Systemic meningococcal infections in patients with acquired complement deficiency

Congenital deficiency of the late components of the complement may predispose the individual to systemic meningococcal infection. Assuming that patients with acquired complement deficiencies may also have an increased risk of contracting meningococcal infections, a retrospective and prospective study to assess this association was conducted. Over 20 years (1970-1989), 30 patients with meningococcemia or meningococcal meningitis, proven by blood or CSF culture, were treated at the Beilinson Medical Center. Only one patient died of the infection. Risk factors were found in three patients (10%). One had a congenital deficiency of C7, and two had acquired complement deficiency due to systemic lupus erythematosus (SLE) and membranoproliferative glomerulonephritis (MPGN). These latter two patients had low serum concentration of C3 and C4 and reduced complement hemolytic activity before onset of the infection. Since the incidence of culture-proven systemic meningococcal infection in the Jewish population in central Israel is 1/100,000, and the prevalence of SLE and MPGN is, at most, 250/100,000, the finding of two patients with meningococcal infection and these rare disorders is over 100 times the expected incidence. We conclude that patients with acquired complement deficiency are at significant risk of meningococcal infection.     

Traumatic tricuspid regurgitation complicating endocarditis and right-to-left intracardiac shunt. A case report of successful operation

OBJECTIVE: To assess the prevalence of cystinuria and cystine stone disease among families of patients with cystine stones, and to determine their distribution by age, sex and associated morbidity. SUBJECTS AND METHODS: The study comprised 180 relatives (87 males and 93 females, mean age 43 years) descended from two brothers over four generations who live in two areas in northern Jordan. Data were collected using a questionnaire and home visits, by urinary cystine testing and radiology to detect stone, and assessing hypertension and renal impairment. RESULTS: Of the 180 subjects, 104 (58%) had a positive reaction for cystine in urine; 33 (32%) of these were younger than 15 years. Twenty members (11%) of the families had evidence of renal cystine stone disease. Hypertension and renal impairment were detected in a significant proportion of individuals with cystine stone disease. CONCLUSION: Cystinuria is a major risk factor for cystine stone formation. Family screening is valuable in detecting the cystinuric population and in assessing individuals with stones. Early recognition, treatment and counselling result in better management and prevention. The establishment of a cystine study group in our region is essential.     

Autologous human monocyte-derived dendritic cells genetically modified to express melanoma antigens elicit primary cytotoxic T cell responses in vitro: enhancement by cotransfection of genes encoding the Th1-biasing cytokines IL-12 and IFN-alpha

DNA-based immunization strategies designed to elicit cellular antitumor immunity offer an attractive alternative to protein- or peptide-based approaches. In the present study we have evaluated the feasibility of DNA vaccination for the induction of CTL reactivity to five different melanoma Ags in vitro. Cultured, monocyte-derived dendritic cells (DC) were transiently transfected with plasmid DNA encoding human MART-1/Melan-A, pMel-17/gp100, tyrosinase, MAGE-1, or MAGE-3 by particle bombardment and used to stimulate autologous PBMC responder T cells. CTL reactivity to these previously identified melanoma Ags was reproducibly generated after two or three stimulations with genetically modified DC. Co-ordinate transfection of two melanoma Ag cDNAs into DC promoted CTL responders capable of recognizing epitopes from both gene products. Coinsertion of genes encoding the Th1-biasing cytokines IL-12 or IFN-alpha consistently enhanced the magnitude of the resulting Ag-specific CTL reactivity. Importantly, DC transfected with a single melanoma Ag cDNA were capable of stimulating Ag-specific CTL reactivity restricted by multiple host MHC alleles, some of which had not been previously identified. These results support the inherent strengths of gene-based vaccine approaches that do not require prior knowledge of responder MHC haplotypes or of relevant MHC-restricted peptide epitopes. Given previous observations of in situ tumor HLA allele-loss variants, DC gene vaccine strategies may elicit a greater diversity of host therapeutic immunity, thereby enhancing the clinical utility and success of such approaches.     

Vascular pathology of malignant cervical lymphadenopathy: qualitative and quantitative assessment with power Doppler ultrasound

BACKGROUND: Malignant vascular pathology has traditionally been studied with invasive angiography or in vitro immunohistochemistry. The objective of this study was to investigate the vascular patterns and vascular density of benign and malignant cervical lymphadenopathy using power Doppler ultrasound combined with a computed quantitative image processing system. METHODS: Investigations of 189 cervical lymph node lesions were undertaken prospectively using a 5-10 MHz linear array transducer in power mode. The types of vascular patterns displayed with power Doppler ultrasound, after sweep-scanning over the whole lymph node, were classified as hilar, spotted, peripheral, or mixed. Quantitative assessment of vascularity was made by sampling three parallel planes of each lymph node. A computed image processing system automatically calculated the density of vascular signals (called the "vascularity index" in this study) within the lymph node plane. RESULTS: Malignant lymph node lesions were shown to have higher vascularity indices (0.169+/-0.147, P < 0.01). The vascular patterns of benign lesions were mostly of avascular or hilar type (in 83% of cases). Malignant lesions were characterized by patterns of mixed (47%), spotted (20%), or peripheral type (11%). When vascular pattern (nonhilar type) and vascularity index (maximum > or = 0.09) were combined, the specificity for diagnosing malignant lymphadenopathy was as high as 97%. Variance in tumor vascularity was noted in both the benign and malignant groups. CONCLUSIONS: Power Doppler ultrasound combined with a computed image processing system provided an objective tool for assessing tumor vascularity quantitatively. Using this modality, the vascular pathology of malignant lymphadenopathy was found to be characterized by higher vascular density and aberrant vascular patterns.     

A heroin-, but not a cocaine-expecting, self-administration state preferentially alters endogenous brain peptides

The effects of L-type voltage-dependent Ca2+ channel blockers on apomorphine, bromocriptine and morphine-induced changes in locomotor activity were examined in mice. Apomorphine (4 mg/kg) and morphine (20 mg/kg) produced locomotor stimulation. Bromocriptine (8 mg/kg) produced a biphasic effect on motor behaviour, an early depressant phase, followed by locomotor stimulation. Amlodipine (2.5 mg/kg), nicardipine (10 mg/kg), diltiazem (10 mg/kg) and verapamil (10 mg/kg), which by itself did not affect locomotor activity, inhibited the stimulant phase of bromocriptine without altering the depressant phase, while they did not affect apomorphine- and morphine-induced locomotor stimulation. Apomorphine, bromocriptine and morphine-induced locomotor stimulation was decreased by SCH 23390 (R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7- ol) (0.05 mg/kg) or haloperidol (0.1 mg/kg). These results indicate that L-type voltage-dependent Ca2+ channels are involved in the motor stimulant effect of bromocriptine, but not in apomorphine- and morphine-induced locomotor stimulation. The effects of Ca2+ channel blockers on the dopaminergic system appears not to be directly related to dopamine receptor blockade.     

Effects of guan-fu base a on experimental cardiac arrhythmias and myocardial contractility

Guan-fu base A (GFA) is a terpenoid alkaloid isolated from the tuber of Aconitum coreanum in our institute. GFA (20-30 mg.L-1) reduced the ventricular tachycardia (VT) and ventricular fibrillation (VF) rate induced by K(+)-free and high Ca2+ solution in Langendorf heart of rats. Pretreatment of conscious rats with GFA 2.5-10 mg.kg-1 iv, increased the amount of beiwutine necessary to produce arrhythmias. Ouabain-induced VT in conscious dogs was reverted to sinus rhythm in 1-2 min by iv GFA 9-10 mg.kg-1. GFA 10-20 mg.kg-1 iv was also found to be effective in protecting anesthetized dogs from atrial fibrillation induced by topical application of ACh. GFA 10 mg.kg-1 iv obviously decreased heart rate and prolonged the P-R interval, but slightly affected the myocardial contractility in anesthetized dogs. GFA showed no obvious effect on stroke volume and cardiac output in conscious dogs. In conclusion, GFA showed therapeutic and prophylactic effect on different models of experimental arrhythmias without causing marked effect on myocardial contractility.     

Sorption of ethene and ethane on the V2O5(001)/TiO2(001) anatase interface

Simulation techniques have been employed to investigate the differences in the low energy adsorption configurations of ethene and ethane on the TiO₂ supported and unsupported V₂O₅(001) surface. We find that the ethene molecule approaches much closer to thesupported V₂O₅(001) surface which is reflected in the 40 kj mol^–1 higher adsorption energy. The low energy adsorption configuration located for ethane on the supported V₂O₅ shows that the molecule does not approach as close to the supported V₂O₅ surface as does ethene, resulting in the adsorption energy of ethane being 52 kJ mol^–1 lower than that of ethene on the supported V₂O₅ surface.     

INFLUENCE OF EXTRUSION ON DAMPING CAMCITIES OF AS-SPRAY DEPOSITED HIGH SILICON ALLOY ZA27 MODIFIED BY CERIUM

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