Localized involutional lipoatrophy: a clinicopathologic study of 16 patients

BACKGROUND: Localized loss of adipose tissue without antecedent clinical or histologic inflammation is termed idiopathic lipoatrophy. OBJECTIVE: Our purpose was to study the clinical and pathologic features in 16 patients with clinically focal lipoatrophy and a distinct pathologic pattern of fat lobule involution. METHODS: A retrospective study of 16 patients was performed. RESULTS: The buttocks and proximal extremities were involved most frequently. Lesions were solitary in 10 patients and multiple in six. Nine patients had received intramuscular or intraarticular corticosteroid or antibiotic injections in the affected areas before the development of lipoatrophy. Histologic examination showed that individual fat cells were decreased in size and separated by hyaline material. Progressive reduction in the size and number of adipocytes resulted in diminutive fat lobules with prominent vessels resembling embryonic fat lobules. Some adipocyte masses were acidophilic. Scattered macrophages, confirmed by immunoperoxidase staining for CD68 (KP-1), were identified within the fat lobules and surrounding connective tissue. Yellow-gray granules were recognized within the cytoplasm of macrophages in nine cases. Macrophages becoming lipophages were observed by electron microscopy in one case. Other inflammatory cells were not prominent. CONCLUSION: This is a common pattern of postinjury response to fat tissue characterized by macrophage infiltration of the fat lobules in variable numbers. The term involutional lipoatrophy is justified by the resemblance of the distinctive pathologic changes to embryonic fat lobules.     

An open multicentre study of tropisetron for cisplatin-induced nausea and vomiting

1. P2X-receptors are ligand-gated ion channels which activate within milliseconds of agonist binding, causing rapid cellular depolarization and excitation. This makes them ideally suited to mediate the rapid neurotransmitter functions of adenosine 5'-triphosphate (ATP). 2. The initial postjunctional response of the vas deferens and most blood vessels to sympathetic nerve stimulation is a rapid, transient excitatory junction potential (EJP). With sufficient stimulation EJPs summate and the membrane depolarizes sufficiently to open voltage-dependent calcium channels, initiating a calcium action potential and contraction. 3. EJPs are inhibited by desensitization of the P2X-receptor by the stable agonist alpha, beta-methyleneATP (alpha, beta-meATP) and by the P2X-receptor antagonists ANAPP3, suramin and pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid, indicating that they are consequent upon activation of the P2X-receptor. 4. The P2X-receptor was originally defined by contractile studies in smooth muscle preparations, where a rank order of agonist potency of alpha, beta-meATP > > 2-methylthioATP (2-meSATP) > or = ATP was found. However, recent results show that the potency of ATP and 2-meSATP, but not alpha, beta-meATP, is decreased by 100-to 1000-fold by breakdown and when this is prevented, ATP and 2-meSATP are more potent than alpha, beta-meATP as agonists at the P2X-receptor. 5. This conclusion was supported by the cloning and functional expression of the P2X1-receptor from the rat bladder. A total of seven P2X-subunits have since been cloned and the P2X1-subunit is thought to be the predominant subunit expressed in vascular smooth muscle cells.     

Contribution to activity of histidine-aromatic, amide-aromatic, and aromatic-aromatic interactions in the extended catalytic site of cysteine proteinases

Within the papain family of cysteine proteinases few other residues in addition to the catalytic triad, Cys25-His159-Asn175 (papain numbering) are completely conserved [Berti & Storer (1995) J. Mol. Biol. 246, 273-283]. One such residue is tryptophan 177 which participates in a Trp-His-type interaction with the catalytic His159. In all enzymes of this class for which a three-dimensional structure has been reported, an additional highly conserved tryptophan, Trp181, also interacts with Trp177 via an aromatic-aromatic interaction in which the planes of the indole rings are essentially perpendicular. Also, both indole rings participate as pseudo-hydrogen bond acceptors in interactions with the two side chain amide protons of Asn175. Clearly, the proximity of Trp177 and Trp181 to the catalytic triad residues His159 and Asn175 and their network of interactions points to potential contributions of these aromatic residues to catalysis. In this paper, using cathepsin S, a naturally occurring variant that has a phenylalanine residue at position 181, we report the kinetic characterization of mutants of residues 175, 177, and 181. The results are interpreted in terms of the side chain contributions to catalytic activity and thiolate-imidazolium ion-pair stability. For example, the side chain of Asn175 has a major influence on the ion-pair stability presumably through its hydrogen bond to His159. The magnitude of this effect is modulated by Trp177, which shields the His159-Asn175 hydrogen bond from solvent. The His159-Trp177 interaction also contributes significantly to ion-pair stability; however, Trp181 and its interactions with Asn175 and Trp177 do not influence ion-pair stability to a significant degree. The observation that certain mutations at positions 177 and 181 result in a reduction of kcat/Km but do not appear to influence ion-pair stability probably reflects the contributions of these residues to substrate binding.     

High frequency and error-prone DNA recombination in ataxia telangiectasia cell lines

The only specific DNA repair defect found in ataxia telangiectasia (A-T) cells is mis-repair of cleaved DNA. In this report we measured DNA recombination, given its role in DNA repair and genetic instability. Using plasmids containing selectable reporter genes, we found a higher frequency of both chromosomal recombination (>100 times) and extra-chromosomal recombination (27 times) in SV40-transformed A-T cell lines compared with in an SV40-transformed normal fibroblast cell line. Southern analysis of single A-T colonies exhibiting post-integration recombination revealed that 24/27 had undergone aberrant rearrangements; recombination in normal fibroblast colonies was achieved by gene conversion in 8/11 clones and 10/11 clones showed unchanged copies of the plasmid. Using co-transfection of two integrating plasmids, each containing a separate deletion in the xgprt reporter gene, the 27 times difference in extra-chromosomal recombination was found when the plasmids were cleaved at a distance from the reporter gene. When the plasmids were cleaved within the reporter gene, the co-transfection frequency was reduced in A-T, but was increased in normal cells. We conclude that A-T cell lines have not only a high frequency chromosomal and extra-chromosomal recombination, but also exhibit error-prone recombination of cleaved DNA.     

An outbreak of type A botulism associated with a commercial cheese sauce

BACKGROUND: Although botulism is rare, recognition of a possible case of this illness represents a public health emergency. To prevent more cases, prompt investigation must be done to determine whether illness is linked to commercial product or restaurant. Botulism can masquerade as other illnesses, and seemingly unlikely foods can harbor botulinum toxin. OBJECTIVE: To confirm the diagnosis and determine the cause and extent of an outbreak of botulism associated with food served at a delicatessen. DESIGN: Retrospective cohort study of patrons of the delicatessen; laboratory analysis of food, serum samples, and stool samples; and traceback of implicated food. SETTING: Community in Georgia. PARTICIPANTS: Patrons of the delicatessen. MAIN OUTCOME MEASURES: Botulinum toxin in food, serum, or stool and Clostridium botulinum in food and stools. RESULTS: 8 of 52 patrons (15%) met the case definition for botulism. In 4 of the 8 patrons, and illness other than botulism was initially diagnosed. Five of the 8 were hospitalized, and 1 died. Stool cultures from 4 patrons yielded type AC. botulinum, and two serum samples contained botulinum toxin. All ill persons ate food from the delicatessen on 1 October 1993. Of the 22 persons who ate at the delicatessen that day, all 8 ill persons but none of the 14 well persons ate a potato stuffed with meat and cheese sauce. An open can of cheese sauce contained type A botulinum toxin and yielded C botulinum on culture. Cheese sauce experimentally inoculated with C botulinum spores became toxic after 8 days at a temperature of 22 degrees C (room temperature). CONCLUSIONS: A commercial, canned cheese caused a botulism outbreak. This product readily becomes toxic when contaminated by C botulinum spores and left at room temperature. Mild botulism caused by unusual vehicles may be misdiagnosed. Botulism should be included in the differential diagnosis of persons with signs or symptoms of acute cranial nerve dysfunction.     

Diffusion-weighted magnetic resonance imaging during brief focal cerebral ischemia and early reperfusion: evolution of delayed infarction in rats

The purpose of this study was to ascertain if the signal intensity ratio and the lesion area determined by diffusion-weighted magnetic resonance imaging during brief focal ischemia and early reperfusion predict outcome determined by diffusion-weighted magnetic resonance imaging and T2-magnetic resonance imaging at 24 h. Seventeen rats were imaged before and during 30 min of endovascular middle cerebral artery occlusion and at 15 min, and 23.5 h after the onset of reperfusion. Both hemisphere and basal ganglia signal intensity ratio increased significantly from baseline during ischemia, decreased significantly from ischemic levels during early reperfusion, and increased again at 24 h. However, signal intensity ratio during ischemia or after 45 min of reperfusion did not correlate statistically with diffusion-weighted-signal intensity ratio at 24 h. Both hemisphere signal intensity ratio and basal ganglia signal intensity ratio at 15 min of reperfusion correlated, but only moderately, with diffusion-weighted-signal intensity ratio at 24 h (r = 0.52, p < or = 0.05). Although lesion areas during ischemia were comparable to those observed at 24 h, lesion areas at both 15 and 45 min of reperfusion were significantly smaller than those observed during ischemia and at 24 hr. Thus, sequential imagining demonstrated partial resolution and delayed recurrence of magnetic resonance-defined ischemic lesions during reperfusion after brief focal ischemia.     

A review of hybrid integral transform solutions in fluid flow problems with heat or mass transfer and under Navier–Stokes equations formulation

Abstract

The Generalized Integral Transform Technique (GITT) is reviewed as a hybrid numerical–analytical approach for fluid flow problems, with or without heat and mass transfer, here with emphasis on the literature related to flow problems formulated through the full Navier–Stokes equations. A brief overview of the integral transform methodology is first provided for a general nonlinear convection–diffusion problem. Then, different alternatives of eigenfunction expansion strategies are discussed in the integral transformation of problems for which the fluid flow model is either based on the primitive variables or the streamfunction-only formulations, as applied to both steady and transient states. Representative test cases are selected to illustrate the different eigenfunction expansion approaches, with convergence being analyzed for each situation. In addition, fully converged integral transform results are critically compared to previously reported simulations obtained from traditional purely discrete methods.