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PubMed1986

Calcium-transport function of the chick embryonic chorioallantoic membrane. II. Functional involvement of calcium-binding protein, Ca2+-ATPase and carbonic anhydrase.

This study aimed to investigate the mechanism of active calcium transport in the chick embryonic chorioallantoic membrane (CAM) by assessing the functional involvement of three previously identified, putative components of the transport pathway. These components are a calcium-binding protein (CaBP), Ca2+-activated ATPase and carbonic anhydrase. Using specific reagents, including antibodies and enzyme inhibitors in vivo and in vitro in CAM calcium uptake assays, it was shown that these biochemically identified components were all functionally involved. The results of these studies also indicate that active calcium uptake by the CAM requires the presence of the CaBP on the cell surface in a laterally mobile manner, while carbonic anhydrase appeared to be a cytosolic component. We further analysed the subcellular location of the calcium-uptake activity by gel filtration and density-gradient fractionation of cell-free microsomes of the CAM and the results suggest that this activity is associated with the plasma membrane.

Animals↗

PubMed1989

[Effects of grayanotoxin III on liver function and renal function in rats].

The grayanotoxin III (GTX III) was given intraperitoneally to rats at a dose of 0.8 or 2.8 mg/kg. To study the effects of GTX III on rats, biological tests in serum for functions of liver and kidney and their pathological observation were performed 1 h after the administration. Using analysis of variance, multiple comparison and correlation on biological parameters, activities of glutamic-pyruvic transaminase (GPT), guanase and leucine aminopeptidase and concentrations of total protein, albumin, creatinine, uric acid and K increased significantly. These parameters showed dose-effect relations with GTX III. Though GPT and free fatty acid increased significantly, dose-effect relations were not shown. The activity of choline esterase and the concentrations of bilirubin, urea-N, lipoperoxide, cholesterol, triglycerides, Na and Cl were not significantly different. Pathological changes were not observed in the liver and kidney of rats. These results show that GTX III may affect the functions of liver and kidney in rats.

Alanine Transaminase↗

PubMed1982

Clinical evaluation of left ventricular function in acute myocardial infarction--analysis of factors affecting left ventricular function.

The clinical significance of the possible factors which may affect the cardiac function and prognosis of the patients with acute myocardial infarction were evaluated in 112 patients with this disease. Patients were subdivided into 4 groups according to the levels of pulmonary capillary wedge pressure (PCWP) and left ventricular stroke work index (SWI): Group I (52 patients) PCWP less than 18 mmHg, SWI less than or equal to 30 g.m/m2; Group II (18 patients) PCWP greater than or equal to 18 mmHg, SWI greater than or equal to 30 g.m/m2; Group III (15 patients) PCWP less than 18 mmHg, SWI less than 30 g.m/m2; Group IV (27 patients) PCWP greater than or equal to 18 mmHg, SWI less than 30 g.m/m2. Immediate mortality rate (4 weeks after the onset of myocardial infarction) was 17.0% in all patients and Group IV had the highest mortality rate (48.1%), in contrast to the lowest mortality rate (3.8%) in Group I. The episodes of previous myocardial infarction were noted more frequently in Group IV (74.1%) than in Groups I (7.7%) and II (11.1%) (p less than 0.001). Mean age in Group IV (68.0 +/- 5.2 (SE) years) was also significantly higher than those of the remaining 3 groups (p less than 0.001). In 55 patients without previous myocardial infarction, mean infarct size estimated from total released creatine phosphokinase (CPK) (sigma CPK) in Group IV was largest among the 4 groups, although it was similar to that in Group II: 919.0 +/- 70.0 (SE) IU/ml in Group I, 1470.0 +/- 126.0 in Group II, 958.0 +/- 107.0 in Group III and 1493.0 +/- 145.0 in Group IV. The number of involved coronary arteries differed significantly between Groups I and IV: in Group I involved coronary artery (75% narrowing) was absent or one at most, while in Group IV all 9 patients had at least one coronary lesion and 3 of 9 had triple vessel disease. In this study no significant difference was observed between the incidence of anterior and inferior myocardial infarctions in Groups I, III and IV. Thus, we conclude that age, previous myocardial infarction, infarct size and the number of involved coronary arteries may determine the cardiac function in acute phase of myocardial infarction and hence, immediate mortality of this disease.

Adult↗

PubMed1979

A study of the Stiles-Crawford (S-C) function at 35 degrees in the temporal field and the stability of the foveal S-C function peak over time.

Directional sensitivity of the retina (the Stiles-Crawford function of the first kind) was measured at a point 35 degrees from fixation and at the point of fixation. Three normal observers were used. The peripheral test point intercepted the retina between the optic nerve head and the ora serrata. At both test points, photopic and scotopic (one subject) Stiles-Crawford function peaks were contained within the pupillary bound and approximated the center of the pupil. Directionality at the two points was rather similar. These findings add strength to the argument that retinal receptors align approximately with the center of the exit pupil of the eye. Evidence for stability in Stiles-Crawford peak location in time is also presented.

Adolescent↗

PubMed2003

Autonomously functioning thyroid nodules in a former iodine-deficient area commonly harbor gain-of-function mutations in the thyrotropin signaling pathway.

BACKGROUND: Somatic activating mutations of the thyrotropin (thyroid-stimulating hormone (TSH)) receptor (TSHR) and G(alphas) protein have been detected in solitary toxic adenomas and toxic multinodular goiters, but their role in the pathogenesis of autonomous nodules is debated. The frequency of mutations is highly variable among populations and is inversely proportional to iodine intake. DESIGN AND PATIENTS: We screened 28 clinically and histologically heterogeneous autonomous nodules from 24 Greek patients for the presence of TSHR and G(alphas) mutations. RESULTS: By direct sequencing of genomic DNA, we detected 11 somatic heterozygous gain-of-function mutations in TSHR and one in G(alphas). Forty-three percent (12 of 28) of all nodules and 57% (four of seven) of solitary toxic adenomas harbored an activating mutation. Typical adenomas and hyperplastic nodules did not differ in mutation frequency. Substitutions I568T and T632I were detected in both histological types of nodules. CONCLUSIONS: Our findings indicate that activating somatic mutations in the TSH signaling pathway are frequent in autonomous nodules in Greece. This may be due to earlier exposure of the population to iodine deficiency, which was corrected in Greece only over the past two decades. Gain-of-function mutations are shared by nodules with varying histological and clinical presentations. Thus, they may represent a common molecular mechanism underlying the pathogenesis of non-autoimmune thyroid autonomy.

Adenoma↗

PubMed2005

Extended clinical phenotype, endocrine investigations and functional studies of a loss-of-function mutation A150V in the thyroid hormone specific transporter MCT8.

OBJECTIVE: Thyroid hormones, besides having other functions, are known to be essential for the development of the human brain. Recently the monocarboxylate transporter 8 (MCT8) was identified as a thyroid hormone transporter which is expressed in different regions of the human brain. Here we describe in detail the clinical and biochemical features in response to thyroid hormone administration of a boy carrying an MCT8 mutation (A150V) in the second transmembrane domain. METHODS: To study the functional impact of the mutation we performed triiodothyronine (T3) uptake, immunofluorescence and dimerization studies. RESULTS: Thyroid hormone (l-thyroxine (LT4) and LT3) administration did not result in any significant clinical changes; however, with high doses of LT4, alone or in combination with T3, TSH suppression was achieved. We could show a robust uptake of (125)I-T3 for wild type (WT) MCT8, whereas no specific uptake could be detected for the mutant A150V. Subcellular localization of WT and mutant MCT8 revealed a strong cell surface expression for the WT MCT8, in contrast to A150V, which is mostly retained intracellularly with only weak cell surface expression. We could also demonstrate for the first time that WT MCT8 as well as the mutant are able to form multimers. CONCLUSION: Our findings open a wide field of possible interaction within the central nervous system and will help to understand the crucial role of MCT8 in early fetal brain development.

Animals↗

PubMed2004

[Executive functions in children with phenylketonuria: variations as a function of phenilalanine plasm level].

The present study investigates the hypothesis of a specific executive function deficit in children with Phenilketonuria (PKU) whose Phenilalanine level is between 360 and 600 mmol/l. Participants were 21 early and continuously treated 9-month-old children with PKU and 18 9-month-old controls. The children with PKU were divided into two groups on the basis of their mean phenilalanine level prior to the study: the group of children whose level was between 120 and 360 mmol/l, and the group of children whose level was between 360 and 600 mmol/l. Although the three groups did not differ with regard to performance on a test of global mental development, the PKU children with high phenilalanine performed significantly worse than both the low phenilalanine PKU children and the control children on a task that assesses executive functioning.

Attention↗

PubMed1991

The structure-function relationship of GLP-1 related peptides in the endocrine function of the canine pancreas.

In order to clarify the relationship between the structure and function of glucagon-like peptide (GLP) 1 in the endocrine function of the pancreas, the response of insulin and glucagon to various synthetic GLP-1-related peptides was investigated in anesthetized dogs. GLP-1-related peptides were administered in a dosage of 400 pmol within 10 min into the pancreatic artery during glucose or arginine infusion and the changes in plasma insulin and glucagon in the pancreatic vein were studied. GLP-1 (7-36) and (7-37), as well as glucagon enhanced insulin release during glucose infusion, whereas neither GLP-1 (1-37), (7-20), (6-37) nor (8-37) stimulated insulin release. The administration of GLP-1 (1-37), (7-36) and (7-37) reduced glucagon release during glucose infusion. When arginine was infused, GLP-1 (7-20), (7-36), (7-37), and glucagon enhanced insulin release. In contrast, glucagon release was increased by the administration of GLP-1 (7-20), (8-37), and (7-37). The present study indicates that histidine at the 7th position of GLP-1 is important in eliciting biological action and that only truncated GLP-1 (7-36), (7-37), and (7-20) showed an insulinotropic action as strong as glucagon in dogs. Furthermore, it is suggested that the response of insulin and glucagon to GLP-1-related peptides is dependent on a background condition.

Animals↗

PubMed1995

Effects of basic fibroblastic growth factor on the function and proliferation of human clinically non-functional pituitary adenomas which secreted glycoprotein hormones in vitro.

The effects of human recombinant basic fibroblastic growth factor (bFGF) on the secretion, viability, proliferation, attachment and morphology of ten dispersed human clinically non-functional (NF) adenomas were examined in vitro. Four clinically NF adenomas secreting FSH and/or LH in vitro were unaffected by 10 nM bFGF over a 4-h period. Over 4 days 10 nM bFGF stimulated LH secretion (66% and 72%, P < 0.01) from two out of seven clinically NF adenomas secreting LH, whilst FSH (three tumours) and alpha-subunit secretion (three tumours) were unaffected. One adenoma co-secreting LH and alpha-subunit and one secreting LH alone were studied over 21 days; LH secretion fell progressively, but the decline was significantly less (P < 0.05) with bFGF (10 nM) treatment after 14 and 21 days in both adenomas, whilst the fall in alpha-subunit secretion was unaffected by bFGF treatment. A 24-h GnRH test performed at the start and end of the 21-day period in one of these tumours showed an increase in both basal and stimulated LH secretion in the bFGF-treated group over control (124%, P < 0.001). There was no effect of bFGF (10 nM) on viability, S-phase proliferation, attachment or morphology of adenoma cells over a 4-day period. These results suggest that bFGF has a role in tumorous LH secretion from these adenomas, but is not mitogenic (at least over 4 days) and is without effect on other parameters of in vitro differentiated function.

Adenoma↗

PubMed1992

The development of functional and equivalence classes in high-functioning autistic children: the role of naming.

The development of functional and equivalence classes was studied in four high-functioning, preschool-aged autistic children. Initially, all subjects failed to demonstrate match-to-sample relations indicative of stimulus equivalence among two three-member classes of visual stimuli. Then, 2 subjects showed emergence of those relations after they were taught to assign the same name to all members in each class. Next, subjects were taught names for new stimuli outside the match-to-sample format. On subsequent match-to-sample tests, 2 subjects demonstrated untrained conditional relations among the stimuli given a common name. New, unnamed stimuli were then related via match-to-sample training to stimuli from sets of named stimuli. Tests for emergent conditional relations between the new unnamed stimuli and the named stimuli yielded positive results for 1 subject and somewhat mixed results for 3 subjects. Finally, without naming, 2 subjects developed stimulus equivalence among two new three-member classes of visual stimuli. These data suggest that naming may remediate failures to develop untrained conditional relations, some of which are indicative of stimulus equivalence.

Association Learning↗

PubMed2006

Hyalp1 in murine sperm function: evidence for unique and overlapping functions with other reproductive hyaluronidases.

While Sperm adhesion molecule 1 (SPAM1) is the highly conserved mammalian sperm hyaluronidase (hyase), multiple hyases are present in the mouse testis. In this study we show that one of the murine hyases, Hyalp1, which is predominantly expressed in the testis in a 24-kd isoform has neutral enzymatic activity. On sperm, Hyalp1 is localized on the plasma membrane of the anterior head and was shown to have neutral hyase activity for an isoform of approximately 55-56 kd, contributing modestly to the overall neutral hyase activity. This activity is associated with in vitro cumulus penetration, since antibody inhibition of Hyalp1 significantly (P = .034) retarded the rate of penetration of wild-type (WT) sperm. Antibody-inhibited Spam1 null sperm were more severely retarded (P = 4.2 x 10(-19)), suggesting an up-regulation of Hyalp1 in these mice. A functionality test of the hyaluronic acid (HA) receptor domain identified in the N-terminus by in silico analysis revealed that sperm Hyalp1 is significantly (P = .006) involved in the progesterone-induced HA-enhanced acrosome reaction. Finally, developmental reverse transcription polymerase chain reaction (RT-PCR) shows that testicular transcripts of Hyalp1 are detected as early as 6 days postparturition, similar to transcripts for Spam1, suggesting that the gene might also play a role in the developing testes prior to spermiogenesis. Taken together, the findings reveal that Hyalp1 likely has a unique function in the adult testis, and redundant overlapping ones with Spam1 and may compensate for it in Spam1 null mice.

Amino Acid Sequence↗

PubMed1999

The effects of functional knee bracing on muscle function and performance.

When applied, knee braces compress the soft tissues of the thigh and leg. External compression may abnormally elevate intramuscular pressure beneath the straps of the knee brace, decrease local muscle blood flow and muscular oxygenation, and induce premature muscle fatigue. Functional knee braces may give valuable support to athletes with unstable knees. They may also be a valuable rehabilitative tool in patients following surgery for knee joint instability. However, prophylactic and functional knee braces do not improve performance and may even inhibit performance in asymptomatic athletes. Athletes and coaches should be aware of the serious adverse effects of knee bracing.

Athletic Injuries↗

PubMed1996

Endothelial cell function: biologic and physiologic functions in health and disease.

Endothelial cells (EC) form a monolayer with a strategic role in the control of many physiologic and biologic pathways. Although the endothelium initially was thought to be an inert and passive barrier of the vasculature, the diverse functions of EC have been better defined in the past decade. EC play an important role in the control of coagulation, vasomotor tone, growth of vascular smooth muscle cells, white cell trafficking, ischemic and reperfusion injuries, and the development of arteriosclerosis. Owing to their location in the arterial tree, EC also are considered a potential target for gene therapy. The introduction of foreign DNA into EC by in vitro transfection with viral vectors has produced encouraging results when using genes that encode for proteins such as insulin and urokinase. The seeding of EC onto vascular grafts appears to convey the thromboresistant properties of saphenous vein to an artificial surface. This review focuses on the important biologic and physiologic functions of EC in health and disease.

Animals↗

PubMed2006

Hyperphagia, severe obesity, impaired cognitive function, and hyperactivity associated with functional loss of one copy of the brain-derived neurotrophic factor (BDNF) gene.

The neurotrophin brain-derived neurotrophic factor (BDNF) inhibits food intake, and rodent models of BDNF disruption all exhibit increased food intake and obesity, as well as hyperactivity. We report an 8-year-old girl with hyperphagia and severe obesity, impaired cognitive function, and hyperactivity who harbored a de novo chromosomal inversion, 46,XX,inv(11)(p13p15.3), a region encompassing the BDNF gene. We have identified the proximal inversion breakpoint that lies 850 kb telomeric of the 5' end of the BDNF gene. The patient's genomic DNA was heterozygous for a common coding polymorphism in BDNF, but monoallelic expression was seen in peripheral lymphocytes. Serum concentration of BDNF protein was reduced compared with age- and BMI-matched subjects. Haploinsufficiency for BDNF was associated with increased ad libitum food intake, severe early-onset obesity, hyperactivity, and cognitive impairment. These findings provide direct evidence for the role of the neurotrophin BDNF in human energy homeostasis, as well as in cognitive function, memory, and behavior.

Adult↗

PubMed2004

Effects of dietary sodium chloride intake on renal function and blood pressure in cats with normal and reduced renal function.

OBJECTIVE: To determine effects of variations in dietary intake of sodium chloride (NaCl) on systemic arterial blood pressure (ABP) in cats with normal and reduced renal function. ANIMALS: 21 adult cats (7 with intact kidneys [control cats; group C], 7 with unilateral renal infarction with contralateral nephrectomy [remnant-kidney model; group RK], and 7 with unilateral renal infarction and contralateral renal wrapping and concurrent oral administration of amlodipine [remnant-wrap model; group WA]). PROCEDURE: All cats were sequentially fed 3 diets that differed only in NaCl content (50, 100, or 200 mg of Na/kg); each diet was fed for 7 days. The ABP was recorded continuously by radiotelemetry, and renal function (glomerular filtration rate [GFR]) was determined on the sixth day of each feeding period. RESULTS: Dietary supplementation with NaCl did not affect ABP, but it increased GFR in groups C and WA. The renin-angiotensin-aldosterone axis was activated in groups RK and WA at the lowest NaCl intake, but supplementation with NaCl suppressed this activation in group WA. The lowest NaCl intake was associated with hypokalemia and a high fractional excretion of potassium that decreased in response to supplementation with NaCl. Arterial baroreceptor resetting was evident after chronic hypertension but was not modified by dietary supplementation with NaCl. CONCLUSIONS AND CLINICAL RELEVANCE: Low NaCl intake was associated with inappropriate kaliuresis, reduced GFR, and activation of the renin-angiotensin-aldosterone axis without evidence of a beneficial effect on ABP. Therefore, this common dietary maneuver could contribute to hypokalemic nephropathy and progressive renal injury in cats.

Analysis of Variance↗

PubMed1989

Non-radical hysterectomy and the function of the lower urinary tract. I: Urodynamic quantification of changes in storage function.

The intermediate sequelae of non-radical abdominal and vaginal hysterectomies on the storage function of the lower urinary tract were studied by comparison of pre- and postoperative urodynamic parameters. A statistically significant reduction in maximum cystometric capacity after abdominal extrafascial and vaginal hysterectomies was found, together with a decline in bladder compliance. Both findings are attributed to a decrease in the musculoelastic properties of the detrusor muscle caused by edema and surgical injury. This reduction in capacity and compliance, however, appeared to have no clinical importance. Sensory innervation remained unaltered. In general no evidence was found that hysterectomy contributed to the development of involuntary detrusor contractions and motor urge incontinence. Urethral competence, assessed by urethral pressure profilometry and urethral leakage pressure measurement, remained unaffected. No increase in stress incontinence was seen after hysterectomy. Vaginal hysterectomy appeared to influence storage function slightly more than abdominal hysterectomy did. Postoperative lower urinary tract dysfunction is for the most part determined by the preoperative urological status.

Female↗

PubMed1989

Non-radical hysterectomy and the function of the lower urinary tract. II: Urodynamic quantification of changes in evacuation function.

The intermediate sequelae of non-radical abdominal and vaginal hysterectomies on the evacuation function of the lower urinary tract were studied by comparison of pre- and postoperative urodynamic parameters. No significant changes were observed in detrusor contractility or the contribution of abdominal straining after hysterectomy. Pressure-flow studies revealed no development towards obstructive patterns. Uroflowmetry did not demonstrate any changes in flow rates or in flow patterns. Except in one woman, no major variations were seen in residual urine volumes. There were no differences between abdominal and vaginal hysterectomies. It is concluded that lower urinary tract evacuation function remains unaltered by total hysterectomy.

Abdomen↗

PubMed1989

Radical hysterectomy and the function of the lower urinary tract. Urodynamic quantification of changes in storage and evacuation function.

The intermediate sequelae of radical hysterectomy on the storage and evacuation function of the lower urinary tract were studied by comparison of pre- and postoperative urodynamic parameters. A modified surgical technique was employed in order to remove only the necessary part of the upper part of the vagina and paravaginal tissues. A non-significant reduction in bladder capacity and compliance was found. Urethral function remained unaltered. The most prominent finding was a significant reduction in detrusor contractility and the development of abdominal straining in order to empty the bladder. The pathophysiologic mechanisms by which lower urinary tract is changed after radical hysterectomy are a decrease in the musculo-elastic properties of the bladder wall caused by surgical injury, and partial damage to the neural innervation of the bladder.

Female↗