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Biomedical subjects

J M Lipton

Publications and source records attributed to J M Lipton.

At least 163 records · Page 9Linked to original sources
PubMed1981

Thermoregulatory disorders after removal of a craniopharyngioma from the third cerebral ventricle.

Aspiration and dissection of a cystic tumor from the third ventricle of a 3-year-old child resulted in several hypothalamic symptoms. One of the most persistent and troubling symptoms was marked hyperthermia which could not be traced to an infectious origin. The elevated temperature was not reduced by acetaminophen and there were abnormalities of circadian temperature cycles. In thermal stimulation tests the high body temperature was defended against induced cooling but the body temperature was raised above 40 degrees C without evoking physiological heat-loss responses and thermal discomfort. The unusual thermoregulatory status of this patient is similar to that seen in laboratory animals with hypothalamic lesions and to that observed with certain naturally occurring hypothalamic lesions in man. This dysthermia has been successfully treated with chlorpromazine.

Body Temperature↗
PubMed1981

Effects of diazepam on body temperature of the aged squirrel monkey.

Hypothermia was produced by IM administration of diazepam (0.125-0.5 mg/kg) to squirrel monkeys of various ages (2-16 years) in a thermoneutral (23 +/- 0.5 degrees C) environment with animals over eight years of age having slightly greater responses. Hypothermia caused by an intermediate dose (0.25 mg/kg) was augmented in a cold environment (15 degrees C), especially in the older animals. There was no marked alteration in the temperature change/age regression after 0.25 mg/kg diazepam in a hot environment (30 degrees C) compared with the control response. Injections of diazepam (1.25-5.0 microgram) into the lateral cerebral ventricle in a thermoneutral environment produced hyperthermia rather than hypothermia in all animals, and the magnitude of the induced hyperthermia was smaller in older monkeys. The results support previous case reports in man and suggest that this commonly used drug can induce hypothermia, especially in older primates exposed to cold. The drug action responsible for this temperature change appears to take place peripherally rather than within the brain.

Aging↗
PubMed1981

Hypothermic and antipyretic effects of centrally administered ACTH (1--24) and alpha-melanotropin.

ACTH (1--24) and alpha-melanotropin (alpha-MSH), peptides previously shown to influence body temperature when administered centrally and to occur naturally in brain regions important to temperature control, were injected intracerebroventricularly (ICV) in rabbits. The peptides in doses of 1.25, 2.5 and 5.0 micrograms produced dose-related hypothermias in a 23 degrees C environment, and greater decreases in body temperature when the experiments were repeated in the cold (10 degrees C), but the largest dose had no effect on temperature in the heat (30 degrees C). These results indicate that the peptides do not reduce the central set-point of temperature control. Rather, they appear to selectively inhibit heat conservation and production responses. Five microgram of ACTH reversed vasoconstriction and inhibited rises in temperature caused by leukocytic pyrogen (LP) given IV and ICV. The same dose of alpha-MSH also reduced fever produced by IV and ICV LP, but the reduction was not as great as after ACTH. Both peptides (5 micrograms) also reduced temperature rises and vasoconstriction caused by ICV PGE2. ACTH reduced d-amphetamine-induced hyperthermia without altering vasoconstriction which suggests that this peptide can reduce temperature rises by inhibiting heat production alone. One of the most important findings was that the peptides are antipyretic in that they reduce fever at doses (0.25 microgram, ICV) that do not affect normal temperature. The powerful effects of these peptides on resting body temperature, hyperthermia and fever, together with their presence in brain tissue important to temperature control, suggest that the endogenous central peptides participate in thermoregulation, perhaps by limiting fever and influencing normal temperature.

Adrenocorticotropic Hormone↗
PubMed1981

Central and peripheral injections of ACTH (1-24) reduce fever in adrenalectomized rabbits.

Central administration of ACTH (1-24) reduces fever in normal rabbits in doses that have no effect on afebrile body temperature. Previous experimental and clinical reports indicate that peripheral administration of both ACTH and corticosteroids reduces fever, and since central injection of corticosteroids can also lower fever it might be that the antipyretic effect of intracerebroventricular (ICV) ACTH (1-24) is due to adrenal stimulation. To learn whether this endogenous central peptide can produce antipyresis independently, ACTH (1-24) was injected ICV in bilaterally adrenalectomized (ADX) rabbits made febrile by IV injections of leukocytic pyrogen (LP). ACTH (250 ng) given ICV reduced fever in these animals and had a slight hypothermic effect when given to the same rabbits when they were afebrile. Doses of 25-75 ng reduced fever without influencing normal body temperature. Intravenous injections of ACTH (2.5 micrograms) also lowered fever caused by IV LP in ADX rabbits. The present findings raise the possibility that release of endogenous central ACTH, and perhaps entry into the brain of circulating ACTH, the release of which is known to increase in fever, limits the magnitude of the febrile response by influencing central temperature controls.

Adrenalectomy↗
PubMed1981

The effect of fever on central alpha-MSH concentrations in the rabbit.

The recent demonstration of the ability of centrally administered alpha-MSH to reduce pyrogen-induced fever in rabbits suggested a role for the peptide in central temperature control. Using a sensitive radioimmunoassay we have established the presence of immunoreactive alpha-MSH (ir alpha-MSH) in discrete CNS sites of the rabbit and have demonstrated a distribution of this activity similar to that seen in other species. Pyrogen-induced fever did not alter concentrations of ir alpha-MSH in tissue extracted from the paraventricular region of the hypothalamus, median eminence, midbrain central grey, preoptic/anterior hypothalamic region, pineal or pituitary. A decrease in arcuate nucleus ir alpha-MSH content was seen in febrile animals, although this change was not statistically significant. Significantly higher levels of ir alpha-MSH were detected in septal extracts of febrile rabbits (0.81/+-0.10 pg/micrograms protein, n=9) than in extracts from afebrile controls (0.54/+-0.04, n=17). This finding suggests the septum to be the central site of action of alpha-MSH to inhibit fever and further implies a modulatory role of the peptide in the central control of thermoregulation.

Animals↗
PubMed1981

Effects of central administration of alanine on body temperature of the rabbit: comparisons with the effects of serine, glycine and taurine.

Alanine, an amino acid that shares neural inhibitory effects with serine, glycine and taurine, like these three amino acids also lowers body temperature when given centrally. In the present experiments the effects of alanine on central temperature controls were examined in more detail to determine the relations between its central action and those of the other amino acids. Intracerebroventricular (ICV) injections of alanine (0.5--2.0 micrograms) caused small decreases in body temperature in a 23 degrees C environment, and greater decreases in a 10 degrees C environment. The 2.0 microgram dose had no effect at high temperature (30 degrees C). These results indicate that alanine shares the hypothermogenic activity of the other inhibitory amino acids. In common with these amino acids, alanine (2.0 microgram) also reduced LP fever and PGE2 hyperthermia. The hypothermogenic effect of alanine in 10 degrees C environment was additive with that of glycine but slightly subadditive with that of serine and of taurine. In previous experiments serine was additive with taurine and subadditive with glycine in lowering body temperature in the cold. The combined results indicate that alanine has an influence on central temperature controls that is comparable to those of glycine and taurine. Alanine, glycine, serine and taurine appear to act on similar receptors in the central thermoregulatory pathway, with serine and taurine possibly acting at additional receptor sites as well.

Alanine↗
PubMed1981

Hypothermia produced in aged squirrel monkeys by central administration of taurine.

Accidental hypothermia and heatstroke are more common in aged populations. While peripheral factors are undoubtedly important to the high incidence of dysthermia in the aged, alterations in central temperature controls associated with aging may be primarily responsible. It has been shown that the sensitivity of the hypothalamus to neurotransmitters is changed in aged animals, and it may be that similar alterations in central temperature controls underlie the increased susceptibility to dysthermia. As a first step in testing this hypothesis the responsiveness of central temperature controls of aged squirrel monkeys to taurine, a putative inhibitory neurotransmitter or neuromodulator, was tested. Intracerebroventricular (i.c.v.) administration of this sulfonated amino acid (0.5-4.0 mg) produced dose-related hypothermia in squirrel monkeys over nine years of age in a thermoneutral environment (23 degrees C). Younger animals had significantly smaller hypothermias. In a hot environment (30 degree C) there were no significant differences between the temperature decreases of the two age groups after any dose. However, in a cold environment (17 degrees C), in which young animals developed slightly larger hypothermias than in the thermoneutral environment, core temperature of the aged squirrel monkeys dropped so rapidly in response to even the lowest dose that they had to be removed and warmed to prevent death by hypothermia. The temperature controls of the aged squirrel monkey appear to be extremely sensitive to taurine. The findings indicate that a rise in central taurine concentration in old primates can, in a cold environment, produce an effect very much like accidental hypothermia in aged man.

Aging↗
PubMed1981

Control of the simian fetal hemoglobin switch at the progenitor cell level.

This investigation was designed to define the cellular level at which the gamma to beta globin switch is established in the developing simian fetus in order to determine whether the switch is controlled by environmental influences within differentiating erythroid precursors or predetermined by the genetic program of erythroid progenitors. Samples of marrow and liver were obtained from rhesus fetuses throughout the switch period, and marrow was obtained from adult rhesus monkeys. Globin chain synthesis was then measured in differentiated erythroblasts and in erythroid progenitor-derived colonies grown in semisolid media. The relative rates of synthesis of gamma and beta chains were determined by the uptake of [(3)H]leucine into the respective chains separated by Triton gel electrophoresis and in some cases by urea carboxymethyl cellulose chromatography. Four periods of the switch were defined during fetal development. In the preswitch period both erythroblasts and progenitor-derived colonies produced <5% beta globin. In the early switch erythroblasts produced 5-15% beta globin, while progenitor-derived colonies produced 10-35% beta globin. In mid-switch erythroblasts synthesized 50% beta globin, whereas progenitor-derived colonies produced only 15-35% beta. At the completion of the switch erythroblasts produced 100% beta globin, while progenitor-derived colonies produced as little as 40% beta chains. We conclude that the program of globin synthesis that characterizes the fetal switch is established at the level of erythroid progenitors. Fetal erythroid burst-forming units (BFU-E) dominate the marrow prior to the switch. The early switch period is heralded by the appearances of adult erythroid burst-forming units programmed to express increasing beta chain synthesis in colonies. By mid-switch a second class of adult erythroid progenitors capable of giving rise to fetal and adult hemoglobin synthesis in in vitro colonies becomes apparent. These shifting populations of erythroid progenitors with unique globin synthesis programs give rise to the erythroblasts that create the sigmoid pattern of the fetal to adult hemoglobin switch in the developing simian fetus.

Age Factors↗
PubMed1981

ACTH and alpha-melanotropin in central temperature control.

Adrenocorticotropin (ACTH) and alpha-melanotropin (alpha-MSH) occur in brain tissue known to be important to temperature control. These peptides cause hypothermia if they are injected centrally in sufficient doses, but they do not act on the central set point of temperature control. Instead they appear to inhibit central pathways for heat conservation and production. In addition to their hypothermic capability, these peptides are antipyretic when given centrally in doses that have no effect on normal body temperature. ACTH has previously been associated with fever reduction in both clinical and experimental studies, and it may be that endogenous central ACTH is important for limitation of maximal fever. The hypothermic and antipyretic effects of ACTH do not depend on stimulation of the adrenal cortex because they are also observed in adrenalectomized rabbits. Nor is the antipyretic effect limited to the rabbit inasmuch as a comparable effect has been demonstrated in the squirrel monkey. The two peptides may be involved in central mediation of normal thermoregulation and fever, perhaps limiting the febrile response and other rises in body temperature by acting as neurotransmitters or neuromodulators in central thermoregulatory pathways.

Adrenocorticotropic Hormone↗
PubMed1981

Absence of common ALL antigen on normal bipotent myeloid, erythroid, and granulocyte progenitors.

The presence of the common acute lymphoblastic leukemia antigen (CALLA) on leukemic cells from the great majority of patients with non-T cell acute lymphoblastic leukemia and chronic myelogenous leukemia in blast crisis suggests that CALLA could be differentiation antigen expressed by normal lymphoid and myeloid stem cells. Treatment with a murine monoclonal anti-CALLA antibody and complement lysed CALLA-positive leukemic cells quantitatively, whereas similar treatment of nucleated cells from peripheral blood and bone marrow failed to affect the expression, in semisolid culture, of CFU-G/E, BFU-E, CFU-E, or CFU-C. These data suggest that CALLA is not a normal differentiation antigen of the myeloid bipotent cell or its committed progenitors.

Acute Disease↗
PubMed1981

Phase I study of 2'-deoxycoformycin in acute lymphoblastic leukemia.

2'-Deoxycoformycin (2'-dCF), a tight-binding inhibitor of adenosine deaminase, was administered to 26 pediatric patients with acute lymphoblastic leukemia in a Phase I study. Doses ranged from 0.25 to 1.0 mg/kg given i.v. for 3 consecutive days. Common toxicity included nausea, vomiting, diarrhea, hepatocellular enzyme elevations, and conjunctivitis. Lymphopenia occurred in all patients. The most serious adverse effects were acute tubular necrosis and central nervous system toxicity, which appeared to be dose related. In addition, two patients given the 0.75-mg/kg dose developed severe hepatic toxicity, although this could not be ascribed definitively to 2'-dCF. Antitumor activity was observed in eight patients, two of whom experienced a complete remission. Inhibition of lymphoblast adenosine deaminase activity was noted in the majority of cases and was observed at all doses. Antileukemic activity occurred at doses of 2'-dCF which were not associated with limiting toxicities. These results suggest that 2'-dCF is active against acute lymphoblastic leukemia and that a starting dose of 0.5 mg/kg/day be utilized in Phase II studies.

Adenosine Deaminase Inhibitors↗
PubMed1981

Response of three classes of human erythroid progenitors to the absence of erythropoietin in vitro as a measure of progenitor maturity.

The effect of erythropoietin (Ep) deprivation (epoprival state) on plasma clot cultures of human bone marrow and peripheral blood erythroid progenitors was examined. In normal individuals, there was a marked reduction of CFUE derived colony expression if Ep was withheld from the culture for even one day. Peripheral blood BFUE retained substantial function during the epoprival state for up to 2 to 5 days while bone marrow-derived BFUE had intermediate sensitivity. Thus the capacity of erythroid progenitors to withstand incubation in semi-solid media in the absence of Ep is a characteristic of immature, rather than mature, erythroid progenitors.

Bone Marrow Cells↗
PubMed1980

Mature bone marrow erythroid burst-forming units do not require T cells for induction of erythropoietin-dependent differentiation.

Cell-cell interactions between mature T cells and peripheral blood null cells induce erythropoietin-stimulated differentiation of peripheral blood-derived erythroid progenitors. By the use of complement-fixing cytolytic murine hybridoma and antibody uniquely reactive with mature T lymphocytes, this dependence of immature peripheral blood erythroid burst-forming unit (BFU-E) differentiation upon mature T cells or a T cell conditioned medium is confirmed. By using the same antibody, it is demonstrated that the differentiation of mature bone marrow BFU-E does not require either mature T cells or lymphocyte mitogenic factor. These findings do not preclude the presence in the bone marrow of other cells, perhaps even immature T cells, that influence erythropoietin-dependent erythroid differentiation of mature marrow BFU-E.

Bone Marrow Cells↗
PubMed1980

Management of acute asthma in childhood. A randomized evaluation of beta-adrenergic agents.

We examined the efficacy of several beta-adrenergic agents commonly used to treat asthma and evaluated the optimum route of administration. Two hundred and sixty-nine persons aged 5 to 21 years who came to the emergency ward while suffering from acute asthma were treated with either (1) inhalation isoetharine hydrochloride or (2) subcutaneous epinephrine or terbutaline sulfate. Patients were evaluated using clinical scores and pulmonary function tests and were monitored for adverse side effects. Regardless of mode of therapy, the acute attack was either treated successfully, terminated in hospital admission, or required further therapy within 24 hours in a comparable number of patients. Adverse side effects were more common with terbutaline sulfate than with either epinephrine or isoetharine in the doses used. Thus, inhalation of beta-adrenergic agents is as effective as subcutaneous administration in the treatment of acute asthma in childhood.

Acute Disease↗
PubMed1980

Central administration of peptides alters thermoregulation in the rabbit.

Sixteen peptides were injected intracerebroventricularly to test their effects on rectal temperature of rabbits in a thermoneutral environment. In initial tests 5 micrograms alpha-MSH, ACTH(1--24), oxytocin, vasopressin and glucagon altered body temperature while ACTH(1--10), cholecystokinin, contraceptive tetrapeptide, gastrin, insulin, interferon, leupeptin, LHRH, panhibin (somatostatin), and proctolin did not. Bombesin also altered body temperature but in no consistent direction. In further tests on the effective peptides 1.25--5.0 micrograms alpha-MSH and ACTH(1--24) produced dose-related decreases in rectal temperature as great as 1.0 degrees C. The same doses of oxytocin and glucagon produced small, prolonged hyperthermias which did not exceed 0.4 degrees C. Vasopressin caused rapid development of small increases in rectal temperature; temperature returned to normal in 2--3 hr. The results suggest that five of the peptides tested may have roles in central mediation of normal body temperature, hypothermia, hyperthermia and fever.

Body Temperature Regulation↗
PubMed1980

Aplastic and hypoplastic anemia.

Aplastic anemia is an acquired or constitutional trilineage bone marrow failure with peripheral pancytopenia, evidence of cellular hypoplasia of marrow, and replacement of normal cellular elements by fat. In some cases the marrow may be hypoplastic and the peripheral cytopenia relatively mild. The condition may persist for years and result in acute leukemia. In other cases, hypoplasia may involve only a single cell line. Basic research is directed toward understanding the multitude of cells, with a view toward selective manipulation of the cells themselves, interacting hormones, or cellular regulators. Early bone marrow transplantation presently offers the most hope when compatible donors are available.

Adolescent↗
PubMed1980

Monocytes do not inhibit peripheral blood erythroid burst forming unit colony formation.

To determine a possible role of peripheral blood monocytes in erythroid differentiation, various fractions of peripheral blood mononuclear cells were prepared from normal volunteers. The fractions contained 3-95% monocytes. These freshly prepared monocytes did not inhibit erythroid burst forming unit expression in plasma clot erythroid colony culture. Null cell preparations contaminated by up to 84% monocytes expressed erythroid burst forming unit colony formation when either T lymphocytes or T-cell conditioned medium was added. These results indicate that certain peripheral blood null cells engage the program of erythroid differentiation in the presence of T cells and erythropoietin. Monocytes do not inhibit this engagement.

Adult↗