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Biomedical subjects

M Michel

Publications and source records attributed to M Michel.

At least 19 recordsLinked to original sources
PubMed1992

Effects of 9, 12, 15-octadecatrien-6-ynoic acid on the metabolism of arachidonic acid in platelets and on platelet aggregation.

An acetylenic fatty acid: 9,12,15-octadecatrien-6-ynoic acid (dicranin) was extracted from Dicranum Scoparium and preincubated with platelets which were then stimulated by exogenous arachidonic acid (20:4 n-6). This molecule at 10(-4) M weakly inhibited the cyclooxygenase activity as assessed by measurement of 12-hydroxy-heptadecatrienoic acid (HHT) In contrast, the 12-hydroxy-eicosatetraenoic acid (12-HETE) synthesized by the 12-lipoxygenase was strongly increased by about 650%. The same effects were observed with 10(-5) M and with 10(-6) M of dicranin but to a lesser extent. Platelet hydroxylated dicranin metabolites were also found and the structure of the main compound determined by GC-MS was a 13-hydroxy derivative. Its origin has not yet been elucidated. Platelet aggregation induced by 1 microgram/ml of U46619, a structural PGH2 analogue was completely abolished in the presence of dicranin. Platelet aggregation induced either by thrombin or by arachidonic acid was inhibited by 10(-4) M of dicranin only after preincubation. This observation indicates that the formation of metabolites of dicranin are necessary to effect this inhibition. Dicranin is thus a new inhibitor of platelet aggregation and may prove to be useful for elucidating the effects of 12-HETE in biological systems.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1992

In vivo T cell activation, in vitro defective IL-2 secretion, and response to influenza vaccination in elderly women.

IL-2 secretion in response to mitogenic stimulation, assayed in vitro, is significantly reduced in circulating T lymphocytes isolated from healthy old people, but the significance of this abnormality and how it relates to in vivo IL-2 secretion remain unclear. We found that IL-2 secretion in response to PHA plus PMA by peripheral blood T cells isolated from 10 out of 32 (31%) healthy old individuals (mean age 86 yr, range 74-97) was significantly decreased compared with results obtained in 23 younger individuals (mean age 34 yr, range 23-46). This IL-2 secretion defect in vitro was reversible after a 3-day incubation in the absence of activators. The 10 healthy old individuals who had defective IL-2 secretion in vitro also showed increased levels of serum IL-2. T cells from 22 healthy old and 22 young individuals, who had normal IL-2 secretion (geometric mean +/- log of 1 SD: 139 +/- 0.3 U/ml and 212 +/- 0.31 U/ml, respectively) in vitro, showed a remarkable transient T cell defect in IL-2 secretion (15 +/- 0.47 U/ml for the old, 54 +/- 0.28 U/ml for the young) 15 days after influenza vaccination. IL-2 secretion became normal again 30 days after vaccination. The T cell-IL-2 activity, expressed as a T cell-IL-2 activity score (calculated as the logarithm of the serum IL-2 U/ml divided by the logarithm of the IL-2 secretion U/ml, in vitro) was significantly increased in elderly non-responders after influenza vaccination (mean +/- 1 SD: 1.4 +/- 0.51) compared with elderly (0.44 +/- 0.13) and younger responders (0.3 +/- 0.2). Our data suggest that in vitro defective IL-2 secretion is a consequence of T cell activation which seems to occur in a significant proportion of healthy elderly individuals and may be clinically relevant inasmuch as it appears to prevent the normal vaccine-induced antibody response.

Aged↗
PubMed1992

Effects of 9,12,15-octadecatrien-6-ynoic acid on the metabolism of arachidonic acid in platelets and on the platelet aggregation.

An acetylenic fatty acid: 9,12,15-octadecatrien-6-ynoic acid (dicranin), extracted from Dicranum Scoparium was preincubated with platelets stimulated by exogenous arachidonic acid (20:4 n-6). Dicranin (10(-4) M) weakly inhibited the cyclooxygenase activity as assessed by measurement of 12-hydroxy-heptadecatrienoic acid (HHT) In contrast, the 12-hydroxy-eicosatetraenoic acid (12-HETE) synthesized by the 12-lipoxygenase was strongly increased by about 650%. The same effects were observed with 10(-6) M of dicranin but to a lesser extent. The main platelet hydroxylated dicranin metabolite determined by GC-MS was a 13-hydroxy derivative Platelet aggregation induced either by thrombin or by arachidonic acid or by U46619, an structural PGH2 analogue was inhibited by 10(-4) M of dicranin.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1992

Characterization of cultured rat aortic endothelial cells.

We describe a new method to obtain rat aortic endothelial cells without contamination by vascular smooth muscle cells. The endothelial cells were characterized up to the 20th passage by low density lipoprotein incorporation, the absence of alpha-smooth muscle actin, the production of endothelium derived relaxing factor, and an elevation in intracellular free calcium concentration in response to bradykinin and ATP but not to AMP and angiotensin II.

Animals↗
PubMed1992

The relationship between influenza vaccine-induced specific antibody responses and vaccine-induced nonspecific autoantibody responses in healthy older women.

The effect of aging on human humoral immunity was investigated by studying in vivo the relationship between influenza specific antibody responses and nonspecific vaccine-induced autoantibody responses in 32 independent, well-nourished older women volunteers (mean age 86 yr, range 74-97) and 23 young women volunteers (mean age 34 yr, range 23-46). Anti-influenza A/Taiwan/1/86(H1N1) antibody titers were determined by a hemagglutination inhibition test (HI-test), and serum anti-dsDNA antibodies were measured by ELISA prior to, 15, and 30 days after influenza vaccination. The mean postvaccination fold increase (FI) of the anti-influenza antibody response was significantly lower in elderly individuals as compared to younger individuals. In contrast, the mean anti-dsDNA autoantibody level measured 30 days after vaccination was significantly increased in older volunteers as compared to younger ones. There was a significant negative correlation between the level of the FI of the anti-influenza antibody response and the anti-dsDNA antibody response (r = -.441, p less than .01). Our results suggest that the altered influenza specific antibody response was associated with an age-related increase in autoimmunity in aging individuals.

Adult↗
PubMed1992

Parental response to cystic fibrosis: a contextual analysis of the diagnosis phase.

A contextual framework guided the measurement of specific stressors encountered by parents of children recently diagnosed with cystic fibrosis (CF). Three variables were assessed within the context of the parenting role: illness-specific tasks, normal parenting tasks, and strains in family roles. These situation-specific stressors were contrasted with global measures of parenting stress in their ability to predict depression. Sixty-four parents (36 mothers, 28 fathers) of infants and toddlers recently diagnosed with CF completed a structured interview and standardized measures in the home. Parents reported elevations in both situation-specific and global parenting stress, and a greater number of depressive symptoms than a norm group. Mothers reported significantly greater strain in managing their caregiving role and higher levels of depression than fathers. Controlling for situation-specific parenting stress and marital satisfaction, regression analyses indicated that role strain related to CF was associated with greater depression in mothers, but not fathers. Furthermore, stressors measured contextually rather than globally accounted for substantially greater proportions of the variance in depression. The findings highlight the need to measure ongoing strains specific to the medical condition, and to assess role-related changes.

Adaptation, Psychological↗
PubMed1992

The role of computed tomography in the management of peritonsillar abscess.

Twenty-four patients who fulfilled the clinical criteria for peritonsillar abscess (PTA) were randomized into two groups over a 6-month period. Group A (n = 13) underwent CT with contrast, whereas group B (n = 11) was managed without radiologic investigation. In group A, CT with contrast enabled differentiation of PTA from peritonsillar cellulitis in all 13 cases (100%) and demonstrated abscesses in 11 patients (85%), thereby allowing drainage at first attempt. Two patients with peritonsillar cellulitis were successfully managed with antibiotics only. In group B, all patients underwent needle aspiration. In seven patients (64%), pus was found after needle aspiration at first attempt and in one patient after needle aspirations at two locations. In three patients (27%), no pus was found after needle aspirations at three different locations. We conclude that CT enhances diagnostic accuracy, obviating unnecessary drainage procedures, and reduces patient morbidity.

Anti-Bacterial Agents↗
PubMed1990

Immune responses to defined epitopes of the circumsporozoite protein of the murine malaria parasite, Plasmodium yoelii.

We have investigated the immunogenicity of defined sequences of the circumsporozoite (CS) protein of the murine malaria parasite, Plasmodium yoelii. A 21-ner synthetic peptide from the nonrepetitive region of the CS protein (position 59-79, referred to as Py1) induced T cell proliferative responses in H-2d and, to a lesser extent, in H-2b mice. Conversely, a synthetic peptide (referred to as Py4) consisting of four (QGPGAP) repeats of the P. yoelii CS protein, induced an antibody response only in H-2b mice. No antibody response was observed when the Py3 peptide, consisting of three (QGPGAP) repeats, was used as an immunogen. When cross-linked to the Py4 repetitive peptide, the Py1 sequence behaved as a T helper epitope allowing the production of anti-Py4 antibodies in H-2d mice. Several long-term T cell lines and clones specific for the nonrepetitive Py1 peptide were originated in vitro from both H-2d and H-2b mice. These lines and clones were CD4+ and proliferated in a major histocompatibility complex-restricted fashion. Furthermore, Py1-specific T cell lines and clones did not proliferate in the presence of synthetic peptides from an analogous region of another rodent malaria parasite, P. berghei, despite the high degree of homology existing in this sequence of the two CS proteins. Finally, supernatants from 7 out of 13 clones (from BALB/c mice) produced detectable amounts of interleukin 2 and interferon-gamma; whereas supernatants from the 4 clones from C57BL/6 and 2 from BALB/c mice contained detectable amounts of interleukin 5. These results show that functionally heterogenous CD4+ T cell populations, belonging to either TH1 or TH2 subset, are activated upon immunization of mice with the P. yoelii Py1 synthetic peptide. It is not yet known what differential role these CD4+ subsets play during the malaria infection or after immunization with different malaria T cell epitopes. This knowledge may have a particular impact in the design of effective subunit vaccines against malaria.

Amino Acid Sequence↗
PubMed1990

Major malformations in a case of infantile myofibromatosis.

A case of infantile myofibromatosis associated with oesophageal atresia, annular pancreas, additional sacral vertebra and hypoplatic right kidney in a male neonate is reported. The possibility of associated malformations in this rare disease is outlined.

Abnormalities, Multiple↗
PubMed1990

Segmental liver transplantation from living donors. Report of the technique and preliminary results in dogs.

A technique of orthotopic liver transplantation using a segmental graft from living donors was developed in the dog. Male mongrel dogs weighing 25-30 kg were used as donors and 10-15 kg as recipients. The donor operation consists of harvesting the left lobe of the liver (left medial and left lateral segments) with the left branches of the portal vein, hepatic artery and bile duct, and the left hepatic vein. The grafts are perfused in situ through the left protal branch to prevent warm ischemia. The recipient operation consists of two phases: total hepatectomy with preservation of the inferior vena cava using total vascular exclusion of the liver and veno-venous bypass, implantation of the graft in the orthotopic position with anastomosis of the left hepatic vein to the inferior vena cava and portal, arterial and biliary reconstruction. Preliminary experiments consisted of four autologous left lobe transplants and nine non survival allogenic left lobe transplants. Ten survival experiments were conducted. There were no intraoperative deaths in the donors and none required transfusions. One donor died of sepsis, but all the other donor dogs survived without complication. Among the 10 grafts harvested, one was not used because of insufficient bile duct and artery. Two recipients died intraoperatively of air embolus and cardiac arrest at the time of reperfusion. Three dogs survived, two for 24 hours and one for 48 hours. They were awake and alert a few hours after surgery, but eventually died of pulmonary edema in 2 cases and of an unknown reason in the other. Four dogs died 2-12 hours postoperatively as a result of hemorrhage for the graft's transected surface. An outflow block after reperfusion was deemed to be the cause of hemorrhage in these cases. On histologic examination of the grafts, there were no signs of ischemic necrosis or preservation damage. This study demonstrates the technical feasibility of living hepatic allograft donation. It shows that it is possible, in the dog, to safely harvest non ischemic segmental grafts with adequate pedicles without altering the vascularization and the biliary drainage of the remaining liver. We propose that this technique is applicable to human anatomy.

Animals↗
PubMed1990

Use of synthetic peptides in the study of the antibody response to Plasmodium vivax sporozoites.

Synthetic peptides reproducing 4 DRADGQPAG (D4) and a sequential array of DRADGQPAG and DRAAGQPAG repeats (DDAAD) of the Plasmodium vivax circumsporozoite (CS) protein were investigated for their potential use in the detection of P. vivax sporozoite antibodies in human sera. These peptides specifically inhibited the binding of monoclonal antibodies to the P. vivax CS protein in Western blots. However, when D4 and DDAAD peptides were used in an enzyme-linked immunosorbent assay (ELISA) for the detection of human antibodies, more sera bound to the DDAAD (61%) than to the D4 peptide (22%). This binding was specific, and suggested that the DDAAD peptide contained epitopes constituted by the sequential array of DRADGQPAG and DRAAGQPAG repeat variants and absent in the D4 peptide. The ELISA using the DDAAD peptide was applied to the detection of P. vivax CS protein antibodies in a large number of sera from Kataragama, an endemic area in Sri Lanka. The prevalence of these antibodies increased with age, reaching 40% in adults greater than 50 years old. The ELISA employing the DDAAD peptide represents a simple and useful tool for the analysis of the antibody response to P. vivax sporozoites in naturally exposed individuals.

Age Factors↗
PubMed1990

[Orthotopic liver transplantation and living donors. An experimental study in the dog].

Orthotopic liver transplantation (OLT) using partial grafts harvested from living donors would represent a further alternative to the limited supply of hepatic grafts, especially in pediatrics. We report herein the results of an original technique of living donor OLT that we have developed in the dog. This study was conducted in male mongrel dogs weighing 25-30 kg for the donors and 10-15 kg for the recipients. The donor operation consisted in harvesting the left lobe of the liver as a graft. The recipient operation consisted in the implantation of the graft in the orthotopic position after total hepatectomy with preservation of the inferior vena cava. Ten survival experiments were undertaken. The first donor died of infected liver necrosis of the quadrate lobe. All other donors survived without major complication. Among the 10 grafts, only 9 were used. Substantial survival could be obtained in 3 dogs. On recipient survived for 48 hours and 2 for 24 hours but their graft was functioning and producing bile. Two dogs died intraoperatively. The 4 other recipients developed an outflow block of the graft after reperfusion leading to lethal hemorrhage from the transected surface. This work is, to our knowledge, the first experimental study of OLT using living donors. It provides a technical basis to the clinical use of living hepatic allograft donors which otherwise depends on ethical issues.

Animals↗
PubMed1989

Histologic and immunologic study of uterine biopsy tissue of women with incipient abortion.

Biopsy specimens taken from the region of the placental bed were examined for the presence of phloxinophilic granulated mononuclear cells in women with a history of recurrent miscarriage and who would eventually miscarry a current pregnancy. They were compared with biopsy specimens from women with intact pregnancies presenting for elective termination of pregnancy and those with "missed abortion." Cells with large cytoplasmic granules (greater than or equal to 1 micron) were abundant in the group of ongoing pregnancies whereas cells with smaller granules (less than 1 micron) that were similar to large granular lymphocytes were more abundant relative to cells with large granules in the biopsy specimens from failing pregnancies. Immunosuppressive activity was tested in the supernatants of cultured biopsy samples of each group and found to be significantly lower in the incipient miscarriage group. These findings could represent alterations associated with the process of miscarriage, such as inflammation, or there may be deficient suppressor cell activity at the fetomaternal interface as the reason for "rejection" of the early embryo.

Abortion, Habitual↗
PubMed1989

T lymphocyte subsets in leprosy. A study of 24 Egyptian patients.

Phenotypic analysis was done on 24 Egyptian leprosy patients and 11 healthy controls. The type of leprosy, duration of disease at the time of testing, and age were found to affect T cell subset distribution. As compared with controls, neural leprosy tended to have a decreased total T cell percentage, borderline leprosy an increased T suppressor cell percentage, and reactional borderline leprosy an increased T helper/suppressor ratio. Patients with the disease for less than 1 year had a higher mean percentage of T suppressor cells and a lower mean T helper/suppressor ratio than patients with leprosy for more than 1 year. The same was true in older (50-70 years old) versus younger (12-41 years old) patients.

Adolescent↗
PubMed1989

High pressure freezing comes of age.

High pressure freezing permits the successful cryoimmobilization of thick biological specimens (up to approx. 500 microns). A very high yield of adequately frozen specimens, in which no segregation patterns due to ice crystal formation is apparent after freeze-substitution or freeze-fracturing, is obtained with suspensions of microorganisms as well as plant and animal tissue. This very high yield is attributed to an optimized transfer of pressure and cold to the biological specimen. This is achieved by replacement of extraspecimen water or buffer by 1-hexadecene, a chemically inert, hydrophobic paraffin oil of low viscosity and low surface tension.

Animals↗