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Biomedical subjects

J M Lipton

Publications and source records attributed to J M Lipton.

At least 181 records · Page 10Linked to original sources
PubMed1980

Virus and cell requirements for Friend virus granulocytic leukemogenesis in long-term bone marrow cultures of NIH swiss [N:NIH(S)] mice.

The effect of hematopoietic stem cell age on leukemogenesis in vitro was tested in nonrecharged, corticosterold-supplemented NIH Swiss [N:NIH(S)] mouse long-term bone marrow cultures infected with Friend murine leukemia virus of anemia-inducing strain (F-MuLV-A) or spleen focus-forming virus (SFFV) [Rauscher murine leukemia virus (R-MuLV)], a pseudotype virus derived by rescue of the SFFV genome from SFFV-Balb/3T3 clone A31 nonproducer cells with clonal helper R-MuLV. Cultures at 33 degrees C derived from 10-day-old or adult mouse marrow generated colony-forming unit culture granulocytic macrophage (CFUc) progenitor cells for over 20 weeks and colony-forming unit spleen cells for 14 weeks and generated permanent granulocytic leukemia cell lines after infection with F-MuLV-A at week 1, 2, or 4 but not at week 8. Leukemia lines were of granulocyte phenotype whether induced by F-MuLV-A or SFFV (R-MuLV) and synthesized myeloperoxidase and lysozyme but were restricted in ability to generate superoxide in response to phorbol myristate acetate stimulation. Cultures (31 degrees C) infected with temperature-sensitive (ts) helper virus mutant pseudotypes of SFFV as well as SFFV (R-MuLV) generated granulocytic leukemia lines, whereas only SFFV (R-MuLV) pseudotype virus-infected cultures became leukemic at 37 degrees C. R-MuLV wild type or ts mutant helper virus infection alone increased cell proliferation and numbers of CFUc but did not generate leukemia. These data indicated that gene(s) specific to F-MuLV-A or a virus rescued from SFFV-Balb/3T3 clone A31 nonproducer cells are required for transformation in vitro of a hematopoietic stem cell present in early but absent in late bone marrow cultures.

Animals↗
PubMed1980

Cell-cell interactions in in vitro erythropoiesis.

Cell-cell interactions between T and null lymphocytes induce erythropoietin-stimulated differentiation of peripheral blood-derived erythroid progenitors. Monocytes do not inhibit the engagement of this differentiation. By the use of murine hybridoma antibodies, which are uniquely reactive with mature T lymphocytes, the dependence of immature peripheral blood BFU-E differentiation on mature T lymphocytes, or a T cell-conditioned medium is confirmed. Studies with the same antibody show that the more mature and numerous BFU-E found in marrow have no requirement for mature T cells or T cell-conditioned medium. These findings do not preclude the presence in bone marrow of immature T or even non-T cells which may serve as inducers of erythropoietin-dependent erythroid differentiation of mature marrow BFU-E.

Cell Communication↗
PubMed1979

Effects of central administation of probenecid on fevers produced by leukocytic pyrogen and PGE2 in the rabbit.

1. Single intracerebroventricular (I.C.V.) injections of probenecid (PBCD, 0.125--0.5 mg) enhanced and prolonged fever caused by I.V. administration of leukocytic pyrogen (LP) in rabbits resting in neutral (23 degrees C), cold (10 degrees C) and hot (30 degrees C) environments. Similar effects were produced by single I.C.V. injections of PBCD given before PGE2 (0.5 microgram) was injected I.C.V. in the three ambient temperatures. 2. Fever produced by IV. LP was also prolonged by infusion and by multiple injections of PBCD. 3. PBCD given I.P. (100 mg/kg) enhanced and prolonged fever caused by I.V. injection of Salmonella typhosa endotoxin. 4. Hyperthermia produced by I.C.V. PGE2 was not augmented by subsequent PBCD infusion. However, pre-treatment with PBCD followed by PGE2 injection and PBCD infusion caused hyperthermia that was very high and prolonged, and, in some cases, lethal. 5. Acetaminophen (2 mg, I.C.V.) and indomethacin (10 mg/kg, I.V.) lowered body temperature when given during fever induced by LP and prolonged by PBCD infusion. 6. The concentration of PGE in cerebrospinal fluid (c.s.f.) samples taken from the third or lateral ventricles rose or stabilized during PBCD infusions made during LP fever. However, similar changes in PGE concentration also occurred during control infusions when body temperature was low. 7. We conclude that termination of the actions of both central endogenous pyrogen and centrally administered PGE2, and the subsequent reduction of fevers produced by them, require a PBCD-sensitive facilitated transport system. The reduction of PBCD-prolonged PL fevers by antipyretics which block PGE synthesis suggests that prolongation by PBCD of LP fever is not due to blockade of PGE transport in a subsequent step in fever mediation per se, but is due to inhibition of transport of LP itself, or of other mediators associated with it.

Animals↗
PubMed1979

Central effect of taurine and its analogues on fever caused by intravenous leukocytic pyrogen in the rabbit.

1. Taurine infused I.C.V. after I.V. injection of leukocytic pyrogen (LP) inhibited the initial rise in body temperature and prolonged fever when infusion was stopped. 2. Similar infusion of taurine also inhibited the hypertermic effect of I.C.V. PGE2 (0.5 microgram) but did not cause prolonged hyperthermia. 3. I.C.V. administration of the taurine analogues hypotaurine and beta-alanine, compounds which have been shown previously to compete with taurine for facilitated transport in C.N.S. tissue, also inhibited the initial increase in body temperature and prolonged LP fever. 4. These results suggest that taurine prolongs LP fever by preferentially occupying a carrier system normally required for termination of the effects of endogenous pyrogens or related central mediators of fever. There was no evidence that taurine prolongs fever by blocking inactivation of central PGE2, a substance proposed previously to be a central mediator of fever.

Animals↗
PubMed1979

Influence of sex and age on febrile responses to peripheral and central administration of pyrogens in the rabbit.

1. Intravenous injections of leucocytic pyrogen in doses of 15, 30 and 60 mul./kg caused febrile reactions in male rabbits that were related to age of the animal: rabbits under 2 yr of age developed fevers that were related to dose of pyrogen, while rabbits 2-3 yr old showed large febrile responses which were not dose-related.2. Female rabbits of comparable ages generally showed smaller febrile reactions to I.V. leucocytic pyrogen, and still older females (3-5 yr) developed fever only after the largest dose.3. Dose-related febrile responses to 2.5, 5 and 10 mul. leucocytic pyrogen given intracerebroventricularly (I.C.V.) were greater in male rabbits 1-3 yr old than in females of comparable age. Female rabbits 3-5 yr old showed dose-related fevers that were smaller than those of younger animals of both sexes.4. There were no major differences in response to 125, 250 and 500 ng PGE(2), given I.C.V., between male and female rabbits under 2 yr of age. Females 2-3 yr of age had greater responses to PGE(2) than males of comparable age whilst the oldest females showed smaller responses.5. It is concluded that the febrile response of the rabbit to peripheral and central leucocytic pyrogen varies with both age and sex. Differences in sensitivity of central fever controls to endogenous pyrogen in animals of different ages and sexes may account for the different responses to peripheral pyrogen.

Aging↗
PubMed1978

Thermolability in Wernicke's encephalopathy.

A patient with signs of Wernicke's disease had low body temperature and showed thermolability when challenged with cold and heat. This man expressed no feelings of thermal discomfort about his persistently low core temperature or about induced changes in his core temperature. He also showed abnormalities in his febrile response to pyrogen and in his circadian temperature rhythm. Treatment with thiamine hydrochloride resulted in substantial improvement in these thermoregulatory deficits.

Alcoholism↗
PubMed1978

Differential effects on temperature of chlorpromazine injected into PO/AH and medulla oblongata of the rat.

Hyperthermic responses developed after injections of chlorpromazine into the preoptic/anterior hypothalamic (PO/AH) region of unrestrained rats. Sites near hte posterior border of the anterior hypothalamus were the most sensitive. Injections of chlorpromazine into the medulla oblongata did not alter rectal temperature in intact rats but caused hypothermic responses when the PO/AH region had been destroyed. These results provide additional evidence for a secondary temperature control in the medulla which ordinarily responds minimally to drugs and which may be suppressed by an intact primary control in the PO/AH region.

Animals↗
PubMed1977

Hypothermia and persisting capacity to develop fever. Occurrence in a patient with sarcoidosis of the central nervous system.

A patient with central nervous system and systemic sarcoidosis had profound hypothermia and dementia with associated lymphadenopathy and hypernatremia. His capacity to develop fever remained; despite the persistent marked hypothermia, sweating and shivering in response to peripheral heating and cooling were maintained. Postmortem neuropathologic studies indicated that the hypothalamic region, generally considered to contain the primary temperature control, had been severely damaged by granulomatous sarcoid disease. These results confirm and extend previous findings of temperature disturbance in hypothalamic sarcoidosis and suggest that the integrity of the primary control of body temperature is not essential to fever production and "broad-band" regulation against environmental temperature extremes.

Central Nervous System Diseases↗
PubMed1977

Analogs of endoperoxide precursors of prostaglandins: failure to affect body temperature when injected into primary and secondary central temperature controls.

It is known that central administration of prostaglandins of the E series has marked effects on body temperature. The purpose in the present experiments was to learn whether stable analogs of the cyclic endoperoxide precursors of PGE2, PGF2alpha and PGD2, injected into the primary temperature control in the preoptic/anterior (PO/AH) hypothalamic region and into a presumed secondary control in the medulla oblongata, can produce rises in body temperature similar to those caused by PGE2. Injection of the analogs U-44069 and U-46619 (1.0 and 2.0 microng) into the PO/AH region of the rat, where both PGE2 and PGE1 caused hyperthermia, had no effect on Tre. Likewise, injections into the medulla oblongata, in the region where PGE2 and PGE1 caused hypothermia, were ineffective in altering body temperature. That neurons important to the control of body temperature are selectively sensitive to PGE2 and not to analogs of prostaglandin precursors suggests that local cyclic endoperoxides can influence body temperature only through bioconversion to prostaglandin.

Animals↗
PubMed1977

Intracerebroventricular taurine in rabbits: effects of normal body temperature, endotoxin fever and hyperthermia produced by PGE1 and amphetamine.

1. Intracerebroventricular (I.C.V.) injections of taurine into rabbits resting at an ambient temperature (Ta) of 10 degrees or 23 degrees C caused hypothermia but at 30 degrees C ambient temperature, rectal temperature was unchanged. 2. An I.C.V. bolus of 0=5 mg taurine immediately followed by a slow infusion of taurine (0-01--0-2 mg/min) into rabbits at 23 degrees C ambient temperature caused sedation and peripheral vasodilation and blocked the febrile response to Salmonella typhosa endotoxin (1 microng/kg i.v.). Sustained fevers, characteristic of fevers caused by central administration of pyrogens, developed after taurine infusions were stopped. Control infusions of taurine at the same rates in the same rabbits when they were afebrile had little effect on rectal temperature. 3. An I.C.V. injection of 0-5 mg taurine reduced the hyperthermia caused by prostaglandin E1 (PGE1; 2 microng) given I.C.V. A dose of 5-0 mg not only blocked PGE1 hyperthermia but also caused marked hypothermia. 4. Bilateral injections of taurine into the preoptic/anterior hypothalamic region, at sites where injections of Salmonella typhosa endotoxin caused long-lasting fevers, had no effect on rectal temperature. Similar injections into the reticular substance of the medulla oblongata, in the region believed to be concerned with a secondary temperature control function, were also without effect on body temperature. 5. Taurine (0-5 and 5-0 mg, I.C.V.) had no consistent effect on hyperthermia induced by amphetamine (2 mg/kg, I.V.) 6. We conclude that the hypothermic effect of taurine is not due to an action on the central neurone pool or pools concerned with the integrative control of thermoregulatory effectors. This amino acid appears to inhibit neuronal activity in efferent pathways which control peripheral vasomotor tone and heat production and to depress the level of arousal. Taurine delays the onset and extends the duration of endotoxin-induced fever, perhaps by two separate action: by inhibiting activity in central thermoregulatory pathways and by promoting accumulation of endogenous pyrogen in the brain.

Amphetamines↗
PubMed1976

Persistence of febrile response to pyrogens after PO/AH lesions in squirrel monkeys.

Observation of a patient who developed fever in spite of severe CNS sarcoidosis led us to test the idea that febrile responses require mediation by neurons in the preoptic/anterior hypothalamic (PO/AH) region. Changes in rectal and skin temperatures and oxygen consumption were recorded after intravenous and intracerebroventricular injections of endotoxin, after intracerebroventricular prostaglandin E1 (PGE1), and after intravenous injections of leukocyte pyrogens in animals in which the PO/AH region had been destroyed. The capacity to develop fever persisted after PO/AH destruction, and the patterns of heat production and heat loss were unchanged. Pyrogens were still effective after intracerebroventricular 6-hydroxydopamine and intraperitoneal reserpine given to reduce brain amines in monkeys with PO/AH lesions. It is unlikely that a secondary control in the medulla oblongata is responsible for the persisting sensitivity to pyrogens, since multiple injections of endotoxin into this region did not cause fever either before or after the PO/AH region was destroyed. The results do not support the idea that control of fever is localized in the PO/AH region alone. Rather, it appears that in the brains of primates there is either multiple central representation of fever control or an inherent capacity to develop sensitivity to pyrogens and to produce coordinated febrile responses.

Animals↗
PubMed1974

Complementary lowering of the behavioural and physiological thermoregulatory set-points by tetrodotoxin and saxitoxin in the cat.

1. Injections of tetrodotoxin or saxitoxin (25 ng in 0.10 ml.) into a lateral cerebral ventricle caused deep body temperature of cats to fall approximately the same amount (2 degrees C) whether the animals were resting in the cold (4 degrees C) or were responding to escape heat.2. Continuous exposure to heat either prevented the hypothermic response or enhanced the level of tachypnoea required to lower body temperature. Tetrodotoxin also caused hypothermia when an animal was lever pressing to obtain heat in the cold environment.3. These results provide evidence that agents which alter the set-point for physiological thermoregulatory activity produce a complementary shift in the behavioural set-point as well.

Animals↗