Laboratory infection of primates with Ascaris suum to provide a model of allergic bronchoconstriction

Wild-caught non-human primates are naturally sensitive to Ascaris antigen and provide a useful model for studying atopic asthma. The present study was carried out to determine the effect of experimentally infecting home-bred macaques with the nematode Ascaris suum and hence provide an alternative for the naturally occurring model. Following oral infection with the parasite the animals developed a blood eosinophilia and specific antibodies to purified Ascaris antigen. These antibodies appeared to be of the IgE class as they could be detected by a radiometric assay using a radiolabelled antibody to human IgE. However, on further investigation, using the passive cutaneous anaphylaxis test, two classes of antibody were found, a heat labile (56 degrees C) and a heat stable antibody. Lung lavage cells taken from monkeys infected with Ascaris suum were shown to include cells morphologically characteristic of mast cells and released histamine when challenged in vitro with Ascaris antigen. Hence this model of immediate hypersensitivity provides a simple alternative to the less accessible natural model.     

The affinity glycated hemoglobin in a family with hereditary spherocytosis and in other non-hemoglobinopathic hemolytic anemias

The glycated hemoglobin (GHb) is lowered by hemolytic anemia. The cation-exchange HbA1 has been shown to be lowered by hereditary spherocytosis (HS). The HbA1, however, can be increased by elevations of fetal hemoglobin (HbF). The affinity GHb, a parameter related to, but not identical with, the HbA1, and unaffected by HbF, has been shown to be low in hemoglobinopathies but not, to our knowledge, in HS and other non-hemoglobinopathic hemolytic anemias. Therefore, the affinity GHb and HbF was determined in four members of an HS family and in nine other cases of non-hemoglobinopathic hemolytic anemia, including three autoimmune hemolytic anemias, four red cell fragmentation syndromes (two "Waring blender" syndromes, one thrombotic thrombocytopenic purpura in association with tumor, and one case of disseminated intravascular coagulation), and two red cell membrane defects: paroxysmal nocturnal hemoglobinuria and another case of hereditary spherocytosis. The GHb for these nine cases was 3.6 +/- 1.7 percent (normal 6.0 +/- 2.0 percent; p less than 0.001). The reticulocyte count, available in four cases, was 0.23 +/- 0.14 and correlated negatively with the GHb. The average GHb in the HS family was 3.9 +/- 0.8 percent, which was significantly less than the normal of 6.0 +/- 2.0 percent (p less than 0.001); the HbF was less than 1.0 percent. It is concluded that the GHb is diminished in hemolytic anemias not associated with hemoglobinopathies and that this lowering reflects the shortened red cell life span in these processes. To our knowledge, this is the first report of low GHb in hemolytic anemia not associated with hemoglobinopathy, by the affinity chromatographic technique, as opposed to the cation-exchange chromatographic technique.     

Marfan syndrome: exclusion of genetic linkage to the COL1A2 gene

Marfan Syndrome is a genetic disorder of the connective tissue. Individuals from one large family with this disorder were genotyped for COL1A2 gene associated RFLPs. Our results demonstrated that the COL1A2 gene, encoding the proa2(I) collagen chain, segregated independently of the phenotype and it is therefore excluded as the mutant locus in this family.     

Kinetics of estimated human muscle capillary blood flow during recovery from exercise

The kinetic characteristics of muscle capillary blood flow (Qcap) during recovery from exercise are controversial (e.g. one versus two phases). Furthermore, it is not clear how the overall Qcap kinetics are temporally associated with muscle oxygen uptake (VO2m) kinetics. To address these issues, we examined the kinetics of Qcap estimated from the rearrangement of the Fick equation (Qcap=VO2m/C(a-v)O2) using the kinetics of pulmonary VO2 (VO2p, primary component) and deoxy-haemoglobin concentration ([HHb]) as indices of VO2m and C(a - v)O2 (arterio-venous oxygen difference) kinetics, respectively. VO2p (l min-1) was measured breath by breath and [HHb] (microm) was measured by near infrared spectroscopy during moderate (M; below lactate threshold, LT) and heavy exercise (H, above LT) in nine subjects. The kinetics of Qcap were biphasic, with an initial fast phase (tauI; M=9.3+/-4.9 s and H=6.0+/-3.8 s) followed by a slower phase 2 (tauP; M=29.9+/-8.6 s and H=47.7+/-26.0 s). For moderate exercise, the overall kinetics of Qcap (mean response time [MRT], 36.1+/-8.6 s) were significantly slower than the kinetics of VO2p (tauP; 27.8+/-5.3 s) and [HHb] (MRT for [HHb]; 16.2+/-6.3 s). However, for heavy exercise, there was no significant difference between MRT-[HHb] (34.7+/-10.4 s) and tauP for VO2p (32.3+/-6.7 s), while MRT for Qcap (48.7+/-21.8 s) was significantly slower than MRT for [HHb] and tauP for VO2p. In conclusion, during recovery from exercise the estimated Qcap kinetics were biphasic, showing an early rapid decrease in blood flow. In addition, the overall kinetics of Qcap were slower than the estimated VO2m kinetics.     

Exclusion testing in pregnancy for Huntington''s disease.

The results of DNA analysis are presented for a series of 90 couples, with one partner at 50% risk for Huntington's disease (HD), who were referred for exclusion testing in pregnancy over a three year period. Thirty-seven couples were studied in detail. The aims of the study were to evaluate attitudes towards prenatal testing, before pregnancy and afterwards, and the effectiveness of our counseling and methods of organising the service. Problems which could arise in relation to presymptomatic testing are documented. It is concluded that exclusion testing is a valuable form of prediction for some couples, particularly where family structure does not permit prediction for the person at risk. The need for intensive counselling was highlighted by the difficulties experienced by many couples in understanding how the test worked. Particular ethical and organisational problems may arise which require careful consideration beforehand and some recommendations are made. The proportion of couples who will continue to request exclusion testing as pre-symptomatic testing becomes more widely applicable remains unknown.     

A closely linked DNA marker for facioscapulohumeral disease on chromosome 4q.

Close linkage of a hypervariable DNA probe on chromosome 4q (pH30, locus D4S139) has been found with the locus for facioscapulohumeral disease. Three recombinants were identified in a total of 140 meioses, giving a maximum lod score of 36.77 at a recombination fraction of 0.02. All but two of the families studied proved informative with this probe; all informative families showed evidence of linkage (except one family with a single scorable meiosis), making genetic heterogeneity unlikely from our data. The close linkage and highly informative nature of the probe will make it suitable for clinical application in presymptomatic and prenatal diagnosis. We have also confirmed loose linkage with the marker (Mfd22, locus D4S171) used to establish the initial assignment of the disorder to chromosome 4.     

Cooperation between the Cdk inhibitors p27KIP1 and p57KIP2 in the control of tissue growth and development

Cell cycle exit is required for terminal differentiation of many cell types. The retinoblastoma protein Rb has been implicated both in cell cycle exit and differentiation in several tissues. Rb is negatively regulated by cyclin-dependent kinases (Cdks). The main effectors that down-regulate Cdk activity to activate Rb are not known in the lens or other tissues. In this study, using multiple mutant mice, we show that the Cdk inhibitors p27^KIP1 and p57^KIP2 function redundantly to control cell cycle exit and differentiation of lens fiber cells and placental trophoblasts. These studies demonstrate that p27^KIP1 and p57^KIP2 are critical terminal effectors of signal transduction pathways that control cell differentiation.     

Influence of dietary protein level on protein self-selection and plasma and brain amino acid concentrations

Control of protein intake was studied in young rats that were allowed to choose between either protein-free and 55% casein diets or 15% and 55% casein diets. Animals on the protein-free vs. 55% casein regimen exhibited a lower weight gain, a lower cumulative energy intake and a greater cumulative total protein intake during the 13-day study compared to rats selecting between 15% and 55% casein. The daily average proportion of total food selected as casein by animals choosing between protein-free and 55% casein diets increased from 15% to 38% during the course of the study. In contrast, rats choosing between 15% and 55% casein chose 18-22% of total food as protein throughout the entire study. Long-term protein intake or protein selection did not correlate significantly with whole-brain contents of 5-HT or 5-HIAA. Our results suggest that protein intake is not regulated at a constant proportion of total calories, but is controlled between a minimum level that will support rapid growth and a maximum that, if exceeded, would require the animal to undergo substantial metabolic adaptation. The mechanism controlling protein selection may involve diet-induced changes in the brain content of total free indispensable amino acids.     

Permanent impairment of embryo development by hydrosalpinges

Recent reports suggest a deleterious effect of hydrosalpinges on pregnancy outcome for in-vitro fertilization (IVF) and improvement following surgical treatment. We compared the effect of hydrosalpinx on pregnancy outcome in 286 patients having 348 IVF cycles and followed the development of untransferred embryos for 7 days to determine if hydrosalpinges affect oocyte quality or embryo development. The delivery rate per retrieval was significantly lower for patients with hydrosalpinx, but was restored by surgical treatment to that of patients without hydrosalpinx. However, the implantation rate per embryo transferred and normal blastulation of untransferred embryos, which were significantly decreased in patients with hydrosalpinx, and growth arrest and degeneration of untransferred embryos, which were significantly increased compared to patients without hydrosalpinx, were not restored by surgical treatment of hydrosalpinges. We conclude that surgical treatment of hydrosalpinges decreases early pregnancy loss and improves pregnancy outcome, possibly by diminishing reversible deleterious effects exerted on the endometrium. As we have seen in our laboratory, hydrosalpinges may have a permanent negative influence on ovarian function, follicular development and oocyte quality since implantation of transferred embryos and normal blastulation of untransferred embryos remain low, and in-vitro growth arrest and degeneration remain high despite surgical treatment of hydrosalpinges.      

Abdominal pain in children and symptoms of somatization disorder

Children seen in a multispecialty medical clinic for abdominalpain were divided into three groups: 21 with confirmed organicfindings related to the abdominal pain, 14 with confirmed organicfindings unrelated to the pain, and 108 whose physical examinationswere negative (the functional pain group). For children withfunctional abdominal pain (but not for the others) the numberof symptoms of somatization disorder (Briquet's syndrome) wassignificantly related to the chronicity of the child's condition.Children with functional pain and no prior complaint had a meanof 1.95 symptoms; those with complaints of less than 1 year'sduration, 2.21 symptoms; those with complaints of more thana year since age 6, 4.04 symptoms; and those with complaintsfor more than a year with onset prior to age 6 years, 4.55 symptomsfrom the Somatization Disorder list. Findings were interpretedas preliminary evidence for a distinct, chronic, polysymptomatichysterical disorder beginning in childhood.