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PubMed1979

Ultrastructure and ATPase activity of the rectal gland of the chondrichthyean fish Hydrolagus colliei (Holocephali).

The anatomy, histology, ultrastructure and ATPase activity of the intramural rectal gland of the chondrichthyean Hydrolagus colliei, are described. The cells of the rectal gland of Hydrolagus demonstrate the same well developed lateral and basal cisternae, elongate mitochondria and luminal border as those of their elasmobranch counterparts. ATPase activity within the rectal gland of Hydrolagus is as intense as that in a number of elasmobranchs examined in the course of the study. Despite its primitive intramural location the rectal gland of Hydrolagus represents a homolog of the more specialized and better known elasmobranch gland and appears as well suited for cation excretion.

Adenosine Triphosphatases↗

PubMed1975

[Familial glucocorticoid insufficiency (author's transl)].

Familial glucocortivoid insufficiency--also called hereditary lack of response of the adrenals to ACTH-has not yet been described in Europe. Isolated glucocorticoid insufficiency combined with intact secretion of aldosterone and high plasma level of ACTH are characteristic. The diagnostic difficulties are demonstrated by the deaths before diagnosis of 13 siblings of 21 patients from 9 families. One such family is described. The first of 3 children died at the age of 3-1/2 years after a two day illness interpreted as encephalitis. Another boy, aged 4-1/2 years, had a hypoglycemic attack. 3 months later he died in status epilepticus after a short feverish illness. At autopsy the adrenals were very small. Histologically only the glomerulous zone was developed. An the hypophysis there was hyperplasia of the R cells producing ACTH. The 6 year old sister had been pronouncedly pigmented from the age of a few months onwards. Age in terms of height and bone development corresponded to 8-1/2 and 7-1/2 years. After intravenous insulin and synacthen plasmacorticoids could not be found. With normal and low supply of salt, the following data were found: Renin-activity 2.9 and 5.6 ng/ml p.h. respectively; rate of aldosterone secretion 62.6 and 151.5 mug/24 hrs.; average aldosterone plasma concentration 9.39 and 27.7 ng/100 ml respectively; MCR 666 and 5471 p/24 hrs. Plasma ACTH in this patient (5086--7200 pg/ml) and, post mortem, in her brother (8100 pg/ml), were extremely reaised.

Adrenal Glands↗

PubMed1977

Dissociation between cortisol-induced pycnosis and inhibition of [3H]uridine incorporation in rat thymocytes.

Treatment of rat thymocytes with cortisol induced an inhibition of [3H]uridine incorporation after 30-90 min, an accumulation of pycnotic cells after 90 min, and a decrease in cell viability after several hours. No cortisol-resistant cells could be distinguished, and dose-response curves for a number of glucocorticoids showed a correlation to the saturation of the glucocorticoid receptors. The pycnotic effect of cortisol increased between pH 5.2--7.0 in parallel with a stimulation of the spontaneous development of pycnotic cells. The cortisol-induced accumulation of pycnotic cells and inhibition of [3H]uridine incorporation varied independently as a function of the cell density, and in a glucose-salt medium only the pycnotic effect of cortisol became inhibited. The inhibition of [3H] uridine incorporation is therefore not an integral part of the pycnotic change of the cells. The glucocorticoid sensitivity was found to increase with the age of the animals, before the onset of thymus involution.

Animals↗

PubMed1977

[Functional morphology of the hypothalamo-hypophyseal neurosecretory system and adrenal cortex in myocardial infarct].

The hypothalamo-hypophyseal neurosecretory system (HHNS) was studied in patients dying at various intervals after the onset of the first clinical manifestations of myocardial infarction. All the 75 cases were divided into two groups depending on the presence or absence of decompensation with disorders of the water-salt metabolism. Despite the duration and pattern of its course, myocardial infarction was shown to be always accompanied by a high activity of the HHNS and adrenal cortex, although different variants of its intensity could be distinguished by the studies of the secretory cycle in neurosecretory nuclei. When infarction was complicated by cardiac decompensation, there developed the state of hypervasopressinism constantly accompanied by hyperthrophy of the glomerular zone of the adrenal cortex producing aldosteron and by an increased concentration of intracellular sodium.

Adrenal Cortex↗

PubMed1977

Posthypophysectomy taste abnormalities: their relationship to remote effects of cancer.

Abnormalities in taste sensation have been studied in 15 patients consisting of five normal controls, five patients with diffuse neoplasm and five patients post hypophysectomy. Threshold recognition for salt and HC1 in the three groups studied was the same. Sucrose and urea recognition was higher in patients with neoplasm as compared to normal controls. Patients post hypophysectomy had a lower threshold recognition for sucrose than both normal individuals and patients with neoplasm. The threshold recognition has markedly shifted for both sucrose (decreased) and urea (increased) post hypophysectomy. These observations are in support of previous findings and suggest that the pituitary plays at least a necessary permissible factor in the development of abnormalities in taste as observed in patients with disseminated cancer.

Breast Neoplasms↗

PubMed1975

Characteristics of the dephosphorylated form of phosphorylase purified from rat liver and measurement of its activity in crude liver preparations.

The phosphorylated form of liver glycogen phosphorylase (alpha-1,4-glucan : orthophosphate alpha-glucosyl-transferase, EC 2.4.1.1) (phosphorylase a) is active and easily measured while the dephosphorylated form (phosphorylase b), in contrast to the muscle enzyme, has been reported to be essentially inactive even in the presence of AMP. We have purified both forms of phosphorylase from rat liver and studied the characteristics of each. Phosphorylase b activity can be measured with our assay conditions. The phosphorylase b we obtained was stimulated by high concentrations of sulfate, and was a substrate for muscle phosphorylase kinase whereas phosphorylase a was inhibited by sulfate, and was a substrate for liver phosphorylase phosphatase. Substrate binding to phosphorylase b was poor (KM glycogen = 2.5 mM, glucose-1-P = 250 mM) compared to phosphorylase a (KM glycogen = 1.8 mM, KM glucose-1-P = 0.7 mM). Liver phosphorylase b was active in the absence of AMP. However, AMP lowered the KM for glucose-1-P to 80 mM for purified phosphorylase b and to 60 mM for the enzyme in crude extract (Ka = 0.5 mM). Using appropriate substrate, buffer and AMP concentrations, assay conditions have been developed which allow determination of phosphorylase a and 90% of the phosphorylase b activity in liver extracts. Interconversion of the two forms can be demonstrated in vivo (under acute stimulation) and in vitro with little change in total activity. A decrease in total phosphorylase activity has been observed after prolonged starvation and in diabetes.

Adenosine Monophosphate↗

PubMed1979

A gel-sandwich technique for the qualitative and quantitative determination of dehydrogenases in the enzyme histochemistry. I. Development of the new methods on the example of LDH (E.C. 1.1.1.27).

A gel-sandwich technique for the histochemical demonstration of dehydrogenase is introduced with LDH set up as an example. Especially suitable, of the gels examined, for this technique is 1.5% W/V agar-agar low gel strength. In it several reaction ingredients for the histochemical reaction are dissolved. Considering LDH the following gel composition showed good results: 1.5% W/V agar-agar low gel strength, 5 mM TNBT in 150 microliter DMF, 120 mM L-lactate, 3--5 mM NAD+, 10 mM amytal, 22,4--32 X 10(-5) M Meldola Blue, 160 mM soldium phosphate buffer pH 7.6 (total solution of 1 ml). After the solidification of the gel, gel-bars were frozen with CO2-snow. The 40--80 micrometer thick gel slices were gained in the cryostat. Of the three different arrangement possibilities of the gel slices and the tissue-sections a sandwich arrangement (cover-gel slice--tissue section--ground-gel slice) produced the best results. The enzyme reaction is started by thawing of the gel slices (together with the tissue sections) and by putting them between the hotplate and the evaporator-head-piece, especially developed for this technique. The gel slices also remain in combination with the tissue sections after the reaction. The influence of the gel in combination with the electron carrier Meldola Blue on the spontaneous reduction rates of ditetrazolium salts in day light, were examined as well as the diffusion rates of TNBT and NADH out of gel slices and the influence of DMF and DMSO on the LDH activity. This technique prevents both, the loss of enzymes and the loss of reduction equivalents. There are given presuppositions for qualitative and quantitative histochemical investigations as well. The advantages of the new gel technique are discussed.

Adrenal Glands↗

PubMed1978

Adrenal-regeneration hypertension in Wistar-Furth rats.

The susceptibility of young virgin female Wistar-Furth (W/Fu) rats to adrenal-regeneration hypertension (ARH) was evaluated by comparing the blood pressure of adrenal-enucleated, mononephroadrenalectomized, salt-loaded rats with that of similarly treated rats having one intact adrenal over a period of 5 weeks. Hypertension began to appear in animals of the first group by the 3rd week, affected all of them by the 4th week, and increased in severity during the 5th week. Control rats remained normotensive during the study. Hypertensive rats developed marked enlargement of the heart and kidney, which frequently displaced myocardial scarring and nephrosclerosis, respectively. These studies do not support the contention that W/Fu rats display heightened resistance to ARH to which, in fact, they appear to be just as susceptible as are most other strains.

Adrenal Glands↗

PubMed1978

Blood pressure in conscious and anesthetized adrenal-enucleated Sprague-Dawley and Wistar-Furth rats.

Systolic blood pressure was measured weekly in conscious and in anesthetized female Sprague-Dawley (SD) and Wistar-Furth (W/Fu) rats following adrenal enucleation, unilateral nephrectomy, and the imposition of a high salt intake. SD rats quickly developed adrenal-regeneration hypertension (ARH) which progressed rapidly, and was identifiable in both the conscious and the anesthetized state. W/Fu rats slowly developed mild ARH, which, with a single exception, was identifiable only in conscious animals; the arterial pressures were within the normotensive range under anesthesia. The depressor effect of ether was also greater in adrenal-enucleated W/Fu than in similarly prepared SD rats, and in hypertensives than in normotensives. It is concluded that blood pressure measurements taken under anesthesia may not be representative of the true resting blood pressures: this is likely to be a particularly crucial problem in identifying early hypertension under circumstances and in rat strains highly susceptible to the depressor effects of ether.

Adrenal Glands↗

PubMed1975

[The role of deiodase and iodase in disturbed iodination processes in the thyroid].

Together with A. Costa of Turin, we have found adequate iodine in the food along the Northern slopes of the Alpine range in Valais, Switzerland, which has been known as a goitrous zone from time immemorial. In various statistical reports it has been pointed out that ostensibly the morbidity of goiter only regresses after the iodine added to the cooking salt is increased from 5 mg to 10 mg per kg. We see a regression of juvenile goiter only, because after puberty, 50 per cent of the Swiss population over the age of 50 have already developed goiter. We have found a goiter in rabbits and other experimental animals after feeding them cabbage and after the application of organic and inorganic sulfur compounds. After cabbage, a pre-Basedow type of goiter developed, after the application of sulfur the goiter was of a degenerative type, since in the latter case the iodase is first blocked by the thyroid and later destroyed.

Adolescent↗

PubMed1978

Salt taste and disease.

Sodium appetite reflects the importance of sodium homeostasis and the relative scarcity of sodium for many terrestrial animals. Man, for various reasons, also seems to have a specific preference for salt which he consumes in excess of need, and this has been characterized as an important contributor to hypertension. Gustatory sensibility is necessary for the development of sodium appetite. Thus, research on the possible role salt taste sensitivity plays in controlling NaCl consumption in the sodium deficient rat was reviewed as a potential model for the study of salt taste and hypertension in man. Taste acuity experiments began first by examining salt taste thresholds. These studies found that thresholds were not altered by sodium deficiency in rat and the results in hypertensive humans were inconclusive. Threshold determinations may not reveal true sensitivity differences because they varied significantly across experiments and because they are restricted to a small portion of the intensity domain. When research was directed to suprathreshold stimuli, concentrations a rat or man might normally experience, the evidence suggested that hypertensive humans, like sodium-deficient rats, were less sensitive to the taste of salt. This reduced sensitivity may account, in part, for the fact that these two groups consume more salt.

Adrenal Glands↗

PubMed1979

[Dynamics of renin production by the juxtaglomerular and mesangial cells of individual rat kidney glomeruli following adrenalectomy].

Adrenal incompetence developed in rats 6 weeks after adrenalectomy without any salt and hormonal compensation. In individual fragments of the isolated glomeruli containing juxtaglomerular cells (JGC) renin activity increased 1.2 times on the average, and there was revealed renin-like activity (RLA) in the fragments containing mesangial cells (MC). Signs of intensified renin secretion (expressed in reduction of granule count, marked development of granular endoplasmic reticulum, Golgi complex and microtubules) were noted in the JGC. In MC such organoids were well developed, but no granules were revealed. The following occurred in 8 to 12 weeks with the restoration of the 11-OCS and sodium level in the plasma: renin JGC activity became normal, RLA activity in MC disappeared, and the initial ultrastructure of both of these cells was restored. The reserve role of MC as the source of renin-like substances was confirmed.

Adrenal Glands↗

PubMed1975

Angiotensin stimulated AVP-release in humans.

Release of arginine vasopressin (AVP) from rat neurohypophysis in in vitro studies is significantly augmented by the addition of angiotensin (A-II), and in in vivo studies in dogs renin and A-II were found to stimulate secretion of AVP. Both these results suggest the existence of a direct relationship between the salt regulating renin-angiotensin-aldosterone system and the water controlling AVP system. To evaluate whether such observations apply also in man a sensitive double antibody radioimmunoassay for AVP was developed [17, 18]. Basal plasma levels of AVP in recumbent humans without salt and fluid restriction at room temperature were 3.4 plus or minus 2.2 pg/ml, and 30 min after the onset of an A-II infusion at a concentration of 3-30 ng/min-kg, a significant increase of AVP was found. Maximum measurements were 2-5 times basal levels which returned to normal within 90 min. During the A-II infusion one also noted a 20 mm Hg rise in blood pressure, accompanied by a significant decrease in plasma renin activity. During the same period serum osmolality and serum sodium concentration did not change. Elevation of blood pressure by norepinephrine was not followed by any detectable change of plasma AVP levels, thus excluding a nonspecific blood pressure effect.

Angiotensin II↗

PubMed1976

Histochemical and ultrastructural studies of the adrenal cortex in spontaneously hypertensive rats with high salt solution.

The response of the adrenal cortex in weanling Spontaneously Hypertensive Rats (SHR, Okamoto and Aoki) and Wistar-Kyoto Rats (WKR) when given 1% NaCl in drinking water was studied histochemically and electron microscopically. The development of hypertension was accelerated in SHR given 1% NaCl in drinking water. The thickness of the zona glomerulosa in WKR receiving 1% NaCl in drinking water remarkably diminished following the course of experiment and lipid droplets in the zona glomerulosa decreased gradually. The zona glomerulosa cells revealed shrinkage of the cells and a decreased number of mitochondrial cristae were observed at three weeks of experiment. The remaining tubular cristae of mitochondria possessed a milled outline. Golgi apparatus became small and fragmental. Membrane-bounded dense bodies were prominent in the peripheral portion of the cell and around Golgi apparatus. In SHR given 1% NaCl in drinking water, the width of the zona glomerulosa less diminished. A marked decrease in number and size of lipid droplets was seen. However, there was no distinct alteration of cytoplasmic organelles. These morphological changes were discussed from the standpoint of functional state in the zona glomerulosa with relation to the development of hypertension in SHR.

Adrenal Cortex↗

PubMed2026

Commensal Dysbiosis Alters Primary Bile Acid Signaling to Drive Mammary Gland Inflammation and Breast Tumor Dissemination.

UNLABELLED: Breast cancer is the most commonly diagnosed malignancy and a leading cause of cancer-related mortality. Hormone receptor-positive (HR+) tumors represent the most prevalent metastatic subtype, and early dissemination remains a major clinical challenge. Commensal dysbiosis, defined as an inflammatory gut microbiome with low biodiversity, promotes metastasis by inducing mammary gland inflammation. In this study, we investigated systemic mechanisms governing dysbiosis-induced metastasis. Metabolomic profiling revealed elevated primary bile acids (BA) in the dysbiotic fecal microbiome. Sequestration and supplementation approaches demonstrated that beyond driving metabolic disease and mammary gland inflammation, primary BAs orchestrated enhanced HR+ tumor dissemination via a prostaglandin E2 (PGE2)-dependent pathway. Analysis of The Cancer Genome Atlas showed that BA, insulin resistance, and PGE2 gene signatures are associated with reduced survival in patients with HR+ tumors. In complementary analyses using the Epic Cosmos electronic health record database, BA sequestrant use was associated with longer restricted mean survival time among patients with metastatic disease. Together, these findings reveal that commensal dysbiosis-associated loss of microbial BA metabolism elevates primary BAs and promotes HR+ metastatic progression through PGE2 signaling. SIGNIFICANCE: Dysbiosis-induced bile acids drive systemic and mammary tissue-specific inflammation that promotes HR+ breast tumor metastasis, supporting the development of strategies targeting microbiome-derived metabolites to reduce metastatic risk in vulnerable populations.

Female↗

PubMed1975

Molecular properties of purified (sodium + potassium)-activated adenosine triphosphatases and their subunits from the rectal gland of Squalus acanthias and the electric organ of Electrophorus electricus.

The chemical properties of two highly purified preparations of (sodium + potassium)-activated adenosine triphosphatase (NaK ATPase) and their subunits have been compared. One preparation is derived from the rectal gland of the spiny dogfish shark, Squalus acanthias and the other preparation is derived from the electric organ of the electric eel, Electrophorus electricus. Ouabain binding and phosphorylation from [gamma-32-P]ATP for both enzymes ranged from 4000 to 4300 pmol per mg of protein. This gives a stoichiometry for ouabain binding and phosphorylation of 1:1 for both enzymes. The molar ratios of catalytic subunit to glycoprotein was 2:1 for both enzymes, suggesting a minimum molecular weight of 250, 000, which agrees with the molecular weight obtained by radiation inactivation. Assuming that only one of the two catalytic subunits is phosphorylated and binds ouabain per (sodium + potassium)-activated adenosine triphosphatase molecule the data on phosphorylation and ouabain binding also give a molecular weight of 250, 000. The data on phosphorylatiion, ouabain binding, subunit composition, and molecular weight based on radiaion inactivation are thus all internally consistent. A technique has been developed for isolation of pure catalytic subunit and glycoprotein in good yields by preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A variety of chemical studies have been carried out with the purified subunits. The amino acid composition of the catalytic subunit was different from that of the glycoprotein, but the amino acid composition of each of the two subunits was essentially the same for both species. However, the NH2-terminal amino acid for the catalytic subunit was alanine for the rectal gland enzyme and serine for the electric organ enzyme, suggesting some differencesin amino acid sequences for the two species. The NH2-terminal amino acid for the glycoprotein was alanine for the two species. The glycoproteins from both species contained the same carbohydrates but in quite differing amounts. The carbohydrates were glucosamine, sialic acid, fucose, galactose, mannose, and glucose. The release of all the sialic acid from the electric organ enzyme and the release of 40% of the sialic acid from the rectal gland enzyme did not affect (sodium + potassium)-activated adenosine triphosphatase activity. Both enzymes contained the following phospholipids, which accounted for 98 to 100% of the total phospholipid phosphorus: sphingomyelin, lecithin, phosphatidylserine, phosphatidylethanolamine, and phosphatidylinositol. With the exception of phosphatidylethanolamine, and phosphatidylinositol. With the exception of phosphatidylserine, the amount of any phospholipid per mg of enzyme as well as the total phospholipid content were quite different for the two enzymes.

Adenosine Triphosphatases↗

PubMed1975

Characteristics of a solubilized thyrotropin receptor from bovine thyroid plasma membranes.

The thyrotropin receptor from bovine thyroid plasma membranes has been solubilized using lithium diiodosalicylate, and an assay to measure thyrotropin binding to the solubilized receptor has been developed. Both the solubilized thyrotropin receptor and the thyrotropin receptor on thyroid plasma membranes have effectively identical nonlinear Scatchard plots and negatively sloped Hill plots, i.e. both preparations have receptors which appear to exhibit a similar negatively cooperative relationship. Although the pH optimum of thyrotropin binding to the solubilized receptor is the same as that of the thyroid plasma membrane receptor, pH 6.0, the pH dependency curve of the solubilized receptor is slightly different in its outline. Thyrotropin binding to the solubilized receptor is less sensitive to salt inhibition than is binding to the thyroid plasma membrane receptor; however, optimal binding remains at 0 degrees. The relative affinities of thyrotropin and two glycoprotein hormones which can be considered structural analogs, luteinizing hormone and human chorionic gonadotropin, are 100:10:5, respectively, toward plasma membrane receptors, but 100:25:40 toward the solubilized receptors. The solubilized receptor preparation is heterogeneous in size in that it has binding components with molecular weights of 286,000, 160,000, 75,000, and 15,000 to 30,000. Tryptic digestion converts all three higher molecular weight components to the 15,000 to 30,000 molecular weight species, and the 15,000 to 30,000 molecular weight receptor component has all of the binding properties of the solubilized receptor preparation before tryptic digestion including an identical nonlinear Scatchard plot. It has the same size as and coelutes from Sephadex G-100 with a 15,000 to 30,000 molecular weight receptor released by tryptic digestion of bovine thyroid plasma membranes or tryptic digestion of bovine or dog thyroid cells in culture. The tryptic fragment of the solubilized receptor or preparations has been purified almost 250-fold by affinity chromatography on thyrotropin-Sepharose columns. The binding activity is lost when the solubilized thyrotropin receptor preparation is exposed to beads of neuraminidase-Sepharose or conconavalin A-Sepharose.

Animals↗