Expression and function of the homoeotic genes Antennapedia and Sex combs reduced in the embryonic midgut of Drosophila

Drosophila homoeotic genes control the formation of external morphological features of the embryo and adult, and in addition affect differentiation of the nervous system. Here we describe the morphogenetic events in the midgut that are controlled by the homoeotic genes Sex combs reduced (Scr) and Antennapedia (Antp). The midgut is composed of two cell layers, an inner endoderm and an outer visceral mesoderm that surround the yolk. Scr and Antp are expressed in the visceral mesoderm but not in the endoderm. The two genes are required for different aspects of the midgut morphogenesis. In Scr null mutant embryos the gastric caeca fail to form. Scr is expressed in the visceral mesoderm cells posterior to the primordia of the gastric caeca and appears to be indirectly required for the formation of the caeca. Antp is expressed in visceral mesoderm cells that overlie a part of the midgut where a constriction will form, and Antp null mutant embryos fail to form this constriction. An ultrastructural analysis of the midgut reveals that the visceral mesoderm imposes the constriction on the endoderm and the yolk. The mesodermal tissue contracts within the constriction and thereby penetrates the layer of the midgut endoderm. Microtubules participate in the morphological changes of the visceral mesoderm cells. The analysis of the expression of Scr in Antp mutant embryos revealed a case of tissue-specific regulation of Scr expression by Antp. In the epidermis, Antp has been shown to negatively regulate Scr, but it positively regulates Scr in the visceral mesoderm.     

Hormonal treatment of endometrial carcinoma: An overview and new development in biology

Progestins are routinely used in the treatment of endometrial carcinomas with about 30% response rate. After a 10–12 month mean response time, the tumors begin to regrow. This clinical situation has been reproduced in the experimental model for human endometrial carcinomas, developed by us. The model consists of growth and maintenance of human endometrial carcinomas of different histologic grade and sex steroid receptor content, in defined hormonal milieu, by serial transplantation in athymic nude mice. Biologically and clinically relevant information on the role of steroid receptors in eliciting hormonal responses, the effect of combination treatment with tamoxifen and progestin and the mechanism of resistance to this treatment after an initial response have been obtained. These studies form the basis for designing and testing rational treatment strategies for human endometrial carcinomas.     

Tired,weak, or in need of rest: fatigue among general practice attenders.

OBJECTIVES--To determine the prevalence and associations of symptoms of fatigue. DESIGN--Questionnaire survey. SETTING--London general practice. PARTICIPANTS--611 General practice attenders. MAIN OUTCOME MEASURES--Scores on a fatigue questionnaire and reasons given for fatigue. RESULTS--10.2% Of men (17/167) and 10.6% of women (47/444) had substantial fatigue for one month or more. Age, occupation, and marital status exerted minor effects. Subjects attributed fatigue equally to physical and non-physical causes. Physical ill health, including viral infection, was associated with more severe fatigue. Women rather than men blamed family responsibilities for their fatigue. The profile of persistent fatigue did not differ from that of short duration. Only one person met criteria for the chronic fatigue syndrome. CONCLUSIONS--Fatigue is a common complaint among general practice attenders and can be severe. Patients may attribute this to physical, psychological, and social stress.     

Effectiveness and hazards of case finding for a high cholesterol concentration.

OBJECTIVE--To see whether adults with high blood cholesterol concentrations (greater than 6.5 mmol/l) detected by case finding return to their doctor, receive appropriate advice, and report changes in their diet and whether adults found not to have high cholesterol concentrations on case finding are discouraged from changing their diet. DESIGN--Follow up study. SETTING--Seven general practices in the lower Hunter region of Australia. PARTICIPANTS--600 Men and women aged 25-65 who had their blood cholesterol concentrations measured three to four months earlier while attending their general practitioner. Analysis conducted on 552 (92%) who returned follow up postal questionnaires. MEASUREMENTS AND MAIN RESULTS--Of the 125 subjects found to have blood cholesterol concentrations greater than 6.5 mmol/l, 102 (82%) returned to their doctor and 83 of these recalled receiving dietary advice. 93 (75%) Subjects with high concentrations reported changing their diet compared with 72 (46%) subjects with concentrations of greater than 5.5-6.5 mmol/l and 44 (17%) subjects with lower concentrations. Overall 333 (61%) of all respondents who answered reported not changing their diet, the most common reason (nearly half the sample; n = 266) being that their cholesterol concentration was "all right." Adults without high cholesterol concentrations who returned to their doctor were also significantly more likely to recall their doctor saying that they did not need to lower their concentrations (less than or equal to 5.5 mmol/l = 61%; greater than 5.5-6.5 mmol/l = 12%; greater than 6.5 mmol/l = 5%) and significantly less likely to recall receiving dietary advice (less than or equal to 5.5 mmol/l = 13%; greater than 5.5-6.5 mmol/l = 60%; greater than 6.5 mmol/l = 82%). CONCLUSIONS--High risk strategies which require everyone to be tested for high cholesterol concentrations may interfere with population strategies designed to reduce everyone''s dietary intake of fat.     

Phase I study of combination recombinant interleukin-2 and interferon gamma in patients with advanced malignancies

A phase I trial of interleukin-2 and interferon gamma combination treatment in patients with advanced malignancies was performed based on preclinical in vitro and in vivo data which demonstrated synergistic antitumor effect. The toxicities, immune parameters, and tumor responses are described. The clinical and biologic maximal tolerated doses were extrapolated from these data.