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Biomedical subjects

C Hill

Publications and source records attributed to C Hill.

At least 289 records · Page 16Linked to original sources

[Premature mortality in France: relative importance of the main causes of death according to the number of years of life lost].

The importance of major causes of deaths in France have been studied for 1972 and 1982, using years of potential life lost before age 65 and in relation to life expectancy. These indicators of premature mortality have been compared to death rates. Unintentional injuries and malignant neoplasms are the two main causes of mortality before age 65. There is an important excess mortality for males, particularly for unintentional injuries. Total premature mortality declined between 1972 and 1982, but cancer mortality for males and suicide and chronic bronchitis mortality for both sexes have increased. Cardiac mortality decreased only for females.

Adolescent↗

Occurrence of an endogenous inhibitor of platelet-activating factor in rat liver.

Hepatocytes obtained from livers derived from fed rats perfused with a collagenase-containing mixture were found to contain significant levels of platelet-activating factor activity as isolated by Silica Gel G thin layer chromatography. However, when soybean trypsin inhibitor was included in the collagenase-containing perfusion medium for hepatocyte preparation, platelet-activating factor activity could not be detected on Silica Gel G chromatograms. Examination of the lipids extracted from freeze clamped perfused rat livers revealed low, but detectable, levels of platelet-activating factor. Further investigation of these observations indicated that a lipid-like inhibitor was present in freeze-clamped perfused livers as well as in hepatocytes isolated in the presence of soybean trypsin inhibitor. In each instance platelet-activating factor and this newly discovered inhibitor, which comigrated at the same RF value on Silica Gel G thin layer chromatography plates, could be separated by further chromatography on high performance thin layer plates. The present study shows that platelet-activating factor is present in unstimulated liver and that its detection is masked by an endogenous lipid-like inhibitor.

Animals↗

Development of High-Frequency Delivery System for Transposon Tn919 in Lactic Streptococci: Random Insertion in Streptococcus lactis subsp. diacetylactis 18-16.

The conjugative transposon Tn919, originally isolated in Streptococcus sanguis FC1, is capable of low-frequency transfer (10 and 10 per recipient) on membrane filters to a wide number of streptococcal recipients including the industrially important lactic streptococci. The introduction of pMG600 (Lac Lax; a lactose plasmid capable of conjugative transfer at high frequencies and which, in certain hosts, confers an unusual clumping phenotype) into a Streptococcus lactis CH919 donor, generating S. lactis CH001, resulted in a significant improvement in the transfer frequency of Tn919 to S. lactis CK50 (1.25 x 10 per recipient). In addition, these matings could be performed on agar surfaces, allowing the recovery of a greater number of recipients than with filter matings. Tn919 also transferred at high frequency to S. lactis subsp. diacetylactis 18-16S but not to Streptococcus cremoris strains. Insertion in 18-16S transconjugants generated from filter matings with an S. lactis CH919 donor was random, occurring at different sites on the chromosome and also in plasmid DNA. Thus, the conditions necessary for the practical exploitation of Tn919 in the targeting and cloning of genes from a member of the lactic streptococci, namely, high-frequency delivery and random insertion in host DNA, were achieved.

Journal Article↗

[Small cell bronchial cancer: epidemiology].

Small cell lung carcinoma is the most frequent cancer in man. In France, the geographic distribution is not homogenous and the frequency is time-dependent. The main risk factors are smoking and some professional exposures.

Carcinogens, Environmental↗

Is it useful to remove internal mammary nodes in operable breast cancer?

From September 1963 to January 1968, 243 patients with operable breast cancer were included in a randomized trial designed to compare classical radical mastectomy (RM) alone to extended mastectomy (EM), i.e. RM plus internal mammary dissection. One hundred and seventeen patients underwent RM, and 126 EM. After a mean follow-up time of 20 years, no significant differences were observed between the two treatment groups for overall survival, for the relapse-free survival rates, nor for distant metastasis, or locoregional recurrence rates. From a regression model, significant interactions were found between risk of death, EM, and both nodal status and site of the tumour. When compared to RM, EM significantly decreased the risk of death for patients with internal or medial tumour and positive axillary nodes (P = 0.05). No beneficial effect of EM was observed for any of the other patients; on the contrary, EM seemed to increase the risk of death for the patients with external tumour and negative axillary nodes (P = 0.07).

Breast Neoplasms↗

Monoclonal antibodies distinguish titins from heart and skeletal muscle.

Murine monoclonal antibodies specific for titin have been elicited using a chicken heart muscle residue as antigen. The three antibodies T1, T3, and T4 recognize both bands of the titin doublet in immunoblot analysis on polypeptides from chicken breast muscle. In contrast, on chicken cardiac myofibrils two of the antibodies (T1, T4) react only with the upper band of the doublet indicating immunological differences between heart and skeletal muscle titin. This difference is even more pronounced for rat and mouse. Although all three antibodies react with skeletal muscle titin, T1 and T4 did not detect heart titin, whereas T3 reacts with this titin both in immunofluorescence microscopy and in immunoblots. Immunofluorescence microscopy of myofibrils and frozen tissues from a variety of vertebrates extends these results and shows that the three antibodies recognize different epitopes. All three titin antibodies decorate at the A-I junction of the myofibrils freshly prepared from chicken skeletal muscle and immunoelectron microscopy using native myosin filaments demonstrates that titin is present at the ends of the thick filaments. In chicken heart, however, antibodies T1 and T4 stain within the I-band rather than at the A-I junction. The three antibodies did not react with any of the nonmuscle tissues or permanent cell lines tested and do not decorate smooth muscle. In primary cultures of embryonic chicken skeletal muscle cells titin first appears as longitudinal striations in mononucleated myoblasts and later at the myofibrillar A-I junction of the myotubes.

Animals↗

Consumption of dairy produce and alcohol in a case-control study of breast cancer.

In a French case-control study of 1,010 breast cancer cases and 1,950 controls with nonmalignant diseases, the risk of breast cancer was found to be positively associated with frequency of cheese consumption and the level of fat in the milk consumed. A negative association was found between frequency of yogurt consumption and the risk of breast cancer. No association was found between the consumption of butter and the risk of breast cancer. The positive association between a daily consumption of alcohol and the risk of breast cancer previously reported was not altered when dairy produce consumption was taken into account.

Aged↗

Elevated plasma renin activity associated with renal dysfunction.

Elevated plasma renin activity (PRA) has been documented in patients with established acute renal failure. To study the association of PRA and renal dysfunction, 53 patients who were at risk of developing acute renal failure had serial measurements of PRA, renal function, and urinary beta 2-microglobulin. Those entered for study had pneumonia, septicaemia, volume loss with hypotension, or major surgical procedures with complications. Patients were divided into groups of abnormal or normal renal function. Abnormal renal function was defined by an elevated plasma urea and/or creatinine level with a submaximal urine urea to plasma urea ratio. The mean values of PRA for the abnormal and normal renal function groups, respectively, were 29 and 5.2 ng/ml/h (p less than 0.0001) and for beta 2-microglobulin 16.2 and 6.4 micrograms/l X 10(3) (p less than 0.0005). A linear regression of the logs of PRA to beta 2-microglobulin for the total group of patients gave an r value of 0.526 (p less than 0.001). These data show an association of PRA to renal dysfunction and tubular injury/dysfunction in the prerenal phase of renal failure, suggesting an effect of the renin-angiotensin system at this phase. It is not possible, however, to conclude from our study that the renin-angiotensin system has a direct role in the development of established acute tubular necrosis, since only 3 patients fell within this category.

Acute Kidney Injury↗

Long-term results of treatment of 283 patients with lung and bone metastases from differentiated thyroid carcinoma.

We assessed the results of treatment in 283 patients with lung or bone metastases from differentiated thyroid carcinoma who were followed for up to 40 yr (median, 44 months) after the discovery of the metastases. The survival rates from the time of discovery of the metastases were 53% at 5 yr, 38% at 10 yr, and 30% at 15 yr; 156 patients died. Multivariate analysis revealed that only 4 variables had an independent prognostic significance for survival. They were extensive metastases, older age at discovery of the metastases, absence of radioiodine uptake by the metastases, and moderately differentiated follicular cell type. The site of metastases (lung or bone) was not a prognostic factor for survival after treatment of metastatic disease. Remission was achieved in 79 patients after metastases were found. The only predictive factor for 5-yr disease-free survival after treatment of metastases was the initial extent of disease. Our results suggest that the aim of management should be to detect and treat metastases in patients with thyroid cancer as early as possible.

Adult↗

Monoclonal antibodies for purification and assay of IL-2.

Mouse monoclonal antibodies (Mac 002 and Mac 003) raised against recombinant human Interleukin-2 (rec IL-2), were developed for use as assay and purification reagents. In the Immunoradiometric assay, (IRMA), 125I-Mac 002 is used as tracer, with sheep polyclonal anti-rec IL-2 on the solid phase. This reliably measures rec IL-2 in the range 3-1000 ng/ml. The assay measures natural IL-2 with a lower sensitivity. For some samples of IL-2, the amount detected by IRMA is greater than expected from the biological assays, presumably because there are IL-2 molecules with antigenic, but not biological activity. This is a possible source of variation in the specific activities observed in different preparations of of IL-2. In the purification reagent, Mac 003 is immobilised on sepharose CL-4B to purify recombinant IL-2 from less than 1% in an E. Coli extract, to greater than 90% purity, in a single step with greater than 80% yield.

Animals↗

Monoclonal antibodies to titin in conjunction with antibodies to desmin separate rhabdomyosarcomas from other tumor types.

Titin is a major constituent protein of sarcomeric muscles and is thought to give rise to an elastic filament component underlying the myofibrillar organization. Monoclonal antibodies to titin have been characterized on normal and pathological human material and on human cell lines in culture. A positive immunocytochemical reaction was restricted to sarcomeric muscles and did not occur on visceral or vascular smooth muscles or on various nonmuscle tissues. When different tumor types were examined titin antibodies reacted solely with rhabdomyosarcomas and did not react with leiomyosarcoma or leiomyoma, or with the nonmuscle tumor types tested. In rhabdomyosarcomas a noticeably smaller population of cells were positive with antibodies to titin than with antibodies to desmin showing that individual cells within a rhabdomyosarcoma achieve different degrees of myogenic differentiation. The results reinforce the use of desmin as a marker for muscle sarcomas and show that a positive identification of rhabdomyosarcoma can be achieved by immunocytochemistry with the parallel use of desmin and titin antibodies.

Animals↗

[Study of the distribution of HLA antigens within a population and a comparison between 2 populations].

HLA complex is made up of numerous loci whose alleles are codominant. Several associations between HLA antigens and diseases have been identified. Analysis of these associations require statistical methods taking into account the number of tests and the existence of alleles which have not yet been identified. Statistical methods for the estimation and the comparison of alleles frequencies are presented for genotypic, phenotypic and marginal data. An example concerning patients with medullary thyroid carcinoma illustrates these methods.

Alleles↗

External radiotherapy in thyroid cancers.

Surgery is the most effective treatment for thyroid cancer; however, in some subsets of patients, the role of radiotherapy (RT) is important. The main indication for external-beam RT is incomplete surgery. When neoplastic tissue is left behind at operation, RT must be considered, but only if an experienced surgeon feels that everything that can be done has been done. Generally, in those patients, the neoplastic tissue involves the larynx, trachea, esophagus, blood vessels or mediastinum. Of 539 patients with differentiated thyroid cancer treated at Villejuif, France, until 1976, 97 were treated by external radiotherapy after an incomplete surgical excision. Fifteen years after irradiation, the survival rate is 57% and is approximately 40% at 25 years. The relapse-free survival is lower (39% at 15 years). In patients irradiated with an adequate dose (greater than or equal to 50 Gy) to residual neoplastic tissue after incomplete surgery, the incidence of local recurrence is low (actuarial probability of local recurrence 11% at 15 years versus 23% for patients treated by surgery alone, although the irradiated patients had larger and more extensive tumors). This demonstrates the efficacy of external-beam radiotherapy. The effects of radiotherapy on a residual tumor can be monitored by a serum thyroglobulin assay. With regard to local control of tumors, the effectiveness of radioiodine administration is clearly lower. However, since radioiodine facilitates early detection of distant metastases, a combination of external RT and radioiodine is indicated and is well-tolerated. For inoperable patients, the results of RT are limited: although complete remissions are sometimes obtained, the incidence of local recurrence is high. External RT is effective in medullary carcinoma despite the slow shrinkage of the tumor after irradiation. Assay of the calcitonin level helps to monitor the effects of the treatment during follow-up and has demonstrated in some patients the efficacy of cervical RT. In undifferentiated cancers, the results of RT are poor. Combination of RT and chemotherapy are being explored despite the disappointing preliminary results of this combination.

Calcitonin↗