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Biomedical subjects

C Giroux

Publications and source records attributed to C Giroux.

17 recordsLinked to original sources

Quantification of cellular adhesion molecules on malignant B cells from non-Hodgkin's lymphoma.

The expression of five cellular adhesion molecules (CAMs), CD54, CD58, CD11a, CD29 and CD49d, was studied in 113 B cell non-Hodgkin's lymphomas (NHL) and in normal B cells from 12 control lymph nodes. Rather than reporting the percentage of positive cells, which does not discriminate between NHL subtypes, we quantified the intensity of CAM expression using flow cytometry. Apart from CD49d the expression of all these CAMs was statistically different among the NHL subtypes as defined by the REAL classification. Low grade NHL-small lymphocytic, follicular and mantle cell lymphoma--which are derived from quiescent cells and show an indolent disease course, expressed low levels of CAMs. Conversely, high grade NHL-diffuse large cell lymphoma--which are derived from proliferating cells and are clinically aggressive, expressed high levels of CAMs. These results indicate that in malignant NHL B cell tumour growth and clinical aggressiveness may be related to the adhesive capacities of the tumour cells.

Cell Adhesion Molecules↗

Relationships between susceptibility to LAK cell-mediated lysis, conjugate formation and expression of adhesion molecules in B-cell derived non-Hodgkin's lymphomas.

Adoptive immunotherapy with LAK cells has been investigated for the treatment of B-cell-derived lymphomas, but only a few significant tumor regressions were obtained. In order to explain this refractory state, the sensitivity to normal LAK-mediated lysis of 30 non-Hodgkin's lymphoma (NHL) malignant B-cells was determined using flow cytofluorimetry. A large heterogeneity was found, and we report a close correlation (p < 0.001) between the extent of lysis of malignant B-cells and their ability to form conjugates with LAK cells; which is the first step in LAK-mediated cytolysis. The levels of expression of HLA class I molecules, LFA-1 (CD11a/CD18), CD54 and CD58 were also studied and found to be expressed very heterogeneously. CD54 expression on malignant B-cells plays a major role in the initial conjugate formation with LAK cells (p < 0.001), and this was confirmed by inhibition experiments. Our results suggest that a weak expression of CD54 could constitute one mechanism by which NHL tumor B-cells escape natural immune surveillance and resist LAK cells immunotherapies.

Adult↗

Malignant B lymphocytes from non-Hodgkin's lymphoma induce allogeneic proliferative and cytotoxic T cell responses in primary mixed lymphocyte cultures: an important role of co-stimulatory molecules CD80 (B7-1) and CD86 (B7-2) in stimulation by tumor cells.

We analyzed the stimulating capacities of malignant B cells from non-Hodgkin's lymphomas (NHL) to induce an allogeneic response in primary mixed lymphocyte reaction (MLR). T cells purified from a single healthy donor (KS) were used to compare the responses induced by either malignant or hyperplastic cells. Malignant B cells induced strong proliferation of KS cells independently of their level of expression of adhesion molecules. The KS cells after MLR were predominantly CD3+, CD25+, HLA-DR+, Ki67+ and CD45RO+ T cells, and the CD4/CD8 ratio was heterogeneous (from 0.8 to 2.7). To investigate the role of co-stimulatory molecules CD80 and CD86 for the stimulatory capacities of B cells, the expression of both molecules was analyzed before and during the MLR. Most fresh malignant B cells were negative for CD80 and CD86, whereas co-cultured B cells expressed high levels of both molecules. This expression was crucial for T cell proliferation, since monoclonal antibodies directed against CD80 and CD86 completely abrogated the MLR. We also report that KS responding cells at the end of co-culture were able to lyse fresh B cells used as stimulator cells to different extents (from 10 to 51%), and the level of lysis was enhanced after PMA activation of the target cells. Inhibition experiments using CD8 and CD4 mAb showed that effector cells were mainly CD8+. This report is the first to describe the accessory function of human malignant B cells from NHL and their sensitivity to lysis mediated by CD8+ T cells, and suggests new strategies for the development of antitumor immunity in NHL.

Adolescent↗

Analysis of the spectrum of mutations induced by the rad3-102 mutator allele of yeast.

The product of the RAD3 gene of Saccharomyces cerevisiae is required for mitotic cell viability and excision repair of UV-induced pyrimidine dimers. Certain rad3 mutant alleles (originally called rem1) increase the rates of both spontaneous mitotic recombination and mutation. The increase in mutation rates is not dependent upon the presence of the RAD6 error-prone pathway. The mutator phenotype suggests that the wild-type RAD3 gene product may be involved in the maintenance of fidelity of DNA replication in addition to its known role in excision repair. To investigate the role that RAD3 might play in mutation avoidance, we have utilized a well-characterized shuttle vector system to study the mutational spectrum occurring in rad3-102 strains and compare it to that seen in RAD3 strains. The results put constraints on the role that the rad-102 mutant gene product must play if the RAD3 protein is a component of the replication complex. Alternatively, the mutational spectrum is consistent with the hypothesis that the rad3-102 mutant protein interferes with postreplication mismatch repair.

Adenosine Triphosphatases↗

[Sensory neuropathy of the trigeminal nerve and scleroderma].

Sensory neuropathy of trigeminal nerve is one of the neurological complications of systemic diseases, particularly scleroderma. Three cases are reported in which onset occurred at different stages of the disease, the main symptom being painful dysesthesias. All three branches of the trigeminal nerve may be affected but a preference is apparent for V2 and V3. Signs are usually limited to hypoesthesia and the chronic course is influenced little by treatment.

Cranial Nerve Diseases↗

[Neuropathy caused by cisplatin. 7 cases including one with an autopsy study].

The clinical, electrophysiological and histopathological features in seven cases of cisplatinum peripheral neuropathy are reported and compared with the literature data. The neuropathy appears for an average intake of 500 mg/m2 of DDP. The symptoms are those of a symmetric, distal, predominantly sensitive neuropathy of an axonal type with major involvement of proprioception. Neurological improvement is poor after withdrawal of the drug. A post mortem study performed in one case showed a degeneration of the posterior column in the cord and residual nodules of Nageotte in a lumbar spinal ganglion. The systematic study of the tendon reflexes and distal pallesthesia in subjects treated with the drug, may reveal the neuropathy before the onset of the most disabling symptoms (paresthesia, ataxia, pain, Lhermitte's sign).

Adult↗

Decreased skin response to intradermal histamine in cancer patients.

The skin response to intradermal injections of serial dilutions of histamine was studied in 68 cancer patients and 29 noncancer, nonallergic subjects. In cancer patients with primary tumor with or without metastasis, incidence and size of wheals and flare were markedly depressed by comparison with control subjects. Pseudopods were rare, and itching was absent. Similar results were observed in patients in which excisions of the primary tumor dated from less than 5 weeks. In contrast, when excision dated from greater than 2 months, skin tests returned to almost normal values. Intermediate values were obtained in patients with metastases alone. This decrease in skin response to histamine was not due to a peripheral neuropathy in cancer patients, since results of electrophysiologic studies were not different in cancer and noncancer patients. The presence of a tumor mimics the effects of general administration of histamine H1 antagonists on the skin response to histamine.

Adult↗

[Adie's syndrome and polyneuropathy: apropos of a new case and a case of pupillotonia, polyneuropathy and generalized amyloidosis sparing the nerve].

The association of Adie's syndrome and of neuropathy of chronic evolution is not a frequent occurrence; first made known by Togi in 1967, four cases have been described ever since. The authors report two new observations: one concerns a man showing a unilateral tonic pupil associated to sensory neuropathy, raised C.S.F. protein, rarefaction of myelinated fibres with schwannian proliferation, without amyloid deposit. The other is that of a woman affected with bilateral pupillotonia, motor neuropathy of the four limbs and generalized amylosis. If the first observation is comparable to the five cases reported, the second is more questionable: the absence of amyloid deposit on three nerve biopsies and at the ciliary ganglion level does not absolutely exclude the possibility of amyloid neuropathy.

Adie Syndrome↗

[Diagnostic contribution of 2 electrophysiological methods in a case of central pontine myelinolysis. Early auditory evoked potentials and blink reflex].

A case of central point myelinolysis is described in a heavy beer drinker who was found to have severe water and electrolyte disturbances on admission. The patient subsequently developed quadriparesis with pseudobulbar symptoms. The authors stress the diagnostic value of brain stem auditory-evoked responses and of blink-reflex, which were restored to normal as the patient recovered.

Adult↗

[Post-meningococcal rheumatism].

Two cases of post-meningococcal inflammatory arthritis with a relapsing course in one case are reported. The authors then recall the characteristics of the joint manifestations during meningococcal infections in the light of other cases in the literature. These arthropathies are generally aseptic and their resistance to antibiotics is remarkable, whilst non- steroid anti-inflammatory drugs, even used alone as in one of the cases reported here, are remarkably effective. The pathogenesis of these cases of arthritis is not clear: it seems however according to Greenwood and Whittle that they are manifestations of immuno-allergic type. This "post-meningococcal rheumatism" may be compared to the gonococcal rheumatism of certain cases of Reiter's syndrome.

Adult↗

Diabetic peripheral neuropathy: effects of age, duration of diabetes, glycemic control, and vascular factors.

The aim of this study was to determine the factors associated with diabetic peripheral neuropathy and more particularly its relation to precisely assessed microangiopathy. Peripheral neuropathy was assessed in 135 diabetic patients: 28 insulin-dependent diabetes mellitus (IDDM), 85 non-insulin-dependent diabetes mellitus (NIDDM), and 22 insulin-treated NIDDM patients, on the basis of both clinical findings and extensive electrophysiological testing (four motor nerves and four sensory nerves, and right and left Hoffmann's reflex), using a total of 20 parameters. The percentage of women with severe clinical neuropathy was significantly higher than that of men, and the clinical neurological stage correlated significantly with age and duration of diabetes. According to multivariate analysis the clinical stage correlated only with gender and duration of diabetes. Several electrophysiological parameters were significantly more abnormal in women and correlated with age, type and duration of diabetes, and recent glycemic control. The multivariate analysis showed that 17 electrophysiological parameters correlated with duration of diabetes, nine correlated with age, seven with glycemic control, and only one with gender. The presence of clinical neuropathy also correlated with presence of retinopathy, arterial hypertension, macroangiopathy, and biological signs of nephropathy. All the electrophysiological parameters were significantly more abnormal in patients with retinopathy or macroangiopathy than in patients without these complications. Separate parameter analysis showed that at least one abnormal electrophysiological parameter was almost always found in patients with retinopathy, macroangiopathy, or incipient nephropathy, but abnormalities were also found to a slightly lesser extent in patients without these complications. Multivariate analysis showed that when duration of diabetes, retinopathy, macroangiopathy, and biological signs of nephropathy were introduced into the model, 11 electrophysiological parameters correlated with duration of diabetes, 11 with retinopathy, seven with macroangiopathy, and five with a sign of nephropathy. This study demonstrates that age and glycemic control have an effect, and diabetes duration a major effect on peripheral nerve function. It suggests that vascular factors may participate in the development of nerve lesions.

Adolescent↗

Factors involved in cardiac autonomic neuropathy in diabetic patients.

The role cardiac autonomic neuropathy (CAN) plays in diabetes is not well known. The aim of this study was to identify the factors involved in CAN in diabetic patients. One hundred patients, 44 insulin-dependent (IDDM) and 56 non-insulin-dependent (NIDDM), were investigated, using five standard tests. Three of these tests were for parasympathetic control (cardiac response to the lying-to-standing, deep breathing, and Valsalva tests), and the other two measured sympathetic control (testing for orthostatic hypotension and evaluating heart and blood pressure response to the handgrip test). Results were compared to those found in a series of 40 healthy volunteers. An age-adjusted comparison with the controls, showed that 34 patients had one abnormal parasympathetic test, 23 had two, and 6 patients had three. Cardiac parasympathetic neuropathy was thus present in 63% of the patients. The handgrip test was completed by 84 diabetic patients. There was evidence of orthostatic hypotension and/or an abnormal cardiac response to the handgrip in 15 of these patients, who all had a parasympathetic abnormality as well. There was no significant association between the type of diabetes and the presence of CAN. The duration of diabetes was significantly longer in patients with CAN (9.3 +/- 0.9 years) (p < 0.01) than in those with all three parasympathetic tests normal (5.8 +/- 0.9 years) (p < 0.01). The HbA1c level was also higher in patients with CAN than in those with three normal parasympathetic tests (9.95 +/- 0.35% versus 8.17 +/- 0.42%, p < 0.005). There was a significant association between the presence of retinopathy, observed by angiofluorography, and the presence of peripheral neuropathy confirmed by the electrophysiological investigation and the presence of CAN (p < 0.001). However, more than half the patients without retinopathy or nephropathy had CAN, and 11 of the 31 patients with a normal electrophysiological investigation also had CAN. Eighteen patients (6 IDDM) without retinopathy and nephropathy, who had been diabetic for less than 2 years, also had CAN. This study shows that CAN occurs early and is frequently found in a population of unselected diabetic patients. Metabolic factors may play an important role in its occurrence. CAN is significantly associated with the presence of retinopathy, which suggests that an impairment of autonomic peripheral blood flow control might be a contributing factor in the formation of microvascular lesions.

Adolescent↗

Surface EMG and motor unit activity of partially denervated human muscle during fatiguing submaximal isometric contraction.

The extent to which the normal fatigue compensatory mechanisms are disturbed in partially denervated muscles was investigated in human patients. Surface EMG, as well as motor unit electrical and mechanical activity, were analyzed from the partially denervated first interosseous muscle, during fatiguing isometric submaximal contraction. The EMG power and frequency changes which reveal the local fatigue process of healthy muscle have not been systematically found. Motor unit firing rate changes were rather normal and twitch contraction time did not increase during the fatiguing exercise. Differences between normal and partially denervated muscles could be explain by the occurrence of a central fatigue process more or less important in neurogenic lesions.

Adult↗