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Biomedical subjects

J Da Silva

Publications and source records attributed to J Da Silva.

17 recordsLinked to original sources
PubMed2002

The impact of callosities on the magnitude and duration of plantar pressure in patients with diabetes mellitus. A callus may cause 18,600 kilograms of excess plantar pressure per day.

BACKGROUND: The importance of high peak plantar pressure (PP) in the development of foot ulcer is well known. However, few studies have analyzed the real impact of callosities on plantar pressure and ulcer formation. METHODS: The plantar pressure (PP) in patients with diabetes mellitus was studied in three groups, of a total number of 33 type 2 diabetic patients, without neuropathy or peripheral vascular disease: subjects with callus (A) (n = 10), subjects without callus (B) (n = 10), and a separate group of patients with callus which was submitted to callus removal (C) (n = 13). The plantar pressure (PP) parameters were measured by FSR 174 sensors and computer analyses were performed by LabView. RESULTS: Both maximum peak PP and duration of PP are significantly higher in patients with callus (peak PP: 314 +/- 52 kPa vs 128 +/- 16 kPa, p < 0.005; duration of PP: 621 +/- 27 ms vs 505 +/- 27 ms, p < 0.05). The intervention group C before and after callus removal showed an identical trend. Callus removal has decreased the peak PP by 58% (p < 0.001) and duration of PP has been decreased by 150 milliseconds by step (p < 0.05). CONCLUSION: This study has shown the deleterious role of callus and assuming that an average person walks about 10,000 steps a day, a callus may cause 18,600 kg of excess plantar pressure per day. In addition, this study has proven the importance of early and regular removal of hyperkeratotic tissue. Even more aggressive removal could be recommended in patients with neuropathy and peripheral vascular disease.

Adult↗
PubMed2001

Stromal cells and human malignant neuroblasts derived from bone marrow metastasis may share common karyotypic abnormalities: the case of the IGR-N-91 cell line.

BACKGROUND: Stage IV neuroblastoma is characterized by tumor invasion and metastatic dissemination. Cell lines derived from such neuroblastomas have a high in vitro proliferation capacity. PROCEDURE: We established three neuroblastoma cell lines derived from involved bone marrow of three patients with stage IV neuroblastoma and performed a cytogenetic study. RESULTS: Various culture conditions allowed us to distinguish two cell subpopulations: malignant neuroblasts (Nb-type) and substrate-adherent stromal cells (Str-type). Karyotypic analyses revealed two specific chromosomal abnormalities in diploid malignant IGR-N-331 neuroblasts, der(1)t(1;7)(p22;q11) and der(5)t(5;17)(q35;q21), one unbalanced translocation der(1)t(1;17)(p35;q21)x2 in hyperdiploid malignant IGR-N-337 neuroblasts, and a normal karyotype in both corresponding stromal subpopulations. In contrast, in the IGR-N-91 model, both cell types shared two unbalanced translocations, t(1;4)(q12;p15) and t(2;10)(p14;q11), suggesting that stromal cells and malignant neuroblasts originate from a common stem cell. CONCLUSIONS: Based on our findings, we postulate that genetically modified stromal cells may influence the metastatic potential of malignant neuroblasts.

Bone Marrow Cells↗
PubMed2000

A new ambulatory foot pressure device for patients with sensory impairment. A system for continuous measurement of plantar pressure and a feed-back alarm.

Abnormal and excessive plantar pressure is a major risk factor for the development of foot ulcers in patients with loss of protective pain sensation. Repeated pressure with each step can result in inflammation at specific points, followed by ulcer formation. Patients with peripheral nerve disease are unable to prevent the development of such lesions, which often lead to amputation. For this reason, it has been suggested that a fundamental therapeutic intervention should be the reduction of high plantar pressure. We have developed a portable, battery-operated ambulatory foot pressure device (AFPD) which has two important functions: (1) to determine the areas of high plantar pressure, and (2) to provide an acoustic alarm, adjusted to a specific pressure load, which is triggered when weight-bearing exceeds the predetermined plantar pressure. A memory of plantar pressure parameters allows for downloading of the data and sequential analysis during the investigation period. Such an alarm device could replace the lack of pain sensation and may play an important role in the prevention of ulcer development and lower extremity amputation.

Aged↗
PubMed1998

[Oncogenic factors of metastatic dissemination in neuroblastoma].

Disseminated neuroblastoma frequently show a very poor prognosis. N-myc gene amplification, 1p deletion and lack of CD44 gene expression, are all genetic factors associated with the disease's dissemination. Human neuroblastoma xenografts in nude mice has permitted to characterize, in disseminated neuroblasts, oncogenes overexpression, inactivation of tumor suppressor genes as well as detoxifying genes activation which contributes to increase cellular resistance to chemotherapy. These genetic abnormalities permit to propose a nosology of this very aggressive pediatric solid tumor. Hopefully, this genetic classification could be of great value for new therapeutic approaches.

Animals↗
PubMed1997

Blockade of p38 mitogen-activated protein kinase pathway inhibits inducible nitric-oxide synthase expression in mouse astrocytes.

Treatment of mouse astrocyte cultures with combined interleukin (IL)-1alpha and tumor necrosis factor (TNF)-alpha induced expression of inducible nitric-oxide synthase (iNOS), resulting in sustained release of large amounts of nitric oxide, whereas TNF-alpha and IL-1alpha individually were unable to induce iNOS expression in astrocytes. The role of MAPK cascades and of NF-kappaB activation in the early intracellular signal transduction involved in iNOS transcription in TNF-alpha/IL-1alpha-stimulated astrocytes was investigated. TNF-alpha and IL-1alpha activated all p42/44(MAPK), p38(MAPK), and p54(JNK) pathways as determined by immunoprecipitation kinase assays using specific antibodies and substrates. The p38(MAPK) pathway is specifically involved in TNF-alpha/IL-1alpha-induced iNOS expression, since iNOS protein and nitric oxide release in the presence of a specific inhibitor of p38(MAPK), 4-(4-fluorophenyl)-2-2-(4-hydroxyphenyl)-5-(4-pyridyl)-imidazole (FHPI), were dramatically diminished. In contrast, PD98059, a specific inhibitor of MEK1 had no effect on iNOS expression. p38(MAPK) did not couple NF-kappaB to iNOS transcription, but NF-kappaB had a clear role in iNOS transcription regulation. Northern blot analysis showed that the p38(MAPK) pathway controlled iNOS expression at the transcriptional level, since iNOS mRNA was reduced in the presence of FHPI in TNF-alpha/IL-1alpha-stimulated astrocytes. iNOS expression was investigated with TNF receptor (TNFR)-1- and TNFR-2-deficient mice. The TNF-alpha activity in TNF-alpha/IL-1alpha-stimulated astrocytes was exclusively mediated through TNFR-1, most likely because TNFR-2-mediated signals in astrocytes did not connect to the p38(MAPK) pathway. These data suggest that TNF-alpha/IL-1alpha-induced iNOS expression depends on a yet undetermined second pathway in addition to p38(MAPK).

Animals↗
PubMed1996

Cisplatin-induced apoptosis and p53 gene status in a cisplatin-resistant human ovarian carcinoma cell line.

Cisplatin-induced apoptosis and p53 gene status were analyzed in human ovarian carcinoma using a parental IGR-OV1 line and a derived cisplatin-resistant IGR-OV1/DDP subline. Compared with parental cells, cisplatin-resistant cells exhibited a 5-fold higher resistance index and a 2-fold longer doubling time. Cisplatin induced apoptosis in both cell lines, as assessed by cell morphology and the presence of a DNA ladder. However, high concentrations were necessary to induce apoptosis in resistant cells. These cells elicited a 5-fold decrease in the number of platinum atoms bound per nucleotide. IGR-OV1/DDP cells also exhibited enhanced drug efflux and a higher glutathione content. Our data suggest that the levels of cisplatin-DNA lesions are critical for drug sensitivity and apoptosis induction in this in vitro ovarian carcinoma model. Comparative analysis of the p53 gene in sensitive and resistant cells revealed the presence of the same heterozygous mutation in exon 5. A 2-fold increase in p53 mRNA and protein amounts was observed in resistant cells as assessed by Northern and Western blots, respectively. Immunocytochemical staining revealed a higher percentage of p53 stained nuclei in resistant cells. RT-PCR analysis of p53 transcripts showed that both wild-type and mutated alleles were transcribed in sensitive as well as in resistant cells. However, mutated transcripts were 1.5-fold more abundant than wild-type transcripts in sensitive cells, whereas they were 2-fold higher in resistant cells. In addition, mdm-2 protein was over-expressed in resistant cells. Our results address the question of the functionality of p53 protein and its possible role in apoptosis induction in this model. In resistant cells, p53 protein might be inactivated by 2 mechanisms: mutation and complexation with mdm-2 protein. Therefore, the presence of non-functional p53 in resistant cells might be involved in the relative failure of cisplatin-induced apoptosis in these cells.

Adenocarcinoma↗
PubMed1994

Coactivation of the MDR1 and MYCN genes in human neuroblastoma cells during the metastatic process in the nude mouse.

In metastatic human neuroblastoma, MYCN amplification and MDR1 overexpression are frequently observed. No in vivo model is yet available for the study of the regulation of these two genes during the metastatic process of this disease. Culture of an involved bone marrow of a patient with stage IV neuroblastoma gave rise to an established in vitro neuroblastoma cell line, IGR-N-91, and a subsequent s.c. xenograft model in nude mice. When cultured in vitro, blood cells, bone marrow, and the myocardium of mice bearing s.c. tumor xenograft reproducibly yielded cells with morphological and molecular features of neuroblastoma cells, including consistent MYCN amplification (60 copies/haploid genome). Compared to the neuroblastoma cells of the primitive s.c. tumor xenograft, metastatic cells showed a significant increase in the MYCN gene transcript levels associated with an overexpression of the MDR1 gene mRNA levels leading to a P-glycoprotein capable of extruding Adriamycin. This study offers compelling evidence that (a) IGR-N-91 is a human neuroblastoma xenograft model able to induce metastasis in nude mice, (b) an increase in MYCN and MDR1 transcripts levels is associated with the metastatic process, and (c) IGR-N-91 provides a biological tool for the study of gene activations during tumor dissemination in neuroblastoma.

Animals↗
PubMed1991

Antigenic properties associated with Vinca alkaloid resistance in ovarian cancer cells: identification of a 92,000 Da protein.

In order to characterize the membrane changes related to Vinca alkaloid resistance, we raised monoclonal antibodies (mAbs) against a Vincristine resistant subline (OV1/VCR) derived from a human ovarian adenocarcinoma cell line (OV1/p). Among three monoclonal antibodies selected for a higher binding to OV1/VCR than to OV1/p cells, one designated OVR09, recognized a Mr 92,000 protein. This protein appears to be gradually overexpressed along the drug resistance establishment in vitro, and to decrease slowly in absence of drug. Further, mAb OVR09 showed a much higher binding to the vinblastine resistant epidermoid tumor cell line KbV1 than to its parental counterpart. The Mr 92,000 protein was also detected in various tumor cell lines and in an ovarian carcinoma surgical sample.

Animals↗
PubMed1989

Over-expression of MDR1 gene with no DNA amplification in a multiple-drug-resistant human ovarian carcinoma cell line.

Human ovarian adenocarcinoma cells IGROV1 were induced to become resistant in vitro to Vincristine (VCR) by continuous and discontinuous stepwise exposure to the drug. Both sublines exhibited similar indexes of resistance (approx. 800). The acquisition of VCR resistance was associated with changes of morphology and with cross-resistance to Adriamycin, VP16 and actinomycin D. Addition of verapamil enhanced sensitivity of resistant cells to VCR. This multi-drug-resistant (MDR) phenotype was associated with high levels of human MDR1 gene transcripts (25- to 100-fold). In contrast to other reports, no significant amplification of the locus could be observed. Reactivity with MRK16, a monoclonal antibody (MAb) directed against the MDR 170 kDa protein, was found to be related to the level of MDR1 transcription. In addition, both OV1/VCR sublines exhibited a marked loss of tumorigenicity. Besides the chromosomal markers of OV1/p, the two resistant sublines revealed a common cytogenetic rearrangement: a deletion of the short arm of one chromosome 11: del(11)(p12). We suggest that the acquisition of this marker might be associated with the non-tumorigenic phenotype of OV1/VCR-resistant sublines.

Adenocarcinoma↗
PubMed1989

Drug-related chromosomal changes in chemoresistant human ovarian carcinoma cells.

Four resistant sublines were derived from the sensitive human ovarian carcinoma IGROV 1 (OV1-P) cell line by exposure to increasing concentrations of vincristine, doxorubicin, and cisplatinum. The vincristine-resistant sublines expressed the MDR phenotype associated with a complete reversion of malignant properties. Cytogenetic studies of sensitive and resistant cells have been repeatedly performed over a 1-year period. Consistent and stable drug-related chromosomal structural rearrangements have been observed in each resistant population affecting chromosomes 3, 4, 6, 8, 11, 22, and X. The most significant result was the presence in OV1/P cells of a minor subclone with a del(11)(p13) marker that represented the whole OV1/VCR population. This result suggests a possible role of this deletion either in the drug-selection process, or in the malignant reversion.

Adenocarcinoma↗
PubMed1988

The management of penetrating injuries of the back. A prospective study of 230 patients.

This is a prospective study of 230 patients with penetrating injuries of the back. The decision to operate or observe was taken exclusively on the abdominal physical findings. One hundred ninety-five patients (85%) did not require operation, 30 (13%) underwent a therapeutic laparotomy, four (1.7%) an unnecessary operation, and one patient (0.4%) had a completely negative laparotomy. The diagnosis and management was delayed in five (2.2%) patients with no serious consequences. Mortality rates were not recorded in this series. The initial physical examination was accurate in 95.2% of the patients. We suggest that penetrating injuries of the back should be assessed in the same way as anterior abdominal injuries. Physical abdominal examination is reliable in detecting significant intra-abdominal injuries.

Abdomen, Acute↗
PubMed1985

Characterization of a human ovarian adenocarcinoma line, IGROV1, in tissue culture and in nude mice.

A cell line, IGROV1, originating from an ovarian carcinoma of a 47-year-old woman was established in tissue culture and in nude mice. Maintained in monolayer cultures, IGROV1 cells exhibited a 20-h doubling time and highly tumorigenic properties. The s.c. injection of 2 X 10(6) cultured cells into nude mice gave rise to fast growing tumors, while the i.p. route induced a peritoneal carcinomatosis with ascites which killed the animals in 2 months. The epithelial morphology of IGROV1 cells was retained during in vitro and in vivo passages, as judged by both the light and the electron microscopes. Two cytogenetic markers characterize IGROV1 cells: a paracentric inversion of chromosome 3, and a translocation between chromosomes 2 and 5. The constitutional karyotype of the patient was normal. These characteristics make the IGROV1 cell line a suitable experimental model for the treatment of human ovarian carcinomas and for biological studies of human solid tumors.

Adenocarcinoma↗
PubMed1984

Does the natriuretic hormone play a role in hypertension in South African blacks?

It has been suggested that circulating natriuretic hormone may be important in the pathogenesis of essential hypertension by inhibiting the ouabain-sensitive Na+, K+-ATPase pump and that this effect should be more pronounced in low-renin hypertensives. We have studied serum and red blood cell sodium and potassium concentrations in vitro, before and after exogenous ouabain, in White normotensives and Black subjects with essential hypertension and in two groups of renal patients. No convincing evidence of sodium or potassium inhibition could be found in Blacks with either low-renin or high-renin hypertension. Striking inhibition was seen in the renal groups, supporting a circulating natriuretic factor, but there were anomalies within the renal groups, which suggest additional cell membrane abnormalities.

Adult↗
PubMed1983

Culture of clonogenic cells from various human tumors: drug sensitivity assay.

Cells obtained from human solid tumor biopsies and from ascites of various histological origin were cultured in soft agar. Forty-six out of 72 malignant biopsy specimens, consisting mainly of ovarian and breast adenocarcinoma, were grown successfully. Cloning efficiencies ranged from 0.001 to 1%. In a few cases large variations occurred in the different specimens from the same patient. The cells in the colonies had the same morphological characteristics as those of the original tumor. The soft agar assay was used to study the chemotherapeutic response of ovarian tumors.

Adenocarcinoma↗
PubMed1982

Sodium and potassium status, plasma renin and aldosterone profiles in normotensive and hypertensive Johannesburg blacks.

Many studies have suggested that there is an association between the sodium status, plasma renin and aldosterone profile and essential hypertension. We measured serum, urine and red blood cell (RBC) sodium and potassium, plasma renin and aldosterone levels in normotensive Whites, normotensive Blacks, mildly hypertensive Blacks, severely hypertensive Blacks and Blacks with malignant hypertension. There were no important differences between the groups studied as regarded the serum sodium, serum potassium and urinary sodium excretion values. However, the urinary potassium excretion was significantly lower in normotensive and hypertensive Blacks than in Whites. RBC sodium concentrations showed no significant differences in the mean values across the range of degrees of hypertension in Blacks, although they tended to be higher in the more severely hypertensive groups. Blacks with mild-to-moderate hypertension as well as the severely hypertensive group had significantly lower plasma renin levels than the normotensive group; only in the malignant hypertensives with advanced renal failure did the plasma renin and aldosterone levels rise.

Adult↗