PubMed Health⌕ Search

Biomedical subjects

C Jacob

Publications and source records attributed to C Jacob.

At least 19 recordsLinked to original sources
PubMed1992

[Endothelin, a peptidic vasoconstrictor].

Endothelin is a 21 aminoacids peptide belonging to the family of endothelium-derived contracting factors. It exists as 3 isoforms which have similar actions. It is principally, but not exclusively, synthesized and secreted by the vascular endothelial cells. Hypoxia, physical stretching and various endogenous substances stimulate its secretion. Its specific receptors are widespread in tissues, and the endothelin-receptor binding process produces a rise of intracellular calcium through the formation of inositol phosphate. Endothelin is the most potent of known vasoconstrictor substances. In addition, it acts on the myocardium and has a contracturant effect on other smooth muscle fibres. It also contributes to the release of endogenous peptides, inhibits platelet aggregation and has mitogenic properties. Endothelin can be determined in biological fluids, such as plasma, urine and cerebrospinal fluid, using immunoanalysis methods. Several pathological situations are associated with an increase of plasma endothelin concentrations; these situations include arterial hypertension, myocardial infarction, cardiogenic shock and renal failure. Although not all physiopathological applications of endothelin have been elucidated, our current knowledge of this substance indicates that it will be of importance in human medicine.

Acute Kidney Injury↗
PubMed1992

Recombinant human basic fibroblast growth factor (Rh-bFGF) in three different wound models in rabbits: corneal wound healing effect and pharmacology.

Prior to a clinical trial in humans, we studied the effect and pharmacological distribution of recombinant human basic fibroblast growth-factor (Rh-bFGF) in vivo. Healing experiments on de-epithelialized rabbits corneas (n = 24 animals) compared the efficacy of three bFGF doses to controls and revealed a significantly increased healing rate for both 200 ng and 500 ng per application Rh-bFGF treatment groups compared to the control groups. To assess possible side effects of Rh-bFGF (500 ng topically applied for up to 7 days, twice daily), ten rabbits were involved in a model of an anterior keratectomy wound (performed with Draeger's roto-keratome to a depth of 0.15 mm). Light microscopy of thin sections of treated corneas showed an increased fibrogenesis in the anterior stroma with a more pronounced activation of keratocytes. No evidence for abnormal neovascularization or inflammation was observed when compared to control corneas. Ocular penetration and systemic distribution of topically applied labelled 125I FGF was assessed in three models (iodine vapour epithelial burn, anterior keratectomy and penetrating autokeratoplasty) in 24 rabbits. No intraocular penetration of bFGF occurred as shown by direct gamma counting. Macroautoradiography showed a selective labelling of epithelial basement membrane when denuded and intact, as previously described. Evidence for systemic absorption of breakdown products was confirmed by heparin-sepharose chromatography of blood and urine samples. Under these conditions, we suggest that topical Rh-bFGF promotes corneal wound healing without morphological adverse reaction or intraocular and systemic penetration.

Animals↗
PubMed1992

Lactate dehydrogenase (LDH) activity of the cultured eukaryotic cells as marker of the number of dead cells in the medium [corrected].

One significant problem in monitoring a culture's evolution is to assess change in cell viability. We have demonstrated that LDH release could be a good indicator of cellular damage of many cell lines, especially during shear stress or sonication. Moreover, we have found a significant correlation between the number of dead cells, determined by Trypan Blue staining, and LDH activity measurements in the supernatant of hybridoma strains, whatever the culture conditions. We have also shown that when viability is still near 100% no LDH is released even at high cell concentrations. Therefore, LDH should serve as a potential marker of cell injury and death.

Animals↗
PubMed1992

Human recombinant bFGF stimulates corneal endothelial wound healing in rabbits.

We have previously shown that bovine, human placenta extracted and recombinant human basic Fibroblast Growth Factor (bFGF) are effective in enhancing corneal epithelial wound healing in vivo. In the present study, we investigated the effect of rh-bFGF on the regeneration of injured rabbit endothelium. A standardized wound was created by scraping of endothelial cells with a special device within the boundaries of a central epithelial trephine mark of 7 mm in diameter. A single dose of 1.5 micrograms rh-bFGF was injected into the anterior chamber immediately after wounding, while control eyes received the vehicle only (n = 27). Functional recovery and wound closure rates were assessed by means of ultrasonic pachymetry, corneal button wet weight, endothelial vital staining as well as direct computer assisted surface analysis of Janus green stained corneal buttons. Measurements were carried out 1, 2, 4, and 7 days after injury. Morphological evaluation and cell counts at D4 and D7 were also performed. Significant stimulation of endothelial regeneration in rh-bFGF treated eyes, was observed with all methodological approaches. These results demonstrate the effectiveness of rh-bFGF in enhancing experimental corneal endothelial wound healing and advocate for a possible clinical application of this growth factor in order to preserve endothelial cell function or to promote healing of this important monolayer in case of disease or injury.

Animals↗
PubMed1992

[L-carnitine: metabolism, functions and value in pathology].

Although L-carnitine is not considered as an essential nutrient, endogenous synthesis may fail to ensure adequate L-carnitine levels in neonates, especially those born prematurely. Free L-carnitine is found in many foods, mainly those from animal sources. Absorption of free L-carnitine is virtually complete. Lysine and methionine are necessary ingredients for the biosynthesis of L-carnitine. All tissues in the body can produce deoxy-carnitine but, in humans, the enzyme that enables hydroxylation of deoxy-carnitine to carnitine is found only in the liver, brain and kidneys. Complex exchanges of carnitine and its precursors occur between tissues. Muscles take up carnitine from the bloodstream and contain most of the body carnitine stores. L-carnitine and L-carnitine esters are eliminated mainly through the kidneys, which may play a central role in the homeostasis of this compound. Thyroid hormones adrenocorticotrophin (ACTH), and diet all influence urinary excretion of L-carnitine. Free L-carnitine can be assayed in plasma and urine and is occasionally measured in muscle biopsy specimens. Plasma L-carnitine levels may not accurately reflect L-carnitine body stores. L-carnitine ensures transfer of fatty acids to the mitochondria where they undergo oxidation. This process is associated with production of short-chain acylcarnitine which exit from the mitochondria or peroxisomes. L-carnitine ensures regeneration of coenzyme A and is thus involved in energy metabolism. L-carnitine also ensures elimination of xenobiotic substances. Carnitine deficiencies are common. Currently, these deficiencies are classified into two groups. In deficiencies with myopathy, only the muscles are deficient in L-carnitine, perhaps as a result of a primary anomaly of the L-carnitine transport system in muscles. In systemic deficiencies, L-carnitine levels are low in the plasma and in all body tissues. Systemic L-carnitine deficiencies are usually the result of a variety of disease states including deficient intake in premature infants or long-term parenteral nutrition; renal failure; organic acidemias; and Reye's syndrome. Modifications in L-carnitine metabolism have also been reported in patients with diabetes mellitus, malignancies, myocardial ischemia, and alcohol abuse. A large number of supplementation trials have been carried out.

Adolescent↗
PubMed1992

[Significance of the level of carcinoembryonic antigen in the alveolar lavage fluid in cancerous and non-cancerous bronchopulmonary pathology].

In a prospective study the level of carcinoembryonic antigen (ACE) were simultaneously measured in plasma and bronchoalveolar lavage liquid (LBA), in fifteen patients suffering from bronchopulmonary cancer and fifteen patients suffering from non-malignant pulmonary disease. In these two groups the level of ACE in LBA liquid (cancer 8,990 +/- 4,050 ng/ml; controls 2,510 +/- 1,060 ng/ml) were clearly more elevated than the corresponding plasma levels (cancer 1,931 +/- 1,760 ng/ml; controls 8.2 +/- 2 ng/ml) and the plasma levels of ACE were more elevated in the cancer group; in the same group the ACE levels in the LBA liquid were more elevated in the tumour group (4,770 +/- 2,180 ng/ml versus 808 +/- 300 ng/ml). This study has also shown the elevated levels of ACE in the LBA liquid in patients suffering from chronic bronchial inflammation (2,510 +/- 1,060 ng/ml) and during the course of acute bacterial pneumonia. The contribution of the ACE level in LBA liquid in relation to the plasma levels in the diagnosis of bronchopulmonary cancer would thus appear to have no clinical value, but the exact relationships between the phenomenon of chronic bronchial inflammation and metaplasia of the bronchial epithelium merit further study.

Biomarkers, Tumor↗
PubMed1991

Preclinical and clinical studies with recombinant human basic fibroblast growth factor.

Basic fibroblast growth factor is a polypeptide belonging to a family of natural proteins also known as heparin-binding growth factors endowed with a pleiotropism of biological activities, the most striking of which are related to wound healing. Large quantities of recombinant human basic fibroblast growth factor (rh-bFGF) of a clinical grade were obtained and used to undertake preclinical and clinical studies. In vivo the wound healing effect of rh-bFGF was evaluated in experimental targets such as the cornea and the tympanic membrane, showing a significantly increased epithelial healing rate in drug-treated animals. The deposition of labeled rh-bFGF after topical applications in ocular wounding models did not result in a systemic absorption of the intact rh-bFGF molecule. The acute and the subchronic toxicity studies undertaken after iv and topical administration of a stable pharmaceutical formulation of rh-bFGF did not result in irritation, and no signs of general toxicity were observed. Altogether these data permitted us to start recently with human studies, which are still ongoing, aimed to evaluate the tolerability and the activity of rh-bFGF on tegumental targets such as the cornea and the skin.

Animals↗
PubMed1989

Psychiatric morbidity in clients of social workers: social outcome.

141 clients referred to social service department local social work teams (area workers) and general practice attachments were interviewed to assess their levels of psychiatric morbidity. 101 cases received clinical and social reassessment at twelve months. A substantial proportion (63%) had a positive social outcome according to the client and social worker, a finding confirmed by an independent social assessment. Family break up, more common in the area setting, was associated with a better clinical outcome. Attachment clients had significantly higher levels of psychiatric morbidity, and in clinical terms improved more frequently than area cases, but not significantly so. Clinically improved cases had a higher number of GP-social worker contacts. Both social and clinical variables contributed to the prediction of clinical outcome. By reducing the availability of attached workers, social services departments are removing a valuable source of help for people with psychiatric disorders.

Affective Symptoms↗
PubMed1989

Psychiatric morbidity in the clients of social workers: clinical outcome.

Out of 141 new referrals to a Social Services Department 101 were assessed at inception and twelve-month follow-up using the Present State Examination (PSE), the Social Maladjustment Schedule (SMS) and the Case Review Form (CRF). Mental illness, financial and housing problems were the three problems most frequently identified by the social workers. At inception 72 (51%) of the subjects were PSE cases (ID greater than 5) and 25% at follow-up. The type of social work help offered to cases and non-cases did not differ. Social and clinical data collected at inception and follow-up were used to classify (using discriminant function analysis) caseness at inception and follow-up and clinical change. Caseness at inception (82% of subjects were correctly classified) was associated with depression, subjective social problems and poverty. Caseness at follow-up (74% correctly classified) was associated with poor coping abilities at inception and clinical features of depression. Clinical change (worsening) (71% correctly classified) was associated with seeing a Community Psychiatric Nurse and poor coping abilities at inception. The ability to classify correctly cases and change was enhanced when additional data from follow-up interviews were used. In the PSE cases, only clinical worsening was correctly classified by a high GHQ score at inception, age and poor coping abilities. The last result is similar to that obtained in general practice by Mann et al. (1981).

Adaptation, Psychological↗
PubMed1989

[Effects of subcutaneous administration of sandostatine (SMS 201.995) in 18 cases of thyroid medullary cancer].

Recent studies have suggested that somatostatin could reduce calcitonin plasma levels (CT) in normal subjects and in medullary thyroid carcinoma (MTC). The aim of this study was to examine the usefulness of the somatostatin analog, sandostatine (SMS 201.995) in MTC with elevated residual CT levels post-thyroidectomy with or without metastases. 18 patients (17-64 years, 12 men and 8 women) with CT greater than 850 pg/ml (N less than 150 pg/ml) and with metastases in 12 cases, were studied. MTC was sporadic in 11 cases, familial in 4 cases and of undefined form in 3. Initial posology was 300 micrograms/d of sandostatin (3 injections/day). It was then increased by 300 micrograms/d every 9 day till a maximum of 1500 micrograms/d. Treatment duration was 37 days in 11 cases and 60 days in 7 cases. Plasma CT and carcinoembryonic antigen levels (CEA) were measured before treatment and at the end of each dosage plateau. Morphologic evaluation of metastases was done at 0, 30, 60 days. 7/18 patients were reevaluated 2 to 8 months after with drawal of sandostatine. Treatment was well tolerated. Flushes improved in 4 out of 5 cases but diarrhea in only 2 out of 9 patients. Sandostatine was without any effect on plasma CEA. Heterogenous responses were observed for plasma CT levels (CT decreases greater than 20% in 8/18 patients when 900 to 1500 micrograms/day were administered). Patients were subdivised into 3 groups according to CEA levels and presence or absence of metastases. Group A (n = 9) had elevated CEA levels (greater than 10 mg/ml) and metastases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

NMR study of the complexes between a synthetic peptide derived from the B subunit of cholera toxin and three monoclonal antibodies against it.

The contact interactions between a synthetic peptide and three different anti-peptide monoclonal antibodies have been studied by nuclear magnetic resonance (NMR). The synthetic peptide is CTP3 (residues 50-64 of the B subunit of cholera toxin) suggested as a possible epitope for synthetic vaccine against cholera. The hybridoma cell lines TE33 and TE32 derived after immunization with CTP3 produce antibodies cross-reactive with the native toxin. The cell line TE34 produces anti-CTP3 antibodies that do not bind the toxin. Selective deuteriation of the antibodies has been used to simplify the proton NMR spectra and to assign resonances to specific types of amino acids. The difference spectra between the proton NMR spectrum of the peptide-Fab complex and that of Fab indicate that the combining site structures of TE32 and TE33 are very similar but differ considerably from the combining site structure of TE34. By magnetization transfer experiments with selectively deuteriated Fab fragment of the antibody, we have found that in TE32 and TE33 the histidine residue of the peptide is buried in a hydrophobic pocket of the antibody combining site, formed by a tryptophan and two tyrosine residues. The hydrophobic nature of the pocket is further demonstrated by the lack of any pH titration effect on the chemical shift of the C4H of the bound peptide histidine. In contrast, for TE34 we have found only one tyrosine residue in contact with the histidine of the peptide.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗