Fatty change in the brain in perinatal and unexpected death

The presence of fat-laden cells in the cerebrospinal fluid is usually associated with a fatty change found particularly in the area of the tapetum in the postnatal infant. In a series of 307 child deaths the presence of fatty change in this area of the brain was age-related, decreased with age, and was rarely present over the age of 4 years. It was particularly common in stillborns and in children dying with respiratory distress, but was rare in children dying from acute surgical conditions or from acute infections. It was found in one-half of a series of 41 infants found unexpectedly dead and in whom no adequate cause of death was found. The most likely cause of this fatty change is thought to be chronic hypoxia.     

Fetal and oncofetal antigens — Regulators of immune reactions

This paper proposes the hypothesis that cells which express fetal antigen activate a variety of suppressor mechanisms and thus induce a state of immunological tolerance. Clinical and experimental evidence is cited which supports the hypothesis and indicates that foreign antigens, expressed in association with fetal antigen, are actively tolerated. Thus the fetus, which bears foreign histocompatibility antigens and neoplastic tumours which re-express fetal antigens, fail to evoke appropriate immunological rejection responses, but rather induce a state of active tolerance.     

Is there a threshold level of fetal hemoglobin that ameliorates morbidity in sickle cell anemia?

When the clinical manifestations of 272 patients with sickle cell anemia are compared with their level of fetal hemoglobin (HbF), the results suggest that there may be a threshold above which HbF is effective in ameliorating the morbidity of this disease. The age of entry of these SS patients into the study ranged from birth to 56 yr; the average length of follow-up was 11 yr for a total of 3,011 patient- years of clinic observation. HbF was determined quantitatively by microchromatographic procedures; the mean for HbF was 10% +/- 6% with a range from 2% to 32%. For major organ failure, analyzed as termination events of morbidity, such as stroke or aseptic necrosis, the threshold appears to be 10%, whereas for recurrent clinical events, such as crisis or pulmonary disorders, it is 20%. No linear trend was found between HbF levels and morbidity. If a threshold exists, it is important to recognize this fact when attempts are made to raise the level of HbF in patients with sickle cell disease.     

The mouse alpha-globin locus regulatory element

We have identified and cloned the major alpha globin locus regulatory element in the mouse (m alpha RE). This element shows a high level of sequence homology to its human counterpart (HS -40) and lies between the same two exons of an upstream, widely expressed gene in both species. Footprinting and band shift studies of the core element show conservation of many (but not all) of the protein binding sites identified as functionally important in HS -40. The functional equivalence of the mouse element was shown by attaching it to a human alpha globin gene and examining expression in transgenic mice. Readily detectable levels of human alpha mRNA were produced in these mice but they were lower than the endogenous gene expression and did not show copy number dependence. These results suggest that sequences additional to this major regulatory element may be necessary to obtain complete regulation of the alpha globin genes in both species.     

Carcinogenic effects of Di(2-hydroxypropyl)nitrosamine (DHPN) in male Wistar rats: promotion of pancreatic cancer by a raw soya flour diet

Di(2-hydroxypropyl)nitrosamine was administered to rats fed raw or heated (control) soya flour diets. The group fed raw soya flour developed hyperplastic and adenomatous pancreatic nodules and pancreatic adenocarcinomata. We conclude that a diet of raw soya flour augments the carcinogenicity of pancreatic carcinogens in the rat.     

A three-colour flow cytometry technique for measuring trophoblast intracellular antigens: the relative expression of TAP1 in human cytotrophoblast and decidual cells

Flow cytometry is conventionally used to measure cell-surface antigen expression. However, many antigens are found within the cytoplasm, and it is necessary to fix and permeabilize cells to enable antibodies to gain access to them. In this study we have established the conditions for studying intracellular antigens in human trophoblast cells by flow cytometry using an antibody to TAP1 (a key molecule in the process of Class I MHC assembly). We have previously shown by immunocytochemistry that TAP1 expression is apparently greater on Class 1 positive extravillous cytotrophoblast than on any other fetal or maternal tissue. However, as immunohistochemistry is not quantitative we have used three-colour flow cytometry to measure the expression of TAP1 in different trophoblast populations. Villous and extravillous cytotrophoblast were identified in first trimester and term placental and decidual digests on the basis of their expression of cytokeratin and Class I MHC antigens. The level of expression of TAP1 for each population was investigated using a commercial kit that determines the number of antibody-binding sites per cell. TAP expression was found to be three- to fivefold higher in extravillous cytotrophoblast, confirming our previous findings. The techniques developed here are directly applicable to the measurement of other intracellular molecules in trophoblast, in particular cytokines.     

Percutaneous transluminal angioplasty of subclavian arteries

The clinical records and procedural details of 30 subclavian angioplasty procedures attempted in 27 patients were reviewed. Long-term follow-up was obtained through referring physician records and direct telephone contact with the patients. Eight patients presented with neurologic symptoms only, six had arm claudication only, nine had both neurologic and arm symptoms, three underwent dilations to provide graft inflow, and one was asymptomatic. Procedural complications included a stroke in the contralateral carotid distribution, occurring during follow-up arch aortography, and an embolus in the fifth digit of the left hand, which was of no clinical significance. Long-term success did not correlate well with degree of stenosis, lesion length, or postangioplasty appearance. The patients with arm and neurologic symptoms who were followed up for 3 years experienced immediate relief and remained symptom free or improved, except for the patient who suffered the stroke and one patient with labyrinthitis.