A developmental study of interphotoreceptor retinoid-binding protein (IRBP) in single and double homozygous rd and rds mutant mouse retinae

Interphotoreceptor retinoid-binding protein (IRBP) was studied using immunochemical and immunocytochemical techniques in retinae of mice with allelic combinations at the rd and rds loci at different stages of development and degeneration. Until postnatal day 7 (P7), IRBP is located intracellularly in developing retinae of the different genotypes. Thereafter, IRBP is present mainly in the interphotoreceptor matrix. As previously noted, cell death is slowest in the heterozygous +/+,rds/+ mutant with loss increasing in order in +/+,rds/rds, rd/rd, rds/rds and rd/rd,+/+ animals. The IRBP content of the total retina also approximates this pattern, with lowest amounts by far in rd/rd, rds/rds and rd/rd,+/+ mutants (after P14). Interestingly though, IRBP loss significantly precedes visual cell loss in the rd/rd,rds/rds retina. In all the mutants, the remaining rod cells in the outer nuclear layer exhibit synthesis of intracellularly located IRBP at late stages of degeneration. In the single homozygous rd/rd,+/+ and the double homozygous rd/rd,rds/rds mutants, IRBP is present intracellularly during the entire degenerative process with somewhat less intracellular IRBP in the rd/rd,rds/rds mutant. Retinae of homozygous +/+,rds/rds and heterozygous +/+,rds/+ animals exhibit a normal distribution pattern of IRBP immunoreactivity until loss of photoreceptor cells becomes pronounced at later stages of the disease. Many of the remaining cells at this time are probably cone elements although they are structurally changed. Double labeling with IRBP and S-antigen demonstrates, in many but not all, the presence of both proteins in the same cell body. Immunocytochemistry clearly demonstrated the presence of IRBP in remaining photoreceptor cells at late stages of the disease. Thus, the biochemically measured loss of IRBP appears to be a complex process neither directly dependent on the loss of photoreceptor outer segments and reduced interphotoreceptor matrix space (e.g. there is a sustained IRBP level in rodless rds mutants) nor simply due to cell death (e.g. in the rd/rd,rds/rds mutant, IRBP loss significantly precedes cell loss). That this IRBP is mainly intracellular, however, may indicate an abnormality in secretion which, combined with other factors, induces a degenerated and less differentiated phenotype.     

Poliomyelitis outbreak in Natal/KwaZulu, South Africa, 1987-1988. 1. Epidemiology.

An epidemic of type 1 poliomyelitis occurred in Natal/KwaZulu in the eastern part of South Africa between December 1987 and November 1988. 412 poliomyelitis cases were reported, of whom 74% were younger than 5 years. The case-fatality rate was 8%. It is suggested that massive floods, experienced in the area 2 months earlier, triggered the outbreak.     

Cellular and humoral reactivity pattern to the mycobacterial heat shock protein HSP65 in adjuvant arthritis susceptible and resistant Wistar rats.

We have analyzed the cellular and humoral immunity to the mycobacterial 65 KDa heat shock protein (hsp65) in a group of Freund's Adjuvant-immunized rats with a limited susceptibility to Adjuvant arthritis. According to the arthritis indices during the period of study (35 days), two different groups of rats could be distinguished; a) autoimmune Adjuvant arthritic rats (AA), and b) Non-arthritic animals (NA), including both rats which did not display any disease symptoms and rats suffering mild transient inflammation. The cellular response to the immunizing agent (Mycobacterium tuberculosis) or the mitogen Concanavalin A was comparable between both groups of rats. However, we detected an impaired cellular response to the individual hsp65 antigen in the animals that did not develop the disease. On the contrary, the level of hsp65-specific antibodies was much higher in NA animals than in AA rats suggesting a protective role for the hsp65 specific antibodies.     

Cardiovascular applications of magnetic resonance imaging and phosphorus-31 spectroscopy.

Recent advances in cardiovascular applications of magnetic resonance (MR) imaging and phosphorus-31 spectroscopy are reported. MR velocity mapping is a valuable adjunct to conventional imaging techniques, providing information on flow velocities as well as on absolute blood flow volume in the aorta and pulmonary arteries. Recently, ultrafast MR techniques have become available to evaluate myocardial perfusion with the aid of MR contrast agents as perfusion marker. Dynamic MR imaging is a powerful tool to assess cardiac function and ventricular mass. In particular, right ventricular function and mass can be evaluated with great accuracy, contributing to improved assessment of the significance of disease processes which may affect the right heart. The role of phosphorus-31 spectroscopy of the heart is expanding for the evaluation of ischemic myocardial disease and cardiomyopathies. The phosphocreatine to adenosine triphosphate ratio appears to be a marker of disease in patients with cardiac hypertrophy. In conclusion, MR imaging and phosphorus-31 spectroscopy is gaining widespread acceptance for evaluation of many cardiovascular disease processes.     

On the precision of diffusion/perfusion imaging by gradient sensitization.

Computer simulation is used to assess the precision and accuracy of diffusion and perfusion parameters derived from a set of gradient-sensitized images. Under ideal experimental conditions, a moderate signal-to-noise level (ca. 40) suffices to estimate diffusion coefficients to within 20% relative precision. However, estimation of a typical cerebral perfusion fraction of 5% to within 20% relative precision requires signal-to-noise levels of ca. 400. Simulations also show that systematic errors in perfusion fraction estimation, as well as underestimation of the uncertainties in perfusion parameters (by chi-squared analysis), will be found at moderate signal-to-noise levels.     

Referral pattern of patients with oral mucosal lesions in The Netherlands

The referral pattern of 140 Dutch patients with oral mucosal lesions, who had been referred to a Department of Oral & Maxillofacial Surgery and Oral Pathology, shows that patients with oral mucosal lesions consult the dentist as often as the family doctor as the first source of help or information. Furthermore, family doctors were much more used to refer patients with oral mucosal disease to medical specialists rather than to the dentist or the oral and maxillofacial surgeon.     

Renovascular hypertension and renal insufficiency treated with left nephrectomy and right autotransplantation

A patient presented with renal failure and severe hypertension. Arteriography showed a non-functioning kidney due to occlusion of the renal artery. The artery of the other contralateral kidney seemed unaffected. Converting enzyme inhibition resulted in normalization of the blood pressure, but this was accompanied by worsening of the renal failure. This was the clue for the detection of an origostenosis of the artery of the contralateral kidney, which could only be diagnosed by oblique angiograms. A revascularisation procedure by renal autotransplantation was performed. Simultaneously the non-functioning kidney was excised. The procedure resulted in an uneventful recovery of renal function. Diagnostic and therapeutic issues are discussed.     

Frequent administration of Dabis Maleate, a phase I study.

Dabis Maleate (1,4-bis(2'-chloroethyl)-1,4-diazabicyclo[2.2.1] Heptane dihydrogen dimaleate) (NSC 262666) is an alkylating quaternary nitrogen compound. In a previous phase I study using a once-every-3-weeks administration the dose-limiting toxicity was neurotoxicity and the recommended dose for phase II studies was 750 mg/m2 iv every 3 weeks. In vitro studies suggested a higher activity after more frequent administration, and in vivo studies a better therapeutic index with prolonged infusion. We studied 11 patients with solid tumors. Dose levels tested ranged from 250-750 mg/m2, either as a day 1-3 regimen or weekly, the latter as bolus administration or as prolonged infusion. The dose-limiting toxicity was neurotoxicity consisting of paresthesias and ataxia. Nausea and vomiting were moderate. No other major toxicity was observed. The dose recommended for phase II studies is 500 mg/m2/week as a 6-hour iv infusion for 6 weeks, followed by a 3-week rest period.