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Biomedical subjects

S M Russell

Publications and source records attributed to S M Russell.

At least 91 records · Page 5Linked to original sources
PubMed1989

Effects of insulin-like growth factors I and II on growth and differentiation of transplanted rat embryos and fetal tissues.

The objective of our study was to obtain comparative information on the roles of insulin-like growth factors (IGFs) I and II in the growth and differentiation of rat embryos and fetuses in an in vivo experimental system. Ten-day-old rat embryos or 16-day-old fetal rat paws were transplanted under the capsule of both kidneys of syngeneic hosts, where they grew rapidly, and tissue differentiation occurred in an essentially normal manner. Infusion of a rabbit antiserum to human (h) IGF-I for 6 days into the renal artery of one kidney caused only a slight inhibition (approximately 20%) of growth of transplanted embryos on that kidney. However, 9 days of treatment with the antiserum caused highly significant growth retardation of transplanted embryos by 40-45%. Exposure of fetal paws to the same antiserum for 9 days inhibited their growth by 27%. Infusion of synthetic hIGF-II or partially purified rat IGF-II [(MSA)multiplication-stimulating activity], for 6 days stimulated the growth of embryo transplants directly, and MSA was more effective than hIGF-II. By contrast, infusion of purified natural hIGF-I did not promote their growth. Growth of fetal paw transplants in hypophysectomized (HX) hosts was reduced by 70% compared to that in intact hosts. In the HX hosts infusion of the MSA was more effective than the hIGF-I at promoting the growth of paw transplants. Both MSA and IGF-I promoted ossification in the fetal paws in the HX hosts. These results suggest that both IGFs could be involved in regulating the growth and differentiation in prenatal rats, and IGF-II may be the more effective of the two factors as a growth-promoting agent in utero.

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PubMed1988

Antiviral immunity induced by recombinant nucleoprotein of influenza A virus. I. Characteristics and cross-reactivity of T cell responses.

The gene for the nucleoprotein of the A/NT/60/68 influenza virus was expressed in bacteria and the recombinant protein purified. Lymph node cells from mice immunized with recombinant nucleoprotein proliferated in response to in vitro stimulation with a range of type A influenza viruses. Proliferation was inhibited by mAb to CD4 and class II MHC gene products. IFN-gamma was produced and type-specific CTL were generated in stimulated cultures of immune lymph node cells. These CTL were CD4+ and restricted to class II MHC gene products. Immunization with recombinant nucleoprotein generated Th cells in vivo as measured by the ability to generate an accelerated response to hemagglutinin after challenge with inactivated virus. The results are discussed with reference to a cross-reactive vaccine against influenza.

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PubMed1987

Insulin exerts metabolic and growth-promoting effects by a direct action on the liver in vivo: clarification of the functional significance of the portal vascular link between the beta cells of the pancreatic islets and the liver.

The functional significance of the portal vascular link between the beta cells of the pancreatic islets and the liver has not been established. Previous studies indicated that insulin does not acutely regulate glucose metabolism by a direct hepatic effect. More recent observations suggest that the role of insulin in regulating body growth may be mediated, at least in part, by the liver. Our experiments were designed to test whether insulin can promote body growth and regulate glucose metabolism by a direct hepatic action in vivo. Rats were made diabetic by injections of streptozotocin, and insulin or solvent was infused into the jugular vein (JV) or the hepatic portal vein (HPV) for 14 days using catheters that were attached to osmotic minipumps. Infusion of a low dose of insulin (2 units per kg per day) into the JV had no effects on the hyperglycemia, body weight gain, tail growth, tibial epiphysial cartilage plate thickness, or serum levels of somatomedin C in the diabetic rats. However, the same dose given into the HPV caused a 30% reduction of blood glucose and stimulated a significant degree of growth, as determined by all indices. Infusion of a higher dose of insulin (5 units per kg per day) into either vein caused full restoration of body weight gain and tail growth and it restored the glycemic status almost to normal. However, it did not increase the tibial epiphysial plate width or serum somatomedin C levels above those of the rats given the low dose of the hormone into the HPV. These results indicate that insulin can act directly on the liver to promote body growth and to regulate glucose metabolism. The significance of direct delivery of insulin from the pancreatic beta cells to the liver may be as much for growth control as for glucose homeostasis.

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PubMed1987

Growth and differentiation of transplanted rat embryos in intact, diabetic and hypophysectomized hosts: comparison with their growth in situ.

The objectives of this investigation were to evaluate the suitability of a transplant system for studying the endocrine control of growth and differentiation in rat embryonic/fetal tissues, and to gain information on the development of their hormone dependence. Whole 10-day-old rat embryos were transplanted under the kidney capsule of intact, hypophysectomized (Hx) or diabetic (Db) juvenile syngeneic female hosts, and grown there for 3, 6, 9 or 12 days. The wet weight, DNA and protein content of the transplants and of age-matched in situ embryos/fetuses were measured to assess their growth. The transplants in intact hosts increased more than 300-fold in all parameters during 12 days of incubation. However, this increase was only about 4% of the in situ growth. The severe impairment in growth occurred mainly during the first 3-day period when the transplants grew only 5% as much as the in situ embryos. Between days 13 and 22 of gestational age, the increment in transplant growth was 70% of that occurring in situ. Tissue differentiation of the transplants in intact hosts was essentially normal, although they grew as teratomas. Growth and differentiation of transplants in Db and Hx hosts were delayed or inhibited. This inhibition occurred as early as day 3 after transplantation and was corrected by appropriate hormone replacement therapy of the hosts. We conclude that rat embryos/fetuses develop a dependence on a growth hormone-dependent factor (possibly somatomedin) and/or insulin for growth before day 13 of development. This transplant system will be useful for studying other aspects of the control of growth and differentiation of rat embryos/fetuses between days 10 and 22 of gestation.

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PubMed1986

Evidence suggesting that the direct growth-promoting effect of growth hormone on cartilage in vivo is mediated by local production of somatomedin.

We have used a catheterization system that permits chronic infusion into the arterial supply of one hindlimb of rats to study the direct effects of rat growth hormone and human somatomedin C on growth of the tibial epiphyseal cartilage plate in hypophysectomized rats. Rat growth hormone (0.4 microgram per day) or human somatomedin C (0.25, 1, or 4 micrograms per day) stimulated growth of the epiphyseal plate of the infused limb but not of that of the contralateral noninfused limb. The somatomedin C had a dose-related effect. Rabbit antiserum to human somatomedin C, but not normal rabbit serum, completely abolished the direct growth effect of the rat growth hormone when it was co-infused with the hormone. These results support the concept that growth hormone stimulates long bone growth by inducing local production of somatomedin, which in turn stimulates cell proliferation in an autocrine or paracrine fashion. However, they do not exclude the possibility that serum somatomedin may also play a role.

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PubMed1986

A direct growth effect of growth hormone in rat hindlimb shown by arterial infusion.

We have developed a method for infusing substances into one hindlimb of the rat via the arterial supply. A catheter attached to an osmotic minipump is inserted into the right superior vesical artery and advanced to the junction of the right common iliac artery. This arrangement permits either constant or pulsatile infusion for 7 days. We employed this method to study the direct action of rat growth hormone (rGH) on the proximal tibial epiphysial plate in hypophysectomized rats. Infusion of neither the solvent nor ovine prolactin (2 micrograms X rat-1 X day -1) affected epiphysial plate width compared with control (uninfused) legs. The rGH infused at 0.4 and 2.0 micrograms X rat-1 X day-1 produced dose-related local growth effects that were of similar magnitude with either constant or pulsatile (eight 1-h pulses/day) infusion. However, the higher dose of rGH also resulted in a systemic effect (i.e., epiphysial plate growth in the uninfused limb), and the pulsatile mode produced a greater systemic effect than that produced by constant infusion. Our results indicate that GH can act directly on cartilage in vivo to maintain growth and that its effectiveness is not enhanced by pulsatile delivery. In contrast, the indirect (i.e., systemic) growth effects of the hormone may be enhanced by intermittent infusion. Our infusion system is well suited for studying the direct effect of substances on hindlimb tissues in conscious, unrestrained rats over extended periods.

Animals↗
PubMed1986

Growth and differentiation of fetal rat intestine transplants: dependence on insulin and growth hormone.

We have studied the role of hormones in the growth and differentiation of fetal rat intestine. Pieces of small intestine from 15-day fetal rats were transplanted under the renal capsule of either normal, hypophysectomized (HX), or diabetic adult rats and grown for 11 days. Intestine transplants in control hosts showed normal differentiation and they increased 60-fold in protein content and wet weight. Growth of transplants in HX and diabetic hosts was reduced by 50 and 25%, respectively. Transplants in diabetic hosts were histologically normal, while those in HX hosts failed to develop villi and discrete smooth muscle layers. Normal growth and differentiation in HX and diabetic hosts were completely restored by administration of growth hormone (GH) or insulin, respectively. Our data indicate that both GH and insulin are necessary for normal growth of the transplanted intestine during a period corresponding to late fetal and early neonatal life, but only the former is required for normal differentiation.

Animals↗
PubMed1985

Lactogenic hormones stimulate the liver to secrete a factor that acts synergistically with prolactin to promote growth of the pigeon crop-sac mucosal epithelium in vivo.

We have investigated whether the liver is a source of a PRL-synergizing activity (i.e. synlactin) and we have obtained some information on endocrine control of its secretion. Livers were removed from 3-month-old Long-Evans rats (male, virgin, pregnant, or lactating female) or from virgin females that were injected with saline, bovine GH, or ovine PRL for 7 days, and hepatic slices were prepared for in vitro incubation in medium 199. The media were tested for synlactin activity by determining whether they could augment the pigeon crop-sac response to locally injected ovine PRL. Only the media containing factors from the liver of pregnant or lactating females and PRL-injected virgins had significant synlactin activity. They augmented the crop-sac mucosal growth response by 130%, 140%, and 103%, respectively. Medium in which slices of kidney from virgin or pregnant rats were incubated did not have detectable synlactin activity. The medium samples that had synlactin activity were also tested for the presence of bioactive (crop-sac assay) and immunoreactive (RIA) rat PRL, and none had detectable amounts of the hormone. Hence, the augmenting effect is not due to PRL that is sequestered in and released by the liver. The levels of insulin-like growth factor I/somatomedin-C in medium samples that did or did not have synlactin activity (from pregnant and virgin females, respectively) were measured by RIA and were found to be equivalent. Hence, synlactin activity is probably not due to insulin-like growth factor I. Overall, our results indicate that lactogenic hormones (i.e. pituitary PRL, and presumably placental lactogens in the pregnant rats) stimulate the liver to secrete synlactin activity. The hepatic PRL receptors which increase in number in pregnant females may be involved in the secretion of synlactin, which could then act in concert with ovarian steroids and GH and/or PRL to promote mammary growth.

Animals↗
PubMed1985

The internal milieu of the pregnant rat is not growth promoting for maternal tissues and it reduces growth of fetal paw transplants.

We have investigated whether the internal milieu of the pregnant female rat is growth promoting to fetal or adult tissues. Adult female littermates were divided into two groups, one of which remained virginal while the other was bred repeatedly. Four successive pregnancies did not affect skeletal growth (i.e. tail length increase) or BW gain. Three-month-old females were hypophysectomized (HX) or sham HX on day 13 of pregnancy. Age-matched virgins were treated similarly. Eight days after surgery, the width of the tibial epiphysial plate of the HX virgins had decreased from 146.2 +/- 5.6 mu to 98.4 +/- 2.5 mu. In the pregnant rats, the width of the plate in the shams was reduced to 120.8 +/- 7.6 mu, and hypophysectomy tended to further reduce its width to 103.2 +/- 8.4 mu. Paws from 14- to 15-day fetal rats were transplanted under the kidney capsule of adult nonpregnant or pregnant hosts and grown there for 6 or 11 days. In the nonpregnant hosts the paws grew substantially during both periods, but in gravid females their growth was inhibited by about 35%. Paws were also transplanted to the kidney of HX pregnant and HX nonpregnant females to determine whether the internal milieu of the gravid female retains more growth-promoting/growth-supporting activity after pituitary removal than does that of HX virgin hosts. In both types of HX hosts, transplant growth was inhibited to the same degree (65-70%) relative to growth in intact hosts. The growth-inhibiting properties of the internal environment of the gravid hosts were not due to ovarian steroids because injections of estradiol plus progesterone had no effect on transplant growth. We also tested the effects of placental transplants and placental extracts on the growth of transplanted paws in juvenile female hosts. Both placental treatments caused inhibition of transplant growth by 25-30%. Overall, our results indicate that the internal milieu of the pregnant rat is not somatotrophic for her tissues, and it actually suppresses growth of fetal tissue transplants. The placenta may be responsible for this growth-inhibitory effect.

Animals↗
PubMed1985

Local injections of human or rat growth hormone or of purified human somatomedin-C stimulate unilateral tibial epiphyseal growth in hypophysectomized rats.

The growth-promoting actions of GH are thought to be mediated by somatomedin(s) (Sms), but unilateral bone growth in hypophysectomized (HX) rats given local injections of human (h) GH has been reported. Using slightly different methods, we have confirmed these results with purified hGH and have extended them to show that four daily injections directly into the tibial epiphyseal plate of 1 or 5 micrograms/day purified rat GH or recombinant DNA-derived hGH, but not of hPRL (6 micrograms/day) caused significant cartilage growth compared to that of the vehicle-injected contralateral tibia in rats that had been HX 14 days before the first injection. Thus, it is unlikely that the effects of GH are due to contaminating growth factors in the GH preparations, because the bacteria-derived preparation of hGH, which is unlikely to have such contaminants, was also active. Furthermore, we have shown that similar injections of 100 or 500 ng/day purified hSm-C caused unilateral tibial growth in rats HX 8 days, but not 14 days, before the first injection. These results demonstrate that both GH and Sm-C have direct growth-promoting effects on cartilage in vivo and are compatible with the theory that GH may act by stimulating local SM synthesis.

Animals↗
PubMed1985

Intracellular degradative fate of transplanted and microinjected proteins.

The mechanisms of intracellular protein catabolism have not been elucidated in spite of 42 years since Schoenheimer's treatise on "The Dynamic State of Body Constituents". Protein catabolism (cf. Protein Synthesis) involves multiple mechanisms, several of which occur reliably only in cells, not test-tubes. Elucidation of the mechanisms relies on both cell biological and enzymological approaches. Transplantation and microinjection of proteins into target cells, although naturally not without experimental and interpretive difficulties, provide the means of identifying the molecular and cell biological events in intracellular protein degradation. In short, these techniques provide the bioassay system to probe the functions of known catalysts and inhibitors of proteinolysis and provide the means of identifying the currently unknown features of the cytoplasmic surveillance system which present the protein substrates for destruction.

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