Thyroid hormone resistance. Clinical, biochemical and genetic study of a family

OBJECTIVE: To investigate the incidence rate of IDDM in China. RESEARCH DESIGN AND METHODS: The Chinese IDDM registry was established in 1991 as part of the World Health Organization's Multinational Project for Childhood Diabetes (DiaMond) project. Twenty-two centers were developed to monitor the incidence of IDDM in children < 15 years of age. The population under investigation includes > 20 million individuals, representing approximately 7% of the children in China. Capture-recapture methods were used to estimate the ascertainment. RESULTS: The overall ascertainment-corrected IDDM incidence rate in China was 0.51 per 100,000, the lowest rate ever reported. There was a 12-fold geographic variation (0.13-1.61 per 100,000). In general, the incidence rate was higher in the north and the east. There was a sixfold difference among ethnic groups (highest: Mongol group, 1.82 per 100,000; lowest: Zhuang group, 0.32 per 100,000). CONCLUSIONS: China has an extremely low overall IDDM incidence rate. China also has the greatest geographic and ethnic variation seen for any country.     

Engagement of T cell receptor triggers its recruitment to low-density detergent-insoluble membrane domains

T-cell receptors (TCRs) upon binding to peptide-MHC ligands transduce signals in T lymphocytes. Tyrosine phosphorylations in the cytoplasmic domains of the CD3 (gammadeltaepsilon) and zeta subunits of the TCR complex by Src family kinases initiate the signaling cascades via docking and activation of ZAP-70 kinase and other signaling components. We examined the role of the low-density detergent-insoluble membranes (DIMs) in TCR signaling. Using mouse thymocytes as a model, we characterized the structural organization of DIMs in detail. We then demonstrated that TCR engagement triggered an immediate increase in the amount of TCR/CD3 present in DIMs, which directly involves the engaged receptor complexes. TCR/CD3 recruitment is accompanied by the accumulation of a series of prominent tyrosine-phosphorylated substrates and by an increase of the Lck activity in DIMs. Upon TCR stimulation, the DIM-associated receptor complexes are highly enriched in the hyperphosphorylated p23 zeta chains, contain most of the TCR/CD3-associated, phosphorylation-activated ZAP-70 kinases and seem to integrate into higher order, multiple tyrosine-phosphorylated substrate-containing protein complexes. The TCR/CD3 recruitment was found to depend on the activity of Src family kinases. We thus provide the first demonstration of recuitment of TCR/CD3 to DIMs upon receptor stimulation and propose it as a mechanism whereby TCR engagement is coupled to downstream signaling cascades.     

Is the treatment of left ventricular systolic dysfunction different according to the etiology?

Matrix metalloproteinase inhibitors of general formula (1) were synthesised by a route involving an Ireland-Claisen rearrangement which enables systematic modification of the substituent alpha to the hydroxamic acid. An analogue (12c) possessing an alpha-cyclopentyl group is a potent broad spectrum inhibitor that displays high and sustained blood levels following oral dosing in both the rat and marmoset ex-vivo bioassays. This compound and analogues are also potent inhibitors of TNF alpha release.     

Immunodominance does not result from peptide competition for MHC class II presentation

Despite the fact that Ca2+ transport into the sarcoplasmic reticulum (SR) of muscle cells is electrogenic, a potential difference is not maintained across the SR membrane. To achieve electroneutrality, compensatory charge movement must occur during Ca2+ uptake. To examine the role of Cl- in this charge movement in smooth muscle cells, Ca2+ transport into the SR of saponin-permeabilized smooth muscle cells was measured in the presence of various Cl- channel blockers or when I-, Br-, or SO42- was substituted for Cl-. Calcium uptake was inhibited in a dose-dependent manner by 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) and by indanyloxyacetic acid 94 (R(+)-IAA-94), but not by niflumic acid or 4,4'-dinitrostilbene-2,2'-disulfonic acid (DNDS). Smooth muscle SR Ca2+ uptake was also partially inhibited by the substitution of SO42- for Cl-, but not when Cl- was replaced by I- or Br-. Neither NPPB nor R(+)-IAA-94 inhibited Ca2+ uptake into cardiac muscle SR vesicles at concentrations that maximally inhibited uptake in smooth muscle cells. These results indicate that Cl- movement is important for charge compensation in smooth muscle cells and that the Cl- channel or channels involved are different in smooth and cardiac muscle cells.     

Laparoscopic appendectomy in the adult

AIM OF THE STUDY: The benefits of laparoscopic appendectomy remain controversial. The aim of the study was to evaluate the advantages and disadvantages of this technique. MATERIAL AND METHODS: Four hundred and forty-eight patients operated on for suspected appendicitis during a 5-year period were analysed in a retrospective study. The preoperative diagnosis was corrected in 21.4% of the cases (8.1% for males and 28.7% for females) and the conversion rate was 9.7%. There were 17 patients with generalized peritonitis and 28 with localized peritonitis. During the past year, this surgical method was introduced in another hospital and a prospective study included 92 consecutive patients operated on for appendicitis. The operating time was 53 minutes and the conversion rate was 7.6%. There were five patients with generalized peritonitis and eight with localized peritonitis. RESULTS: There were no postoperative deaths. In the first period, the morbidity rate was 2.3% in the laparoscopic group without conversion. After pathological examination, there was a 14.2% rate of normal appendix. The mean hospital stay was 4.3 days. In the second period, there were only three minor complications and the mean hospital stay was 4.19 days. CONCLUSION: The choice of laparoscopic approach is associated with some advantages: corrections of the diagnosis (mainly in young women) and simplification of the postoperative course, provided that the surgeon has sufficient experience.     

Breast implants

We describe the case - to our knowledge unique - of an 8-year-old boy who presented with acute onset of lower cranial nerve palsy and tetraparesis caused by a hematoma in a dorsal exophytic pilocytic astrocytoma of the medulla oblongata. The boy showed near-complete recovery after neurosurgical management in two stages: first, emergency evacuation of the hematoma with tumor biopsy, and second, complete tumor removal 5 months after the initial event. Intraoperative electrophysiological monitoring techniques for the lower cranial nerves are of value in preserving their functional integrity. Ultrasonography is helpful in assessing the extent of tumor removal. Although the pathological diagnosis of a pilocytic astrocytoma would not justify radiotherapy, local field radiotherapy was added mainly because of the unexpectedly rapid tumor progression during the interval between the two surgical procedures. The literature on brainstem and tumor hematoma in children is reviewed.     

Adrenomedullin and CGRP receptors mediate different effects in the rat adrenal cortex

Adrenomedullin (AM) exerts its effects through two distinct receptor subtypes: the AM receptor, and the CGRPI receptor. In most tissues activation of these subtypes brings about similar effects, with only the magnitude of the effect varying. In the rat adrenal cortex, however, this does not appear to be the case. Both CGRPI and AM receptors are present in the rat adrenal cortex. Incubation of zona glomerulosa cells with AM caused an increase in aldosterone secretion, but AM had no effect on angiotensin II-stimulated aldosterone secretion. The action of AM was not affected by CGRP8-37, the CGRP receptor antagonist, suggesting that its effect was mediated by the adrenomedullin receptor. CGRP on the other hand, did not significantly affect basal aldosterone although it attenuated the response to angiotensin II. These data suggest that the CGRP receptor and the AM receptor mediate different effects in the rat adrenal zona glomerulosa.     

Markers and determinants of progression of HIV-1 infection

A 68-year-old man underwent mitral valve replacement because of mitral regurgitation (prolaps of anterior mitral leaflet) using parasternal incision (Delos M. Cosgrove, minimally invasive surgery). He had been treated as pulmonary tuberculosis previously and had undergone esophagus operation using stomach role reconstruction beneath the sternum four years before the mitral valve procedure. We could not select median-sternotomy as an approach due to stomach role beneath the sternum, nor left posterolateral thoracotomy because of the heavy left-side pleural adhesion. Cardio-pulmonary bypass cannulations were performed through the same incision, because severe atherosclerosis was found at the distal arteries of the abdominal aorta.