Fluid and Protein Secretion by the Submandibular Glands of Weanling Rats in Response to Cholinergic and Peptidergic Agonists at Various Doses

Fluid and protein secretion by the submandibular glands of 25-day-old rats were examined and compared in response to three cholinergic and four peptidergic sialogogues at various doses. All cholinergic and peptidergic agonists used were potent sialogogues for the submandibular glands of the weanling rats over the wide range of doses used. The cholinergic agonists, bethanechol and methacholine and the peptidergic agonists, substance P, substance P^Tyr8 and eledoisin-related peptide used intravenously, acted similarly to each other on the submandibular glands of the rats, late in the natural weaning period, but carbachol and physalaemin had slightly different effects. Of the peptidergic agonists, physalaemin was the most potent sialogogue among four tachykinins tested at the low dose. The types of protein secreted by the submandibular glands of the weanling rats in response to all sialogogues used here were typical of the β-type. These results indicate that all agonists used could mainly stimulate the acinar cells of the submandibular glands of the weanling rats which have already fully developed functionally at this time.     

Regulatory mechanisms of C4b‐binding protein (C4BP)α and β expression in rat hepatocytes by lipopolysaccharide and interleukin‐6

Summary. Background: C4b‐binding protein (C4BP), a multimeric protein structurally composed of α chains (C4BPα) and a β chain (C4BPβ), regulates the anticoagulant activity of protein S (PS). Patients with sepsis have increased levels of plasma C4BP, which appears to be induced by interleukin (IL)‐6. However, it is not fully understood how lipopolysaccharide (LPS) and IL‐6 affect the plasma C4BP antigen level and C4BPα and C4BPβ expression in hepatocytes. Objectives: To assess the effect of LPS and IL‐6 on plasma C4BP, PS–C4BP complex levels, PS activity, and C4BP expression by rat liver in vivo and on C4BP expression by isolated rat hepatocytes in vitro. Results: Plasma C4BP antigen level transiently decreased from 2 to 12 h after LPS (2 mg kg^?1) injection, and then it abruptly increased up to 24 h after LPS injection. Plasma C4BP antigen level increased until 8 h after IL‐6 (10 μg kg^?1) injection, and then gradually decreased up to 24 h after IL‐6 injection. LPS significantly decreased the protein and mRNA expression of both C4BPα and C4BPβ in rat hepatocytes, and this effect was inhibited by NFκB and MEK/ERK inhibitors. IL‐6 mediated increase in C4BPβ expression in rat hepatocytes, which leads to increased plasma PS–C4BP complex level and to decreased plasma PS activity, was inhibited by inhibition of STAT‐3. Conclusion: LPS decreases both C4BPα and C4BPβ expression via the NFκB and MEK/ERK pathways, whereas IL‐6 specifically increases C4BPβ expression via the STAT‐3 pathway, causing an increase in plasma PS–C4BP complex, and thus decreasing the anticoagulant activity of PS.     

Randomized comparative trial of three antivenoms in the treatment of envenoming by lance-headed vipers (Bothrops jararaca) in Sao Paulo, Brazil

In São Paulo City, Brazil, 121 patients with moderatelysevere envenoming by Bothrops snakes (principally B. jararaca)were randomized for treatment with Brazilian polyspecific Bothropsantivenoms: Instituto Butantan (39 patients), Instituto VitalBrazil (41), Fundação Ezequiel Dias (FUNED) (41).The initial dose was four ampoules (40 ml) in 89 patients withless severe envenoming and eight ampoules (80 ml) in 32 patientswith more severe envenoming. A second dose of four ampouleswas required in 20 patients. Patients receiving the three antivenoms were comparable in allrespects before treatment There were no deaths. The majorityshowed rapid clinical improvement, resolution of local envenoming,cessation of bleeding and restoration of blood coagulability.No differences in the efficacy of the three antivenoms wererevealed by clinical or laboratory observations, including measuresof haematological, haemostatic and biochemical ab normalities.Twelve patients developed abscesses (Butantan 1, Vital Brazil6, FUNED 5) and seven developed local necrosis (3,1,3). Of 88patients followed up 20–30 days after the bite 33 (37.5%)still had symptoms or signs of local envenoming, especiallyswelling. Early (anaphylactic) reactions were unexpectedly frequent afterall three antivenoms but were significantly more frequent withButantan (87%) than with Vital Brazil (37%) or FUNED (56%) antivenoms(p < 0.001). A possible explanation was the higher totalprotein content and percentage immunoglobulin of Butantan antivenom. The doses of antivenom recommended in Brazil and used in thisstudy may be unnecessarily high, resulting in an unacceptablyhigh incidence of reactions. Results of the study should prompta critical re-evaluation of antivenom production techniquesand dosage recommendations in Brazil.     

A Discordant Movement in Urine Calcium Excretion in Relation to Serum Calcium and Parathyroid Function Occurring Immediately after Birth

ABSTRACT. We studied the relationship between serum calcium and urinary calcium excretion in association with the parathyroid function in 28 neonates at birth and at five days of age. At birth, the urine calcium was low in spite of high cord serum calcium and a low parathyroid hormone level. On the fifth day of birth, urinary calcium excretion increased despite the reduction in serum calcium and an increase in the parathyroid hormone. These results suggest that the large increase in renal blood flow and the consequent increase in calcium load on the immature renal tubule occurring after birth may be the main cause for the change in this serum calcium-urinary calcium relationship. This finding can in part explain the temporary hypocalcemia during this period.     

Role of vagotony in sinus node dysfunction in children with symptomatic congenital long QT syndrome

The present study examined chronotropic dysfunction and the role of vagotony in congenital long QT syndrome, sinus node function and the effects of parasympathetic blockade. Six patients with congenital long QT syndrome were studied. The four males and two females, aged 1–15 years, had episodes of syncope and malignant ventricular arrhythmias. Congenital long QT syndrome was defined as a corrected QT interval greater than 0.45 s, T wave alternans and the age at diagnosis. The sinus heart rate measured from a 24 h electrocardiograph was abnormally low (< 50 min) in three patients (1, 4 and 5 years old) and did not increase sufficiently with the administration of atropine in five of the six patients with congenital long QT syndrome. From intracardiac electrophysiological studies, the corrected sinus node recovery time was prolonged in three patients and the total sinoatrial conduction time was prolonged in two patients. In most patients who had an abnormally long sinoatrial conduction time and corrected sinus node recovery time, these values returned to normal following atropine administration. In one patient, the corrected sinus node recovery time was prolonged paradoxically by atropine. Sinus node dysfunction in congenital long QT syndrome was affected by vagotony associated with a right sympathetic nerve system abnormality.     

Personality differences in the Munich Personality Test between patients with major depression and panic disorder

This study attempted to determine whether patients with major depression and panic disorder could be differentiated by personality features, measured by the Munich Personality Test (MPT). One of the six MPT personality dimensions, `rigidity', was developed in relation to the `melancholic type of personality', which may be a specific personality feature of depressive subjects. We therefore hypothesized that the MPT might be sensitive to possible personality differences between patients with major depression and panic disorder. Sixty-six patients with major depression and 27 patients with panic disorder, taken from consecutive intakes at an outpatient unit, were compared in terms of six personality dimensions of the MPT. The results demonstrated that rigidity could significantly differentiate the two patient groups, even after the possible confounding effects on the personality assessments were statistically partialled out. The MPT was suggested to be powerful for describing distinctive personality features of depressive subjects from anxiety subjects.     

Functional CD86 (B7-2/B70) is predominantly expressed on Langerhans cells in atopic dermatitis

Recently, we reported the functional expression of CD86 on cultured human Langerhans cells derived from normal epidermis. In the present study, we investigated the expression and function of co-stimulatory molecules in the pathogenesis of atopic dermatitis. In immunohistochemical analysis, CD80 and/or CD86 were detected on dendritic-shaped cells not only in the epidermis but also in the dermis in the inflammatory lesions of atopic dermatitis (n = 12). CD80 was expressed in only five cases (42%), while CD86 was expressed in all cases (100%). These molecules were not detected in normal control subjects (n = 8). In non-lesional skin of atopic dermatitis (n = 4). CD86 but not CD80 was detected in one case. CD86 was preferentially induced on dendritic-shaped cells in positive patch test sites to Dermatophagoides pteronyssinus or house dust allergen in atopic dermatitis (n = 4). The CD80- or CD86-positive cells were confirmed as Langerhans cells by double immunostaining using anti-CD1a monoclonal antibody. Neither CD86 over that CD80 was detected n keratinocytes. Similar results of the stronger expression of CD86 over that of CD80 were obtained from psoriasis vulgaris (n = 11) and from contact dermatitis (n=7), although CD86 was expressed only in 57% of the contact dermatitis cases. The percentage of Langerhans cells positive for CD86 was higher than for CD80, i.e. 48% compared with 9%, respectively, in the epidermis of lesional skin of atopic dermatitis (n=8). The expression rate of these molecules on Langerhans cells increased in the dermis. To investigate the function of co-stimulatory molecules on Langerhans cells in atopic dermatitis, we conducted an inhibition test with antibodies. Anti-CD86 monoclonal antibody almost completely nhibited T-cell proliferation stimulated with crude extract of D. pteronyssinus in the presence of epidermal cells as antigen-presenting cells, whereas anti-CD80 monoclonal antibody produced less of an inhibitory effect. These data indicate that CD86 expressed on Langerhans cells may play an important part in the pathogenesis of atopic dermatitis.for Investigative Dermatology. Washington, DC (1–5 May 1996).     

STUDIES ON CELL-MEDIATED IMMUNITY IN PATIENTS WITH COLORECTAL CANCER: LEUCOCYTE MIGRATION INHIBITION TEST USING ALLOGENIC 3M KCI EXTRACT

Leucocytes from patients with colorectal and other malignant and non-malignant gastrointestinal diseases as well as those from normal subjects were tested by the leucocyte migration inhibition test (LMIT), employing the method of Clausen, using five different allogenic 3M KCI soluble extracts of colorectal cancer tissue. The normal range of migration index (Ml) was found to be > 0.82 and > 1.20 by calculating the mean Ml ± 2SD of ten normal subjects with cancer extracts. Mis out of this range were considered to be pathological. In LMIT with a single tumour extract, a pathological Ml was found in 46% of 50 colorectal cancer patients, a significantly higher figure than found in the three other groups of patients (4% to 16%). In the panel mode of LMIT, that is, testing each blood sample with five different tumour extracts, 40/50 (80%) of patients with colorectal cancer were reactive, while 2/15 (13%) of gastric cancer patients showed a “positive” reaction; no positive reactivity was observed in the other two groups of patients. Thus “positive” reactivity was significantly commoner in patients with colorectal cancer than in patients belonging to the other groups. The frequency of “positive” reactivity was higher in patients with Dukes C carcinoma than in those with Dukes A or B carcinomas, though differences were not significant. In the follow-up study, marked depression of reactivity was seen 10 to 14 days after curative resection. In patients without recurrence, leucocyte migration was found to be in the normal range during the two to four weeks after surgery. “Positive” reactivity reappeared in patients with local recurrence. Thus the LMIT, particularly when tested by a panel mode, by demonstrating cell-mediated immunity against tumour-associated antigens of colorectal cancer, provides a method of monitoring colorectal cancer activity.     

Hemophagocytic lymphohistiocytosis in a human immunodeficiency virus-positive homosexual high school student

The spread of human immunodeficiency virus (HIV) infection has exploded over the past two decades and such infections in young people are no longer uncommon. However, the major infection route of pediatric patients remains vertical transmission, and sexual, especially homosexual transmission, is highly unusual. We herein describe the case of a 17-year-old boy who developed hemophagocytic lymphohistiocytosis (HLH). Although HLH was remitted soon with dexamethasone therapy, an HIV infection caused by homosexual transmission was detected.