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J Johnson

Publications and source records attributed to J Johnson.

At least 19 recordsLinked to original sources

Immunosuppression in vivo by a soluble form of the CTLA-4 T cell activation molecule.

In vitro, when the B7 molecule on the surface of antigen-presenting cells binds to the T cell surface molecules CD28 and CTLA-4, a costimulatory signal for T cell activation is generated. CTLA4Ig is a soluble form of the extracellular domain of CTLA-4 and binds B7 with high avidity. CTLA4Ig treatment in vivo suppressed T cell-dependent antibody responses to sheep erythrocytes or keyhole limpet hemocyanin. Large doses of CTLA4Ig suppressed responses to a second immunization. Thus, costimulation by B7 is important for humoral immune responses in vivo, and interference with costimulation may be useful for treatment of antibody-mediated autoimmune disease.

Abatacept

Syntheses, resolution, and structure-activity relationships of potent acetylcholinesterase inhibitors: 8-carbaphysostigmine analogues.

The synthesis of a series of 1,2,3,3a,8,8a-hexahydroindeno[2,1-b]pyrrole 5-alkylcarbamates and their resolution are reported. These compounds are structurally related to physostigmine with substitution of a methylene group in place of the NMe group at position 8 of physostigmine. Many of these 8-carbaphysostigmine analogues are more potent acetylcholinesterase inhibitors in vitro and less toxic in vivo than physostigmine. The (-)-enantiomer (e.g., 1d and 1g) possessing the same absolute configuration at C3a and C8a as that of physostigmine, is about 6 to 12-fold more potent at inhibiting acetylcholinesterase than the corresponding (+)-enantiomer (e.g., 1e and 1h).

Animals

Service utilization and social morbidity associated with depressive symptoms in the community.

OBJECTIVE: To estimate service utilization and social morbidity in the community associated with depressive symptoms. Estimates were made using an epidemiologic measure, population attributable risk. Population attributable risk is a compound measure reflecting both the morbid risk to an individual with a disorder and the prevalence of the disorder in the community. DESIGN: Epidemiologic survey. PARTICIPANTS: Eighteen thousand five hundred seventy-one adults in the Epidemiologic Catchment Area Study interviewed from a complex random sample in five US communities. OUTCOME MEASURES: Suicide attempts, use of psychoactive medications, self-reported physical and emotional health, time lost from work, and general medical services or use of emergency departments for emotional problems. RESULTS: Major depression-dysthymia (lifetime prevalence, 6.1%) and depressive symptoms (lifetime prevalence, 23.1%) were associated with increased service utilization and social morbidity as measured by the outcome variables. On a population basis, however, as much or more service burden and impairment was associated with depressive symptoms as with the clinical conditions of depression or dysthymia. The equal association results from the greater prevalence of depressive symptoms. Population attributable risk percentages associated with depressive symptoms (not disorder) were as follows: emergency department use (11.8%) or medical consultations for emotional problems (21.5%); use of tranquilizers (14.6%), sleeping pills (21.0%), or antidepressants (22.2%); fair or poor self-reported emotional health (15.3%); days lost from work (17.8%); and suicide attempts (25.0%). CONCLUSIONS: Estimates of population attributable risk indicated that physicians actually provided services to more persons with depressive symptoms than to persons with formally defined conditions of depressive disorders. Subclinical depression, as a consequence of high prevalence, is a clinical and public health problem. Attention to diagnostic and treatment issues is indicated.

Absenteeism

Social phobia. Comorbidity and morbidity in an epidemiologic sample.

Selected sociodemographic and clinical features of social phobia were assessed in four US communities among more than 13,000 adults from the Epidemiologic Catchment Area study. Rates of social phobia were highest among women and persons who were younger (age, 18 to 29 years), less educated, single, and of lower socioeconomic class. Mean age at onset was 15.5 years, and first onsets after the age of 25 years were uncommon. Lifetime major comorbid disorders were present in 69% of subjects with social phobia and usually had onset after social phobia. When compared with persons with no psychiatric disorder, uncomplicated social phobia was associated with increased rates of suicidal ideation, financial dependency, and having sought medical treatment, but was not associated with higher rates of having made a suicide attempt or having sought treatment from a mental health professional. An increase in suicide attempts was found among subjects with social phobia overall, but this increase was mainly attributable to comorbid cases. Social phobia, in the absence of comorbidity, was associated with distress and impairment, yet was rarely treated by mental health professionals. The findings are compared and contrasted with prior reports from clinical samples.

Adolescent

Depressive symptoms as relative and attributable risk factors for first-onset major depression.

Using longitudinal data from a community study of 9900 adults drawn from four sites in the United States and interviewed twice, 1 year apart, we investigated the predictors of first-onset major depression. Using odds ratios to estimate relative risk, we found that persons with depressive symptoms, compared with those without such symptoms, were 4.4 times more likely and persons with dysthymia were 5.5 times more likely to develop a first-onset major depression during a 1-year period. The lifetime prevalence rate for depressive symptoms was 24%. The attributable risk is a compound epidemiologic measure that reflects both the relative risk associated with depressive symptoms (4.4) and the prevalence of exposure to that risk (24%). It is a useful measure to document the burden of a risk to the community, and it was determined to be greater than 50%. Thus, more than 50% of cases of first-onset major depression are associated with prior depressive symptoms. The high prevalence of depressive symptoms in the community and their strong association with first-onset major depression make them important from a public health perspective. Because depressive symptoms are often unrecognized and untreated in clinical practice, we conclude that their identification and the development of effective treatments could have implications for the prevention of major depression.

Adolescent

Evaluating the diagnostic criteria for panic disorder: measures of social morbidity as criteria.

Over 9% of the subjects in the NIMH Epidemiologic Catchment Area sample reported a history of at least one panic attack, yet only 1.5% of the sample met DSM-III criteria for panic disorder. In light of the revisions of these criteria for DSM-IV, two of those diagnostic criteria, frequency of panic attacks and number of symptoms during a panic attack, are examined in this paper. We evaluated the relationship between those criteria and each of three measures of social morbidity:psychiatric hospitalization, emergency room (ER) use for emotional problems, and suicide attempts. Although only symptom count was significantly associated with either ER use or suicide attempts, both diagnostic criteria were associated with psychiatric hospitalization. The threshold for symptom count was also considered and while three appeared to have slightly better sensitivity and specificity, the continued use of four symptoms seemed acceptable. The diagnostic and clinical implications of the findings are considered.

Catchment Area, Health

Increased HLA A1 and diminished HLA A3 in lymphocytic colitis compared to controls and patients with collagenous colitis.

Lymphocytic colitis is a newly described chronic diarrheal disorder. Although its etiology is unknown, the possibility has been raised that autoimmunity may play a role in both lymphocytic and collagenous colitis, a similar clinicopathologic illness. The frequencies of HLA class I and class II antigens were examined in 24 white patients with lymphocytic colitis and in 47 white patients with collagenous colitis. Frequencies in these two disorders were compared to control white populations and to each other. An increased frequency of HLA-A1 was noted in 16 of 24 lymphocytic colitis patients (66.6%) compared with 1089 of 3942 controls (27.6%) (P less than 0.005; relative risk 5.2). Furthermore, HLA-A3 was found in decreased frequency in lymphocytic colitis patients: 0 of 24 (0%) compared with 1017 of 3942 controls (25.8%) (P less than 0.05; relative risk 0.0). Collagenous colitis patients had no significant deviation from control frequencies of HLA antigens. In lymphocytic colitis, there was no significant increase in B8 or DR3 antigens, which are found in linkage disequilibrium with A1 and associated with many autoimmune diseases. Moreover, the frequency of autoimmune-associated class I HLA antigens was not increased in lymphocytic colitis. Statistically significant differences existed between lymphocytic and collagenous colitis in HLA-A1, A3, Bw6, and B7 antigen frequencies. The HLA patterns noted previously in other gastrointestinal disorders, including ulcerative colitis and Crohn's disease, were not apparent in lymphocytic or collagenous colitis. HLA typing provides further evidence that lymphocytic colitis is a distinct form of chronic intestinal inflammatory disease associated with HLA class I phenotypes.

Colitis

Prenatal literature testing: a pilot project.

A pilot study was conducted in 1987-1988 to evaluate current health literature utilized for prenatal health education of the high risk population in County Health Departments in Arizona. Towards that end, sixty-five distinct pamphlets were obtained from Arizona's County Health Departments and assessed for reading level using the SMOG Readability Formula. The majority of the prenatal literature were found to be 10th to 12th grade reading level, higher than the typical reading level of the high risk prenatal population. A modified literature testing instrument was further utilized to test eight general prenatal pamphlets to assess the printed literature for accuracy, usability, believability, appeal, and cultural relevance. Four pamphlets of those tested, two English and two Spanish, were identified as being the most appropriate for the high risk prenatal population.

Arizona

Depressive symptoms in women in the six months after miscarriage.

This study, the first systematic investigation of the psychiatric impact of miscarriage, tests whether miscarriage markedly increases depressive symptoms in the 6 months after loss. We interviewed 382 miscarrying women entering the study at 2 weeks, 6 weeks, or 6 months after loss and, for comparison, 283 pregnant women and 318 community women not recently pregnant. Among women interviewed 2 weeks after miscarriage the proportion highly symptomatic on the Center for Epidemiologic Studies-Depression scale was 3.4 times that of pregnant women (95% confidence limits 2.0 and 5.0) and 4.3 times that of community women (95% confidence limits 3.0 and 5.8). Among women first interviewed 6 weeks and 6 months after miscarriage the proportion highly symptomatic was three times that of the community women. Women reinterviewed at 6 weeks and 6 months did not have elevated symptom levels, a result attributed to the unintended therapeutic and test effects of study interviews. Interviews were fully structured, readily administered by telephone by nonmedical personnel. The possibility that such interviews afford miscarrying women substantial psychologic benefits merits future investigation.

Abortion, Spontaneous

Na+/K(+)-ATPase activity and its alpha II subunit gene expression in rat skeletal muscle: influence of diabetes, fasting, and refeeding.

We have examined the effects of diabetes, fasting, and refeeding on Na+/K(+)-adenosine triphosphatase (ATPase) activity and its catalytic alpha II subunit gene expression in skeletal muscle. Two hypoinsulinemic states, streptozotocin-induced diabetes and 48-hour fasting caused a significant decrease (P less than .05) in skeletal muscle Na+/K(+)-ATPase activity and a marked increase (P less than .01) in the levels of alpha II subunit mRNA. A decrease in enzyme activity was observed on the 2nd and the 14th day of diabetes, whereas an increase in alpha II mRNA levels was found only on the 14th day. The levels of alpha I mRNA were not affected, while the levels of mRNA of the structural beta subunit were decreased on the 14th day of diabetes. Correction of hyperglycemia with insulin restored enzyme activity and alpha II isoform mRNA levels toward normal in diabetic animals. Refeeding for 48 or 72 hours restored these parameters to normal in skeletal muscle of previously fasting rats. These observations suggest that a decrease in muscle Na+/K(+)-ATPase activity may lead to a compensatory increase in its alpha II subunit gene expression. The levels of insulin and not of glycemia appear to be critical in modulating Na+/K(+)-ATPase activity and gene expression.

Animals

Human EBV-transformed lymphocytes of patients with Schistosoma japonicum infection secrete idiotypically related immunoregulatory antibodies.

Lymphocytes derived from the peripheral blood of individuals infected with Schistosoma japonica were transformed in vitro with Ebstein-Barr virus (EBV). Serological characterization of antibody molecules revealed both antigen reactive (idiotypic) and anti-idiotypic transformants. One idiotypic EBV transformant, LO2C2, describes a major cross-reactive idiotype associated with anti-antigen binding molecules. Other antibody populations expressing idiotypic cross-reactivity were derived from separate individuals showing shared idiotypy in S. japonicum field study populations in the Republic of Philippines. Both idiotypic and anti-idiotypic molecules suppressed parasite antigen-driven blastogenesis of heterologous human peripheral blood lymphocytes. The data show a serologically related immunoregulatory immune network in patients in the Republic of the Philippines which is serologically distinct from idiotypy expressed in other selected S. japonicum endemic areas in the Far East.

Animals

The validity of major depression with atypical features based on a community study.

This article reports on evidence for the validity of major depression (MDD) with atypical features (defined as overeating and oversleeping) as a distinct subtype based on cross-sectional and 1-year prospective data from the Epidemiologic Catchment Area study. MDD with atypical features, when compared to MDD without atypical features, was associated with a younger age of onset, more psychomotor slowing, and more comorbid panic disorder, drug abuse or dependence, and somatization disorder. These differences could not be explained by differences in demographic characteristics or by symptom severity. This study, based on a community sample, found that major depression with atypical features may constitute a distinct subtype.

Adult

Alterations in renal function in psoriasis patients treated with cyclosporine, 5 mg/kg/day.

BACKGROUND: Cyclosporine has been used to treat a variety of cutaneous and immune-mediated diseases. Nephrotoxicity is the most common major adverse side effect. OBJECTIVE: The study was designed to investigate the frequency of alterations in serum creatinine in patients with psoriasis receiving 5 mg/kg/day of cyclosporine. METHODS: Sixteen patients with severe refractory psoriasis received cyclosporine, 5 mg/kg/day, for 12 weeks. Serum creatinine was evaluated with respect to each patient's baseline. RESULTS: Serum creatinine levels remained in the normal range, but 10 of 16 patients had a 30% elevation and 5 of 16 patients had a 50% elevation of serum creatinine compared with the patient's baseline value. CONCLUSION: These results indicate that a significant elevation in serum creatinine occurs in many patients who receive cyclosporine for psoriasis.

Adult

Factors influencing sensory-specific satiety.

In the first part of this study, subjects tasted small portions of a set of foods (rating set) and rated their liking of these foods before and after eating a serving of one of the foods (test meal). These foods were chosen to vary in both macronutrient composition and sensory qualities. Measurements of hunger were taken before and after the test meal. The amount of sensory-specific satiety produced by a test meal differed depending on the food eaten. There was a trend for high-protein foods, which were also the least-liked foods, to decrease more in liking than low-protein foods. Buttered rolls and Coke, when eaten as test meals, dropped the least in liking. Initial liking and the variety of sensory qualities within a food were investigated as potential factors which could influence sensory-specific satiety. Subjects tasted and rated their liking of the test meals, which varied in the level of initial liking and the level of variety of sensory qualities within a food, before and after eating. There was a non-significant trend for the less-liked test meals to drop more in liking than the well-liked test meals. There was also a slight trend for the low-variety test meals to drop slightly more in liking than the intermediate and high-variety test meals.

Female