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P Pace

Publications and source records attributed to P Pace.

16 recordsLinked to original sources
PubMed1997

Human estrogen receptor beta binds DNA in a manner similar to and dimerizes with estrogen receptor alpha.

The cloning of a novel estrogen receptor beta (denoted ERbeta) has recently been described (Kuiper, G. G. J. M., Enmark, E., Pelto-Huikko, M., Nilsson, S., and Gustafsson, J-A. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 5925-5930 and Mosselman, S., Polman, J. , and Dijkema, R. (1996) FEBS Lett. 392, 49-53). ERbeta is highly homologous to the "classical" estrogen receptor alpha (here referred to as ERalpha), has been shown to bind estrogens with an affinity similar to that of ERalpha, and activates expression of reporter genes containing estrogen response elements in an estrogen-dependent manner. Here we describe functional studies comparing the DNA binding abilities of human ERalpha and beta in gel shift assays. We show that DNA binding by ERalpha and beta are similarly affected by elevated temperature in the absence of ligand or in the presence of 17beta-estradiol and the partial estrogen agonist 4-hydroxy-tamoxifen. In the absence of ligand, DNA binding by ERalpha and beta is rapidly lost at 37 degrees C, while in the presence of 17beta-estradiol and 4-hydroxy-tamoxifen, the loss in DNA binding at elevated temperature is much more gradual. We show that the loss in DNA binding is not due to degradation of the receptor proteins. However, while the complete antagonist ICI 182, 780 does not "protect" human ERalpha (hERalpha) from loss of DNA binding at elevated temperature in vitro, it does appear to protect human ERbeta (hERbeta), suggestive of differences in the way ICI 182, 780 acts on hERalpha and beta. We further report that ERalpha and beta can dimerize with each other, the DNA binding domain of hERalpha being sufficient for dimerization with hERbeta. Cell and promoter-specific transcription activation by ERalpha has been shown to be dependent on the differential action of the N- and C-terminal transcription activation functions AF-1 and AF-2, respectively. The existence of a second estrogen receptor gene and the dimerization of ERalpha and beta add greater levels of complexity to transcription activation in response to estrogens.

Animals↗
PubMed1997

Idoxifene is equipotent to tamoxifen in inhibiting mammary carcinogenesis but forms lower levels of hepatic DNA adducts.

Tamoxifen is an effective agent preventing mammary carcinogenesis in rats but causing liver tumours. Idoxifene is a more potent antioestrogen and is effective in patients with advanced breast cancer. We therefore compared the effects of idoxifene with tamoxifen on mammary carcinogenesis and hepatic DNA adduct formation. To do this, we undertook a study designed to compare tamoxifen with idoxifene as a chemopreventive agent in rats inoculated with N-methylnitrosourea (MNU) and also measured hepatic adduct formation. We examined the time to mammary tumour development in 272 female Ludwig/Wistar/Olac rats treated with MNU followed by tamoxifen (5 mg kg(-1)), equimolar idoxifene or vehicle three times a week for up to 24 weeks. To determine duration of effect, a second study was carried out whereby all of the 129 animals surviving at the end of treatment were entered into a surveillance programme for 27 weeks after the end of the administration period. Hepatic DNA adduct formation was examined by 32P-postlabelling in a group of rats after 24 weeks' treatment. In the first study, both idoxifene and tamoxifen were effective in preventing tumour growth as only 2 out of 21 (10%) MNU and vehicle-treated animals were alive and tumour free after 24 weeks compared with 13 out of 22 (59%) animals receiving MNU followed by idoxifene or tamoxifen (P < 0.001). The second study showed that, in both idoxifene- and tamoxifen-treated animals, a progressive regrowth of tumours occurred after cessation of therapy, as by the end of the observation period only four idoxifene-treated animals and one tamoxifen-treated animal were free from disease. In the subset of animals tested, tamoxifen-treated animals had approximately 100 times higher levels of DNA hepatic adducts than idoxifene-treated animals. Adducts were not seen in the control group. These results indicate that idoxifene is as effective a chemopreventive agent as tamoxifen in the rat while causing only very low levels of DNA adducts in liver tissue and suggest that idoxifene may be a well-tolerated chemopreventive agent in women who are at increased risk of breast cancer.

Animals↗
PubMed1993

Correction of a lysosomal deficiency by contact-mediated enzyme transfer after bone marrow transplantation.

The effectiveness of bone marrow transplantation for treating lysosomal deficiency diseases relies on the ability of bone marrow cells to provide the missing enzyme to various tissues of the recipient. This has been shown to occur in vitro by endocytosis of enzyme secreted by bone marrow-derived cells and also by direct cell-to-cell-contact. To investigate the mechanism of enzyme replacement therapy in vivo we have used, as enzyme donors, bone marrow cells from coat color mouse mutants that secrete very low or very high levels of a lysosomal enzyme, beta-glucuronidase. Our results show that the level of beta-glucuronidase activity acquired by the tissues of recipient, enzyme-deficient mice is not related to the ability of the donor bone marrow-derived cells to secrete the missing enzyme. This finding suggests that cell-to-cell transfer of lysosomal enzymes may play an important role in the correction of lysosomal diseases by bone marrow transplantation.

Alleles↗
PubMed1993

Depression and neuropsychological performance in asymptomatic HIV infection.

OBJECTIVE: The authors examined the effect of depression on neuropsychological performance in HIV-infected men. Previous studies have suggested that depression may account for the neuropsychological abnormalities observed in some patients with HIV infection, but few studies have specifically examined this question. METHOD: An extensive neuropsychological test battery was administered to 121 HIV-seropositive asymptomatic men and 42 HIV-seronegative comparison subjects. The seropositive subjects were grouped into depressed and non-depressed groups on the basis of scores on the Beck Depression Inventory, Hamilton Rating Scale for Depression, and Structured Clinical Interview for DSM-III-R. RESULTS: Statistical comparisons revealed very few measures on which the depressed seropositive subjects scored significantly worse than either of the nondepressed comparison groups. The nondepressed seropositive group differed consistently from the seronegative comparison subjects on measures of verbal memory and dexterity. CONCLUSIONS: These data indicate that the subtle neuropsychological abnormalities observed in some asymptomatic HIV-seropositive subjects cannot be attributed to depression. These data also indicate the advantages of a multifaceted approach to assessment of depression.

Adult↗
PubMed1992

Long-term effects of bone marrow transplantation on lysosomal enzyme replacement in beta-glucuronidase-deficient mice.

This study uses bone marrow transplantation (BMT) between congenic strains of mice as an experimental model to examine enzyme replacement therapy of lysosomal storage diseases. Bone marrow cells from donor mice which have normal levels of the lysosomal enzyme beta-glucuronidase (Gus), which is heat-stable, rapidly repopulated the haematopoietic compartment of irradiated recipient mice which have only low levels of a thermolabile form of this enzyme. Gus activity was found to increase progressively in the tissues of the recipients, including the liver, heart and skeletal muscle. Elevated levels were also observed in the kidney and brain. The increase in enzyme activity in the host tissues was not due to the presence of contaminating blood cells, but rather to the acquisition of new, heat-stable enzyme from the donor bone marrow cells. High levels of Gus activity persisted for at least 72 weeks, showing the potential therapeutic value of BMT for enzyme deficiency diseases.

Animals↗
PubMed1992

A cross sectional epidemiological survey of shipyard workers exposed to hand-arm vibration.

The hand-arm vibration syndrome, widely known as vibration white finger, is a disorder of nerves and blood vessels that occurs in workers exposed to segmental vibration. A cross sectional symptom survey was performed on a sample of workers employed by a large shipyard in the north eastern United States. Random samples were drawn from departments composed of full time dedicated pneumatic grinders, workers with part time exposure to vibration, and other workers not exposed to vibratory tools. Of the 375 workers sampled, 79% responded. The prevalence of white finger symptoms was 71%, 33%, and 6% among the three exposure groups respectively. Similarly, the prevalence of numbness and tingling in the hands and fingers in the three exposure groups was 84%, 50%, and 17%. Workers were classified according to the Stockholm Workshop staging systems for vascular and sensorineural symptom severity. Exposure-response analyses of both vascular and sensorineural stage showed monotonically increasing prevalence of higher disease stages with increasing duration of exposure. Logistic regression analysis, performed to control for potential confounding factors including age and current smoking state, produced highly significant (p less than 0.001) associations between cumulative duration of exposure and prevalence of symptoms. In these analyses smoking state was significantly related to vascular and sensorineural symptoms and age was not. Average latency to onset of symptoms was less than five years of full time equivalent work with vibratory tools. Logistic regression analyses were performed to assess the effect of use of particular work practices on reported symptoms. Further study of this workforce with objective, quantitative measures of peripheral neurological and vascular function is required to characterise the clinical and subclinical effects of vibration exposure.

Cross-Sectional Studies↗
PubMed1990

Detailed clinical assessment of neurological function in symptomatic shipyard workers.

Forty eight patients with extensive occupational exposure to pneumatic grinding tools were evaluated at a university sponsored occupational health clinic. All patients were interviewed and examined by a physician and assessed neurologically with standard clinical, functional motor, quantitative vibrotactile, and electrodiagnostic tests. Sensorineural symptoms were nearly universal; 47 patients (98%) reported numbness and tingling of the hands and fingers. Among clinical tests, two point discrimination and 30 Hz vibration perception were most frequently abnormal. In order to evaluate associations between quantitative test results and sensorineural symptoms, patients were stratified into two groups of symptom severity according to a consensus sensorineural staging system. The tests that discriminated best between the groups of more and less symptomatic patients were hand strength dynamometry, and vibrotactile thresholds. Age standardised 120 Hz vibrotactile thresholds were significantly raised in digit II in 41% of hand measurements. Nerve conduction studies were neither significantly different between more and less symptomatic groups nor correlated with clinical and quantitative sensory tests. Twenty five per cent of the patients had slowing of sensory conduction velocities in the median nerve at the wrist (less than 48 m/s). Of this subset of patients only two showed abnormal slowing of the median nerve distal to the wrist, but half also showed ulnar nerve slowing (less than 47 m/s). This observation highlights the difficulty of differentiating median nerve entrapment from diffuse distal neuropathy in workers exposed to vibration and points to the need for concomitant quantitative sensory and functional motor assessment.

Adult↗
PubMed1989

[6 new cases of spasmus nutans].

Six new born presenting an acquired nystagmus, associated with rhythmic head movements, have been explored clinically, electrophysiologically and neuroradiologically. Etiopathogenic hypotheses and experimental models are proposed. A twenty last years literature review is mentioned. It seemed interesting to authors to practice head scanners to find an organic lesion. The ethnic incidence is not negligible.

Black or African American↗
PubMed1987

Proposal of new gradual dilation metal dilators.

The Authors suggest a new conceived line of metal cervical dilators, testing them on a group, made up of 69 patients, who will undergo Voluntary Pregnancy Interruption (VPI). Comparing the results with those obtained within a further test-group, made up of 69 women who have undergone a cervical dilation, performed by traditional Hegar dilators, it has been noticed that the new dilators are less traumatic on the cervical canal of the uterus; they can be used more easily and a wider employment is foreseen.

Abortion, Induced↗
PubMed1985

Evidence that aldosterone influences transport in target tissues by dissimilar mechanisms.

The present study was performed to answer the question: Is the action of aldosterone on electrolyte transport and electrical properties similar in all target tissues? Studies were performed in vivo in control animals and rats with secondary hyperaldosteronism, caused by a sodium-free diet, to compare the effects of hyperaldosteronism on distal colon with hormone-induced changes in proximal colon. In distal colon aldosterone increased net sodium absorption and potassium secretion approximately threefold. Transmural potential difference increased from -15 +/- 2 to -83 +/- 3 mV (lumen negative) and ISC rose from 167 +/- 26 to 1,023 +/- 17 microA X cm-2. These aldosterone-induced responses were completely inhibited by 0.1 mM amiloride. In contrast, in proximal colon potential difference was unchanged or increased slightly in experimental animals and ISC increased only 28% above control, although increases in net sodium and potassium transport were similar to changes observed in distal colon. Amiloride did not reduce sodium absorption in proximal colon of animals with hyperaldosteronism; ISC was decreased by 43%. These studies demonstrate that rat proximal colon is an aldosterone-sensitive tissue, but that the mechanism by which aldosterone influences sodium transport is not identical in distal and proximal portions of colon.

Aldosterone↗
PubMedDate not supplied

[20 years (1960-1980) of bacterial meningitis in childhood. II. Therapy and diagnosis].

In this article we review the global therapy for purulent meningitis in childhood and present personal data derived from a twenty year survey study (1960 to 1980). We recommend the prompt use of adequate antibiotics at correct doses largely following the intravenous pathway in order to achieve active antimicrobial levels in the cerebrospinal fluid. On the basis of our experience we favour a more large use of either systemic chloramphenicol or intrathecal even in the neonatal period. Moreover, we think glucose infusions should be employed with great caution due to worsening of metabolism (lactate accumulation) and perfusion in the cerebral tissue.

Ampicillin↗
PubMedDate not supplied

[Neuropathology of the Turner syndrome].

We report the neuropathologic examination of a neonatal case of Turner's syndrome (45,XO). We have found some mild irregularities in the cortical organization, notably in frontal and hippocampal regions. In the frontal cortex such anomalies affected particularly the more superficial layers essentially sparing the migrating process which was largely achieved in its fundamental phases. The hippocampal dentate gyrus appeared abnormally infolded. The cerebellum was hypoplasic and contained three types of abnormalities, at least: abundant paradentate matrix cell nests, a large mass of dysplastic cerebellar gyri along the ventral wall of the 4th ventricle and, finally, multiple voluminous heterotopias of macroneurons (possibly, Purkinje cells) in the subcortical white matter. In addition, there were two small olivary heterotopias in the medulla oblongata. The correct identification of all neuropathologic anomalies has been possible for having employed the method of whole brain serial sectioning. We have correlated such cortical, cerebellar and truncal abnormalities to those encountered in similar conditions as lissencephaly, Zellweger's disease and chromosomal trisomies. The pathogenetic mechanisms triggered by the absence of an X chromosome can affect the neuronal migration, but only after the cortical hemispheric one has been almost completely ended. This could explain why cerebellar and olivary neuronal migration are exclusively affected, being there the migration process chronologically slowed down during the normal neurogenesis. There means we might date after the 4th fetal months the neuronal migration trouble. Finally, we would suggest the soft cortical changes in such crucial regions as the frontal and hippocampal cortex to be possibly responsible for the degree of mental retardation seen in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain↗
PubMedDate not supplied

[20 years (1960-1980) of bacterial meningitis in childhood. I. Epidemiological and clinical data].

One hundred forty six children having suffered bacterial meningitis at any age have been collected and retrospectively studied over a period of a twenty year survey (1960 to 1980). In our series we can confirm the prominent epidemiologic and clinical features emerging from the literature. It is notewborty to outline the great percentage of cases lacking any bacterial identification due to previous antimicrobial treatment for parameningeal foci. This raises some major problems about early diagnosis, validity and signification of lumbar punctures, and usefulness of starting treatment with large spectrum antibiotics.

Aminoglycosides↗
PubMedDate not supplied

[Congenital hydrocephalus: clinico-pathological picture].

The authors review the main pathologic causes of congenital hydrocephalus from ischemic-vascular injuries, embryofoetal infections and dysraphisms to genetic ones. Abundant illustrations of each condition are furnished and particular attention is paid to each situation, discussing the available pathogenetic mechanisms and hypothesis. Genetic "sine causa" hydrocephalus and X-linked hydrocephalus are mainly stressed, presenting some personal data. The clinic aspects of the varying forms of hydrocephalus are continuously kept in mind and a terminal paragraph details the clinical and neuroradiological means determinant in differential diagnosis versus similar conditions such as hydranencephaly, porencephaly, aracnoid cysts, holoprosencephaly and agenesis of corpus callosum.

Brain↗