RELATIVE CONTRIBUTIONS OF EXTRACELLULAR Ca2+ AND Ca2+ STORES TO SMOOTH MUSCLE CONTRACTION IN ARTERIES AND ARTERIOLES OF RAT, GUINEA-PIG DOG AND RABBIT

1. These studies describe the functional effects of modulation of the sarcoplasmic reticulum (SR) Ca²⁺ stores at three levels of the vasculature: (i) large arteries (rat and guinea-pig aorta); (ii) small resistance arteries (rat tail artery, rabbit mesenteric artery, dog mesenteric artery); and (iii) arterioles (guinea-pig submucosal arterioles of the small intestine). 2. All tissues responded to phenylephrine (PE; 10 μmol/L) with a transient contraction in Ca²⁺-free Krebs', reflecting Ca²⁺ release from PE-sensitive Ca²⁺ stores. After pretreatment with cyclopiazonic acid (CPA; 30 μmol/L) or thapsigargin (TSG; 1 μmol/L), putative SR Ca²⁺ pump inhibitors, the PE-induced contraction in a Ca²⁺-free medium was significantly inhibited in arterial tissues at all levels of the vasculature. Similarly, ryanodine (RYA; 30 μmol/L), an agonist that enhances Ca²⁺ release from the SR, also reduced the PE contraction in a Ca²⁺-free solution. 3. CPA or TSG alone in the presence of extracellular Ca²⁺, caused marked and sustained contraction in the rat and guinea-pig aorta and marked but transient or no contraction in the resistance arteries. In the rat and guinea-pig aorta, RYA caused a slowly developing tension. Little increase in basal tension was produced by RYA in resistance arteries and arterioles. 4. The findings show that an agonist-releasable Ca²⁺ pool is present at all levels of the vasculature that is independent of the size of the vessels and suggest that under normal physiological conditions there is an intimate balance between the roles of the plasma membrane and of the SR in the maintenance of vascular contractility. It appears that the role of the SR diminishes as the arteries become smaller, while Ca²⁺ fluxes across the plasma membrane predominates.     

Mortality in Systemic Sclerosis (Scleroderma)

Two hundred and thirty-seven patients with systemic sclerosiswere followed prospectively in a scleroderma clinic. The overall3, 6, and 9-year survival rates were 86, 76 and 61 per centrespectively. Renal, cardiac and pulmonary disease, and olderage at enrolment were adverse prognostic factors associatedwith reduced survival. There were no significant differencesin survival between males and females or in patients with restrictedcompared to those with diffuse skin thickening. Death from systemicsclerosis was most frequently due to pulmonary hypertension,with fewer than expected deaths from renal or cardiac causes.Twenty-eight per cent of deaths were due to causes unrelatedto systemic sclerosis, most commonly cancer and ischaemic heartdisease, and in older patients     

The value of immunohistochemical markers in the diagnosis of cervical neoplasia

Summary. This study was designed to determine whether immunohistochemical stains for tumour-associated markers may be useful in the detection and differential diagnosis of premalignant and malignant lesions of the cervix. The expression of four markers detected by monoclonal antibodies, human milk fat globule 1 and 2 (HMFG-1 and 2), Cal and anti-carcinoembryonic antigen (anti-CEA) on conventional histological sections of various cervical lesions has been investigated. None of these markers was specific for neoplastic lesions of the cervix and all four markers were expressed by metaplastic as well as neoplastic cells, and it was concluded that their application in the histopathological examination of the cervix is limited.     

Lumbar myelography with iohexol and metrizamide: a comparative multicenter prospective study

Diagnostic quality of radiographs and adverse reactions associated with the use of metrizamide and iohexol as contrast agents in lumbar myelography were compared in a prospective randomized double blind study in 350 patients at seven centers. The contrast media were administered in comparable volumes at a concentration of 180 mg I per ml. Overall quality of radiographic visualization was graded good or excellent in 95% of 175 metrizamide studies and in 98% of 175 iohexol studies. Ninety-three patients examined using metrizamide (53%) and 130 patients examined using iohexol (74%) experienced no discomfort during or after myelography. Postmyelographic headache was associated with 38% of metrizamide examinations and 21% of iohexol examinations. Nausea and vomiting were also more common with metrizamide. Five patients examined using metrizamide (3%) experienced transient confusion and disorientation following lumbar myelography. No such reactions were observed following iohexol myelography.     

Gammadelta intraepithelial lymphocytes are essential mediators of host-microbial homeostasis at the intestinal mucosal surface

The mammalian gastrointestinal tract harbors thousands of bacterial species that include symbionts as well as potential pathogens. The immune responses that limit access of these bacteria to underlying tissue remain poorly defined. Here we show that γδ intraepithelial lymphocytes (γδ IEL) of the small intestine produce innate antimicrobial factors in response to resident bacterial "pathobionts" that penetrate the intestinal epithelium. γδ IEL activation was dependent on epithelial cell-intrinsic MyD88, suggesting that epithelial cells supply microbe-dependent cues to γδ IEL. Finally, γδ T cells protect against invasion of intestinal tissues by resident bacteria specifically during the first few hours after bacterial encounter, indicating that γδ IEL occupy a unique temporal niche among intestinal immune defenses. Thus, γδ IEL detect the presence of invading bacteria through cross-talk with neighboring epithelial cells and are an essential component of the hierarchy of immune defenses that maintain homeostasis with the intestinal microbiota.     

Patients with partial seizures: evaluation by MR, CT, and PET imaging

Fifty patients who experienced partial seizures were imaged with computed tomography (CT) and magnetic resonance imaging (MR); 14 of these also had imaging studies of local cerebral glucose metabolism with positron emission tomography (PET). Thirteen patients with attenuation abnormalities on CT scans also had abnormal signals on MR images; ten other patients had MR-image signal abnormalities but normal CT scans. In all seven patients undergoing PET who had MR-signal and sometimes also CT-attenuation abnormalities, areas of metabolic asymmetry were present. Positive PET scans were also seen in three patients with no evidence of abnormality on CT and MR studies. Focal cerebral substance loss on CT and MR studies, present in 21 patients, did not correlate well with electroencephalographic findings. MR is utilized as the initial imaging procedure in patients with partial seizures because it is more readily available and less invasive than PET and more sensitive than CT scanning.