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S Toma

Publications and source records attributed to S Toma.

At least 91 records · Page 5Linked to original sources
PubMed1991

A new human growth hormone production process using a recombinant Bacillus subtilis strain.

We constructed a series of hybrid plasmids which directed the synthesis of different human growth hormone (hGH) precursor sequences in Bacillus subtilis. In addition to the 191 amino acids of the hormone, the precursors had in common an amino-terminal extension characterized by the presence of a methionine at position 1 and of the tetrapeptide Ile-Glu-Gly-Arg preceding the first residue (Phe) of hGH. The sequence between the methionine and the tetrapeptide was specific for each precursor and, because of the presence of charged residues, conferred particular properties to the molecules. Long homopolymeric tail-containing precursors such as MRRRRRRIILM-IEGR appeared insoluble whereas shorter sequences of the type MRR-IEGR and MEELM-IEGR augmented the solubility of the precursors with respect to Met-hGH. The soluble precursors could be easily purified from the bulk proteins taking advantage of the charged residues present on the N-terminal tail. After purification, the natural hGH was obtained by treating the precursors with the protease Factor Xa which cleaves after the arginine residue of the tetrapeptide IEGR. A protocol for the production and purification of authentic hGH from a strain expressing one of these soluble precursors is reported.

Amino Acid Sequence↗
PubMed1991

In vitro effects of beta-carotene on human oral keratinocytes from precancerous lesions and squamous carcinoma.

Human keratinocytes, obtained from bioptic specimens of healthy and preneoplastic oral mucosa, and from human cell lines from oral cavity tumors (KB and SCC-25) were treated with beta-carotene (10 microM). The colony forming efficiency (CFE), the proliferation rate and the frequency of micronucleated cells were measured in these cultures. CFE was significantly reduced (p less than 0.05) by beta-carotene treatment in cells from healthy mucosa and in KB cells. Decreases (p greater than 0.05; NS) were also observed in cells from pathological mucosa and in SCC-25 cells. Cell proliferation rate was not substantially affected by beta-carotene in all cultures. Finally, a decreased frequency of micronucleated cells was found in treated cultures, but significant reductions (p less than 0.05) were only observed in cultures from oral mucosa (healthy and pathological) as well as in KB cell cultures. Our results indicate that beta-carotene is able to reduce the clonogenic activity (CFE), even if it does not seem to influence cell proliferation, and that it has a protective effect against genotoxic damage.

Adolescent↗
PubMed1991

[Metabolic fate of bufalin in rats].

In an attempt to evaluate the metabolic fate of "Kyushin", which is a traditional medicine containing Toad venom, a 3H-labeled compound of bufalin, which is one of the main active components, has been synthesized. The metabolic fate of the 3H-bufalin was studied after its single and repeated oral administration in rats. After a single administration of the 3H-bufalin (20 micrograms/kg), the radioactivity in the blood reached a maximum level at 15 min. The radioactivity in the blood declined in a triphasic manner with half-life times of 18 min, 2.6 and 86 h. Within 24 h after the single administration, the excretion of the radioactivity into the urine and feces amounted to 1.3% and 81% of the administered dose, respectively. Tissue radioactivity was higher in the stomach, small intestine, liver, lung, kidney and pancreas, while the radioactivity in other tissues was lower than that in blood. Radioactivity disappeared rapidly from any tissues. In case of repeated administration for 14 d, the disposition of radioactivity was almost same as the result after a single dosing, and radioactivity scarcely remained in any tissues after the last administration.

Administration, Oral↗
PubMed1991

[Metabolic fate of bufalin and cinobufagin].

In the course of study of the metabolic fate of "Kyushin", a traditional medicine containing toad venom, the metabolic fates of bufalin and cinobufagin, main constituents of toad venom, have been studied. Six metabolites were detected in the extracts from incubation mixture of rat liver slice with bufalin, and one main metabolite shown by mass spectroscopy and high performance liquid chromatography (HPLC) to be 3 alpha-bufalin. Serum levels of bufalin and 3 alpha-bufalin were determined by HPLC after oral administration of 2000 micrograms/kg of bufalin, and both compounds appeared in the rat serum. On the other hand, only 3 alpha-bufalin appeared after administration of 20 or 200 micrograms/kg. 3 alpha-Bufalin levels increased dose dependently. Serum levels of cinobufagin and its metabolites and digitoxin were compared after repeated intravenous administration (5 h interval) of cinobufagin or digitoxin. Although digitoxin was accumulated in the rat serum, cinobufagin and its metabolites were not. Inhibitory activities of metabolites of bufalin and cinobufagin on (Na+ + K+)-adenosine triphosphatase were less than those of original compounds.

Administration, Oral↗
PubMed1991

[Pharmacological studies of reiousan which contains bezoar and ginseng: III. Effects on experimental cerebral ischemia].

Pharmacological effects of Reiousan, a crude drug preparation consisting of bezoar and ginseng, on experimental cerebral ischemia and anoxia were studied. After administration of Reiousan, the survival time of mice subjected to hypobaric hypoxia and the gasping duration of isolated rat head tended to increase. Reiousan inhibited all the following: lipid peroxides production in rat brain homogenate, tissue swelling induced by the xanthine-xanthine oxidase system in rat brain cortical slices, rat brain swelling induced by freezing, lipid peroxides production in the rat brain after ligation of bilateral common carotid arteries, and lipid peroxides production in Mongolian gerbil brain after reperfusion following ligation of bilateral common carotid arteries. These effects may result from antioxidant activity of bilirubin, a constituent of bezoar.

Animals↗
PubMed1991

Selenium therapy in patients with precancerous and malignant oral cavity lesions: preliminary results.

Baseline selenium (Se) levels in serum samples were collected from 22 patients with precancerous and 19 with malignant oral cavity lesions as well as from 13 healthy controls of the same geographic areas. Mean serum Se levels were 105, 101, and 77.03 ng/ml in the precancerous, controls, and malignancy groups, respectively. A statistically significant difference (p less than 0.005) was found between the neoplastic and both the precancerous and control groups. After careful clinical evaluation, precancerous patients received three 4-week cycles of Se, in either inorganic or organic form. Of the 22 precancerous patients entering the study, 18 were available for evaluation of clinical response. The analysis of serum Se variations revealed that serum Se levels tended to increase after the first and second cycles and then gradually returned to baseline values. At the end of the therapy, there were two complete responses (CR), five partial responses (PR), six minor responses (MR), and five stable diseases (SD) with an objective response (CR + PR) of 38.8%. Progression after suspension of therapy occurred in 7 of 18 patients; this may indicate the need of a longer treatment period with this essential trace element.

Adult↗
PubMed1990

Structural features of neutral protease from Bacillus subtilis deduced from model-building and limited proteolysis experiments.

The overall folding of neutral protease from Bacillus subtilis has been predicted by computer-aided modelling, taking as a basis the known three-dimensional structure of thermolysin. As expected from the 50% similarity of sequence between the two proteins, the structure of B. subtilis protease is similar to that of thermolysin, including the two-domain topology and location of elements of regular secondary structure (helices and strands), whereas specific differences were predicted in loop regions. A protruding and loose loop predicted in B. subtilis has been detected also experimentally by a limited proteolysis approach. Incubation of B. subtilis protease at pH 9.0 for 24 h at room temperature with trypsin at 20:1 ratio (by mass) leads to a specific and almost quantitative fission of the Arg214-Asn215 peptide bond located in a highly exposed, and thus probably flexible, loop of the protease. On the other hand, thermolysin was completely resistant to tryptic hydrolysis when reacted under identical conditions. The 'nicked' B. subtilis protease can be isolated by gel filtration chromatography at neutral pH, whereas the two constituting fragments 1-214 and 215-300 are separated under protein-denaturing conditions. Overall, these results indicate that the limited proteolysis approach can pinpoint a peculiar difference in surface structure between the two similar protein molecules of B. subtilis neutral protease and thermolysin and emphasize the potential use of proteolytic enzymes as structural probes of globular proteins.

Amino Acid Sequence↗
PubMed1990

Intraarterial chemotherapy through carotid transposition in advanced head and neck cancer.

We report results of intraarterial chemotherapy (IAC) in patients with advanced unresectable (T4, N0-3, MO) squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) of the oral cavity, oropharynx, or facial skin, given through a subcutaneously transposed external carotid artery by a fine gauge needle. Forty patients entered the study and 39 were evaluable for clinical response and toxicity. The infusion technique was done in two consecutive series of patients with the same characteristics: 17 had treatment with vincristine, bleomycin, and methotrexate (VBM), and 22 received cisplatin and bleomycin (PB) with a median number of six and five cycles, respectively. The total objective response (OR) rate was 76.9%, which included 12.8% of complete response (CR). A better percentage of OR was attained in BCC than SCC (83.3% versus 75.8%), in tumors of the skin of the face than other sites (87.5% versus 74.2%), and in the group that received PB than the group that received VBM (77.3% versus 76.5%). Our series had an overall technique-related toxicity of 18%; 10.3% with neurologic disturbances and 7.7% with skin inflammation (almost all were reversible). The most common systemic toxic side effects were generally mild and well tolerated (30.8%), whereas major toxicities (severe modifications of the cardiopulmonary function) occurred in four patients (10.3%) in the group that received VBM. After chemotherapy, 28 patients (71.8%) were deemed resectable; 23 of these patients (82.1%) agreed to surgery. Pathologic CR were obtained in 13 patients (56.5%). Our technique has significant advantages over the conventional methods of infusion, because tumor perfusion is feasible and selective, technique-related and catheter-related complications are almost completely eliminated, and fatal drug-related side effects are avoided.

Adult↗
PubMed1990

Epidoxorubicin plus ifosfamide in advanced and/or metastatic soft-tissue sarcomas.

We undertook this phase II study to evaluate the efficacy and toxicity of epidoxorubicin and ifosfamide in the treatment of locally advanced and/or metastatic soft-tissue sarcomas. We used escalating doses of epidoxorubicin (from 60 to 75 mg/m2) on day 1 and 1.2 g/m2 ifosfamide on days 1-5. Chemotherapy courses were repeated every 3-4 weeks. A total of 16 patients--13 who had not previously been treated and 3 who had undergone prior therapy with anthracyclines--entered the study. In all, 15 patients were evaluable for response and 16, for toxicity. At least two courses of chemotherapy were given. A complete remission (CR) was seen in 1 patient, a partial remission (PR) in 5, and a minor response (MR) in 1, for an objective response rate (CR + PR) of 40% (6/15); this value reached 50% in non-pretreated patients (6/12). Stable disease (SD) was observed in 40% (6/15) of patients. The relative dose intensity of epidoxorubicin ranged from 10 to 23.3 mg/m2 (median, 16.6 mg/m2). The time to objective response ranged from 4 to 12 weeks (median, 8.5 weeks). The duration of response was 4 months for the single CR, and that for the five PRs was 6+ months (range, 4-18 months). Toxicity was evaluated according to WHO criteria in 16 patients; it was mild and consisted mainly of alopecia, nausea and vomiting, and leucopenia. In only three patients did we observe grade 3 leucopenia. In one case an ifosfamide-associated encephalopathy occurred, but it regressed after 24 h. Neither chronic nor acute cardiac toxicity was reported. In this preliminary analysis, the response rate obtained with the combination of epidoxorubicin and ifosfamide was encouraging and the toxicity was acceptable.

Adolescent↗
PubMed1990

5-Fluorouracil and high-dose folinic acid as second-line chemotherapy in head and neck cancer.

Experimental and clinical data support the concomitant use of 5-fluorouracil (5-FU) and high-dose folinic acid (HDFA). To verify the role of such a combination in far advanced head and neck cancer, we performed a phase II study employing weekly HDFA, 500 mg/m2 in 2-h infusions, and 5-FU, 600 mg/m2 bolus injection. Twenty-seven evaluable patients with recurrent disease entered the study. One complete response, seven partial responses, 10 stable disease, and nine progressions were observed: the overall response rate was 29.6%. Oral mucositis and diarrhea were major side effects; five patients discontinued the treatment due to toxicity; no deaths correlated to the treatment were detected. Considering the characteristics of our patients, the 5-FU/HDFA combination has shown a satisfactory antitumoral activity, but toxicity was similar to other chemotherapy regimens.

Aged↗
PubMed1990

[Biological aspects and perspectives applicable to the chemoprevention of cancer of the upper respiratory-digestive tract].

After defining chemoprevention a description is given of the phases of differentiation in normal epithelial cells and the features of proliferation in neoplasias developing in this epithelium. The latest studies on carcinogenesis indicate various types of prevention with which one can alter this transformation process. Epidemiological studies have shown that subjects with low serum levels of Vit-A or Beta carotenoids are at high risk of developing epithelial cancer. Three main categories of agents inducing cell transformation are described: a) physiological induction agents; b) non physiological induction agents; c) cytotoxic drugs. In regard to clinical use, some studies have focussed on the importance of Vit-A in chemoprevention of risk conditions (pre-cancerous lesions) and in prevention of cancer recurrence. The authors point out the increasing interest in the use of retinoids in the chemoprevention of head and neck cancer and report some personal clinical experience.

Adult↗
PubMed1990

[Epidemiology and natural history of cancer of the upper respiratory-digestive tract].

Squamous cell carcinoma of the upper aero-digestive tract represents 86% of all malignant neoplasms developing in the head and neck. In Italy a comparison of the standardized incidence data shows that such cancer is more frequent in the northern than in the central and southern parts of the country. Males are more often affected than females. After considering the most important risk factors the authors analyze the epidemiology and natural history of cancer of each organ of the head and neck.

Carcinoma, Squamous Cell↗
PubMed1989

Analysis of 16 patients with metastatic squamous cell carcinoma of the head and neck: implications for treatment.

The present paper reports a retrospective analysis of 16 patients with distant metastases from squamous cell carcinoma of the head and neck observed in our Institute in the last 10 years. Nine patients out of 16 underwent chemotherapy (7 patients), chemotherapy and radiotherapy (1 patient), or an alternating chemo-radiotherapy regimen (1 patient). The remaining 7 patients were not considered for a palliative treatment because of a poor performance status. Two complete responses, 2 partial responses, 2 stable diseases and 3 progressions were observed, with an overall response rate of 44%. Chemotherapy, when administrable, showed a temporary effectiveness, at least in patients with lung metastases. The combination of cisplatin and 5-fluorouracil seems to maintain the efficacy already shown in patients with locally relapsed disease.

Adult↗
PubMed1989

Effect of Glu-143 and His-231 substitutions on the catalytic activity and secretion of Bacillus subtilis neutral protease.

On the basis of the homology with the Bacillus thermoproteolyticus zinc endopeptidase thermolysin, we hypothesized that Glu-143 and His-231 are the key residues for the catalytic activity of the Bacillus subtilis neutral protease. To test this possibility by site-directed mutagenesis, we substituted these two residues with Ala, Ser, Trp and Arg, and Leu, Val and Cys respectively. All these substitutions dramatically affected the amount of secreted mutant proteins, as determined by immunological methods, and their catalytic activities. No appreciable secretion was observed with the three Glu mutants Trp, Ser and Arg, whereas the Glu----Ala mutant enzyme was secreted at a level of a few hundred micrograms per litre of culture. The His mutants were all secreted at higher levels (in the order of a few milligrams per litre) and their residual catalytic activity could be determined using Z-Ala-Leu-Ala as substrate. Our results confirm the key role played by Glu-143 and His-231 in catalysis and moreover suggest the existence of a relationship between the catalytic activity of the enzyme and the extent of its secretion. In this context, we present data suggesting an autoproteolytic mechanism of cleavage of the precursor form of the enzyme, analogous to the one previously reported for the B. subtilis subtilisin.

Amino Acid Sequence↗
PubMed1989

Detection of urinary antigens of Legionella pneumophila serogroup 12 by broad-spectrum enzyme-linked immunosorbent assay.

The first Canadian case of Legionella pneumophila serogroup 12 infection is reported. The initial diagnosis was made with a urine specimen by a broad-spectrum enzyme-linked immunosorbent assay; further serogrouping was done by indirect fluorescent-antibody and tube agglutination tests. This case emphasizes the importance of multivalent urinary antigen detection for the diagnosis of legionellosis.

Agglutination Tests↗
PubMed1989

[Precancerous oral lesions. Diagnostic and therapeutic protocol].

The NRC (National Research Council) task force on head and neck cancer issued this document to help clinicians involved in diagnosing and treating precancerous oral diseases. Chapter 1 includes definition, epidemiology, risk factors (alcohol, smoking, poor oral hygiene), WHO classification, clinical picture of leukoplakias, erythroplasia, lichen planus, as well as their natural history. Chapter 2 points out the clinical signs to be looked for in order to make a proper diagnosis and discusses biopsy techniques. Chapter 3 deals with therapeutic procedures (surgical technique and medical treatment), while Chapter 4 concerns follow-up according to the clinical and histological diagnosis. Finally, some statistical forms are enclosed: Form 1 consists of information regarding educational qualifications, occupation, alcohol consumption, smoking and dietary habits; Form 2 consists of information about previous diseases and the history of the present disease; Form 3 records the signs and symptoms observed for the precancerous lesion; Form 4 records treatment modalities; Form 5 records patient follow-up.

Humans↗
PubMed1988

Alternating cisplatin-5-fluorouracil and radiotherapy in head and neck cancer.

Thirty-four patients with advanced (stage IV) or relapsing squamous cell carcinoma of the head and neck (SCC-HN) were treated alternately with chemotherapy (CT) and radiotherapy (RT). Patients' characteristics were as follows: male: female ratio, 27:7; median age, 55 (34-76), median P.S., 1 (ECOG scale) (range 0-2). Patients studied had no renal, hepatic, or cardiac impairments, a life expectancy of greater than or equal to 3 months, and no previous treatment with RT or CT. Seventeen patients were previously untreated, and 17 had a relapse after radical surgery. The CT regimen consisted of 20 mg/m2 cisplatin, with 2 h forced diuresis, from day 1 to 5, and 200 mg/m2 i.v., from day 1 to 5, every 3 weeks, administered four times. The RT was performed after the first, second, and third CT course, and consisted of three courses of 20 Gy each, 2 Gy daily, 5 days per week. Weekend intervals were planned between CT and RT treatments. The 17 previously untreated patients showed an overall response rate of 88.2% [eight complete response (CR), seven partial response (PR), one stable disease (SD), one progression disease (PD)]; the 17 patients treated at relapse after radical surgery reached an overall response rate of 64.7% (six CR, five PR, six PD). Actuarial median survival is 47 weeks: 51 weeks in untreated patients, and 42 weeks in previously treated patients. Toxicity was mild, and only 10 patients suffered from grade III (WHO scale) gastrointestinal (2 patients), hematological (5 patients), mucosal (2 patients), and neurological (1 patient) toxicity. Neither grade IV toxicity nor treatment-related deaths have been observed. In our study, cisplatin and 5-FU alternating with RT has shown an interesting antitumor activity and moderate side effects.

Adult↗