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PubMedDate not supplied

Infant head molding: a cultural practice.

Our research indicates that infant head molding, the application of pressure or bindings to cranial bones to alter their shapes, is prevalent among various Caribbean, Latino, European, African American, Asian, and Native American groups. The data emerged during a cross-cultural anthropological study of child care practices. The documentation of the practice of intentional infant cranial molding, specifically during the first year after birth, has far-reaching implications, particularly for those medical personnel assessing children with dysmorphic crania suggestive of idiopathic craniosynostosis and craniostenosis.

Adult↗
PubMed1997

Lack of expression of E-cadherin is associated with dissemination of Langerhans' cell histiocytosis and poor outcome.

Langerhans' cell histiocytosis (LCH) often occurs in children as a cutaneous disease. The course of the disease is characterized by either spontaneous resolution or multivisceral dissemination with poor prognosis. The pathogenesis of LCH is not known. Since E-cadherin mediates homophilic adhesion of normal Langerhans' cells to keratinocytes and is also a ligand of the alpha E beta 7 intraepithelial lymphocyte integrin, this study was undertaken to investigate whether its expression on LCH cells correlates with the clinical behaviour of the disease. Clinical records of 14 children with LCH, all of whom had cutaneous involvement, were retrospectively analysed. The expression of E-cadherin was studied by in situ immunohistochemistry on 22 frozen biopsy samples with two specific monoclonal antibodies. LCH cells of the seven children with only skin involvement were positive for E-cadherin. By contrast, LCH cells of the seven children who further developed extensive LCH disclosed a negative or low expression of E-cadherin. This study shows that dissemination and poor prognosis are associated with lack of E-cadherin expression on LCH cells. Aggressive clinical evolution of LCH may therefore be related to the loss of functions mediated by E-cadherin.

Biomarkers↗
PubMed1997

UV but not gamma-irradiation induces specific transcriptional activity of p53 in primary hepatocytes.

The mechanisms are poorly understood by which p53 can stimulate different downstream events, including growth arrest, DNA repair, and apoptosis, after DNA damage. Changes in protein levels do not predict a particular p53 response, but it is possible that differences in functional activities such as transactivation are important. The present report describes the successful use of a specific p53 reporter plasmid transfected into primary murine hepatocytes to evaluate p53 transactivation activity over time after two different genotoxic injuries (gamma-irradiation, 15 Gy and UV-c irradiation, 10 J/m2) known to produce p53-dependent growth arrest in this cell type. The results show that UV injury to hepatocytes was followed by a transient increase in transcriptional activation of the reporter plasmid by p53 and that this response preceded changes in p53 protein levels, as assessed by immunocytochemistry. By contrast, gamma-irradiation injury failed to induce detectable changes in either transactivation activity or hepatocyte p53 protein levels. The data show that p53 responses to DNA damage are dependent on both cell and injury type and suggest that in hepatocytes they can be independent of protein concentration and specific transcriptional activity. The results have implications for how particular dysfunctional p53 mutations in carcinogenesis could alter hepatocyte responses to different DNA injuries.

Animals↗
PubMed1986

T-cell lymphoma revealed by a peripheral neuropathy. A report of two cases with an immunohistologic study on lymph node and nerve biopsies.

In two patients a peripheral neuropathy was the presenting symptom of a noncutaneous peripheral T-cell lymphoma. In the first patient, the neuropathy had a relapsing and remitting course, the symptoms improved under corticosteroid therapy. The second patient suffered from a relentless neuropathy. In both cases the lymphoma infiltrated the peroneal nerve with an angiocentric and perivascular pattern resembling that observed in central nervous system lymphomas. The characterization of T-cell subsets in the lymph node showed cells with the helper/inducer and suppressor/cytotoxic phenotype in the first case and a predominance of cells with the helper/inducer phenotype in the second case. In the nerve, lymphocytes beard the helper/inducer phenotype antigen. A typical paraneoplastic vasculitis of nerve showed clearly different immunologic features.

Adult↗
PubMed2000

Trends in incidence and management of gallbladder carcinoma: a population-based study in France.

BACKGROUND: Little is known, at a population level, about the incidence and management of gallbladder carcinoma. The objective of this study was to determine trends in incidence, treatment, stage at diagnosis, and prognosis of gallbladder carcinoma in a well defined population. METHODS: A series of 484 patients diagnosed over a 20-year period (1976-1995) in a French well defined population was used. Incidence rates were calculated by gender, age groups, and 5-year periods. Prognosis was determined using crude and relative survival rates. A multivariate relative survival analysis was performed. RESULTS: Age-standardized incidence rates were 0.8 per 100,000 inhabitants for men and 1.5 per 100,000 inhabitants for women. There were no significant time trends in incidence in both genders. The proportion of cases resected for cure increased from 18. 1% (1976-1980) to 42.4% (1991-1995) (P < 0.001) as well as the proportion of cases limited to the gallbladder wall, respectively from 15.7% to 27.8% (P < 0.001). Relative survival rates were 16.6% at 1 year and 6.2% at 5 years. Age, stage at diagnosis, and period of diagnosis significantly influenced the prognosis of gallbladder carcinoma. The 5-year relative survival rate rose from 2.7% (1976-1985) to 10.2% (1986-1995). The multivariate analysis showed that age and stage at diagnosis were independent prognostic factors. CONCLUSIONS: This study demonstrated that gallbladder carcinoma incidence is stable in France and that substantial advances in its management have been achieved, but there is evidence that further improvements are necessary to increase survival.

Adult↗
PubMed2000

Utility of simultaneously acquired gradient-echo and spin-echo cerebral blood volume and morphology maps in brain tumor patients.

An interleaved gradient-echo (GE) / spin-echo (SE) EPI sequence was used to acquire images during the first pass of a susceptibility contrast agent, in patients with brain tumors. Maps of 1) GE (total) rCBV (relative cerebral blood volume), 2) SE (microvascular) rCBV, both corrected for T(1) leakage effects, and 3) (DeltaR(2)*/DeltaR(2)), a potential marker of averaged vessel diameter, were determined. Both GE rCBV and DeltaR(2)*/DeltaR(2) correlated strongly with tumor grade (P = 0.01, P = 0.01, n = 15), while SE rCBV did not (P = 0.24, n = 15). When the GE rCBV data were not corrected for leakage effects, the correlation with tumor grade was no longer significant (P = 0.09, n = 15). These findings suggest that MRI measurements of total blood volume fraction (corrected for agent extravasation) and DeltaR(2)*/DeltaR(2), as opposed to maps of microvascular volume, may prove to be the most appropriate markers for the evaluation of tumor angiogenesis (the induction of new blood vessels) and antiangiogenic therapies. Magn Reson Med 43:845-853, 2000.

Blood Volume↗
PubMed2001

Enantiomeric analysis of the five major monohydroxylated metabolites of methaqualone in human urine by chiral capillary electrophoresis.

Methaqualone (MQ; 2-methyl-3-o-tolylquinazolin-4(3H)-one) is a hypnotic and anticonvulsive drug in which the rotation about the nitrogen-to-aryl bond between the planar 2-methyl-quinazolin-4(3H)-one structure and the o-tolyl moiety is sterically hindered at body temperature. MQ and its five major monohydroxylated metabolites found in urine, 4'-hydroxymethaqualone (4'OH-MQ), 2'-hydroxymethaqualone (2'-OH-MQ), 3'-hydroxymethaqualone (3'OH-MQ), 2-hydroxymethaqualone (2OH-MQ) and 6-hydroxymethaqualone (6OH-MQ), are thus chiral substances whose enantiomers are shown to be separable by chiral capillary electrophoresis at pH 2.1 in the presence of 50 mM (2-hydroxypropyl)-beta-cyclodextrin (OHP-beta-CD). Other neutral derivatives of beta-CD, namely (2-hydroxypropyl)-gamma-CD, (2,3,6-trimethyl)-beta-CD, and (2,6-di-O-methyl)-beta-CD were found to be able to resolve the enantiomers of some but not all of these six components. With OHP-beta-CD, simultaneous analysis of the enantiomers of MQ and its five metabolites is hampered by the difficulty in separating MQ and 4'OH-MQ, the major urinary metabolite. A two-step solid phase extraction process is shown to permit discrimination between these two compounds and thus analysis of MQ enantiomers in unhydrolyzed urines that were collected overnight after administration of 250 mg of racemic MQ. Furthermore, analysis of liquid/liquid or solid-phase extracts of enzymatically hydrolyzed urines reveals the distribution of the enantiomers of the five hydroxymetabolites of MQ and, for the first time, insight into the stereoselectivity of the MQ metabolism. The major metabolite, 4'OH-MQ, is shown to be excreted almost exclusively as single enantiomer. The two urinary enantiomers of 6OH-MQ are present at about equal amounts, whereas unequal amounts are noted for the enantiomers of 3'OH-MQ, 2OH-MQ, and 2'OH-MQ.

Cyclodextrins↗
PubMed1994

Autosomal dominant Muckle-Wells syndrome associated with cystinuria, ichthyosis, and aphthosis in a four-generation family.

Muckle-Wells syndrome is a rare autosomal dominant disorder characterized by chronic recurrent urticaria, periodic arthritis, sensorineural deafness, general signs of inflammation, and secondary amyloidosis (AA type). We report on a 4-generation family with 7 persons sharing various signs of this syndrome associated with bipolar aphthosis in 5 cases and cystinuria in one. Two other relatives in the family had ichthyosis.

Adolescent↗
PubMed1980

Origin of bipedalism.

Human and chimpanzee locomotor behaviors are described and compared using field patterns derived from measurements of the motions at the joints. Field patterns of human and ape bipedalism are so different that it is doubted whether the nonhuman type could ever have been a precursor of the human type. Chimpanzee quadrupedal vertical climbing and human bipedalism are, on the other hand, similar and a particular variety of this kind of climbing probably was the precursor of human bipedalism. Animals adapted to this variation would have had some brachiation-like morphological traits in their pectoral limbs and some hominid-like morphological traits in their pelvic limbs, traits anticipating the human condition. The australopithecines possessed these traits and must have been adapted to arboreal quadrupedal vertical climbing, having the capacity, at the same time, to perform facultative terrestrial bipedalism, moving on the ground in a manner visually identical to that of humans.

Animals↗
PubMed1992

Corticosteroid injection of the sacroiliac joint in patients with seronegative spondylarthropathy.

OBJECTIVE: We report our experience with the use of corticosteroid injections into the sacroiliac joint in the treatment of patients with seronegative spondylarthropathy. METHODS: We performed 42 injections, constituting 24 procedures in 22 patients (2 patients had the procedure performed twice). RESULTS: The response was considered very good or good in 19 of 24 procedures (79.2%) and 34 of 42 joints (81%). Improvement persisted in 14 patients after a mean +/- SD followup time of 9.6 +/- 4.2 months. CONCLUSION: This technique appears to be safe, easy to apply into ambulatory patients, and quite effective.

Adolescent↗
PubMed1997

Induction of interleukin-1 and subsequent tissue factor expression by anti-proteinase 3 antibodies in human umbilical vein endothelial cells.

OBJECTIVE: To assess the ability of anti-proteinase 3 (anti-PR3) classic antineutrophil cytoplasmic antibodies (cANCA) to stimulate endothelial expression of tissue factor (TF), which is the main initiator of the coagulation cascade that can lead to endothelial injury and thrombosis in patients with Wegener's granulomatosis. METHODS: Human umbilical vein endothelial cells (HUVEC) were grown to confluence and stimulated with affinity-purified anti-PR3 antibodies, Igs from healthy subjects, and endotoxin (lipopolysaccharide) as positive control. RESULTS: TF activity was generated in anti-PR3-stimulated cells, as shown by a chromogenic test. This activity was inhibited by specific anti-TF antibodies. TF messenger RNA (mRNA) was found in anti-PR3-stimulated cells, as detected by reverse transcriptase-polymerase chain reaction, but not in cells stimulated with irrelevant human Igs or Igs from normal control sera. TF expression reached maximum levels 12 hours after exposure to the anti-PR3 cANCA, and did not require complement. TF mRNA expression was inhibited by cycloheximide, suggesting a requirement for protein synthesis. When added to the incubation medium, interleukin-1 (IL-1) receptor antagonist inhibited the induced TF mRNA expression, suggesting that cANCA-stimulated cells initiate IL-1 synthesis. Moreover, cANCA induced IL-1alpha mRNA before TF mRNA. CONCLUSION: This study showed that anti-PR3 treatment of HUVEC induces sequential expression of IL-1alpha mRNA and TF mRNA, as well as their corresponding proteins. Both proteins could have pathogenic roles in the vasculitic process, since TF is the main initiator of the coagulation cascade.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2003

Capillary electrophoresis to assess drug metabolism induced in vitro using single CYP450 enzymes (Supersomes): application to the chiral metabolism of mephenytoin and methadone.

Capillary electrophoresis (CE) with multiwavelength absorbance detection is demonstrated to be an effective tool for the assessment of in vitro drug metabolism studies using microsomes containing single human cytochrome P450 enzymes (CYPs) expressed in baculovirus-infected insect cells (Supersomes). Mephenytoin (MEPH), dextromethorphan, diclofenac, caffeine, and methadone (MET) were successfully applied as test substrates for CYP2C19, CYP2D6*1, CYP2C9*1, CYP1A2, and CYP3A4, respectively. For each system, the CE-based assay could be shown to permit the simultaneous analysis of the parent drug and its targeted metabolite. Using a chiral micellar electrokinetic capillary chromatography assay, the aromatic hydroxylation of MEPH catalyzed by CYP2C19 could thereby be confirmed to be highly stereoselective, an aspect that is in agreement with data obtained via urinary analysis after intake of racemic MEPH by extensive metabolizer phenotypes. The MET to 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) conversion was investigated with a chiral zone electrophoresis assay. Incubation of racemic and nonracemic MET with CYP3A4 revealed no stereoselectivity for the transformation to EDDP, whereas no EDDP formation was observed with CYP1A2. CYP2C9 and CYP2C19 provided enhanced formation of R-EDDP and CYP2D6 incubation resulted in the preferential conversion to S-EDDP. Investigations using racemic MET and human liver microsomes revealed a modest stereoselectivity with an R/S EDDP ratio < 1 which is similar to the in vivo findings in urine.

Aryl Hydrocarbon Hydroxylases↗
PubMed2003

Assessment of the stereoselective metabolism of methaqualone in man by capillary electrophoresis.

Methaqualone (MQ) and its hydroxylated metabolites are quinazoline derivatives that exhibit atropisomerism. As a continuation of our previous work with these compounds (Electrophoresis 2001, 22, 3270-3280), chiral capillary zone electrophoresis with hydroxypropyl-beta-cyclodextrin as buffer additive and multiwavelength absorbance detection is shown to be an effective tool to provide insight into the stereoselectivity of the MQ metabolism. The five major monohydroxy MQ metabolites formed during biotransformation do not show enantiomerization at temperatures up to 85 degrees C. Enzymatic and acidic hydrolysis of urines that were collected after concomitant administration of 250 mg of MQ and 25 mg diphenhydramine (DH) chloride are both shown to provide stereoselective metabolic patterns with 4'-hydroxymethaqualone, the major urinary metabolite, being excreted almost exclusively as a single enantiomer. A stereoselectivity in the formation of 2'-hydroxymethaqualone and 2-hydroxymethaqualone was also observed in vitro using human liver microsomes and preparations containing the cytochrome P450 enzyme (CYP) CYP3A4 only. The presence of DH during incubation with human liver microsomes did not reveal a difference in the metabolic pattern obtained. Furthermore, CYP2D6 and CYP2C19 do not significantly contribute to the metabolism of MQ. This was independently observed in vitro and via analysis of urines of individuals that are either efficient metabolizer phenotypes or poor metabolizer phenotypes for the two polymorphic enzymes. Although interindividual differences in the monitored metabolic patterns were noted, no marked difference could be related to a CYP2D6 or CYP2C19 polymorphism.

Biotransformation↗