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Biomedical subjects

R Rossi

Publications and source records attributed to R Rossi.

At least 307 records · Page 17Linked to original sources
PubMed1993

Involvement of proliferating cell nuclear antigen in DNA repair after damage induced by genotoxic agents in human fibroblasts.

The association of the proliferating cell nuclear antigen (PCNA) to DNA synthesis sites during the process of DNA repair, was investigated in human diploid fibroblasts after treatment with different genotoxic agents. For this purpose, confluent cultures were treated with agents that form primarily DNA adducts, such as u.v.-C, 8-methoxypsoralen (8-MOP) and 4,4',6-trimethylangelicin (TMA), or with agents that induce strand breaks, such as X-rays or bleomycin (BLM). Chromatin-associated PCNA was detected with a monoclonal antibody and indirect immunofluorescence labelling. Quantitative analysis was performed by flow cytometry. Not all of the tested agents were able to activate the association of PCNA with chromatin. X-rays, u.v.-C and BLM induced a significant increase in PCNA complex as compared to the control samples. In contrast, 8-MOP and TMA did not show any detectable effect on the levels of associated PCNA, even at post-incubation repair times as long as 10 h. However, these drugs damaged DNA, as shown by the formation of micronucleated cells 48 h after treatment. The lack of PCNA activation was not due to an inhibition of the repair mechanism, since in TMA-treated fibroblasts, subsequent irradiation with u.v.-C induced an increase in PCNA levels comparable to that found in cells treated with u.v.-C alone. These results indicate that PCNA is involved in DNA excision repair of genotoxic agents, but suggest that similar types of lesions may be repaired with alternative pathways not requiring PCNA.

Bleomycin↗
PubMed1993

Remission of subclinical adrenocortical failure in subjects with adrenal autoantibodies.

Idiopathic Addison's disease is a chronic organ-specific autoimmune disorder with a long subclinical period characterized only by the presence of adrenal autoantibodies (AA) with or without adrenal function failure. The aim of this longitudinal study was to evaluate the behavior of AA using, an indirect fluorescence method, and adrenal function in 20 AA-positive and 50 AA-negative patients screened by an investigation of a large population of organ-specific autoimmune disease patients without clinical Addison's disease. As controls, 100 normal age-matched subjects were tested only once. In the 20 AA-positive and 50 negative patients, AA and adrenal functional tests were evaluated every 4 months for 5 yr. The AA-positive patients were grouped into 5 adrenal functional stages, specifically: stage 0, normal adrenal function; stage 1, high PRA and low (or normal) aldosterone levels alone; stage 2, along with impaired cortisol response to ACTH, stage 3, along with increased ACTH levels; and stage 4, clinically overt Addison's disease. On the basis of the behavior of AA, the 20 positive patients were grouped as follows: group A, 11 patients with AA titer of 1:8 or higher at the first observation and persistently AA positive in subsequent observations, with titers ranging from 1:8 to 1:64; group B, 6 patients with initial AA titers of 1:8 or lower and AA disappearance in subsequent observations; and group C, 3 patients with AA titer of 1:32 or higher, undergoing corticosteroid therapy after the start of the study and showing AA disappearance in subsequent observations. With respect to adrenal function in group A, 2 patients initially in stage 1 and 1 patient initially in stage 2 did not progress to the upper stages, whereas 5 patients initially in stage 0 and 3 initially in stage 1 progressed subsequently to the upper stages, in 2 cases reaching overt clinical Addison's disease (stage 4). On the other hand, all of the patients of group B showed both a spontaneous disappearance of AA and recovery of adrenal function during the study span. Also, the 3 patients of group C showed disappearance of AA after corticosteroid therapy with recovery of adrenal function. None of the 50 patients who were initially AA negative became AA positive subsequently or showed impairment of adrenal function. We reached the following conclusions. 1) AA, even if present initially in some subjects without clinical Addison's disease, can subsequently disappear. 2) Restoration of adrenal function after disappearance of AA indicates that a spontaneous remission of subclinical adrenocortical failure can occur.(ABSTRACT TRUNCATED AT 400 WORDS)

Addison Disease↗
PubMed1993

Modulatory effect of the renin-angiotensin system on the plasma levels of calcitonin gene-related peptide in normal man.

Calcitonin gene-related peptide (CGRP) has positive chronotropic and inotropic effects in animals and humans, and produces the most potent vasodilation known for an endogenous peptide. Yet, a physiological role for CGRP in the regulation of vascular tone and blood pressure has not been demonstrated. We studied the effects of 1) assumption of the upright position and 2) iv infusion of angiotensin-II (sequential doses of 8, 16, and 32 ng/kg.min, each dose for 20 min) in eight normal subjects (four men). Serial venous blood samples were taken to determine the plasma CGRP, epinephrine, norepinephrine, and aldosterone levels and PRA. Blood pressure and heart rate were continuously monitored at the finger with a Finapres 2300 instrument. After assumption of the upright posture, a quick rise in plasma CGRP levels was observed together with the expected increases in plasma norepinephrine and aldosterone and PRA. A transient increment was also observed for diastolic blood pressure and heart rate. Angiotensin-II infusion caused dose-dependent increases in plasma CGRP and aldosterone concentrations, already significant at the lowest infusion rate and parallel with the blood pressure rise. Plasma catecholamines significantly increased only at higher infusion rates. Our data demonstrate that modifications of plasma CGRP concentrations are part of the normal response to postural and vasomotor changes. These findings suggest a physiological role for CGRP in regulation of the peripheral vascular tone and possibly blood pressure in man.

Adult↗
PubMed1993

Detection of androgen receptor (AR) mRNA by the reverse transcription polymerase chain reaction (RT-PCR) in human thyroids.

In order to demonstrate that Androgen binding activity in thyroid is caused by the canonic Androgen Receptor (AR), member of steroid receptor family, we studied the presence of AR mRNA in human thyroid tissues and primary cultured cells. Here we report a polymerase chain reaction protocol (RT-PCR) that we have designated to investigate the presence of AR mRNA in human cells. AR cDNA was synthesized and amplified with primers specific for C-terminal sequence of the protein. We demonstrated that AR gene expression i) is present in thyroid samples studied and ii) in a primary culture of follicular adenoma where it seems to be modulated by steroid hormones.

Adenoma↗
PubMed1993

[Ifosfamide-induced nephrotoxicity].

BACKGROUND: A number of acquired De-Toni-Debre-Fanconi-Syndromes have been reported after cytostatic treatment with Ifosfamide. For the majority of these patients prognosis of renal function was poor. In our study we evaluated the frequency of subclinical tubulopathies, the influence of the cumulative Ifosfamide dose and other risk factors and the prognosis of once established tubular dysfunction. METHODS: 79 patients after polychemotherapy regimens employing Ifosfamide (n = 39), Ifosfamide plus Cisplatinum (n = 35) or Cisplatinum (n = 5) were examined at least 3 months after completion of therapy. Beside the creatinine-clearance we evaluated glomerular and tubular function by measurement of transferrin, immunoglobuline G, Alpha-1-microglobuline and N-Acetyl-beta-D-Glucosamidaseexcretion and by tubular reabsorption of phosphate and aminoacids. RESULTS: Renal hyperaminoaciduria was found most often, and there was no linear correlation between the cumulative Ifosfamide-dose and phosphate reabsorption. A reduced glomerular filtration rate and glomerular proteinuria were found in about 10.5% of patients. Approximately half of the patients had tubular dysfunction. Impairment of phosphate reabsorption once established did not normalize in the majority of patients. Cisplatinum was found to worsen the Ifosfamide-induced tubulopathy. CONCLUSION: Our results indicate subclinical tubulopathy after Ifosfamide in a high proportion of patients. This Ifosfamide induced nephrotoxicity is worsened by Cisplatinum and seems to be irreversible for the majority of patients. To describe and to prevent Ifosfamide-induced nephrotoxicity, further studies should focus on: 1. the identification of the risk-groups/patients and additional risk factors, 2. the estimation of the prognosis of once established renal damage, 3. the clarification of the pathomechanism.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

[Liver injury in abdominal trauma. Review of the literature and personal observations].

In patients who suffered abdominal trauma, the liver is the most frequently involved organ, except the spleen. The % rises from 1520% to 30% if trauma is closed or open. Liver injury may spread from a simple parenchymal contusion to a break in vessels or biliary ducts. Life risk is related to hemorrhage. The mortality is due to: 1) extension of the injured liver surface, 2) possible damage to big vessels, 3) intra or extra abdominal associated injury in case of multiple trauma. It is important to known the kind of injury to choose the best therapy, not necessary surgical. The authors report on 15 patients with thoracoabdominal trauma and liver damage, comparing their cases with literature observations.

Abdominal Injuries↗
PubMed1993

[Ultrasonographic changes in the abdominal organs in the 10th decade of life].

10 patients in perfect health, aged between 90 and 101 (mean age: 93 +/- 3), have been studied with echography in order to investigate the possible changes in volume and echo-pattern of abdominal organs, linked to the "physiological" aging. Our resulting data (reduced volume of liver and kidneys, changes in echo-pattern of pancreatic parenchyma, reduced thickness of renal cortical-medullary) seem to confirm the well known data of an atrophic change interesting the parenchyma of abdominal organs in aging: this latter, however, remains compatible with function preservation.

Abdomen↗
PubMed1992

Detection of mycoplasma contamination through modulation (stimulation or inhibition) of thymidine incorporation by unstimulated mouse spleen cells.

In the present report we describe a rapid and sensitive assay for mycoplasma detection in cell cultures. The assay is based on the ability of contaminated culture supernatants to modulate [3H]TdR incorporation by unstimulated mouse splenocytes. Several mycoplasma species (Mycoplasma orale, culturable and non-culturable strains of Mycoplasma hyorhinis) inhibited [3H]TdR incorporation and permitted the detection of some contaminated cell cultures that would otherwise have escaped detection in assays measuring [3H]TdR incorporation by mitogen-stimulated splenocytes. On the other hand, several other mycoplasma species (Mycoplasma arginini, Mycoplasma hominis) strongly enhanced [3H]TdR incorporation by unstimulated splenocytes. This enhancement was optimally detectable on day 2 after initiation of the cultures. The sensitivity of the assay was determined for a mycoplasma species (culturable M. hyorhinis) that inhibited as well as for one (M. arginini) that enhanced [3H]TdR incorporation. In both cases, the sensitivity was such that 1-3 x 10(2) mycoplasma colony-forming units (CFU) could be detected.

Animals↗
PubMed1992

Monitoring of somatosensory evoked potentials during carotid endarterectomy.

Somatosensory evoked potentials (SEPs) were monitored in the course of 368 carotid endarterectomies (CEAs) carried out in 312 patients. In an initial group of 26 patients the shunt was used routinely while in a second group, involving 342 CEAs, it was applied selectively on the basis of modifications which the SEP underwent during clamping. The criterion for shunting was the progressive reduction, up to 50%, of the N20-P25 amplitude. New postoperative neurological deficits appeared in 6 patients, all of whom displayed a transitory SEP flattening. The SEPs of 2 of these returned to normal by the time they awoke and both showed a clinical deficit homolateral to the operated side. In only 2 cases did the deficit fail to regress completely and their postoperative CT scans revealed ischaemic lesions. A positive relationship emerged between SEP changes and back pressure values; nonetheless, as many as 75% of the patients with low residual back pressure values (less than 25 mmHg) tolerated the clamping. SEP monitoring appears to provide a reliable basis for selectively applying a shunt when there is a high risk of haemodynamic ischaemia during clamping.

Adult↗
PubMed1992

Tubular function and histological findings in ifosfamide-induced renal Fanconi syndrome--a report of two cases.

Two patients developed renal Fanconi syndrome (RFS) after intensive long-term chemotherapy for metastatic Ewing sarcoma and disseminated neuroblastoma. Whereas RFS was diagnosed in patient 1 before he developed osteomalacia, patient 2 experienced severe rickets and growth retardation. Renal function studies revealed slight glomerular impairment and severe tubular defects leading to increased excretion of glucose, amino acids, inorganic phosphate and low molecular weight proteins, indicating proximal tubular damage. Patient 2 additionally showed distal tubular dysfunction with acidosis and diminished concentrating capacity. Renal biopsy in patient 1 revealed marked proximal tubular defects without interstitial lymphocytic infiltration. In both patients renal damage could most likely be ascribed to previous ifosfamide (IFOS) therapy. Our patients showed no improvement in renal function after cessation of IFOS treatment, indicating a poor prognosis of once established RFS after IFOS therapy. Measurement of tubular reabsorption capacities provides exact information on the extent of tubular toxicity induced by IFOS and may be used to monitor IFOS treated patients.

Adolescent↗
PubMed1992

Hormonal and immunological pattern in a patient with acquired immunodeficiency syndrome related complex and Cushing's syndrome.

A case of Cushing's syndrome in a 24-yr-old homosexual with an AIDS-related complex is reported. In this patient certain symptoms common to both diseases, i.e. weakness, myalgia and muscle atrophy were accentuated, whereas other symptoms pathognomic of the human immunodeficiency virus (HIV) infection, i.e. lymphoadenopathies and weight loss, were less pronounced by the high levels of circulating adrenal steroids. Ketoconazole was administered po in order to block adrenal steroidogenesis, the drug caused a remarkable fall of cortisol serum concentrations, but was unable to modify significantly the immunological pattern of the patient. Our data suggest that changes of serum adrenal steroid levels have little effect on the immune network of patients with AIDS.

AIDS-Related Complex↗
PubMed1992

Cardiomyoplasty does not preclude heart transplantation.

Stimulated skeletal muscle grafts have been proposed to improve left ventricle function in patients with severe myocardial failure. In 1 particular case reported here, however, the postoperative functional improvement was only transient and disabling heart failure recurred after 9 months in spite of a vigorous latissimus muscle contraction. Heart transplantation was proposed to this patient and performed successfully. Technically, the key to heart removal depends on the retrograde dissection of the ventricular cavities, starting from the right atrioventricular groove. The intraoperative observations confirmed the viability of the latissimus dorsi muscle, inefficient on a highly dilated cardiomyopathy. Histopathological examination of the latissimus dorsi muscles showed that the transformation process of the stimulated muscle was good. Thus, severe cardiac dilatation seems to be one of the limitations of cardiomyoplasty. Cardiomyoplasty, when it fails, does not preclude heart transplantation. The histochemical studies confirm the electrophysiologic principle of cardiomyoplasty in humans.

Assisted Circulation↗
PubMed1992

In vivo modulation of lymphokine-activated killer cell activity by cell wall components of Candida albicans.

We have previously reported that inoculating CD2F1 mice intraperitoneally with five doses of 2 x 10(7) inactivated Candida albicans (CA) cells was associated with the induction of lymphokine-activated killer (LAK)-like effectors. In this study we investigated the ability of some purified cell wall components of CA (CA-CW) to induce LAK-like cells in vivo. Multiple administrations of glucan ghost (GG), a mannoprotein mixture (MP) and a low-protein mannan fraction (M) at variance with whole CA did not induce LAK-like cells in the peritoneal cavity. However, the broad-spectrum antitumor cytotoxicity induced by CA could be recalled to a high level by a booster dose of MP and M, but not GG, given up to 70 days after the multiple CA-treatment. This induced cytotoxicity was maximum when the booster was given on Day +14 after CA-treatment and minimum on Day +70. In CA-treated mice, inoculated on Day +30 with CA or MP, LAK-like cytotoxicity was already significantly increased 4 hr after the booster, but the maximum value was reached at 24 hr. Anti-mannan antibodies did not interfere with LAK-like cells induction by CA because splenectomy before CA-treatment or passive administration of anti-mannan antibodies had no effect on the rapid activation of cytotoxicity by CA or a booster dose of MP. Administration of recombinant human interleukin-2 (rhIL-2) to CA-treated mice induced a higher level of NK activity than that induced by the same dose in untreated control mice, but did not activate LAK-like effectors. The results indicate that LAK-like effectors are easily generated in the peritoneal cavity by a booster with a defined antigenic constituent of CA cell wall for a long period in CA-sensitized mice.

Animals↗
PubMed1992

Pregnancy modulates the expression of beta-N-acetylhexosaminidase in rat serum and tissues.

1. beta-N-Acetylhexosaminidases in maternal rat serum were separated by DEAE-cellulose chromatography and compared with those of adult rat serum. 2. In pregnant serum there is an increase of the isoenzymes which are entirely composed of beta-subunits (B and intermediate forms). 3. These alterations could be compared to those already described in human pregnancy. 4. The levels of beta-N-acetylhexosaminidase and the relative expression of alpha- and beta-subunits in normal and pregnant serum correlate with the above isoenzyme expression. 5. The increase of B and intermediate forms as well as the increase of specific activity during pregnancy was not peculiar to maternal serum but was also demonstrated in several foetal tissues and in maternal tissues, in which cases the beta-N-acetylhexosaminidase isoenzyme patterns closely resemble the foetal ones rather than those of the adult rat tissues. 6. These analogies strongly suggest that the expression of beta-subunit of beta-N-acetylhexosaminidase is regulated by hormones or other factors related to pregnancy.

Animals↗