T helper-2 type of interleukins with de novo germinal center formation in the spleen during murine pregnancy

von Hippel-Lindau (VHL) disease is a dominantly inherited disorder predisposing those afflicted to hemangioblastomas of the central nervous system and the retina, renal cell carcinomas, pheochromocytomas, and pancreatic tumors. The disease has been associated with mutations of the VHL gene. The screening of 92 unrelated patients with VHL disease for point mutations in this gene revealed 61 DNA variants. In addition, a search for EcoR1 rearrangements revealed germline anomalies in 5 patients. The 61 variants could be subdivided in 20 mutations predicted to alter the open reading frame (8 nonsense mutations, 8 frame shift mutations, and 4 mutations in consensus splicing sites) and 43 DNA sequence variants of a priori unknown biological consequence (4 in-frame insertions or deletions, 36 missense mutations, and 3 apparently silent variations). The 3' end of the coding sequence of the VHL gene, which encodes the Elongin binding domain was the site of 5 of 20 truncating mutations (25%) and of 18 of 41 DNA variants (44%) causing uncertain functional impairment. A similar screening in 18 patients with sporadic hemangioblastoma revealed 2 missense DNA variants. In order to corroborate this latter observation, a systematic screening for germline alteration of the VHL gene might be performed in a larger series of sporadic hemangioblastoma. If this preliminary result is confirmed, more than 10% of sporadic hemangioblastoma might be related to a mild VHL disease, thus a follow-up program similar to that recommended in cases of VHL disease should probably be discussed in the corresponding families.     

Dengue virus-induced cytotoxic factor suppresses immune response of mice to sheep erythrocytes

The present study was undertaken to investigate if the suppressed cell-mediated immune responses observed in dengue type 2 virus (DV)-infected mice could be due to the cytotoxic factor (CF) produced in the spleens of DV-infected mice. We have observed that CF given intravenously (i.v.) kills splenic cells and reduces the total cells in the spleen. Mice treated with CF have a significantly depressed immune response to sheep erythrocytes, viz. delayed-type-hypersensitivity as measured by footpad swelling reaction at 24 hr; Jerne's antibody plaque-forming cells in the spleen; and migration inhibition of spleen cells in presence of antigen. These findings are similar to those seen earlier in DV-infected mice.     

The effects of propranolol HCl in hippocampal-lesioned rats

Experiments were conducted to determine the effects of propranolol administration in rats lesioned in the hippocampal area. Chronic oral administration of propranolol to intact rats produced a significant decrease in mean systolic blood pressure. No significant changes in blood pressure were produced with propranolol treatment in rats lesioned in the septal or anterior hypothalamic areas, whereas, in rats lesioned in the hippocampal area, a significant elevation of blood pressure was observed. These findings confirm previous results that suggest that the hypotensive effects observed with chronic propranolol administration are mediated via the hippocampus.     

Prevention of supraventricular tachyarrhythmias after open heart operation by low-dose sotalol: a prospective, double-blind, randomized, placebo-controlled study

BACKGROUND: The aim of this prospective, double-blind, placebo-controlled trial was to assess the preventive effect and safety of low-dose sotalol after heart operation. METHODS: Two hundred fifty-five consecutive patients referred for elective coronary artery bypass grafting (n = 220) or aortic valve operation (n = 35) were randomized to receive either 80 mg of sotalol twice daily (n = 126) or matching placebo (n = 129) for 3 months, with the first dose given 2 hours before operation. RESULTS: There were no significant baseline differences between the groups. Overall, supraventricular tachyarrhythmias occurred in 36% of patients (82% atrial fibrillation). Hospital stay was 11.6 +/- 5 days in patients with supraventricular arrhythmias, versus 9.5 +/- 2.4 days in patients without it (p < 0.0001). Low-dose sotalol reduced the rate of supraventricular arrhythmias from 46% (placebo) to 26% (sotalol; p = 0.0012), or by 43%. On the fourth postoperative day, heart rate was lower in the sotalol group (74 +/- 12 beats/min versus 85 +/- 15 beats/min; p < 0.0001) but the QT interval corrected for the heart rate was not prolonged (sotalol group, 0.44 +/- 0.03 second; placebo group, 0.43 +/- 0.03 second; p = not significant). Study medication had to be discontinued because of side effects in 5.6% of sotalol and 3.9% of placebo patients (p = not significant), with one possible proarrhythmic event occurring in a patient receiving sotalol. CONCLUSIONS: Because more than 90% of supraventricular arrhythmic episodes occurred within 9 days after operation and 70% of all possibly sotalol related side effects occurred after day 9, the findings in this study imply that prophylactic treatment with sotalol may be limited to the first 9 postoperative days.     

The relationship between abutment taper and resistance of cemented crowns to dynamic loading

This study investigated the relationship between abutment total occlusal convergence angle (taper) and the resistance of cemented crowns subjected to dynamic loading. Crown and abutment analogs were placed using zinc-oxide-eugenol, zinc-phosphate, glass-ionomer, or resin composite cement. Total occlusal convergence angles of 2.5, 5, 10, 15, 20, 30, and 40 degrees were used. Dynamic stresses were applied to the luted components until the bond failed or the components reached 10(6) load cycles. The data were analyzed using the staircase technique. The relationship between convergence and resistance was approximately linear for all the cements tested. Crowns luted with resin composite cement were more resistant to dynamic lateral loading than those placed using glass-ionomer or zinc-phosphate cements. Crowns luted with zinc-oxide-eugenol cement presented the least resistance to cyclic lateral stresses.     

An audit of the (ab)use of thyroid function tests

Lyme disease and tick-borne encephalitis have similar principal epidemiological features chiefly associated with their basic carrier and determinants of human infection. The cases of Lyme disease, as evidenced by laboratory studies, indicate that there are active natural foci of this infection in the city, frequently combining with natural foci of tick-borne encephalitis. At the same time a great quantity of cases of tick-borne encephalitis and Lyme disease (mixed infection) is notified in Tomsk.     

Regulation of B lymphocyte development by the truncated immunoglobulin heavy chain protein Dmu

Neural damage in 16 lateral retinacula excised at the time of Insall proximal realignments or isolated lateral retinacular releases performed in patients with symptomatic patellofemoral malalignment was evaluated by means of conventional histology and immunohistochemical and morphometric analyses. A relationship between clinical and histologic findings was found. An increase in the proportion of innervated tissue was correlated with anterior knee pain syndrome. We found a significant relationship between total neural area and pain. The group with moderate pain had the highest number of nerves and the highest neural area. In reference to total neural area and pain, there was a significant difference only between the patients with moderate pain and those with light pain, but not between patients with severe pain and those with moderate pain. The group with severe pain also showed a high neural area, although with a lower number of nerves. The severe-pain group had the largest nerves (24% of nerve fibers surpassing 25 microns diameter) in a zonal disposition, in which there were groups of nerve fibers in some fields and no nerve fibers in others. The group with moderate pain had an increase in medium and small nerve fibers (mean diameter, 18 microns), predominantly of tiny perivascular fibers. Moreover, we believe that instability in patients with patellofemoral malalignment can be explained in part because of loss of proprioception due to neural damage.     

A case of hydroa vacciniforme with unusual ear mutilation

A 22 year-old man visited our department with a 18-year-history of recurrent vesicular eruption on his skin when exposed to the sun. History revealed that the skin lesions developed as vesicles at first, then over the next several days, they formed crusts and healed with scarring. We were able to induce skin lesions by a repetitive UV-A provocation test. By the clinical and histologic features of the induced lesions, the case was diagnosed as hydroa vacciniforme (HV). However, no vesicular lesions were found on physical examination. Instead, in addition to varioliform scarring, we found various unusual clinical manifestations: burn-like lesions and crusts, flexion contracture of the digitum, and ear lobe mutilation. The ear lobe mutilation, which had not been reported previously in HV, was especially interesting.     

Structure-activity relation of NH2-terminal human parathyroid hormone fragments

Human parathyroid hormone (hPTH) is involved in the regulation of the calcium level in blood. This hormone function is located in the NH2-terminal 34 amino acids of the 84-amino acid peptide hormone and is transduced via the adenylate cyclase and the phosphatidylinositol signaling pathways. It is well known that truncation of the two NH2-terminal amino acids of the hormone leads to complete loss of in vivo normocalcemic function. To correlate loss of calcium level regulatory activity after stepwise NH2-terminal truncation and solution structure, we studied the conformations of fragments hPTH-(2-37), hPTH-(3-37), and hPTH-(4-37) in comparison to hPTH-(1-37) in aqueous buffer solution under near physiological conditions by circular dichroism spectroscopy, two-dimensional nuclear magnetic resonance spectroscopy, and restrained molecular dynamics calculations. All peptides show helical structures and hydrophobic interactions between Leu-15 and Trp-23 that lead to a defined loop region from His-14 to Ser-17. A COOH-terminal helix from Met-18 to at least Leu-28 was found for all peptides. The helical structure in the NH2-terminal part of the peptides was lost in parallel with the NH2-terminal truncation and can be correlated with the loss of calcium regulatory activity.