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Biomedical subjects

A Baldi

Publications and source records attributed to A Baldi.

At least 91 records · Page 5Linked to original sources
PubMed1998

Changes of plasma insulin, urea, amino acids and rumen metabolites in somatotropin treated dairy cows.

An experiment was performed to evaluate the effects of somatotropin on plasma free amino acid, urea and insulin concentrations and rumen fermentation pattern and to assess their relationships. Four Italian Friesian dairy cows fitted with rumen cannulae were used in a switch-back design. Slow releasing recombinant bovine somatotropin (640 mg/cow) was injected every 28 days for two consecutive periods. Rumen fluid and blood samples were collected before and after feeding at 0, 7 and 21 days after rbST injection. Exogenous rbST increased plasma insulin concentration and the insulin response to feeding, and decreased plasma urea and free essential and branched chain amino acid concentrations. rbST did not affect rumen fermentation pattern. No correlation was found between rumen and plasma parameters measured after feeding. Our results are consistent with the notion that the main effect of somatotropin is post-absorptive.

Amino Acids↗
PubMed1998

Lesions in donor kidneys: nature, incidence, and influence on graft function.

The aim of this study was to assess the influence of kidney-donor transmitted pathology on graft function. Light and immunofluorescent microscopic findings from a surgical biopsy taken prior to transplantation from 114 cadaveric kidney donors were analyzed. Moderate to severe mesangial IgA deposits were considered consistent with IgA nephropathy. Pathological abnormalities were correlated together with donor age, number of mismatches, and type of immunosuppression by multivariate statistical analysis with the serum creatinine values from patients who experienced no acute rejection at 1 year. Serum creatinine values (n = 52) were not correlated with either non-specific light microscopic lesions or immunofluorescent deposits found in the majority of kidney donors or with changes consistent with IgA nephropathy observed in 9% of the cases. There was, however, a correlation with donor age, which was also correlated with the extent of chronic lesions (P < 0.001).

Adolescent↗
PubMed1998

Development of a densitometric method for the determination of cephalexin as an alternative to the standard HPLC procedure.

A HPTLC-densitometric method was developed in order to obtain a reliable procedure for routine analysis of cephalexin in pharmaceutical formulations. Optimization of TLC conditions for the densitometric scanning was reached by eluting HPTLC silica gel plates in an horizontal developing chamber. Quantitation of cephalexin was performed in single beam reflectance mode by using a computer-controlled densitometric scanner and applying a five-point calibration. A linear regression has been found in the 200-1000 ng range. The setup method is precise, reproducible and accurate. Recovery was also assessed by comparison with the HPLC USP XXIII alternate method. In this case HPTLC-densitometry appears worth of consideration as being relatively inexpensive and time-saving (up to 12 samples can be determined simultaneously in less than 15 min with a solvent consumption of about 15 ml). The results suggest that the proposed method may be used in place of HPLC for the routine quantitation of cephalexin in both pure and dosage forms.

Calibration↗
PubMed1998

The RB-related gene Rb2/p130 in neuroblastoma differentiation and in B-myb promoter down-regulation.

The retinoblastoma family of nuclear factors is composed of RB, the prototype of the tumour suppressor genes and of the strictly related genes p107 and Rb2/p130. The three genes code for proteins, namely pRb, p107 and pRb2/p130, that share similar structures and functions. These proteins are expressed, often simultaneously, in many cell types and are involved in the regulation of proliferation and differentiation. We determined the expression and the phosphorylation of the RB family gene products during the DMSO-induced differentiation of the N1E-115 murine neuroblastoma cells. In this system, pRb2/p130 was strongly up-regulated during mid-late differentiation stages, while, on the contrary, pRb and p107 resulted markedly decreased at late stages. Differentiating N1E-115 cells also showed a progressive decrease in B-myb levels, a proliferation-related protein whose constitutive expression inhibits neuronal differentiation. Transfection of each of the RB family genes in these cells was able, at different degrees, to induce neuronal differentiation, to inhibit [3H]thymidine incorporation and to down-regulate the activity of the B-myb promoter.

Animals↗
PubMed1998

BDNF and NT-3 applied in the whisker pad reverse cortical changes after peripheral deafferentation in neonatal rats.

It has been known for a long time that subcortical input drives the specification of cortical areas. Molecular signals mediating this instructive effect from the periphery are poorly understood. In foetal or neonatal rats, ablation of whisker follicles, transection of the infraorbital nerve, inhibition of axonal transport, but not impulse activity blockade, prevent formation of barrels in the primary somatosensory cortex (S1). These findings suggest that a chemical signal, possibly arising from the skin or the follicle, may be responsible for somatotopic pattern formation in S1. Neurotrophins promote survival and differentiation of primary sensory neurons, and are expressed in the whisker pad during development. Neonatal rats received gelfoam impregnated with NGF, BDNF or NT-3 under the whisker pad following surgical denervation of whisker rows D and E on P0. Barrel formation in S1 was assessed on P7 by acetylcholinesterase histochemistry and 5-HT-immunohistochemistry. BDNF and NT-3, but not NGF, promoted development of the cortical barrels corresponding to denervated whiskers. Furthermore, BDNF and NT-3 prevented the lesion-induced expansion of row C barrels, while NGF appeared to promote row C expansion. Our results suggest that BDNF and NT-3 arising from the whisker pad are involved in the formation and/or maintenance of the barrel pattern in S1. These findings are potentially relevant for the prevention of sensory disturbances possibly due to reorganization of central sensory circuits after peripheral nerve lesions in humans.

Acetylcholinesterase↗
PubMed1998

Cytidine-5'-diphosphocholine improves visual acuity, contrast sensitivity and visually-evoked potentials of amblyopic subjects.

PURPOSE: Cytidine-5'-diphosphocholine (CDP-choline) therapy is currently used to improve the consciousness level in patients with brain lesions and as a complement to levodopa therapy in Parkinson's disease. Recently, the substance has been shown to improve the visual acuity (VA) of both eyes of adults with amblyopia. This study aims at establishing whether Contrast Sensitivity (CS) and visually-evoked potentials (VEPs) also change after CDP-choline treatment. METHODS: VA, CS, and VEPs were measured in a group of amblyopic volunteers (n = 10, mean age 24.8 years) before treatment with Neuroton (CDP-choline, 1 g/day intramuscularly [IM] for 15 days) and the day after termination of the same. CS was evaluated, using a forced-choice, automatic procedure (QUEST: Watson and Pelli, 1983). Steady-state VEPs were recorded in response to counterphased (8 Hz) sinusoidal gratings (2 c/deg) of different contrasts. RESULTS: On average, after treatment, VA improved 1.4-1.5 lines in the amblyopic eyes and 0.4 lines in the normal eyes. CSs improved in both dominant and amblyopic eyes by about 3 dB. VEPs increased in amplitude (about 30%) and advanced in phase (about 0.2 pi rad). Amplitude and phase changes were not correlated. CONCLUSIONS: Treating adult amblyopes with CDP-choline has the effect of improving their VA, CS and VEPs. Changes occur in both eyes, although to different extents, and resemble those previously reported for levodopa treatment.

Adolescent↗
PubMed1998

p21waf1/cip1mda-6 expression in non-small-cell lung cancer: relationship to survival.

In order to clarify critical events during bronchial carcinogenesis, and to evaluate a possible prognostic role for p21 immunohistochemical detection, we assessed the immunohistochemical expression of p21 protein in 60 surgically resected non-small-cell lung cancers (NSCLCs) that had been investigated previously for their p53 protein status. We found that p21 protein was expressed in both normal and neoplastic tissue. In normal tissue, p21 immunoreactivity was detectable in a low percentage of well-differentiated cells. We found immunostaining for p21 in 80% of the investigated neoplasms. In 73.3% of the neoplasms, p21 was considered to be overexpressed. No relationship was found between p21 overexpression and tumor stage or tumor-nodal-metastatic (TNM) status. The histologic grading was slightly correlated with the p21 status (P = -0.51), with no significant differences noted between squamous carcinomas and adenocarcinomas. Survival percentage curves for our lung-cancer patients, based on a comparison of different p21 expression levels and constructed through a Kaplan-Meier analysis, showed significant differences in mean (P < 0.001) and overall (P < 0.001) survival time between patients of different p21 status, suggesting a favorable prognostic value of p21 immunostaining for NSCLC patients.

Adenocarcinoma↗
PubMed1998

Expression of the retinoblastoma-related gene Rb2/p130 correlates with clinical outcome in endometrial cancer.

PURPOSE: The retinoblastoma gene is the prototype of tumor-suppressor genes and has been shown to be involved in the pathogenesis and progression of several human malignancies. In this study, we determined the relation between the expression of a newly discovered retinoblastoma-related gene Rb2/p130 and outcome in patients with endometrial carcinoma. PATIENTS AND METHODS: pRb2/p130 expression was determined immunohistochemically in specimens of endometrial carcinoma (stages I to IV) from 100 patients who underwent surgery as the first treatment. The pRb2/p130 status was analyzed in relation to the length of disease-free survival and disease-specific survival. RESULTS: Decreased levels of pRb2/p130 in endometrial cancer cells was significantly associated with a decreased probability of remaining disease-free after treatment (P = .003) and with decreased probability of survival (P < .0001). In a multivariate analysis, pRb2/p130 status (P = .004), tumor stage (P = .009), and ploidy status (P = .02) were independent predictors of clinical outcome. The risk of dying of disease was increased substantially (risk ratio, 4.91; 95% confidence interval, 1.66 to 14.54) among patients with decreased levels of pRb2/p130 in tumor cells. CONCLUSION: In patients with endometrial carcinoma who did not receive radiotherapy or chemotherapy before surgery, the presence of decreased levels of pRb2/p130 in tumor cells is associated with a significantly increased risk of recurrence and death of disease, independent of tumor stage and ploidy status.

Aged↗
PubMed1997

A unique domain of pRb2/p130 acts as an inhibitor of Cdk2 kinase activity.

The Cdk2 kinase has long been known to be involved in the progression of mammalian cells past the G1 phase restriction point and through DNA replication in the cell cycle. The Rb family of proteins, consisting of pRb, p107, and pRb2/p130, has also been shown to monitor progression of G1 phase, mostly through their interaction with E2F family members. p107 is able to inhibit Cdk2 kinase activity through this interaction via a p21-related domain present in the C terminus of the protein. We show here that pRb2/p130 also possesses this activity, but through a separate domain. Moreover, we correlate the increased expression of pRb2/p130 during various cellular processes with the decreased kinase activity of Cdk2. We hypothesize that pRb2/p130 may act not only to bind and modify E2F activity, but also to inhibit Cdk2 kinase activity in concert with p21 in a manner different from p107.

Animals↗
PubMed1997

Prognostic role of the cyclin-dependent kinase inhibitor p27 in non-small cell lung cancer.

Despite its potential role as a tumor suppressor, p27 gene, a member of the Cip/Kip family of cyclin-dependent kinase inhibitor genes, has never been found mutated in human tumors. We investigated p27 protein expression in a series of 108 non-small cell lung cancers (57.4% stage 1, 16.7% stage 2, and 25.9% stage 3) to determine whether the lack or altered expression of this protein correlates with neoplastic transformation and/or progression. We performed immunohistochemistry and Western blot analysis of each specimen. We found that tumors expressing low to undetectable levels of p27 contained high p27 degradation activity. When we evaluated the outcome of the patients in relationship to p27 expression, we found p27 to be a prognostic factor correlating with the overall survival times (P = 0.0012). The possibility of a simple assay, such as the immunohistochemical analysis of p27 expression on routinely formalin-fixed, paraffin-embedded specimens, has considerable value for the prognosis of patients who undergo surgical resection. In addition, confirmation of the involvement of the proteasome-mediated proteolysis in p27 degradation should stimulate new strategies of nonsurgical treatments of non-small cell lung cancer.

Adenocarcinoma↗
PubMed1997

Enterocyte differentiation is compatible with SV40 large T expression and loss of p53 function in human colonic Caco-2 cells. Status of the pRb1 and pRb2 tumor suppressor gene products.

Transfer of the SV40 large-T (LT) oncogene into isolated human and murine intestinal epithelial cells induced alterations of the ultrastructural organization and polarization of the resulting immortalized cell lines. We now demonstrate that the functional expression of the SV40 LT antigen in Caco-2 cells did not alter phenotypic markers of differentiation, including expression of villin, sucrase-isomaltase, brush border and dome formation. As compared to parental cells, the transfected Caco-2 LT9 cells exhibited similar growth curves and no invasive properties in vitro. The major oncogenic function of the SV40 LT antigen in transfected Caco-2 cells is associated with reduced latency times necessary for the manifestation of tumors in athymic nude mice. The Caco-2 cell line contained deleted and mutant p53 alleles (stop codon in position 204) and has no detectable truncated p53 protein by Western blot. Molecular complexes between the SV40 LT antigen and the retinoblastoma-related proteins pRb1 and Rb2 were clearly identified at the different phases of the growth curve. When compared to normal human colonic crypts, Caco-2 cell differentiation is related to partial redistribution of pRb1 into hypophosphorylated, antiproliferative forms. The pRb2 protein is found elevated in a subset of human colorectal tumors and their corresponding liver metastases. We conclude that: (1) Caco-2 cells exert a dominant control against the oncogenic functions of the LT antigen; (2) loss of p53 function is not restrictive for the establishment of polarity and differentiation of the enterocyte lineage; (3) the levels and phosphorylation status of the Rb1 and Rb2 proteins may play important roles in the proliferation and differentiation of normal and neoplastic human colonic mucosa.

Animals↗
PubMed1997

Differentiating agents modulate topoisomerase I activity in U-937 promonocytic cells.

Phorbol 12-myristate 13-acetate (PMA), N,N'-hexamethylenebisacetamide (HMBA) and retinoic acid induce cell differentiation in U-937 promonocytic cells. This report examines the effects of these agents on DNA topoisomerase I activity. A decrease in enzyme activity could be detected as early as 30 min after treatment with all three differentiating compounds and lasted at least 48 h. No alteration in the levels of DNA topoisomerase I transcript or protein was observed during these treatments. The results might be explained by post-translational events that render DNA topoisomerase type I less active.

Acetamides↗
PubMed1997

Fas-induced changes in cdc2 and cdk2 kinase activity are not sufficient for triggering apoptosis in HUT-78 cells.

Recent evidence suggested a role for the cell cycle dependent kinases cdc2 and cdk2 in apoptosis. An important mechanism by which many cell types could undergo apoptosis is through the activation of the Fas molecule on the cell membrane. To investigate whether Fas-induced cell death activated cdc2 and cdk2 kinases inappropriately, the human T lymphoma cells HUT-78, which express a high copy number of Fas, and two other previously characterized subclones of the same cell line which express mutant, cell death-deficient dominant-negative forms of Fas, were Fas-challenged and the changes in cdc2 and cdk2 kinase activity monitored. In both wild-type and Fas-mutated HUT-78 cells, apoptosis was associated simultaneously with decreased cdc2 and increased cdk2 activity. This association suggested that changes in cdc2 and cdk2 kinase activity are secondary events in cell death mediated by Fas.

Apoptosis↗
PubMed1997

CDC2-related kinase PITALRE phosphorylates pRb exclusively on serine and is widely expressed in human tissues.

Mammalian cell cycle progression is regulated by sequential activation and inactivation of cyclin-dependent kinases (cdks). Recently, several new members of the cdk family were cloned, and some of these were shown to complex with different cyclins and to be active at discrete stages of the cell cycle. PITALRE, a new member of this family, was cloned by our laboratory and was shown to be able to phosphorylate pRb protein in vitro. In the current work, we found that PITALRE kinase activity phosphorylated pRb at sites similar to those phosphorylated by the CDC2 kinase, which itself is known to mimic, in vitro, the in vivo phosphorylation of pRb. Phosphorylation of pRb by the PITALRE-associated kinase activity was on Ser residues exclusively. Moreover, we investigated the expression pattern of PITALRE in normal human tissues, using immunohistochemical techniques so as to gain additional data on the characteristics of this new cdk family member. The protein was widely expressed, although a different tissue distribution and/or level of expression was found in various organs. Some specialized tissues such as blood, lymphoid tissue, ovarian cells, and the endocrine portion of the pancreas showed a high expression level of PITALRE. The specific expression pattern found suggests that PITALRE may be involved in specialized functions in certain cell types.

Antibodies↗