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Biomedical subjects

J J Miller

Publications and source records attributed to J J Miller.

At least 73 records · Page 4Linked to original sources
PubMed1992

Adaptation to juvenile rheumatic disease: a controlled evaluation of functional disability with a one-year follow-up.

Compared the adaptation of 165 patients with juvenile rheumatic disease (JRD) to that of their healthy siblings. Patients were divided into those with mild functional disability and those with moderate/severe disability. Adaptation in several domains was assessed by parents and children on two occasions 1 year apart. The adjustment difficulties of the JRD children were limited primarily to social functioning but appeared also in the psychological and family problems domains. Compared to "mild" patients, "moderate/severe" patients had more adjustment difficulties; in some areas, mild patients functioned as well as their healthy siblings. Some Time 1 differences were replicated at Time 2. The results help to delineate (a) the specific domains in which children with chronic disease have adjustment difficulties and (b) the factors that put children at risk for developing adjustment problems.

Activities of Daily Living↗
PubMed1992

Antibodies to lipid A in pauciarticular juvenile arthritis: clinical studies.

IgG antibodies to monophosphoryl lipid A (MPL) are more concentrated in synovial fluids than in the blood of children with pauciarticular juvenile arthritis. Correlations between IgG anti-MPL levels and numbers of inflamed joints were highly significant in 2 of 10 patients followed for 8 years and suggestive in 2 patients followed for shorter periods. A fifth patient had a correlation between IgM anti-MPL and joint count.

Adolescent↗
PubMed1991

Angiotensin carboxypeptidase activity in urine from normal subjects and patients with kidney damage.

Angiotensin carboxypeptidase (ACP) activity has been detected in urine samples from normal subjects and patients with hypertension and diabetes by determining the enzyme's ability to convert angiotensin I to des-Leu angiotensin I. Gel filtration chromatography of a concentrated urine sample indicated that about equal amounts of the enzyme exist as 100 kDa and 500 kDa molecular weight forms, respectively. This ACP activity co-eluted with activity that cleaved histidine from des-Leu angiotensin I to form angiotensin II and activity that cleaved tyrosine from benzyloxycarbonyl-glutamyl-tyrosine (ZGT). These results suggest that the urinary ACP activity is due to cathepsin A as we have reported previously for the porcine kidney enzyme. Analysis of sequential urine samples from a single individual over a 6-day period revealed as much as a 6-fold fluctuation in creatinine-normalized ACP activity. Of five male healthy adult subjects, the creatinine-normalized urinary ACP activity ranged from 1.7 to 3.7 mU/mL with a mean of 2.8 mU/mL. However, five male patients with renovascular hypertension had elevated levels of ACP activity with a mean of 11.6 mU/mL. Of five male patients with diabetic nephropathy, all had elevated ACP activity levels with a mean of 21.0 mU/mL. It is concluded that ACP activity in the urine is due to cathepsin A probably derived from kidney tissue, and that the release is increased in patients with kidney damage. We suggest that urinary ACP activity should be evaluated further for a possible relationship to renal hypertension and as a potentially early marker for diabetic nephropathy.

Carboxypeptidases↗
PubMed1991

Complement C5a receptor assay for high throughput screening.

The complement C5a receptor on U937 cells, a human histiocytic lymphoma cell line, stimulated with dibutyryl-cAMP have been stabilized for at least 3 months at a dilute, ready to use concentration. [125I]-Bolton Hunter labeled C5a, (recombinant, human) has been prepared by reverse phase HPLC to 2200 Ci/mmol. Using a filtration binding assay the Kd from receptor saturation analysis is 10-40 pM and there are 50,000-100,000 receptor sites per cell. These reagents have permitted the development of a reliable, reproducible and convenient drug screening assay, in kit format, for compounds acting at the C5a receptor.

Complement C5a↗
PubMed1991

Antibodies to core lipid fractions of endotoxin in children with rheumatic disease.

The titer of IgG and IgM antibodies to two fragments of endotoxin derived from Salmonella minnesota R 595, lipid A width a 2-keto-3-deoxyoctanate oliosaccharide (KDO lipid A), and monophosphoryl lipid A (mono-P lipid), were measured in normal children, children with cystic fibrosis, and children with SLE and all forms of chronic juvenile arthritis. Elevated titers of IgM anti mono-P lipid A were found in all of the rheumatic diseases, but not in cystic fibrosis. The elevated IgM titers were not correlated with concentration of activation fragments of C3 or C4, but IgG anti mono-P lipid A titers, even though not usually elevated, did correlate with C3a and C3d concentrations. The elevated IgM titers to mono-P lipid A may represent a genetically determined hyper-reactivity to normal gastrointestinal antigens, an increased antigenic stimulus from the intestinal tract, or polyspecificity of an antibody of undetermined primary reactivity.

Antibodies, Bacterial↗
PubMed1991

Approaches to minimizing interference by cross-reacting molecules in immunoassays.

Here we review techniques useful in eliminating or reducing interferences caused by molecules that cross-react in immunoassays. The biochemical rationale for using these techniques is discussed. Examples are taken from recent studies aimed at reducing interferences caused by endogenous molecules such as digoxin-like immunoreactive factors or steroid hormones. In this context the role of protein-binding of cross-reacting molecules is also considered. Immunoassay ligand selectivity can be inherently limited by the heterogeneity of the antigenic response or by the structural similarity of epitopes on multiple ligands. Certain empirical approaches have proved useful in maximizing the analytical specificity of immunoassays. These approaches include isolating the relevant ligands before immunoassay, adjusting the kinetic or equilibrium conditions used during the assays, and developing more specific antisera. The physicochemical properties of the cross-reacting molecule best dictate which technique(s) to use. The approaches discussed here are general and apply to minimizing interference caused by a wide variety of both endogenous and exogenous cross-reacting molecules.

Antibody Specificity↗
PubMed1990

Characteristics of a thrombin inhibitor secreted by activated platelets.

A 77-kDa complex of thrombin and a protein secreted by activated platelets had little if any thrombin amidolytic activity, indicating that the secreted protein is an inhibitor. The molecular weight of the inhibitor before reaction with thrombin was approximately 50,000. The apparent second-order rate constant for complex formation was estimated to be 1.3 x 10(6) M-1 s-1 (mean of four measurements); it was not affected by heparin or heparinase. These properties distinguish this inhibitor from other protease inhibitors secreted by platelets. The inhibitor reacted with trypsin and possibly with urokinase but not with factor Xa.

Antithrombins↗
PubMed1990

C3 activation products correlate with antibodies to lipid A in pauciarticular juvenile arthritis.

IgM antibodies to monophosphoryl-lipid A were found to be elevated in sera from children with all forms of juvenile arthritis (JA) and systemic lupus erythematosus. Of more interest, in patients with pauciarticular JA, IgG antibody titers to monophosphoryl-lipid A were found to be correlated with the C3a concentration and the C3d:C3 ratio. Although the full specificity of these antibodies is unknown, they are the first that have been found to be correlated with complement activation products in any form of JA.

Arthritis, Juvenile↗
PubMed1990

Immunologic abnormalities of juvenile arthritis.

Many immunologic abnormalities have been found in children with all forms of chronic arthritis, but few are clinically useful or well understood. However, in children with arthritis it is important to distinguish among those with rheumatoid factor, antinuclear antibodies, or hypogammaglobulinemia. Rheumatoid factor is specific for adult-type rheumatoid arthritis; the presence of antinuclear antibodies increases the likelihood that the child may develop uveitis; and hypogammaglobulinemia may be associated with complicating infections. Other unusual antibodies, autoantibodies, antigen-antibody complexes, and complement activation products are found in children with arthritis, but none of these define a diagnostic or consistent group of diseases. Similarly, changes in the numbers of immunologically active cells and regulating mechanisms occur but not in specific patterns. As yet, none of the known immunologic abnormalities explain the pathogenesis of these diseases and only a few appear disease specific.

Agammaglobulinemia↗
PubMed1989

Impact of juvenile arthritis on families. An educational assessment.

State of the art patient education programs have as their goals changes in behaviors, coping styles, health status, and/or costs. The accomplishment of these goals often involves not only the patient but also his or her whole family. This is especially true if the patient is a child. Based on this premise, we undertook an educational needs assessment of 50 children with juvenile arthritis (JA) and their families. Through utilization of a grounded theory methodology, open-ended questionnaires were completed by JA children, their parents, and their siblings. The resulting analysis suggests (1) the need for family-based education, (2) differing needs of various family members, and (3) several hypotheses for further study.

Adolescent↗
PubMed1989

Metabolic effects of adding sucrose and aspartame to the diet of subjects with noninsulin-dependent diabetes mellitus.

This study compared the effects of adding sucrose and aspartame to the usual diet of individuals with well-controlled noninsulin-dependent diabetes mellitus (NIDDM). A double-blind, cross-over design was used with each 6-wk study period. During the sucrose period, 45 g sucrose (9% of total daily energy) was added, 10 g with each main meal and 5 g with each between-meal beverage. An equivalent sweetening quantity of aspartame (162 mg) was ingested during the aspartame period. The addition of sucrose did not have a deleterious effect on glycemic control, lipids, glucose tolerance, or insulin action. No differences were observed between sucrose and aspartame. Sucrose added as an integral part of the diabetic diet does not adversely affect metabolic control in well-controlled NIDDM subjects. Aspartame is an acceptable sugar substitute for diabetic individuals but no specific advantage over sucrose was demonstrated.

Aged↗
PubMed1989

Breath hydrogen excretion in infants with colic.

Breath hydrogen excretion as an index of incomplete lactose absorption was measured in 118 healthy infants who were either breast fed or given a formula feed containing lactose, some of whom had colic. Infants with colic (n = 65) were selected on the basis of the mother's report of a history of inconsolable crying lasting several hours each day. Infants in the control group (n = 53) were not reported to cry excessively by their mothers. Breath samples were collected using a face mask sampling device preprandially, and 90 and 150 minutes after the start of a feed. Normalised breath hydrogen concentrations were higher in the group with colic than in the control group at each time point. The median maximum breath hydrogen concentration in the colic group was 29 ppm, and in the control group 11 ppm. The percentage of infants with incomplete lactose absorption (breath hydrogen concentration more than 20 ppm) in the colic group was 62% compared with 32% in the control group. The clinical importance of the observed association between increased breath hydrogen excretion and infantile colic remains to be determined. Increased breath hydrogen excretion indicative of incomplete lactose absorption may be either a cause or an effect of colic in infants.

Breast Feeding↗
PubMed1988

Photoaffinity labeling of dopamine D1 receptors.

A high-affinity radioiodinated D1 receptor photoaffinity probe, (+/-)-7-[125I]iodo-8-hydroxy-3-methyl-1-(4-azidophenyl)-2,3,4,5-tetra hyd ro- 1H-3-benzazepine ([125I]IMAB), has been synthesized and characterized. In the absence of light, [125I]IMAB bound in a saturable and reversible manner to sites in canine brain striatal membranes with high affinity (KD approximately equal to 220 pM). The binding of [125I]IMAB was stereoselectively and competitively inhibited by dopaminergic agonists and antagonists with an appropriate pharmacological specificity for D1 receptors. The ligand binding subunit of the dopamine D1 receptor was visualized by autoradiography following photoaffinity labeling with [125I]IMAB and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Upon photolysis, [125I]IMAB incorporated into a protein of apparent agents in a stereoselective manner with a potency order typical of dopamine D1 receptors. In addition, smaller subunits of apparent Mr 62,000 and 51,000 were also specifically labeled by [125I]IMAB in these species. Photoaffinity labeling in the absence or presence of multiple protease inhibitors did not alter the migration pattern of [125I]IMAB-labeled subunits upon denaturing electrophoresis in both the absence or presence of urea or thiol reducing/oxidizing reagents. [125I]IMAB should prove to be a useful tool for the subsequent molecular characterization of the D1 receptor from various sources and under differing pathophysiological states.

Affinity Labels↗