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Biomedical subjects

G Leo

Publications and source records attributed to G Leo.

At least 55 records · Page 3Linked to original sources

Immunoradiometric detection of pS2 and total cathepsin D in primary breast cancer biopsies: their correlation with steroid receptors.

Commercially available immunoradiometric assays were used for pS2 and total cathepsin D determination in the cytosol fraction obtained from 266 primary breast cancers. We show that pS2 and cathepsin D values were significantly associated (Spearman's rank correlation: P < 0.0001) in tumours from lymph node-positive patients (N+), while such association did not reach significance in tumours taken from patients with negative lymph nodes (N-). Moreover, cathepsin D concentrations in pS2-rich tumours (pS2 above the median value, 5 ng mg-1 protein) were significantly higher (Mann-Whitney-Wilcoxon's rank-sum test: P = 0.00001) than those obtained in the samples expressing less than 5 ng of pS2 per mg of protein. pS2 was also correlated to both the oestrogen receptor (ER) (Spearman's rank correlation: P < 0.0001) and the progesterone receptor (PR) (Spearman's rank correlation: P = 0.022). No significant differences in the expression of pS2 and cathepsin D taken from N+ and N- patients were found. Furthermore, no significant differences in pS2 and cathepsin D expression were obtained by stratifying tumours on the basis of their size (T). pS2 and cathepsin D values obtained in ER-positive/PR-positive tumours did not significantly differ from the values obtained in ER-positive/PR-negative and in ER-negative/PR-positive tumours. We conclude that pS2 could have a role in cathepsin D expression, and that it can be used in the assessment of a functioning oestrogen response machinery in those tumours that express only ER.

Adult↗

Reference values for respiratory rate in the first 3 years of life.

BACKGROUND: Raised respiratory rate is a useful sign to diagnose lower respiratory infections in childhood. However, the normal range for respiratory rate has not been defined in a proper, large sample. OBJECTIVE: To assess the respiratory rate in a large number of infants and young children in order to construct percentile curves by age; to determine the repeatability to the assessment using a stethoscope and compare it with observation. METHODS: Respiratory rate was recorded for 1 minute with a stethoscope in 618 infants and children, aged 15 days to 3 years old, without respiratory infections or any other severe disease when awake and calm and when asleep. In 50 subjects we compared respiratory rate taken 30 to 60 minutes apart to assess repeatability, and in 50 others we compared simultaneous counts obtained by stethoscope versus observation. RESULTS: Repeatability was good as the standard deviation of differences was 2.5 breaths/minute in awake and 1.7 breaths/minute in asleep children. Respiratory rate obtained with a stethoscope was systematically higher than that obtained by observation (mean difference 2.6 breaths/minute in awake and 1.8 breaths/minute in asleep children; P = .015 and P < .001, respectively). A decrease in respiratory rate with age was seen for both states, and it was faster in the first few months of life when also a greater dispersion of values was observed. A second degree polynomial curve accurately fitted the data. Reference percentile values were developed from these data. CONCLUSIONS: The repeatability of respiratory rate measured with a stethoscope was good. Percentile curves would be particularly helpful in the first months of life when the decline in respiratory rate is very rapid and prevents to use cut off values for defining "normality."

Aging↗

Enzyme-linked immunosorbent assay of HER-2/neu gene product (p185) in breast cancer: its correlation with sex steroid receptors, cathepsin D and histologic grades.

One hundred and nine primary breast cancers were analyzed to assess the presence of the HER-2/neu gene product (p185), the oestrogen (ER) and the progesterone (PR) receptors, and the total cathepsin D status. An enzyme-linked immunosorbent assay (ELISA kit, Oncogene Science Inc.) was used for the evaluation of p185 in pellets obtained after a 100,000 x g centrifugation, ER and PR were measured by enzyme immunoassay (EIA kit, Abbott Laboratories), and the total cathepsin D content was evaluated by immunoradiometric assay (IRMA kit, CIS Biointernational). We showed that the ELISA kit is feasible to quantify the p185 present in breast cancer cell membranes, and that the detector antibody recognises a protein of apprroximatly M(r) 185,000. The detected antigen was inversely related to both ER and PR, but it did not correlate to total cathepsin D. No significant differences were found in the expression of p185, ER, PR, cathepsin D between infiltrating ductal carcinomas without special features (NOS) and non-ductal (non-NOS) carcinomas. Nevertheless, in NOS carcinomas, a trend was observed in the p185 levels expressed by the tumours with different histological grades, in that p185 concentration was higher in the poorly differentiated grade 3 with respect to grade 2 and grade 1.

Adult↗

p53 associated with cathepsin D in primary breast cancer.

The p53 protein was identified in primary breast carcinomas by specific binding of PAb1801 and PAb240 antibodies. Using sodium dodecyl sulfate electrophoresis followed by immunoblotting on nitrocellulose membrane, the p53 protein was identified in 36 nuclear fractions obtained from 60 primary breast cancers; semiquantitation of p53 was performed by densitometric scanning. The total cathepsin D content, the estrogen and progesterone receptor concentration values and the axillary lymph node involvement were also assessed. Tumors expressing p53 had significantly higher levels of cathepsin D than those in which p53 was undetectable. p53 expression was strongly associated with low or negative estrogen receptor values; progesterone receptor concentrations were also significantly higher in p53-negative tumors than in those tumors with detectable p53 levels. Finally, a significant relationship between p53 expression and lymph node metastasis was observed. It was concluded that a positive association between p53 and cathepsin D values exists which is of prognostic interest in that both cathepsin D and p53 are associated with a high tumor grade and metastatic activity.

Breast Neoplasms↗

Expression of cathepsin D in malignant and in the corresponding non-malignant node-negative laryngeal samples: correlation with receptors for androgen, glucocorticoid, oestrogen and progesterone.

A standard immunoradiometric technique was used to investigate the distribution of the intracellular aspartic proteinase cathepsin D in 33 malignant and in the corresponding histologically-proven non-malignant fragments obtained from lymph node negative patients suffering from larynx cancer. In both tissues the androgen, glucocorticoid, oestrogen and progesterone receptors were also assayed. Our data indicate that cathepsin D was present in both tissues, with level significantly higher (P < 0.0001) in the cancerous fragments (with a mean of 33 +/- 3.4 pmol/mg protein) than in the corresponding non-cancerous specimen (with a mean of 20.8 +/- 2 pmol/mg protein). A significant positive association (P < 0.001) between cathepsin D and PR concentration values in the cancerous larynx was observed; accordingly, tumours expressing PR had significantly (P = 0.0005) higher cathepsin D levels than the tumours which did not contain the receptor. In contrast, such a relationship was absent in the non-malignant specimens. As regards the other steroid receptors, no significant relationship between them and cathepsin D was observed. We conclude that cathepsin D may have a role also in laryngeal carcinoma and that its association with the PR could indicate a possible role of the receptor in the biology of this disease.

Aged↗

Role of bronchial and bronchoalveolar lavage in chronic obstructive lung disease.

The authors review the role of bronchoalveolar and bronchial lavage in chronic obstructive lung disease patients. Only a few papers were published in the last ten years on this matter. In addition, data are incomplete and often conflicting, mainly because of the limited number of patients sampled and of non-standardized techniques of analysis. However, both bronchoalveolar and bronchial lavage are likely to be useful research tools to understand the pathophysiologic mechanisms underlying chronic obstructive lung disease.

Bronchi↗

Relation of cathepsin D level to the estrogen receptor in human breast cancer.

Seventy-three primary human breast cancers were analyzed to assess the presence of estrogen and progesterone receptors, the p29 protein, and the total cathepsin D status. No significant relationship was found between cathepsin D concentration and the presence of ER or PR, either by Fisher's exact test or Spearman's rank correlation (P greater than 0.1). However, a significant association was found between cathepsin D and p29 (Fisher's exact test, P less than 0.001) and between cathepsin D and steroid receptor status in samples expressing both estrogen and progesterone receptors (positive by steroid binding assay and enzyme immunoassay) (P less than 0.05). This association was more significant in tissues expressing estrogen and progesterone receptors as well as p29 (P less than 0.001). In contrast, cathepsin D synthesis was not related to tumor size, lymph node involvement, or patient's age (P greater than 0.05). Steroid receptors and cathepsin D were also assayed in samples of non-malignant tissue from 16 mastectomies; there was a significantly higher relative concentration of cathepsin D in the malignant specimens (Student's t-test, P less than 0.001).

Adult↗

Type II oestrogen binding site is associated with the major 4S oestrogen receptor isoform in breast tumours.

Using high resolution isoelectric focusing we have been able to identify a low affinity/high capacity oestrogen binding protein, which exhibits an apparent pI of 7.0. Using this system it can be separated from the previously described high affinity oestrogen receptor (ER) isoforms which focus at pI 6.1, 6.3, 6.6 and 6.8. The pI 7.0 protein was detected in 30/30 breast tumours analysed and had the binding characteristics of the cytoplasmic Type II ER (Kd = 88 +/- 8 nM). The concentration of this protein was shown to be significantly correlated with the concentration of the pI 6.6 species, which represents the major 4S isoform. It is not related to any other isoform of ER, and is expressed independently of the progesterone receptor. The importance of this observed relationship with respect to ER function remains obscure, but it may provide new insights into the role of the Type II oestrogen binding site in breast cancer.

Binding Sites↗

Steroid receptor status in malignant and non-malignant larynx.

We investigated for the first time the relationships among all the different steroid receptor classes and between steroid receptor status and lymph node involvement in laryngeal carcinoma. Androgen (AR), oestrogen (ER), progesterone (PR) and glucocorticoid (GR) receptors were assayed in the high-speed soluble fraction and in the nuclear extract from 73 carcinomas of the larynx. Forty-one, 26, 15, and 13 tumours expressed cytosolic GR, ER, AR, and PR, respectively, while 33, 26, 13 and 13 biopsies were nuclear-positive for GR, ER, AR, and PR, respectively. Data obtained in histologically-proven non-cancerous larynx (N = 20) compared to those obtained in the malignant specimens showed a significant loss of ER and PR in cancerous larynx over that in the non-cancerous tissue. Lymph node metastases were evaluated in only 53 of the 73 patients and they were noted in 22 cases (41.5%). No significant relationships were found either among the different classes of steroid receptors or between steroid receptors and lymph node involvement. Despite the apparent absence of any interrelationships among the different receptors or tendency towards metastasis, the presence of steroid receptors would justify the use of hormonal manipulations which could be effective in the management of this disease.

Adult↗

Tamoxifen binding sites heterogeneity in breast cancer: a comparative study with steroid hormone receptors.

Steroid receptors and tamoxifen binding sites (TBS) were assayed in the soluble fraction of 121 primary breast cancers. Scatchard analysis of TBS in high speed supernatant (100,000 g) showed one population of binding sites; however, biphasic plots were obtained in low speed supernatants (40,000 g). Isoelectric focussing of supernatants preincubated with radioactive tamoxifen identified two classes of TBS (pI 4.1-4.6) which have different binding affinities and bind neither oestradiol nor diethylstilbestrol. Association between TBS and steroid receptors was: TBS positive/progesterone receptor positive 32.6%, TBS positive/glucocorticoid receptor positive 52.7%, TBS positive/oestrogen receptor positive 60% and TBS positive/androgen receptor positive 72.2%. We conclude that heterogeneous TBS are present in low speed fractions and can be easily separated from the oestrogen receptor by isoelectric focussing. The association between TBS and steroid receptor status could be of clinical value in the management of primary breast cancer.

Breast Neoplasms↗

Serologic and virologic analysis of type D simian retrovirus infection in a colony of Celebes black macaques (Macaca nigra).

Celebes macaques were tested for type D simian retrovirus (SRV) infection. SRV infection was first detected in one serum sample collected during 1980. By 1983, 32 of 46 monkeys (70%) were infected. Serotyping of the SRV isolates determined that 0/26 of the isolates were SRV-1; 24/26 were SRV-2; 1/26 was SRV-5; and 1/26 could not be typed. Restriction endonuclease mapping confirmed the SRV-2C and SRV-5 isolates. In addition, two SRV-2C variants were detected.

Animals↗

Gallstone ileus: report of 23 cases with emphasis on factors affecting survival.

The records of 23 patients operated for gallstone ileus in a ten-year period were reviewed. The mean age was 75 and surgical procedure consisted always in the simple relief of obstruction without cholecystectomy and fistula interruption. Operative mortality was overall 17%; excluding two patients already perforated on admission; actual mortality due to uncomplicated ileus was 9%. One patient was at his second episode of gallstone ileus and in another the obstruction was sustained by two stones. The most common site of impaction was distal ileum, while a pyloro-duodenal obstruction with Bouveret's syndrome was noted in two cases. Since age was seen to be the only variable correlated with mortality it was concluded that surgical treatment of gallstone ileus in the elderly patient should be limited to simple relief of obstruction, in case leaving cholecystectomy to a subsequent second operation.

Age Factors↗

Induction of hapten-specific cell-mediated immunity in rhesus monkeys treated with adsorbent purified antilymphocyte antibody.

Rhesus monkeys were treated with sufficient amounts of rabbit antilymphocyte sera and immunoadsorbent purified antilymphocyte antibody to retain full-thickness skin grafts 23 and 29 days respectively. During this immunosuppressed period hapten-specific cell-mediated immunity was induced in six of seven rhesus monkeys immunized with p-azophenylarsono-N-acetyltyrosine (R-tyr) in complete Freund's adjuvant. These observations suggest that in rhesus monkeys different populations of T cells may be responsible for cutaneous sensitization to antigen and rejection of skin grafts.

Animals↗

Volume transmission and wiring transmission from cellular to molecular networks: history and perspectives.

The present paper deals with a fundamental issue in neuroscience: the inter-neuronal communication. The paper gives a brief account of our previous and more recent theoretical contributions to the subject and also reports new recent data that support some aspects of our proposal on two major modes of communication in the central nervous system: the wiring and the volume transmission. There exist two competing theories on inter-neuronal communication: the neuron doctrine and the theory of the diffuse nerve network, supported by Cajal and Golgi, respectively (see their respective Nobel Lectures). The present paper gives a brief account of a view on inter-neuronal communication in the brain, the volume and wiring transmission concept that to a great extent reconcile these two theories. Thus, the theory of volume and wiring transmission are summarized and its recent developments that allow to extend these two modes of communication from the cellular network to the molecular network level is also briefly illustrated. The explanatory value of this broadened view is further enhanced by our recent proposal on the existence of a Global Molecular Network enmeshing the entire central nervous system. It may be interesting to note that also the Global Molecular Network theory is reminiscent of the old reticular theory of Apathy. Finally, the so-called 'tide hypothesis' for diffusion of signals in the brain is briefly discussed and its possible extension to the molecular level is for the first time introduced. Early indirect evidence supporting volume transmission in the brain was the discovery of transmitter-receptor mismatches. Thus, as an experimental part of the present paper a new approach to evaluate transmitter-receptor mismatches is given and evidence for inter-relationships between temperature micro-gradients and mismatches is provided.

Cell Communication↗