Microtubular inclusions in normal skin of systemic lupus erythematosus patients

Biopsy specimens of clinically normal skin of 9 consecutive patients with SLE were examined ultrastructurally to determine the presence and frequency of microtubular inclusions. Ten blood vessels were examined in each specimen; every specimen contained at least two positive blood vessels, and some contained 80 to 100% positive vessels. No correlation was found between the frequency of the inclusions and either the disease duration or antinuclear factor titer. The inclusions tended to be more frequent in patients with more acute disease. The absence of inclusions in normal skin may mitigate a diagnosis of SLE.     

Procoagulant activity of reversibly acylated human factor Xa

The plasma clotting factors used to treat hemophiliacs who have developed inhibitory antibodies have a shared history of limited clinical safety and utility. To improve on existing bypass factors, we have developed a reversibly acylated form of human plasma factor Xa capable of providing a time-dependent release of procoagulant activity. Factor Xa was treated with p-amidinophenyl p'-anisate to generate anisoyl Xa. The chemical modification of the protein involves acylation of the active site serine residue of factor Xa. Anisoyl Xa deacylated in a time, pH, and temperature-dependent manner. Active factor Xa generated on deacylation of anisoyl Xa exhibited amidolytic and prothrombinase complex activities in in vitro assays, the level being comparable to those of untreated factor Xa. When Anisoyl Xa was infused into rabbits, active factor Xa was generated on deacylation of the acylated enzyme, which shortened the activated partial thromboplastin time (APTT) in a dose-dependent manner. The duration of effect on rabbit APTT could be directly correlated to the level of human plasma factor Xa. Because anisoyl Xa bypasses the "tenase" complex that is compromised in hemophilia A and B and is unaffected by inhibitory antibodies, it has the potential to be used as an effective bypass therapy.     

Increased incidence in post-transplant diabetes mellitus in children: a case-control analysis

There is limited information regarding the incidence and features of post-transplant diabetes mellitus (PTDM) in pediatric renal transplant recipients. We noted a recent increased frequency of PTDM and reviewed charts of children who underwent renal transplantation from 1 September 1986 to 31 August 1999 to characterize the risk factors and natural history of PTDM. Sixteen children were identified with PTDM, and were each matched with two transplanted controls who did not develop PTDM. Clinical presentation varied from asymptomatic hyperglycemia to hyperosmolar dehydration or diabetic ketoacidosis. The mean time from transplantation to PTDM presentation was 1.2 years (range 1 day to 6.2 years). Significant risk factors for PTDM included: first degree family history of type 2 DM [odds ratio (OR) 23.9]; second degree family history of type 2 DM (OR 5.8); tacrolimus use (OR 9.1 versus cyclosporin); and hyperglycemia in the 2 weeks immediately after transplantation (OR 4.7). Seven of eight children with persistent PTDM continue to receive insulin. Patients with persistent PTDM had later onset disease (mean 1.9 years) compared to those with transient PTDM (0.3 years), suggesting different pathophysiologic processes. We suggest that all children undergoing renal transplantation be screened routinely for PTDM after transplantation, and that such patients may benefit from the avoidance of tacrolimus, as it may cause permanent beta-cell injury. Received: 23 March 2001 / Revised: 23 August 2001 / Accepted: 24 August 2001     

Ultrastrukturelle Veränderungen am Nierenparenchym durch ESWL unter Acetylsalicylsäure (ASS)

BACKGROUND: The risk of hemorrhagic complications after extracorporeal shock-wave lithotripsy (ESWL) increases in patients with aspirin intake, but the hematoma-inducing mechanism has not been understood completely at the ultrastructural level. METHODS: The effect off shock-waves on the kidneys of male Wistar-rats (n=24) was investigated in an experimental setting using a special ESWL device. Ultrastructural examination was performed by light-, transmission electron- and scanning electron microscopy. RESULTS: Shock-wave induced tissue damage appeared in all kidneys independently of aspirin intake. Endothelial detachment, lethal cell injury, gaps and mechanical disruption of the glomerular basement membrane were regularly found. After 1 week, repair processes were completed with evidence of permanent fibrosis in some cases. CONCLUSIONS: ESWL can induce modest as well as fatal damage to renal tissue cells. Therefore, after an ESWL-induced hematoma a second ESWL should not be performed within 1 week of the first treatment.     

Monoclonal antibodies to human platelet glycoprotein IIb beta that initiate distinct platelet responses

Hybridomas secreting monoclonal antibodies (MoAbs) to human platelet membrane glycoprotein IIb (GPIIb) were prepared by fusing cells of a mouse myeloma line to spleen cells from a BALB/c mouse immunized with purified GPIIb. Six of the hybridomas secreted MoAbs that recognized epitopes on the 23,000-dalton, disulfide-linked subunit of GPIIb, GPIIb beta. All six of these MoAbs agglutinated platelets in the absence of calcium. The agglutination titers of three of the MoAbs, however, were enhanced between 2 and 6 log2 dilutions when titrated in the presence of mmol/L of calcium. The enhancement in titer was the result of MoAb- induced platelet activation followed by platelet aggregation, a reaction that could also be initiated by the monovalent Fab fragments prepared from one of the MoAbs. The MoAbs did not significantly agglutinate platelets from patients with Glanzmann's thrombasthenia, confirming biochemical evidence that there is a paucity of GPIIb beta in the membranes of these cells. Our results show that MoAbs to epitopes on GPIIb beta initiate distinct platelet responses; therefore, they should be useful for studying the ways in which regions of surface glycoproteins are involved in platelet-platelet interactions. In addition, these reagents may prove of value in diagnosing and typing patients with Glanzmann's thrombasthenia.     

Minactivin expression in human monocyte and macrophage populations

Adherent monolayer cultures of human blood monocytes, peritoneal macrophages, bone marrow macrophages, and colonic mucosa macrophages were examined for their ability to produce and secrete minactivin, a specific inactivator of urokinase-type plasminogen activator. All except colonic mucosa macrophages produced and secreted appreciable amounts of minactivin, but only blood monocytes were stimulated by muramyl dipeptide (adjuvant peptide) to increase production. The minactivin from each of these populations could be shown to preferentially inhibit urokinase-type plasminogen activator and not trypsin, plasmin, or "tissue"-type plasminogen activator (HPA66). A plasminogen-activating enzyme present in monocyte cultures appeared unaffected by the presence of minactivin and could be shown to be regulated independently by dexamethasone.     

Monetary incentives enhance processing in brain regions mediating top-down control of attention

To evaluate the effect of an abstract motivational incentive on top-down mechanisms of visual spatial attention, 10 subjects engaged in a target detection task and responded to targets preceded by spatially valid (predictive), invalid (misleading) or neutral central cues under three different incentive conditions: win money (WIN), lose money (LOSE), and neutral (neither gain nor lose). Activation in the posterior cingulate cortex was correlated with visual spatial expectancy, defined as the degree to which the valid cue benefited performance as evidenced by faster reaction times compared to non-directional cues. Winning and losing money enhanced this relationship via overlapping but independent limbic mechanisms. In addition, activity in the inferior parietal lobule was correlated with disengagement (the degree to which invalid cues diminished performance). This relationship was also enhanced by monetary incentives. Finally, incentive enhanced the relationship of activation in the visual cortex to visual spatial expectancy and disengagement for both types of incentive (WIN and LOSE). These results show that abstract incentives enhance neural processing within the attention network in a process- and valence-selective manner. They also show that different cognitive and motivational mechanisms may produce a common effect upon unimodal cortices in order to enhance processing to serve the current behavioral goal.     

Deep fungal and higher bacterial skin infections in Thailand: clinical manifestations and treatment regimens

BACKGROUND: Deep fungal and higher bacterial skin infections occur fairly frequently in Thailand. METHODS: Cases with a provisional diagnosis of deep fungal and higher bacterial infections were prospectively collected from 1994 to 1997 in the Granuloma Clinic, Department of Dermatology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand. Demographic data, clinical manifestations, causative organisms, histologic features, treatment, and outcome were investigated. RESULTS: The total cases in a 4-year period numbered 27. The male to female ratio was approximately 1:1. Mycetoma was most common, followed by chromoblastomycosis. Actinomycetoma was similar in incidence to eumycetoma. The only causative organism that could be identified among the mycetoma cases was Cladosporium carrionii, which caused mycetoma of the buttock of an aplastic anemia patient at the site of bone marrow aspiration. Surgical treatment was recommended for eumycetoma. Chromoblastomycosis was caused by C. carrionii and F. compactum and responded well with itraconazole orally. Mycotic abscesses were found in four cases, basidiobolomycosis in two cases, and cutaneous nocardiosis in one case. Cotrimoxazole was recommended in the treatment of actinomycetoma, cutaneous nocardiosis, and basidiobolomycosis. CONCLUSIONS: Localized, chronic, slow, progressive, and usually asymptomatic were the main cutaneous manifestations of deep fungal and higher bacterial skin infections. A skin biopsy for histologic study and culture identification should be performed in every suspected case. The causative organisms were found in the histologic sections of every case, but only about one-third were found by culture.     

射频毁损治疗肝脏肿瘤

肝脏肿瘤包括肝原发性肿瘤和肝转移瘤,其治疗目前仍首选手术切除,但确诊时85％～95％的患者已失去手术切除时机,对难以手术治疗的患者已有多种介入治疗方法,如肝动脉栓塞化疗(TAE)、经皮无水酒精注射、微波、激光、冷冻、高功率超声聚焦等。射频毁损(radiofrequency ablation,RFA)是近年国外刚用于肝脏肿瘤治疗的新技术,具有安全性高、并发症少、患者易耐受、肿瘤复发可重复治疗等优点,具有良好的应用前景。 1 射频治疗仪及治疗机制 1868年法国的d'Arsonval发现高于10KHz的高变电流通过活体组织时,并不引起神经肌肉的应激,但局部产热造成组织毁损,自此射频毁损术在神经及心血管领域得以应用并     

Cloning of the LH/CG receptor implications for a unique G-protein coupled receptor.

The proteins encoded by the rat and porcine luteinizing hormone (LH)lchorionic gonadotropin (CG) receptor cDNAs appear to be unique members of the G -protein-coupled receptor family. Although they have the characteristic seven transmembrane domains, the LH/CG receptors have relatively low homology to other members o f this family, do not have a G-protein-coupling domain corresponding to that of the a-adrenergic receptor, and contain an unusual long extracellular domain. Experience in the molecular dissection of this receptor family will help guide investigation of the LHICG receptor's functional domains. Further studies are needed to clarify the origin and significance of the various mRNA species hybridizing on Northern blot analyses. Finally, the rat and porcine receptor cDNAs should permit cloning of the human LH/CG receptor, as well as cloning of the thyroid-stimulating hormone and follicle-stimulating hormone receptors.