Minor histocompatibility antigens as determinants for graft‐versus‐host disease after allogeneic haematopoietic stem cell transplantation

Minor histocompatibility antigens (minor H antigens) are genetically polymorphic peptides that have been shown to elicit immune response when mismatched between donor and recipient of haematopoietic stem cell transplantation (HSCT). Depending on the expression profiles, mismatches in these genes may either lead to harmful graft‐versus‐host (GvH) reaction or desired graft‐versus‐leukaemia (GvL) effect. We analysed retrospectively the effect of HLA‐restricted matching 11 established autosomal minor H antigens on the risk of graft‐versus‐host disease and relapse in 311 HLA‐matched sibling HSCT of a single centre. Increased incidence of chronic GvH disease was shown to be associated with mismatches in the HA‐8 and ACC‐1. The mRNA expression profiles in a large set of healthy and malignant tissue samples of minor H antigen genes demonstrated in silico that the expression profiles of HA‐8 and ACC‐1 were surprisingly different: HA‐8 gene was expressed in practically all tissues, whereas ACC‐1 gene had a restricted profile. The results demonstrated that mismatches in minor H antigens HA‐8 and ACC‐1 predisposed to chronic graft‐versus‐host disease (GvHD).     

Symptoms and diagnostic delay in patients with carcinoma of oesophagus and gastric cardia: a retrospective study of 225 patients

A retrospective review of 225 patients was made with regard to the symptoms of carcinoma of the oesophagus and gastric cardia, and the duration of the symptoms before medical attention was sought and before the establishment of the diagnosis. The age of the patients was 37-84 (mean 62·5) years (139 male, 86 female). The most common symptoms were dysphagia (93%), loss of weight (46%), vomiting (33%), gastric pain (25%) and thoracic pain (21%).     

Long-term maintenance of therapeutic response to lovastatin in patients with familial and non-familial hypercholesterolemia: a 3-year follow-up

The 3-year efficacy of lovastatin alone or in combination with colestipol was evaluated in 54 patients with type 2 hyperlipoproteinemia (22 non-familial and 32 familial hypercholesterolemic patients). A sufficient and sustained reduction in LDL cholesterol was achieved in non-familial hypercholesterolemia with lovastatin alone (average dose 74 mg/day, range 40-80 mg/d), whereas combination therapy with lovastatin 80 mg/d and colestipol (average dose 11.9 g/d, range 5-20 g/d) was required in familial hypercholesterolemia. The percentage changes from baseline at 3 years in serum LDL cholesterol, HDL cholesterol and total triglycerides were in the lovastatin-only group -53%, +10% and -15%, respectively, and in the two-drug group -58%, +22% and -18%, respectively. A subgroup analysis in patients with non-familial hypercholesterolemia indicated that the lipid-modifying effects of lovastatin were similar in type 2A and 2B phenotypes, except for a greater triglyceride lowering effect in type 2B. The lovastatin-alone regimen was well tolerated, whereas addition of colestipol caused subjective side effects in many patients. Serious side effects or discontinuations due to therapies did not occur. Both therapies caused slight but significant increases (within normal limits) in average serum transaminase levels. After 36 months a significant rise of 1.7 kg in mean body weight was observed in the lovastatin-only group. The ophthalmological follow-up did not reveal any cataractogenic effect attributable to treatment during the 3.8-year follow-up period.     

Carboplatin and Etoposide (Care) Combined with Radiotherapy and Vincristine, Doxorubicin and Cyclophosphamide (Vac) In Limited Small Cell Lung Cancer a Phase Ii Study

Sixty-eight patients with limited small cell lung cancer were treated between April 1988 and October 1990 with combination carboplatin 450 mg/m² i.v. on day 1 and etoposide 100 mg/m² i.v. on days 1-3 (CarE) for two courses, followed by thoracic radiotherapy (TRT) 50 Gy, and then vincristine 1 mg/m², doxorubicin 50 mg/m² and cyclophosphamide 750 mg/m² on day one (VAC) for four courses. Prophylactic cranial irradiation (30 Gy) was given to patients with CR after completion of chemotherapy. Sixty patients (89%) achieved an objective response (40% complete responses). The median time to progression was 8.5 months and median survival time 12.1 months. Predicted one- and two-year survival was 50% and 12% respectively. Myelosuppression was the main toxicity, with WHO grade 3 and 4 leukopenia occurring in 32% of VAC courses. There were 5 (7%) treatment-related deaths, all of them during VAC. We conclude that the present combination is active in terms of response rate, but it did not demonstrate any superiority in survival. The frequency of haematological toxicity was substantial during VAC courses.     

Identification of Discrete Polyadenylate-containing RNA Components Transcribed from HeLa Cell Mitochondrial DNA

Polyacrylamide gel electrophoresis and sedimentation analysis under denaturing conditions of poly(A)-containing RNA from the polysome region of the sedimentation pattern of a HeLa-cell mitochondrial lysate has revealed the occurrence of a discrete RNA component, which sediments in the native state with a sedimentation constant of about 7 S. From the sedimentation behavior under native and denaturing conditions and the poly(A) content, a molecular weight of about 9 x 10(4) has been estimated for this component. RNA.DNA hybridization experiments have indicated that this component is coded for by the light strand of mitochondrial DNA. Evidence for the occurrence of a poly(A)-containing RNA component sedimenting at about 9 S and coded for by the heavy strand has also been obtained.