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F Mena

Publications and source records attributed to F Mena.

At least 19 recordsLinked to original sources
PubMed2005

Genome scan of schizophrenia families in a large Veterans Affairs Cooperative Study sample: evidence for linkage to 18p11.32 and for racial heterogeneity on chromosomes 6 and 14.

Genome-wide linkage analyses of schizophrenia have identified several regions that may harbor schizophrenia susceptibility genes but, given the complex etiology of the disorder, it is unlikely that all susceptibility regions have been detected. We report results from a genome scan of 166 schizophrenia families collected through the Department of Veterans Affairs Cooperative Studies Program. Our definition of affection status included schizophrenia and schizoaffective disorder, depressed type and we defined families as European American (EA) and African American (AA) based on the probands' and parents' races based on data collected by interviewing the probands. We also assessed evidence for racial heterogeneity in the regions most suggestive of linkage. The maximum LOD score across the genome was 2.96 for chromosome 18, at 0.5 cM in the combined race sample. Both racial groups showed LOD scores greater than 1.0 for chromosome 18. The empirical P-value associated with that LOD score is 0.04 assuming a single genome scan for the combined sample with race narrowly defined, and 0.06 for the combined sample allowing for broad and narrow definitions of race. The empirical P-value of observing a LOD score as large as 2.96 in the combined sample, and of at least 1.0 in each racial group, allowing for narrow and broad racial definitions, is 0.04. Evidence for the second and third largest linkage signals come solely from the AA sample on chromosomes 6 (LOD = 2.11 at 33.2 cM) and 14 (LOD = 2.13 at 51.0). The linkage evidence differed between the AA and EA samples (chromosome 6 P-value = 0.007 and chromosome 14 P-value = 0.004).

Adult↗
PubMed2003

Modest evidence for linkage and possible confirmation of association between NOTCH4 and schizophrenia in a large Veterans Affairs Cooperative Study sample.

Wei and Hemmings [2000: Nat Genet 25:376-377], using 80 British parent-offspring trios, identified a number of NOTCH4 variants and haplotypes that showed statistically significant evidence of association to schizophrenia. Specifically, the 10 repeat allele of a (CTG)(n) marker and the 8 repeat allele of a (TAA)(n) marker demonstrated excess transmission to affected individuals; SNP21 and haplotypes SNP2-(CTG)(n) and SNP12-SNP2-(CTG)(n) also showed significant associations. In an attempt to replicate these findings, we tested for linkage and association between the same five markers used by Wei and Hemmings in 166 families collected from a multi-center study conducted by the Department of Veterans Affairs (DVA) Cooperative Study Program (CSP). The families include 392 affected subjects (schizophrenia or schizoaffective disorder, depressed) and 216 affected sibling pairs. The families represent a mix of European Americans (n = 62, 37%), African Americans (n = 60, 36%), and racially mixed or other races (n = 44, 27%). We identified moderate evidence for linkage in the pooled race sample (LOD = 1.25) and found excess transmission of the 8 (P = 0.06) and 13 (P = 0.04) repeat alleles of the (TAA)(n) marker to African American schizophrenic subjects. The 8 and 13 repeat alleles were previously identified to be positively associated with schizophrenia by Wei and Hemmings [2000: Nat Genet 25:376-377] and Sklar et al. [2001: Nat Genet 28:126-128], respectively.

Alleles↗
PubMed2001

Examination of genetic linkage of chromosome 15 to schizophrenia in a large Veterans Affairs Cooperative Study sample.

Previous studies have reported genetic linkage evidence for a schizophrenia gene on chromosome 15q. Here, chromosome 15 was examined by genetic linkage analysis using 166 schizophrenia families, each with two or more affected subjects. The families, assembled from multiple centers by the Department of Veterans Affairs Cooperative Study Program, consisted of 392 sampled affected subjects and 216 affected sibling pairs. By DSM-III-R criteria, 360 subjects (91.8%) had a diagnosis of schizophrenia and 32 (8.2%) were classified as schizo-affective disorder, depressed. Participating families had diverse ethnic backgrounds. The largest single group were northern European American families (n = 62, 37%), but a substantial proportion was African American kindreds (n = 60, 36%). The chromosome 15 markers tested were spaced at intervals of approximately 10 cM over the entire chromosome and 2-5 cM for the region surrounding the alpha-7 nicotinic cholinergic receptor subunit gene (CHRNA7). These markers were genotyped and the data analyzed using semiparametric affecteds-only linkage analysis. In the European American families, there was a maximum Z-score of 1.65 between markers D15S165 and D15S1010. These markers are within 1 cM from CHRNA-7, the site previously implicated in schizophrenia. However, there was no evidence for linkage to this region in the African America kindreds.

Adult↗
PubMed2000

Department of Veterans Affairs Cooperative Studies Program genetic linkage study of schizophrenia: ascertainment methods and sample description.

To help clarify the genetics of schizophrenia, the Department of Veterans Affairs Cooperative Studies Program has completed data collection for a genetic linkage study of schizophrenia. This article describes the methodological details of the data collection. Subsequent articles will describe the results of our genome scan, which is now in progress. The data collection protocol included the Diagnostic Interview for Genetic Studies, the Family Interview for Genetic Studies, a review of medical records, and the collection of blood for transformation into lymphoblast cell lines. Among relatives of schizophrenic probands, we assessed auditory attention and verbal memory with neuropsychological tests. Among the 166 families ascertained for the study, 143 had a single affected sib-pair, 17 had three affected siblings, one had five affected siblings and five had two sets of affected siblings. There was a total of 216 affected sib-pairs in these families. Using the n-1 rule, these families contain 188 independent affected sib-pairs.

Adult↗
PubMed1999

Mammary gland sympathetic innervation is a major component in type 1 deiodinase regulation.

Recent observations have shown that in lactating rats previously deprived of suckling, either suckling stimulus or ip injection of norepinephrine was capable of increasing mammary deiodinase type 1 (M-D1) mRNA content and enzyme activity. In the present work, we show that intact efferent sympathetic mammary innervation is required to restore both mammary D1 mRNA content and enzyme activity, whereas suckling-induced secretion of catecholamines from the adrenal glands does not seem to participate in M-D1 enzyme regulation. The data also indicate that the sympathetic reflex activation in response to suckling involves two complementary autonomic components: (1) activation, presumably through mammary segmental arrangement affecting neighboring mammary glands; and (2) an individual reflex regulatory mechanism capable of maintaining M-D1 activity within each mammary gland. In addition to these findings, we show that the suckling-induced sympathetic activation of M-D1 activity could be blocked by prior activation of ductal mechanoreceptors. This set of regulatory and counterregulatory mechanisms seems to ensure the optimal control of mammary energetic expenditure according to litter size.

Adrenal Glands↗
PubMed1998

Performance of a semiautomated Papanicolaou smear screening system: results of a population-based study conducted in Guanacaste, Costa Rica.

BACKGROUND: Automated cytology devices have utility in quality assurance applications, but the effectiveness of these devices in primary screening is unknown. METHODS: Enrollment smears obtained from 7323 women participating in a population-based study sponsored by the National Cancer Institute were screened manually in Costa Rica and then evaluated independently in the U.S. with the PAPNET system (Neuromedical Systems, Inc., Suffern, NY), a semiautomated, neural network-based device. Smears with abnormal PAPNET images were microscopically rescreened and then diagnosed by a U.S. cytopathologist. ThinPrep slides (Cytyc Corporation, Boxborough, MA), prepared from rinses of the cytologic sampler, and cervigrams (National Testing Laboratories, Fenton, MO) were also evaluated. Women with any abnormal cytologic diagnosis or a positive cervigram were referred for colposcopy with biopsy and definitive therapy if indicated. RESULTS: Based on the U.S. cytotechnologist's review of the PAPNET images, 1017 (13.9%) of 7323 smears were selected for manual screening, resulting in the selection of 492 (6.7%) possibly abnormal slides for referral to the U.S. pathologist. Ultimately, 312 smears (4.3% of the total) were diagnosed as containing squamous cells of undetermined significance or a more severe abnormality (> or =ASCUS), resulting, hypothetically, in the referral of 66.5% of women with a final diagnosis of a squamous intraepithelial lesion or a more severe abnormality (> or =SIL) and 86.0% of patients with > or =high grade SIL. Conventional microscopic screening performed in Costa Rica resulted in the hypothetical referral of 6.5% of patients with > or =ASCUS for colposcopy, including 69.5% of patients with > or =SIL and 79.8% of those with > or =high grade SIL. CONCLUSIONS: In this study, PAPNET-assisted cytologic screening accurately identified smears obtained from women with high grade SIL or carcinoma. Determination of the clinical cost-effectiveness of PAPNET-assisted screening in routine practice awaits future study.

Cohort Studies↗
PubMed1998

Comparison between once a day vs twice a day G-CSF for mobilization of peripheral blood progenitor cells (PBPC) in normal donors for allogeneic PBPC transplantation.

Despite the wide use of G-CSF for mobilization of PBPC the best dose and schedule of G-CSF has not been definitively established. In this study we have compared three different schedules of G-CSF for mobilization of PBPC in normal donors including a single daily dose of 10 microg/kg/day for 5 days (21 donors) and doses of 6 (21 donors) or 8 microg/kg/12 h (6 donors) for 5 days. We demonstrate that G-CSF at doses of 6 and 8 microg/kg/12 h mobilizes significantly more CD34+ cells/ml of blood (83.3 +/- 6.7 and 121 +/- 6.9, respectively) than 10 microg/kg/day (71.6 +/- 6.5). Mobilization with 6 or 8 microg/kg/12 h of G-CSF was also associated with collection of significantly more CD34+ cells in comparison with 10 microg/kg/24 h (2.24 +/- 1.2 and 2.46 +/- 1.22 vs 1.15 +/- 0.8 CD34+ cells/kg of donor/blood volume). PBPC collection was associated with a significant decrease in platelet count which was not significantly different between the three groups. Ten days after the last PBPC collection platelet counts were within normal limits while there was a decrease in WBC and ANC. We conclude that G-CSF administered every 12 h at doses of 6 microg/kg provides better CD34+ cell yield than 10 microg/kg once a day in normal donors which may translate into a decrease in the number of aphereses required to obtain enough numbers of CD34+ cells for allogeneic PBPC transplant.

Adolescent↗
PubMed1997

Cervical specimens collected in liquid buffer are suitable for both cytologic screening and ancillary human papillomavirus testing.

BACKGROUND: Several new techniques have been developed to improve the sensitivity of cervical carcinoma screening and reduce equivocal cytologic diagnoses referred to as atypical squamous cells of undetermined significance (ASCUS). This study evaluates the effectiveness of combining two newly introduced diagnostic techniques: preparation of thin-layer cytologic slides from ThinPrep liquid buffer and selected Hybrid Capture testing for human papillomavirus (HPV) DNA. Because HPV DNA detection has been strongly associated with the presence of a cervical carcinoma precursor ("squamous intraepithelial lesion," or SIL), HPV testing might be useful for identifying women with ASCUS who have an underlying SIL. METHODS: Two hundred specimens demonstrating diverse cervical abnormalities were selected from a prospective population-based study of 9174 women conducted in Costa Rica. The entire cohort had been screened with conventional cervical smears; ThinPrep slides made from liquid buffer, PAPNET, a computerized slide reading system; and Cervicography. Patients with any abnormal screening test were referred for colposcopy, punch biopsy, and loop excision of cases with high grade cytologic abnormalities not explained by punch biopsy. For this investigation, the results of ThinPrep cytology and HPV testing alone and in combination were compared with the final diagnoses, with an emphasis on the detection of carcinoma and high grade SIL. RESULTS: The 200 subjects studied included 7 women with a final diagnosis of carcinoma, 44 with high grade SIL, 34 with low grade SIL, 51 with a variety of equivocal diagnoses, and 64 with normal diagnoses. A ThinPrep cytologic diagnosis of SIL or carcinoma was made in 39 (76%) of the 51 women with final diagnoses of high grade SIL or carcinoma. Hybrid Capture testing detected carcinoma-associated types of HPV DNA in 100% of women with carcinoma, 75% with high grade SIL, 62% with low grade SIL, 20% with equivocal final diagnoses, and 12% of normal women. If colposcopy referral had been limited to women with a ThinPrep diagnosis of SIL or a diagnosis of ASCUS associated with the detection of carcinoma-associated HPV DNA from the same vial, 100% of women with carcinoma and 80% with high grade SIL would have been examined. To achieve this high sensitivity in the entire population of 9174 women would have required the referral of about 7% of the population. The combined screening strategy would have performed marginally better than optimized conventional screening with referral of any abnormal cytology (ASCUS and above). CONCLUSIONS: A cervical carcinoma screening technique which uses a single sample for cytopathology and HPV testing to triage equivocal diagnoses may be promising if it proves to be cost-effective.

Carcinoma↗
PubMed1995

Central effects of catecholamines upon mammary contractility in rats are neurally mediated.

We injected, i.e., intracerebroventricularly (ICV) or systematically, small amounts of adrenaline (ADR), noradrenaline (NA), isoproterenol (ISOP) and dopamine (DA) in urethane-anesthetized lactating rats, and determined the effects on isometrically recorded intramammary pressure (IMP) responses to exogenous oxytocin (OXY). While centrally administered ADR, NA and DA provoked increased IMP responses to OXY, the beta-adrenergic agonist ISOP induced the opposite effect. These effects were reversible, dose related and also occurred in hypophysectomized rats. However, when injected systematically, all adrenergic agonists but DA depressed IMP responses to OXY. Further experiments showed that central effects of catecholamines were exerted by regulating ductal tone, through the direct innervation of the mammary glands. Thus, whereas complete blockage of these effects occurred after selective denervation of the mammary glands, increased ductal tone resulted from ICV administration of ISOP. Finally, evidence was also obtained that antagonistic alpha- and beta-adrenergic mechanisms may interact with each other to regulate milk ejection, and with afferent signals from the mammary glands. Thus, beta-adrenergic inhibition upon IMP was counteracted by either NA administration or by activation of ductal mechanoreceptors. Together, these results suggest that regulation of milk ejection may involve neurally mediated influences on mammary contractility. Such actions would interact closely with afferents from the mammary gland influencing ductal tone.

Adrenergic Agents↗
PubMed1995

Effects of centrally administered prolactin upon mammary contractility in anesthetized lactating rats.

The possibility was investigated that centrally administered rat prolactin (PRL), i.e., intracerebroventricularly (ICV) or intrathecally (IT), may influence mammary contractility in urethane-anesthetized lactating rats. In addition to the monomer (23 kD PRL), the 16- and 7-kD PRL fragments were also tested and their effects were determined on isometrically recorded intramammary pressure (IMP) responses to exogenous oxytocin (OXY). ICV injection of 23 kD PRL provoked increased IMP responses; similar, but inconsistent effects were obtained after 16 kD PRL, and no effect occurred after either saline or the 7 kD PRL fragment. The 23 kD PRL effect had a latency of about 5 min, reached plateau at 10-15 min and its magnitude was dose-dependent. Also, a stronger dose-related effect was shown by 23 kD PRL after IT than after ICV administration, which suggests that lower threshold for the PRL actions exist at the spinal level. On the other hand, ICV or IT injections of antiserum to PRL, but not of normal rabbit serum, fully prevented the respective facilitatory effects of 23 kD PRL on mammary contractility. Further experiments into the mechanisms involved showed that neither adrenalectomy nor hypophysectomy prevented the PRL effect whereas complete blockage occurred after either spinal cord transection, ventral root section (T8-T10 level), or i.v. or ICV administration of the adrenergic beta-blocker propranolol. These results indicate that central effects of PRL upon mammary contractility were neurally mediated and may have resulted from depressed beta-adrenergic control of ductal tone.

Adrenalectomy↗
PubMed1992

Regulation of prolactin transformation in the rat pituitary.

We have investigated the mechanisms involved in the inhibition by dopamine of the transformation of prolactin within the anterior pituitary of the lactating rat. The degree of inhibition depends on the intracellular age of prolactin, being greater in newly synthesized (<1 hour) and in older (>12 hours since biosynthesis) hormone and lesser in prolactin synthesized 4-8 hours earlier. Transformation occurs in prolactin granules and involves an increase in oligomeric forms of prolactin at the expense of the monomeric form. A reversible disulphide-linked mechanism may be involved in dopamine inhibition of prolactin transformation; it is dependent upon the intracellular and/or intragranular pH via a Na+/H+ exchange mechanism. Transient suppression of dopamine inhibition may lower the intracellular/intragranular pH and subsequently cause transformation of the hormone. Developmentally, dopamine secretion by tuberoinfundibular neurons is seriously impaired and the response of pituitary lactotrophs to dopamine is reduced in adult rats deprived of milk prolactin during Days 2-5 post partum. These results suggest milk prolactin ingested during a critical post partum period may exert an organizational effect upon dopamine secretion and its function on the pituitary lactotroph during adulthood.

Animals↗
PubMed1992

Changes in molecular variants during in vitro transformation and release of prolactin by the pituitary gland of the lactating rat.

PRL transformation involves a dopamine (DA)-controlled, thiol-mediated decrease in pituitary PRL detectability that precedes and may determine increased PRL release. The present studies were designed to determine 1) whether structural changes occur to adenohypophyseal (AP) PRL during in vitro transformation and may account for decreased PRL detectability; 2) whether such changes occur within AP PRL granules; 3) the type and proportion of secreted PRL variants; and 4) the influence of DA and/or thiol reducing agents upon AP PRL molecular changes. Quartered APs of 8 h nonsuckled lactating rats, injected or not with [3H]leucine (5 mCi/g body wt, 8 h before death) were incubated for 30-240 min. The effects of DA (50 microM) with or without reduced glutathione (10 mM), and the alkylant N-ethylmaleimide (1 mM) were compared to the changes in PRL molecular variants occurring in control incubated AP fragments. Polyacrylamide gel electrophoresis (PAGE) under native conditions and sodium dodecyl sulfate (SDS)-PAGE under reducing (R) or nonreducing (NR) conditions were used to resolve molecular variants of PRL and [3H]PRL, followed by Western blotting and densitometric/liquid scintillation techniques, respectively. Up to 5 and 10 major forms of immunoreactive PRL were resolved by PAGE and SDS-PAGE, respectively. The spontaneous transformation after 30 min incubation was correlated with a decrease of 23K PRL and 23K [3H]PRL bands and an increase in high mol wt (80 to greater than 100K) PRL forms. These changes were reversible upon reduction of the proteins before electrophoresis or after extraction of preparative gels. DA and N-ethylmaleimide prevented, whereas reduced glutathione induced these changes. Similar changes were observed in isolated granules from nonincubated and incubated pituitary fragments. Secreted PRL was also polymorphic, with a high predominance of 23K PRL and 23K [3H]PRL. In addition, a polymeric PRL variant, which in reducing gels showed an apparent mol wt of 27K, was secreted in high proportion, similar to that of 23K PRL. The nature of this polymeric variant of PRL is unclear at present. Altogether, these results suggest that a dynamic interconversion of PRL molecular variants occur during transformation. The decreased detectability associated with PRL transformation appears to involve the association of 23K PRL molecules into a 80 to greater than 100K disulfide-linked oligomer. This association is reversible upon reduction and takes place within secretory granules. DA appears to inhibit PRL transformation by preventing thiol-disulfide interchange.

Animals↗
PubMed1990

Age-related stimulatory and inhibitory effects of suckling regulate lactation in rabbits.

Milk production and the duration of lactation were compared between control rabbits nursing their own pups and those whose litters were replaced by younger, i.e., 4-6 days old, or older pups (20-23 days old) starting at pp days 4, 10 or 15. In rabbits whose pups were exchanged on pp day 4 by older pups, an early decline of milk secretion was induced and similar yields to those of late-lactating controls were produced during mid lactation. Conversely, yields similar to those of mid-lactating controls were produced in late-lactating mothers nursing young pups continuously since pp day 10 and high yields were maintained in these animals until pp day 45. When litter exchanges, by either older or younger pups, were delayed until pp day 15, yields were not significantly different from controls. These results indicate that qualitative changes in suckling stimulation develop as the litter grows older, i.e., young pups stimulate milk secretion, whereas old pups inhibit it. Thus, suckling itself may determine the overall pattern of milk secretion in these species.

Age Factors↗
PubMed1990

Prolactin and propranolol prevent the suckling-induced inhibition of lactation in rabbits.

The normal once-a-day frequency of suckling in the rabbit was increased on day 31 (late lactation) by the addition of two extra sucklings (8 and 16 hr after) the daily suckling. In confirmation of previous data, two additional sucklings significantly decreased milk yield acutely on day 31 in comparison with the average 4-day milk yield before and after day 31. The decrease in milk secretion after the two additional sucklings was prevented by a single injection of 3 mg prolactin (given 24 hr before the two extra sucklings) and/or by injections of the beta-adrenergic-blocking drug, propranolol (100 micrograms/kg b. wt. given 30 min before each additional suckling). Since prolactin secretion is decreased in these species and the mammary gland is less responsive to the hormone during late lactation, the present results suggest that in addition to these factors, suckling-induced activation of sympathetic influences may contribute to the decline in milk production at this stage of lactation. Taken together, these results suggest that suckling may regulate lactation in the rabbit through antagonistic mechanisms at different stages of lactation.

Animals↗
PubMed1989

Differential effects of thyrotropin-releasing hormone on in vitro release of in vivo or in vitro newly synthesized and mature prolactin by lactating rat adenohypophyses. Further evidence for a sequential pattern of hormone release.

We studied the basal and thyrotropin-releasing hormone (TRH)-stimulated in vitro release of newly synthesized and mature prolactin (PRL) by lactating rat pituitary fragments. Newly synthesized PRL was defined as that resulting from either in vivo pulse labelling with [3H]-leucine (injected i.v. 10 min before removing the pituitary glands for in vitro incubation); or in vitro labelled by a 5-min preincubation period of adenohypophyseal fragments. Mature PRL was defined as that labelled in vivo 8 h before incubation. Medium PRL was quantified by polyacrylamide-gel-electrophoresis densitometric and liquid scintillation techniques. Under basal conditions, both total (unlabelled) and 8-hour labelled (mature) PRLs showed an in vitro release pattern characterized by an initial period of faster and higher secretion that lasted for 30-60 min followed by a lower secretion rate that extended from 60 to 240 min of incubation. Secretion of newly synthesized PRLs was detected since the first 30 min, but did not reach maximum levels until 90-120 min of incubation. Accordingly, PRL release during the first 30-60 min of incubation consisted primarily of mature PRL, whereas secretion during the rest of incubation included the release of newly synthesized hormone. These results confirm previous data on the sequential, rather than preferential, release of different age PRLs. TRH (0.35 microM) stimulated (about 30% above control) the release of both total and mature PRLs. No effect could be detected upon the release of in vivo labelled new PRL, while the same dose of TRH strongly stimulated (about 100% above control) the release of in vitro labelled new PRL.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗