Localization of luteinizing hormone receptor protein in the human ovary.

The luteinizing hormone receptor (LHR) plays a pivotal role during follicular development. Consequently, its expression pattern is of major importance for research and has clinical implications. Despite the accumulated information regarding LHR expression patterns, our understanding of its expression in the human ovary, specifically at the protein level, is incomplete. Therefore, our aim was to determine the LHR protein localization and expression pattern in the human ovary. We examined the presence of LHR by immunohistochemical staining of human ovaries and western blots of mural granulosa and cumulus cells aspirated during IVF treatments. We were not able to detect LHR protein staining in primordial or primary follicles. We observed equivocal positive staining in granulosa cells and theca cells of secondary follicles. The first appearance of a clear signal of LHR protein was observed in granulosa cells and theca cells of small antral follicles, and there was evidence of increasing LHR production as the follicles mature to the pre-ovulatory stage. After ovulation, LHR protein was ubiquitously produced in the corpus luteum. To confirm the expression pattern in granulosa cells and cumulus cells, we performed western blots and found that LHR expression was stronger in granulosa cells than in cumulus cells, with the later demonstrating low, but still significant, amounts of LHR protein. In summary, we conclude that LHR protein starts to appear on granulosa cells and theca cells of early antral follicles, and low but significant expression of LHR exists also in the cumulus cells. These results may have implications for the future design of clinical protocols and culture mediums for in vitro fertilization and especially in vitro maturation of oocytes.

Establishment and validation of a model for non-luteinized human mural granulosa cell culture.

Cell culture techniques of human mural granulosa cells (MGCs) serve as a major in vitro tool. However, the use of luteinized MGCs has major limitations due to their luteinized state. Our aim was to establish a standardized protocol for the culture of MGCs as a model for different stages of folliculogenesis. We showed that early-non-luteinized, preovulatory-non-luteinized and luteal-MGCs have distinct gene expression pattern. After 4 days of incubation of luteinized-MGCs, ovulatory genes mRNA's achieve expression levels similar to the early non-luteinized follicles. FSH stimulation for 48 h of these 4 days cultured MGCs showed ovulatory genes mRNA's expression similar to the pre-ovulatory non-luteinized follicles. These FSH-stimulated cells responded to hCG stimulation in a pattern similar to the response of pre-ovulatory follicles. This novel model may provide a standardized research tool for delineation of the molecular processes occurring during the latter stages of follicular development in the human ovary.

Regulated expression of galectin-1 after in vitro productive infection with herpes simplex virus type 1: implications for T cell apoptosis.

Apoptosis of cytotoxic T lymphocytes by herpes simplex virus type-1 (HSV-1) has been reported to be a relevant mechanism of viral immune evasion. Galectin-1 (Gal-1), an endogenous lectin involved in T-cell apoptosis, has recently gained considerable attention as a novel mechanism of tumor-immune evasion. Here we investigated whether infection of cells with HSV-1 can modulate the expression of Gal-1. Results show that pro-apoptotic Gal-1, but not Gal-3, is remarkably up-regulated in cell cultures infected with HSV-1. In addition, this protein is secreted to the extracellular milieu, where it contributes to apoptosis of activated T cells in a carbohydrate-dependent manner. Since many viruses have evolved mechanisms to counteract the antiviral response raised by the infected host, our results suggest that HSV-1 may use galectin-1 as a weapon to kill activated T cells and evade specific immune responses.

Sonographic diagnosis of Fallopian tube carcinoma.

Primary Fallopian tube carcinoma (FTC) is one of the rarest gynecological malignancies, accounting for 0.18% to 1.6% of all malignant neoplasms of the female reproductive tract. Preoperative diagnosis of FTC has been previously reported; however, most patients with FTC undergo laparotomy with a presumed diagnosis of ovarian carcinoma. The final diagnosis of FTC is usually established at the time of surgery or on pathological examination. To our knowledge, this is the first report in the English scientific literature in which the preoperative diagnosis of FTC was established by the presence of an adnexal mass with an incomplete septation on transvaginal sonography.

The role of galectins in the initiation, amplification and resolution of the inflammatory response.

Inflammation involves the sequential activation of signalling pathways leading to the production of both pro-inflammatory and anti-inflammatory mediators. Galectins constitute a family of structurally related beta-galactoside-binding proteins, which are defined by their affinity for poly-N-acetyllactosamine-enriched glycoconjugates and sequence similarities in the carbohydrate recognition domain. By crosslinking specific glycoconjugates, different members of the galectin family behave as pro-inflammatory or anti-inflammatory agents, acting at different levels of acute and chronic inflammatory responses. Recent studies highlighted immunomodulatory roles for galectins in vivo in several experimental models of chronic inflammation, suggesting that these carbohydrate-binding proteins may be potential targets for the design of a novel generation of anti-inflammatory agents. In this study, we review recent advances on the role of galectins in the initiation, amplification and resolution of the inflammatory response. In particular, we examine the influence of individual members of this family in regulating cell adhesion, migration, chemotaxis, antigen presentation, immune cell activation and apoptosis. From a better understanding of the molecular basis of galectin-induced immune regulation, we may become able to exploit the potential of these sugar-binding proteins and their glycoligands as suitable therapeutic agents in acute and chronic inflammatory disorders.

Induction of allogenic T-cell hyporesponsiveness by galectin-1-mediated apoptotic and non-apoptotic mechanisms.

Galectin-1, a beta-galactoside-binding protein expressed at sites of T-cell activation and immune privilege, has shown specific immunosuppressive properties. Because of the implications of this protein in T-cell tolerance and its potential use to avoid graft rejection, we investigated the immunosuppressive effects of galectin-1 in the course of the human allogenic T-cell response. Galectin-1 induced a dose- and carbohydrate-dependent inhibition of the allogenic T-cell response. Addition of galectin-1 to alloreactive lymphocytes resulted in significant apoptosis of CD45R0-positive cells. This negative regulatory effect was accompanied by caspase activation, Bcl-2 downregulation and was prevented by addition of exogenous IL-2. In addition, a significant decrease of IFN-gamma production was detected in the non-apoptotic cell population, following exposure of alloreactive lymphocytes to galectin-1. Moreover, the immunosuppressive activity of this protein did not involve TGF-beta-mediated mechanisms. Since galectin-1 is expressed by activated T cells and could be acting by an autocrine negative loop to control human T-cell reactivity, we finally examined the regulated expression of this protein throughout the allogenic T-cell response. Expression of endogenous galectin-1 was detected at 24 h of cell culture, reaching its maximal levels after 72 h of allostimulation. The present study sets the basis for a potential use of galectin-1 as a selective immunosuppressive agent to limit T-cell-mediated reactivity during the effector phase of the alloimmune response.

Diaphragm adaptations elicited by severe chronic obstructive pulmonary disease: lessons for sports science.

In humans, the diaphragm adapts to severe chronic obstructive pulmonary disease with (a) fast-to-slow transformations of the fiber types and myofibrillar proteins and (b) increases in the activity of mitochondrial oxidative enzymes. We suggest that progressive endurance training over several decades accounts for these adaptations.

[Galectins: a novel family of proteins involved in the regulation of the immune response. Implications in immunopathological processes]. / Galectinas: una nueva familia de proteínas involucradas en la regulación de la respuesta inmune. Implicancias en procesos inmunopatológicos.

Galectins have emerged as a new family of closely related carbohydrate-binding proteins, which exert their functions by virtue of their ability to decipher glycocodes on complex glycoconjugates. They have been implicated in different immunological processes, such as lymphocyte adhesion, cytokine production, cell growth regulation, apoptosis and central and peripheral immune tolerance. In the present article we analyze the implications of this protein family in different immune pathologies with up- or down-regulated immune responses, such as autoimmune disorders, acute and chronic inflammation, allergic diseases, infection and metastases. The use of recombinant galectins or their antagonists will have future implications in the diagnosis, prognosis and treatment of these diseases, widening the horizons of molecular immunopathology.

Human skeletal myosin heavy chain genes are tightly linked in the order embryonic-IIa-IId/x-ILb-perinatal-extraocular.

Myosin heavy chain (MyHC) is the major contractile protein of muscle. We report the first complete cosmid cloning and definitive physical map of the tandemly linked human skeletal MyHC genes at 17p13.1. The map provides new information on the order, size, and relative spacing of the genes. and it resolves uncertainties about the two fastest twitch isoforms. The physical order of the genes is demonstrated to contrast with the temporal order of their developmental expression. Furthermore, nucleotide sequence comparisons allow an approximation of the relative timing of five ancestral duplications that created distinct genes for the six isoforms. A firm foundation is provided for molecular analysis in patients with suspected primary skeletal myosinopathies and for detailed modelling of the hypervariable surface loops which dictate myosin's kinetic properties.

The distribution of myosin heavy chain isoforms among rat extraocular muscle fiber types.

PURPOSE: To determine the distribution of myosin heavy chain isoforms in each extraocular muscle (EOM) fiber type. METHODS: Serial sections of adult rat EOMs were stained with isoform-specific monoclonal antibodies against an array of myosin heavy chains. Immunofluorescent antibody staining of whole adult rat EOMs, examined by confocal microscopy, demonstrated the longitudinal variations of isoforms along individual fibers. RESULTS: Each global fiber type reacted predominantly with a single isoform-specific antibody and showed no longitudinal variation. Two major orbital fibers were defined, and both contained multiple myosin heavy chains. Both orbital singly and multiply innervated fibers stained proximal and distal to the neuromuscular junction with antibody to embryonic myosin heavy chain, but this isoform was sharply and completely excluded from the domain of the neuromuscular junction. Orbital singly innervated fibers also contained the EOM-specific isoform at the neuromuscular junction. Orbital multiply innervated fibers did not contain the EOM-specific isoform, but additionally contained a slow isoform along their entire length. CONCLUSIONS: Adult rat EOMs show unique fiber types with arrangements of myosin heavy chain isoforms not seen in other skeletal muscles. Moreover, unique cellular mechanisms must exist to target each isoform to its proper domain along individual orbital fibers.

Developmental myosin heavy chains in the adult human diaphragm: coexpression patterns and effect of COPD.

In preliminary experiments we noted developmental (i.e., embryonic and neonatal) myosin heavy chains (MHCs) in the diaphragms of patients with severe chronic obstructive pulmonary disease (COPD). We hypothesized that this finding represented new fiber formation secondary to injury associated with the mechanical stress of COPD or previously undescribed MHCs in the human diaphragm. To distinguish between these possibilities, we analyzed diaphragmatic biopsies obtained from 9 patients with severe COPD (forced expiratory volume in 1 s = 21 +/- 2% predicted, residual volume = 283 +/- 22% predicted) and 10 age-matched controls. First, using immunocytochemistry with specific monoclonal antibodies, we noted that control diaphragms had greater proportions of fibers expressing embryonic (50 +/- 2 vs. 28 +/- 3%, P < 0.0001) and neonatal (52 +/- 2 vs. 32 +/- 3%, P < 0.001) MHCs than COPD diaphragms. Second, SDS-PAGE demonstrated that these developmental MHCs represented only a very small fraction of the diaphragmatic MHC content. Third, the RT-PCR demonstrated mRNA coding for embryonic and neonatal MHCs in COPD and control diaphragms. Last, COPD and control diaphragms exhibited normal histology on light microscopy. We conclude that the presence of developmental MHC isoforms does not indicate new fiber formation in diaphragms of patients with severe COPD. Although these results represent the first systematic description of embryonic and neonatal MHCs in normal adult human diaphragms, their function remains to be elucidated.

Up-regulation of type XIX collagen in rhabdomyosarcoma cells accompanies myogenic differentiation.

Rhabdomyosarcomas are known to recapitulate some of the early events in skeletal muscle embryogenesis, and cultures derived from these tumors have been extensively used to elucidate processes associated with the differentiation of primitive mesenchymal cells. These neoplasms have also provided important systems for studying different collagen types. This aspect is particularly relevant to type XIX collagen, which was originally identified from rhabdomyosarcoma cDNA clones. Although this collagen has been localized in vivo to basement membrane zones in a wide variety of tissues, including skeletal muscle, the tumor cells appear to be a unique source of its expression in vitro. We have found that one particular cell line-derived from a peritesticular embryonal rhabdomyosarcoma-produced relatively large amounts of type XIX collagen, especially in those rare instances in which these cells appear to spontaneously differentiate. To characterize this phenomenon, tumor cells were grown under conditions known to induce differentiation in normal myoblast cultures. In response to this treatment, the typical tumor cell morphology consistently and reproducibly switched from polygonal to round/spindle-shaped with the subsequent appearance of some structures resembling myotubes. Concurrently, the cultures commenced a dramatic up-regulation of type XIX collagen and skeletal muscle myosin heavy chain and alpha-actinin in a time-dependent fashion, whereas protein and mRNA levels of other matrix proteins were either decreased or unchanged. Moreover, immunocytochemical analysis revealed that only a subpopulation of the cells was responsible for the increased synthesis of type XIX collagen, alpha-actinin, and myosin, and that the same cells which stained positive for the collagen also stained positive for the muscle proteins. Taken together, the results suggested that type XIX collagen may be involved in the initial stages of skeletal muscle cell differentiation.

Evidence for three adult fast myosin heavy chain isoforms in type II skeletal muscle fibers in pigs.

Three main fiber types (one slow [type I] and two fast [type IIA and IIB] can be distinguished using conventional actomyosin ATPase (AM-ATPase) histochemistry after acidic pretreatment in mature pig skeletal muscle. We report the isolation, characterization, and identification of four adult 3'-untranslated regions corresponding to types I, IIA, IIB, and IIX myosin heavy chains (MyHC) from a cDNA library. Identification of different type II clones was based on sequence homology, in situ hybridizations (ISH), AM-ATPase histochemistry, and immunocytochemistry. Enzyme histochemistry, immunocytochemistry, and ISH were performed on serial transverse sections of longissimus and red portion of semitendinosus muscle. Results showed that all three fast MyHC transcripts were expressed in the longissimus, whereas only type IIA and IIX transcripts were present in deep red semitendinosus muscle. Type I and IIA fibers contained mostly type I and IIA transcripts, respectively, whereas type IIB fibers contained a heterogeneous population of transcripts. In longissimus muscle, 18, 31, and 51% of conventional IIB fibers were pure IIX, hybrid IIX/IIB, and pure IIB fibers, respectively. Conversely, conventional IIB fibers were actually IIX in deep red semitendinosus muscle. Expression of the three fast adult MyHC isoforms in longissimus was spatially regulated around the typical islets of type I fibers encountered in pig skeletal muscle. Thus, IIA fibers were contiguous to type I fibers, pure IIX fibers were in the direct vicinity of type I and IIA fibers, and hybrid IIX/IIB fibers were located mostly within primary fascicles between the islets of type I fibers; however, pure IIB fibers were located mainly at the periphery of the rosettes near the edges of primary fascicles. In light of the present study, conventional IIB fibers, as defined with AM-ATPase staining, are a heterogeneous population that should be split into pure IIX, hybrid IIX/ IIB, and pure IIB fibers for a more accurate fiber typing.

Transitory expression of alpha cardiac myosin heavy chain in a subpopulation of secondary generation muscle fibers in the pig.

Unlike the random distribution of fiber types seen in skeletal muscles of most mammals, pig muscle exhibits a rosette pattern consisting of islets of slow fibers surrounded by concentric circles of type IIA and IIB fibers. Within each islet of slow fibers, one of the central fibers is a primary myofiber, whereas all others are secondary fibers. The present study demonstrates that a subpopulation of the slow secondary fibers transiently expresses alpha-myosin heavy chain (MHC). Two cDNA libraries were made from longissimus dorsi skeletal muscle of 14-day-old piglet and adult pig atrium; the latter muscle is mainly composed of alpha-MHC. Screening of the libraries with a human anti-alpha-MHC mAb (F8812F8) demonstrated the presence of positive MHC clones in both libraries; the nucleotide sequence of the 3'-untranslated region (3'-UTR) was identical in both libraries. As this MHC 3'-UTR had 75% homology with the human alpha-MHC, it was identified as pig alpha-MHC. Using specific cRNA probes and mAbs against pig alpha-cardiac and beta/slow/type I MHC, we studied the expression of these MHCs in developing pig semitendinosus muscle by combining in situ hybridization and immunocytochemistry on serial sections at 90 days of gestation, and at 1, 6, 35 days and 6 months of age. The results showed that a subpopulation of secondary fibers that directly abut primary fibers, transiently produced alpha-MHC, both at the levels of the protein and its transcript. Subsequently, these fibres expressed beta-MHC. At 1 day, immunocytochemistry showed that 16% of the secondary fibers expressed alpha-MHC, among which 20% did not yet express beta-MHC. At 6 days, alpha- and beta-MHCs were mostly present in the same fibers, i.e., 23% of the secondary fibers. Thereafter, the proportion of secondary fibers reacting with alpha-MHC mAb decreased to 10% at 5 weeks and 0% at 6 months, whereas beta-MHC was still accumulating in about 38% of the secondary fibers. During the period studied, the distribution of alpha- and beta-MHC transcripts closely matched that of the corresponding proteins. Expression of alpha-MHC was not detected in primary type I muscle fibers and slow type I secondary fibers at the periphery of the rosettes of slow fibers. This study is the first unequivocal demonstration of a transitory expression of alpha-MHC in a subpopulation of secondary fibers in a limb skeletal muscle during mammalian development.

Transvaginal color Doppler sonography of the ureteral jets: a method to detect ureteral patency.

OBJECTIVE: To evaluate the feasibility of the detection of ureteral jets into the bladder in obstetric-gynecologic patients using transvaginal color Doppler ultrasound. METHODS: Fifty-two women were recruited and categorized into four groups: 1) 20 normal nonsurgical, 2) 17 post-cesarean delivery, 3) 12 post-total abdominal hysterectomy, and 4) three with only one functional kidney or ureter. In the first three groups, transvaginal color Doppler sonography was used to evaluate the time to detection of the first jet and the number of jets in 5 minutes bilaterally. In the last group, the presence or absence of the jet was documented only on the functional side. Statistical analysis was performed using Student t test and analysis of variance followed by Tukey honestly significant difference. RESULTS: Urine jets could be detected bilaterally in all women except for those with only one functional kidney (accuracy 100%). Time to detection of the first jet did not differ significantly in the nonsurgical, cesarean, or hysterectomy patients on either the right side (P = .07) or the left side (P = .43). The total number of jets was similar in the nonsurgical and cesarean patients, but was significantly lower in the hysterectomy group (right side P = .006; left side P = .004). In the women with one functional kidney, the normal side was identified in all cases. CONCLUSION: Transvaginal color Doppler sonography is a simple, accurate technique that can be used to evaluate ureteral jets into the bladder in women. The length of time to detection of the first jet is not affected by the postoperative status. Fewer jets should be expected in women who have undergone hysterectomies. This method should be used when ureteral integrity is in question, especially after surgery.

Transvaginal gray-scale imaging of ureteral jets in the evaluation of ureteral patency.

We have previously reported on the value of transvaginal color Doppler evaluation of the ureteral jets to confirm ureteral patency. In this study, we attempt to validate the simple and widely available gray-scale ultrasound technique to perform the same task. Fifty consecutive patients without a history of urinary complaints were recruited. The presence or absence of the right and left ureteral jets was registered using gray-scale imaging, comparing the technique to color Doppler as the 'gold standard'. The time to the detection of the first jet as well as the total scanning time were documented for each side. The jets were seen with equal frequency on both the right and the left sides (34 observations each). In 24 patients, both jets were visualized. The median time to detection of the first jet was 47 s (range 34-79 s) for the right jet and 53 s (36-84 s) for the left jet (p = 0.42). The median total scanning time was 176 s (139-259 s). Gray-scale imaging was associated with a sensitivity of 68% and a positive predictive value of 100%. Although color Doppler results may be more attractive because of their impressive color-coded appearance, the major disadvantage of this technique is that it requires sophisticated and costly equipment. Transvaginal gray-scale imaging is a reliable and useful test for the detection of ureteral jets in the bladder. It can be used as a first-line diagnostic tool, particularly in settings where color Doppler is not available. Its benefits include safety, low cost, convenience and simplicity. With a positive predictive value of 100%, this test may be used in the postoperative patient, especially when ureteral patency is in question.

Prenatal diagnosis of the split hand anomaly: how early is early?

A case of split hand anomaly detected by transvaginal sonography at 18 weeks of gestation is reported in which the diagnosis was difficult to establish. Different aspects of this pathology are discussed. Sonographic diagnosis of hand anomalies may be difficult to establish, even with experience. The ideal timing for the prenatal detection of this anomaly remains to be determined.

Transvaginal sonographic detection of adducted thumbs, hydrocephalus, and agenesis of the corpus callosum at 22 postmenstrual weeks: the masa spectrum or L1 spectrum. A case report and review of the literature.

Prenatal diagnosis of non-chromosomal syndromes relies, among others, on the detection of specific morphological findings. In rare syndromes the index case may not be prenatally diagnosed but subsequent pregnancies may benefit from early diagnosis. In this article we discuss the clinical spectrum of an X-linked hereditary disease which contains hydrocephalus, congenital agenesis of the corpus callosum, adducted thumbs, shuffling gait, aphasia, mental retardation, and at times other associated findings. The purpose of this case report is to describe the prenatal sonographic findings of a fetus affected with adducted thumbs, hydrocephaly, and agenesis of te corpus callosum. The patient was referred at 22 1/2 weeks' gestation for prenatal diagnosis. Ultrasound revealed a male fetus with dilatation of the lateral ventricles and partial agenesis of the corpus callosum. The fetal hands showed the thumbs to be fixed in a flexed-adducted position. These findings were consistent with the MASA spectrum (mental retardation-aphasia-shuffling gait-adducted thumbs) present in the older brother. The patient elected to terminate the pregnancy and autopsy confirmed the sonographic findings. In conclusion, prenatal sonography, especially the presence of adducted thumbs, allowed prenatal diagnosis of the second affected child with the MASA spectrum in this family. This morphology-based approach becomes feasible between postmenstrual weeks 15 and 20. Prior to this gestational age, the diagnosis should rely on molecular biology tests.

Characterization of a human perinatal myosin heavy-chain transcript.

Using a monoclonal antibody specific to the neonatal myosin heavy chain, we have cloned the full-length heavy chain cDNA from an 18-week human fetal cDNA library. Ribonuclease protection assays were used to survey a human muscle collection ranging from 11 weeks gestation to 16 years. Expression of the RNA encoded by this cDNA was observed at 20 and 21 weeks gestation and at 2 days after birth. No expression was observed at 13.5 weeks, before 2 years, at 2 years, or after 2 years gestation. Due to the timing of its expression, this cDNA appears to represent of the human fetal myosin heavy chain. Sequencing of the entire 6010 bases showed high similarity to the rat perinatal myosin heavy chain [Periasamy, M., Wieczorek, D. F. & Nadal-Ginard, B. (1984) J. Biol. Chem. 21, 13,573-13,578]. However, moderate divergence was observed when compared to a previously described human perinatal myosin heavy chain [Karsch-Mizrachi, I., Feghali, R., Shows, T. B. & Leinwand, L. A. (1990) Gene 89, 289-294; Feghali, R. & Leinwand, L. A. (1989) J. Cell Biol. 108, 1791-1797]. Restriction fragment-length polymorphism analyses of sites in both the S1 and rod domains showed the presence of this fetal myosin heavy chain sequence in all 27 genomic samples examined. Restriction fragment-length polymorphism analysis failed to find the previously described perinatal isoform in any sample.

Effect of hypothyroidism on myosin heavy chain expression in rat pharyngeal dilator muscles.

Although the association between hypothyroidism and obstructive sleep apnea is well established, the effect of thyroid hormone deficiency on contractile proteins in pharyngeal dilator muscles responsible for maintaining upper airway patency is unknown. In the present study, the effects of hypothyroidism on myosin heavy chain (MHC) expression were examined in the sternohyoid, geniohyoid, and genioglossus muscles of adult rats (n = 20). The relative proportions of MHC isoforms present were determined using MHC-specific monoclonal antibodies and oligonucleotide probes. All control muscles showed a paucity of type I MHC fibers, with greater than 90% of fibers containing fast-twitch type II MHCs. In the genioglossus muscle, a population of non-IIa non-IIb fast-twitch type II fibers (putatively identified as type IIx MHC fibers) were detected. Hypothyroidism induced significant changes in MHC expression in all muscles studied. In the sternohyoid, type I fibers increased from 6.2 to 16.9%, whereas type IIa fibers increased from 25.9 to 30.7%. Type I fibers in the geniohyoid increased from 1.2 to 12.8%, whereas type IIa fibers increased from 34.1 to 42.7%. The genioglossus showed the smallest relative increase in type I expression but the greatest induction of type IIa MHC. None of the muscles examined demonstrated reinduction of embryonic or neonatal MHC in response to thyroid hormone deficiency. In summary, hypothyroidism alters the MHC profile of pharyngeal dilators in a muscle-specific manner. These changes may play a role in the pathogenesis of obstructive apnea in hypothyroid patients.