bluuebunny/crossref_metadata_2025_split huggingface dataset:
Surgical debulking of pituitary macroadenomas causing acromegaly improves control by lanreotide
Authors: Karavitaki N. , Turner H. E. , Adams C. B. T. , Cudlip S. , Byrne J. V. , Fazal‐Sanderson V. , Rowlers S. , Trainer P. J. , Wass J. A. H. 
Published: May 2008

SummaryBackground  Macroadenomas causing acromegaly are cured surgically in only around 50% of patients. Primary medical treatment with somatostatin analogues has been suggested to be a means of treating patients with a potentially poor surgical outcome. Previous retrospective studies have also suggested that surgical debulking of pituitary tumours causing acromegaly improves control by somatostatin analogues. No prospective study using lanreotide has been carried out thus far to assess whether this is the case.Objective  We carried out a prospective study to assess whether surgical debulking of pituitary macroadenomas causing acromegaly improved the subsequent control of acromegaly by the somatostatin analogue lanreotide.Patients and methods  We treated 26 consecutive patients [10 males and 16 females – median age 53·5 years (range 22–70)] with macroadenoma causing acromegaly unselected for somatostatin response for 16 weeks with lanreotide, maximizing GH and IGF‐I suppression, if necessary, by incremental dosing. Surgical resection was carried out and the patients were re‐assessed off medical treatment at 16 weeks following surgery. Those with nadir GH > 2 mU/l in the oral glucose tolerance test (OGTT) and a mean GH in the GH day curve (GHDC) > 5 mU/l were subsequently restarted on lanreotide and the responses were assessed at the same time points as during the preoperative lanreotide treatment.Results  GH values fell on lanreotide treatment and prior to surgery they were considered ‘safe’ (mean GH in GHDC < 5 mU/l) in eight patients (30·7%). After surgery, they were ‘safe’ in 18 patients (69·2%). The figures for normal IGF‐I were 11 (42·3%) before surgery and 23 (88·5%) after surgery. After surgery, six patients had nadir GH > 2 mU/l in the OGTT and ‘unsafe’ GH levels (mean GH in GHDC > 5 mU/l); on re‐exposure to lanreotide, GH levels fell in all patients and at the end of 16 weeks postsurgery, they were ‘safe’ in three of them (50%) (P < 0·05). Pituitary tumour volume was also assessed prospectively, preoperatively on lanreotide and showed a mean fall of 33·1%. Eighty‐three percent of patients had > 20% shrinkage.Conclusions  In this first prospective study using lanreotide, surgical debulking of pituitary tumours causing acromegaly improved subsequent postoperative control by the somatostatin analogue lanreotide. Surgery should, therefore, be considered in patients with macroadenoma causing acromegaly, even if there is little prospect of surgical cure. Lanreotide causes significant pituitary tumour shrinkage in the majority of patients.
GH replacement reduces increased lipid peroxidation in GH‐deficient adults
Authors: Karbownik‐Lewinska Malgorzata , Kokoszko Agnieszka , Lewandowski Krzysztof C. , Shalet Stephen M. , Lewinski Andrzej 
Published: May 2008

SummaryBackground  GH replacement improves numerous metabolic abnormalities in GH‐deficient patients; increased lipid peroxidation (LPO) has been observed in GH‐deficient patients; however, it is unknown if LPO is influenced by GH replacement.Aim and methods  To evaluate the extent to which GH replacement might reverse the increased LPO in GH‐deficient adults and to analyse if this phenomenon might be involved in the improvement of metabolic disturbances due to GH treatment. Serum concentrations of malondialdehyde + 4‐hydroxyalkenals (MDA + 4‐HDA), as an index of LPO, were measured at baseline, and after 12 and 24 months of GH replacement in 40 adult patients with severe GH deficiency (both in adult‐ and childhood‐onset) and in 40 healthy volunteers, matched for sex, age and body mass index (BMI). Correlations were evaluated between LPO and lipids, IGF‐I, metalloproteinase‐2 and ‐9 (MMP‐2, ‐9), vascular endothelial growth factor (VEGF), BMI and GH dose.Results  LPO values in GH‐deficient patients were several‐fold higher than in controls [55·36 ± 2·27 vs. 4·19 ± 0·42 nmol/mg protein (mean ± SEM), P < 0·0001] and decreased significantly over time with GH replacement to 38·61 ± 2·15 nmol/mg protein (i.e. by approximately 30%), though still remaining markedly elevated compared with controls (P < 0·0001). The proatherogenic lipid profile parameters correlated positively with LPO in the childhood‐onset subgroup before GH replacement. GH replacement restored the positive correlation between LPO and age in male patients (r = 0·57, P = 0·013; r = 0·8, P < 0·001, at 12 and 24 months of GH replacement, respectively).Conclusions  GH replacement partially reverses the grossly abnormal LPO in GH‐deficient adults. It is highly probable, therefore, that oxidative mechanisms are involved in the overall improvement of metabolic changes due to GH replacement.
Reduced attenuation of bone resorption after oral glucose in type 2 diabetes
Authors: Chailurkit La‐or , Chanprasertyothin Suwannee , Rajatanavin Rajata , Ongphiphadhanakul Boonsong 
Published: May 2008

SummaryObjective  To investigate the effect of oral glucose on bone resorption and osteoprotegerin (OPG) in subjects with varying degrees of glucose tolerance.Design and Patients  In a cross‐sectional study, 163 postmenopausal women aged 50–88 years without previous history of diabetes, impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) were recruited. All subjects underwent a 75‐g oral glucose tolerance test (OGTT) and were then classified as having normal glucose tolerance (NGT), IFG, IGT or diabetes according to American Diabetes Association (ADA) criteria.Measurements  Plasma glucose, serum insulin, C‐terminal telopeptide of type I collagen (CTX‐I) and OPG were measured.Results  Fasting insulin levels increased progressively from subjects with NGT, IFG/IGT to diabetes. After adjusted for age and body mass index (BMI), there was no significant difference in fasting CTX‐I and OPG levels across the various degrees of glucose tolerance. After oral glucose, there was a significant decrease in serum CTX‐I and OPG (P < 0·001) except for serum OPG in diabetic subjects. In addition, the percentages of change from baseline for both serum CTX‐I and OPG were significantly less in diabetic subjects when compared to those in NGT subjects (–40·9% and 0·6% for diabetes and –50·2% and –10·6% for NGT, respectively).Conclusions  Oral glucose intake causes suppression of serum CTX‐I and OPG in postmenopausal women. The effect is attenuated in women with type 2 diabetes.
Continuous glucose monitoring in patients with insulinoma
Authors: Munir Alia , Choudhary Pratik , Harrison Barney , Heller Simon , Newell‐Price John 
Published: May 2008

SummaryBackground  Insulinomas are rare neuroendocrine tumours that are usually small and may take time to localize. They cause recurrent life‐threatening spontaneous hypoglycaemia. Recurrent hypoglycaemia causes loss of hypoglycaemia awareness, putting the patient at further risk, but this has rarely been described in insulinoma. We describe the utility of continuous glucose monitoring (CGM) in patients with insulinoma.Patients and methods  Three patients, aged 72 years (patient 1), 37 years (patient 2) and 24 years (patient 3), with suspected insulinoma attended our investigation unit, in a university teaching hospital. Biochemical diagnosis was confirmed by elevated plasma insulin and C‐peptide during biochemical hypoglycaemia [plasma glucose < 2·2 mM (40 mg/dl)]. Surgery confirmed histology in all. CGM was used to monitor frequency and time of hypoglycaemia during diagnosis and medical treatment, and after definitive surgical treatment.Results  All patients had evidence of hypoglycaemia unawareness. At diagnosis in patients 1–3, CGM revealed 6·1%, 21·9% and 71·0% of time spent in moderate hypoglycaemia (plasma glucose 2·2–3·0 mM), and 1·4%, 11·4% and 48·1% of time in severe hypoglycaemia (plasma glucose < 2·2 mM), respectively. On diazoxide this reduced to 0·6%, 5·4% and 5·7% time in moderate hypoglycaemia, and no severe hypoglycaemia in patients 1 and 3, and 0·5% in patient 2. Octreotide therapy in patients 2 and 3 resulted in 5·8% and 0% of time in moderate hypoglycaemia, respectively, and no severe hypoglycaemia. After surgical excision CGM confirmed cure in all.Conclusions  CGM in insulinoma is useful in detecting hypoglycaemia, and hypoglycaemia unawareness, monitoring response to medical therapy and for confirming cure postoperatively, and is useful in the management of this uncommon but dangerous condition.
Host‐plant quality alters grass/forb consumption by a mixed‐feeding insect herbivore, Melanoplus bivittatus (Orthoptera: Acrididae)
Authors: JONAS JAYNE L. , JOERN ANTHONY 
Published: May 2008

Abstract 1. Factors affecting the nutritional ecology of mixed‐feeding, polyphagous herbivores are poorly understood. Mixed‐feeding herbivores do better when they consume both forb and grass species although they typically feed primarily on forbs, which are of relatively higher protein content than grasses.2. In a field experiment, we examined the effects of nitrogen and phosphorus fertilization and associated changes in host‐plant C:N:P on proportional grass consumption by a mixed‐feeding insect herbivore, Melanoplus bivittatus, using natural abundance stable carbon isotope (12C/13C) methods. We also examined a grass‐feeding (Phoetaliotes nebrascensis) and forb‐feeding (Hesperotettix viridis) species.3. The C isotope signatures of M. bivittatus collected from plots fertilized with nitrogen (+N), phosphorus (+P), nitrogen and phosphorus (+N+P) and no fertilizer were compared with the C isotope signatures of plants in those plots to determine the proportion of assimilated C derived from C4 grasses and C3 forbs in each plot. We also examined the relationship between M. bivittatus diets and plant C:N:P stoichiometry.4. The proportion of grass assimilated approximately doubled in N‐fertilized treatments (39.1 ± 0.1%) compared with non‐fertilized treatments (19 ± <0.1%), an increase associated with decreased C:N and increased N:P of grasses.5. These results indicate that mixed‐feeding M. bivittatus can selectively feed to balance C:N:P intake even when choosing between two structurally and chemically different groups of plants.6. The strong relationship between diet selection and grass stoichiometry also suggests that plant nutrient composition may be more important than defensive chemistry in food choice.
Redundancy renders the glycoprotein 96 receptor scavenger receptor A dispensable for cross priming in vivo
Authors: Tewalt Eric F. , Maynard Jason C. , Walters Julie Jo , Schell Amanda M. , Berwin Brent L. , Nicchitta Christopher V. , Norbury Christopher C. 
Published: May 2008

SummaryCD8+ T cells (TCD8+) differentiate into effector cells following recognition of specific peptide–major histocompatibility complex (MHC) class I complexes (pMHC‐I) on the surface of professional APCs (pAPCs), such as dendritic cells. Antigenic pMHC‐I can be generated from two spatially distinct sources. The direct presentation pathway involves generation of peptide from protein substrate synthesized within the cell that is presenting the pMHC‐I. Alternatively, the cross presentation pathway involves presentation of antigen that is not synthesized within the presenting cell, but is derived from exogenous proteins synthesized within other donor cells. The mechanisms by which cross presentation of exogenous antigens occur in vivo remain controversial. The C‐type lectin scavenger receptor A (SR‐A) has been implicated in a number of potential cross presentation pathways, including the presentation of peptide bound to heat shock proteins, such as glycoprotein 96 (gp96), and the transfer of pMHC‐I from a donor cell to the pAPC. We demonstrate here that initiation of TCD8+ responses is normal in mice lacking SR‐A, and that the redundancy of ligand binding exhibited by the SR family is likely to be an important mechanism that ensures cross presentation in vivo. These observations emphasize the requirement to target multiple receptors and antigen‐processing pathways during the rational design of vaccines aimed at eliciting protective TCD8+.
Sex Determination and Differentiation of the Mammalian Gonad
Authors: Short R. V. 
Published: May 2008

There is growing evidence to suggest that the presence of a single gene on the Y chromosome, which also codes for the expression of the H‐Y antigen, causes the primordial gonad to develop structurally as a testis: in the absence of this gene, an ovary is formed. Whether the gonad subsequently becomes capable of producing viable gametes depends on the sex chromosome makeup of the germ cells that migrate into it; XY or XO germ cells seem to be capable of developing into either oocytes or spermatocytes, depending on the environment, whereas germ cells with two X chromosomes can only develop as oocytes, and will not survive in a testicular environment. The H‐Y antigen probably plays no role in the sexual differentiation of the germ cell.There is another gene on the Y chromosome that determines testis size, and testes: body weight ratios vary widely in different mammals. Amongst the higher primates the gorilla has the lowest ratio (0.018%), man is intermediate (0.079%) and the chimpanzes have the highest (0.269%). Testis size is predominantly determined by the amount of tubular tissue, and appears to be closely related to copulatory frequency, and hence to the mating behaviour of the species. It is important to take these marked species differences in testis size into account when using primate models for human male contraceptive research and development.
Homologies of Structure and Function in Mammalian Testes and Ovaries
Authors: Ross Griff T. , Lipsett Mortimer B. 
Published: May 2008

In mammalian testes and ovaries, gametogenic and steroidogenic compartments interact in producing gametes and secreting sex steroid hormones. Components of these compartments share a number of structural and functional homologies. In the gametogenic compartments, Sertoli cells in testicular tubules and granulosa cells in ovarian follicles form diffusion barriers between germ cells and substances in blood and lymph, secrete luminal fluid and synthesize proteins and steroid hormones. However, steroid hormone concentrations in spermatic and ovarian veins represent the secretory activities of steroidogenic compartments.Interstitial cells in testes and ovaries synthesize and secrete androgens but whether they are the major source of estrogens in ovarian venous blood remains controversial. There are data which suggest that androgens and estrogens, acting on Sertoli cells and granulosa cells, mediate the role of gonadotrophins in induction and maintenance of gametogenesis in testis and ovary. Collectively, the numerous homologies of structure and function provide evidence for conservation and adaptation of mechanisms in mammalian gonads.
Nature and Mechanisms of Action of Inhibin: Perspective in Regulation of Male Fertility
Authors: Franchimont P. , Demoulin A. , Verstraelen‐Proyard J. , Hazee‐Hagelstein M. T. , Walton J. S. , Waites G. M. H. 
Published: May 2008

Inhibin extracted from human seminal plasma and from rete testis fluid is a protein substance. Two forms of inhibin exist in RTF and each has a different molecular weight. The species of higher molecular weight systematically yields a product of lower molecular weight during chromatography. This phenomenon could represent depolymerization of the molecule, an associated transport protein or alternatively a precursor form of inhibin.The inhibin preparations utilized selectively lowered the levels of FSH as assessed both in vivo and in vitro. This action was not totally specific since increasing doses of inhibin also produced a lowering of the levels of LH. In contrast, these preparations did not influence the secretion of TSH, growth hormone or prolactin in vivo or in vitro.A direct effect of inhibin on pituitary cells has been clearly established by demonstrating a reduction in the release of FSH in response to GnRH and its synthesis in the pituitary cells. Additional direct effects on the hypothalamus and on gametogenesis in the testis remain to be excluded. On the basis of selective effects of inhibin on FSH secretion, one could envisage the utilization of this hormone as an antifertility agent.
Effects of Testicular and Ovarian Inhibin‐Like Activity, Using In Vitro and In Vivo Systems
Authors: de Jong F. H. , Welschen R. , Hermans W. P. , Smith S. D. , van der Molen H. J. 
Published: May 2008

Inhibin‐like activities in charcoal‐treated bovine follicular fluid (FF) and medium from cultured Sertoli cells (SCCM) were assayed in an in vitro bioassay system, using cultured pituitary cells. Addition of both fluids resulted in parallel dose‐dependent decreases of the concentration of follicle‐stimulating hormone (FSH) in the medium, both in the presence or absence of luteinizing hormone‐releasing hormone (LH‐RH).A single injection of FF into immature and adult male and female rats resulted in decreased peripheral levels of FSH, but not of LH, after 4 or 8 h. This decrease was larger and occurred faster in adult female rats than in prepubertal female animals. Injection of FF into adult female rats, immediately after unilateral ovariectomy (ULO) prevented the specific increase of FSH levels, occurring in control animals. This suppression could not be obtained after treatment with steroids.Daily treatment of adult female or immature male rats for periods longer than 5 days did not result in prolonged suppression of circulating FSH concentrations; LH levels were significantly increased. The female animals showed cyclic vaginal smear changes and normal ovulation; in the male rats testis weight and numbers of spermatogenic cells were reduced.It is concluded that testicular and ovarian inhibin‐like activities have similar properties. Injections of FF into male and female rats cause similar effects on FSH and LH. The effect of FF in ULO‐animals suggests that inhibin could play a role in the short‐term regulation of the number of developing follicles in the ovary. Injection of FF into male rats causes a probably transient impairment of spermatogenesis through an initial suppression of FSH.
Progestin Receptors in the Anterior Pituitary and Hypothalamus of Male Rats
Authors: Naess Oddvar , Attramadal Arne 
Published: May 2008

Properties of progestin receptors in the pituitary and hypothalamic cytosol fraction of male rats were studied using the highly potent progestin (3H) R 5020 (17,20‐dimethyl‐19‐nor‐pregna‐4,9‐diene‐3,20‐dione). As shown by sucrose gradient analysis, specific binding of (3H) R 5020 is associated with components migrating at 7 S and 4 S. The isoelectric point of the binding components were 5.8. The binding of (3H) R 5020 is highly specific since it is easily displaced by unlabelled R 5020 and progesterone. The affinity of unlabelled testosterone, 17β‐estradiol and cyproterone acetate was much lower, whereas unlabelled cortisol had no affinity for the progestin receptor. The dissociation constant of pituitary R 5020 binding is approximately 1 times 10‐9 M.Pretreatment of the animals with 17β‐estradiol‐valerate greatly increased the progestin receptor levels in the tissues.
Inhibition of Leydig Cell Steroidogenesis: Effect of Actinomycin D Before and After Preincubation of Leydig Cells In Vitro
Authors: Cooke B. A. , Janszen F. H. A. , van Driel M. J. A. 
Published: May 2008

The effect of preincubating purified Leydig cells in Eagle's medium and the subsequent effect of the mRNA synthesis inhibitor actinomycin D on LH‐stimulated testosterone synthesis has been investigated. The inhibitory effect obtained was found to decrease with the period of preincubation; with 0, 1, 2 and 3 h preincubation before the addition of LH (100 ng/ml) 36.5 ± 3.9, 31.2 ± 2.5, 17.8 ± 3.8 and 13.6 ± 2.9% inhibition occurred respectively when actinomycin D (6.4 μM) was added and the cells were incubated for 2 h (means ± SEM, n = 5). During the first hour of incubation with LH and actinomycin D no inhibition occurred in cells that had been preincubated for 3 h.These results suggest that during preincubation and independently of LH, synthesis of intermediates (possibly mRNA(s)) required for stimulation of steroidogenesis may take place and that subsequent stimulation of steroidogenesis by LH occurs without further de novo mRNA synthesis.
Temperature Dependence of Sertoli Cell Function
Authors: Hagenäs L. , Ritzén E. M. , Svensson J. , Hansson V. , Purvis K. 
Published: May 2008

Spermatogenesis as well as Sertoli cell function, monitored by ABP secretion, is severely impaired at 37°C in vivo and in vitro. A closer understanding of the biochemical mechanisms behind this phenomenon may lead to future methods for fertility control.The cryptorchid Sertoli cell was shown to be exposed to normal or increased levels of the two main stimulatory hormones, testosterone and FSH. Androgen receptor concentrations in hypophysectomized rat testes were not changed by cryptorchidism. However, FSH and to some extent LH receptors showed a gradual decline during 28 days of cryptorchidism. Even in the absence of hormones, Sertoli cells in vitro produced less ABP at 37 than at 32°C. This shows that 1) Testicular FSH receptors can be practically eliminated in vivo. 2) The basal secretion of protein by the Sertoli cell, in the absence of hormones, is impaired at elevated temperature. An elucidation of the biochemistry involved in that impairment may also yield possible points of attack in the search for a male contraceptive.
The Presence of an Androgen Controlled Phospholipase A in Rat Epididymis
Authors: Bjerve Kristian S. , Reitan Liv Jorunn 
Published: May 2008

The presence of a phospholipase A (EC 3.1.1.4) and a lysophospholipase (EC 3.1.1.5) has been demonstrated in a postmitochondrial preparation from rat epididymis. Three different enzyme assays using both endogenous and exogenous substrates were employed. Phospholipase A was the rate limiting enzyme in the hydrolysis of lecithin to sn‐3‐glycerophosphorylcholine which also was the main product of the hydrolysis. The enzyme preparation did not show any phospholipase D (EC 3.1.4.4) nor glycerophosphinicocholine glycerophosphohydrolase (EC 3.1.4.2) activity. A small amount of phosphorylcholine was liberated during the hydrolysis indicating the presence of a glycerophosphinicocholine cholinephosphohydrolase (EC 3.1.4.38).The phospholipase A activity per mg of protein was 10 times higher in the cauda than in the caput epididymidis, while the corpus epididymidis possessed an intermediate specific activity. Castration reduced the specific activity of the enzyme with about 50% in the caput and with about 95% in the cauda epididymidis. Testosterone supplementation restored the enzyme activity nearly to normal in the castrated animals.This work suggests that the androgen control of the epididymal concen tration of sn‐3‐glycerophosphorylcholine is exerted via a control of the phospholipase A activity in the epididymal epithelial cells. It is suggested that this enzyme controls the concentration of epididymal glycerophosphorylcholine and the supply of long chain fatty acids to epididymal spermatozoa.