Evaluation of thyroid nodules by shear wave elastography: a review of current knowledge.

PURPOSE: Shear wave elastography (SWE), as a tool for diagnosing thyroid malignancy, has gathered considerable attention during the past decade. Diverging results exist regarding the diagnostic performance of thyroid SWE. METHODS: A comprehensive literature review of thyroid SWE was conducted using the terms "Thyroid" and "shear wave elastography" in PubMed. RESULTS: The majority of studies found SWE promising for differentiating malignant and benign thyroid nodules on a group level, whereas results are less convincing on the individual level due to huge overlap in elasticity indices. Further, there is lack of consensus on the optimum outcome reflecting nodule elasticity and the cut-off point predicting thyroid malignancy. While heterogeneity between studies hinders a clinically meaningful meta-analysis, the results are discussed in a clinical perspective with regard to applicability in clinical practice as well as methodological advantages and pitfalls of this technology. CONCLUSION: Technological as well as biological hindrances seem to exist for SWE to be clinically reliable in assessing benign and malignant thyroid nodules. Structural heterogeneity of thyroid nodules in combination with operator-dependent factors such as pre-compression and selection of scanning plane are likely explanations for these findings. Standardization and consensus on the SWE acquisition process applied in future studies are needed for SWE to be considered a clinically reliable diagnostic tool for detection of thyroid cancer.

Both intrathymic and peripheral selection modulate the differential expression of V beta 5 among CD4+ and CD8+ T cells.

Murine T cells expressing V beta 5 are characterized by (a) intrathymic deletion in the presence of I-E and products of endogenous mouse mammary tumor viruses, and (b) a greater representation in CD8+ relative to CD4+ peripheral T cells, thought to be due to more efficient intrathymic positive selection on class I rather than class II major histocompatibility complex antigens. We have engineered mice that are transgenic for a rearranged gene encoding a V beta 5+ beta chain of the T cell receptor for antigen. Deletion is not predicted in I-E- V beta 5+ transgenic mice, and until the age of 2 wk, the CD4/CD8 ratio of peripheral T cells is > 3:1 and indistinguishable between transgenic and nontransgenic mice. Transgenic mice then show a rapid, age-dependent decline in the ratio of CD4+ to CD8+ T cells in the lymphoid periphery, reaching a low of 1:10 by 7 mo of age. Furthermore, the percent of peripheral CD4+ cells that express the transgene drops with age, reaching a low of about 60% at 7 mo, while the percent of CD8+ cells that express V beta 5 remains greater than 95% at all ages. The lymphoid periphery is implicated in this selection against CD4+ V beta 5+ T cells as it occurs more rapidly in thymectomized transgenic mice, and can be delayed in mice whose peripheral T cells are replaced by recent thymic emigrants after depletion by in vivo treatment with anti-Thy-1 antibodies. These results indicate that the relative expression of V beta 5 in T cell subsets can be influenced not only intrathymically in I-E+ V beta 5+ transgenic mice, but also by events in the periphery, in the absence of I-E expression.

Positive and negative selection invoke distinct signaling pathways.

During T cell development, interaction of the T cell receptor (TCR) with cognate ligands in the thymus may result in either maturation (positive selection) or death (negative selection). The intracellular pathways that control these opposed outcomes are not well characterized. We have generated mice expressing dominant-negative Ras (dnRas) and Mek-1 (dMek) transgenes simultaneously, either in otherwise normal animals, or in animals expressing a transgenic TCR, thereby permitting a comprehensive analysis of peptide-specific selection. In this system, thymocyte maturation beyond the CD4+8+ stage is blocked almost completely, whereas negative selection, assessed using an in vitro deletion protocol, is quantitatively intact. This suggests that activation of the mitogen-activated protein kinase (MAPK) cascade is necessary for positive selection, but irrelevant for negative selection. Generation of gamma/delta and of CD4-8- alpha/beta T cells proceeds normally despite blockade of the MAPK cascade. Hence, only cells that mature via conventional, TCR-mediated repertoire selection require activation of the MAPK pathway to complete their maturation.

Unsedated transnasal endoscopy: a Canadian experience in daily practice.

BACKGROUND: Esophagogastroduodenoscopy (EGD) is the most frequently performed diagnostic procedure for upper gastrointestinal disorders. The procedure is routinely performed under conscious sedation in North America. A significant proportion of morbidity and mortality associated with EGD is related to hypoxia due to conscious sedation. The use of sedation is also associated with an increase in cost, loss of work on the day of endoscopy and the need for the patient to be accompanied home after the procedure. Transnasal endoscopy has advantages such as no sedation and less patient monitoring, nursing time and expenses than conventional per oral EGD. OBJECTIVES: To assess the feasibility and acceptability of unsedated transnasal EGD in daily practice. METHODS: Patients due to undergo EGD were given a choice of either unsedated transnasal EGD or per oral EGD with sedation. Patients who chose unsedated transnasal EGD had the procedure performed in the office by a senior gastroenterologist with experience in transnasal EGD. All procedures were performed using a small-calibre esophagogastroduodenoscope. All patients were surveyed using a patient satisfaction questionnaire, and were asked to give specific scores in terms of choking sensation, sore throat, nasal discomfort and abdominal discomfort. All variables were assessed by scores between 0 and 10, with 10 indicating the most severe degree of each variable. Any complications were also recorded. RESULTS: Between March 2002 and August 2003, 231 patients underwent transnasal EGD. The median age of the patients was 57 years (range 15 to 87 years). Complete examinations were possible in 98% of patients. Patients reported a high degree of acceptability (mean score 6.6, range 1 to 10) and low degrees of choking sensation (mean 1.8, range 0 to 10), nasal discomfort (mean 1.7, range 0 to 10), sore throat (mean 0.8, range 0 to 9) and abdominal discomfort (mean 1.1, range 0 to 10). The only complications reported by the patients were epistaxis (n=2, 0.9%) and sinusitis (n=1, 0.4%). Some patients also reported transient light-headedness (n=12, 5%) and mucous discharge (n=2, 0.9%). When asked, 185 patients (88%) stated that they were willing to undergo the same procedure in the future if medically indicated. Of the 84 patients who had conventional EGD under conscious sedation in the past, 52 patients (62%) preferred transnasal EGD without sedation. CONCLUSIONS: Transnasal EGD is generally well tolerated, feasible and safe. It can be performed with topical anesthesia in an outpatient setting. The low complication rate, high patient satisfaction and potential cost savings make transnasal endoscopy an attractive alternative to conventional EGD to screen patients for upper gastrointestinal tract diseases.

Effects of parent age at mating on reproductive response of Glyptapanteles flavicoxis (Hymenoptera: Braconidae), a larval parasitoid of the gypsy moth (Lepidoptera: Lymantriidae).

Glyptapanteles flavicoxis (Marsh) (Hymenoptera: Braconidae) is a gregarious larval parasitoid of the Indian gypsy moth Lymantria obfuscata (Walker) (Lepidoptera: Lymantriidae), that is believed to have potential for inundative releases against gypsy moth populations, because it can be reared in large numbers with few hosts. Unfortunately, sex ratios in laboratory reared G. flavicoxis are usually male-biased, hindering efforts to mass release this species for biological control by making the production of females costly. Because parental age at time of mating is known to affect the sex ratio in some Braconidae, we crossed haploid males and virgin females at 0, 1, 4, 9, and 16 d old with at least 10 trials for each of the 25 combinations. Numbers and sex ratios of progeny produced by females each day were recorded. Both progeny and sex ratios (percentage of females) among progeny produced by ovipositing females of G. flavicoxis decreased markedly over time, so only the first days production need be used in mass rearing. The reduction in the proportion and numbers of females among progeny as females aged is consistent with sperm depletion. Approximately 30% of females in all age classes mated to newly emerged males (day 0) produced all male progeny, whereas only 10-15% of those mated to older males failed to produce any daughters. When crosses with only male progeny were excluded from the analysis, females mated to males 1 d old had higher sex ratios in progeny than those mated to males in other age classes. In addition, females mated the day that they emerged tended to have progeny with the highest sex ratios.

A novel activating function of c-Src and Stat3 on HGF transcription in mammary carcinoma cells.

In the normal breast, hepatocyte growth factor (HGF) is primarily expressed by stromal cells, and stimulates in a paracrine manner epithelial cells expressing the HGF receptor (Met). In invasive human breast carcinomas, HGF and Met are frequently overexpressed, possibly establishing an autocrine HGF/Met loop that promotes tumour cell invasion. However, the mechanisms leading to autocrine HGF expression in carcinoma cells are not known. We previously demonstrated a cooperative effect between c-Src and Stat3 in the activation of HGF transcription in mammary carcinoma cells. The present report defines a novel Stat3 consensus site at nt -95 in the HGF promoter that is highly conserved in human and mouse, and is required for c-Src and Stat3 to activate HGF transcription in breast epithelial cells. DNA-protein binding studies demonstrated high affinity binding of a Stat3-containing complex to the nt -95 site. Endogenous Stat3 binding to this region of the HGF promoter in carcinoma cells expressing HGF was demonstrated using a chromatin immunoprecipitation assay. In addition, coexpression of Stat3 and activated c-Src caused increased expression of endogenous HGF mRNA and protein and marked cell scattering in breast epithelial cells. Our results delineate a novel c-Src/Stat3-dependent mechanism that regulates HGF promoter activity, and is linked to transformation of mammary epithelial cells.

Dysphagia, Speech, Voice, and Trismus following Radiotherapy and/or Chemotherapy in Patients with Head and Neck Carcinoma: Review of the Literature.

Introduction. Patients with head and neck cancer suffer from various impairments due to the primary illness, as well as secondary consequences of the oncological treatment. This systematic review describes the effects of radiotherapy and/or chemotherapy on the functions of the upper aerodigestive tract in patients with head and neck cancer. Methods. A systematic literature search was performed by two independent reviewers using the electronic databases PubMed and Embase. All dates up to May 2016 were included. Results. Of the 947 abstracts, sixty articles met the inclusion criteria and described one or more aspects of the sequelae of radiotherapy and/or chemotherapy. Forty studies described swallowing-related problems, 24 described voice-related problems, seven described trismus, and 25 studies described general quality of life. Only 14 articles reported that speech pathologists conducted the interventions, of which only six articles described in detail what the interventions involved. Conclusion. In general, voice quality improved following intervention, whereas quality of life, dysphagia, and oral intake deteriorated during and after treatment. However, as a consequence of the diversity in treatment protocols and patient characteristics, the conclusions of most studies cannot be easily generalised. Further research on the effects of oncological interventions on the upper aerodigestive tract is needed.

Limitations of postmortem assessment of human coronary artery size and luminal narrowing: differential effects of tissue fixation and processing on vessels with different degrees of atherosclerosis.

Numerous studies have utilized histologic sections of coronary arteries as the standard for testing the validity of the angiographic determination of coronary artery dimensions. However, little attention has been given to artifactual dimensional changes that occur during fixation and histologic processing of tissues (dehydration, clearing, embedding, sectioning and staining). Using planimetric techniques, the dimensional changes that occurred with fixation and processing were quantitated in 61 coronary artery segments with minimal or moderate to severe atherosclerosis obtained from 12 patients studied at autopsy. In vessels with minimal atherosclerotic narrowing, fixation and processing resulted in a decrease in total vessel cross-sectional area and luminal cross-sectional area (p less than or equal to 0.05), whereas absolute wall area (total vessel cross-sectional area minus luminal cross-sectional area) did not change (p = NS). These disproportionate changes resulted in an alteration in the relation between lumen and wall areas so that luminal cross-sectional area decreased from 47.6 +/- 8.5% of the total vessel cross-sectional area observed before fixation to 36.2 +/- 7% after processing (p less than or equal to 0.05). In vessels with moderate to severe atherosclerosis, both the total cross-sectional area and wall area decreased after fixation and processing (p less than or equal to 0.05), but luminal area did not change (p = NS). As a result, the percent luminal cross-sectional area in these vessels increased from 21.1 +/- 10.1% before fixation to 28.7 +/- 9.7% after processing (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of reduced maternal lipoprotein-cholesterol availability on placental progesterone biosynthesis in the baboon.

Maternal low density lipoprotein (LDL) is the principal source of cholesterol substrate for progesterone biosynthesis in the primate placental syncytiotrophoblast. The relationship of LDL-cholesterol availability and other potential cholesterol-yielding pathways to placental progesterone production have not, however, been demonstrated in vivo in a nonhuman primate. Therefore, maternal peripheral lipoprotein-cholesterol and progesterone concentrations were determined in blood samples obtained by venipuncture, from day 72 until day 100, from pregnant baboons (Papio sp) that were either untreated (n = 4) or treated (n = 3) with the inhibitor of hepatic lipoprotein production, 4-aminopyrazolo [3-4-d]pyrimidine (4-APP, 10 mg/kg BW) on days 98-99 of pregnancy (term = 184 days). Although LDL-cholesterol and progesterone levels remained unchanged in untreated animals, LDL-cholesterol concentrations were 9-fold lower (P < 0.005) in baboons receiving 4-APP than in untreated baboons 2 days following initial administration. Commensurate progesterone levels were 3.5-fold lower (P < 0.03) in 4-APP-treated baboons than in untreated baboons. RT-PCR was used to approximate relative changes in transcription of messengers RNAs (mRNAs) for selected cholesterol-sensitive pathways in placental tissue collected on day 100. Thus, expression of mRNAs for LDL receptor and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase appeared enhanced, whereas acyl-coenzyme A:cholesterol acyl transferase (ACAT) mRNA was diminished in syncytiotrophoblast-enriched cell fractions as a result of 4-APP administration. No relative differences in mRNAs were apparent in whole placental villous tissue, however, as a result of 4-APP treatment. In summary, this experiment demonstrates a significant decline in progesterone production elicited by maternal LDL-cholesterol withdrawal, and attests to the efficacy of 4-APP administration during baboon pregnancy. These results also suggest a commensurate regulation of cholesterol-sensitive pathways in primate syncytiotrophoblast. However, no relative differences were apparent in mRNA levels for LDL receptor, HMG-CoA and ACAT in whole placental villous tissue as a result of LDL-cholesterol withdrawal, which may suggest potential disparities in the mechanisms regulating cholesterol homeostasis in steroidogenically active syncytiotrophoblasts vs. those in proliferative nonendocrine placental constituents.

Serum leptin concentrations and expression of leptin transcripts in placental trophoblast with advancing baboon pregnancy.

Leptin is a polypeptide hormone originally thought to be produced exclusively by adipocytes. Recently, however, both leptin messenger ribonucleic acid (mRNA) and leptin protein were identified in human placental trophoblast cells, suggesting a potential role in primate pregnancy. In the present study, venous blood samples were collected at 5-day intervals during gestation from baboons (Papio sp), an established model for the study of human pregnancy, as well as from nonpregnant baboons, and leptin concentrations were determined by RIA. Additionally, placental villous tissue was collected upon cesarean delivery at early (days 60-62; n = 5), mid (days 98-102; n = 5), and late (days 159-167; n = 5) gestation (term = approximately 184 days), and leptin mRNA was quantitated by competitive RT-PCR. Finally, in situ hybridization was employed to localize transcripts to specific placental cell types. Results determined that maternal leptin levels (mean +/- SEM), which were dramatically greater (P<0.01) than those in nonpregnant cycling baboons (1.4+/-0.1 ng/mL), increased (P<0.005) with gestational age from 63.6+/-10.4 ng/mL on day 60 of gestation to 157.8+/-16.1 near term. Levels declined to those found in cycling baboons by 15 days postdelivery. In contrast to maternal leptin concentrations, placental leptin mRNA decreased (P<0.02) with advancing pregnancy, as transcript abundance declined approximately 8-fold from early to late gestation. Maternal peripheral leptin concentrations were positively correlated (r = 0.66; P<0.001) whereas placental leptin mRNA levels were negatively correlated (r = -0.64; P<0.01) with gestational age. Expression of leptin mRNA transcripts, as evidenced by RT-PCR in villous tissue, was localized principally within syncytiotrophoblast by in situ hybridization. In summary, changes in maternal peripheral leptin concentrations and placental leptin mRNA abundance that occur commensurate with advancing gestational age may imply evolving roles for the polypeptide with advancing primate pregnancy. In this capacity, localization of leptin transcripts within the baboon syncytiotrophoblast suggests the potential for autocrine or paracrine interactions within this endocrinologically active tissue. Finally, both the similarities in leptin ontogeny in baboon and human pregnancy and the singular enhancement of maternal leptin levels inherent throughout baboon gestation emphasize the potential of this nonhuman primate model for the study of leptin action in the maternal-fetoplacental unit.

Regulation of leptin and leptin receptor in baboon pregnancy: effects of advancing gestation and fetectomy.

Leptin, a product of both adipose tissue and the placental syncytiotrophoblast and a potential regulator of primate conceptus development, increases in the maternal circulation with advancing gestation. This increase may be potentiated by estrogens, which also increase as pregnancy progresses. In the present study adipose tissue was collected from nonpregnant (n = 5) baboons (Papio sp) and in baboons during early (days 58-62; n = 5), mid (days 98--102; n = 5), and late (days 158-162; n = 5) pregnancy (term, approximately 184 days). Additionally, placental estrogen production was inhibited in pregnant baboons by the removal of fetal androgen precursors via fetectomy at midgestation, with tissues collected from fetectomized (n = 5) baboons approximately 60 days later. Leptin, estrogens, and androgens were quantitated in maternal serum by RIA. Leptin (LEP) and leptin receptor (LEP-R(L) and LEP-R(S) isoforms) messenger ribonucleic acids (mRNAs) were quantitated by competitive RT-PCR, and leptin concentrations were determined by RIA in maternal adipose and placental villous tissues. Although LEP transcript abundance in adipose tissues was unchanged as a result of pregnancy or with advancing gestation, the leptin protein level was higher (P < 0.02) in pregnant baboons in early gestation than in nonpregnant baboons and increased with gestational age (P < 0.04). Maternal serum estrogens (estradiol and estrone) and androgens (androstenedione and testosterone) were lower (P < 0.0001) in fetectomized baboons than in intact controls. Serum leptin concentrations were unchanged by fetectomy, but the abundance of LEP mRNA transcripts was lower (P < 0.003) in sc adipose tissue and 3-fold higher (P < 0.05) in placenta. Similarly, the leptin protein level declined (P < 0.05) in sc adipose tissue and increased (P < 0.05) in placenta in fetectomized baboons. Although LEP-R(L) mRNA levels were unchanged after fetectomy, placental LEP-R(S) transcript abundance was lower (P < 0.04) than in pregnancy-intact baboons matched for gestational age. Results suggest that both adipose tissue and the placenta may contribute to maternal hyperleptinemia during normal primate pregnancy. Furthermore, the withdrawal of placental steroids results in the enhanced placental leptin production that is commensurate with a decline in production by sc adipose tissue.

Descemet's membrane in penetrating keratoplasties of the human eye.

The response of Descemet's membrane in penetrating keratoplasty wounds was studied by light microscopy in 23 human eyes. Although only parts of the grafted areas could be sectioned in each eye, 15 splittings, full-thickness flanges, or fragmentations of Descemet's membrane were found in ten specimens. Seven of these abnormalities resulted in incarceration of Descemet's membrane into the wound. Malapposition of the wound edges was a causative factor in two additional eyes. Six of these incarcerations produced a visible stromal wound defect. Exacting surgical apposition of the stromal edges of the graft and recipient cornea can therefore be expected to reduce, but not eliminate, these healing abnormalities. Great care must be taken in cutting the graft and removing the recipient tissue to avoid stripping the tough Descemet's membrane from the overlying softer stroma with dull instruments or overlapping cuts.

Bowman's layer in penetrating keratoplasties of the human eye.

Light microscopy disclosed ten examples of Bowman's layer incarcerations into the stromal wound in nine of 23 penetrating keratoplasty globes obtained either after death or by enucleation. Two cases involved separation of Bowman's layer from the underlying stroma. In the others, this layer remained attached to its stroma, and incarceration resulted from either fragmentation or malapposition of wound edges. Six of the incarcerations produced wound defects, and, of these three were associated with epithelial growth into the wound. These properties of Bowman's layer must be considered in the repair of corneal lacerations as well as in the performance of penetrating keratoplasties and epikeratophakia.

High altitude retinopathy in mountain climbers.

Retinal hemorrhages appear to be a frequent, though often unappreciated, occurrence in unacclimated climbers experiencing prolonged exposure to altitudes above approximately 3,658 meters (12,000 ft), heights frequently attained by American moutaineers. This condition has not received attention in the ophthalmologic literature, though several reports of retinal and vitreous hemorrhages have appeared in nonophthalmologic journals. Of six surviving members of a climbing expedition of Mt. Aconcagua, four had retinal hemorrhages. Two had permanently disturbed vision with paracentral scotomas plotted on a tangent screen.

Hemodynamics within a canine femoral arteriovenous fistula.

Blood flow and pressures around a canine femoral arteriovenous fistula, constructed from an autogenous carotid artery, were measured to determine the pressure-flow relationships within the fistula, as well as to determine the presence or absence of retrograde flow in the distal artery and vein. The findings indicate that retrograde arterial flow occurs only when the proximal femoral artery is occluded and, even then, the contribution to fistula flow is small and well below control femoral arterial flow. Retrograde distal venous flow is negligible. Pressure within the fistula is high at the arterial end but is rapidly dissipated across the loop fistula to equal systemic venous pressure on the venous side. Modest distal venous hypertension accompanies this type of fistula. For these reasons, a loop-type, arteriovenous fistula is preferable to other types of fistulas for most clinical surgical indications.

Adrenergic mechanisms in the hepatic arterial circulation of baboons.

The effects of intra-arterial injections and infusions of three adrenergic amines upon hepatic arterial blood flow were measured in anesthetized baboons before and after alpha and beta adrenergic blockade with intravenous phenoxybenzamine and propranolol. Injections of norepinephrine or epinephrine caused dose-dependent decreases in hepatic arterial blood flow. These responses were attenuated by alpha adrenergic blockade and were unchanged by beta adrenergic blockade. Injections of isoproterenol caused dose-dependent increases in hepatic arterial flow. These increases were relatively small and were reversed to constriction at low doses and attenuated at high doses of the agonist by beta adrenergic blockade. Intrahepatic arterial infusions of constrictors were unaccompanied by autoregulatory excape. The degree of constriction was attenuated by alpha adrenergic blockade but was not potentiated by beta adrenergic blockade. Intrahepatic arterial infusion of a relatively large dose of isoproterenol was required to evoke a relatively modest, but sustained, increase in hepatic arterial blood flow. This response was not potentiated by alpha adrenergic antagonism, but was attenuated by beta adrenergic blockade. These observations suggest an apparent and relative decrease in beta adrenergic receptor activity in the hepatic arterial bed of the baboon when compared to other regional circulations such as the mesenteric and femoral beds. These beta receptors are relatively resistant to both stimulation and blockade.

Adrenergic mechanisms in the hindlimb circulation of baboons.

The effects of the adrenergic agonists norepinephrine, epinephrine, isoproterenol, and phenylephrine upon femoral arterial blood flow were measured in baboons before and after alpha (phenoxybenzamine) and beta (propranolol) adrenergic receptor blockade. Flow was measured with an electromagnetic flowmeter. Arterial and venous pressures were recorded simultaneously. Femoral vascular resistance was calculated from these data. Catecholamines were injected intra-arterially (10(-3)--10(0) mug, base, kg.(-1) and intravenously (1.0 mug kg.(-1) in a randomized sequence. All four adrenergic amines were vasodilators at low dose (10(-3) mug kg.(-1), intra-arterially) and this effect was abolished during beta adrenergic receptor blockade. Intra-arterial isoproterenol elicited dose-dependent increases in femoral flow; the other amines were vasoconstrictors at high doses. Alpha adrenergic blockade "reversed" the vasoconstrictor effects of these three amines. At the same dose isoproterenol increased flow more through the intra-arterial than the intravenous route. Conversely, norepinephrine and epinephrine were potent femoral vasodilators when injected intravenously. The findings indicate that the classical adrenergic amines are all vasodilators of the subhuman primate hindlimb at low doses due to their interaction with beta receptor sites. The fact that epinephrine and norepinephrine exert a greater increase in flow when given intravenously than when given intra-arterially is presumably secondary to increased arterial pressure, in turn due to the vasoconstrictor effects of these agents on other regional circulations.

Expression of placental leptin and leptin receptor transcripts in early pregnancy and at term.

OBJECTIVE: To demonstrate the expression of messenger RNA (mRNA) transcripts for placental leptin and leptin receptor in early gestation and at term, to quantitate transcriptional changes relative to stage of gestation, to localize transcripts within specific placental cell types, and to determine if transcripts also are expressed in cultured cells. METHODS: Expression of leptin and leptin receptor was assessed by reverse transcriptase-polymerase chain reaction, and leptin quantitated against a leptin mRNA competitor (MIMIC), in human placental villous tissue collected at term cesarean deliveries and earlier during gestation (7-14 weeks) upon elective terminations. In situ hybridization was used to identify cell types exhibiting transcripts for genes of interest. Additionally, tissue was dispersed enzymatically, cytotrophoblast cells progressed to syncytiotrophoblastic maturity in culture, and transcripts were assessed. RESULTS: Placental leptin and leptin receptor transcripts were identified in early (n = 6) and late (n = 5) gestation. Although no changes (P > .05) were apparent for receptor, leptin mRNA declined (P < .005) from (mean+/-standard error) 1.815+/-.491 attomoles/microg total RNA early in gestation to .013+/-.003 attomoles/microg total RNA at term. Leptin and leptin receptor transcripts were localized in trophoblast by in situ hybridization and were expressed in culture. CONCLUSION: Results suggest an ontogenetic decline in leptin mRNA with advancing gestation. Localization of leptin and leptin receptor transcripts in syncytiotrophoblasts, cells also responsible for the production of hormones vital to pregnancy maintenance, suggest a potential for autocrine or paracrine interactions within this tissue. Finally, transcript expression in cultured cells suggests the suitability of in vitro paradigms for future studies of leptin in pregnancy.