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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Repeated injections of adult mice with recombinant murine TNF prolong the survival of NZB/W F1 mice, and suppress type I insulin-dependent diabetes mellitus (IDDM) in non-obese diabetic (NOD) mice. To determine whether repeated TNF injections suppress T cell function in adult mice, we studied the responses of influenza hemagglutinin-specific T cells derived from T cell receptor (HNT-TCR) transgenic mice. Treatment of adult mice with murine TNF for 3 wk suppressed a broad range of T cell responses, including proliferation and cytokine production. Furthermore, T cell responses of HNT-TCR transgenic mice also expressing the human TNF-globin transgene were markedly reduced compared to HNT-TCR single transgenic littermates, indicating that sustained p55 TNF-R signaling is sufficient to suppress T cell function in vivo. Using a model of chronic TNF exposure in vitro, we demonstrate that (a) chronic TNF effects are dose and time dependent, (b) TNF suppresses the responses of both Th1 and Th2 T helper subsets, (c) the suppressive effects of endogenous TNF produced in T cell cultures could be reversed with neutralizing monoclonal antibodies to TNF, and (d) prolonged TNF exposure attenuates T cell receptor signaling. The finding that anti-TNF treatment in vivo enhances T cell proliferative responses and cytokine production provides evidence for a novel regulatory effect of TNF on T cells in healthy laboratory mice. These effects are more pronounced in chronic inflammatory disease. In addition, our data provide a mechanism through which prolonged TNF exposure suppresses disease in animal models of autoimmunity.
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PMID:Chronic tumor necrosis factor alters T cell responses by attenuating T cell receptor signaling. 915 95

In the Netherlands the general practitioner (GP) plays an important role in prevention. Every Dutch citizen has to be registered with one GP and GPs know their patients well. Face-to-face contact is a relatively effective means of influencing behavior; if preventive advice is related to a patient's state of health, compliance may be stimulated. However, Dutch GPs have shown reluctance toward preventive work. Curing rather than preventing disease is emphasized in medical school. Many GPs doubt that they are entitled to interfere with a patients' lifestyle unless asked. Some GPs are aware of their limited knowledge of nutrition. Preventive work requires some reorganization of medical practice and can lead to an increased workload, without financial compensation. Then there is the "prevention paradox": preventive actions that have a demonstrable effect on the whole population bring only small benefits for individuals. Since 1989 the Dutch College of General Practitioners has published 60 standards for general practice. Several of these include advice on lifestyle and diet, eg, for non-insulin-dependent diabetes mellitus, hypertension, hypercholesterolemia, peptic ulcer, and heart failure. Prevention work in general practice must use only interventions proved to be effective and they must be feasible in the context of general practice. A trial collaboration of 118 GPs and 5 public health authorities between 1988 and 1990 for screening and lifestyle management of hypertension was a limited success. It brought to light the practical problems of this type of work in general practice. Present government priorities for GP-public health collaboration are influenza vaccination and cervical screening.
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PMID:Challenges to prevention in Dutch general practice. 917 99

Influenza viruses are highly contagious viruses that are transmitted from person to person, usually by the airborne route. Persons in semi-closed or crowded environments, such as students and residents of nursing homes, are at high risk of exposure. The illness attack rate in children ranges from 14% to 40% yearly. Fatality rates are highest in persons who have chronic medical conditions, such as chronic obstructive lung disease, cardiovascular disease, and diabetes mellitus, particularly if they are elderly. The effectiveness of influenza vaccine in preventing or attenuating illness varies, depending primarily on (1) the degree of similarity between the virus strains included in the vaccine and those that circulate during the influenza season, and (2) the age and immunocompetence of the vaccine recipient. When there is a good match between vaccine and circulating viruses, influenza vaccine has been shown to prevent illness in approximately 70% to 90% of healthy persons less than 65 years of age. Adverse events following influenza vaccine include mild, local reactions at the injection site (up to 20%) and occasionally fever in approximately 1% of vaccinees. Despite the availability of an effective vaccine, only 55% of persons 65 years of age and older reported receiving influenza vaccine in 1994. Vaccination levels are even lower in persons less than 65 years of age with high-risk medical conditions. Important procedures to improve vaccination rates are (1) assessment of a practice's or medical facility's current vaccination rates, (2) identification of target populations for vaccination, (3) formation of a specific goal (ie, percentage of target population to be immunized), (4) development of a plan of action, and (5) provision of ongoing feedback to the individual physicians about vaccination rates of their own patients.
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PMID:Influenza, influenza vaccine, and amantadine/rimantadine. 926 68

Several recent trends in the vital statistics of the United States continued in 1996, including an increase in life expectancy and declines in infant mortality, births to teenage mothers, age-adjusted death rates, and death rates for children and adolescents. In 1996, there were an estimated 3 914 953 births in the United States. The preliminary birth rate remained unchanged at 14.8 births per 1000 population, and the fertility rate, births per 1000 women 15 to 44 years of age, was essentially the same at 65.7. Fertility rates rose slightly for most racial and ethnic groups except black women, for whom the rate hit a historic low of 70.8. Overall, fertility remains particularly high for Hispanic women, although there is considerable variation within this heterogenous group. For the fifth consecutive year, birth rates dropped for teenagers. Birth rates for women >/=30 years of age continued to increase. The birth rate for unmarried women declined 1% in 1996 to 44.6 births per 1000 unmarried women, continuing the decline noted in 1995 for the first time in 2 decades. The percentage of women who began prenatal care in the first trimester rose in 1996 to 81.8%, whereas the percentage with late (third trimester) or no care dropped to 4.1%. The rise in timely prenatal care was greatest for black and Hispanic women. The percentage of low birth weight (LBW) infants reached 7.4% in 1996, its highest level since 1975. The very low birth weight rate remained unchanged at 1.4%. The rise in LBW occurred primarily among white women, whereas the LBW rate for black women dropped to 13.0%, the lowest rate reported since 1987. The rise among white women is only partially a result of increases in multiple births, because LBW rates have also risen among white singleton births. The multiple birth ratio rose again in 1996 by 2%, as it has since 1980. The rise was particularly large for higher-order multiple births. Infant mortality reached an all time low level of 7.2 deaths per 1000 births, based on preliminary 1996 data. Neonatal and postneonatal rates declined, as did rates for both black and white infants. National birth weight specific mortality rates are reported here for the first time. In 1995, 63% of infant deaths occurred to the 7.3% of the population that was born LBW. The four leading cause of infant death were congenital anomalies, disorders relating to short gestation and unspecified birth weight, sudden infant death syndrome, and respiratory distress syndrome, accounting for more than half of infant deaths in 1996. Despite the declines in infant mortality, the United States continues to rank poorly in international comparisons of infant mortality. Expectation of life at birth reached a new high in 1996 of 76.1 years for all gender and race groups combined. Age-adjusted mortality rates declined in 1996 for diseases of the heart, malignant neoplasms, cerebrovascular diseases, accidents and adverse effects, chronic liver disease and cirrhosis, and suicide. They rose, as in the past several years, for chronic obstructive pulmonary diseases, diabetes mellitus, and pneumonia and influenza. For the first time since human immunodeficiency virus infection was created as a special cause-of-death category in 1987, death rates for human immunodeficiency virus infection declined from 15.6 in 1995 to 11.6 in 1996. The homicide rate also declined, as it has since 1991. Death rates for children between 1 and 19 years of age declined in 1996, with an estimated 29 183 deaths to children. Unintentional injury mortality has dropped by approximately 50% among children and adolescents since 1979, although it remains the leading cause of death for all age groups of children from 1 to 19 years. Homicide was the fourth leading cause of death for children 1 to 4 and 5 to 9 years of age, the third leading cause for children 10 to 14, and the second leading cause for 15 to 19 year olds.
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PMID:Annual summary of vital statistics--1996. 978 65

Mice that express influenza hemagglutinin under control of the rat insulin promoter (INS-HA) as well as a class II major histocompatibility complex (MHC)-restricted HA-specific transgenic TCR (TCR-HA), develop early insulitis with huge infiltrates, but progress late and irregularly to diabetes. Initially, in these mice, INS-HA modulates the reactivity of antigen-specific lymphocytes, such that outside the pancreas they do not cause lethal shock like their naive counterparts in single transgenic TCR-HA mice, when stimulated with high doses of antigen. Inside the pancreas, the antigen-specific cells do not initially attack the islet cells, and produce some IFN-gamma as well as IL-10 and IL-4. Spontaneous progression to diabetes, which can be accelerated by cyclophosphamide injection, is accompanied by a 10-fold increase in IFN-gamma and a 3-fold decrease in IL-10 and IL-4 production by the locally residing antigen-specific T cells. Also, total islets from non-diabetic mice contain more TNF-alpha, compared with diabetic mice. This scenario is consistent with the view that beta cell destruction depends upon the increased production of certain pro-inflammatory cytokines by infiltrating T cells. Our inability to detect Fas expression on beta cells, but not on lymphoid cells, in diabetic and non-diabetic mice, puts some constraints on the role of Fas in beta cell destruction.
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PMID:Changes in function of antigen-specific lymphocytes correlating with progression towards diabetes in a transgenic model. 942 42

Continuous antigenic stimulation in vivo can result in the generation of so-called "anergic" CD4(+) or CD8(+) T cells that fail to proliferate upon antigenic stimulation and fail to develop cytolytic effector functions. Here we show that class II major histocompatibility complex-restricted T cells specific for influenza hemagglutinin (HA) that become anergic in mice expressing HA under control of the immunoglobulin kappa promoter exhibit an impaired effector function in causing diabetes in vivo, as compared to their naive counterparts, when transferred into immunodeficient recipients expressing HA under the control of the insulin promoter. Furthermore, HA-specific T cells anergized in vivo contain higher levels of interleukin (IL)-4 messenger RNA (mRNA) than naive and recently activated T cells with the same specificity and more than a 100-fold higher levels of IL-10 mRNA. The higher expression of the IL-10 gene is also evident at the protein level. These findings raise the interesting possibility that T cells rendered anergic in vivo have in fact become regulatory T cells that may influence neighboring immune responses through the release of IL-10.
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PMID:Interleukin 10 secretion and impaired effector function of major histocompatibility complex class II-restricted T cells anergized in vivo. 943 75

To investigate the clinical and serological responses to an inactivated influenza vaccine (split-virion A/Singapore/6/86-like strains H1N1 (15 ug HA), A/Beijing/353/89-like H3N2 (15 ug HA) and B/Yamagata/16/88-like strain (15 ug HA): MFV-JECT, Merieux, UK) in persons with HIV infection, diabetes, obstructive lung diseases, elderly adults and healthy volunteers. Forty-nine HIV-infected persons received 2 doses of the vaccine at one-month intervals; 34 healthy volunteers, 30 elderly persons, 29 with insulin and non-insulin diabetes and 14 with obstructive airways diseases were vaccinated with one single dose between October 1992 to January 1993. Serological testing of antibody responses was done using haemagglutination assay. Beta2-microglobulin in HIV-infected persons was measured using radioimmunodiffusion between 1st and 2nd dose. Fructosamine levels in diabetic persons were assessed for diabetic control and peak expiratory flow rate (PEFR) was self monitored in persons with lung diseases. All groups apart from the elderly filled in a symptom score chart for the first 5 days following vaccination. A 4-fold rise in titre equal to or more than 1:64 to all the 3 antigens occurred in 20 (58.8%) of healthy volunteers compared with 13 (44.8%) diabetics, 5 (35.7%) with lung diseases, 10 (33.3%) elderly and 13 (26.5%) with HIV infection. A significant correlation of serological response to number of CD4 count in persons with HIV infection was noted (H1N1 P=0.0013, H3N2 P=0.025, BYAM P=0.0018). Mean beta2-microglobulin levels did not change significantly post 1st and 2nd vaccination. Mean fructosamine level did not change significantly. There was no significant change in PEFR. The vaccine was well tolerated. Persons with HIV infection and low CD4 count do not serologically respond well to influenza vaccine even with 2 doses compared to the other 4 groups. The other 4 groups had adequate protective serologic responses. The vaccine was well tolerated in all groups.
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PMID:Clinical and serological responses to an inactivated influenza vaccine in adults with HIV infection, diabetes, obstructive airways disease, elderly adults and healthy volunteers. 943 53

The effectiveness of influenza vaccination in reducing hospitalization of people with diabetes for influenza, pneumonia, or diabetic events during influenza epidemics was assessed in a case control study in Leicestershire, England. Cases were 80 patients on the Leicestershire Diabetes Register who were admitted and discharged from hospital with International Classification of Disease codes for pneumonia, bronchitis, influenza, diabetic ketoacidosis, coma and diabetes, without mention of complications, during the influenza epidemics of 1989-90 and 1993. One hundred and sixty-controls, who were not admitted to hospital during this period, were randomly selected from the Register. Immunization against influenza was assessed in 37 cases and 77 controls for whom consent was obtained to access their clinical notes and for whom notes were available. Significant association was detected between reduction in hospitalization and influenza vaccination during the period immediately preceding an epidemic. Multiple logistic regression analysis estimated that influenza vaccination reduced hospital admissions by 79% (95% CI 19-95%) during the two epidemics, after adjustment for potential confounders.
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PMID:Effectiveness of influenza vaccine in reducing hospital admissions in people with diabetes. 944 Apr 37

Diabetes patients suffer frequent complications and some excess mortality after influenza virus infection. Despite widespread agreement that diabetic patients should be routinely vaccinated against influenza, some reports claim that diabetics have a poor immune response to influenza vaccine. We have performed a pilot study to examine the humoral immune response of juvenile diabetics and matched healthy controls vaccinated with inactivated trivalent influenza vaccine. By enzyme-linked immunospot assay we found that both groups had comparable magnitude and kinetics of influenza-specific antibody secreting cell response. The influenza-specific antibody response in both serum and oral fluid were similar for both groups, and also showing a kinetic profile in accordance with our earlier data for healthy adults. Our study did not detect a difference in the humoral immune response between juvenile diabetics and healthy controls.
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PMID:Systemic and local immune responses after parenteral influenza vaccination in juvenile diabetic patients and healthy controls: results from a pilot study. 960 24

In type I diabetes in both rodents and humans, genetic susceptibility to disease is strongly linked to MHC class II alleles. In some cases, however, certain class II alleles provide resistance to disease. To examine this effect in a well-defined system, we studied double transgenic mice expressing influenza hemagglutinin (HA) on pancreatic islet beta cells and an HA-specific TCR on CD4 T cells. On a susceptible B10.D2 background, 70% of double transgenic mice develop an early-onset spontaneous autoimmune diabetes. MHC heterozygosity induced variable protection from diabetes, depending on the specific nonpermissive allele, but insulitis was invariably present. Autoreactive T cells retained the ability to induce diabetes because cyclophosphamide treatment induced diabetes in 81% of young MHC(d/b) transgenic mice, although the effect was diminished in older mice. Most importantly, treatment induced higher IFN-gamma/IL-4 ratios among CD4 T cells, suggesting a strong shift toward Th1 development, perhaps through direct effects on patterns of gene expression in CD4 T cells.
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PMID:Protection against diabetes by MHC heterozygosity and reversal by cyclophosphamide. 963 Aug 37


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