Induction of antibody responses to breast carcinoma associated mucins using synthetic peptide constructs as immunogens

A strategy for directing and enhancing B cell immune responses against synthetic peptide determinants has been developed in order to produce antibodies specifically against protein epitopes of clinical relevance. A peptide sequence based upon the MUC-1 mucin protein core was selected for this purpose since anti-MUC-1 antibodies have proven diagnostic application and therapeutic potential in human breast and ovarian cancer. Peptide constructs were synthesised co-linearly linking the immunodominant B cell determinant region, PDTRPAP, in the protein core of the MUC-1 mucin, to sequence 111 – 120 of influenza haemagglutinin A/X-31, a determinant recognised by T helper cells through association with MHC class II molecules. Induction of anti-MUC-1 antibodies to the B cell determinant region by immunisation with peptide was shown to be dependent upon both the presence and the position of the T cell determinant. In addition, haplotype mismatching with respect to the T cell determinant resulted in a significant lowering of the anti-MUC-1 antibody response in peptide construct immunised mice. These findings are relevant to the design of immunogens to produce antibodies against peptide epitopes of tumour associated proteins and glycoproteins.     

Inclusion of satellites in an 18/21 translocation chromosome shown by ammonical-silver staining (sat-banding) in case of partial trisomy 18.

A male infant with a partial trisomy 18 and a 46,XY, --21, t(18;21)(18qter replaced by 18q12::21 p13 replaced by 21 qter) chromosome complement is described. The translocation chromosome is of special interest because it includes the satellites of chromosome 21. This was shown by differential satellite staining with the ammoniacal-silver technique.     

A new selective differential medium for isolation ofStenotrophomonas maltophilia

A new selective differential medium for the isolation ofStenotrophomonas (formerlyXanthomonas) maltophilia was developed. The medium, VIA agar, contained vancomycin, imipenem, and amphotericin B as selective agents and incorporated a mannitol/bromothymol blue indicator system. Compared withXanthomonas maltophilia Selective Medium (XMSM), VIA agar was less inhibitory toStenotrophomonas maltophilia and was more selective than XMSM in preventing the growth of unwanted bacteria from contaminated specimens. Although vancomycin-resistant strains ofEnterococcus faecium may grow on VIA agar, these can be easily distinguished fromStenotrophomonas maltophilia because of mannitol fermentation.     

Intrarenal haemodynamic and glomerular responses to inhibition of nitric oxide formation in rabbits.

1. The renal effects of inhibiting nitric oxide (NO) formation using N-nitro-L-arginine (NOLA, 20 mg kg-1) were examined using micropuncture techniques in pentobarbitone-anaesthetized rabbits. 2. Renal vascular resistance doubled from 2.7 +/- 0.5 to 5.0 +/- 1.1 mmHg ml-1 min-1 after NOLA (P < 0.01), with similar percentage increases in both pre- (149 +/- 38%, P < 0.01) and postglomerular (158 +/- 42%, P < 0.01) resistance. 3. Glomerular capillary pressure rose from 33 +/- 1 to 40 +/- 1 mmHg after NOLA (P < 0.01) but despite this, glomerular filtration rate (GFR) and single nephron glomerular filtration rate did not significantly change. 4. Blood pressure increased 18 +/- 1 mmHg (P < 0.001) within 10 min of NOLA administration and remained near this level for the next 90 min. 5. The glomerular ultrafiltration coefficient (Kf) decreased significantly from 0.085 +/- 0.022 to 0.035 +/- 0.006 nl s-1 mmHg-1 (P < 0.05). 6. Urine flow and sodium excretion increased markedly (26 +/- 9 to 337 +/- 102 microliters min-1 and 5 +/- 2 to 342 +/- 12 mumol min-1 respectively, (P < 0.001)) and sodium fractional excretion rose from 1.0 +/- 0.3 to 8.0 +/- 2.2% (P < 0.01). 7. Thus, administration of NOLA to rabbits caused vasoconstriction of both pre- and postglomerular vessels, diuresis and natriuresis without significant change in GFR, and a reduction in Kf. The results suggest that NO may play an important role in the regulation of renal haemodynamics and glomerular function.     

Human mini-chromosomes in mouse embryonal stem cells

We have introduced human mini-chromosomes of 4 Mb and approximately 15 Mb in size into mouse embryonal stem cells. Although these human mini- chromosomes are stable in hamster and chicken cells, they re-arrange or segregate aberrantly in the embryonal stem cells and are rapidly lost in the absence of selection. However, one of the mini-chromosomes re- arranged, acquired mouse centromeric sequences and was then stably maintained for at least 60 population doublings in culture. This mini- chromosome, which is 4 Mb in size, is a candidate for a mouse germ line chromosome vector.      

Targeted therapy comes of age in scleroderma

Systemic sclerosis (SSc, also known as scleroderma) has the highest case-specific mortality among the rheumatic diseases; however, advances in understanding of pathogenesis and an appreciation of the clinical heterogeneity of this disease, together with therapeutic advances in other areas, have raised the possibility of substantial improvements in its management. Key areas of advance include the development of clinical and laboratory methods for early detection of complications and the integration of vascular, immunomodulatory and antifibrotic therapies. Disease models have facilitated the identification of key mediators or processes that could be targeted therapeutically and have provided a platform for preclinical testing of novel candidate therapies. This review will consider current clinical aspects of SSc and the emergence of targeted therapy that is linked to key pathogenic processes or that targets pivotal mediators.     

Partial Artificial Heart (ALVAD) Use with Subsequent Cardiac and Renal Allografting in a Patient with Stone Heart Syndrome

The abdominal left ventricular assist device (ALVAD) is an order of magnitude more effective than conventional intra-aortic balloon pumping (IABP) in unloading and providing circulatory support to the failing left ventricle. This is a report of a unique case which demonstrates that in the absence of pulmonary vascular obstruction or constriction, the ALVAD can substitute for both left and right heart function. A 21-year-old patient with a congenital bicuspid aortic valve developed acute valvular endocarditis which rapidly progressed to congestive heart failure. An operation was undertaken, the mitral and aortic valves were excised and replaced by porcine heterografts, and a fistula from the right sinus of Valsalva to the right ventricle was closed. When coronary circulation was restored, irreversible ischemic contracture of the left ventricle, or "stone heart" syndrome, developed and emergency ALVAD or partial artificial heart implantation was effected. This device functioned as a total artificial heart for nearly six days, while a donor heart was sought. The patient then underwent removal of the ALVAD and cardiac and renal allografting. The transplanted heart functioned well, but the patient expired fifteen days later from gram-negative sepsis.