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Biomedical subjects

R Martinelli

Publications and source records attributed to R Martinelli.

At least 37 records · Page 2Linked to original sources
PubMed1999

Cadmium concentrations in the testes, sperm, and spermatids of mice subjected to long-term cadmium chloride exposure.

BACKGROUND: Exposures to cadmium have been reported to reduce male fertility and there are several hypotheses that suggest how reduced male fertility may result from incorporation of cadmium into sperm chromatin. The purpose of this study was to determine whether mice subjected to long-term intraperitoneal cadmium exposure incorporated cadmium into their sperm chromatin. METHODS: Male mice were exposed to 0.1 mg/kg body weight cadmium in the form of CdCl2 via intraperitoneal injection once per week for 4, 10, 26, and 52 weeks and then sacrificed. The cadmium contents of the liver, testes, pooled sperm, and pooled spermatids from dosed and control animals were determined by atomic absorption spectroscopy. Cadmium and zinc contents in individual sperm and spermatid heads were determined by particle-induced x-ray emission. RESULTS: Atomic absorption spectroscopy revealed that although cadmium accumulated in the liver and testes, cadmium was not detected in pooled sperm or spermatid samples down to minimum detectable limits of 0.02 microg/g dry weight. Particle-induced x-ray emission analyses did not show the presence of cadmium in any sperm or spermatid head down to minimum detectable limits of 15 microg/g dry weight. Particle-induced x-ray emission analyses also demonstrated that phosphorus, sulfur, and zinc concentrations in individual sperm and spermatid heads were not altered by exposure to CdCl2. CONCLUSIONS: Because cadmium was not incorporated into sperm chromatin at levels above 0.02 microg/g dry weight, the data cast doubt on hypotheses that suggest that reduced male fertility may result from incorporation of cadmium into sperm chromatin.

Animals↗
PubMed1999

Role of the 75-kDa TNF receptor in TNF-induced activation of neutrophil respiratory burst.

The exclusive role of the 55-kDa TNF receptor (TNF-R55) as the signaling receptor in TNF-induced activation of respiratory burst by human polymorphonuclear leukocytes residing on biologic surfaces has been inferred from results obtained with receptor-specific monoclonal and polyclonal Abs. In this work, we confirm this assumption by a more direct approach, i.e., by using receptor-specific TNF mutants (p55TNF and p75TNF) and, as a novel contribution, we show that cooperation of the 75-kDa TNF receptor (TNF-R75) is required for a full blown response to the cytokine. This conclusion stems from three sets of data: 1) none of the TNF-R55-specific agonists used, i.e., mAbs or p55TNF, induced a respiratory burst comparable with that induced by TNF; 2) selective down-modulation of TNF-R75 resulted in a diminished response to TNF but not to TNF-R55-specific agonists or to the chemotactic peptide FMLP; and 3) mAbs that either block or stabilize binding of TNF to TNF-R75 inhibited the response to the cytokine, suggesting that cooperation requires not only TNF binding to the receptor but also an appropriate dissociability from it. The inhibitory effect of the Abs increased as the cytokine concentrations decreased, indicating that cooperation by TNF-R75 becomes more relevant at low TNF doses. Such a cooperation does not seem to rely on the activation of a TNF-R75-linked signaling pathway independent of TNF-R55, since the response to p55TNF and p75TNF given in combination was not higher than the response to p55TNF alone. The possible mechanisms of cooperation are discussed.

Antigens, CD↗
PubMed1997

Oncogenes belonging to the CSF-1 transduction pathway direct p53 tumor suppressor effects to monocytic differentiation in 32D cells.

Expression of exogenous wt-p53 in different tumor cell lines can induce growth arrest, apoptosis, or differentiation. Several experimental works have highlighted the relevance of cellular context in the determination of p53-mediated final outcomes. We recently observed that these diverse wt-p53 effects can also be induced by overexpressing wt-p53 in a single cell type-the 32D myeloid progenitors-transformed with different activated oncogenes. Here we show that 32D cells transformed with two different oncogenes, v-src or c-fms [S301,F969], both belonging to the CSF-1 transduction pathway, respond to exogenous wt-p53 expression with the same final outcome-monocytic differentiation. This result is particularly significant since 32D cells do not spontaneously express the CSF-1 receptor, whereas they undergo granulocytic differentiation upon G-CSF stimulation. These data strongly support the idea that wt-p53 suppressing effects result from interactions between p53 activity and the signaling pathways activated in different transformed cells.

Cell Differentiation↗
PubMed1997

[The application of the multileaf collimator in radiotherapy: the dosimetric problems and the technical implications for its clinical use].

INTRODUCTION: The multileaf collimator (MLC) now commercially available as an integral or optional retrofit component of linear accelerator heads, permitting to shield automatically irregular fields by computerized movements of multiple tungsten leaves. In the present paper we discuss the main characteristics of different MLC versions, MLC dosimetric drawbacks and the clinical fields where the MLC could he widely used. MATERIALS AND METHODS: Since February, 1995, we have studied the dosimetric characteristics and clinical implications of a multileaf collimator of a Clinac 2100 C/D linear accelerator used to replace conventional low melting alloy blocks. The scalloping effect of isodoses and the effective penumbra produced by the multileaf collimator in an irregular field were analyzed accurately. Secondly, radiation leakage through tungsten leaves was measured and compared with the values of low melting alloy blocks. Finally, the MLC was extensively used in clinical practice for the radiotherapy of different tumors. RESULTS: Different dosimetric steps were followed to obtain the monitor units/dose ratio. Our single MLC-shielded irregular fields measurements also showed several physical and dosimetric disadvantages related to wider effective penumbra than with conventional shielding when the angle between field margin and the normal to the direction of leaf travel is 45 degrees. In clinical practice, the MLC can be widely used for the conformal radiotherapy of pelvic and thoracic tumors. Conventional low melting alloy blocks should be replaced with MLC for radiotherapy of selected brain and head and neck cancers. DISCUSSION: The current use of a multileaf collimator improves both the accuracy and the effectiveness of radiation therapy and reduces the time for every treatment dose, which potentially increases the number of patients treated every day. The multileaf collimator is presently an important technical tool either to replace conventional shielding for static conformational radiotherapy or to administer 3D-planned dynamic radiotherapy.

Equipment Design↗
PubMed1996

Removal of Cr(VI) from ground water by Saccharomyces cerevisiae.

Chromium can be removed from ground water by the unicellular yeast, Saccharomyces cerevisiae. Local ground water maintains chromium as CrO42- because of bicarbonate buffering and pH and Eh conditions (8.2 and +343 mV, respectively). In laboratory studies, we used commercially available, nonpathogenic S. cerevisiae to remove hexavalent chromium [Cr(VI)] from ground water. The influence of parameters such as temperature, pH, and glucose concentration on Cr(VI) removal by yeast were also examined. S. cerevisiae removed Cr(VI) under aerobic and anaerobic conditions, with a slightly greater rate occurring under anaerobic conditions. Our kinetic studies reveal a reaction rate (Vmax) of 0.227 mg h-1 (g dry wt biomass)-1 and a Michaelis constant (Km) of 145 mg/l in natural ground water using mature S. cerevisiae cultures. We found a rapid (within 2 minutes) initial removal of Cr(VI) with freshly hydrated cells [55-67 mg h-1 (g dry wt biomass)-1] followed by a much slower uptake [0.6-1.1 mg h-1 (g dry wt biomass)-1] that diminished with time. A materials-balance for a batch reactor over 24 hours resulted in an overall shift in redox potential from +321 to +90 mV, an increase in the bicarbonate concentration (150-3400 mg/l) and a decrease in the Cr(VI) concentration in the effluent (1.9-0 mg/l).

Aerobiosis↗
PubMed1996

Wild-type p53 induces diverse effects in 32D cells expressing different oncogenes.

Expression of exogenous wild-type (wt) p53 in different leukemia cell lines can induce growth arrest, apoptotic cell death, or cell differentiation. The hematopoietic cell lines that have been used so far to study wt p53 functions have in common the characteristic of not expressing endogenous p53. However, the mechanisms involved in the transformation of these cells are different, and the cells are at different stages of tumor progression. It can be postulated that each type of neoplastic cell offers a particular environment in which p53 might generate different effects. To test this hypothesis, we introduced individual oncogenes into untransformed, interleukin-3 (IL-3)-dependent myeloid precursor 32D cells to have a single transforming agent at a time. The effects induced by wt p53 overexpression were subsequently evaluated in each oncogene-expressing 32D derivative. We found that in not fully transformed, v-ras-expressing 32D cells, as already shown for the parental 32D cells, overexpression of the wt p53 gene caused no phenotypic changes and no reduction of the proliferative rate as long as the cells were maintained in their normal culture conditions (presence of IL-3 and serum). An accelerated rate of apoptosis was observed after IL-3 withdrawal. In contrast, in transformed, IL-3-independent 32D cells, wt p53 overexpression induced different effects. The v-abl-transformed cells manifested a reduction in growth rate, while the v-src-transformed cells underwent monocytic differentiation. These results show that the phenotype effects of wt p53 action(s) can vary as a function of the cellular environment.

Animals↗
PubMed1996

Clinical effects of intermittent, intravenous cyclophosphamide in severe systemic lupus erythematosus.

To evaluate the clinical effectiveness of intermittent intravenous cyclophosphamide in the treatment of severe systemic lupus erythematosus, 20 patients with systemic lupus erythematosus (SLE) and evidence of severe renal involvement or systemic vasculitis, consecutively admitted to the hospital were studied. Cyclophosphamide was administered intravenously at a dosage of 1.0 g/m2 monthly, during 6 months and maintained every 3 months during 12 additional months. Of 10 patients with active lupus nephritis, a reduction or disappearance of proteinuria and maintenance of normal renal function was recorded in 6. Improvement of renal function was observed in 4 out of 7 patients with renal insufficiency at initial evaluation; resolution of renal insufficiency was more frequently observed in patients with recent onset renal failure. At the end of the follow-up (18.0 +/- 14.5 months) disappearance or reduction of nephrotic range proteinuria was recorded in 6 out of 14 patients; there was progression toward renal failure in 4 patients (20%). Response to intravenous cyclophosphamide therapy was observed in 4 of 5 patients with severe extrarenal SLE. Side effects, recorded in 12 patients, were mild and transient and in no patient was the treatment discontinued. Four patients died during the follow-up, although in 2 of them the deaths were not attributable to therapy. Even though this was an open and uncontrolled study, intermittent, intravenous cyclophosphamide was an effective therapy for severe, steroid refractory SLE.

Adolescent↗
PubMed1995

Clinical course of focal segmental glomerulosclerosis associated with hepatosplenic schistosomiasis mansoni.

To analyze the clinical course and response to therapy 15 patients (9 male and 6 female) with the hepatosplenic form of schistosomiasis mansoni and focal segmental glomerulosclerosis (FSGS) were prospectively studied (mean follow-up = 115.8 +/- 93.2 months). Nephrotic syndrome was the most frequent clinical presentation, followed by abnormalities of urinalysis. The clinical course was progressive: at final evaluation 9 patients (60%) had developed renal failure. Hypertension or/and renal insufficiency at initial evaluation and persistence of the nephrotic syndrome were associated with progression toward advanced renal failure. Response to immunosuppressive therapy was recorded in 30% of the patients; all responsive patients still had normal renal function at final evaluation. The treatment of the Schistosoma mansoni infection did not influence the clinical course of the renal disease. It is concluded that FSGS in patients with hepatosplenic schistosomiasis mansoni is a disease progressing to advanced stage independently of the presence of the parasite.

Adolescent↗
PubMed1994

H1TF2A, the large subunit of a heterodimeric, glutamine-rich CCAAT-binding transcription factor involved in histone H1 cell cycle regulation.

H1TF2 is a CCAAT transcription factor that binds to the histone H1 subtype-specific consensus sequence, which has previously been shown to be necessary for temporal regulation of histone H1 transcription during the cell cycle (F. La Bella, P. Gallinari, J. McKinney, and N. Heintz, Genes Dev. 3:1982-1990, 1989). In this study, we report that H1TF2 is a heteromeric CCAAT-binding protein composed of two polypeptide doublets of 33 and 34 kDa and 43 and 44 kDa that are not antigenically related. The 33- and 34-kDa species were not detected in our previous studies (P. Gallinari, F. La Bella, and N. Heintz, Mol. Cell. Biol. 9:1566-1575, 1989) because of technical problems in detection of these heavily glycosylated subunits. The cloning of H1TF2A, the large subunit of this factor, reveals it to be a glutamine-rich protein with extremely limited similarity to previously cloned CCAAT-binding proteins. A monospecific antiserum produced against bacterially synthesized H1TF2A was used to establish that HeLa cell H1TF2A is phosphorylated in vivo and that, in contrast to the H2b transcription factor Oct1 (S. B. Roberts, N. Segil, and N. Heintz, Science 253:1022-1026, 1991; N. Segil, S. B. Roberts, and N. Heintz, Cold Spring Harbor Symp. Quant. Biol. 56:285-292, 1991), no gross change in H1TF2A phosphorylation is evident during the cell cycle. Further immunoprecipitation studies demonstrated that H1TF2 is heterodimeric in the absence of DNA in vivo and identified several H1TF2-interacting proteins that may play a role in H1TF2 function in vivo.

Amino Acid Sequence↗
PubMed1989

Human glyceraldehyde-3-phosphate dehydrogenase pseudogenes: molecular evolution and a possible mechanism for amplification.

We screened two human genomic libraries and isolated 14 different clones, designated lambda G1 and EG1-EG13, homologous to human glyceraldehyde-3-phosphate dehydrogenase (GAPD) cDNA. Subcloning and sequencing these recombinant phages led us to classify them as five different pseudogenes (psi G1-psi G5). All these sequences show such features typical of processed pseudogenes as numerous mutations, insertions, and deletions. The identity of numerous mutated sites among these pseudogenes and the presence of two Alu sequences flanking both ends of psi G1 suggest that GAPD pseudogenes originated from a unique reverse transcribed mRNA followed by gene duplication. The rate of nucleotide substitutions per site per year for known GAPD functional genes is low both for the synonymous substitutions (1.87 x 10(-9] and for the nonsynonymous substitutions (0.12 x 10(-9] and indicates that the GAPD cDNA sequence is well conserved not only at the amino acid level, but also at the nucleotide level. The rate of nucleotide substitutions per site per year for GAPD pseudogenes shows a higher value (5.9 x 10(-9] and suggests that these pseudogenes do not have any functional role.

Base Sequence↗
PubMed1989

Schistosoma mansoni-induced mesangiocapillary glomerulonephritis: influence of therapy.

Schistosomiasis mansoni has been well documented as one of the causes of infectious glomerulopathy, with mesangiocapillary glomerulonephritis being the most frequent lesion observed in this condition. Twenty-one patients with hepatosplenic schistosomiasis mansoni and biopsy-documented mesangiocapillary glomerulonephritis (MCGN) were studied and compared with 19 patients with the idiopathic form of MCGN. Nephrotic syndrome was the most frequent clinical presentation in both groups. At the time of diagnosis nine patients with hepatosplenomegaly (4 with associated arterial hypertension) and 12 (8 with arterial hypertension) among the patients with idiopathic MCGN had renal insufficiency. At the end of the follow-up period 16 patients with hepatosplenic schistosomiasis and MCGN (75.2 months) and 15 with the idiopathic form (52.1 months) had renal failure. Also, when compared at 48 months of follow-up, no difference in renal function could be detected in both groups. No benefits related to anti-parasitic treatment in the schistosomiasis group and immunosuppression therapy in either group could be documented. The progression of the renal disease, as assessed by the reciprocal of serum creatinine versus time, and the survival curve, were not different between the two groups. It is concluded that MCGN in patients with the hepatosplenic form of schistosomiasis mansoni is a progressive disease not influenced by anti-parasitic or immunosuppressive therapy, and presents a clinical course similar to that of the idiopathic form.

Adult↗
PubMed1989

[Radiotherapy of seminoma in the 2d stage].

The radiotherapy of seminoma in second stage, i.e. with lumbo-aortic lymph nodes metastases, is debated. Some authors restrict the radiation therapy to under-diaphragmatic lymph nodes, with saving chemotherapy by platinum, only in relapses; for others, the radiotherapy is eligible for all, under and over-diaphragmatic lymph nodes. The author analyzed 30 patients with seminoma, 26 in state IIA and 4 in stage IIB; all patients was treated with extended irradiation. The total survival was 96%. There is not long-term radiation injury. With regards to this results, the author think that the extended radiotherapy still represent the first treatment to patients with seminoma in stage II, in consideration of potential damage of chemotherapy, and percentage of 20/25% relapses over the diaphragm.

Cobalt Radioisotopes↗
PubMed1987

The influence of anti-parasitic therapy on the course of the glomerulopathy associated with Schistosomiasis mansoni.

Although several aspects of the association between S. mansoni infection and renal disease are well known, the influence of the anti-parasitic therapy on the clinical course of the glomerulopathy remains undefined. With the aim of studying this aspect, 16 patients with glomerulopathy associated with schistosomiasis mansoni were evaluated (proteinuria and levels of BUN and creatinine) before therapy, 1 week, 1 month, 2-3 months and 6 months after therapy of the parasitic infections. During the follow-up of such cases no benefit could unquestionably be demonstrated in the patients. Also, no permanent deterioration of renal function related to anti-parasitic therapy could be documented. It is concluded that the treatment of the S. mansoni infection, once the consequent glomerulopathy is clinically apparent, does not influence the clinical course of the disease.

Humans↗
PubMed1986

Imidazole has similar behavioural effects to yohimbine.

A number of animal behavioural models were used to study the activity of imidazole (IMID) on the central nervous system. IMID antagonized in a dose-related fashion penile erections (PE) as well as stretching and yawning (SY) elicited in male rats by B-HT 920, an alpha 2 and dopamine (DA) autoreceptor agonist. Inhibition of B-HT 920-induced PE and SY was also exhibited by haloperidol, a DA receptor blocker, and yohimbine, but not by prazosin, alpha 2 and alpha 1 receptor antagonists respectively. Moreover IMID behaved similarly to yohimbine in: 1) counteracting clonidine-induced hypothermia in mice; 2) antagonizing sedation and sleep induced by clonidine and B-HT 920 in chicks, while haloperidol was ineffective. When administered to sexually active rats before the copulatory test, IMID at low doses, significantly altered some aspects of mating, a result which is interpretable in terms of enhanced sexual arousal and resembling the aphrodisiac effect reported for yohimbine. The neurochemical mechanisms involved in these effects are discussed.

Adrenergic alpha-Agonists↗
PubMed1985

Renal involvement in visceral leishmaniasis.

In a prospective study of 50 patients with visceral leishmaniasis, laboratory abnormalities suggestive of renal involvement were not infrequent. Proteinuria and/or microscopic hematuria or pyuria were observed in 51% of such cases. Twenty-four hour urinary protein excretion was elevated in 57% of patients in all cases below 1g/24 hours. An abnormal acid-load test was demonstrated in 12 of 18 patients studied before therapy of the parasitic infection with N-methyl-glucamine. Of interest was the demonstration of tubulo-interstitial involvement in the renal histology of all seven patients studied; also, in five of seven patients there was a proliferative glomerulonephritis, usually mild, on histologic examination. In general, there was a tendency to subsidence of abnormal laboratory findings within one month after specific therapy. Renal involvement in visceral leishmaniasis was mild and seemed to revert with the cure of the leishmanial infection.

Adolescent↗
PubMed1984

The complete sequence of a full length cDNA for human liver glyceraldehyde-3-phosphate dehydrogenase: evidence for multiple mRNA species.

A recombinant M13 clone (O42) containing a 65 b.p. cDNA fragment from human fetal liver mRNA coding for glyceraldehyde-3-phosphate dehydrogenase has been identified and it has been used to isolate from a full-length human adult liver cDNA library a recombinant clone, pG1, which has been subcloned in M13 phage and completely sequenced with the chain terminator method. Besides the coding region of 1008 b.p., the cDNA sequence includes 60 nucleotides at the 5'-end and 204 nucleotides at the 3'-end up to the polyA tail. Hybridization of pG1 to human liver total RNA shows only one band about the size of pG1 cDNA. A much stronger hybridization signal was observed using RNA derived from human hepatocarcinoma and kidney carcinoma cell lines. Sequence homology between clone 042 and the homologous region of clone pG1 is 86%. On the other hand, homology among the translated sequences and the known human muscle protein sequence ranges between 77 and 90%; these data demonstrate the existence of more than one gene coding for G3PD. Southern blot of human DNA, digested with several restriction enzymes, also indicate that several homologous sequences are present in the human genome.

Adult↗
PubMed1984

In vitro activity of six beta-lactam antibiotics against non-beta-lactamase producing and producing enterobacteria and antibiotic resistance transfer.

beta-Lactamase production was evaluated by chromogenic cephalosporin 87/312 in 184 enterobacteria isolated from clinical sources. Minimal inhibitory concentrations (MICs) of six beta-lactam antibiotics (Ampicillin, Cephaloridine, Cephalexine, Cefazoline, Cefuroxime, Cefotaxime) were determined on 90 non beta-lactamase producing and 94 beta-lactamase producing strains by a miniaturized dilution method. beta-lactamase production transfer and antibiotic resistance transfer were observed in a receiving E. coli K12 C600 NA- after conjugation with 94 producing strains. Cefotaxime showed high antibacterial activity both against beta-lactamase producing and non producing bacteria. Cefuroxime, Cephalexine and Cefazoline were active only against high percentage of non beta-lactamase producing bacteria. Ampicillin and Cephaloridine showed low antibacterial activity both against producing and non producing bacteria. About 19% (18/94) of beta-lactamase producing bacteria transferred beta-lactamase producing capacity to E. coli K12 by conjugation and a significant increase of MICs of each antibiotic, except that of Cefotaxime, was observed in E. coli K12 that acquired capacity to produce beta-lactamase by conjugation. Resistant strains that produce beta-lactamase transfer antibiotic resistance by conjugation to E. coli in variable percentages to the antibiotics under examination. Antibiotic resistance to Ampicillin, Cephaloridine, Cephalexine and Cefazolin observed in receiving strains after conjugation is not only due to beta-lactamase transfer. All strains acquiring Cefuroxime and Cefotaxime resistance never acquire beta-lactamase producing capacity.

Anti-Bacterial Agents↗