A longitudinal study of insulin antibodies and anti-insulin cytotoxicity in type I diabetes mellitus.

Insulin antibodies and T-cell lymphocyte cytotoxic reactivity against insulin and its related peptides were studied longitudinally in 3 groups of patients with type I diabetes mellitus (DM). Group 1 patients were those in whom the diagnosis was made within 1 week of the initiation diagnosis. They were subdivided into those receiving MC porcine (A) or MC bovine (B) insulin. Group 2 patients were those with a duration of DM for 2-6 years who were receiving either MC porcine (A) or MC bovine (B) insulins. Group 3 subjects were those who had been on conventional recrystallized insulin and then switched to MC porcine (A) or MC bovine (B) insulins for 2 weeks before the start of the study. The incidence of cytotoxic reactions and insulin antibodies were approximately 40-50% for group 1 (either 1A or 1B) at the initiation of the study. At 3-month follow up all patients in group 1B developed insulin antibodies (p less than 0.02) and a significant increase in the frequency of cytotoxic reactions (p less than 0.01). By contrast there was a decline in the frequency of cytotoxic reactions in group 1A (p less than 0.01 at 1 year) and the increase in insulin antibodies was non-significant. Group 2B had higher frequency in cytotoxic reactions (p less than 0.005) and of insulin antibodies (p less than 0.05) than group 2A. A significant decrease (p less than 0.01) in cytotoxic reactions was observed at 3 months following the switch of patients from conventional bovine insulin preparations to 'A' but not to 'B'. However in both subgroups insulin antibodies persisted for at least 12 months. Cross-reactivity between antibodies to human, porcine and bovine insulins was evident in all groups. The early cellular and humoral immune phenomena were positively correlated in both group 1A and 1B suggesting their common involvement in the pathogenesis of DM.

The human cellular immune response to insulin: a study in unexposed control subjects and type I diabetic patients on acute and chronic treatment.

Using a cellular cytotoxicity assay, we have investigated the antigenicity of pharmaceutical insulins and of highly purified insulin constituents (unformulated monocomponent (MC) insulin, insulin B-component and C-peptide) in control, insulin naive, subjects and in three groups of type I diabetic patients. These were: Group 1, newly diagnosed patients receiving either porcine or bovine MC insulins for less than one week; Group 2, established patients receiving porcine or bovine MC insulin for 2-6 years; Group 3, established patients receiving conventional bovine insulin for 2-6 years, and tested within two weeks of switching to either porcine or bovine MC insulins. In control subjects, there was a higher incidence of cytotoxic reactions with beef (72%) than with porcine (33%) pharmaceutical preparations (p less than 0.01) but there was a similar incidence of reactions with the purified beef and pork constituents. All patients, except those Group 3 patients receiving bovine MC insulins, had a significantly increased incidence of aggregate reactions to the spectrum of antigens. In porcine treated patients, there was an increase in the incidence of reactions to pharmaceutical preparations in Group 1 (p less than 0.05) and Group 3 (p less than 0.001), but this was absent from each of the bovine treated groups. All patient groups showed significant increases in the incidence of reactions against insulin constituents of their therapeutic analog. In Groups 1 and 2, but not 3, there was significant analog cross reactivity. We deduce that the reactivity seen in control subjects is principally directed against unidentified formulation constituents of bovine pharmaceutical preparations. Patients on both acute and chronic therapy with insulin show T-cell sensitization to MC insulin and its components. Chronic therapy with conventional bovine insulin induces tolerogenesis, but this is reversed on exposure to a fresh insulin analog.

Periarthritis: another duration-related complication of diabetes mellitus.

The association between periarthritis of the shoulder and diabetes mellitus is well recognized. A study of 100 hospitalized patients with diabetes was performed, comparing them with 100 control subjects. The mean +/- SEM age of the subjects was 47 +/- 2 yr. Nineteen percent of the patients with diabetes had periarthritis. The afflicted subjects had a higher incidence of retinopathy (P less than 0.005) and albuminuria (P less than 0.005). The duration of shoulder pain correlated with the duration of the diabetes mellitus (P less than 0.001). However, the presence of other complications in subjects with periarthritis was not as well correlated with the duration of the diabetes mellitus. These data emphasize the common occurrence of periarthritis in subjects with diabetes mellitus and its extension to people of diverse backgrounds.

Prolactin in seminal fluid.

Prolactin appears to modulate male reproduction by regulating hormone receptor levels in the testis and accessory sex organs and by facilitating spermatozoal biochemical processes associated with capacitation. A large portion of immunoreactive prolactin (iPRL) seems to be transported from blood to semen via the accessory sex organs and takes several days to make this transition. The iPRL in semen is heterogeneous in size and a unique portion may be associated with spermatozoa. Data from several clinical studies of seminal fluid prolactin are inconsistent. The variability of patient populations classified as fertile or infertile, the differences in prolactin assays used, and the lack of information about sample processing have been major causes of this difficulty.

Medullary carcinoma of the thyroid masquerading as idiopathic vocal cord paralysis.

The following conclusions may be drawn as a result of our study: 1. Serum calcitonin by radioimmunoassay proved to be the only valid preoperative indicator in a case of medullary carcinoma of the thyroid occurring with vocal cord paralysis. This test should be considered in all cases of idiopathic recurrent laryngeal nerve paralysis, especially when obscure thyroid pathology is suspected. 2. Provocative calcitonin testing, such as a calcium infusion test, may help verify presence or absence of disease in equivocal cases of calcitonin assay. 3. Vocal cord paralysis may be the first sign of intrathroid malignancy. 4. In the furture, serum calcitonin assay (drawn posttreatment) may be a valuable prognostic indicator and may guide the need for additional treatment.

Size heterogeneity of immunoreactive prolactin in stored semen and seminal plasma.

The difference between semen and seminal plasma immunoreactive human prolactin (iPRL) correlates with sperm count. Seminal plasma separated from sperm before freezing (SPB), after freezing (SPA), and serum were fractionated by G100 Sephadex chromatography. SPA contained four different molecular weight fractions of iPRL. Each fraction contained approximately 25% of the total iPRL measured. SPB and serum each had three molecular weight fractions and most of the iPRL coeluted with monomeric 125I-hPRL.

The effect of freezing and storage on seminal immunoreactive prolactin.

Thirteen subjects were studied to compare changes in seminal immunoreactive prolactin produced by storage and freezing of semen and seminal plasma separated within 2 hours of ejaculation. Seminal prolactin was significantly higher in semen than in seminal plasma (paired t test, t = 3.29, p less than 0.005). The difference in prolactin between the two values correlated with sperm count (linear regression analysis, r = 0.65, p less than 0.02). This study suggested that variations in reported correlations between sperm count and seminal prolactin might be explained in part by the time interval of semen collection, centrifugation, and/or freezing.

Correlations between seminal radioimmunoreactive prolactin, sperm count, and sperm motility in prevasectomy and infertility clinic patients.

Semen samples were collected from 50 prevasectomy patients and 43 infertility clinic patients. Various parameters were measured, including semen radioimmunoreactive prolactin (rPRL) levels. Linear correlations were tested between the measured parameters, and a significant correlation was found between semen rPRL concentration and sperm count for both the prevasectomy (r = 0.73, P less than 0.00002) and the clinic patients (r = 0.72, P less than 0.00002). For the clinic patients a correlation was also found between the amount of ejaculate rPRL and sperm motility (r = 0.46, P less than 0.002) and between ejaculate volume and motility (r = 0.36, P less than 0.02).

Comparison of prolactin levels in human semen and seminal plasma.

Semen samples were collected from 35 men and the levels of prolactin in semen and seminal plasma were measured. There was no significant difference in prolactin concentrations between the two fluids (t = 0.333, P greater than 0.7). There was also no correlation between the prolactin concentration and the kinematic viscosity of the semen (r = 0.065, P greater than 0.7).

Seminal immunoreactive prolactin before and after vasectomy.

Seminal fluid was assayed for prolactin by radioimmunoassay in eleven healthy males 8-12 weeks following vasectomy. The results were compared with those obtained in 34 age matched subjects prior to undergoing vasectomy. The mean values (+/- 1 SD) for prolactin were similar (postvasectomy = 11.4 +/- 3.2 ng/ml, prevasectomy = 12.7 +/- 6.1 ng/ml) and there was no statistically significant difference (t = 0.66, P = greater than 0.05). This study shows that prolactin is found in secretions of the prostate and/or seminal vesicles.