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Biomedical subjects

J Stack

Publications and source records attributed to J Stack.

At least 55 records · Page 3Linked to original sources

Biosynthesis and processing of pro-opiomelanocortin-derived peptides during fetal pituitary development.

We have investigated the molecular weight forms of pro-opiomelanocortin (POMC)-derived peptides present in rat pituitaries during fetal and early postnatal development (embryonic Day 14 to 3 day neonate). At all early ages examined, the major immunoreactive form of corticotropin (ACTH) was POMC. Only during late fetal and early postnatal stages did progressively larger amounts of 4.5K ACTH, a major POMC processing end product, appear. This form was found almost exclusively in isolated anterior lobes. In contrast, 3.5K size endorphin(s), another POMC derivative, were present in whole glands even at early stages (Day 14), and were the major POMC derivative(s) found in isolated intermediate-posterior lobes of older fetuses. Despite the early appearance of 3.5K endorphin(s), alpha-MSH did not appear until Day 19 and was detected only in isolated intermediate-posterior lobes. We have also cultured dispersed fetal pituitary cells in the presence of radioactive amino acids. After immunoprecipitation using affinity-purified antisera, followed by fractionation of the radiolabeled products, we found that POMC biosynthesis does occur in cultures of Day 14 embryonic pituitary cells, and that the major POMC-derived end product produced is 3.5K size endorphin(s). These findings demonstrate that POMC is synthesized at least by Day 14 of rat pituitary development and that lobe-specific processing characteristic of the corresponding adult lobe is apparent at the earliest stages that the lobes can be separated. The presence of 3.5K-sized endorphins at early ages is consistent with the possibility that POMC synthesis first occurs in the intermediate lobe. The noncoordinate appearance of alpha-MSH, 1-39 ACTH, and endorphins implies that the activities of certain cleavage enzymes and acetylation enzymes responsible for lobe-specific post-translational POMC processing may be expressed at different times during development.

Adrenocorticotropic Hormone↗

Computed tomographic arteriography in the pre-surgical evaluation of hepatic tumours.

Five patients with hepatic neoplasms considered suitable for surgical resection were examined by computed tomography (CT), hepatic angiography and then a combination of angiography and CT (CTA). In each patient the tumour was more clearly defined and its extent more accurately determined than by routine CT. Three patients were spared surgery when further hepatic tumour was shown by CTA. The left lobe was shown to be free of tumour in the other two patients and surgical resection was carried out. Examination by CTA is recommended in all patients with hepatic tumours considered suitable for hepatic resection.

Aged↗

Effect of leucogenenol, a thymothyroid hormone, on the growth of immature and neonatally thymectomized rats.

The reports of early investigators that growth is delayed by thymectomy of immature animals have been confirmed. Although growth is delayed by thymectomy, thymectomized animals approach asymptotically with age the same final weight as corresponding intact animals. Treatment with leucogenenol, a thymothyroid hormone, accelerates the rate of growth of immature neonatally thymectomized rats to that of normal rats. However, treatment with leucogenenol does not increase the rate of growth of normal rats. Treatment with leucogenenol does not change levels of growth hormone (GH) or thyroxine (T4) in the serum of either thymectomized or intact immature and adult rats. Neither is the depression in levels of serum leucogenenol that follows thymectomy associated with a change in serum levels of GH or T4. Thus it is apparent that levels of serum leucogenenol do not affect the rate of growth of immature animals by increasing serum levels of GH or T4. By analogy with the finding that treatment with leucogenenol increases the rate at which committed cells of the bone marrow and cells involved in the immune response develop into functional cells, it is suggested that the levels of serum leucogenenol are one of the factors that determine the rate at which types of body cells that make up bone and other body tissues develop from committed precursors.

Animals↗

Ethanol dependence and the pituitary-adrenal axis in mice. I. Genotypic differences in hormone levels.

Resting pituitary levels of beta-endorphin-(beta-EP-IR), ACTH-(ACTH-IR), and alpha-MSH-(alpha-MSH-IR)-like immunoreactive material were found to differ among 16 inbred mouse strains. Hormone levels correlated genetically with severity of withdrawal from ethanol, which also differed among the strains. Ethanol dependence led to reduced pituitary beta-EP-IR in 4 of 5 strains studied. After 24 hr of withdrawal, 3 of those 4 showed elevated pituitary beta-EP-IR. These results are consistent with the hypothesis that genetically-determined difference in pituitary hormone functioning underlie some of the genetically-determined differences in ethanol withdrawal severity.

Adrenocorticotropic Hormone↗

Potassium-modulated secretion of immunoreactive melanocyte-stimulating hormone and endorphin from mouse neuro-intermediate lobes: evidence for stimulus-secretion uncoupling and rate sensitivity.

UNLABELLED: A multi-chamber perifusion system, capable of detecting transient secretory events, was used to define the roles of stepwise changes and gradients of K+ concentration in modulation of alpha-MSH and endorphin secretion. Fifteen dispersed mouse neuro-intermediate lobes per chamber were perifused with Dulbecco's Modified Eagle Medium at 0.5 ml/min. One-min fractions were collected. Ten min of 67 mM K+ elicited an immediate, very brief 4-fold increase in secretion of both hormones. Surprisingly, the return to normal K+ elicited a similar increase in secretion. Ten min K+-free medium produced an immediate decrease in secretion. Exposure to a 10-min 0-67 mM K+ gradient did not produce an increase in secretion; however, the stepwise return to normal K+, identical to that in the first experiment, elicited an immediate, brief increase in secretion. CONCLUSIONS: 1) The rapid decline in secretory activity during 67 mM K+ cannot be explained either by "down regulation" of receptors, since this secretagogue is not receptor-mediated, or by depletion of labile hormone, since a second secretory episode occurred immediately following termination of high K+. This suggests that some other cellular mechanism "uncouples" stimulus-secretory mechanisms. 2) Although depolarization with high K+ and hyperpolarization with K+-free medium were associated with increases and decreases, respectively, in secretion, it appears that it is the rate of ion flux rather than polarization which is responsible for stimulus-secretion coupling.

Animals↗

Limitations in response capacity of the newt, Notophthalmus viridescens, to soluble and particulate antigens.

We have investigated the cellular basis of the failure of primitive extant vertebrates, e.g. Notophthalmus viridescens, the American common newt, to respond to soluble thymus-dependent (TD) antigens, e.g. keyhole limpet hemocyanin (KLH). We have found that KLH can be used to prime for amplification of a response to hapten, 2,4,6-trinitrophenyl (TNP) when it is conjugated to KLH, only if both the unconjugated and conjugated KLH are adsorbed onto bentonite particles. The response is monitored in terms of antigen binding cells in the spleen. Moreover, prior injection of colloidal carbon, which is actively engulfed by phagocytes throughout the body, will prevent the response from taking place. Injection of colloidal carbon diminished responses to heterologous erythrocytes and to soluble or bentonite-coated 2,4-dinitrophenylated (DNP) dextran. Comparable colloidal carbon treatment did not reduce response levels to either soluble or bentonite adsorbed TNP-lipopolysaccharide (LPS) of E. coli. We suggest that the limitation in response capacity to soluble TD antigens may be associated with regulatory phagocytes. Moreover, the phagocytic cells of this primitive vertebrate appear to mediate responses to naturally particulate TD antigens and certain thymus-independent (TI) carriers, e.g. dextran, but not to LPS.

Animals↗

Electroencephalographic sleep in unipolar depressive subtypes: support for a biological and familial classification.

A tripartite classification of unipolar disease based on family history has been proposed by Winokur. In this study, we sought to investigate whether the familial pure depressive disorder (FPDD) and the sporadic depressive disorder (SDD) populations could be differentiated on the basis of baseline EEG sleep as effected by a tricyclic pharmacological probe. A subject group consisting of 26 females and 10 males yielding 18 FPDD/SDD pairs matched for age was selected. Both groups of patients demonstrated a considerable amount of sleep continuity disturbance with an overall sleep efficiency of 80.5 per cent in the pure depressive (FPDD) group and 83 per cent in the sporadic (SDD) group. Examination of the rapid eye movement (REM) sleep variables revealed the usual shortened REM latency as well as increased REM activity and REM density changes. However, the only significant difference between the two groups on baseline was the presence of more stage 3 and 4 sleep in the sporadic group, but stage 3 and 4 sleep was found in less than 40 per cent of the total sample. In contrast, analysis of the first two nights of EEG sleep on 50 mg of amitriptyline demonstrated several significant findings between the two groups. While considerable REM sleep suppression occurred in both groups, REM activity, REM intensity, and the number of REM periods were significantly more suppressed in the pure group than the sporadic group. Application of these variables led to a successful discrimination of 75 per cent of all the cases. These findings suggest a hyper-reactivity of sleep in patients with FPDD to a pharmacological probe.

Adult↗

Tolerance to ethanol hypothermia in inbred mice: genotypic correlations with behavioral responses.

Hypothermia was studied 5 min before, and 30 and 60 min after intraperitoneal administration of ethanol (3 g/kg) in 20 inbred strains of mice. Ethanol was given daily for 8 days, and temperatures were taken on Days 1, 3, 5, and 8. Tolerance was indexed by the reduction in hypothermia over days. There were large strain differences in baseline temperature, the hypothermic effect of ethanol, and in development of tolerance to hypothermia. Some strains of mice (DBA/1J, DBA/2N, MA/MyJ, and PL/J) did not develop tolerance to the hypothermic effect of ethanol. Initial sensitivity to the hypothermic effect of ethanol was significantly genetically correlated with tolerance development, indicating control of these responses by common genes. Ethanol-induced changes in activity and ataxia, as well as blood ethanol concentrations, were also assessed. Although there were significant strain differences in activity reduction, ataxia, blood-ethanol concentrations, and changes in these parameters during the course of chronic treatment, none of these variables could explain the genetic differences in hypothermic sensitivity and tolerance.

Animals↗

Strain differences in pituitary beta-endorphin and ACTH content in inbred mice.

The whole pituitary contents of beta-endorphin and ACTH were found to vary widely among 5 inbred strains of mice. beta-endorphin values were 2.5-fold different and ACTH values 1.5-fold. Strains low in beta-endorphin were also low in ACTH. The existence of genetic differences raises the possibility that there exist, or can be developed, strains with extremely low or high levels of these peptides that would aid research directed at elucidating the physiology of opioid peptides.

Adrenocorticotropic Hormone↗

A guideline to the management of patent ductus arteriosus in infants and children.

Experience with multiple ligation of the patent ductus arteriosus (PDA) at the Hospital for Sick Children, Great Ormond Street, London, is presented. One hundred and sixty-one consecutive cases between January 1971 and December 1974 have been reviewed. Fifty-four children (33%) were less than one year of age. In the majority of cases the diagnosis was made on clinical grounds. Cardiac catheterization and angiography were carried out when associated intracardiac lesions were suspected. The overall mortality was 2.5%. All the deaths occurred in infants less than six months of age who had associated cardiac lesions. There were no deaths in patients who had an uncomplicated PDA or who were more than one year of age. Multiple ligation of the PDA is a simple and safe operation. The risk of operative treatment is affected more by the presence of associated cardiac lesions and the age of the patient than by the surgical technique employed.

Cardiac Catheterization↗