bluuebunny/crossref_metadata_2025 huggingface dataset:
Using ChIP-chip technology to reveal common principles of transcriptional repression in normal and cancer cells
Authors: Komashko Vitalina M. , Acevedo Luis G. , Squazzo Sharon L. , Iyengar Sushma S. , Rabinovich Alina , O’Geen Henriette , Green Roland , Farnham Peggy J.
Published: March 2008

We compared 12 different cell populations, including embryonic stem cells before and during differentiation into embryoid bodies as well as various types of normal and tumor cells to determine if pluripotent versus differentiated cell types use different mechanisms to establish their transcriptome. We first identified genes that were not expressed in the 12 different cell populations and then determined which of them were regulated by histone methylation, DNA methylation, at the step of productive elongation, or by the inability to establish a preinitiation complex. For these experiments, we performed chromatin immunoprecipitation using antibodies to H3me3K27, H3me3K9, 5-methyl-cytosine, and POLR2A. We found that (1) the percentage of low expressed genes bound by POLR2A, H3me3K27, H3me3K9, or 5-methyl-cytosine is similar in all 12 cell types, regardless of differentiation or neoplastic state; (2) a gene is generally repressed by only one mechanism; and (3) distinct classes of genes are repressed by certain mechanisms. We further characterized two transitioning cell populations, 3T3 cells progressing from G0/G1 into S phase and mES cells differentiating into embryoid bodies. We found that the transient regulation through the cell cycle was achieved predominantly by changes in the recruitment of the general transcriptional machinery or by post-POLR2A recruitment mechanisms. In contrast, changes in chromatin silencing were critical for the permanent changes in gene expression in cells undergoing differentiation.
Going‐concern Uncertainties in Pre‐bankrupt Audit Reports: New Evidence Regarding Discretionary Accruals and Wording Ambiguity
Authors: Arnedo Laura , Lizarraga Fermín , Sánchez Santiago
Published: March 2008

This paper extends the traditional view of audit failures related to the going‐concern (GC) assumption to two circumstances scarcely analyzed in the audit literature: the earnings overstatement that characterizes firms without a going‐concern uncertainty (GCU) in their audit reports and the wording used by auditors in the GC qualifications. We find significant differences between the discretionary accruals of Spanish GC and non‐GC companies. After discounting their effect, the client's financial condition loses its significance in the multivariate explanation of the GCU and auditor size is the variable that better explains the qualifications. We also find that a large percentage of GCUs are written ambiguously and with an overuse of conditional language, but no client or auditor attributes significantly explain differences in the GCU wording. Our results support the need to strengthen the enforcement mechanisms, as a GC audit Standard is not, by itself, enough to efficiently control auditor behaviour.
Ferritin Synthesis in Inflammation: I. PATHOGENESIS OF IMPAIRED IRON RELEASE
Authors: Konijn A. M. , Hershko C.
Published: March 2008

Summary. Plasma iron turnover (PIT) and ferritin synthesis in the liver and spleen were studied in rats within the first 24 h of inflammation produced by turpentine injection. Comparison of the sequential changes in PIT and ferritin synthesis showed that alterations in ferritin synthesis preceded the changes in plasma iron exchange throughout the study. Thus, after 4 h inflammation ferritin synthesis was twice normal whereas plasma iron and PIT were still unchanged. Conversely, maximal reduction in plasma iron occurred after 12 h inflammation, at a time when ferritin synthesis had already declined to normal rates. These correlations seem to indicate that, in analogy with other acute phase reacting proteins, increased ferritin synthesis is a primary nonspecific response which is part of a general pattern of the systemic effects of inflammation. This increase in ferritin synthesis is assumed to be responsible for the diversion of labile iron into ferritin stores, and its reduced availability for release from tissues.
Refractory Anaemia with Excess of Myeloblasts in the Bone Marrow: a Clinical Trial of Androgens in 90 Patients
Authors: Najean Y. , Pecking A.
Published: March 2008

Summary. In a cooperative trial, 90 patients with refractory anaemia with an excess of blast cells in the marrow were evaluated and treated with androgens.

The clinical presentation was very similar to previously published observations: features of medullary insufficiency were less marked than in primary aplastic anaemia; bone marrow blastic infiltration varied from case to case, and remained stable until death or until an acute leukaemic change.

All the patients were treated with high doses of androgens as for aplastic anaemia. The efficacy of this therapy was poor. The average life expectancy was 13 months, 64% of deaths being associated with a change to acute myeloid leukaemia. A severe bone marrow deficiency foreshadowed early death, but myeloblastic transformation was observed whatever the initial degree of blastic infiltration of the bone marrow.

A comparison with the literature suggests that androgen therapy may accelerate the change to acute leukaemia.
IgG4 Autoantibodies against Erythrocytes, without Increased Haemolysis: a Case Report
Authors: von dem Borne A. E. G. Kr , Beckers Do , van der Meulen F. W. , Engelfriet C. P.
Published: March 2008

Summary. A patient is described who, notwithstanding a strongly positive direct antiglobulin test with anti‐IgG serum, apparently did not suffer from haemolytic anaemia. The survival of the patient's red cells, measured with 51Cr, was only slightly decreased.

In vitro, the sensitized cells of the patient showed only a minimal tendency to adhere to monocytes. The patient's spleen functioned normally, since 51Cr‐labelled donor erythrocytes, either sensitized with IgG‐anti‐D or damaged by heating, were eliminated rapidly from the circulation and sequestered in the spleen.

These apparently contradictory findings could be explained by the fact that the patient's red cells were sensitized with autoantibodies, mainly belonging to the IgG4 subclass. Only weak IgGi and IgG3 autoantibodies were detectable. Since previously the patient had suffered from a severe haemolytic anaemia, it is postulated that a switch has occurred from ‘active’ to ‘inactive’ IgG autoantibodies, perhaps induced by prednisone therapy.
Infection with the roundworm Toxocara canis leads to exacerbation of experimental allergic airway inflammation
Authors: Pinelli E. , Brandes S. , Dormans J. , Gremmer E. , Van Loveren H.
Published: March 2008

Background
Epidemiological studies performed in developing as well as in western countries suggest that infection with Toxocara canis contributes to the development of atopic diseases.

Objectives
To investigate the association between infection with this helminth and allergy, we examined the effect of T. canis infection on experimental allergic airway inflammation.

Methods
BALB/c mice were infected by oral administration with 500 embryonated T. canis eggs followed by ovalbumin (OVA) sensitization and challenge to induce allergic airway inflammation.

Results
Infection with T. canis in combination with OVA treatment leads to exacerbation of pulmonary inflammation, eosinophilia, airway hyperresponsiveness, OVA specific and total IgE. Relative quantification of cytokine expression in the lungs of these mice showed increased expression of IL‐4 compared with mice that were only T. canis infected or OVA treated. Increased expression of IL‐5 and IL‐10 was measured in the lungs of T. canis‐infected or OVA‐treated mice compared with controls; however, combining infection and OVA treatment did not significantly change the expression of these cytokines.

Conclusion
A previous infection with T. canis leads to exacerbation of experimental allergic airway inflammation. These results have important consequences for findings on the helminths–allergy association. Several factors, including parasite species, infection of definitive vs. accidental host, parasite load and timing of infection, may influence whether an infection with helminths protects one from or enhances allergic manifestations.
CALCITONIN IN BREAST AND LUNG CANCER
Authors: HILLYARD CARMEL J. , COOMBES R. C. , GREENBERG P. B. , GALANTE LEONORA S. , MacINTYRE I.
Published: March 2008

Immunoreactive calcitonin was found in extracts of seven out of eight consecutive breast carcinomas and four selected lung carcinomas, but not in extracts of benign breast lesions or normal tissues.

This suggests that the high plasma calcitonin levels observed in patients with a wide variety of cancers reflect ectopic production of calcitonin by cancer tissue, and that the radioimmunoassay for calcitonin could prove to be of value in the detection and management of malignant disease, particularly breast cancer.
DELAYED ADJUSTMENT OF THE PITUITARY RESPONSE TO VARIATIONS IN CIRCULATING THYROID HORMONES IN A CASE OF SUBACUTE THYROIDITIS
Authors: DEMEESTER‐MIRKINE N. , BRAUMAN H. , CORVILAIN J.
Published: March 2008

In a case of subacute de Quervain thyroiditis characterized by a period of pronouced hypermetabolism followed by hypometabolism, levels of T4, T3 and the TSH response to TRH were repeatedly measured.

As expected, the response to TRH was absent or low during the hypermetabolic phase, high during the hypometabolic phase and returned to normal with recovery. However, at the beginning and at the end of the hypometabolic phase, while circulating levels of T3 and T4 both lay in the subnormal range, two periods of inadequate response to TRH could be demonstrated. During the first period, the response to TRH was zero or very small; during the second period, stimulation by TRH was exaggerated.

The response to TRH thus depends not only on the level of circulating thyroid hormones but on other factors such as the previous state of pituitary stimulation or inhibition.
TOTAL BODY POTASSIUM CONTENT IN MALES WITH X AND Y CHROMOSOME ABNORMALITIES
Authors: EAST BRIAN W. , BODDY KEITH , PRICE W. H.
Published: March 2008

Total body potassium has been measured in chromatin positive males (Klinefelter's syndrome) and males with a 47,XYY karyotype. In patients with an extra X chromosome the level of potassium was very significantly less than in normal males. Its concentration referred to lean body mass, estimated from the patient's height and weight, was also greatly reduced and not significantly different from values found in normal women.

In 47, XYY males individual values were low but there was no reduction in the mean value for the group if allowance was made for the obesity of some XYY subjects. The significance of these findings, however, is difficult to assess as ther height frequently exceeded that of the controls on which the predicted potassium values were based.

From these findings it would seem taht when characteristics which are normally associated with the female sex occur in males, as in Klinefelter's syndrome, there is also a reduction in body potassium either in the total content or the lean tissue concentration, or in both.

By comparison, 47, XYY males appear to be more normal in these respects but further normal data is requird in order to interpret the results.

The possibility that abnormal androgen production in the chromatin positive men may be influencing the potassium levels is the subject of further investigation.
INHIBITORY EFFECT OF SEROTONIN ANTAGONISTS ON GROWTH HORMONE RELEASE IN ACROMEGALIC PATIENTS
Authors: FELDMAN JEROME M. , PLONK JAMES W. , BIVENS CARL H.
Published: March 2008

We evaluated the effect of the serotonin antagonists cyproheptadine (Cypro) and methysergide (Methy) on growth hormone secretion in six patients with acromegaly. Two days administration of Cypro deceased the plasma GH concentration during oral glucose tolerance tests in four of the six patients evaluated; 2 days administration of Methy reduced the plasma GH levels of only one of the four patients evaluated. The one patient whose palsma GH concentration was lowered by Methy, did not have a decerase in plasma GH concentration after Cypro administration. Acromegalic patients have normal serum serotonin concentration and normal 5‐hydroxyindoleacetic acid excretion. If Cypro lowers plasma GH by antagonizing serotonin, our data would suggest that serotoninergic neruonal pathways are important in the regulation of pituitary GH secretion in some patients with acromegaly.
APPLICATION OF MASS SPECTROMETERY TO THE SEQUENCING OF PROTEINS
Authors: WILLIAMS DUDLEY H.
Published: March 2008

Mass spectrometry is now established as a viable method for determing the sequence of amino acids in proteins. The approach involves chemical and enzymic digestion of the protein (as in classical methods) to small peptides (ten residues) which are then chemically modified to increase their volatility. The chemical modifications are (i) acetylation of basic nitrogen sites and (ii) Permethylation. The derivatives so obtained may be sequenced in the mass spectrometer as mixtures of several peptides. This is achieved by a temperature gradient in the mass spectrometer source, which effects partial, or total separation of the derivatized peptides according to their volatilities. In this way, much tedious separation work (sometimes the rate‐determining factor in classical approaches) may be avoided. The sequencing process is carried out from the N‐terminal residue, utilizing the preferential cleavage of the ionized petide at the amide bonds; each amino acid is associated with a characteristic mass increment and thus the sequence can be determined. Mass spectrometry is especially useful in the detection and characterization of novel amino acids which might otherwise be difficult to identify. Although almost all work to date has used electron impact mass spectrometery, in the future it is possible that newer methods of ionization, such as field desorption and chemical ionization, might be profitably used.
MODE OF ACTION OF PEPTIDE HORMONES
Authors: NEHER ROBERT , MILANI ALFRED
Published: March 2008

The mode of action is discussed of the peptide hormones which trigger neosynthesis of a specific product in their target cells without being involved in any release step. Particular attention is paid to the early events elicited by ACTH in isolated adrenocortical cells. It is shown that extracellular calcium ions at physiological concentrations can serve as first messenger activating steroidogenesis if the isolated cells are pretreated in an appropriate ionic environment. Among other factors the extracellular calcium/phosphate ratio seems to be of importance. A model is proposed where calcium serves as direct messenger in the physiological activation by ACTH, cyclic AMP being a subserving factor maintaining full steroidogenesis.
THE MESSAGE SEQUENCE OF α‐MELANOTROPIN: DEMONSTRATION OF TWO ACTIVE SITES
Authors: EBERLE ALEX , SCHWYZER ROBERT
Published: March 2008

The purpose of this investigation was to elucidate the biological significance of lysine11 and of the tripeptide sequence ‐Lys‐Pro‐Val‐NH2 for the biological activity of α‐melanocyte‐stimulating hormone. To this end the in vitro melanotropic activities of twenty‐four synthetic peptides related to the hormone were determined. Extension or reduction of the length of the lysine11 side chain results in a marked decrease of the melanotropic potency of the respective analogue. The C‐terminal tripeptide (11‐13), the tetrapeptide (10‐13), and the pentapeptide (9‐13) were found to be hormonally active in the same order of magnitude as the central hexapeptide (5‐10). The following conclusion was drawn: α‐MSH possesses (in contrast to ACTH) two message sequences (active sites), (i) ‐Glu‐His‐Phe‐Arg‐Trp‐, and (ii) ‐Gly‐Lys‐Pro‐Val‐NH2 which are capable of independently triggering the hormone receptor responsible for melanin dispersion. Thus, despite the close structural similarity of the two hormones, α‐MSH and ACTH appear to react with their respective target cell receptors by quite different chemical mechanisms, implying different receptor structures.
REGULATION OF VITAMIN D: AN EVOLUTIONARY VIEW
Authors: MacINTYRE I. , COLSTON KAY W. , EVANS IMOGEN M. A. , LOPEZ EVELYNE , MacAULEY S. J. , PIEGNOUX‐DEVILLE JACQUELINE , SPANOS E. , SZELKE M.
Published: March 2008

The regulation of vitamin D metabolism by the kidney is now known to be multifactorial. Three regulatory factors are discussed: 1,25(OH)2D3 itself; parathyroid hormone, and phospate. The influence of 1,25(OH)2D3 probably depends on new protein synthesis, while the mode of action of phosphate is unknown. Parathyroid hormone is not essential for regulation but may have an important biological role. The direction of its effect varies, perhaps due to a complex inter‐relation of changes in calcium and phosphorus metabolism and the level of kidney adenyl cyclase activity.
RECENT ADVANCES IN OUR UNDERSTANDING OF THE METABOLISM OF VITAMIN D AND ITS REGULATION
Authors: DeLUCA HECTOR F.
Published: March 2008

Potent new methods of separation of vitamin D metabolites and analogues have been developed using high pressure liquid chromatography and silica gel columns. Utility of this new method in the further study of vitamin D metabolism has been demonstrated. With this technique it has been possible to demonstrate that the natural product, 24,25‐dihydroxyvitamin D3 (24,25‐(OH)2D3), has its hydroxyl in the R configuration. With 3H‐1α‐hydroxyvitamin D3 (1α‐OH‐D3), which has been recently synthesized in this laboratory, it has been possible to show that it is rapidly converted to 1,25‐dihydroxyvitamin D3 (1,25‐(OH)2D3) predominantly by liver and that this conversion occurs in ample time to account for its biological activity. Chick intestine possesses some 25‐hydroxylating ability whereas rat intestine does not. It seems likely that 1α‐OH‐D3 is biologically active almost entirely by virtue of its conversion to 1,25‐(OH)2D3.

The 24R,24,25‐(OH)2D3 is almost as biologically active as 25‐hydroxyvitamin D3 (25‐OH‐D3) in the rat, but has low activity in the chick. The S isomer is essentially without activity in either species except for intestinal calcium transport in the rat. Radioactive 24,25‐(OH)2D3 has been used to demonstrate that in the chick it is rapidly metabolized and excreted suggesting that the 24‐hydroxylation in the chick is an important biological inactivation mechanism. In the rat it is possible that the 24‐hydroxylation has functional significance.

Finally, the 1α‐hydroxylase of 25‐OH‐D3 in chick kidney has been successfully solubilized and the cytochrome P‐450 as well as the renal ferredoxin has been isolated and recombined with beef adrenal flavoprotein to produce a reconstructed 25‐OH‐D3‐1α‐hydroxylase system with very high specificity and high enzymatic activity. The results show conclusively that the 1‐hydroxylase system requires NADPH to reduce a flavoprotein which in turn reduces a renal ferredoxin which in turn reduces the cytochrome P‐450. The cytochrome P‐450 carries out the hydroxylation using molecular oxygen and 25‐OH‐D3.
THE VITAMIN D3 METABOLITE‐TYPE ACTIVITY OF SOLANUM MALACOXYLON
Authors: BASUDDE C. D. K. , HUMPHREYS D. J.
Published: March 2008

1. Administration of an aqueous extract of the dried leaves of Solanum malacoxylon (DLSM) to rats causes a rapid hyperphosphataemia and a decrease in plasma alkaline phosphatase activity; the two effects are typical of 1,25(OH)2D3, the hormonally active metabolite of vitamin D3.

2. DLSM, like both vitamin D3 and parathyroid hormone, increases plasma calcium and citrate levels in rats. The effect of DLSM in influencing plasma citrate, and the role of this important metabolite in mineral metabolism is discussed.

3. A decrease of plasma magnesium levels occurs in rats following treatment with DLSM. This decrease, which is associated with a renal loss of this cation, is remarkably similar to that produced by hypervitaminosis D3.

4. Prolonged administration of DLSM to vitamin D deficient rats causes a polyuria, hypercalciuria, hyperphosphaturia, hypermagnesuria, an increase in urinary total hydroxyproline, an increase in plasma total hexosamines, and a corresponding decrease in the bone total hexosamines. These effects, some of which can also be produced by hyperparathyroidism, or following the administration of parathyroid extract (PTE), large doses of vitamin D3, or 1,25(OH)2D3, suggest that DLSM, like the latter compounds, is capable of causing bone mineral mobilization, and the dissolution of bone organic matrix.
THE CHEMISTRY AND CONFORMATIONAL AND BIOLOGICAL ANALYSIS OF VITAMIN D3, ITS METABOLITES AND ANALOGUES
Authors: NORMAN ANTHONY W. , JOHNSON R. LORNE , OSBORN TERRY W. , PROSAL DANA A. , CAREY STEPHEN C. , HAMMOND MILTON L. , MITRA MANINDARAN N. , PIRIO MARCEL R. , REGO ALBERT , WING RICHARD M. , OKAMURA WILLIAM H.
Published: March 2008

The chemical properties, sterochemical relationships and solution confromation, as assessed in part by proton NMR spectroscopy, for vitamin D3, its major metabolites [including 1α, 25‐(OH)2 D3, its hormonally active form] and a number of A‐ring and side chain analogues are evaluated and discussed in relation ot their biological activity. In particular the relative ability of many of these seco‐steroids to compet both with 25‐OHD3 for its chick serum binding protein and 1α, 25‐(OH)2‐D3 for its chick intenstinal cytosol‐chromation receptor systme was quantitated, in vitro, Further, the relative effectiveness of all these metabolites and analogues to mediate in vivo intestinal calcium absorption and bone calcium mobilization was determined. Collectiveily these chemical and bilogical studies constitute a ‘systems analysis’of the various steroid structural parameters both required and tolerated by the multi‐stepped endocrine system associated with the bilogical actions of vitamin D.
TREATMENT OF HYPOPARATHYROIDISM WITH 1,25‐DIHYDROXYCHOLECALCIFEROL
Authors: HILL L. F. , DAVIES M. , TAYLOR C. M. , STANBURY S. W.
Published: March 2008

Five patients with hypoparath;yroidism (three post thyroidectomy and two idiopathic) were treated with synthetic 1,25‐dihydroxycholecalciferol (1,25‐(OH)2‐D3) for up to 6 months. In each case daily oral administration of 1 μg 1,25‐(OH)2D3 either alone or with additional calcium, raised the serum calcium into the normal range. The serum pnhosphorus and the renal tubular reabsorption of phosphorus fell during treatment. None of these patients developed hypercalcaemia and no other complications of treatment have been recorded. 1,25‐(OH)2D3 seems to represent a significant improvement over conventional methods for treating hypoparath;yroidism.
THE HETEROGENEITY OF GASTRIN, WITH REFERENCE TO CONVERSION OF GASTRIN‐17
Authors: REHFELD J. F. , CHRISTIANSEN L. A. , MALMSTRØM J. , SCHWARTZ T. , STADIL F.
Published: March 2008

High‐resolution gel chromatography monitored by a sensitive radioimmunoassay for gastrin has disclosed that gastrin circulates in twenty different components. Since the assay is specific for the biological active sequence of gastrin (‐Trp‐Met‐Asp‐PheNH2), we conclude that all the twenty circulating molecular forms of gastrin encountered in this study may participate in the regulation of gastric acid secretion.

There are two dominating forms of gastrin in serum: gastrin‐34‐like components and gastrin‐17‐like components. The former constitutes 60% and the lattr constitutes approximatly 30% of the immunoreactive gastrins.

We suggest that extragastrointestinal conversion of gastrin‐17, released from tissue, is an important source of gastrin‐34‐like components. Such conversion has been observed in intact man and pig. Studies with the isolated perfused porcine liver indicate that the liver is important in the metabolism of gastrin‐17, and that conversion may be a hepatic function.
REGULATION OF CALCITONIN SECRETION IN VITRO
Authors: ROOS BERNARD A. , DEFTOS LEONARD J.
Published: March 2008

We have developed methods for the long‐term maintenance of monolayer cultures of both human and trout calcitonin‐secreting (C‐) cells (Roos et al., 1974a, 1975). Secreted calcitonin (CT) can be measured by specific and sensitive radioimmunoassays for human calcitonin (HCT) and trout calcitonin (TCT) (Deftos, 1971; Deftos et al., 1974; Roos et al,, 1974b). The combined application of these cell culture and radioimmunoassay methods to the in vitro study of CT secretion has revealed fundamental differences in the regulation by divalent ions of CT secretion in mammalian and nonmammalian C‐cells. Our results also indicate a specific role for secretin as a CT secretagogue in trout. In addition to establishing the individual secretory effects of calcium and the enteric polypeptide hormones on the C‐cells of both species, we have investigated the combined effects of these agents in both human and trout C‐cell cultures. The noncompetitive augmentation of the secretory effects resulting from the actions of specific combinations of these secretagogues in each of these C‐cell populations suggests that CT secretion is regulated by co‐ordinate interaction of specific ionic and peptide secretagogues. An elucidation of the cellular mechanisms involved in such multifactorial control of C‐cell function should result from the continued investigation of CT secretion in these C‐cell cultures.

We have developed methods for the long‐term maintenance of monolayer cultures of both human and trout calcitonin‐secreting (C‐) cells (Roos et al., 1974a, 1975). Secreted calcitonin (CT) can be measured by specific and sensitive radioimmunoassays for human calcitonin (HCT) and trout calcitonin (TCT) (Deftos, 1971; Deftos et al., 1974; Roos et al., 1974b). In addition to establishing the individual secretory effects of calcium and the enteric polypeptide hormones on the C‐cells of both species, we have investigated the combined effects of these agents in both human and trout C‐cell cultures.
VIP MEASUREMENT IN DISTINGUISHING VERNER‐MORRISON SYNDROME AND PSEUDO VERNER‐MORRISON SYNDROME
Authors: BLOOM S. R. , POLAK J. M.
Published: March 2008

1. Plasma VIP immunoreactivity is always diagnostically raised in patients with pancreatic tumour causing the Verner‐Morrison syndrome.

2. Human tumour VIP is physico‐chemically similar to porcine VIP.

3. The only other situation in which plasma VIP is very elevated is in patients with ganglioneuroblastomas associated with diarrhoea.

4. VIP is not elevated in patients with diarrhoea associated with pancreatic islet hyperplasia, designated the pseudo Verner‐Morrison syndrome.
THE DEVELOPMENT OF THE RELEASING FACTOR CONCEPT
Authors: FINK G.
Published: March 2008

?summary

Ater four decades of intense and competitive research, three hypothalamic releasing hormones (formerly factors) hav recently been isolated and characterized. These are the decapeptide gonadotrophin releasing hormone (GnRH), tripeptide thyrotorphin releasing hormone (TRH), and the teradecapeptide somatotain. Some aspects of these hormones are discussed, and CnRH is considered in greater details to demonstrate the difficulties involved in fulfilling completely the criteria which edtermine whether a substance can be accepted as a physiologica releasing hormone. A substance immunologically similar to GnRH is present in rat phypophysial portal vessel blood, but, while the amount of this substance released into the portal circulation can be increased significantyly by electrical stim;ulation of the preoptic area, no significant ch;anges occur during the oestrous cycle or after long‐term castration. This may be due to interference with the normal secretion of GnRH by the trauma and anaesthesia which necessarilyl accompany exposure of the pituitray stalk. However, the possibility exists that our preonceived jnotions regarding the changes in plasma levels of releasing hormones under physiological conditions may be incorrect. Thus it seems likely that changes in the rate of secretion of thyrotrophin is effected by thyroid hormones modulating the responsiveness of the thyrotrophs to steady input of TRH. Evidence is presented for the existence of a similar mechanism for gonadotrophin secretion, and the role of steroid hormones and the priming effect of GnRh in modulating the responsiveness of the gonadotrophs is considered. The interinsic connexions of the hypothalamu;s, the role of the hypothalamic aminergic systems and the autonomy of the hypothalamus with repect to anterior pituitary contro present many problems which will prove difficult to solve.
STRUCTURE ACTIVITY STUDIES ON SOMATOSTATIN
Authors: SARANTAKIS D. , McKINLEY W. A. , JAUNAKAIS I. , CLARK D. , GRANT N. H.
Published: March 2008

Seven synthetic analogues of somatostatin helped clarify structural requirements for suppression of growth hormone secretion in rats. Size of the ring is not critical; deletions of serine‐13, lysine‐4 or asparagine‐5 result in peptides which retain an appreciable fraction of the activity. The analogue des‐Ala1, Gly2, Asn5‐somatostatin lowers plasma growth hormone and insulin levels without affecting plasma glucagon levels significantly.
INHIBITORY ACTIVITY OF ANALOGUES OF LUTEINIZING HORMONE‐RELEASING HORMONE (LH‐RH) IN VITRO AND IN VIVO
Authors: FERLAND L. , LABRIE F. , SAVARY M. , BEAULIEU M. , COY D.H. , COY E. J. , SCHALLY A. V.
Published: March 2008

Improved inhibitors of LH‐RH are those which, beside removal of the histidine residue at position 2 of LH‐RH, include replacement of glycine at position 6 by a d‐amino acid. A still better modification is replacement of the histidine residual at position 2 by d‐phenylalanine. As examples, when tested in pituitary cells in culture, [Des‐His2]LH‐RH, [Des‐His2, D‐Leu6] LH‐RH, [Des‐His2, D‐Phe6]‐LH‐RH, [D‐Phe2]LH‐RH, [D‐Phe2, D‐Leu6]LH‐RH and [D‐Phe2, D‐Phe6]LH‐RH inhibit 50% of LH release induced by LH‐RH at molar ratios (MR50s) of 3000, 500, 60, 1000, 150 and 25, respectively. [D‐Phe2, Phe5, D‐Phe6]LH‐RH have MR50 values of respectively 400, 100, and 75. When evaluated in vivo, some of the mentioned structural modifications permit inhibition of LH‐RH action at molar ratios lower than observed in vitro. At a 500 molar ratio, [D‐Phe2, Phe5, D‐Phe6]‐LH‐RH inhibits the plasma LH rise induced by LH‐RH by 75% up to 5 h after its injection. When administered at 12.00 hours at the dose of 2 mg, this analogue inhibits the sponatenous pro‐oestrus LH surge and ovulation by 85 and 75%, respectively.
ROLE OF GLUCAGON IN HUMAN DIABETIC KETOACIDOSIS: STUDIES USING SOMATOSTATIN
Authors: GERICH JOHN E. , SCHNEIDER VICTOR S. , LORENZI MARA , TSALIKIAN EVA , KARAM JOHN H. , BIER DENNIS M. , FORSHAM PETER H.
Published: March 2008

The present studies demonstrate that endogenous glucagon is hyperglycaemic, lipolytic and ketogenic in man, and that insulin deficiency is necessary, but is in itself not sufficient, to cause fulminant diabetic ketoacidosis. Furthermore, continuous elevation of endogenous glucagon secreation appears to be necessary for the maintenance and continued development of the characteristic metabolic consequences of insulin lack.
HEREDITARY BONE DYSPLASIA WITH HYPERPHOSPHATASAEMIA: RESPONSE TO SYNTHETIC HUMAN CALCITONIN
Authors: HORWITH M. , NUNEZ E. A. , KROOK L. , VITERI F. , TORUN B. , MENA E. , SUH S. M. , EISENBERG E. , MacINTYRE I. , WHALEN J. P.
Published: March 2008

Four cases of familial bone dysplasia with hyperphosphatasaemia were treated with synthetic human calcitonin. Prior to therapy, all four cases were characterized by marked bone deformity, pain, tenderness and elevated levels of serum alkaline phosphatase and urinary hydroxyproline. Treatment with calcitonin produced in each case a striking clinical, biochemical and radiographic remission. Pain and tenderness was greatly diminished and urinary hydroxyproline and serum alkaline phosphatase levels were significantly decreased. Radiographic regression of the bony abnormalities was apparent as early as 41/2 months after the start of treatment, Prior to therapy bones exhibit no real organization. After calcitonin treatment, the radiographic appearance of a normal cortex and medullary cavity was clearly evident for the first time.
CONCEPTS IN ECTOPIC HORMONE PRODUCTION
Authors: REES LESLEY H.
Published: March 2008

Non‐endocrine tumours are capable of production of ectopic hormones, precursor molecules subunits and hormone‐related fragments. The measurement of these may provide biochemical markers of maligancy, allowing presymptomatic diagnosis which may lead ultimatley to an improved prognosis for the patient. The study of ectopic humoral syndromes may yield new insights into the nature of cellular differentiation and the fundamental process of malignant change.
HORMONE RECEPTORS AND CYCLIC NUCLEOTIDE METABOLISM IN CANCER CELLS
Authors: MARTIN T. J. , HUNT N. H. , BOYD HELEN , ELLISON MORAG , MICHELANGELI V. P. , ATKINS D.
Published: March 2008

The possibility of a relationship between cyclic AMP formation and metabolic processes in tumours has been investigated. Changes in basal activity and hormone‐responsiveness of adenylate cyclase were demonstrated in plasma membranes and intact cells from pre‐cancerous liver of rats fed a diet containing the carcinogen 3′‐methyl‐4‐dimethylaminoazobenzene. Basal adenylate cyclase activity in hyperplastic parathyroid gland membranes was 200% higher than that in parathyroid adenoma membranes, corresponding with their relative rates of parathyroid hormone secretion in vitro. Membrane adenylate cyclase activity in hypernephromas was consistently 100–300% higher than in adjacent human renal cortex. Furthermore the adenylate cyclase activity of the tumour membranes was not influenced by a wide range of hormones which were effective stimulants in ‘normal’renal cortex membranes. Conversion of 25‐hydroxycholecalciferol to 1,25‐dihydrocholecalciferol could not be demonstrated in either hypernephroma or adjacent renal cortical tissue. However, three of the four hypernephromas tested secreted a bone‐resorbing factor. Cyclic AMP formation was increased by salmon, human and porcine calcitonins in both plasma membranes and intact cells from a poorly differentiated epidermoid cell carcinoma which was itself secreting calcitonin in culture. This phenomenon might be related to a feedback regulation of calcitonin production in this cell line.

The observations are consistent with the concept of a relationship between cyclic AMP formation and certain metabolic functions (e.g. hormone production) in tumour cells.
Adiponectin, skeletal muscle adiponectin receptor expression and insulin resistance following dexamethasone
Authors: Jang Christina , Inder Warrick J. , Obeyesekere Varuni R. , Alford Frank P.
Published: March 2008

Objective  Skeletal muscle is a major site of adiponectin action and of glucocorticoid‐induced insulin resistance. Little human data exist however, regarding the impact of exogenous glucocorticoids on adiponectin receptors in skeletal muscle.

Design and patients  Twelve subjects with type 2 diabetes and 12 controls underwent blood sampling and muscle biopsy of vastus lateralis before and after 4 days of 4 mg dexamethasone.

Measurements  (i) Total and high molecular weight (HMW) plasma adiponectin, glucose and insulin; (ii) Skeletal muscle adiponectin receptor AdipoR1 and AdipoR2 mRNA levels by quantitative real time RT‐PCR.

Results  Baseline total adiponectin (8·0 ± 0·89 vs. 12·5 ± 1·46 µg/ml, P = 0·013), HMW adiponectin (2·8 ± 0·44 vs. 5·9 ± 1·04 µg/ml, P = 0·014) and AdipoR2 mRNA levels (mean ΔCT 14·71 ± 0·35 vs. 13·37 ± 0·28, P = 0·017) were significantly lower in diabetic subjects. After dexamethasone, AdipoR2 mRNA fell in the controls but there was no change in the diabetic group, while there was a significant increase in total (P = 0·002) and HMW adiponectin (P < 0·001) across both groups. Total and HMW plasma adiponectin correlated with clinical and biochemical measures of insulin sensitivity. However following dexamethasone which increased insulin resistance, the relationship between adiponectin and the biochemical measures was lost.

Conclusions  Plasma adiponectin and skeletal muscle AdipoR2 mRNA expression are reduced in subjects with diabetes; both are likely to contribute to the observed insulin resistance. Dexamethasone inhibits AdipoR2 mRNA expression in nondiabetic subjects, while there is a small rise in plasma adiponectin levels. The close relationship between plasma adiponectin and biochemical measures of insulin sensitivity is lost in the setting of glucocorticoid‐induced insulin resistance.
New Strains of Bacillus licheniformis and Bacillus coagulans producing Thermostable α‐Amylase Active at Alkaline pH
Authors: MEDDA S. , CHANDRA A. K.
Published: March 2008

Two species of Bacillus producing thermostable α‐amylase with activity optima at alkaline pH are reported here. These organisms were isolated from soil and have been designated as Bacillus licheniformis CUMC 305 and B. coagulans CUMC 512. The enzymes released by these two species were partially purified up to about 81‐ and 72‐fold respectively of the initial activity. The enzyme from B. licheniformis showed a wide temperature‐range of activity, with optimum at 91°C. At this temperature it remained stable for 1 h. It retained 40–50% activity at 110°C and showed only 60% of its activity at 30°C. The enzyme showed a broad pH range of activity (4–10) retaining substantial activity on the alkaline side. The optimum pH was 9·5. The enzyme of B. coagulans showed activity up to 90°C, with optimum at 85°C and had a wide pH range with optimum at 7·5–8·5. The hydrolysis pattern of the substrate starch by these enzymes indicated that glucose, maltose, maltotriose and maltotetraose are the principal products rather than higher oligosaccharides.
The Occurrence and Significance of Pseudomonas in Wiltshire Bacon Brines
Authors: GARDNER G. A.
Published: March 2008

Pseudomonas spp. in Wiltshire bacon cover brines taken from seven bacon factories were enumerated at regular intervals over six months. There were differences between factories as assessed by the geometric mean counts (12–2907/ml) or by the percentage of samples exceeding 103/ml (0–75%). Heavy pseudomonad contamination of brines was associated with large populations of Pseudomonas spp. on fresh pork carcasses and vice versa. The curing of defrosted pork carcasses also led to high Pseudomonas spp. counts in brines. The average time for 90% reduction in a Pseudomonas population in brine was 35 d. These data can aid interpretation of the Pseudomonas count of bines when it is used as a part of microbiological quality control. A set of advisory standards proposed.
A Note on the Nature and Sequence of Yeasts during Fermentation of Apples grown in India
Authors: ETHIRAJ S. , ONKARAYYA H. , SURESH E. R.
Published: March 2008

Six morphologically different groups of yeasts comprising Kloeckera apiculata. Candida krusei, Candida valida, Candida sorbosa, Metschnikowia pulcherrima and Saccharomyces chevalieri were isolated from fresh, fermenting and fermented apple juice. This is the first report on the isolation of C. valida, C. sorbosa and S. chevalieri from fermenting and fermented apple juice.
Growth Factors of Bacterial Origin for the Culture of the Rumen Oligotrich Protozoon, Entodinium caudatum
Authors: ONODERA R. , HENDERSON C.
Published: March 2008

Attempts were made to develop an artificial medium suitable for axenic culture of Entodinium caudatum. Agnotobiotic cultures of the protozoon were established as stock cultures for testing the suitability of various growth media. A cell‐free extract of mixed bacteria isolated from the rumen was shown to contain one or more growth factors for the protozoon when supplied with activated charcoal as a carrier. The medium (CYSE medium), which supported the growth of the protozoon in the presence of 50 μg/ml each of penicillin and chloramphenicol, consisted of activated charcoal (20 mg), heat‐treated yeast (Y) (80 mg), 13%β‐sitosterol‐coated rice starch (S) (120 mg), and cell‐free extract of rumen bacteria (1 ml) in 40 ml buffer solution. When culturing the protozoon, the CYSE medium was supplemented daily with 20 mg each of Y and S and half of the medium was replaced with fresh medium once every 5 d. The possible use of this method to establish an axenic culture of E. caudatum is discussed.
Development and growth effects in the Sorghum–Azospirillum association
Authors: Pacovsky R.S.
Published: March 2008

Sorghum plants were inoculated with a pigmented strain of Azospirillum brasilense (Cd) or were not inoculated and received an N‐amended nutrient solution (1.0 mmol/l NH4NO3). A third set of plants were non‐inoculated and not fertilized with N (control). Plants were grown in a steam‐sterilized, low‐fertility soil and harvested after growing for 2, 4, 6, 8 and 10 weeks. Dry weights for Azospirillum‐inoculated plants were significantly greater than the N‐fertilized sorghum at weeks 2 and 4, but A. brasilense‐colonized plants weighed significantly less than the N‐fertilized sorghum at weeks 8 and 10. Shoot and root N concentrations increased for N‐amended plants but remained fairly steady for sorghum inoculated with strain Cd indicating enhanced N‐use efficiency in plants colonized with the endophyte. In general, the concentration of Fe, Mn, Zn and Cu in Azospirillum‐colonized plants was relatively less than that in N‐amended sorghum early in ontogeny when the growth rate of the inoculated plants was greatest. The number of inoculated Cd cells per plant was correlated with percentage increase in dry weight (r= 0.92*) or total N content (r= 0.93*) relative to the N‐fertilized plants. Growth enhancement relative to N‐fertilized sorghum was not observed when the number of Azospirillum cells per gram of root dropped below 1.0 x 105 (or 3.0 x 106 cells/plant). Therefore, the persistence of Azospirillum in the endorhizosphere of sorghum had a direct impact on host growth, physiology and nutrition.
Fermentation of ang‐kak in plastic bags and regulation of pigmentation by initial moisture content
Authors: Lotong N. , Suwanarit P.
Published: March 2008

A method of producing ang‐kak (Chinese red rice) in plastic bags by Monascus sp. NP1 was developed. Advantages of the procedure are described. Fermentation of rice of various moisture contents gave results that agreed with previous findings that ang‐kak could be produced only at a relatively low initial moisture level. The mechanism by which the initial substrate moisture content regulated pigmentation was clarified. It was found that glucoamylase activity increased with increase in initial substrate moisture content. Therefore at high moisture content, as high enzyme activity was produced, glucose was rapidly liberated in amounts that inhibited pigmentation. The sugar was then transformed to ethanol. Addition of various amounts of glucose to rice of low moisture content before fermentation confirmed that the sugar at certain concentration had an inhibitory effect on pigmentation.
Detection of Bifidobacterium species by enzymatic methods*
Authors: Chevalier P. , Roy D. , Ward P.
Published: March 2008

The properties of Bifidobacterium strains of human origin were examined by three enzymic tests and the amounts of acetic and lactic acids produced were also quantified. It was evident that two strains of the American Type Culture Collection (ATCC) did not belong to the genus. Moreover, at least one strain of Bifidobacterium added to some milk preparations did not show distinctive characteristics of the genus. It was also shown that most of bifidobacteria studied produced α‐galactosidase (EC 3.2.1.22) and α‐glucosidase (EC 3.2.1.20). The presence of α‐galactosidase could afford a rapid differentiation of bifidobacteria used in some dairy products since this enzyme was not detected in Lactobacillus strains studied.
17β‐Oestradiol Stimulation of G‐Proteins in Aged and Alzheimer’s Human Brain: Comparison with Phytoestrogens
Authors: Jefremov V. , Rakitin A. , Mahlapuu R. , Zilmer K. , Bogdanovic N. , Zilmer M. , Karelson E.
Published: March 2008

The neuroprotective action of oestrogens and oestrogen‐like compounds is in the focus of basic and clinical research. Although such action has been shown to be associated with neuronal plasma membranes, the implication of G‐proteins remains to be elucidated. This study revealed that micromolar concentrations (μm) of 17β‐oestradiol and phytoestrogens, genistein and daidzein, significantly (P < 0.05) stimulate G‐proteins ([35S]GTPγS binding) in the post‐mortem hippocampal membranes of age‐matched control women with the respective maximum effects of 28, 20 and 15% at 10 μm. In the frontocortical membranes, the stimulation of G‐proteins did not differ significantly from that in hippocampal membranes. Although in the hippocampus and frontal cortex of the Alzheimer’s disease (AD) women's brain, 10 μm 17β‐oestradiol produced significantly (P < 0.05) lower stimulation of G‐proteins than in the control regions, stimulation by phytoestrogens revealed no remarkable decline. 17β‐Oestradiol, genistein and daidzein revealed a selective effect on various G‐proteins (Gαs, Gαo, Gαi1 or Gα11 plus Gβ1γ2) expressed in Sf9 cells. At a concentration of 10 μm, 17β‐oestradiol suppressed the H2O2 and homocysteine stimulated G‐proteins in the frontocortical membranes of control women to a greater extent than phytoestrogens. In AD, the suppressing effect of each compound was lower than in the controls. In the cell‐free systems, micromolar concentrations of phytoestrogens scavenged OH• and the 2.2‐diphenyl‐1‐picrylhydrazyl free radical (DPPH•) more than 17β‐oestradiol did. In the frontocortical membranes of control women, the 20 μm 17β‐oestradiol stimulated adenylate cyclase with 20% maximal effect, whereas, in AD, the effect was insignificant. Genistein did not stimulate enzyme either in control or AD frontocortical membranes. Our data confirm that the agents stimulate G‐proteins in control and AD women's brains, although 17β‐oestradiol and phytoestrogens have similarities and differences in this respect. We suggest that, besides the ER‐dependent one, the ER‐independent antioxidant mechanism is responsible for the oestrogen stimulation of G‐proteins in the brain membranes. Both of these mechanisms could be involved in the neuroprotective signalling of oestrogens that contributes to their preventive/therapeutic action against postmenopausal neurological disorders.