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Biomedical subjects

G Villani

Publications and source records attributed to G Villani.

At least 91 records · Page 5Linked to original sources
PubMed1980

The Cohen syndrome: clinical and endocrinological studies of two new cases.

This report concerns two new cases of the Cohen syndrome and gives further information on the variable phenotypical pattern of the disease. The frequency of major and minor clinical signs is reviewed from all the published reports. Among the minor signs we found previously undescribed skeletal abnormalities in one of our patients. The reported delay onset of puberty, which appears to be a frequent aspect of the syndrome, seems to occur without LH and FSH deficiency, as our patients show.

Adolescent↗
PubMed1980

[Mental retardation and sexual development in chromosomal syndrome (author's transl)].

Mental retardation and natural sexual development appear to be a more consistent feature in the autosomal rather than in the sex chromosome anomalies. On the contrary the anatomical and functional sexual disfunction characterize the sex chromosome syndromes. An early diagnosis and a better knowledge of the chromosomal abnormalities are important for the social integration and the control of the sexual development and behaviour of this patients.

Adolescent↗
PubMed1978

Mechanism of ultraviolet-induced mutagenesis: extent and fidelity of in vitro DNA synthesis on irradiated templates.

The effect of UV irradiation on the extent and fidelity of DNA synthesis in vitro was studied by using homopolymers and primed single-stranded varphiX174 phage DNA as substrates. Unfractionated and fractionated cell-free extracts from Escherichia coli pol(+) and polA1 mutants as well as purified DNA polymerase I were used as sources of enzymatic activity. (DNA polymerases, as used here, refer to deoxynucleosidetriphosphate:DNA deoxynucleotidyltransferase, EC 2.7.7.7.) The extent of inhibition of DNA synthesis on UV-irradiated varphiX174 DNA suggested that pyrimidine dimers act as an absolute block for chain elongation by DNA polymerases I and III. Experiments with an irradiated poly(dC) template failed to detect incorporation of noncomplementary bases due to pyrimidine dimers. A large increase in the turnover of nucleoside triphosphates to free monophosphates during synthesis by DNA polymerase I on irradiated varphiX174 DNA has been observed. We propose that this nucleotide turnover is due to idling by DNA polymerase (i.e., incorporation and subsequent excision of nucleotides opposite UV photolesions, by the 3'-->5' "proofreading" exonuclease) thus preventing replication past pyrimidine dimers and the potentially mutagenic event that should result. In support of this hypothesis, DNA synthesis by DNA polymerase from avian myeloblastosis virus and by mammalian DNA polymerase alpha, both of which are devoid of any exonuclease activity, was found to be only partially inhibited, but not blocked, by UV irradiation of the template and accompanied by an increased incorporation of noncomplementary nucleotides. It is suggested that UV mutagenesis in bacteria requires an induced modification of the cellular DNA replication machinery, possibly an inhibition of the 3'-->5' exonuclease activity associated with DNA polymerases.

Coliphages↗
PubMed1978

Mutagenesis and cell transformation by ultraviolet irradiation: many hypotheses for few results.

UV light-induced mutagenesis in bacteria is a genetically controlled process dependent on induction of some cellular functions, provoked initially by unrepaired photolesions in the DNA. Experiments on the extent and fidelity of in vitro DNA systhesis on UV-irradiated templates by bacterial mammalian DNA polymerases suggest a crucial role for 3' to 5' exonuclease (proofreading) activity in UV light-induced mutagenesis. Two-stage carcinogenesis (initiation and promotion) is discussed in terms of two-stage mutagenesis (mutation fixation in the DNA and mutation expression). A unifying concept for both mutational and viral malignant transformation is proposed.

Cell Transformation, Neoplastic↗
PubMed1976

Bacillus subtilis mutant temperature sensitive in the synthesis of ribonucleic acid.

A Bacillus subtilis temperature-sensitive mutant (PB1653) has been isolated in which the rate of ribonucleic acid (RNA) synthesis sharply decreases after shift to 45 degrees C. Both stable and unstable RNAs are affected by the mutation. The possibility that the block of transcription at high temperature could be due to a "stringent" effect, mediated by an increase in the concentration of "magic spot" nucleotides, has been ruled out. Treatment with chloramphenicol (or streptomycin) rapidly restores the rate of RNA synthesis at 45 degrees C. The synthesis of RNA in the mutant during the early phases of spore germination is not temperature sensitive. The phage-specific transcription during infection with SPP1 phage, at high temperature, is less affected than that of the bacterial chromosome. In vitro experiments indicate that, in the mutant at high temperature, RNA polymerase undergoes a change in template specificity. The rna-53 mutation has been located on the B. subtilis genetic map near the hisA locus.

Bacillus subtilis↗
PubMed1974

Membrane attachment of the chromosome in Bacillus subtilis mutants temperature-sensitive in DNA replication.

We have examined three mutants of Bacillussubtilis temperature sensitive in DNA initiation and one temperature sensitive in DNA elongation, in order to investigate whether these lesions can cause or can result in a detachment of the membrane-bound chromosomal region. Our results argue against any effect of the mutations examined on the association between the chromosome and the membrane.

Bacillus subtilis↗
PubMed1974

Properties of a Bacillus subtilis strain lacking DNA polymerase I.

We have isolated a mutant of Bacillussubtilis deficient in DNA polymerase I, denominated polA42, which shows a reduced ability to repair the damage to DNA by UV radiation, MMS and mitomycin C;the ability to perform recombination is not appreciably impaired.DEAE cellulose chromatography allows the separation of polymerases I and II from the parental strain;a simple procedure is also described which allows to separate rapidly the polymerases II and III of the mutant strain. The three separated polymerases have similar catalytic properties but they can be distinguished for their sensitivity to inhibitors: PCMB inhibits polymerases II and III but not polymerase I; HPUra inhibits only polymerase III. All three enzymes are unaffected by nalidixate. The DNA synthesis occurring in cells of the polA42 strain permeabilized with toluene is inhibited by nalidixate, whereas the synthesis occurring in polA(+) toluenized cells is unaffected by the drug. The polA gene has been mapped by transduction and localized between the phe(12) and argA(3) genes.

Bacillus subtilis↗
PubMedDate not supplied

Prenatal diagnosis of recurrence of cystic hygroma with normal chromosomes.

Cyst-like masses in the neck and back region, simulating an encephalocele, were detected by midtrimester ultrasound examinations in two sib fetuses. After termination, the fetuses were found to have large cystic hygromas. The present observation strongly suggests the existence of an autosomal recessive type of cystic hygroma.

Adult↗
PubMedDate not supplied

Enhanced mutagenesis during post-treatment incubation of Escherichia coli treated with cis-diamminedichloroplatinum(II).

Wild-type Escherichia coli were treated with cis-dichlorodiammineplatinum(II) (DDP) and then kept in a non-dividing state for 4 h. This post-treatment incubation did not increase survival, excision of platinum-DNA lesions was not observed, and post-treatment exposure to thiourea had no effect on the toxicity of DDP. In contrast, the mutation frequency increased by a factor of 3 and reached a plateau after 3 h incubation at 37 degrees C. The quantity of DDP on the bacterial DNA remained constant during this time. Post-treatment exposure to thiourea (which is reported to react with monofunctional platinum-DNA adducts) inhibited but did not reverse the increased mutagenicity. These results may reflect the evolution of monofunctional platinum-DNA lesions into bifunctional mutagenic adducts during post-treatment incubation of bacteria which have been exposed to DDP.

Cell Division↗
PubMedDate not supplied

Repair of platinum-DNA lesions in E. coli by a pathway which does not recognize DNA damage caused by MNNG or UV light.

The adaptive response is an inducible DNA-repair system which diminishes the mutagenic and toxic effects of alkylating agents. A mutant of E. coli constitutive for adaptative repair, BS21, has been isolated. A spontaneous revertant of this strain, BS23, lacks the adaptive response. When compared to its wild-type parent, mutant BS21 showed an increased resistance to the killing and mutagenic effects of a compound which is not a classical alkylating agent, the antitumor drug cis-diamminedichloroplatinum(II) (cis-DDP). However, this resistance to cis-DDP was also found in strain BS23 which lacks the adaptive response. cis-DDP bound to the DNA of all 3 strains with the same efficiency. In addition, we have investigated the effect of UV radiation and we failed to observe a significant difference in the survival and mutagenesis of these strains. This evidence suggests that the resistance of BS21 and BS23 strains to cis-DDP is not a consequence of the adaptive response or increased excision repair.

Cisplatin↗
PubMedDate not supplied

Chemotherapy in the elderly: pharmacologic considerations.

BACKGROUND: The aging of the population has focused interest on the care of elderly cancer patients. A better understanding of the effects of chemotherapeutic agents on older patients with cancer will help to determine the appropriate use of chemotherapy for this age group. METHODS: The authors review recent studies and present pharmacokinetic data on several chemotherapeutic agents, particularly those that have recently become available. RESULTS: Agents such as gemcitabine, vinorelbine, the taxanes, anthracyclines, platinum compounds, topoisomerase I and II inhibitors, and the oral fluoropyrimidines appear to have a beneficial therapeutic index in elderly patients. CONCLUSIONS: Careful attention to the physiologic changes associated with aging, along with dose adjustments for end-organ dysfunction (eg, renal and hepatic), is necessary to ensure the safe administration of antitumor chemotherapy to the elderly.

Aged↗
PubMedDate not supplied

Combination chemotherapy using vincristine, adriamycin, cyclophosphamide (VAC) alternating with ifosfamide and etoposide (IE) for advanced soft tissue sarcomas: a phase II study.

Chemotherapy options in patients with advanced soft tissue sarcomas (STS) remain presently inadequate. In this phase II study the activity and toxicity of a combined alternating VAC/IE regimen in advanced and/or metastatic STS was evaluated. VAC (vincristine, total dose of 2 mg, adriamycin 70 mg/m2 and cyclophosphamide 600 mg/m2) was given as intravenous bolus infusion on day 1, followed after 21 days by IE (ifosfamide, 1.8 g/m2 infused over 1 h, daily for 5 consecutive days, with mesna uroprotection, plus etoposide at 500 mg/m2 infused over 2 h on the first day). Courses were repeated every 3 weeks. Twenty patients were treated, 12 of whom had previously been given chemotherapy for advanced and/or metastatic disease. Treatment was feasible in ambulatory setting, with good patient compliance. Myelosuppression, overall acceptable, was the major dose-limiting toxicity, while non-hematological side effects were minimal. An overall response rate of 45% was observed (95% CI, 26%-66%), with 2 complete and 7 partial remissions, achieving 75% in the subset of untreated patients. Median survival time was 10 months in the whole group (range, 4-26+ months) and 14 months in responder patients (range, 9-26+ months).

Adult↗
PubMedDate not supplied

Liposomal doxorubicin (Caelyx) in advanced pretreated soft tissue sarcomas: a phase II study of the Italian Sarcoma Group (ISG).

BACKGROUND: Doxorubicin remains one of the few drugs with consistent single agent activity in advanced Soft Tissue Sarcomas (STS), with a demonstrated dose-response relationship. Liposomal-encapsulated Doxorubicin (LED) has been shown to be at least as active as free doxorubicin in experimental models, and phase I and II human studies indicate that this novel strategy of drug delivery my have less myocardial toxicity. Few clinical trials in adult STS have been published until now, with disappointing and often contrasting results. PATIENTS AND METHODS: Twenty-five consecutive patients with measurable advanced and/or metastatic STS, previously pretreated with anthracycline-based chemotherapy, were enrolled into the trial. LED (Caelyx) was administered over 1-hour intravenous infusion at the dose of 30 mg/m2 in the first 5 patients, then at the fixed dose of 50 mg/m2 in the subsequent 20 patients. Treatment was given on ambulatory basis, at 3-week intervals. Antiemetics were generally not required and only used if indicated. RESULTS: A total of 98 courses of chemotherapy were given (median 4 per patient, range 2 to 5). Amongst the 25 evaluable patients, there were 3 partial responses (12%, 95% confidence interval 4.2% to 29.9%) lasting 3-9+ months and all occurring in patients treated at 50 mg/m2/cycle. In addition, 2 minor responses (4+ months) and 17 stable disease (2-7+ months) were observed; the remaining 3 patients progressed while on therapy. The median delivered drug dose-intensity was 13.3 mg/m2/week (range 10 to 16.6 mg/m2/week). Treatment was well tolerated, with no patient requiring dose reduction or therapy delay because of toxicity. Only 2 cases of WHO grade 3 toxicity occurred, consisting of neutropenia and scrotal skin toxicity; respectively; no cardiotoxicity was seen. CONCLUSIONS: This study shows that Caelyx has some activity in advanced, anthracycline-pretreated STS, with favourable toxic profile. From the analysis of available experiences it emerges that liposomal doxorubicin has not been tested at doses adequate to exploit the antitumor effects of the drug, being the reached dose-intensity being even lower than those deemed critical for obtaining optimal responses to free doxorubicin. We suggest that further and better addressed studies be performed in STS, including patients with less advanced stages of disease, focused on attempting to delivery the drug at optimal doses.

Adult↗