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Biomedical subjects

P Valenzuela

Publications and source records attributed to P Valenzuela.

At least 19 recordsLinked to original sources

Endometrioid adenocarcinoma of the ovary and endometriosis.

OBJECTIVE: We present a retrospective analysis of 22 cases of endometrioid ovarian carcinoma, reviewed to identify endometriosis and its malignant transformation. STUDY DESIGN: Twenty-two patients with endometrioid ovarian cancer were included in the review. Their clinical and histological data were retrospectively reviewed. The origin of the tumours was considered endometriosis-related when the presence of malignant changes in endometriosis glands leading to endometrioid carcinoma were found. RESULTS: Endometriosis was detected in three cases (3/22=14%). One of them presented a clearly benign to malignant transformation area. In another patient, the transition zone was abrupt and present in both ovaries. In the third, a pre-menopausal woman, ovarian endometriosis with only focal endometrioid carcinoma was observed. The three of them had a clear-cell carcinoma component. The presence of a clear-cell component was significantly greater in patients with endometriosis than in patients without endometriosis Each patient had a different clinical presentation: increase in abdominal perimeter, post-menopausal vaginal haemorrhage and hypermenorrhea. Preoperative CA 125 levels were avalaible in 15 of the patients (15/22=68%). Endometriosis was found in two of these 15 patients, both with the highest CA 125 measured levels, exceeding 1700 U/ml. In the remaining of the patients, CA 125 value did not exceed 35 U/ml. CONCLUSION: Although this association is not very frequent, patients with ovarian endometriosis and a high CA 125 serum level should be managed with special care, regardless of their pre-menopausal or post-menopausal status.

Adenocarcinoma, Clear Cell↗

The effects of time on pH and gas values in the blood contained in the umbilical cord.

BACKGROUND: The pH and gas analysis of umbilical cord blood is an accepted practice in most maternity hospitals. The data that is obtained after a latency period in processing the cord blood samples is evaluated to determine whether it is useful for the clinic. METHODS: The umbilical cords from 50 term infants were clamped immediately after delivery. Samples of artery and vein blood were drawn 5, 60, and 120 min postpartum and pH, pO2, and pCO2 levels were measured. RESULTS: No significant differences were found after 60 min in the average values for pH in the arterial and venous paired samples, though the arterial and venous pCO2 values declined significantly. The arterial pO2 values increased significantly. After 120 min, no significant differences in the average values for the venous pH and pO2 paired samples were found. The arterial pH values increased significantly, however, and the arterial and venous pCO2 values declined significantly. The arterial pO2 values increased significantly. CONCLUSIONS: Though statistically significant differences occurred over time, these changes were so modest clinically that the data could still be used even when an immediate analysis of the umbilical cord was not possible.

Adult↗

Association of adenylate cyclase with an actin-like protein in the human myometrium.

Regulation of muscle contraction by second messengers such as cAMP and regulation of the adenylate cyclase enzyme by the cytoskeleton have been previously described. However, the physical association of both effector and structural elements is still unknown. In this context, we have co-purified a human myometrial adenylate cyclase with an actin-like protein in a two-step purification protocol. The adenylate cyclase catalytic unit was solubilized with Lubrol-PX, submitted to anionic exchange chromatography and purified about 7-fold. The eluate was applied to a forskolin-agarose column obtaining an adenylate cyclase extract enriched 257-fold (enzymatic activity of 1390 pmol/30 min per mg protein) that co-eluted with a 74.6-kDa protein that possessed the 18-27 amino-acid fragment from the N-terminal region of human actin. Under non-reducing conditions, the apparent molecular weight of this protein decreased to 54 kDa, which has been previously described for arthrin. These results provide the first demonstration of the physical association of human myometrial adenylate cyclase with a cytoskeleton-related protein, supporting the hypothesis that adenylate cyclase is regulated by mechanical stimuli.

Adenylyl Cyclases↗

The contribution of the CEA marker to CA 15.3 in the follow-up of breast cancer.

PURPOSE OF INVESTIGATION: The clinical use of tumor markers during breast cancer follow-up is still surrounded by controversy. The objective of this study consisted of determining the contribution of the CEA marker to CA 15.3 in the follow-up of breast cancer patients as applied to clinical practice. METHODS: Three hundred and eighteen cases of women with breast cancer were analyzed retrospectively as far as the sensitivity, the specificity and the positive and negative predictable values of the CA 15.3 and CEA markers. RESULTS: Of the 318 patients, 59 suffered a relapse during the study. After evaluation of both markers the sensitivity was 56.8% (CA 15.3: 47.4%), the specificity 85.3% (CA 15.3: 88.4%), the positive predictable value was 46.4% (CA 15.3: 48.2%) and the negative predictable value was 89.41% (CA 15.3: 88%). CONCLUSIONS: The low sensitivity of studied tumor markers proved of limited use on a clinical scale.

Adult↗

Comparison of cervical smears secured with different instruments.

BACKGROUND: In this presentation we have compared the results from cytologic samples obtained with the cervical brush and Ayre's wooden spatula, against samples obtained with Acellon Combi. METHODS: One thousand cervical smears were collected. This was a cross-sectional study, where it was decided randomly to use cervical brush for sampling of the endocervix and Ayre's wooden spatula for exocervix or Acellon Combi for both. RESULTS: The combination of the cervical brush and the wooden spatula yielded an acceptable quantity of columnar cells in 71.6% of the cases, during both endocervical and exocervical sampling, while the Acellon Combi yielded an acceptable quantity in 61.7% of the cases (p<0.01). The combination of brush/spatula yielded an acceptable quantity of squamous cells from samples of endocervix and exocervix in 87.5% cases, while with the Acellon device amounted to 77.4% (p<0.001). Highly significant differences in the state of cellular preservation of samples from endocervix obtained with cervical brush technique were found upon comparison to Acellon group. CONCLUSIONS: Henceforth, we believe that the use of the cervical brush and the Ayre wooden spatula increases the quantity and preservation of the cells retrieved during cervical smears compared to Acellon Combi.

Adolescent↗

The bacteriophage lambda DNA packaging enzyme: identification of four structural domains of the gpNu1 subunit using limited proteolysis.

Lambda DNA terminase, the enzyme that cleaves virion-length chromosomes from multigenomic concatemers and packages them into the bacteriophage head, is composed of two subunits, gpNu1 and gpA. Direct determination of the structure of gpNu1, the smaller subunit, has not been possible because of its insolubility in aqueous solutions. Therefore, to identify smaller and potentially water-soluble domains of gpNu1, we analyzed the nature of the products obtained by limited digestion of the protein with several proteases. The gpNu1 subunit was obtained from E. coli cells transfected with the plasmid pH6-Nu1 that overproduces the protein. Incubation of gpNu1 solubized in 2.5 M guanidinium chloride with chymotrypsin resulted in the formation of at least eight discrete protein bands, while treatment with endoproteinase glu-C and bromelain yielded three and one major bands, respectively. The peptides generated by digestion with the various proteases were separated by two-dimensional gel electrophoresis and transferred to Immobilon membranes. Amino acid sequencing of the peptides allowed for the precise assignment of their N-terminal amino acid, while their estimated molecular weights permitted the identification of their C-terminal ends. The results reveal that in the presence of 2.5 M guanidinium chloride, gpNu1 is partially folded in at least four distinct structural domains that correspond to functional domains as determined by previously reported genetic experiments. This information is key to design new plasmids to overproduce these domains for further structural analysis.

Amino Acid Sequence↗

Expression of vasoactive intestinal peptide (VIP) receptors in human uterus.

We show the existence of functional vasoactive intestinal peptide (VIP) receptors in normal human female genital tract (endometrium, myometrium, ovary and Fallopian tube) as well as in leiomyoma (a frequent uterine pathology). The correlation between VIP binding and stimulation of adenylyl cyclase activity for all studied tissues was linear (r = 0.86) suggesting the expression of VIP receptors throughout the human female genital tract. Immunodetection of VIP receptor subtypes gave different molecular weights for VPAC(1) (47 kDa primarily) and VPAC(2) (65 kDa), which may be due to different glycosylation extents. In conclusion, this study demonstrates the expression of both subtypes of VIP receptors and their functionality in human female genital tract, suggesting that this neuropeptide could play an important physiological and pathophysiological role at this level.

Adenylyl Cyclases↗

Impairment of adenylate cyclase activity and G-proteins in human uterine leiomyoma.

The mechanisms responsible for the growth of uterine leiomyoma (a frequent cause of infertility in women) are largely unknown. Some data supports that cAMP plays a role in the growth of uterine cells but there are no reports on the status of the cAMP producing system in this human benign neoplasia. In this study, biopsies from leiomyoma and the adjacent myometrium were taken from menstruating women subjected to total hysterectomy for leiomyoma. Adenylate cyclase activity was determined by a protein-binding method, and the expression of alpha(s), alphai1/2, alphai3 and alphai0) G-protein subunits was analysed by immunoblot. The leiomyoma samples exhibited a decreased expression of as and ai1/2 with respect to the adjacent myometrial tissue. No differences were observed in alphai3 and alphaio protein expression. The basal adenylate cyclase activity as well as the efficacy (as assessed by the maximal stimulation levels) of either forskolin or, to a lesser extent, Gpp[NH]p on stimulation the enzyme activity was significantly lower in leiomyoma than in myometrium, whereas the potency (as assessed by the ED50 values) of these two agents did not vary. Present data indicate that the human leiomyoma is associated with low levels of cAMP. It is conceivable that the loss of sensitivity of adenylate cyclase to endogenous regulatory molecules could be related to the pathogenesis of human leiomyomas given that cAMP inhibits the MAP-kinase cascade in uterine tissues.

Adenylyl Cyclase Inhibitors↗

Hepatitis B virus e antigen specific epitopes and limitations of commercial anti-HBe immunoassays.

Current commercial hepatitis B virus (HBV) anti-HBe immunoassays are designed so that anti-HBe is detectable only in the absence of excess HBeAg. Recently, with the use of direct anti-HBe assays, anti-HBe was detected in individuals who had been seropositive for several years for HBeAg [Maruyama et al. (1993) J. Clin. Invest. 91:2586-2595]. Although anti-HBe seroconversion does not necessarily indicate subsequent HBeAg clearance, the ability to detect earlier anti-HBe seroconversion could have clinical significance for monitoring patients undergoing HBV immunotherapy (e.g., alpha interferon therapy). Because the HBeAg and the HBcAg share 149 amino acids, an anti-HBe assay must distinguish anti-HBe from anti-HBc antibodies. Although the HBV HBeAg and HBcAg display distinct immunogenic determinants, much remains unknown regarding the complete epitope spectrum specific to each antigen. The goal of this study was 3-fold. The first objective was to identify HBeAg specific linear epitopes. The second objective was to design an anti-HBe immunoassay capable of detecting anti-HBe specific antibody in the presence of excess HBeAg. The third objective was to characterize early anti-HBe seroconversion antibodies. The major linear epitope residing in the HBeAg amino acid sequence was mapped and 2 novel minor epitopes (delta, gamma) which appear to be HBeAg specific have been identified. An anti-HBe immunoassay capable of detecting anti-HBe specific antibody in the presence of excess HBeAg was designed. Finally, it was found that early anti-HBe seroconversion antibodies appear to be conformational, whereas later seroconversion, more typically associated with the clearance of HBeAg, is characterized by the presence of antibodies to the linear HBeAg epitopes.

Animals↗

[Anorectal congenital malformations and their preferential associations. Experience of the Clinical Hospital of the University of Chile. Period 1979-1999].

BACKGROUND: Anorectal atresia is a relatively frequent malformation in the newborn. According to the Latin American Collaborative Study for Congenital Malformations (ECLAMC), its frequency is 4.1 per 10,000 born alive. AIM: To determine the frequency of anorectal malformations at birth, and compare the figures with those of other maternity hospitals in Chile participating in ECLAMC, with the figures of the whole ECLAMC and with figures from other worldwide monitoring systems. PATIENTS AND METHODS: All births occurred in the University of Chile Clinical Hospital between January 1979 and August 1999, were reviewed. RESULTS: During the study period, 70,242 children were born, 4,486 had a malformation and 54 had an anorectal malformation (7.7 per 10,000 born alive). Fifty nine percent had other associated malformations (of the urinary tract in 42.5%, skeletal in 26% and cardiovascular in 18.5%). Five stillborn babies had other severe malformations. Twenty one children had a fistula. Forty three % were male, 39% female and 18% had ambiguous sex. When compared with normal controls, malformed newborns had a lower birth weight, lower gestational age and a higher mean maternal age, a higher frequency of metrorrhagia during the first trimester of pregnancy, a higher number of siblings with malformations and a higher degree of consanguinity among parents. CONCLUSIONS: The participation of recessive genes in the etiology of anorectal malformations is suggested.

Abnormalities, Multiple↗

Use of a novel hepatitis C virus (HCV) major-epitope chimeric polypeptide for diagnosis of HCV infection.

The genome of hepatitis C virus (HCV) consists of seven functional regions: the core, E1, E2/NS1, NS2, NS3, NS4, and NS5 regions. The U. S. Food and Drug Administration-licensed 2.0G immunoassay for the detection of anti-HCV uses proteins from the core, NS3, and NS4 regions (McHutchinson et al., Hepatology 15:19-25, 1992). The 3.0G enzyme-linked immunosorbent assay includes the protein from the NS5 region (Uyttendaele et al., Vox Sang. 66:122-129, 1994). The necessity of detecting antibodies to viral envelope proteins (E1 and E2) and to different genotype samples has been demonstrated previously (Chien et al., Lancet 342:933, 1993; Lok et al., Hepatology 18:497-502, 1993). In this study we have attempted to improve the sensitivity of the anti-HCV assay by developing a single multiple-epitope fusion antigen (MEFA; MEFA-6) which incorporates all of the major immunodominant epitopes from the seven functional regions of the HCV genome. A nucleic acid sequence consisting of proteins from the viral core, E1, E2, NS3, NS4, and NS5 regions and different subtype-specific regions of the NS4 region was constructed, cloned, and expressed in yeast. The epitopes present on this antigen can be detected by epitope-specific monoclonal and polyclonal antibodies. In a competition assay, the MEFA-6 protein competed with 83 to 96% of genotype-specific antibodies from HCV genotype-specific peptides. This recombinant antigen was subsequently used to design an anti-HCV chemiluminescent immunoassay. We designed our assay using a monoclonal anti-human immunoglobulin G antibody bound to the solid phase. Because MEFA-6 is fused with human superoxide dismutase (h-SOD), we used an anti-human superoxide dismutase, dimethyl acridinium ester-labeled monoclonal antibody for detection. Our results indicate that MEFA-6 exposes all of the major immunogenic epitopes. Its excellent sensitivity and specificity for the detection of clinical seroconversion are demonstrated by this assay.

Antigens, Viral↗

Bilateral massive edema of the ovary.

We present a case of synchronic bilateral ovary mass edema. In spite of the patient's age and the difficulties of the intraoperative study it reveals a high likelihood of malignancy in the preoperative stage.

Adult↗

Serological response to Helicobacter pylori recombinant antigens in Chilean infected patients with duodenal ulcer, non-ulcer dyspepsia and gastric cancer.

We have previously cloned 10 Helicobacter pylori antigen genes from a Chilean strain including: cytotoxin VacA, a truncated region of CagA (called A17), a species-specific protein (Ag26), urease subunits (UreA, UreB), a flagellin, (FlaB), heat shock proteins (HspA and HspB), an adhesin (HpaA) and a lipoprotein (Lpp20). Immunogenicity of these antigens was tested by immunoblot with sera of Chilean infected patients, revealing that HpaA, A17, HspB and VacA were more frequently recognized (86%, 82%, 68% and 68%, respectively). According to the clinical condition, it was determined that Lpp20 was preferentially recognized by sera from non-ulcer dyspepsia patients (80%), A17 and VacA by patients with duodenal ulcer (92% and 83% respectively), and HspB by patients with duodenal ulcer (83%) and gastric cancer (90%). An ELISA was developed with a purified mixture of A17 and VacA antigens to test the different groups of patients. It was found that sera from duodenal ulcer patients showed higher values than those from non-ulcer dyspepsia patients, but this difference was not significant (p<0.2). Moreover, sera from gastric cancer patients showed values lower than those from non-ulcer dyspepsia patients (p<0.019). These results indicate that, in the Chilean population, antibodies raised against VacA and A 7 are not markers either for duodenal ulcer or for gastric cancer.

Adult↗

[Occupational stress in health care personnel].

BACKGROUND: Occupational stress results from the interaction of multiple risk factors, such as the physical environment, biological function disturbances, work content and organization and diverse psychosocial components. AIM: To study the frequency of symptoms and the main sources of job stress, perceived by professional and non professional health care workers and to compare gender differences. SUBJECTS AND METHODS: A group of specially designed, self-administered, questionnaires adapted by the main author and independently validated, were applied. The results of two symptoms, one work satisfaction, and one job stress scales are reported. RESULTS: One hundred sixteen women and 89 men were studied, 143 are professionals and 62 non professionals (clerical and nurse auxiliaries). Forty percent had symptoms of job stress and 82 subjects were defined as "probable cases", according to the ratings on the symptom scales. There were significant differences in the frequency of symptoms between professionals and non professionals (34.3 and 69.2% respectively). The main differences in symptoms, sources of job stress and dissatisfaction were more closely associated to the occupational level than to gender. CONCLUSIONS: A high frequency of job stress symptoms was observed in this sample of health care workers and the risk of occupational stress varies more with the occupational level than with gender.

Adult↗