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Showing papers by "University of São Paulo published in 1996"


Journal ArticleDOI
TL;DR: It is found that 24 h after electrolytic lesion of the rat MRN glandular gastric ulcers occurred, and the immune response to the mitogen concanavalin A was depressed, these results are compatible with the hypothesis that the MRN-dorsal hippocampus 5-HT system attenuates stress by facilitation of hippocampal 5- HT1A-mediated neurotransmission.
Abstract: There are conflicting results on the function of 5-HT in anxiety and depression. To reconcile this evidence, Deakin and Graeff have suggested that the ascending 5-HT pathway that originates in the dorsal raphe nucleus (DRN) and innervates the amygdala and frontal cortex facilitates conditioned fear, while the DRN-periventricular pathway innervating the periventricular and periaqueductal gray matter inhibits inborn fight/flight reactions to impending danger, pain, or asphyxia. To study the role of the DRN 5-HT system in anxiety, we microinjected 8-OH-DPAT into the DRN to inhibit 5-HT release. This treatment impaired inhibitory avoidance (conditioned fear) without affecting one-way escape (unconditioned fear) in the elevated T-maze, a new animal model of anxiety. We also applied three drug treatments that increase 5-HT release from DRN terminals: 1) intra-DRN microinjection of the benzodiazepine inverse agonist FG 4172, 2) intra-DRN microinjection of the excitatory amino acid kainic acid, and 3) intraperitoneal injection of the 5-HT releaser and uptake blocker D-fenfluramine. All treatments enhanced inhibitory avoidance in T-maze. D-Fenfluramine and intra-DRN kainate also decreased one-way escape. In healthy volunteers, D-fenfluramine and the 5-HT agonist mCPP (mainly 5-HT2C) increased, while the antagonists ritanserin (5-HT2A/2C) and SR 46349B (5-HT2A) decreased skin conductance responses to an aversively conditioned stimulus (tone). In addition, D-fenfluramine decreased, whereas ritanserin increased subjective anxiety induced by simulated public speaking, thought to represent unconditioned anxiety. Overall, these results are compatible with the above hypothesis. Deakin and Graeff have suggested that the pathway connecting the median raphe nucleus (MRN) to the dorsal hippocampus promotes resistance to chronic, unavoidable stress. In the present study, we found that 24 h after electrolytic lesion of the rat MRN glandular gastric ulcers occurred, and the immune response to the mitogen concanavalin A was depressed. Seven days after the same lesion, the ulcerogenic effect of restraint was enhanced. Microinjection of 8-OH-DPAT, the nonselective agonist 5-MeO-DMT, or the 5-HT uptake inhibitor zimelidine into the dorsal hippocampus immediately after 2 h of restraint reversed the deficits of open arm exploration in the elevated plus-maze, measured 24 h after restraint. The effect of the two last drugs was antagonized by WAY-100135, a selective 5-HT1A receptor antagonist. These results are compatible with the hypothesis that the MRN-dorsal hippocampus 5-HT system attenuates stress by facilitation of hippocampal 5-HT1A-mediated neurotransmission. Clinical implications of these results are discussed, especially with regard to panic disorder and depression.

914 citations


Journal ArticleDOI
TL;DR: This study tests the feasibility and safety of a new epicardial mapping technique in patients with Chagas’ disease and recurrent ventricular tachycardia.
Abstract: Epicardial Mapping. Introduction: A possible epicardial site of origin may be the reason for unsuccessful endocardial application of radiofrequency energy to control recurrent ventricular tachycardia. This study tests the feasibility and safety of a new epicardial mapping technique in patients with Chagas’ disease and recurrent ventricular tachycardia. Methods and Results: Epicardial mapping was performed through a pericardial puncture as an epidural introducer needle was advanced into the pericardial space under fluoroscopic guidance. Medium contrast was injected to demonstrate the position of the needle tip, and a guidewire was introduced until its tip lay within the pericardial space. A 8-French Hemaquet was advanced and 4-mm deflectable tip catheter introduced into the pericardial sac to map the right and left ventricular epicardium. Transthoracic echocardiographic monitoring was performed on the day of the procedure and on the day of hospital discharge. The pericardial space was reached in all patients with no complications. Electrophysiologic data suggesting the existence of an epicardial circuit was found in one patient. No complications occurred during the hospitalization period. Conclusion: Epicardial mapping can be safely performed through a pericardial puncture in the electrophysiology laboratory.

794 citations


Journal ArticleDOI
Abstract: This study presents a classification of political regimes as democracies and dictatorships for a set of 141 countries between 1950 or the year of independence and 1990. It improves existing classifications by a better grounding in political theory, an exclusive reliance on observables rather than on subjective judgements, an explicit distinction between systematic and random errors, and a more extensive coverage.

769 citations


Journal Article
TL;DR: The present data demonstrate that the psychometric properties of the Portuguese versions of the BDI and STAI are comparable to the original English language versions of these questionnaires, thereby indicating their use in clinical situations.
Abstract: We have validated a Portuguese version of the Beck Depression Inventory (BDI) and State-Trait Anxiety Inventory (STAI) tests by obtaining profiles for three Brazilian samples: 270 university students, 117 panic patients and 30 depressed patients. The mean BDI scores were higher for depressed patients (25.2 +/- 12.6), intermediate for anxious patients (15.8 +/- 10.3) and lower for students (8.5 +/- 7.0). Mean STAI scores for anxious (52.8 +/- 11.4) and depressed patients (56.4 +/- 10.5) were higher than for the student sample (40.7 +/- 8.6). BDI and STAI scores were correlated significantly in all samples. The internal consistency of the Portuguese version of BDI is in agreement with the literature (0.81 for students and 0.88 for depressed patients). The present data demonstrate that the psychometric properties of the Portuguese versions of the BDI and STAI are comparable to the original English language versions of these questionnaires, thereby indicating their use in clinical situations.

750 citations



Journal ArticleDOI
TL;DR: The authors' studies show a clear division of T. cruzi into two major lineages presenting a high phylogenetic divergence and hypotheses are discussed to explain the origin of the two lineages as well as isolates that are hybrid for group 1 and 2 rDNA markers.

548 citations


Journal ArticleDOI
TL;DR: There is an important association between stunting and high weight-for-height in a variety of ethnic environmental and social backgrounds and this association has serious public health implications particularly for lower income countries.
Abstract: A higher risk of obesity in stunted children has been described in Hispanic-American, Jamaican and Andean populations, but little systematic exploration has been done concerning this area in nutrition. This paper examines the relationship between stunting and overweight status for children aged 3-6 and 7-9 y in nationally representative surveys in Russia, Brazil, and the Republic of South Africa and a large nationwide survey in China. Using identical cut-offs for body mass index, the prevalence of child overweight in these countries ranges from 10.5 to 25.6% (based on the 85th percentile); recent NHANES III results indicate that this prevalence is around 22% in the U.S. Stunting is also common in the surveyed countries affecting 9.2-30.6% of all children. Our results showed a significant association between stunting and overweight status in children of all countries. The income-adjusted risk ratios of being overweight for a stunted child ranged from 1.7 to 7.8. Clearly, there is an important association between stunting and high weight-for-height in a variety of ethnic environmental and social backgrounds. Although the underlying mechanisms remain unexplored, this association has serious public health implications particularly for lower income countries. As these countries enter the nutrition transition experiencing large changes in dietary and activity patterns, they may face, among other problems, additional difficulties in their fight against obesity.

495 citations


Journal Article
TL;DR: A thorough understanding of these principles permits clinicians to exercise more control over these variables, thereby improving the quality of their bonded restorations.
Abstract: The insertion of bonded resin composites into cavity preparations leads to a competition between polymerization contraction forces and the strength of bonds to tooth structure. The degree of stress development can be controlled, to some extent, by the cavity design (C-factor), the use of bases, the size, shape, and position of increments of composite resins placed in the cavity, and whether the resin is light- or chemically cured. Stress relief can be accomplished by maintaining the C-factor as low as possible, using chemical-curing resins, low modulus liners, and, over time, by water sorption. A thorough understanding of these principles permits clinicians to exercise more control over these variables, thereby improving the quality of their bonded restorations.

448 citations


Journal ArticleDOI
TL;DR: In this article, a quasi-automatic simulation of propagation of arbitrary cracks in two-dimensional, linear elastic finite element models is presented, where an underlying winged-edge data structure enables automatic local modifications of the mesh along the propagation path without loss of any unaffected structural information.

421 citations


Journal ArticleDOI
TL;DR: A homozygous mutation in the δSG gene (a single nucleotide deletion that alters its reading frame) is the cause of LGMD2F, a heterogeneous group of inherited neuromuscular disorders characterized by proximal muscular weakness of the pelvic and shoulder girdles and a variable progression with symptoms.
Abstract: Limb-girdle muscular dystrophies (LGMD) are a heterogeneous group of inherited neuromuscular disorders characterized by proximal muscular weakness of the pelvic and shoulder girdles and a variable progression with symptoms, ranging from very severe to mild1,2. One autosomal dominant (LGMD1 A, at chromosome 5q22.3–31.3) (ref. 3) and five autosomal recessive (AR) loci responsible for this phenotype have been identified: LGMD2A at 15q (ref. 4); LGMD2B at 2p (ref. 5), LGMD2C at 13q (ref. 6), LGMD2D at 17q (ref. 7) and LGMD2E at 4q (refs 8, 9). In the muscle membrane, dystrophin associates with several proteins and glycoproteins organized in two main subcomplexes: the dystroglycan (DG) and sarcoglycan (SG) complexes9, 10–14. The genes for LGMD2C, LGMD2D and LGMD2E code for proteins of the SG complex7, 8, 15–17. We recently mapped a sixth AR form of LGMD, LGMD2F, to chromosome 5q33–3418 in two Brazilian families. In the same chromosomal interval we also mapped the δSG gene, encoding a novel 35-kD component of the sarcoglycan (SG) complex19. We now show that a homozygous mutation in the δSG gene (a single nucleotide deletion that alters its reading frame) is the cause of LGMD2F.

406 citations


Journal ArticleDOI
TL;DR: The different types of fibres of the collagenous and elastic systems can be demonstrated specifically in tissue sections by comparing the typical ultrastructural picture of each of the fibre types with studies using selective staining techniques for light microscopy, and a practicalmodus operandi, which includes the recommended staining procedures and interpretation of the results, is presented.

Journal ArticleDOI
TL;DR: In this paper, the authors used the Vegetation Condition Index (VCI) to further separate regional NDVI variation from geographical contributions in order to assess regional drought impacts and delineated areas with certain threshold values of the NDVI and VCI.
Abstract: NDVI (Normalized Difference Vegetation Index) images generated from NOAA AVHRR GVI data were recently used to monitor large scale drought patterns and their climatic impact on vegetation. The purpose of this study is to use the Vegetation Condition Index (VCI) to further separate regional NDVI variation from geographical contributions in order to assess regional drought impacts. Weekly NDVI data for the period of July 1985 to June 1992 were used to produce NDVI and VCI images for the South American continent. NDVI data were smoothed with a median filtering technique for each year. Drought areas were delineated with certain threshold values of the NDVI and VCI. Drought patterns delineated by the NDVI and VCI agreed quite well with rainfall anomalies observed from rainfall maps of Brazil. NDVI values reflected the different geographical conditions quite well. Seasonal and interannual comparisons of drought areas delineated by the VCI provided a useful tool to analyse temporal and spatial evolution ...

Journal ArticleDOI
TL;DR: To localize this gene, referred to as SM1, a genome-wide study on 142 Brazilian subjects belonging to 11 informative families showed a linkage to only one region, on chromosome 5q31–q33, with maximum two-point lod scores, indicating a close proximity to CSF1R as the most likely location of SM1.
Abstract: Three hundred million individuals are at risk of infection by schistosomes and around 200,000 die each year of this disease. Severe clinical disease in schistosomiasis is often the consequence of heavy infection which, in several endemic areas, are determined largely by the susceptibility/resistance of individuals. Previously, we reported evidence, based on a segregation analysis in Brazilian pedigrees, that intensity of infection by Schistosoma mansoni was influenced by a major gene, indicating that host genetic factors are probably critical in controlling schistosome infection and disease development. To localize this gene, referred to as SM1, we performed a genome-wide study on 142 Brazilian subjects belonging to 11 informative families Our results show a linkage to only one region, on chromosome 5q31-q33, with maximum two-point lod scores of +4.74 and +4.52 for D5S636 and the colony stimulating factor-1 receptor marker (CSF1R), respectively. This was corroborated by multipoint analysis, indicating a close proximity to CSF1R as the most likely location of SM1. This region contains several candidate genes encoding immunological molecules that were shown to play important roles in human protection against schistosomes.

Journal ArticleDOI
01 Apr 1996-Genetics
TL;DR: QTLs affecting early and late growth were generally distinct, mapping to different chromosomal locations indicating separate genetic and physiological systems for early and later murine growth.
Abstract: Body size is an archetypal quantitative trait with variation due to the segregation of many gene loci, each of relatively minor effect, and the environment. We examine the effects of quantitative trait loci (QTLs) on age-specific body weights and growth in the F2 intercross of the LG/J and SM/J strains of inbred mice. Weekly weights (1-10 wk) and 75 microsatellite genotypes were obtained for 535 mice. Interval mapping was used to locate and measure the genotypic effects of QTLs on body weight and growth. QTL effects were detected on 16 of the 19 autosomes with several chromosomes carrying more than one QTL. The number of QTLs for age-specific weights varied from seven at 1 week to 17 at 10 wk. The QTLs were each of relatively minor, subequal effect. QTLs affecting early and late growth were generally distinct, mapping to different chromosomal locations indicating separate genetic and physiological systems for early and later murine growth.

Journal ArticleDOI
TL;DR: Comparisons between some pro- and antioxidant parameters in erythrocyte, gill, liver and kidney of Nile tilapia, O. niloticus and from a polluted site in the Billings Reservoir provide useful data for future investigations of polluted aquatic sites to provide a data base relating the presence of pollutants to biological effects at a molecular level.

Journal ArticleDOI
TL;DR: The patterns of labral tears found in 37 patients undergoing hip arthroscopy have been analyzed and may be classified in terms of etiology, morphology, and morphology.
Abstract: Acetabular labral tears are well recognized in the pathology of hip disease. The patterns of such tears found in 37 patients undergoing hip arthroscopy have been analyzed. Distinct categories of labral tear were found, and may be classified in terms of etiology (traumatic, 18.9% of cases; degenerative, 48.6%; idiopathic, 27.1%; congenital, 5.4%) and morphology (radial flap, 56.8%; radial fibrillated, 21.6%; longitudinal peripheral, 16.2%; unstable, 5.4%).

Journal ArticleDOI
06 Oct 1996
TL;DR: In this article, the authors describe the control strategy development, design and experimental performance evaluation of a fuzzy logic based variable speed wind generation system that uses a cage type induction generator and double-sided PWM converters.
Abstract: Artificial intelligence techniques, such as fuzzy logic, neural network and genetic algorithm are showing a lot of promise in the application of power electronic systems. The paper describes the control strategy development, design and experimental performance evaluation of a fuzzy logic based variable speed wind generation system that uses a cage type induction generator and double-sided PWM converters. The system can feed a utility grid maintaining unity power factor at all conditions, or can supply to an autonomous load. The fuzzy logic based control of the system helps to optimize the efficiency and enhance the performance. A complete 3.5 kW generation system has been developed, designed and thoroughly evaluated by laboratory tests in order to validate the predicted performance improvements. The system gives excellent performance, and can easily be translated to a larger size in the field.

Journal ArticleDOI
TL;DR: In this article, spectroscopic variations correlated with the photometric near-infrared (NIR) light curve in η Carinae were discovered, which suggests a connection between the S Doradus cycle and the giant bursts.
Abstract: I have discovered spectroscopic variations correlated with the photometric near-infrared (NIR) light curve in η Carinae. The fading of the high-excitation lines is coincident with the peaks in the NIR light curve, strongly resembling an S Doradus type of variability. The cycle, however, is highly stable, and the 5.52 yr period fits well all the shell episodes reported in the last 50 years. This period also recovers the three historical bursts of the last century, in phase with the present low-amplitude oscillations, which suggests a connection between the S Doradus cycle and the giant bursts. The present data reveal that η Car is continuously varying in the He I λ10830 line by thousands of solar luminosities. The last spectra in this line show that the low-excitation phase is already in progress. A test for the strict periodicity will be the confirmation of the central phase epoch of the next shell event, predicted to occur in 1997 December. A very sensitive mapping technique is also proposed for this occasion, in order to prove Homunculus geometry.

Journal ArticleDOI
TL;DR: In this article, the construction and evaluation of a simple and effective mini-reference electrode is presented, which uses high density microporous polyethylene for the restricted flow junction between the internal and external electrolyte and a polypropylene disposable pipette tip as the electrode body.
Abstract: The construction and evaluation of a simple and effective mini-reference electrode is presented. Major innovations are the use of high density microporous polyethylene for the restricted flow junction between the internal and external electrolyte and a polypropylene disposable pipette tip as the electrode body. Low electrolyte bleeding, reduced size, relatively low electrical resistance and simplified procedure of construction are some of the advantages of the presented design. These characteristics make this electrode particularly suitable for use with small-volume cells and flow cells, as well as applications where chloride contamination should be avoided. Other applications for the microporous membrane in electroanalysis are introduced.

Journal ArticleDOI
TL;DR: The TESA blot seems to be useful as a sensitive and specific diagnostic assay in cases of suspected acute or congenital T. cruzi infection and as a general confirmatory test for conventional Chagas' disease serology.
Abstract: Immunoblotting with trypomastigote excreted-secreted antigens (TESA blot) of Trypanosoma cruzi was evaluated as a method for diagnosis of chronic and acute phases as well as congenital (in newborn children) Chagas' disease Serum samples from acute-phase and congenital infections were considered to be positive when they reacted with ladder-like bands of 130- to 200-kDa antigens, recognized by immunoglobulin M (IgM) and IgG antibodies, while IgG from chronic-phase sera recognized a broad band antigen of 150 to 160 kDa Nonchagasic sera were not reactive to these antigens The study was carried out on 512 patients, 111 of whom were nonchagasic but included cases of leishmaniasis or other pathologies, and 401 chagasic patients The latter group comprised 361 chronic cases, 36 acute cases, and 4 congenital cases in newborn children Among the chronic cases, 256 were from areas in which T cruzi is endemic but which differed widely in the pathogenic expression of T cruzi infection and in parasitemia levels These patients at the same time showed a broad range of low, medium, and high reactivity to conventional enzyme-linked immunosorbent assays and indirect immunofluorescence serotests for Chagas' disease For these reasons they may better represent the universe of chagasic patients than would a sample of highly reactive sera obtained from chagasic patients in a single area endemic for T cruzi All acute and congenital cases showed positivity in the IgM and IgG TESA blots, while chronic cases were 100% positive for IgG antibodies In nonchagasic sera, including 30 cases of visceral and muco-cutaneous leishmaniasis, the specificity index was 1000, and no cross-reactions were observed The TESA blot thus seems to be useful as a sensitive and specific diagnostic assay in cases of suspected acute or congenital T cruzi infection and as a general confirmatory test for conventional Chagas' disease serology

Journal ArticleDOI
TL;DR: In this article, the true pyroelectric coefficient p(T) was determined for these materials by a direct method over an appropriate temperature range, which was considerably higher than that of the ferroelectric poly(vinylidene fluoride) (PVDF) and its copolymer vinylidene fluoride-trifluorethylene (VDF-TrFE).
Abstract: Reconstituted collagen membranes (thickness 20-40 microns used in periodontal guided tissue regeneration, were prepared by solubilization of bovine serosa and bovine tendon using an alkaline treatment and by solubilization of bovine serosa in acetic acid. Dielectric properties of these materials were determined in the frequency range of 10 -5 -10 6 Hz (poling temperature = 313 K, poling time = 3 h, E = 10 7 V/m), using a General Radio Bridge system (high frequencies) and a discharge current technique (low frequencies). The true pyroelectric coefficient p(T) was determined for these materials by a direct method over an appropriate temperature range. Their magnitude appear to be in the range of 10 -4 to 10 -5 C/m 2 K -l , which is considerably higher than that of the ferroelectric poly(vinylidene fluoride) (PVDF) and its copolymer vinylidene fluoride-trifluorethylene (VDF-TrFE).


Journal ArticleDOI
TL;DR: Data from heart-infiltrating T cell clones from CCC patients strongly suggest the relevance of molecular mimicry between cardiac myosin and the T. cruzi protein B13 in the pathogenesis of heart lesions in chronic Chagas' disease cardiomyopathy.
Abstract: Heart tissue destruction in chronic Chagas' disease cardiomyopathy (CCC) may be caused by autoimmune recognition of heart tissue by a mononuclear cell infiltrate decades after Trypanosoma cruzi infection. Indirect evidence suggests there is molecular mimicry between T. cruzi and heart tissue. In murine models of CCC, antibodies and CD4+ T cells recognize myosin, the major heart protein. We recently identified a heart-specific epitope of cardiac myosin heavy chain (residues 1442-1447, AAALDK) that is crossreactive with a homologous sequence (AAAGDK) of the immunodominant T. cruzi antigen B13. Furthermore, cardiac myosin-B13 crossreactive antibodies are present in 100% CCC patients vs 14% asymptomatic T. cruzi-seropositive individuals (P = 2.3 x 10(-6)), suggesting a role for molecular mimicry between cardiac myosin and B13 in CCC pathogenesis. In this paper, we obtained heart-infiltrating T cell clones from CCC patients to assess whether molecular mimicry between cardiac myosin and B13 is directly involved in the genesis of heart lesions. We identified T cell clones derived from CCC heart lesions simultaneously responsive to cardiac myosin heavy chain (but not skeletal myosin heavy chain) and B13 T. cruzi protein, but could not find T cell clones primarily reactive to any T. cruzi antigen. Together with the association of myosin-B13 crossreactive antibodies with CCC, the present data strongly suggest the relevance of molecular mimicry between cardiac myosin and the T. cruzi protein B13 in the pathogenesis of heart lesions in chronic Chagas' disease cardiomyopathy.

Journal ArticleDOI
TL;DR: In this paper, a frequency-dependent inversion is determined by the choice of refocusing pulse S, which is applied an even number of times to eliminate phase distortions in the acquired even echo.


Journal ArticleDOI
01 Feb 1996-Bone
TL;DR: Changes in biochemical markers of bone turnover and mineral homeostasis confirmed the effect of ALN to decrease bone turnover to a new steady-state level and is a generally well-tolerated treatment for osteoporosis in postmenopausal women.

Journal ArticleDOI
TL;DR: It is shown that the distributions of particles created by quasiconstant electric fields can be written in a form which has a thermal character and which seems to be universal, i.e., is valid for any theory with quAsiconstant external fields.
Abstract: We study particle creation from the vacuum by external electric fields, in particular, by fields, which are acting for a finite time, in the frame of QED in arbitrary space-time dimensions. In all the cases special sets of exact solutions of the Dirac equation (in and out solutions) are constructed. Using them, the characteristics of the effect are calculated. The time and dimensional analyses of the vacuum instability are presented. It is shown that the distributions of particles created by quasiconstant electric fields can be written in a form which has a thermal character and which seems to be universal, i.e., is valid for any theory with quasiconstant external fields. Its application, for example, to particle creation in an external constant gravitational field reproduces the Hawking temperature exactly. \textcopyright{} 1996 The American Physical Society.

Journal ArticleDOI
TL;DR: The roles of IL-10, TNF, IFN-γ, and IL-12 in the control of parasitism by innate and specific immunity are investigated and superimposable parasitemia curves are observed, indicating that in the absence of T and B cells, endogenous IL- 10 does not limit the efficacy of the innate immune system.

Journal Article
TL;DR: The efficacy of some traditional TMD treatments should be reconsidered, and reversible and conservative procedures should be the first choice for managing TMD patients.
Abstract: The aim of this study was to evaluate the prevalence and need for treatment of temporomandibular disorders (TMD) in students living in Bauru, Brazil The role of occlusal and emotional factors was also addressed The presence and severity of TMD was determined by using a self-reported anamnestic questionnaire composed of 10 questions regarding common TMD symptoms The symptoms were transposed into a severity classification according to the number and frequency of positive responses Occlusal evaluation included an analysis of retruded contact position, intercuspal position, anterolateral guidance, and nonworking side contacts during mandibular movements Palpation of the muscles and temporomandibular joints were performed to detect clinical signs of TMD A chi square test was used to compare clinical and occlusal data with the presence and severity of TMD A total of 065% of the subjects had severe TMD symptoms, 581% had moderate symptoms, and 3484% had mild symptoms Those with severe and moderate symptom levels were interpreted to be in need of treatment Symptoms were found significantly more frequently in females than in males (P < 01) Self-reported emotional tension and parafunctional habits demonstrated strong associations with TMD (P < 01) Occlusion did not seem to influence the presence or severity of TMD Based on these results, the efficacy of some traditional TMD treatments should be reconsidered, and reversible and conservative procedures should be the first choice for managing TMD patients

Journal ArticleDOI
TL;DR: The combined clinical and molecular observations are consistent with previous experimental data suggesting that in humans, LH is necessary for ovulation but follicular maturation can occur in the presence of FSH alone.
Abstract: Hypergonadotropic hypogonadism is characterized by decreased gonadal function due to the inability of the gonads to respond to pituitary gonadotropins. Hypergonadotropic hypogonadism in females has many causes, among which are ovarian dysgenesis and abnormalities of the ovarian receptors for the pituitary gonadotropins. We evaluated a woman who presented with amenorrhea due to hypergonadotropic hypogonadism, but who had structurally normal ovaries. She is a sister of two previously identified 46,XY male pseudohermaphrodites with Leydig cell hypoplasia. Injection of hCG did not cause any change in plasma levels of estradiol or progesterone, suggesting complete ovarian resistance to LH. Analysis of the DNA sequence of the LH receptor gene revealed that the patient is homozygous for the same single base change as her two brothers. This mutation causes substitution of an alanine residue by a proline at position 593. In vitro analysis of the mutant LH receptor in cultured human embryonic kidney 293 cells documented that the receptor is unable to stimulate adenylyl cyclase in response to hCG. Plasma levels of estradiol and progesterone were low, whereas LH and FSH levels were increased. On histological analysis of the ovary, follicles were seen at all developmental stages. Nonetheless, primary amenorrhea had been present for 5 yr, and repeated measurements of plasma estradiol and progesterone indicate that ovulation does not occur. These results document the existence of inherited LH resistance as a cause of primary amenorrhea in women. The combined clinical and molecular observations are consistent with previous experimental data suggesting that in humans, LH is necessary for ovulation but follicular maturation can occur in the presence of FSH alone.