigen still develop by unknown mechanisms in a genetically susceptible host. Objective: We determined the site at which those IgE helper T cells develop. Methods: We administered ovalbumin (OVA) orally to DO11.10 mice and studied CD4 + T cells in Peyer's patches, the spleen, and the liver. Helper activity for IgE response was assessed by adoptively transferring those CD4 + T cells to naive BALB/c mice, followed by systemic immunization with OVA. Results: OVA-specific CD4 + T cells were deleted by cell death in the liver and Peyer's patches of DO11.10 mice fed OVA. OVA-specific CD4 + T cells that survived apoptosis in the liver expressed Fas ligand and secreted IL-4, IL-10, and transforming growth factor β 1 . CD4 + T cells producing IFN-γ were deleted in the liver by repeated feeding of OVA. On transfer of CD4 + T cells to naive mice and systemic immunization with OVA, a marked increase in OVA-specific IgE response developed only in the mice that received hepatic CD4 + T cells from OVA-fed mice, the effect of which was not observed in the recipients of hepatic CD4 + T cells deficient in IL-4. In addition, significant suppression of delayed-type hypersensitivity and IgG 1 /IgG 2a responses to OVA was observed in the recipients of hepatic CD4 + T cells, and this suppression required Fas/Fas ligand interaction. Conclusion: Together, these results suggested that a food antigen might negatively select helper T cells for IgE response to the antigen by preferential deletion of T H 1 cells in the liver. (J Allergy Clin Immunol 2003;111:1375-85.)

Background & Aims: Clonal expansion of T cells is associated with inflammatory bowel diseases, which indicates antigenic activation of the T cells. We investigated whether the introduction of CD4 T cells specific to a microflora would initiate colitis and assessed the cytokine requirements for colitogenic CD4 T cells. Methods: Severe combined immunodeficiency disease (SCID) mice were reconstituted with CD4 T cells, which were either deficient in interleukin (IL)-4/interferon (IFN)-γ production or differentiated in vitro to T-helper (Th) 1/Th 2 and bearing a transgenic T-cell receptor (TCR) specific to ovalbumin (OVA), and then inoculated with an Escherichia coli –producing OVA (ECOVA). Clinical and histologic manifestations of colitis were assessed. Results: Mice with ECOVA colonization and OVA-specific CD4 T cells developed colitis with histologic features of focal infiltration by mononuclear cells, destruction of crypts, and loss of goblet cells. Further, infiltration was initiated in pre-existing lymph follicles. Th1- and IL-4 deficient T cells were diffusely localized in the lamina propria and submucosa, whereas Th2- and IFN-γ–deficient T cells were localized preferentially in lymph follicles. Conclusions: A microbe-associated antigen, non–cross-reactive to colonic tissue, can drive antigen-specific CD4 T cells to cause colitis in SCID mice. Although the presence of IFN-γ and IL-4 in the effector CD4 T cells was not an absolute requirement for the development of colitis, they seemed to regulate it in part by modulating migration of the effector T cells. GASTROENTEROLOGY 2002;123:1949-1961

To examine the relationship between obesity and lipid profiles and to compare the effects of total obesity and central adiposity on lipids in three locations in Tanzania.Cross-sectional epidemiological study.Three areas in Tanzania: Dar es Salaam (urban), Handeni (rural) and Monduli (pastoralists), in August 1998.Five hundred and forty five men and women from a random sample of 600 people aged 46-58 years.Mean BMI, waist circumference, WHR, TC, HDL-C, LDL-C, TG and LDL/HDL ratio. Prevalence rates of overweight,obesity, central obesity and dyslipidaemia.As compared to men, women had higher BMI (24.7 versus 22.5 kg/m2, p0.0001), waist circumference (92.4 versus 89.1 cm, p0.05), TC (4.9 versus 4.2 mmol/L, p0.0001) and LDL-C (3.3 versus 2.6 mmol/L, p0.0001). The urban population demonstrated higher levels of lipid factors than the rural population (TC, men 4.8 mmol/L; women 5.3 mmol/L, p0.0001; TG, men 3.6 mmol/L; women 3.7 mmol/L, p0.0001, LDL-C, men 2.8 mmol/L, p0.0001). BMI and waist circumference correlated positively with serum TC, TG, and LDL-C in both genders. Stepwise regression analysis showed that BMI predicted triglyceride concentration in men (p0.05) and women (p0.0001). Waist circumference predicted levels of TC in women only (p0.0001) and of LDL-C in both genders (men p0.05, women p0.0001). The prevalence of overweight, obesity and central obesity were significantly higher in urban than in rural areas in both men and women. Compared to lean subjects, obese men and women had significantly higher mean serum TC, TG, LDL-C and a higher prevalence of dyslipidaemia. The mean levels of TC, TG and LDL cholesterol increased across successive increases in BMI and waist circumference quintiles in both genders.Subjects from the urban area had greater lipid abnormalities related to obesity than those from the rural area and that, central adiposity had a greater effect on total cholesterol and LDL cholesterol among women than was BMI.

Although some animal models suggest an involvement of CD4 T cells reactive to luminal microbial antigen(s) for the pathogenesis of inflammatory bowel diseases (IBD), direct linkage between microflora-driven clonal expansion of CD4 T cells and the development of colitis has not been well studied. Here, BALB/c and SCID mice were given CD4 T cells purified from Rag-2(-/-) mice crossed to transgenic mice expressing TCR specific to ovalbumin (OVA) then administered with antibiotic-resistant Escherichia coli producing OVA (ECOVA) or LacZ (ECLacZ) via the rectum. The ECOVA-inoculated BALB/c and SCID mice developed a subacute colitis with microscopic features of distortion of crypt architecture, loss of goblet cells, and focal infiltration by mononuclear cells in the lamina propria (LP) and submucosa. Expanding OVA-specific CD4 T cells were detected in colonic follicles of mice with ECOVA. Early in colitis, OVA-specific CD4 T cells producing IFN-gamma predominate in the LP of the colon, which was followed by an emergence of OVA-specific CD4 T cells producing IL-4 and IL-10 at a later time point. Co-transfer of an IL-10-secreting OVA-specific CD4 T cell line prevented colitis. Thus, an expansion of CD4 T cells monospecific to OVA, an antigen non-cross-reactive to colonic tissue, can mediate both induction and inhibition of the colitis which was associated with hyperplasia of lymph follicles.

In this assessment of cardiovascular risk factors, we examined the prevalence of selected risk factors according to the World Health Organisation (WHO) CARDIAC Study protocol and compared them with a similar study conducted more than a decade ago. The survey was carried out in Dar es Salaam (D, urban), Handeni (H, rural) and Monduli (Mo, semi-nomadic area). Subjects aged 47-57 were recruited randomly for blood pressure and anthropometrical measurements, 24 h urine collection and blood sampling. A structured questionnaire was used to obtain dietary information. The 1998 survey studied 446 subjects, while the 1987 survey included 496 men and women. The measured weight, body mass index (BMI) and prevalence of obesity (BMIor = 30 kg/m(2)) increased significantly among women in the 1998 survey in rural Handeni and urban Dar. The overall prevalence of obesity was higher for women in the most recent survey (22.8%, P0.0001). Diastolic blood pressure (DBP) was higher in the most recent survey for women in Handeni. The overall prevalence of hypertension (blood pressure160/95 mmHg, or antihypertensive drug use), rose to 41.1% in 1998, (P0.001) for men and to 38.7% (P0.05) for women. The mean total serum cholesterol and prevalence of hypercholesterolaemia increased significantly in the most recent survey in the three studied areas. The overall prevalence of hypercholestrolaemia (serum cholesterol5.2 mmol/l) was higher in the 1998 survey for both men (21.8%, P0.0001) and women (54.0%, P0.0001). The mean HDL cholesterol increased significantly in the most recent survey, with a significant reduction in the mean atherogenic index, though these were still at higher levels (men 5.8, P0.0001; women 5.1, P0.0001 vs. 1987). A strong positive correlation was observed between blood pressure (SBP and DBP) and body mass index, total serum cholesterol and sodium to potassium ratio. These data suggest that for the past decade there has been an increase in the mean levels and prevalence of selected cardiovascular risk factors in Tanzania.

1. In the present study we investigated the difference in the distribution of selected cardiovascular disease risk factors among three middle-aged Tanzanian populations with different lifestyles. 2. The prevalence of hypertension and overweight was higher in urban areas than in rural areas. Plasma leptin concentration was also highest in urban areas. Based on these results, we speculated that overweight in the urban population may be partly due to adiposity. 3. Resting energy expenditure was lower in urban areas than in other areas for both genders. These findings suggest that the high prevalence of overweight in the urban population may be partly due to low physical activity levels.

Background Several studies have reported osteomyelitis of the jaw (OMJ) as a side effect of bisphosphonates (BPs), and the risk of oral BPs has been recently clarified. However, other systemic risk factors of OMJ remain unclear. Importantly, the possibility of risk classification based on the clinical characteristics of patients has not been explored. Here, we clarified risk factors of OMJ and evaluate the predictive accuracy of risk indices in osteoporosis patients. Methods We performed sub-analysis using a database developed for a retrospective cohort study in patients taking medications for osteoporosis at Kyoto University Hospital. Risk indices for OMJ were constructed using logistic regression analysis, and odds ratios (OR) for OMJ cases and 95% confidence intervals (CI) were estimated. Potential risk factors included in the statistical analysis were age; sex; diabetes; use of oral BPs, corticosteroids, cancer chemotherapy, antirheumatic drugs, and biologic agents; and their interactions. Risk indices were calculated by the sum of potential risk factors of an individual patient multiplied by the regression coefficients. The discriminatory power of the risk indices was assessed by receiver operating characteristic (ROC) analysis. Results In analysis of all patients, oral BPs (OR: 4.98, 95% CIs: 1.94-12.75), age (OR: 1.28, 95% CI: 1.06-1.60) and sex-chemotherapy interaction (OR: 11.70, 95% CI: 1.46-93.64) were significant risk factors of OMJ. Areas under the ROC curves of these risk indices provided moderate sensitivity or specificity regardless of group (0.683 to 0.718). Conclusions Our data suggest that oral BP use, age, and sex-chemotherapy are predictors of OMJ in osteoporosis patients. The risk indices are moderately high, and allow the prediction of OMJ incidence.

Background Recent reports suggest the correlation between rheumatoid arthritis (RA) and periodontal disease (PD). However, it is not clear whether PD affects the disease activity of arthritis or the future introduction of methotrexate (MTX) treatment in non-treated, undifferentiated arthritis patients. Objectives To study whether PD affects arthritis activity and introduction of MTX treatment in non-treated, undifferentiated arthritis patients. We also investigated the relationship between a representative periodontal bacteria, Porphyromonas gingivalis (Pg), and arthritis activity or anti-citrullinated protein (CCP) antibody. Methods We conducted a prospective cohort study in Kyoto University Hospital, Japan. We consequently enrolled patients who first visited the Rheumatic Disease Center without prior use of anti-rheumatic drugs or corticosteroids from May in 2011 to October in 2012. Arthritis disease activity (SDAI etc.) as well as anti-CCP antibody was systemically investigated by rheumatologists. Clinical parameters of PD (pocket depth, etc.) and subgingival plaque samples were collected by dentists and Pg genomic DNA was determined by Taqman q-PCR. Clinical PD was defined as maximal pocket depth more than 4 mm. We followed up all patients until January 2013. Results We enrolled 103 patients, and 11 patients with osteoarthritis 4 patients with remaining teeth less than 10 teeth were excluded from the analysis. PD was associated with higher arthritis disease activity (SDAI 12.9±1.3 in PD group vs 7.3±1.3 in non-PD group, p=0.017), even adjusted for age, sex, smoking, or tooth brushing habit (effect size 0.11, p=0.004). Presence of PD in the first visit was a risk factor for the introduction of MTX treatment in the clinical course (Log-rank p=0.013, Hazard risk 2.77 (95%CI 1.23-6.25)). Although the amount of Pg was associated with pocket depth, it did not correlate with SDAI (10.7±1.6 in PD group vs 10.7±1.3 in non-PD group) or introduction of MTX treatment (Log-rank p=0.72). Either clinical PD or Pg did not correlate with anti-CCP antibody titers in this cohort. Conclusions Clinical PD, but not the presence of Pg, was significantly associated with arthritis activity and predicts the future development of chronic inflammatory arthritis that requires MTX. Disclosure of Interest None Declared