The renal type H+/peptide symporter PEPT2: structure-affinity relationships.

The H(+)/peptide cotransporter PEPT2 is expressed in a variety of organs including kidney, lung, brain, mammary gland, and eye. PEPT2 substrates are di- and tripeptides as well as peptidomimetics, such as beta-lactam antibiotics. Due to the presence of PEPT2 at the bronchial epithelium, the aerosolic administration of peptide-like drugs might play a major role in future treatment of various pulmonary and systemic diseases. Moreover, PEPT2 has a significant influence on the in vivo disposition and half-life time of peptide-like drugs within the body, particularly in kidney and brain. PEPT2 is known to have similar but not identical structural requirements for substrate recognition and transport compared to PEPT1, its intestinal counterpart. In this review we compiled available affinity constants of 352 compounds, measured at different mammalian tissues and expression systems and compare the data whenever possible with those of PEPT1.

Presence of insulin autoantibodies as regular feature of nondiabetic repertoire of immunity.

With an ultrasensitive noncompetitive enzyme-linked immunosorbent assay (ELISA), we tested the hypothesis that the presence of insulin autoantibodies in nondiabetic individuals is a normal event. Plasma and peripheral blood mononuclear cells were obtained from 50 nondiabetic whites for determination of insulin autoantibodies by ELISA and radioimmunoassay (anti-insulin IgG [AI-IgG] and 125I-labeled insulin bound [%]), islet cell antibodies, anti-nuclear antibodies and rheumatoid factor, and HLA class II-type antigens (DR, DRw, and DQ). The range of 125I-insulin binding was significantly less than was seen in pretreatment sera from individuals with diabetes (from -0.4 to 0.4% vs. -0.8 to 7.7%, respectively, P = 0.001). Eighty-eight percent of these nondiabetic individuals had significant levels of AI-IgG with preferential binding to human insulin. The geometric mean of AI-IgG concentrations in individuals with significant levels was 180 pM. Binding to human insulin was seen in 88%, to pork insulin in 42%, and to beef insulin in 24% of individuals (P less than 0.001 overall; P less than 0.05 where more bound to pork than beef insulin). Binding of AI-IgG to human insulin-coated plates was substantially inhibited by preincubation with human insulin (median inhibition 57.6%) with little if any inhibition by glucagon, C-peptide, albumin, or IgG. Four individuals had highly specific human AI-IgG as shown by immunoaffinity studies. AI-IgGs were significantly higher in individuals with the HLA haplotype DR4,DRw53,DQ3 and lower in individuals with DR5,DRw52,DQ1 (P = 0.03 for both).(ABSTRACT TRUNCATED AT 250 WORDS)

Familial gastroesophageal reflux and development of Barrett's esophagus.

The family of an elderly man with Barrett's esophagus was examined for gastroesophageal reflux and development of Barrett's esophagus. All five living children have gastroesophageal reflux or esophagitis, or both, and three have unequivocal Barrett's esophagus. Two third-generation descendents have gastroesophageal reflux. This pattern suggests autosomal dominant transmission of the gastroesophageal reflux trait. The family also has a high prevalence of cancer, which may represent the cancer family syndrome.

Defining scholarly activity in nursing education.

In an attempt to address the question of what activities should be considered scholarly, thereby warranting their inclusion in a nursing faculty evaluation model, a study was undertaken which surveyed all National League for Nursing accredited baccalaureate educational programs. The items in the instrument were generated utilizing the Delphi method and a pilot study established inter-respondent reliability. A response rate of 73% was attained. Scholarly activity was considered highly important in evaluation for promotion and tenure in over 50% of the schools. There were distinct differences in the activities deemed scholarly when respondents were broken down into categories such as size and type of institution and the existence or non-existence of graduate nursing programs in the same institution.

Linkage analysis in a large kindred with autosomal dominant transmission of polyglandular autoimmune disease type II (Schmidt syndrome).

Schmidt syndrome (PGA syndrome type II) is a rare condition characterized by polyglandular failure. It is an autosomal dominant trait with variable expressivity that was inherited over four generations in an the Indiana kindred. Association of HLA-B8 has been reported with Schmidt syndrome. Our proband is a 12-year-old boy with Addison disease, insulin dependent diabetes mellitus (IDDM), and vitiligo. Two of his eight sibs had either IDDM (sister) or vitiligo and hyperthyroidism (brother). His mother had hypothyroidism. Seven members of earlier generations apparently were also affected. We obtained peripheral blood for HLA and genetic analysis from 21 relatives in a family with 8 Schmidt syndrome individuals in three generations. HLA studies on 15 affected and unaffected relatives showed only 2 of 7 persons with B8-containing haplotypes. Therefore, no association exists between the B8-containing haplotype and the syndrome. We identified informative marker loci. No evidence for linkage of the Schmidt locus to any of the 14 markers was found and close linkage to esterase D and adenylate kinase and possibly properdin factor B was excluded.

A prospective analysis of the arthritis syndrome and immune function in jejunoileal bypass patients.

Fifty-two patients undergoing jejunoileal bypass surgery were prospectively evaluated to determine: 1) the incidence of the associated arthritic syndrome; 2) whether we could identify patients at risk for arthritis prior to surgery; and 3) changes in immune function. The incidence of arthritis was 28% and was frequently associated with dermatitis. No preoperative clinical or laboratory parameters identified those patients at risk to develop rheumatic problems. Circulating immune complexes were found in both arthritis and non-arthritis patients after surgery. Mean serum levels of IgA rose significantly after surgery only in patients who developed arthritis, but remained within the normal range. No other immunologic abnormalities were noted.

Serum immunoglobulins and uveitis.

Sixty-two percent of 975 uveitis patients had a statistically significant elevation in the levels of one or more of three serum immunoglobulins. The percentage of cases of above-normal values was greatest for IgM (43.8%), followed by IgA (34.0%), and then by IgG (11.9%). There was no statistically significant difference in immunoglobulin values obtained for one diagnosis as compared with all others, except for men with HLA-B27. They had a higher percent of elevated IgM values than men with all other diagnoses. Testing for immunoglobulins is of little or no value in the etiologic diagnosis of a single case of uveitis, but may be of value in research studies to better understand its pathogenesis.

HLA standardization and proficiency testing in the Southeastern organ Procurement Foundation.

Five years of experience with cell exchanges between laboratories comprising the Southeastern Organ Procurement Foundation (SEOPF) were analyzed in order to evaluate progress in HLA typing proficiency. The results of the analysis of 15 cell exchanges involving a total of 60 cells indicate that the average detection rate was 95% or greater for HLA-A1, 2, 3, 9, 10, 11, 28, and 29; B7, 8, 12, 13, 14, 15, 17, 27, and 40. HLA-A locus antigens were detected more often (85.8%) than B locus antigens (80.9%). False negative results were more frequent than false positive antigen assignments. Errors in antigen assignments tended to be nonrandomly distributed for certain antigens belonging to cross-reacting groups but usually were randomly distributed for well defined antigens. During the period of the study, SEOPF laboratories demonstrated improved proficiency in the identification of most HLA-A, B, and C provisional (w) specificities. The results demonstrate the benefits of interlaboratory proficiency testing and indicate that cell exchanges can be carried out successfully on a regional basis.

A search for stratification-free association between plasma lipids and HLA using dizygotic twins.

A total of 71 pairs of like-sexed dizygotic twins were studied, comparing within-pair differences for plasma total, free and esterified cholesterol, and triglyceride with the number of HLA haplotypes the twins had in common. If associations are present between HLA and the blood lipids studied, the twins with no haplotypes in common would be expected to have the largest within-pair mean square, those with two in common the smallest, and those with one in common an intermediate value. No significant differences were found comparing within- pair mean squares for the variables studied.

Arthritis associated with jejunoileal bypass: clinical and immunologic evaluation.

Arthritis is a common complication of small bowel bypass, occurring in 5-20% of the postsurgical patients. Thirteen patients with arthritis related to jejunoileal bypass were studied. These patients had a symmetrical polyarthritis, and 8 also had extraarticular connective tissue disease manifestations. Immunologic evaluations were done on these patients and on a control group of 12 age- and sex-matched postintestinal bypass patients without arthritis. The incidence of positive ANA, rheumatoid factors, immune complexes, and antibodies to intestinal flora was the same in both groups. Patients in both groups showed similar changes in numbers of circulating T and B lymphocytes. More patients in the group with arthritis than in the control group had elevated IgA levels (38% versus 8%), but the difference was not significant (P less than 0.05). This study demonstrates that immunologic abnormalities occur after jejeunoileal bypass irrespective of the onset of arthritis or related symptoms. No specific immunologic abnormalities could be associated with the arthritis occurring after small bowel bypass.

The human X-chromosome and the levels of serum immunoglobulin M.

The serum concentrations of immunoglobulins G, A and M were measured in a sample of 93 pairs of monozygotic twins, their spouses, and their offspring. The hypothesis that the human X-chromosome carries genes which control the levels of immunoglobulin M was tested with three different approaches. Our results indicate that environmental factors are primarily responsible for the observed variation in the levels of IgG and IgA. The variance of IgM seems to be mostly the result of X-linked gene effects, with women having higher IgM levels than men.

HL-A antigens in North American black families.

The polymorphic HL-A histocompatibility system has been studied in North American black families. The family studies show that haplotype frequencies differ between black and white populations. Seven haplotypes (W28,W5; W28,W17; W28, undefined four; W23,W5; W19,W5; undefined LA,W5; and undefined LA, undefined four) were significantly more frequent in blacks than whites, while haplotypes 1,8 and 3,7 were significantly less frequent. Some of these differences may be accounted for by differences in gene frequencies between the two groups; other differences may be explained by linkage disequilibrium in the white population. No significant linkage disequilibrium between the LA and FOUR loci was found in the black population.

Vitiligo and dysgammaglobulinemia. A case report and family study.

This report concerns an 8 year old female with vitiligo and dysgammaglobulinemia characterized by absent IgA, very low IgG, and normal IgM. The t-cell immune system was intact but other family members had low levels or absence of IgA. The possible relationship of dysgammaglobulinemia and vitiligo is discussed along with the classification and inheritance of the immune cell defects.