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Biomedical subjects

L R Emmons

Publications and source records attributed to L R Emmons.

At least 19 recordsLinked to original sources
PubMed2000

Elevated placental estradiol: a possible etiological factor of human cryptorchidism.

PURPOSE: It has been convincingly argued that the increasing incidence of reproductive abnormalities in human males may be associated with increased estrogen exposure during gestation. We documented the expression of estradiol in the syncytiotrophoblast and placenta of males born with cryptorchidism and normal genitalia, respectively. MATERIALS AND METHODS: Tissue from newborn placentas was fixed in glutaraldehyde and embedded in ePON for immunohistological procedures. Cryptorchidism was unilateral in 6 males and bilateral in 1. Semithin histological sections of placental biopsies of these 7 males and 7 randomly selected, normal male placentas were analyzed immunohistochemically with a polyclonal anti-estradiol-17 beta, 6-keto antibody. RESULTS: The weak expression of estradiol in the placentas of normal males was localized predominantly at the basal part of the syncytiotrophoblast in the terminal placental villi. In contrast, all placentas of cryptorchid males had strong expression of estradiol at the basal portion of the syncytiotrophoblast. CONCLUSIONS: The increased expression of estradiol in the syncytiotrophoblast may have an impact on testicular descent.

Cryptorchidism↗
PubMed1998

Increased apoptosis in the contralateral testes of patients with testicular torsion as a factor for infertility.

PURPOSE: Unilateral testicular torsion is common and leads to bilateral testicular injury. Spermiography is abnormal in 70% of patients after testicular torsion. Histological changes in the contralateral testis at the time of torsion have been previously interpreted as the consequence of a predisposing testicular pathology or a noxious effect of the twisted testis. We hypothesized that increased apoptosis in the contralateral testis in unilateral testicular torsion is a consequence of a breakdown in the blood-testis barrier of the twisted testis, which may increase the risk of infertility. MATERIALS AND METHODS: A total of 17 patients 14 to 34 years old (mean age plus or minus standard deviation 20.7+/-6.1) underwent surgery to alleviate unilateral testicular torsion. Mean time from the first symptoms of torsion to surgery was 4.2+/-3.0 hours (range 0.5 to 11). Bilateral testicular biopsy was performed in all patients, and apoptosis was analyzed by terminal deoxynucleotidyl transferase mediated S-deoxyuridine triphosphate nick end labeling. RESULTS: Compared with controls, the incidence of apoptosis was increased in the contralateral testes in all patients. Apoptosis occurred predominantly in spermatocytes, early and late spermatids, and Sertoli's cells. In contrast, spermatogonia, peritubular connective tissue (fibroblasts and myofibroblasts) and endothelial cells seldom underwent apoptosis. Leydig cells were affected less often than spermatocytes. The extent of apoptosis and necrotic changes within the twisted testicle directly correlated with the duration of torsion. CONCLUSIONS: Extensive apoptosis is a phenomenon that occurs regularly in the germinal epithelium of the contralateral testis in testicular torsion. Specifically primary and secondary spermatocytes are predominantly affected. Notably spermatogonia, capillary endothelium, connective tissue and peritubular fibroblasts are rarely involved. A selection strategy has seemingly evolved that precludes the possibility of the perpetuation of genetic mutations. We hypothesize that trauma to the blood-testis barrier initiated by testicular torsion induces the release of apoptotic activating factors (cytokines), which subsequently cause extensive apoptosis in the germinal epithelium of the contralateral testis. Therefore, it is probable that repeat apoptotic episodes may explain the high incidence of infertility in these patients.

Adolescent↗
PubMed1997

The incidence of seminoma and expression of cell adhesion molecule CD44 in cryptorchid boys and infertile men.

PURPOSE: The incidence of seminoma in men with cryptorchid testes is a contentious issue among physicians. Nevertheless, a positive correlation has been shown between the susceptibility for seminoma in patients with the oligo-asthenoteratospermia syndrome and in those with cryptorchid testes. MATERIALS AND METHODS: We histologically examined 5,231 biopsies from 3,867 patients, including 1,121 men with the oligo-asthenoteratospermia syndrome, 218 men with azoospermia and 2,528 boys with cryptorchidism. Testicular tissue embedded in Epon was analyzed by light microscopy, fluorometry, electron microscopy and immunohistochemistry. Cell adhesion molecule CD44 was detected using a monoclonal antibody in all biopsies of patients suspected of having carcinoma in situ. RESULTS: The incidence of seminoma was identical in boys with cryptorchidism and infertile men with the oligo-asthenoteratospermia syndrome but it was significantly higher than in the normal population. All biopsies were analyzed by a single investigator, including 2,528 from 2,403 cryptorchid boys and 2,322 from 1,339 infertile men. Seminoma was found in 4 cryptorchid boys of whom 3 had intra-abdominal testes. The incidence of seminoma in infertile men with the oligo-asthenoteratospermia syndrome was 6/1,121 (4 stage I and 2 stage II). Overall 10 seminomas were noted in 3,867 patients, including 1 in whom seminomas subsequently developed in both testes. Before the onset of puberty primordial germ cells persisted in 7 of the 2,528 cryptorchid patients, although no invasive seminomas were detected. An anti-CD44 monoclonal antibody was found to bind selectively to seminoma cells in the earliest stages of malignant transformation and metastasis, which to our knowledge represents the first reported incidence of CD44 expression associated with seminoma cells. CONCLUSIONS: The incidence of carcinoma in situ in patients with the oligo-asthenoteratospermia syndrome or cryptorchidism was 0.27%. If the occurrence of primordial germ cells is considered, the overall incidence was 0.46% (17 of 3,659 cases). CD44 was expressed in all seminoma cells as well as in all primordial germ cells. Because CD44 adhesion molecules are expressed in the earliest stages of seminoma development, anti-CD44 monoclonal antibody is an important new tool for positively identifying this type of neoplasm in all cases.

Adolescent↗
PubMed1995

Soluble tumour necrosis factor receptors p55 and p75 in the urine monitor disease activity and the efficacy of treatment of inflammatory bowel disease.

The aim of the study was to discover if soluble tumour necrosis factor receptors (sTNF-R p55 and p75) in the urine of patients with inflammatory bowel disease (IBD) could be used to monitor the different stages of the activity of the diseases. Twenty five patients with either Crohn's disease or ulcerative colitis were followed up during a longterm study. The 16 patients who become acutely ill with either Crohn's disease or ulcerative colitis had significantly higher concentrations of sTNF-R p55 and p75 in their urine compared with those who were in remission, or those who were normal controls. There was a significant correlation between increased concentrations (> 20 ng/ml) of both sTNF-R p55 and p75 in the urine and a high Crohn's disease activity index (CDAI) and colitis activity index (CAI). Therefore, determination of sTNF-R is a good non-invasive parameter that can be used to assess the activity of disease and the efficacy of treatment.

Acute Disease↗
PubMed1993

Inhibition of receptor-mediated platelet activation by nedocromil sodium.

BACKGROUND: Platelet activation by platelet activating factor (PAF) seems to be involved in the inflammatory process in asthma and may serve as a possible target for the antiinflammatory drug nedocromil sodium, which is known to inhibit cell activation by different stimuli. METHODS: We investigated the effect and the mode of action of nedocromil sodium on platelet activation by PAF. In a set of healthy volunteers (n = 45) we investigated seven different parameters of platelet activation by PAF, thrombin, and Ca(2+)-ionophore. RESULTS: Nedocromil sodium inhibited: (1) PAF-induced "shape change" reaction up to 78% (50% inhibitory concentration [IC50]: 3 x 10(-9) mol/L), thrombin-mediated "shape change" up to 80% (IC50 2 x 10(-8) mol/L), but not the Ca(2+)-ionophore-dependent reaction, (2) platelet aggregation by PAF up to 85% (IC50 2 x 10(-9) mol/L); (3) release of thromboxane B2 up to 82% (IC50 5 x 10(-9) mol/L); (4) formation of inositol 1,4,5-triphosphate by PAF (IC50 3 x 10(-7) mol/L), by thrombin (IC50 1 x 10(-7) mol/L), but not by Ca2+ ionophore; (5) increase of intracellular free calcium (IC50 4 x 10(-7) mol/L); (6) formation of diacylglycerol (IC50 9 x 10(-9) mol/L), and (7) translocation of protein kinase C (IC50 1 x 10(-7) mol/L). CONCLUSIONS: In the concentration range of the IC50 values found in these experiments, nedocromil sodium reduced PAF binding to platelets by only 10% to 20%, such that this interference cannot explain the observed effects of the compound. Inhibition of receptor-mediated platelet activation at an early stage in the signal transduction pathway, and without effect on Ca(2+)-ionophore-induced platelet activation, suggests an action of nedocromil sodium at the level of the cell membrane.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1992

Manidipine regulates the transcription of cytokine genes.

Manidipine, a Ca(2+)-channel blocker, at concentrations that lower elevated blood pressure, modulates the transcription rates of cytokine genes in the mesangial cells of humans that had been stimulated with platelet-derived growth factor BB isomer; although the transcription for mRNA of interleukin 1 beta and granulocyte/monocyte colony-stimulating factor was inhibited, the transcription of mRNA for interleukin 6 was enhanced. Additionally, the induction of c-fos, c-jun, and 3-hydroxy-3-methylglutaryl-coenzyme A reductase transcription was inhibited by manidipine. We conclude that manidipine, at nanomolar concentrations, is efficacious in modulating gene transcriptions that are involved in proinflammatory changes of mesangial cells. Thus, manidipine, at pharmacological concentrations that are one to two orders of magnitude lower than those required for inhibition of agonist- or depolarization (K+)-induced vasoconstriction, causes changes in the activity of the genes that code for inflammatory mediators.

Calcium↗
PubMed1992

Cell cultures from cryopreserved human lung tissue.

To assess gene induction in primary human fibroblasts, we have developed a method for cryopreservation of lung biopsies in liquid nitrogen. Fresh biopsies (n = 10) were chopped into 5 x 5 mm pieces and transferred into an ice-cold freezing medium. Biopsies were kept on ice for 15 min, followed by further cooling of the tissue to -70 degrees C. With this method, lung biopsies were preserved for more than 1 year before they were used for generating cell cultures. There was no significant difference in the biological responsiveness of fibroblasts generated from immediately cultured lung biopsies compared with those from cryopreserved tissue. The doubling rate of fibroblasts from fresh tissue was 23.6 +/- 1.1 hr; compared to 23.5 +/- 1.5 hr for fibroblasts generated from cryopreserved tissue. PDGF-BB enhanced de novo synthesis of DNA 100 times, in both the immediately cultured fibroblasts and those generated from cryopreserved biopsies. Macrophages, dendritic cells and endothelial cells could also be recovered from cryopreserved lung tissue. This method permits long-term storage of lung tissue and the possibility of establishing primary cell lines from the same tissue at later times without appreciable changes in their cellular biological characteristics.

Cell Cycle↗
PubMed1992

Occurrence of large granular lymphocytes and natural killer cells in the epithelium of the gut distinguishes two different coeliac diseases.

In a longterm study, we have divided coeliac disease into two distinct entities (abortive and permanent) based on the occurrence of large granular lymphocytes and natural killer cells within the epithelium of the gut. The natural killer and large granular lymphocytes cells were characterised by either immunohistochemical or phase contrast microscopical procedures on the initial biopsies from 15 children with coeliac disease. They were compared with seven individuals with partial villus atrophy and eight with normal villous morphology. Although the histological findings were similar in the initial biopsies of all patients with coeliac disease, the patients with permanent coeliac disease had a significantly lower number (0.41(0.61)cells/mm2) of large granular lymphocytes and natural killer cells compared with those patients with abortive coeliac disease (11.93 (6.23) cells/mm2). Those in the permanent group developed a significantly more pronounced flat mucosa after gluten challenge or provocation compared with the abortive group and had to remain on a strict gluten free diet in contrast with those in the abortive group. Thus, the occurrence of intraepithelial large granular lymphocytes and natural killer cells characterises two distinctly different coeliac diseases. Based on our results neither the histological evaluation of the biopsy nor the utilisation of the revised European Society for Paediatric Gastroenterology and Nutrition (ESPGAN) Criteria are adequate in diagnosing the two types of coeliac disease.

Celiac Disease↗
PubMed1991

Ca(2+)-channel blockers modulate expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase and low density lipoprotein receptor genes stimulated by platelet-derived growth factor.

The effects of Ca(2+)-channel blockers (amlodipine, nifedipine, nitrendipine, and verapamil) on expression of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (EC 1.1.1.88) and low density lipoprotein receptor (LDL-R) genes stimulated by recombinant platelet-derived growth factor BB isomer (PDGF-BB) were evaluated in human skin fibroblasts. The drugs enhanced expression of the LDL-R protein on the plasma membrane of the cells; in contrast, they inhibited expression of the HMG-CoA reductase gene. In addition, PDGF-BB-dependent stimulation of transcription of c-fos mRNA was inhibited also by the Ca(2+)-channel blockers. We conclude that PDGF-BB-dependent activation of the two genes is inhibited effectively by the Ca(2+)-channel blockers, at therapeutic concentrations, although they are unable to lower systemic cholesterol levels at these concentrations; however, they do modify responses of the two genes that are involved crucially in regulation of cellular cholesterol homeostasis.

Amlodipine↗
PubMed1991

Expressions of the low density lipoprotein receptor and 3-hydroxy-3-methylglutaryl coenzyme A reductase genes are stimulated by recombinant platelet-derived growth factor isomers.

The plausible role that platelet-derived growth factor (PDGF) has in the localized pathophysiological changes that occur in the arterial wall during development of atherosclerotic lesions led us to investigate the influence of recombinant (r)PDGF isomers -AA, -AB, and -BB on the expression of low density lipoprotein receptor (LDL-R) and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase [(S)-mevalonate:NAD+ oxidoreductase (CoA-acylating), EC 1.1.1.88] genes. In addition, we clarified the role of protein kinase C (PKC) in expression of the two genes in human skin fibroblasts and vascular smooth muscle cells. The various rPDGF isoforms are distinct in their ability to activate transcription of both genes: (i) Both rPDGF-AA and -BB stimulate transcription of the LDL-R gene; in contrast, rPDGF-BB, but not -AA, activates transcription of the HMG-CoA reductase gene. (ii) All recombinant isoforms of PDGF activate transcription of the c-fos gene. (iii) While rPDGF-dependent transcription of the LDL-R gene occurs independently of PKC, transcription of the HMG-CoA reductase gene appears to involve the action of that enzyme.

Animals↗
PubMed1990

Malignancies in families of women with medullary, tubular and invasive ductal breast cancer.

Breast cancer seems to represent a heterogeneous group of neoplasia originating from the parenchymal epithelium of the mammary gland. Family studies combined with genetic epidemiological analyses and histological evaluations were used to gain an insight into this nosological entity. Special emphasis was given to the type and frequency of neoplasia in close relatives. This study represents pedigrees of 36 histologically defined pure tubular and 22 pure medullary breast cancer patients as well as 171 with the invasive ductal form. The incidence of cancer in the first degree relatives of all three groups is compared to that of the local population. The first degree relatives did not have a higher risk (RR) for the neoplastic diseases. However, breast cancer occurs more frequently in the female relatives of all three groups. Other cancers have different relative risks.

Adenocarcinoma↗
PubMed1990

PAF-dependent phosphatidylinositol turnover in platelets: differences between asthmatics and normal individuals.

The effects of nebulized platelet-activating factor (PAF) on the pulmonary and cardiovascular systems, and on the platelets present in peripheral blood were investigated in 9 normal individuals and in 6 patients with asthma and 3 individuals with lyso-PAF. The inhalation of PAF caused an acute decrease in specific airway conductance. The circulatory system parameters monitored showed an increase in heart rate while blood pressure decreased in both groups that were studied. The inhalation of PAF led to a significant increase in the differential count of polymorphonuclear leukocytes after 15 min; the count returned to the initial level after 24 h. However, the platelet count remained unchanged. The phosphatidylinositol (PI) turnover and in particular the formation of 1,4,5-inositoltrisphosphate (IP3) in platelets were investigated after PAF inhalation. It also mediated an increase in intracellular free calcium concentration, [Ca2+]i, in response to a second challenge with exogenous PAF. The basal levels of IP3 and [Ca2+]i were significantly greater in the platelets of patients with asthma than in those of normal individuals (p less than 0.01). Platelets that had been isolated from normal and asthmatic subjects had a higher concentration of IP3 and [Ca2+]i in the platelets after an in vitro exposure to PAF. After an inhalation challenge with PAF, the platelets of both the normal individuals and the patients with asthma showed a specific refractoriness to the in vitro exposure to PAF. Perhaps, this is an explanation for the PAF-dependent tachyphylaxis that is commonly observed in both normal and asthmatic individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1989

Age-related decrease in an early step of DNA-repair of normal human lymphocytes exposed to ultraviolet-irradiation.

A monoclonal antibody-based immunoassay has been used to detect age-related changes in the rate of loss of photoproduct antigenicity from the DNA of peripheral blood lymphocytes irradiated with 10 J m-2 uv-C. Lymphocytes were obtained from 75 healthy volunteers whose ages ranged from 14 months to 82 years. The samples were divided by age decades into groups of 10 individuals, except the first decade which contained only 5 individuals. The mean loss of antigenicity +/- 1 standard deviation was determined for each group at 10, 30, and 60 min after irradiation. The data were analyzed by Mann-Whitney U test and by the Kruskal-Wallis test. After a recovery period of 10 min the loss of antigenicity was most rapid in group I (0-9 years), less rapid in group II (10-19 years), and least rapid in all other groups. The differences between groups became less at 30 min and were not significant at 60 min incubation. These data obtained from normal cells concur with our previous conclusions, that reductions in the rate of loss of antigenicity in nondiseased cells isolated from patients with melanoma and dysplastic naevus syndrome reflect genetic abnormalities in these patients.

Adolescent↗