Plasmodium vivax and P. chabaudi: inter-species cross-reacting antigens

A monoclonal antibody raised by immunization of BALB/c mice with erythrocytic stages of Plasmodium vivax was shown to react with asexual erythrocytic stages of P. chabaudi. The cross-reactivity molecules are antigens of 200 and 148 kDa in P. vivax and of 190 and 70 kDa in P. chabaudi. Immunofluorescence studies of the erythrocytic stages of P. vivax and P. chabaudi indicated that expression of these antigens increased as the parasites' developed from the ring stage to the schizont stage. In the mature trophozoites of P. chabaudi, immunoelectron microscopy revealed clusters of antigen distributed in the cytoplasm of the parasitized erythrocyte. In the schizont, packets of antigen were found associated with the parasitophorous vacuole and the cytoplasm of the infected host cell. Received: 19 March 1996 / Accepted: 28 August 1996     

Weight loss in a murine cachexia model is not associated with the cytokines tumour necrosis factor-alpha or interleukin-6.

Daily administration of an escalating dose of tumour necrosis factor-alpha (TNF-alpha) to female NMRI mice caused a progressive loss of body weight representing 12% of the original weight over a 6-day period. Weight loss was associated with a decreased food intake and pair-fed controls exhibited a weight loss of similar magnitude to that caused by TNF-alpha. However, weight loss in animals bearing a murine adenocarcinoma (MAC16) occurred without a change in energy intake and thus differed from that produced by TNF-alpha. Anti-TNF-alpha monoclonal antibodies at levels capable of protecting mice against lethal endotoxaemia were ineffective in reversing weight loss in animals bearing the MAC16 tumour and had no effect on the increase in tumour volume. Circulating levels of interleukin-6 were not elevated in animals bearing the MAC16 tumour and with a weight loss between 1.8 and 5.4 g. These results suggest that these cytokines are not involved in the cachexia produced by this murine tumour.     

New developments in sustained-release antihypertensive therapy: formulation and pharmacokinetic considerations.

In order to achieve a consistently absorbed form of nifedipine over 24 hours, a novel formulation approach, INDAS, was used to develop a once-daily, sustained-release (SR) form of nifedipine that could provide effective control of blood pressure at a low total daily dose. The pharmacokinetic characteristics of this new formulation of nifedipine-SR were compared with those of divided doses of conventional nifedipine. The SR formulation was shown to achieve a lower peak plasma nifedipine level but with a prolonged plasma profile characterized by an extended time to peak plasma levels (Tmax), a higher trough plasma level, a longer apparent half-life, and a markedly lower peak-to-trough fluctuation in plasma nifedipine concentrations. In a separate study, the gastrointestinal transit parameters and physical characteristics of the SR tablet were evaluated. This study established that the large intestine is the major site of residence and absorption for this dosage form. The physical erosion and disintegration characteristics of the SR formulation are such that a well-maintained absorption of nifedipine is consistently achieved over the 24 hour dosing interval.     

Liver transplant in a patient with a ventriculoperitoneal shunt.

There are no published accounts of patients with ventriculoperitoneal shunts undergoing liver transplantation in the literature. Because patients with ventriculoperitoneal shunts are prone to infections, this may be a theoretical contraindication to transplantation. We present a case of a patient with cirrhosis who had a ventriculoperitoneal shunt placed many years prior to transplantation. The patient had no neurological complications and the shunt was intact and functioning. Prior to transplantation, the patient underwent a ventriculoperitoneal to ventriculopleural shunt conversion that was reversed posttransplantation. Apart from some minor complications, the patient has done remarkably well from a graft and neurological perspective. In conclusion, patients who have ventriculoperitoneal shunts may be considered for liver transplantation as the risk of infectious and neurological complications is low and there are no deleterious effects on graft survival.     

Regional Variations in Peer Reviewed Liver Allocation Under the MELD System

The Model for End-Stage Liver Disease (MELD) is used to assign priority for liver transplantation candidates. The Organ Procurement and Transplantation Network (OPTN) approved recognized exceptional diagnoses (RED's) for which MELD fails to accurately measure priority. Centers can request increased MELD points in cases not recognized by this policy (non-RED's). Our aim was to compare regional practices to justify non-RED requests for MELD adjustments. The UNOS/OPTN database was queried to extract all adult cases for which a non-RED MELD adjustment was requested from 2/27/02 until 8/27/03. The data were stratified by region and justification. Data for 29,510 listings were available. 26,947 had complete diagnosis information. There were 827 non-RED requests of which 477 (57.7%) petitions were approved by the regional review boards (RRBs). The approval rate varied significantly among regions (range: 28-75%, p<0.0001). The most common non-RED's were complications of portal hypertension (48%). The percentage of patients listed with non-RED's varied significantly among regions (0.7-8.3 %, p<0.0001), as did the proportion of patients transplanted with non-RED's (2.1-31.9%, p<0.0001). Demographics did not differ among regions requesting non-REDs.Widespread regional variations exist in the handling of requests for non-REDs. These variations point to the need for reform to standard exception criteria.     

Screening microarrays of novel monoclonal antibodies for binding to T-, B- and myeloid leukaemia cells

We have developed a microarray (DotScan) that enables rapid immunophenotyping and classification of leukaemias and lymphomas by measuring the capture of cells by immobilized dots of 82 CD antibodies [Belov, L., de la Vega, O., dos Remedios, C.G., Mulligan, S.P., 2001. Immunophenotyping of leukemia using a cluster of differentiation antibody microarray. Cancer Res. 61, 4483; Belov, L., Huang, P., Barber, N., Mulligan, S.P., Christopherson, R.I., 2003. Identification of repertoires of surface antigens on leukemias using an antibody microarray. Proteomics 3, 2147]. The DotScan technology has been used to investigate the properties of 498 new antibodies submitted to the HLDA8 Workshop. These antibodies have been applied as 10 nl dots to a film of nitrocellulose on a microscope slide to make an HLDA8 microarray. After blocking the remaining nitrocellulose surface, individual arrays were incubated with each of 7 cell types from a human leukaemia cell panel consisting of three cell lines, CCRF-CEM (a T-cell acute lymphocytic leukaemia), MEC-1 (derived from B-cell chronic lymphocytic leukaemia) and HL-60 (a promyelocytic leukaemia), and four leukaemias from patients: a T-cell prolymphocytic leukaemia, a B-cell chronic lymphocytic leukaemia, and two acute myeloid leukaemias. Leukaemia cells were captured by those immobilized antibodies for which they expressed the corresponding surface molecule. Unbound cells were gently washed off, bound cells were fixed to the arrays and dot patterns were recorded using a DotScan array reader and quantified using DotScan data analysis software. The data obtained show the unique expression profiles of the 7 cell types in the leukaemia cell panel obtained with the DotScan microarray, and the differential capture patterns for these 7 cell types screened against the 498 antibodies in the HLDA8 microarray constructed for this study.