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Biomedical subjects

C Millet

Publications and source records attributed to C Millet.

17 recordsLinked to original sources

Serum-to-urinary prostate specific antigen ratio: its impact in distinguishing prostate cancer when serum prostate specific antigen level is 4 to 10 ng./ml.

PURPOSE: Benign prostatic hyperplasia (BPH) was shown to be associated with high concentrations of urinary prostate specific antigen (PSA). We investigated the serum-to-urinary PSA ratio in patients undergoing prostate biopsy to assess its efficacy in enhancing serum PSA specificity in the detection of prostate carcinoma. MATERIALS AND METHODS: From November 1995 through January 1996 consecutive patients undergoing prostate biopsy were prospectively included in the study. Serum and urine PSA levels were measured at our laboratory with the Tandem-R assay. Samples were drawn 24 hours before prostate biopsy and at a distance from prostatic manipulation or ejaculation. RESULTS: We studied 73 patients with BPH and 57 with prostate cancer. Differences between BPH and prostate cancer were statistically significant considering serum PSA or serum-to-urinary PSA ratios. In the 50 patients with a serum PSA of 4.0 to 10.0 ng./ml. (35 with BPH and 15 with prostate cancer) the differences between prostate cancer and BPH were still significant only when considering serum-to-urinary PSA ratio. Receiver operating characteristic curves showed that serum-to-urinary PSA ratio was a better predictor of prostate cancer than serum PSA. CONCLUSIONS: Our results suggest that the serum-to-urinary PSA ratio may be useful in distinguishing BPH from prostate cancer, particularly in the diagnostic gray zone of serum PSA between 4.0 and 10.0 ng./ml.

Aged

Serum-to-urinary prostate-specific antigen ratio: a potential means of distinguishing benign prostatic hyperplasia from prostate cancer.

OBJECTIVE: High concentrations of serum prostate-specific antigen (PSA) may be associated with the presence of benign prostatic hyperplasia or prostatitis. We investigated the serum-to-urinary PSA ratio in patients with or without prostate cancer to assess its efficacy in enhancing serum PSA specificity. METHODS: Patients presenting abnormal findings in digital rectal examination or documented prostate carcinoma were prospectively included in the study. A control group, with no evidence of prostate disease, hospitalized in the same time interval was included. Serum and urine PSA levels were measured in our laboratory with the Tandem R assay (Hybritech). Samples were drawn twice at 2-month intervals (M1 and M3). RESULTS: Sixty-eight patients were included in the study divided into 27 cases of benign prostatic hyperplasia, 20 of prostate carcinoma, 10 of prostatitis and 11 patients in the control group. Serum and urine PSA levels were not correlated (r < or = 0.1). There was no significant difference in any group from M1 to M3 as regards urinary PSA (p > or = 0.15). Intergroup comparison showed significantly (p < or = 0.004) high urinary PSA (mean level +/- SEM 28.3 +/- 3.4 micrograms/mmol creatinine) only in the benign prostatic hyperplasia group, mean levels in the prostate carcinoma, prostatitis and control groups being 3.7 +/- 1.1, 11 +/- 2.9 and 5.2 +/- 0.9 micrograms/mmol creatinine, respectively. Differences in urinary PSA levels between the confined prostate carcinoma and benign prostatic hyperplasia groups (p = 0.0008) were further increased when considering the serum-to-urinary PSA ratio (p = 0.0003). CONCLUSION: Our results suggest that the serum-to-urinary PSA ratio may be useful in distinguishing benign prostatic hyperplasia from prostate cancer.

Aged

Role of p53 and RB on in vitro growth of normal umbilical cord blood cells.

Human umbilical cord blood (UCB) is rich in hematopoietic stem cells and progenitors and recently has been used in the clinic as an alternative source for graft and marrow repopulation. We tried to determine in vitro the roles of wild-type (wt) p53 and wt RB tumor/growth suppressor genes in the regulation of proliferation and maturation of hematopoietic UCB cells. CD34+ cells, isolated from mononuclear cells of UCB, were cultured in semisolid medium under conditions that favor growth of hematopoietic cells. We studied the level of expression of p53 and RB mRNAs and proteins during cell culture by Northern blot and cytofluorometry analysis, respectively. Sense (S), antisense (AS), or scrambled (missense [MS]) p53 and RB oligodeoxynucleotides (ODNs) were used to study the behavior of these cells in the absence of expression of p53 and/or RB. Adequate doses of p53 or RB ODNs inducing maximal inhibitory effect were used to study the behavior of these cells in the absence of expression of p53 and/or RB. Adequate doses of p53 or RB ODNs inducing maximal inhibitory effect with minimal cellular toxicity were determined. Exposure of CD34+ cells to p53 or AS, RB AS, or both p53 and RB AS but not other ODNs (sense or missense) resulted in a significantly increased number of colony-forming units-granulocyte/macrophage (CFU-GM) induced by interleukin-3 (IL-3) and/or granulocyte-macrophage colony-stimulating factor (GM-CSF). The number of erythroid colonies (CFU-E) and burst-forming units (BFU-E) derived from CD34+ cells in the presence of erythropoietin (Epo) was not significantly increased, whereas the number of such colonies was markedly increased in the presence of IL-3 + EPO upon p53 AS and/or RB AS treatment with hypothesis that wt p53 and RB are proliferation suppressor genes that interfere with normal maturation of hematopoietic cells.

Antigens, CD34

[Immunoenzymatic assays of c-erbB-2 oncoprotein and epidermal growth factor receptor in breast cancer: correlation with clinical and biological parameters].

Two new immunoenzymatic assays for c-erbB-2 oncoprotein and epidermal growth factor receptor (EGF-R) (Oncogene Science) in human breast cancer were validated. Correlations between these assays and some clinical and biological parameters were also studied. The repeatability and reproducibility of standard curves for the two methods gave a coefficient of variation (CV) of less than 4% and about 10% respectively. The accuracy of c-erbB-2 oncoprotein and EGF-R assays was examined by using dilution and recovery tests throughout the standard curves. The linear relations between theoretical and measured values, for these tests, had slopes close to 1 and an intercept near 0. The median value for EGF-R, measured on solubilized membranes of 290 primary tumors, was 0.12 fmol/micrograms protein, the mean value was 0.37 (range 0 to 35.7). For c-erbB-2 oncoprotein, the median value, measured using the same population, was 2.75 human neu unit/micrograms protein, the mean value was 7.85 (range 1 to 125). There was an inverse relationship between EGF-R values and those for the estrogen receptor (ER), progesterone receptor and pS2 protein as well as menopausal status. C-erbB-2 oncoprotein concentrations were positively correlated with ER, pS2 protein and cathepsin D. Furthermore, a significant positive correlation was observed between EGF-R levels and c-erbB-2 oncoprotein levels. In conclusion, immunoenzymatic assays of EGF-R and c-erbB-2 oncoprotein are easy to use, sensitive and reliable. The accurate standardisation of immunoenzymatic assays could contribute to the clinical use of EGF-R and c-erbB-2 oncoprotein as prognostic factors in breast cancer.

Breast Neoplasms

Cathepsin D in normal and neoplastic thyroid tissues.

BACKGROUND: Cathepsin D is a widely distributed lysosomal acidic endopeptidase. It is an estrogen-regulated protein that is a prognostic factor in breast cancer. The aim of this study was to measure cathepsin D concentrations in thyroid tissues and to correlate these concentrations with clinical and pathologic parameters. METHODS: Cathepsin D and thyroglobulin concentrations were measured in the cytosol of normal thyroid tissues (n = 14), benign nodules (n = 6), and thyroid carcinomas (n = 32) with an immunoradiometric assay. Statistical analysis was based on the Kruskal-Wallis and Wilcoxon tests and on the Spearman rank correlation coefficient. RESULTS: The mean level of cathepsin D, expressed as picomoles per milligram protein minus thyroglobulin, was higher in the 32 carcinomas, 29.1 +/- 15.5, than in the 14 normal thyroid tissues, 8.4 +/- 2.5 (p < 0.001) or in the 6 benign nodules, 11.2 +/- 7.3 (p = 0.003). Cathepsin D concentrations correlated with tumor size; Spearman rank correlation coefficient was rs = 0.44 (p = 0.012). No significant difference was found regarding histologic type. Cathepsin D concentrations were inversely correlated with the thyroglobulin level in the tumor; Spearman rank correlation coefficient was rs = -0.60 (p < 0.001). CONCLUSIONS: Cathepsin D concentration is higher in thyroid carcinoma than in normal thyroid tissue. Increased cathepsin D concentrations correlate with thyroid tumor size but not with histologic type. Further studies should be done to confirm the potential prognostic value of cathepsin D in patients with thyroid carcinomas.

Adult

In vitro p53 and/or Rb antisense oligonucleotide treatment in association with growth factors induces the proliferation of peripheral hematopoietic progenitors.

In this work we intended to determine whether p53 and/or retinoblastoma (Rb) tumor suppressor genes are involved at specific stages in the process of in vitro human peripheral stem cell hematopoiesis. Mononuclear peripheral blood cells were depleted of adherent cells and T lymphocytes (A-T-PMCs). Cells were then cultured in semisolid medium, under conditions that favor the growth of specific progenitor cell types. A-T-PMCs were exposed to p53 and/or Rb sense, scrambled DNA and antisense oligodeoxynucleotides. p53 and/or Rb antisenses (but not their senses or scrambled DNA) treatment of A-T-PMCs resulted in a significantly increase in the number of granulocyte/macrophage colony-forming units (CFU-GM) in the presence of interleukin-3 (IL-3) and/or granulocyte/macrophage colony-stimulating factor (GM-CSF). After antisense treatment, blast forming units/erythroblasts (BFU-E) derived from A-T-PMCs cultured in the presence of IL-3 + erythropoietin (Epo) were also increased whereas colony forming units/erythroblasts (CFU-E) were not markedly affected in the presence of Epo only. Megakaryocytic colony (CFU-Meg) formation from A-T-PMCs in the presence of interleukin-6 (IL-6) + IL-3 + Epo was also increased after antisense oligodeoxynucleotide treatment. These results are consistent with the hypothesis that p53 and Rb tumor suppressor gene products are involved in the control of distinct signal pathways in different peripheral progenitor cells.

Base Sequence

Estrogen receptors and cathepsin D in human thyroid tissue.

BACKGROUND: To investigate the significance of estrogen receptors (ER) in the pathogenesis of thyroid dysplasia, the authors analyzed, by analogy with breast cancers, ER and three estrogen-regulated proteins: progesterone receptor (PR), cathepsin D, and pS2 protein, in cytosols of 42 human thyroid tissues. METHODS: ER and PR were measured by an immunoenzymatic assay and cathepsin D and pS2 by an immunoradiometric assay. Tissue specimens included 7 normal tissues, 6 benign nodules, 8 toxic adenomas, 7 from patients with Graves disease, and 14 carcinomas. RESULTS: ER was present at very low concentrations, with no statistical difference between neoplastic and nonneoplastic tissues. The mean levels of cathepsin D, expressed as pmol/mg protein minus thyroglobulin, were higher in the 14 carcinomas (P = 0.0003), the 7 specimens from patients with Graves disease (P = 0.006), and the 8 toxic adenomas (P = 0.04) than in the 7 normal thyroid tissues. A significant difference also was observed between the carcinomas (P = 0.003) and six benign nodules. Compared to TNM parameters, cathepsin D concentrations correlated with tumor size: higher cathepsin D levels were found in pT4 than in pT2 and pT3 carcinomas. All the tissues tested were negative for PR and pS2 protein. CONCLUSIONS: The results clearly indicate a significant difference between neoplastic and normal thyroid tissue in terms of the amount of cathepsin D, but not that of ER. This suggests that cathepsin D probably is not regulated by estrogen but simply is a marker of protease activity during invasion by thyroid carcinomas.

Adenoma

Effect of bromolevamisole and other imidazo [2,1-b] thiazole derivatives on adenylate cyclase activity.

We studied the effect of bromolevamisole (BL) and other imidazo [2,1-b] thiazole derivatives--bromodexamisole (BD) and levamisole (LV)--on adenylate cyclase (AC) activity. BL and BD both inhibited forskolin-activated human thyroid AC, while LV had no effect. This inhibition was non-stereospecific and the IC50 values, as measured with 1 mM ATP and 40 microM forskolin, were 0.95 and 0.80 mM for BL and BD, respectively. In contrast, human thyroid alkaline phosphatase (ALP) inhibition was stereospecific, with IC50 values of 0.0012 mM for BL and 0.9 mM for BD. LV was a 10-fold weaker inhibitor of ALP than BL. These results show that ALP inhibition is not correlated with forskolin-activated AC inhibition. Furthermore, in the presence of a competitive inhibitor of GTP (0.1 mM guanosine 5'-O-(2-thiodiphosphate), BL retained its antagonizing effect on forskolin-activated AC which suggests a direct action on the catalytic subunit. The inhibition was of the mixed type, indicating a complex interaction between BL and AC. Glucagon-activated AC activity in rat liver membranes was also inhibited by BL, although to a slightly lesser degree than thyroid stimulating hormone (TSH)-activated AC from human thyroid for a given BL concentration. In cultured human thyroid cells, BL (0.25 mM) induced a potent decrease in cAMP accumulation after 2 hr of stimulation by TSH. Taken together, these results show that BL inhibits AC and that this inhibition is not organ-specific.

Adenylyl Cyclase Inhibitors

Congenital dislocation of the hip.

Early diagnosis and treatment are the keys to a successful result in infants with congenital dislocation of the hip. In the neonatal period, a majority of infants with hips that would later be found to be dislocated can be detected and effectively treated. With the use of ultrasonography to supplement clinical suspicion, the number of children with congenital dislocation of the hip diagnosed in the newborn period should be expected to increase. Repeated examination, especially during the first 6 months of life, can be expected to detect those additional children with congenital dislocation of the hip who were not detected in the nursery. The Pavlik harness has been shown to obtain a successful result in most children younger than 6 months of age while holding the incidence of avascular necrosis to nearly zero. Even though these results are encouraging, the problem must be discovered early for the child with congenital dislocation of the hip to be treated optimally. Thus, it is of the utmost importance that the physician have an awareness of this problem. The primary physician must also continue to conscientiously examine the hips of patients on a regular basis even after the initial examination and, when necessary, use the added modalities available to him or her to accurately diagnose questionable hip conditions of patients.

Female

[Neuropeptides and respiratory diseases: prospects in the treatment of asthma].

The autonomic nervous system includes, side by side with the sympathetic and parasymathetic systems, a third, non-adrenergic and non-cholinergic system called NANC. The mediators in this system are peptides acting as neurotransmitters, i.e. neuropeptides. The NANC system has two components: bronchodilator and bronchoconstrictor. The bronchial relaxant system, called non-adrenergic inhibitory system, has several neurotransmitters, viz.: vasoactive intestinal peptide (VIP), isoleucine histidine peptide (IHP) and methionine histidine peptide (MPH), all derived from a common precursor: pre-pro VIP. MHP has been described in man and IHP in some animal species. VIP relaxes the bronchial smooth muscle, is vasodilator and exerts cellular effects in phagocytes, lymphocytes and mast cells. VIP receptors are present on cells. The other component, called non-cholinergic excitatory system, has tachykinins as neuromediators, including substance P, neurokinins A and B, neuropeptide K and calcitonin gene related peptide (CGRP). Substance P contracts the bronchi, increases mucus secretion, dilates vessels and also exerts cellular effects in lymphocytes and phagocytes. Tachykinins act through receptors 3 types of which are now known: NK 1, NK 2 and NK 3. Other neuropeptides have been isolated, including galanin, neuropeptide Y, bombesin, gastrin releasing peptide, enkephalins and katacalcin. The coexistence, in pre- and post-synaptic positions, of the conventional mediators (noradrenaline, acetylcholine) and neuropeptides leads to the concept of co-transmission and makes the notion of nerve impulse transmission more complex. The development of neuropeptide agonists and antagonists opens new therapeutic prospects in the management of asthma.

Asthma

[Congenital pseudohypoaldosteronism: apropos of 6 cases].

Pseudohypoaldosteronism is a congenital disorder, with an as yet unclear pathophysiology, mode of inheritance and frequency. We have recently diagnosed 6 cases in a relatively short period of time, which suggests that the frequency of the disease may be underestimated. This may be due to a high variability in the clinical expression and to the existence of asymptomatic forms. Autosomal dominant and autosomal recessive modes of inheritance have been reported which probably correspond to different underlying mechanisms.

Chromosome Aberrations

Knee braces.

The preceding discussion has profiled the three different types of knee braces which are available on today's market. It also has attempted to discuss the controversies surrounding these braces and to analyze the scientific data presented to date. Prophylactic braces have been shown to be ineffective in preventing knee injuries in its present day design. Evidence also has shown that their use may even lead to increased knee injuries. Rehabilitative braces, on the other hand, do serve a useful purpose in regard to the operative and non-operative treatment of ligamentous knee injuries. With their ease of application and control of joint motion, they are an important addition to the surgeon's armamentarium. One must keep in mind, however, that these braces provide little static anterior/posterior control and the hinge settings may not actually affect true joint motion. Functional knee braces may play a role in the treatment of patients with pathological laxity due to an injury of the anterior cruciate ligament. Combined with an adequate rehabilitation program and activity modification, these braces do limit excessive anterior tibial translation under low loading conditions. However, under conditions of high loading these braces provide little or no resistance to anterior translation. Therefore, in most sporting activities, their efficacy is questionable. Knee bracing continues to be a complex and controversial topic in the field of orthopedic surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Athletic Injuries