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Biomedical subjects

M Christe

Publications and source records attributed to M Christe.

14 recordsLinked to original sources

Cytokines (IL-4 and IFN-gamma) and antibodies (IgE and IgG2a) produced in mice infected with Borrelia burgdorferi sensu stricto via nymphs of Ixodes ricinus ticks or syringe inoculations.

Mice were tolerant to tick bites during three infestations with nymphs of Ixodes ricinus infected with Borrelia burgdorferi sensu stricto. To determine whether tick bites influence the immune response against B. burgdorferi, we examined the production of cytokines IL-4 and IFN-gamma by lymph node cells of BALB/c mice and IL-4 deficient BALB/c mice after tick inoculation versus syringe inoculation of B. burgdorferi. We also measured IgG2a anti-borrelial antibodies and total IgE in these mice. Results showed that BALB/c mice developed a Th2 immune response against B. burgdorferi after tick inoculation and a mixed Th1/Th2 response after syringe inoculation of B. burgdorferi. IL-4 deficient mice produced a Th1 immune response in both cases. IL-4 produced following tick bites greatly decreased the production of anti-borrelial IgG2a antibodies by comparison with the production of anti-borrelial IgG2a antibodies produced following syringe injection of B. burgdorferi.

Animals↗

Influence of the genetic background and parasite load of mice on the immune response developed against nymphs of Ixodes ricinus.

The immune response of BALB/c (H-2d), DBA (H-2d), C57BL/6 (H-2b), C3H (H-2k), CBA (H-2k), SJL (H-2s), and FVB (H-2q) mice infested once with 15 nymphs of Ixodes ricinus is polarized toward Th2 as suggested by cytokines produced by lymph node cells stimulated with concanavalin A. The parasite load does not influence the polarization of the immune response as observed in BALB/c mice, which developed a Th2 response when infested with 5 or 45 nymphs. As assessed by attachment and weights of engorged nymphs, no resistance was acquired by BALB/c, C57BL/6, or C3H mice undergoing three successive infestations. However, these mice produced a gradual increase in IgE.

Animals↗

Susceptibility of BALB/c mice to nymphs and larvae of Ixodes ricinus after modulation of IgE production with anti-interleukin-4 or anti-interferon-gamma monoclonal antibodies.

BALB/c mice infested three times with nymphs or larvae of Ixodes ricinus ticks do not acquire resistance as assessed by evaluation of both tick attachment and the weight of engorged nymphs or larvae. Tick challenge causes a gradual increase in total IgE antibody production from the first to the third infestation. Anti-tick IgG antibodies are never detected. When the mice are treated with anti-interleukin-4 (anti-IL-4) or anti-interferon-gamma (anti-IFN-gamma) monoclonal antibodies (mAbs) 1 day before each infestation, they produce fewer or more IgE antibodies, respectively. No effect is observed on IgG antibodies. In IL-4-deficient mice, no IgE or IgG antibody is produced. However, these treatments and the use of IL-4-deficient mice have no negative effect on either tick attachment or the weight of engorged nymphs or larvae. Treatment with anti-IL-4 mAb and the use of IL-4-deficient mice inhibits and abolishes the switching of IgE, respectively, but these are apparently not sufficient to shift the response toward Th1 cells.

Animals↗

Targeted ablation of the murine alpha-tropomyosin gene.

We created a mouse that lacks a functional alpha-tropomyosin gene using gene targeting in embryonic stem cells and blastocyst-mediated transgenesis. Homozygous alpha-tropomyosin "knockout" mice die between embryonic day 9.5 and 13.5 and lack alpha-tropomyosin mRNA. Heterozygous alpha-tropomyosin knockout mice have approximately 50% as much cardiac alpha-tropomyosin mRNA as wild-type littermates but similar alpha-tropomyosin protein levels. Cardiac gross morphology, histology, and function (assessed by working heart preparations) of heterozygous alpha-tropomyosin knockout and wild-type mice were indistinguishable. Mechanical performance of skinned papillary muscle strips derived from mutant and wild-type hearts also revealed no differences. We conclude that haploinsufficiency of the alpha-tropomyosin gene produces little or no change in cardiac function or structure, whereas total alpha-tropomyosin deficiency is incompatible with life. These findings imply that in heterozygotes there is a regulatory mechanism that maintains the level of myofibrillar tropomyosin despite the reduction in alpha-tropomyosin mRNA.

Animals↗

beta-Arrestin1 knockout mice appear normal but demonstrate altered cardiac responses to beta-adrenergic stimulation.

beta-Arrestin1 knockout mice were studied to define the physiological role of beta-arrestin1 in the regulation of G protein-coupled receptors. beta-Arrestin1 is thought to be involved in the desensitization of many G protein-associated cell surface receptors, particularly beta-adrenergic receptors. Homozygous knockout mice are overtly normal. Resting cardiovascular parameters modulated by beta-adrenergic receptors such as heart rate, blood pressure, and left ventricular ejection fraction are not changed. However, homozygous mutants are more sensitive to beta-receptor agonist-stimulated increases in ejection fraction, consistent with a role of beta-arrestin1 in beta-adrenergic receptor desensitization. We conclude that beta-arrestin1 is important for in vivo G protein-coupled receptor desensitization and that this aspect of desensitization represents a mechanism for fine-tuning responses. However, beta-arrestin1 does not appear to be required for development or for other essential biological functions.

Animals↗

A mouse model of familial hypertrophic cardiomyopathy.

A mouse model of familial hypertrophic cardiomyopathy (FHC) was generated by the introduction of an Arg 403 --> Gln mutation into the alpha cardiac myosin heavy chain (MHC) gene. Homozygous alpha MHC 403/403 mice died 7 days after birth, and sedentary heterozygous alpha MHC 403/+ mice survived for 1 year. Cardiac histopathology and dysfunction in the alpha MHC 403/+ mice resembled human FHC. Cardiac dysfunction preceded histopathologic changes, and myocyte disarray, hypertrophy, and fibrosis increased with age. Young male alpha MHC 403/+ mice showed more evidence of disease than did their female counterparts. Preliminary results suggested that exercise capacity may have been compromised in the alpha MHC 403/+ mice. This mouse model may help to define the natural history of FHC.

Animals↗

Absence of acquired resistance to nymphal Ixodes ricinus ticks in BALB/c mice developing cutaneous reactions.

BALB/c mice underwent 3 successive infestations with 15 Ixodes ricinus nymphs. No resistance was acquired as assessed by evaluating tick attachment, duration of blood meal, weights of engorged nymphs, and molting success. However, the hosts developed cutaneous immediate- and delayed-type hypersensitivity reactions when reinfested. Histological examination of tick attachment sites showed that inflammatory cells consisting of neutrophils, eosinophils, and mononuclear cells (lymphocytes and monocytes) infiltrated the skin more intensively during reinfestations. The number of intact mast cells did not vary between successive infestations, whereas the number of degranulated mast cells increased in the early stages of reinfestations. Basophils, which represent 12% of total infiltrating cells, were only observed and quantified in the skin of reinfested mice using transmission electron microscopy (TEM). Degranulating eosinophils were also observed by use of TEM.

Animals↗

The contact phase of blood coagulation in diabetes mellitus and in patients with vasculopathy.

The contact phase has been studied in diabetics and patients with macroangiopathy. Factor XII and high molecular weight kininogen (HMWK) are normal. C1-inhibitor and also alpha 2-macroglobulin are significantly elevated in diabetics with complications, for alpha 2-macroglobulin especially in patients with nephropathy, 137.5% +/- 36.0 (p less than 0.001). C1-inhibitor is also increased in vasculopathy without diabetes 113.2 +/- 22.1 (p less than 0.01). Prekallikrein (PK) is increased in all patients' groups (Table 2) as compared to normals. PK is particularly high (134% +/- 32) in 5 diabetics without macroangiopathy but with sensomotor neuropathy. This difference is remarkable because of the older age of diabetics and the negative correlation of PK with age in normals.

Blood Coagulation↗

Platelet aggregation, beta-thromboglobulin and platelet factor 4 in diabetes mellitus and in patients with vasculopathy.

We have studied 155 subjects, 48 normals, 36 diabetics without complications, 44 with complications and 27 patients with macroangiopathy. beta-Thromboglobulin (beta-TG) and platelet factor 4 (PF4) are elevated in the patients groups. There is no correlation between the plasma levels of beta-TG and the stages of either retinopathy or macroangiopathy or nephropathy. The difference is more marked between normals and diabetics with neuropathy (p = 0.026). The aggregation response to ADP and platelet activating factor (PAF) is enhanced at lower stimulator concentration. Using the beta-TG, PF4 and aggregation values the discriminant analysis allows a distinction of several subgroups especially with nephropathy and neuropathy (Table 6).

Blood Platelets↗

Fibrinogen, factor VIII related antigen, antithrombin III and alpha 2-antiplasmin in peripheral arterial disease.

In 306 subjects, 217 without and 89 with peripheral arterial disease (PAD), VIIIR:Ag and alpha 2-antiplasmin are significantly higher in PAD (p less than 0.01). In the PAD negative group the ratio alpha 2-antiplasmin/antithrombin III activity is significantly higher 1.11 +/- 0.3 in the patients with an abnormal exercise ECG typical of coronary disease than in normal subjects 1.02 +/- 0.2 (p less than 0.05). In the PAD positive group antithrombin III concentration is higher in patients with a normal exercise ECG than in patients with abnormal exercise ECG (p less than 0.05). The same is true for alpha 2-antiplasmin but not for the antithrombin III activity. Fibrinogen and VIIIR:Ag are higher in patients with a previous myocardial infarction, however, the age is also significantly different as compared to the group without previous myocardial infarction. Disturbance of the cerebral arterial circulation is characterized by an elevation of VIIR:Ag and of alpha 2-antiplasmin as compared to the values obtained in patients without this complication. There is a general tendency towards higher alpha 2-antiplasmin values with the extension of the arterial disease.

Antigens↗

Fifteen coagulation and fibrinolysis parameters in diabetes mellitus and in patients with vasculopathy.

Fifteen haemostasis parameters have been measured in 48 normal persons, 36 diabetic without and 44 with complications and 27 with peripheral arterial disease. Since the patient groups are older than normals, part of the differences are due to age. However, the differences are significant between normals and patients. They become highly significant for the diabetics with complications and nephropathy (Table 7). In diabetics without complications factor VIII functions, fibrinogen and thrombin time are related to age whereas there is a negative correlation for the fibrinolytic activity and antithrombin III. The diabetic complications shade off the correlations, which subsist only for VIIIR:CoF, VIIIR:Ag, ATIII and lysis before stasis. With Hbalc as dependent variable VIIIR:CoF is the only significant predictor variable in diabetics (Table 9).

Adult↗

[Systemic thrombolysis of arterial occlusions of the lower extremities. Comparison of various treatment schedules].

From 1971-1982 121 patients with arterial occlusions of the lower limbs underwent systemic thrombolysis treatment at the Kantonsspital Basel. During 4 time-periods, 3 different treatment schedules were evaluated consecutively: a) individually titrated high dose streptokinase (SK), b) individually titrated low dose SK and c) p-plasmin, followed by low dose SK-infusion. Thrombolytic success rates did not differ significantly with the 3 treatment schedules. Nevertheless, the p-plasmin-SK scheme tended to the thrombolytically more effective (68%) than high-dose (58%) or low-dose (50%) SK. The most frequent side effects were bleeding complications. In 6 out of the 121 patients, intracranial bleeding occurred and was lethal in 1 of the patients. The incidence of this most serious complication of 4/47 during the sequential p-plasmin-SK schedule led the authors to abandon this scheme for the treatment of arterial occlusions. The intracranial bleeding complications are much less frequent in patients with deep venous thrombosis undergoing systemic thrombolysis, and hence seem to be due in part to the generalized arteriopathy often present in patients with arterial occlusions. The p-plasmin-SK schedule induced the strongest systemic proteolysis in the light of thromboplastin time and factor V values. Comparison of these data with those of other authors is very difficult because of differences in patient selection, treatment schedules and observance of contraindications. The serious prognosis for patients with acute arterial occlusions, with an overall hospital mortality of 26% (experience at the Kantonsspital Basel, 1978-1982) relativizes the importance of the side effects due to systemic thrombolysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Susceptibility of Pseudomonas aeruginosa to aminoglycosides: effect of free calcium and magnesium].

The influence of calcium and magnesium in free form on the sensitivity of Pseudomonas aeruginosa to aminoglycoside antibiotics was evaluated on 42 clinical isolates. When compared to the minimal inhibitory concentrations (MIC) measured in Mueller-Hinton broth - a medium almost devoid of Ca and Mg - the MIC obtained in the same medium, supplemented with calcium and magnesium to achieve physiological concentrations of the free divalent ions (50 micrograms/ml and 10 micrograms/ml respectively), increased by a mean factor of 8 for gentamicin. Consequently, the percentage of gentamicin resistant strains increased from 2 to 78% when tested in the supplemented medium containing physiological concentrations of free calcium and magnesium. Similar increases in MIC were observed for tobramycin and amikacin. These results cast doubt on the clinical relevance of antibiotic disc sensitivities performed on Mueller-Hinton agar by the Kirby-Bauer technique. Moreover, they could explain some of the therapeutic failures observed with Pseudomonas aeruginosa strains falsely reported as sensitive to aminoglycosidic antibiotics.

Amikacin↗