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Biomedical subjects

C Thomas

Publications and source records attributed to C Thomas.

At least 235 records · Page 13Linked to original sources
PubMed1995

A primary T-cell immunodeficiency associated with defective transmembrane calcium influx.

We investigated a T-cell activation deficiency in a 3-month-old boy with protracted diarrhea, serious cytomegalovirus pneumonia, and a family history (in a brother) of cytomegalovirus infection and toxoplasmosis. In spite of detection of normal number of peripheral lymphocytes, T cells did not proliferate after activation by anti-CD3 and anti-CD2 antibodies, although proliferation induced by antigens was detectable. We sought to determine the origin of this defect as it potentially represented a valuable tool to analyze T-cell physiology. T-cell activation by anti-CD3 antibody or phytohemagglutinin (PHA) led to reduced interleukin-2 (IL-2) production and abnormal nuclear factor-activated T cell (NF-AT; a complex regulating the IL-2 gene transcription) binding activity to a specific oligonucleotide. T-cell proliferation was restored by IL-2. Early events of T-cell activation, such as anti-CD3 antibody-induced cellular protein tyrosine phosphorylation, p59fyn and p56lck kinase activities, and phosphoinositide turnover, were found to be normal. In contrast, anti-CD3 antibody-induced Ca2+ flux was grossly abnormal. Release from endoplasmic reticulum stores was detectable as tested in the presence of anti-CD3 antibody or thapsigargin after cell membrane depolarization in a K+ rich medium, whereas extracellular entry of Ca2+ was defective. The latter abnormality was not secondary to defective K+ channel function, which was found to be normal. A similar defect was found in other hematopoietic cell lineages and in fibroblasts as evaluated by both cytometry and digital video imaging experiments at a single-cell level. This primary T-cell immunodeficiency appears, thus, to be due to defective Ca2+ entry through the plasma membrane. The same abnormality did not alter B-cell proliferation, platelet function, and polymorphonuclear neutrophil (PMN) function. Elucidation of the mechanism underlying this defect would help to understand the physiology of Ca2+ mobilization in T cells.

Antigens, CD↗
PubMed1995

Tumoricidal response of liver macrophages isolated from rats bearing liver metastases of colon adenocarcinoma.

Intraportal inoculation of CC531 adenocarcinoma cells into syngeneic rats causes an increase of liver macrophage cell number but not of major histocompatibility complex class II antigen expression. On day 1 after inoculation of 10(5) CC531 cells, a fixed number of isolated liver macrophages lysed significantly more target cells in vitro than did control cells. This effect was still present after 4 weeks. A 10-fold higher initial tumor dose significantly suppressed the macrophage response during the first 2 weeks. In contrast to tumoricidal activity induced by lipopolysaccharide in vitro, the tumoricidal response following in vivo challenge with tumor cells appeared not closely related to the production of reactive nitrogen intermediates, as in the latter case it was not abrogated in the presence of nitric oxide synthase inhibitor. Furthermore, the liver macrophage population appeared not fully activated after tumor inoculation as lipopolysaccharide further increased tumoricidal activity in vitro. The observed numerical and functional response of liver macrophages to intraportally inoculated tumor cells points at an important role of these cells in aspecific immune reactivity aimed at the reduction of local tumor growth. Results suggest that mechanistic differences exist between macrophage tumoricidal activity induced by tumor cells as compared with lipopolysaccharide.

Adenocarcinoma↗
PubMed1995

Lack of crucial role of mast cells in pathogenesis of experimental colitis in mice.

Mast cell alterations have been implicated in the pathogenesis of chronic ulcerative colitis (UC). We studied the effect of mast cell deficiency of the severity of inflammation in a murine model of colitis. Colitis was induced in mice using dextran sodium sulfate (DSS). Mast-cell-deficient mice (WBB6F1/J-W/WV; N = 17) and normal littermates (WBB6F1/J-+/+; N = 17) were administered DSS 4% w/v for seven days, then water alone for one week, followed by 5% DSS for six days. Animals were sacrificed at the end of the protocol. Segments of proximal, mid-, and distal colon of each animal were processed for histopathological examination. Mortality and morbidity (diarrhea and weight loss) for each group were assessed. There was no significant difference between the two groups in either their clinical parameters (mortality and morbidity) or the severity of colitis as graded histopathologically. Our findings suggest that mast cells are not crucial for the development of DSS-induced colitis.

Animals↗
PubMed1995

Complications of peripheral blood stem cell harvesting: review of 554 PBSC leukaphereses.

The collection of PBSC for transplantation requires repetitive leukapheresis, typically via central venous catheters (CVC). To assess the complications of this procedure, we reviewed 75 consecutive PBSC transplant candidates requiring 554 leukapheresis on a Haemonetics V50 Plus apheresis system. CVC occlusion necessitating thrombolytic therapy or cancellation of the procedure was the most commonly observed complication, occurring among 37 patients on 86 occasions (15.9% of CVC-aided collections). Thrombolytic therapy was successful in 85%. Of the patients, 16% experienced an infectious complication during the PBSC harvesting; chemotherapy mobilization significantly increased this risk, whereas growth factor mobilization was protective (p < 0.02). Hematologic complications including anemia (median postapheresis nadir hemoglobin 8.8 g/dl) and transient thrombocytopenia (median postapheresis nadir 64,000/microliters) required transfusional support among 30.7% and 14.7% of patients, respectively. The use of chemotherapy mobilization was correlated with increased need for support of both red cells and platelets (p < 0.001). Additional complications included catheter placement problems, symptomatic citrate-related hypocalcemia, transient hypotension, and machine-related malfunctions. Although the complications of the PBSC harvests were manageable, given their frequency the decision to pursue this form of hematopoietic rescue in preference to traditional operative bone marrow harvesting must address these risks.

Bacterial Infections↗
PubMed1995

Halogenated anesthetics form liver adducts and antigens that cross-react with halothane-induced antibodies.

Two halogenated anesthetics, enflurane and isoflurane, have been associated with an allergic-type hepatic injury both alone and following previous exposure to halothane. Halothane hepatitis appears to involve an aberrant immune response. An antibody response to a protein-bound biotransformation product (trifluoroacetyl adduct) has been detected on halothane hepatitis patients. This study was performed to determine cross-reactivity between enflurane and isoflurane with the hypersensitivity induced by halothane. The subcellular and lobular production of hepatic neoantigens recognized by halothane-induced antibodies following enflurane and isoflurane, and the biochemical nature of these neoantigens was investigated in two animal models. Enflurane administration resulted in neoantigens detected in both the microsomal and cytosolic fraction of liver homogenates and in the centrilobular region of the liver. In the same liver, biochemical analysis detected fluorinated liver adducts that were up to 20-fold greater in guinea pigs than in rats. This supports and extends previous evidence for a mechanism by which enflurane and/or isoflurane could produce a hypersensitivity condition similar to that of halothane hepatitis either alone or subsequent to halothane administration. The guinea pig would appear to be a useful model for further investigations of the immunological response to these antigens.

Anesthetics, Inhalation↗
PubMed1995

Connatal Leigh disease.

Two children are described with pathology-proven Leigh disease. Rather than the typical degenerative course with loss of acquired development, they presented with a static encephalopathy manifested by seizures from birth and failure to acquire any milestones. A similar connatal presentation has been reported in other degenerative disorders, such as Pelizaeus-Merzbacher disease. Heredodegenerative disorders should be considered when no cause is discovered for a severe, congenital, static encephalopathy.

Brain↗
PubMed1995

Vertebral artery injury after acute cervical spine trauma: rate of occurrence as detected by MR angiography and assessment of clinical consequences.

OBJECTIVE: The purposes of this study were to assess prospectively the frequency of vertebral artery injuries after major acute cervical spine trauma as determined by MR angiography and to assess the clinical consequences of these injuries. SUBJECTS AND METHODS: During a 6-month period, 37 patients who had major acute nonpenetrating cervical spine trauma were examined with MR imaging, usually within 24 hr of the injury. Routine spin-echo and gradient-echo images were supplemented by two-dimensional time-of-flight MR angiography of the extracranial head and neck vessels. The vertebral arteries were independently assessed by two neuroradiologists for nonvisualization, focal narrowing, or focal widening. Two patients had conventional angiographic correlation. The medical records of these 37 patients were also reviewed to determine the type of spinal injury, neurologic deficit on admission, and evidence of an intracranial neurologic deficit due to vertebral artery injury. The MR angiograms of 37 control subjects were interpreted to help determine the specificity of MR angiography; those studies were assessed only for the presence or absence of the vertebral arteries. RESULTS: Findings on MR angiograms were abnormal in nine patients (24%). In seven cases, one vertebral artery was diagnosed as nonvisualized (occluded) or focally narrowed; one patient had bilateral vertebral artery injuries; and one patient had nonvisualization of the left common carotid and left vertebral arteries. In all 37 control subjects, both vertebral arteries were identified on MR angiograms. A significant difference in the frequency of vertebral artery nonvisualization (occlusion) was found between the trauma and control populations. The patient with bilateral vertebral artery injuries died 2 days after hospital admission of a massive infarction of the right cerebellar hemisphere. The other eight patients with vertebral artery injuries, and the remaining 28 patients with normal findings on MR angiograms, had no intracranial neurologic deficits that could be ascribed to a major arterial injury. CONCLUSION: In our experience, vertebral artery injuries due to major cervical spine trauma as determined by MR angiography are common. Although these vascular abnormalities usually remain clinically occult, a small percentage of patients may suffer devastating neurologic complications of posterior fossa infarction. Noninvasive assessment of the vertebral arteries by means of MR imaging should be an integral part of the evaluation of the acutely injured cervical spine.

Acute Disease↗
PubMed1995

Trifluoroacetylation potentiates the humoral immune response to halothane in the guinea pig.

Halothane hepatitis appears to result from an inappropriate immune response to the products of halothane metabolism. Attempts to produce an animal model for halothane hepatitis have been largely unsuccessful. Although guinea pigs produce neoantigens following treatment with halothane, the subsequent antibody response is weak, possibly accounting for the failure to produce halothane hepatitis in these animals. In order to increase the antibody response to halothane neoantigens, three methods for trifluoroacetylating proteins were used. Guinea pigs were either treated with S-ethylthiotrifluoroacetate, autologous lymphocytes trifluoroacetylated ex vivo, or immunized with trifluoroacetylated mycobacterial protein, followed by exposure to halothane, and examined for anti-halothane metabolite antibodies (anti-TFA antibodies). Animals treated with S-ethylthiotrifluoroacetate developed anti-TFA antibodies, and following exposure to halothane exhibited an enhanced antibody response. Treatment with trifluoroacetylated lymphocytes also resulted in an enhanced anti-TFA antibody response following halothane exposure. Immunization with trifluoroacetylated mycobacterial proteins resulted in very high anti-TFA antibody titers. However, subsequent exposure to halothane had no observable effect on specific antibody titers. Exposure to halothane, regardless of treatment, resulted in the production of anti-microsomal protein antibodies. Signs of halothane hepatitis were not observed, indicating that enhancement of the humoral immune response does not appear to be sufficient for production of halothane hepatitis.

Alanine Transaminase↗
PubMed1995

Modulation of cannabinoid-induced antinociception after intracerebroventricular versus intrathecal administration to mice: possible mechanisms for interaction with morphine.

Dose-effect curves were generated for the cannabinoids [intracerebroventricularly (icv.)] and compared with those previously generated after administration intrathecally (i.t.). The ED50 values after administration of levonantradol, CP 55,940, delta 9-THC and delta 8-THC i.t. vs. icv. did not differ significantly. CP 56,667 was significantly more potent after icv. administration than i.t. administration, and was nearly 10 times more potent than CP 55,940 (icv.). CP 55,940 and CP 56,667, which did not produce greater than additive effects in combination with morphine when the drugs were administered i.t., shifted the morphine (icv.) dose-effect curve in a parallel manner nearly 10-fold after icv. administration. The antinociceptive effects of the cannabinoids (icv.) were not blocked by ICI 174,864 (20 micrograms/mouse), nor-BNI (70 micrograms/mouse) or naloxone (20 micrograms/mouse or 10 mg/kg s.c.). Pertussis toxin pretreatment i.t. for 7 days totally abolished the antinociception produced by the cannabinoids (icv. and i.t.). Pretreatment of the mice with forskolin (i.t.) or Cl-cAMP (10 micrograms/mouse i.t.), which produced no antinociception, significantly attenuated the antinociception produced by the delta 9-THC and CP 55,940. However, when administered icv., forskolin and Cl-cAMP produced antinociception, but did not block or produce greater than additive effects with the antinociception produced by the cannabinoids administered icv. The i.t. administration of calcium and calcium modulators failed to alter the antinociception produced by the i.t. administration of the cannabinoids. Conversely, calcium (icv.) blocked the antinociceptive effects of the cannabinoids. The AD50 values (+/- CL) for calcium-induced block of delta 9-THC, delta 8-THC and CP 55,940 were 215 (94-489), 176 (122-253) and 123 (81-186) nmol/mouse, respectively. omega-Conotoxin (1 micrograms/mouse icv.), which did not alter the antinociceptive effects of delta 9-THC, significantly reversed the calcium-induced blockade of delta 9-THC. Thapsigargin (icv.) blocked the antinociception produced by delta 9-THC and CP 55,940. Apamin, blocker calcium-gated potassium channels, produced a parallel rightward shift in the dose-effect curves of delta 9-THC, delta 8-THC and CP 55,940 (i.t.). However, apamin (5 ng/mouse icv.) failed to block icv. administered cannabinoids. Because acute administration of opiates/opioids have been shown to interact with Gi/o protein-coupled receptors, decrease calcium entry to and content of neurons, reduce cAMP levels and produce hyperpolarization of neurons via both ATP- and apamin-sensitive potassium channels, these three intracellular systems may be common points of interaction with the cannabinoids.

Animals↗
PubMed1995

[Niger: nutritional recuperation and education in a sub-Saharan urban area].

Located in Niamey, capital of Niger, a Sub-Saharian country where the rate of acute malnutrition in children is estimated at 16.8 percent, the National Armed Forces Center for Nutritional Rehabilitation and Education has been expanding its activities since 1986. The center offers curative and educational services to the children of military personnel and the population in neighboring districts. These services are regularly scheduled two and a half or three hours each morning five days a week. In 1990 our center received 115 malnourished children detected either during consultations or infant weighing sessions. Twenty-seven presented moderate protein-caloric malnutrition and 28 serious malnutrition. Medium age at admission was 11 months 16 days and medium length of stay was 9.5 days. Long-term recovery was confirmed in 30.5% while 69.5% were lost from follow-up. Keeping a healthbook throughout the weight control period, enforcing coercive measures for military families, organizing a permanent campaign to maintain awareness of nutritional problems, prolonging opening hours to improve access to the center, and above all improving the level of women's education are necessary to improve these results. Primary prevention requires better family planning with a longer interval between births.

Child Nutrition Disorders↗
PubMed1994

Unconventional cytotoxic T lymphocyte recognition of synthetic peptides corresponding to residues 1-23 of Ras protein.

A peptide corresponding to amino acids 1 through 23 of Ras protein containing a mutation at position 12 was used to induce cytotoxic T lymphocytes (CTL) in mice. Although the CTL were CD8+ and expressed alpha, beta T cell antigen receptors (TCR), their major histocompatibility complex (MHC)-restriction was unconventional. They recognized peptide-treated murine cells of different H-2 haplotypes, but not MHC class I-negative cells. Human HLA class I molecules did not present Ras peptides and hybrid human/mouse MHC molecules revealed that all three extracellular domains alpha 1, alpha 2 and alpha 3 were required for recognition by peptide-specific CTL. Shortening the 23-mer peptide by 5 residues at either the amino or carboxy terminus resulted in loss of CTL recognition. This demonstrates an unusual form of antigen recognition by mouse CTL in which peptide presentation requires murine H-2 class I molecules but is not class I allele restricted, and the peptides recognized are much larger than peptides in conventional class I-restricted responses.

Amino Acid Sequence↗
PubMed1994

Longitudinal patterns of formal and informal social support in an urban elderly population.

Stability and change in the use of formal and informal social support was assessed over a three year period among a representative sample of 1855 elderly urban participants in a longitudinal study of aging and health. Whether people received informal, formal, both types of support or no support was determined in baseline, 12 and 24 month personal interviews. Most respondents retained the same form of support across all three interviews. The extent of stability or change varied according to the form of support reported at baseline. Two-thirds of those with no social support continued without support and 40% of those using both informal and formal support continued to do so at subsequent assessments. The substitution of formal for informal support was infrequent and not statistically significant. Pair wise discriminant function analyses of groups of respondents with the most frequent longitudinal support patterns were performed to identify baseline health and social characteristics associated with stable use, the addition of another form of support or change to nonuse, over time. Changes in the use of support were influenced more by initial levels of health and functional status than by social and economic circumstances. Larger proportions of respondents dropped use of support then added an additional form of support. Respondents using both formal and informal support at baseline died across time in higher proportions than those in other support categories. The extent of stability in support use and nonuse, the character of changes in support use across time and greater attrition among those who were the heaviest users of support, serve to create a relative balance in the use of informal and formal support in this aging cohort, at least over the time frame over which respondents were followed in this study.

Aged↗
PubMed1994

Myelopathy secondary to neonatal bacterial meningitis.

Myelopathy is an infrequently reported complication of bacterial meningitis. Four patients with neonatal meningitis and cervical myelopathy are reported. This complication may be more frequent than presumed and should be closely assessed during evaluation. The conditions of most previously reported survivors improved or resolved and the majority involved the cervical spinal cord.

Atrophy↗
PubMed1994

Malignant vestibular schwannoma.

A 61-year-old woman underwent a translabyrinthine resection of a right intracanulicular acoustic neuroma, which had been detected in the work-up of sudden hearing loss. At the time of surgery, the tumor was roughly twice as large as indicated by the magnetic resonance scan taken only 2 months previously. The tumor eroded the vertical and transverse crests and extended well into the cerebellopontine angle. It was impossible to distinguish the facial nerve proximal to the geniculate ganglion. All visible tumor was resected, along with the facial nerve. Histological evaluation showed a highly cellular tumor, with many mitoses and areas of necrosis, meeting the criteria for malignant schwannoma. The patient has no stigmata of neurofibromatosis, and has no known relatives with that condition. This case is only the fourth reported of a malignant vestibular schwannoma. The relationships between vestibular schwannoma, neurofibromatosis, and malignancy are discussed.

Case Reports↗