The mouse Mid1 gene: implications for the pathogenesis of Opitz syndrome and the evolution of the mammalian pseudoautosomal region

We have recently reported isolation of the gene responsible for X- linked Opitz G/BBB syndrome, a defect of midline development. MID1 is located on the distal short arm of the human X chromosome (Xp22. 3) and encodes a novel member of the B box family of zinc finger proteins. We have now cloned the murine homolog of MID1 and performed preliminary expression studies during development. Mid1 expression in undifferentiated cells in the central nervous, gastrointestinal and urogenital systems suggests that abnormal cell proliferation may underlie the defect in midline development characteristic of Opitz syndrome. We have also found that Mid1 is located within the mouse pseudoautosomal region (PAR) in Mus musculus , while it seems to be X- specific in Mus spretus. Therefore, Mid1 is likely to be a recent acquisition of the M. musculus PAR. Genetic and FISH analyses also demonstrated a high frequency of unequal crossovers in the murine PAR, creating spontaneous deletion/duplication events involving Mid1. These data provide evidence for the first time that genetic instability of the PAR may affect functionally important genes. In addition, we show that MID1 is the first example of a gene subject to X-inactivation in man while escaping it in mouse. These data contribute to a better understanding of the molecular content and evolution of the rodent PAR.      

The use of natural interferon alpha conjugated to a monoclonal antibody anti mammary epithelial mucin (Mc5) for the treatment of human breast cancer xenografts

Summary An immunoconjugate composed of natural interferon (nIFN) bound in a noncleavable fashion to a monoclonal antibody (MoAb) recognizing a breast epithelial membrane mucin (Mc5) was used to treat xenografts of a human mammary carcinoma cell line (MCF-7) growing in nude mice. The immunoconjugate (nIFN/Mc5) was administered as 20 intralesional (i.l.) injections to 1 of 2 xenografts in each animal. It was found that nIFN/Mc5 produced a significant enhancement of the growth inhibitory actions of nIFN on the injected tumors. Further enhancement was obtained when nIFN or nIFN together with Mc5 (at a dose 10 times larger than that present in nIFN/Mc5) were added to the immunoconjugate. Biodistribution experiments showed that the uptake of¹²⁵I-nIFN/Mc5 by the tumors was greater and its elimination slower than for¹²⁵I-nIFN alone or conjugated to irrelevant mouse IgG₁. In addition, the immunoconjugate up-regulated the antigenic expression of a breast epithelial membrane mucin by the carcinoma cells, an up-regulation which was not significantly different from that produced by nIFN alone. The contralateral noninjected tumors exposed to systemic levels of the immunoconjugate showed an enhancement of antitumor effects, but to a lesser extent than the injected tumors. These findings suggest that the enhancement of the growth inhibitory action of the immunoconjugate was related to the specific binding of Mc5 which targeted the IFN to the carcinoma cells and impeded its elimination. It is likely that the targeting was favored by the IFN-mediated up-regulation of antigenic expression by the carcinoma cells, thereby producing a cascade of interrelated effects. The results of this study point out the feasibility and potential usefulness of IFN treatment by means of immunoconjugates as well as the worth of pursuing and improving this form of therapy.     

Home nutrition survey in the UK: the patient's perspective

A detailed survey questionnaire compiled by the executive committee of Patients on Intravenous and Nasogastric Nutrition Therapy (PINNT) was circulated in November 1991 to the postal addresses of all full (patient) members of PINNT in the UK. The objective of the survey was to identify current practices and problems of home nutrition support as seen from the patients perspective. 128 questionnaires were distributed. 87 (68%) analysable questionnaires were completed and returned. 77 were for parenteral nutrition (HPN) patients and 10 for patients on enteral nutrition (HEN). Areas of concern for patients include the practicalities of administration of lipid and additives, and problems associated with the appearance of air in infusion bags. Although most patients appeared happy with the home nutrition support services 18% commented on particular negative aspects. This survey highlights such areas which may not be identified during routine patient/clinician contact.     

Patient expectations and marketing programming for OB/GYN services

A regional medical center OB/GYN practice was perceived as being too large to give personalized attention. A combination of growing market potential and declining market share caused the center administrators to take a bold step and design, open, and operate a new parallel OB/GYN practice. The practice was developed based on analysis of patient perceptions and needs. Research results were used to develop a marketing program. The project involved doctors, nurses, and staff who were interested in patient perceptions and were willing to adjust health care delivery to satisfy patients' expectations.     

EFFICACY OF SUCRALFATE IN PREVENTING GASTROINTESTINAL SIDE EFFECTS OF NSAIDs

To find out the efficacy of sucralfate in preventing gastrointestinal side effects of non-steroidal anti-inflammatory drugs (NSAIDs) a prospective, randomised single blind study was conducted from 1989 to 1992. Patients with osteoarthritis, rheumatoid arthritis and other long standing painful conditions, who were expected to receive NSAIDs for over three months, were recruited into the study. All medicines were discontinued for a period of 10–15 days prior to initial endoscopic assessment. NSAID therapy was started and the patients were randomised to receive either placebo (group A) or sucralfate (group B) in addition. Patient were reassessed clinically every week and an endoscopic examination was repeated after 6–8 weeks of follow-up. A total of 176 patients were studied in group A (n=91) and group B (n=85). At the end of 8 weeks gastrointestinal symptoms were present in 30.6% and 26.4% patients of group A and B respectively. Endoscopic assessment showed superficial lesions in 36.5% and 18.7% while endoscopic ulcer in 2.4% and 1.1% patients of groups A and B respectively. Thus in patients receiving chronic NSAID therapy, simultaneous administration of sucralfate reduces the incidence of superficial gastric lesions but has no significant effect on symptoms or ulcer formation.KEY WORDS: Gastropathy, Sucralfate, Nonsteroidal anti-inflammatory drugs     

Dehydration: a model for (low-temperature) argon laser tissue bonding

Despite considerable investigation, the mechanism of laser assisted vascular anastomosis remains unknown. Indications suggest that bonding is the result of thermal action, particularly the thermal denaturation of tissue proteins. However, our own work has led us to conclude that dehydration is an important factor. Hence, we have proposed that laser anastomosis is the result of dehydration at the apposed tissue faces, induced by laser irradiation. This was investigated by comparing the properties of bonds created by dehydration with those created by laser. The bonds were created using parameters consistent with laser anastomoses created in vivo. Results revealed that anastomoses created by dehydration were equivalent to those created by laser, with little difference in strength, histology or response to rehydration. The only significant difference (p < 0.02) was mean bond strength created at temperatures above the denaturation temperature of the tissue (548 g cm(-2) by laser, 994 g cm(-2) by dehydration). Given the similarity of bonds created by the two methods, we conclude that the same mechanism (i.e. dehydration) is likely to be responsible for bonding in both cases and therefore that argon laser bonding is mediated by dehydration.     

Methylmercury poisoning in Canadian Indians--the elusive diagnosis

A World Health Organization Expert Committee has concluded that symptoms of methylmercury poisoning may appear at blood concentrations of 200-500 ng Hg/ml. Blood levels in this range have been found in several Indian and Inuit communities in Canada. The syndrome of severe methylmercury poisoning (Hunter-Russell syndrome) is well described. However, diagnosis of less severe cases is difficult. This paper review the present situation in Canada. The problems of diagnosis currently being encountered are discussed and are illustrated by the case of an individual who had one of the highest blood concentrations (551 ng Hg/ml) ever described in fish-eating populations outside of the outbreaks in Minamata and Niigata in Japan. Although mercury concentrations in brain were estimated to have been in the "symptomatic" range at least once in the two years prior to his death, neurohistological examination was normal. Detailed examination by two teams of neurologists revealed effects that may be associated with methylmercury poisoning but a definitive diagnosis remained elusive.