Apoptosis in the pancreatic islet cells of the neonatal rat is associated with a reduced expression of insulin-like growth factor II that may act as a survival factor

Islet cell ontogeny will define adult beta-cell mass and will consist of a balance of islet cell birth and death. We have investigated the ontogeny of factors that may be related to developmental apoptosis in the islets, insulin-like growth factor II (IGF-II) and inducible nitric oxide synthase (iNOS), in pancreata of young Wistar rats. Pancreata were collected from rats of 21 days gestation to 29 days postnatal age. In situ hybridization and immunohistochemistry showed that IGF-II was expressed and present in fetal and neonatal islet cells, but declined rapidly 2 weeks after birth. Little IGF-I was associated with fetal or postnatal islets. Apoptosis in islet cells was visualized by molecular histochemistry for DNA breakage in tissue sections. Apoptosis was low in the fetus, but increased in incidence postnatally so that 13% of islet cells were undergoing apoptosis on postnatal day 14, with the incidence declining thereafter. Immunohistochemistry for iNOS showed that it was expressed within beta-cells and was most abundant 12 days after birth. When islets were isolated from rat pancreata 20-22 days after birth, islet cell viability, DNA synthetic rate, and insulin release were reduced after incubation with interleukin-1beta, tumor necrosis factor, or interferon-gamma. An increased rate of islet cell survival was found after simultaneous incubation with IGF-I or -II. Cytokine-mediated islet cell death involved the induction of apoptosis. Islets isolated from neonatal rats were not killed after exposure to these cytokines at the same concentrations, but cytokine-induced cell death was seen when neonatal islets were incubated with a neutralizing antibody against IGF-II. These experiments show that a peak of islet cell apoptosis that is maximal in the rat pancreas 14 days after birth is temporally associated with a fall in the islet cell expression of IGF-II. IGF-II was shown to function as an islet survival factor in vitro. The induction of islet cell apoptosis in vivo may involve an increased expression of iNOS within beta-cells.     

Potential role for wild-type p53 in leukemias with MLL gene translocations

We used single-strand conformation polymorphism (SSCP) analysis of p53 exons 4-8 to screen for possible mutations in 25 pediatric de novo leukemias with translocations of the MLL gene at chromosome band 11q23. Of the 25 patients, 21 were infants. Fifteen cases were acute myeloid leukemia (AML), eight were acute lymphoblastic leukemia (ALL), and two cases were biphenotypic. Nineteen cases were studied at diagnosis and six at time of relapse. p53 mutations were absent in all 19 cases studied at the time of diagnosis. The only mutation was a TGC-->TTC transversion (cys-->phe) at codon 141 in exon 5 in a case of infant ALL at relapse that occurred by subclone evolution after MLL gene translocation. We previously showed that p53 mutations are also absent in pediatric treatment-related leukemias with MLL gene translocations. The absence of p53 mutations at initial transformation may suggest that the anti-apoptotic effect of mutant p53 is not important in leukemias with MLL gene translocations. Alternatively, exogenous DNA damage may be the common feature in treatment-related and de novo cases. Since MLL gene translocations may occur through DNA repair and wild-type p53 is central to DNA repair, the absence of p53 mutations raises the possibility that wild-type p53, not mutant p53, may be important in the genesis of leukemias with these translocations.     

Therapeutic control of plasma concentrations and long-term effect of nortriptyline in recurrent affective disorders

Based on the evidence that therapeutic plasma concentration range in fact exists for the tricyclic antidepressant drug, Nortriptyline (range 50-150 ng/ml), three different investigations were under taken in order to clarify some clinical pharmacological problems during long-term treatment with this drug. The possible prophlactic effect of the drug in recurrent affective disorders was specially examined in a group of patients with a high risk of episodes in their unipolar manic-depressive disease. The results highly demonstrate the value of monitoring plasma levels in achieving therapeutic control. Depressive relapses during treatment, for months and years, were only related to therapeutic insufficient plasma levels of the drug.     

A skin test for pseudorabies virus infection in swine

Heat-inactivated pseudorabies virus caused cutaneous delayed-type hypersensitive reactions when injected intradermally on the dorsolateral aspect of the thorax and tips of the ears of pigs previously exposed to the homologous virus. The reaction induced by subcutaneous injection in the lower eyelid was more easily administered and evaluated. Nonexposed control pigs did not react to the antigen and exposed and control pigs did not react when injected with a cell control antigen prepared in a similar manner. A positive response was detectable as early as seven days after exposure, reached near maximal levels by 28 days, and remained at similar levels for at least 90 days.     

Transient hypertrophic subaortic stenosis in infants of diabetic mothers

Three newborn infants with congestive heart failure had hemodynamic, angiographic, and echocardiographic features of hypertrophic subaortic stenosis (hypertrophic obstructive cardiomyopathy). Treatment with digitalis and diuretic drugs was ineffective, but improvement occurred when these agents were withheld in one patient, and when treatment with propranolol was begun in two patients. Echocardiography was helpful in establishing the diagnosis in two patients and showed resolution of the condition during the first six months of life. Serial cardiac catheterizations confirmed resolution of the outflow obstruction in the third patient. Family studies revealed no evidence of familial cardiomyopathy, but the mothers of two infants had insulin-dependent diabetes mellitus and the mother of the third was presumed to be prediabetic.     

A vitamin, anabolic, stimulant mixture. Is this form of medication advantageous for debilitated geriatric patients?

Of 32 underweight geriatric patients in a double-blind study, 24 were given a therapeutic mixture containing, per dose, 10 mg of methylphenidate, 2.5 mg of methandrostenolone, and a mixture of B vitamins; 8 patients were given placebo only. After eight weeks of this therapy, there was a significant weight gain in the treated patients. In some cases, this was associated with increased bromsulphalein retention. The number of patients who showed clinically evident increases in strength and vitality was no greater than in the control group. The results lend no support to the use of tonic mixtures instead of separate drugs.     

Plasma levels of oestriol-17 beta, oestriol and human placental lactogen during bed rest

Plasma unconjugated oestradiol-17 beta, total oestriol and human placental lactogen levels were measured in twelve healthy volunteers admitted for bed rest in the last trimester of pregnancy. No significant alteration in levels was observed.     

The reaction of nitrogen with titanium between 800 and 1200°C

This paper describes phase formation and mass transport during the reaction of iodine-refined titanium with nitrogen at 760 Torr and 800 to 1200°C. Each titanium-nitrogen phase is present within the composition and temperature range of its thermodynamic stability. Between 882 and 1110°C there are the nitrides, TiN and Ti₂N, and solutions of nitrogen in and -titanium. There is no -titanium below 882°C or Ti₂N above 1110°C. The growth of each phase layer involves some favorably oriented grains from among the many that are nucleated. Nitrogen concentration gradients exist in all phases. Nitrogen is the predominant diffusing species in all phases but a small amount of outward diffusion of titanium occurs through the nitrides, producing -phase porosity above 1100°C. There is some porosity in the outer regions of TiN. All phases remain mechanically sound and coherent with each other. Changes in the relative proportions of phases during cooling are identified, which enables corrections to be made to kinetic data for the reaction.