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Biomedical subjects

S Toma

Publications and source records attributed to S Toma.

At least 55 records · Page 3Linked to original sources
PubMed1997

Staining of micronuclei in squamous epithelial cells of human oral mucosa.

OBJECTIVE: To evaluate the influence of methodologic variables, staining method and sampling, on the frequency of micronuclei scored in squamous epithelial cells of oral mucosa. Micronuclei were used as biomarkers of structural and numerical chromosome damage. STUDY DESIGN: Feulgen and Giemsa stain and fluorescent dyes Hoechst 33258 and propidium iodide were used for micronucleus staining. Cells were collected by either light or vigorous scraping of oral mucosa. RESULTS: Staining of micronuclei by Hoechst 33258 proved more handly, less time consuming and at least equally reliable to the more widely used Feulgen staining. Results with Giemsa stain and propidium iodide were unsatisfactory. Micronuclei were less frequent in superficial layers of the oral mucosa. CONCLUSION: Hoechst 33258 can be recommended for micronucleus staining in squamous epithelial cells of oral mucosa. Differences in scraping may affect the measurement of micronucleus frequency; scraping should therefore be carefully standardized in each laboratory.

Epithelial Cells↗
PubMed1996

Substitution of two variant residues in the protein tyrosine phosphatase-like PTP35/IA-2 sequence reconstitutes catalytic activity.

The PTP35/IA-2 protein shows high homology to protein tyrosine phosphatases (PTPases) but harbours a few changes in invariant PTPase residues. Accordingly, PTP35/IA-2 has been reported to lack catalytic activity in vitro, and its in vivo biological function remains to be determined. We investigated if reversion of selected amino acids to the PTPase consensus could reconstitute enzymatic activity. Substitution of aspartic acid 911 in the putative active site with alanine resulted in the appearance of low but reproducible activity on pNPP dephosphorylation. Moreover, contemporary replacement of alanine 877 with aspartic acid greatly increased the catalytic efficiency of the D911A mutant. The A877D/D911A double mutant protein was also found to specifically dephosphorylate myelin basic protein phosphorylated on tyrosine. These results suggest that the general scaffold of the PTP35 protein is compatible with a common catalytic mechanism shared by PTPases and argue against an intrinsic enzymatic function of the wild type form.

Amino Acid Sequence↗
PubMed1996

Contact interactions method: a new algorithm for protein folding simulations.

Computer simulations of simple exact lattice models are an aid in the study of protein folding process; they have sometimes resulted in predictions experimentally proved. The contact interactions (CI) method is here proposed as a new algorithm for the conformational search in the low-energy regions of protein chains modeled as copolymers of hydrophobic and polar monomers configured as self-avoiding walks on square or cubic lattices. It may be regarded as an extension of the standard Monte Carlo method improved by the concept of cooperativity deriving from nonlocal contact interactions. A major difference with respect to other algorithms is that criteria for the acceptance of new conformations generated during the simulations are not based on the energy of the entire molecule, but cooling factors associated with each residue define regions of the model protein with higher or lower mobility. Nine sequences of length ranging from 20 to 64 residues were used on the square lattice and 15 sequences of length ranging from 46 to 136 residues were used on the cubic lattice. The CI algorithm proved very efficient both in two and three dimensions, and allowed us to localize energy minima not localized by other searching algorithms described in the literature. Use of this algorithm is not limited to the conformational search, because it allows the exploration of thermodynamic and kinetic behavior of model protein chains.

Algorithms↗
PubMed1996

Isolated lung perfusion with platinum in the treatment of pulmonary metastases from soft tissue sarcomas.

A multimodality approach including operation and isolated lung perfusion with platinum was used in six patients with lung metastases from soft tissue sarcomas. Staged thoracotomies were used in two patients with bilateral lesions. The inclusion criteria generally applied for surgical excision were adopted in this study. The pulmonary artery and a portion of the left atrium were isolated from systemic circulation and cannulated. The cannulas were then connected to a perfusion circuit and normothermic isolated lung perfusion was done for 60 minutes. The lung was then flushed and metastasectomy was done. Serial blood (systemic and pulmonary), tissue (normal lung and tumor), and urine samples were obtained for platinum content measurement by flameless atomic absorption spectroscopy. Lung damage was assessed by light and electron microscopy examination and by serial respiratory tests. Isolated lung perfusion was accomplished in all patients without any death, operative complication, or systemic toxicity. After operation, interstitial and alveolar edema developed in two patients (48 hours after treatment), necessitating respiratory support in one case. Total platinum concentrations in pulmonary plasma were about 43 times greater than those in systemic plasma. No differences in platinum concentrations between normal lung and metastatic tissue were found. Thus the proposed isolated lung perfusion technique is feasible and safe enough to be offered as a valid model to study combined chemosurgical approaches in the treatment of lung metastases.

Adult↗
PubMed1996

Increased risk of cardiovascular disease with erythropoietin in chronic dialysis patients.

Recombinant human erythropoietin is widely used in chronic dialysis patients. However, the long-term effect, especially on the incidence of cardiovascular disease, has not been critically evaluated. We observed the annual incidence of stroke and acute myocardial infarction from April 1988 through March 1993 in Okinawa, Japan. Until April 1990, erythropoietin was not generally used. Therefore, we have two periods: pre-erythropoietin, April 1988 through March 1990, and post-erythropoietin, April 1990 through March 1993. Two thousand one hundred and sixteen patients (1,219 males and 897 females) were on chronic dialysis during the study period by March 31, 1993. Every case of stroke and acute myocardial infarction during the study period was registered. The odds ratio was calculated using the data of the general population in each sex and age class obtained in the same area. A total of 86 cases of stroke and 15 cases of acute myocardial infarction were registered during the study period. The annual incidence, per 1,000 patient-years, of stroke was 12.5 (1988), 10.5 (1989), 12.7 (1990), 14.0 (1991), and 17.5 (1992). The incidence of stroke was increased in the post-erythropoietin period compared to the pre-erythropoietin period, odds ratio 1.22 and 95% confidence interval (95% CI 1.06-1.41, p < 0.01). The annual incidence of acute myocardial infarction was 1.0 (1988), 1.8 (1989), 0.8 (1990), 2.9 (1991) and 4.7 (1992). The incidence of acute myocardial infarction was increased significantly in the post-erythropoietin period compared to the pre-erythropoietin period, odds ratio 1.87 (95% CI 1.66-2.10, p < 0.01). The odds ratio of stroke to the general population was 4.25 (95% CI 3.10-5.82) in the pre-erythropoietin and 4.58 (95% CI 2.14-9.80) in the post-erythropoietin period. In acute myocardial infarction, it was 2.98 (95% CI 2.84-3.12) and 3.81 (95% CI 3.18-4.56). The odds ratio of acute myocardial infarction was significantly increased (p < 0.01). The introduction of erythropoietin was associated with an increased risk of cardiovascular disease, especially acute myocardial infarction. Erythropoietin may unmask the sclerotic lesion in chronic dialysis patients.

Cardiovascular Diseases↗
PubMed1996

Epidemiologic analysis of diabetic patients on chronic dialysis.

We retrospectively surveyed all of the available medical records of 404 (191 females and 213 males) chronic dialysis patients, of whom 16 (4%) had insulin-dependent diabetes mellitus (IDDM) and 388 (96%) non-insulin-dependent diabetes mellitus (NIDDM). The patients were among 2,214 dialysis patients in Okinawa, Japan, of whom 443 were diabetic. The patients entered a large population-based dialysis registry. The mean duration from the diagnosis of diabetes mellitus (DM) to dialysis was 181.6 months in the IDDM patients and 150.4 months in the NIDDM patients. The NIDDM patients were classified into four subgroups according to their status when DM was first suspected. The duration from the diagnosis of DM until the onset of dialysis treatment was significantly shorter than in any other subgroup or in the IDDM subgroup with major vascular disease (131.9 months). Otherwise, the course of renal disease in NIDDM patients was similar to that in IDDM individuals. Most of our dialysis patients with DM had NIDDM. In most of the NIDDM patients, the diagnosis had been delayed for several years for unknown reason. However, if diagnosed early, NIDDM shows a clinical time course until dialysis similar to that of IDDM. Whether NIDDM patients contract chronic renal disease at an equal incidence to that of IDDM patients and the fraction of all diabetic patients accepted for chronic dialysis remain to be determined.

Adult↗
PubMed1995

Increased muscle sympathetic nerve activity after glucagon administration in man.

Muscle sympathetic nerve activity (MSNA) after glucagon administration was quantitatively measured in five healthy male volunteers (age: 20-28 years old). After an overnight fasting, 1 mg glucagon dissolved in a 1-ml vehicle was injected i.v. as a bolus. MSNA, ECG and blood pressure were simultaneously recorded 15 min before and after the injection. MSNA (bursts/min), heart rate (HR), and systolic and diastolic blood pressures (dBP and sBP) were significantly increased at 2-3 min after glucagon injection. Their means and standard deviations of control for 15 min vs. 3 min after the injection were in the five subjects; MSNA, 10 +/- 6 vs. 30 +/- 10 bursts/min, HR, 61 +/- 10 vs. 76 +/- 8 beats/min, dBP, 66 +/- 9 vs. 91 +/- 9 mmHg and sBP, 122 +/- 12 vs. 152 +/- 11 mmHg. These results suggest that glucagon has a direct facilitatory effect on the central sympathetic nervous system.

Adult↗
PubMed1995

Response characteristics of cutaneous mechanoreceptors to vibratory stimuli in human glabrous skin.

We investigated the responsiveness of mechanoreceptors in the glabrous skin of the hand to triangular vibratory stimuli when the frequency and applied pressure to the skin were varied. Using a microneurographic technique, 13 single afferent activities were recorded from 4 kinds of mechanoreceptors. Both fast-adapting (FA) and slow-adapting (SA) units were sensitive to the vibratory stimuli. The relationship between the most sensitive frequency and applied pressure to the skin were analyzed as a tuning curve. FA-type I (FAI) was sensitive to vibratory stimuli at 30-40 Hz and the frequency which entrained one-to-one discharge at lower pressure was between 10 and 80 Hz. FA-type II (FAII) sensitivity was augmented sharply over 60-100 Hz. SA-type I (SAI) and SA-type II (SAII) responsiveness was almost the same and characteristic sensitivity to the vibratory stimuli was revealed under 15 Hz. Functional roles of these units, especially type I units, are discussed in relation to active touch such as texture discrimination with a finger.

Adult↗
PubMed1995

Combined management in the treatment of epidoxorubicin extravasation. A case report.

Inadvertent extravasation during intravenous antitumor therapy is not an unusual complication and can cause damage ranging from minor erythema to severe local necrosis. The appropriate management of these iatrogenic accidents as a part of supportive care in oncology has been addressed by several experimental studies, but there has been little clinical study and no conclusive evidence on the best therapeutic strategies to adopt. The case reported here of a patient suffering from severe soft-tissue injury caused by extravasation of epidoxorubicin demonstrates the usefulness of a combined management (medical, surgical and rehabilitative) in the appropriate care of extravasation.

Aged↗
PubMed1995

Ambulatory 4-day continuous-infusion schedule of high-dose ifosfamide with mesna uroprotection and granulocyte colony-stimulating factor in advanced solid tumours: a phase I study.

BACKGROUND: There is evidence that continuous infusion allows the delivery of higher doses of a drug while reducing the incidence of neurologic and renal toxicity. To verify prior to phase II testing the feasibility of ambulatory treatment with high-dose ifosfamide/mesna by continuous infusion in adult solid tumours, the maximum tolerated dose (MTD) and the non-haematological dose-limiting toxicities for the achievement of 2 courses of therapy were determined. PATIENTS AND METHODS: Thirty-two patients with advanced solid tumours were given continuous-infusion ifosfamide, from 9 to 16 g/m2, over 4 consecutive days, with equidose mesna uroprotection and granulocyte colony-stimulating-factor support; courses were repeated every 3 weeks. Total dose/course was escalated by 1 g/m2, in cohorts of 3 to 5 patients until the MTD was determined. RESULTS: At 16 g/m2, the dose-limiting toxicity was renal, with 2 of the 5 patients treated developing renal failure. Haematological toxicity was dose-related and significant at higher dosages, but generally surmountable. Ifosfamide at 15 g/m2/course with mesna uroprotection was identified as the MTD. CONCLUSIONS: The present study shows that high-dose continuous-infusion ifosfamide, administered by portable infusion pumps, is feasible in an ambulatory regimen, with acceptable non-haematological toxicity and good patient compliance.

Adult↗
PubMed1995

Effectiveness of beta-carotene in cancer chemoprevention.

This article reviews the current knowledge on the cancer-preventive potential of beta-carotene, a precursor of vitamin A, and plentiful in fruits and vegetables, which has been studied widely as a promising chemopreventive agent in reducing the risk of cancer in humans. Several retrospective and prospective epidemiological investigations have demonstrated that a diet rich in micronutrients such as vitamins, carotenoids and selenium, could prevent the arising, in 'high-risk' patients, of precancerous and neoplastic lesions of specific sites, particularly of the upper aerodigestive tract. Numerous in vitro expressions have been performed in order to verify the true role played by this agent on cell proliferation and differentiation; until now, findings have been very encouraging, uniformly showing the beta-carotene can affect carcinogenesis, particularly in early stages, through an antigenotoxic action. Antioxidant functions, immunomodulatory effects and control of intercellular messages via gap junctions are possible action mechanisms of the ability of beta-carotene to block the carcinogenetic process. In vivo animal studies partially confirm the results obtained in vitro showing that beta-carotene is able to reduce the induce cancer development; moreover, the association of the carotenoid with other microelements, such as vitamins E, C and glutathione often appears to be more effective than each agent used alone. From a clinical point of view, beta-carotene appears an 'ideal' agent to be used in chemoprevention trials in humans, although optimal doses and intake methods need to be better defined; its almost zero toxicity permits the long-term administration of the drug, a vital condition for its anti-cancer activity, with good patient compliance. Human intervention studies performed so far, both randomized and uncontrolled clinical trials, have showed positive findings in specific cancer sites such as oral cavity, head and neck and colon; less consistent or negative are results on skin, lung and oesophagus cancer. The ongoing studies will provide more answer on these issues. A definitive evaluation of the ability of beta-carotene to prevent cancer in human requires further controlled trials; studies on a larger spectrum of cancer sites and different stages of disease must be encouraged. In addition, further investigation on biomarkers related to cancer risk and cancer incidence are necessary, particularly focused on the measurements for genotoxic damage, eg micronuclei, that may provide a valid and 'easy' marker for early stage carcinogenesis.

Animals↗
PubMed1995

Probing the structure of human growth hormone by limited proteolysis.

Digestion of human growth hormone (hGH) with the Glu-specific protease from Staphylococcus aureus V8 was performed at 20-22 degrees C or 37 degrees C at a 1:20 ratio (by weight) at pH 7.8 with or without 0.2% SDS. There are 14 Glu-residues evenly distributed along the polypeptide chain of hGH as possible sites of proteolytic cleavage of V8-protease. The pattern of fragmentation of hGH was analyzed by electrophoresis and reversed-phase HPLC, and the identity of the proteolytic fragments isolated to homogeneity was established by their partial sequencing and amino acid analysis after acid hydrolysis. Kinetic analysis of the proteolytic digestion process allowed to establish that initial nicking of the protein occurs at Glu33 and subsequently at Glu56 and Glu66. Much slower cleavages occur at Glu30 and Glu186. These cleavage sites are located at chain loops in the hGH molecule, and in particular outside the helical segments of the four-helix bundle of the crystal structure of hGH. Fragments 1-33 and 67-191 comprising entirely the N-terminal helix and the three C-terminal helices of hGH, respectively, were isolated to homogeneity in amounts useful for subsequent conformational and functional studies. The results of this study and of previous ones [Li, C.H. (1982) Mol. Cell. Biochem. 46, 31-41] describing limited proteolysis of hGH by various proteases have been interpreted on the basis of the three-dimensional structure and dynamics of hGH. Overall, it is shown that proteolytic enzymes preferentially cleave hGH at exposed and flexible loops only, thus emphasizing the fact that proteases can be used as reliable probes of protein structure and dynamics.

Amino Acid Sequence↗