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Biomedical subjects

D French

Publications and source records attributed to D French.

At least 37 records · Page 2Linked to original sources
PubMed1995

[Rapid detection of platelet glycoprotein IIb, IIIA gene variety by single strand conformation polymorphism analysis].

Glanzmann thrombasthenia (GT) is the most common inherited disorder of platelet defective function. Most of the molecular defects of GT identified in recent years have been caused by point mutation in the platelet glycoprotein (GP) IIb, IIIa genes. Trying to rapidly detect point mutation (or subtle variety) in GPIIb, IIIa genes, we have used single strand conformation polymorphism analysis (SSCPA) and studied the gene structure of platelet GPIIb. IIIa from normal controls and patients with Glanzmann thrombasthenia. After DNA preparation from peripheral blood, all the exons of GPI-Ib, IIIa were amplified by PCR. Denaturated PCR products were separated on mini polyacrylamide gel and stained by silver staining method in the Phast System. Only the PCR products with different migration on the gel were sequenced. 2 GT patients with point mutations and 1 GT patient with 16 bp deletion were found in our study. At the same time, we determined 3 polymorphisms in GPIIb gene. We conclude that SSCPA is a rapid, sensitive and effective method for detecting platelet IIb, IIIa gene variety.

DNA Mutational Analysis↗
PubMed1995

Papillon-Lefèvre syndrome associated early onset periodontitis: a review and case study.

A case of Papillon-Lefèvre syndrome that has been managed successfully for six years is reported. Papillon-Lefèvre syndrome is a rare form of early onset periodontitis that occurs at a rate of 1-3 per million. Diagnostic features include palmar-plantar hyperkeratosis and rapid periodontal destruction. Although the etiology of this syndrome is unknown, current theories on the nature of the underlying defect fall into three main categories: anatomical, bacterial and host response. Historically, Papillon-Lefèvre syndrome was thought to lead to the inevitable loss of both the primary and permanent dentitions. However, a recently proposed treatment involving antibiotic coverage, extraction of the primary dentition and a period of edentulism has been shown to be effective in maintaining the permanent dentition. Since treatment may begin prior to the eruption of the permanent dentition, early recognition of Papillon-Lefèvre syndrome is critical. Any young patient who exhibits palmar hyperkeratosis should be examined carefully for periodontal breakdown. Since the number of cases available for study is limited, referral of such individuals to University dental clinics may allow for a more specific analysis of immune or bacterial factors that may lead to a better understanding of this disease.

Aggregatibacter actinomycetemcomitans↗
PubMed1995

Discriminative stimulus effects of R-(+)-3-amino-1-hydroxypyrrolid-2-one, [(+)-HA-966], a partial agonist of the strychnine-insensitive modulatory site of the N-methyl-D-aspartate receptor.

The strychnine-insensitive glycine site on the N-methyl-D-aspartate (NMDA) receptor complex is a target for development of a host of therapeutic agents including anxiolytics, antidepressants, antiepileptics, anti-ischemics and cognitive enhancers. In the present experiments, the discriminative stimulus effects of (+)-HA-966 [R-(+)-3-amino-1-hydroxypyrrolid-2-one], a low-efficacy partial agonist of the glycine site, was explored. Male, Swiss-Webster mice were trained to discriminate (+)-HA-966 (170 mg/kg i.p.) from saline in a T-maze under which behavior was controlled by food. Other glycine partial agonists, 1-amino-1-cyclopropanecarboxilic acid and D-cycloserine, fully substituted for the discriminative stimulus effects of (+)-HA-966 despite known differences in other pharmacological effects of these compounds. The glycine site antagonist, 7-chlorkynurenic acid, did not substitute for (+)-HA-966. Likewise other functional NMDA antagonists acting at nonglycine sites of the NMDA receptor also did not substitute: neither the high (dizocilpine) or low affinity (ibogaine) ion-channel blocker, the competitive antagonist, NPC 17742 [2R,4R,5S-2-amino-4,5-(1, 2-cyclohexyl)-7-phosphonoheptanoic acid], nor the polyamine antagonist, ifenprodil, substituted for (+)-HA-966. Although the full agonist, glycine, did not substitute, this compound fully blocked the discriminative stimulus effects of (+)-HA-966. In a separate group of mice trained to discriminate 0.17 mg/kg of dizocilpine from saline, (+)-HA-966 produced a maximum of only 50% dizoclipine-appropriate responses. These data suggest that the discriminative stimulus effects of (+)-HA-966 are based upon its partial agonist actions at the strychnine-insensitive glycine site.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1994

p53 expression and genetic evidence for viral infection in intraepithelial neoplasia of the uterine cervix.

Infections with high-risk strains of human papillomaviruses (HPVs) and with herpes simplex virus type 2 (HSV 2), as well as inactivation of the p53 tumor suppressor gene, are important cofactors in cervical carcinogenesis. We analyzed 41 paraffin-embedded cervical intraepithelial lesions, including 25 cases of low-grade cervical intraepithelia neoplasia (CIN), and 16 cases of high-grade CIN for the presence of HPV 16/18 and HSV 2 genomic sequences and for the nuclear accumulation of the p53 protein. HPV 16 DNA was detected in 24.% of low-grade CINs and in 43.7% of high-grade CINs. HPV 18 was found only in 8.% of low-grade CINs. None of the cases tested scored positive for HSV 2 DNA. Nuclear accumulation of p53 was found in 4% of low-grade CINs, and in 31.2% of high-grade CINs, including 57.1% of the lesions that were positive for HPV 16. These results indicate that HPV 16 infection was over sixfold more common than HPV 18 infection and that p53 overexpression was significantly associated with high-grade lesions.

Adult↗
PubMed1994

The role of home practice in the thermal biofeedback treatment of migraine headache.

The present study examined the role of home practice of hand warming in the thermal biofeedback treatment of migraine headache. Seventeen female migraine sufferers were randomly assigned to one of the following conditions: thermal biofeedback with regular home practice (HP) or thermal biofeedback without home practice (NHP). Biofeedback treatment consisted of 12 training sessions over a 6-week period, and all subjects completed 5 weeks of headache monitoring before and after treatment. Results indicated that subjects in the HP condition experienced decreases in headache activity and medication intake that were both statistically and clinically significant compared with the NHP condition. None of the outcome measures revealed significant improvement in the NHP condition. Thus, regular home practice appears to enhance the efficacy of biofeedback in the treatment of migraine.

Adult↗
PubMed1993

Evidence for nuclear internalization of exogenous DNA into mammalian sperm cells.

Mature sperm cells have the spontaneous capacity to take up exogenous DNA. Such DNA specifically interacts with the subacrosomal segment of the sperm head corresponding to the nuclear area. Part of the sperm-bound foreign DNA is further internalized into nuclei. Using end-labelled plasmid DNA we have found that 15-22% of the total sperm bound DNA is associated with nuclei as determined on isolated nuclei. On the basis of autoradiographic analysis, nuclear permeability to exogenous DNA seems to be a wide phenomenon involving the majority of the sperm nuclei. In fact, the foreign DNA, incubated with sperm cells for different lengths of time, is found in 45% (10 min) to 65% (2 hr) of the sperm nuclei. Ultrastructural autoradiography on thin sections of mammalian spermatozoa, preincubated with end-labelled plasmid DNA, shows that the exogenous DNA is internalized into the nucleus. This conclusion is further supported by ultrastructural autoradiographic analysis on thin sections of nuclei isolated from spermatozoa preincubated with end-labelled DNA.

Animals↗
PubMed1993

Integrin beta 4 expression in the neoplastic progression of cervical epithelium.

Integrin alpha 6 beta 4, a putative laminin receptor, is expressed in normal squamous epithelium and in squamous cell carcinomas. We evaluated by immunohistochemistry the topography of the beta 4 subunit in 35 biopsy samples representative of the sequence from normal exocervical epithelium to invasive squamous cell carcinoma. In normal and metaplastic squamous cervical epithelium, in condylomas, and in squamous epithelium with low-grade dysplasia (CIN 1), beta 4 was detected in basal and parabasal cells. In high-grade CIN (2-3) there was enhanced beta 4 expression and upward shift of beta 4 topography to the whole epithelial thickness. The beta 4 chain was diffusely expressed in most invasive squamous cell carcinomas. These observations suggest that profound alterations in the expression of the alpha 6 beta 4 adhesion glycoprotein occur in the intraepithelial phase of cervical carcinogenesis.

Antigens, Neoplasm↗
PubMed1993

Effects of the dopamine release inhibitor, CGS 10746B, on the locomotor stimulant and discriminative stimulus effects of cocaine and methamphetamine.

CGS 10746B or 5-(4-methyl-1 piperazinyl)-imadazo[2,1-b]1,3,5]benzothiadiazepine maleate is a clozapine analog that, unlike clozapine, produces decreases in neostriatal dopamine release without changing dopamine metabolism or occupying D2 receptors. CGS 10746B also blocks neuronal impulse flow. The ability of this atypical antipsychotic candidate to alter the discriminative stimulus effects induced by cocaine or methamphetamine in rats or the stimulation of locomotor activity in mice was evaluated. A range of doses of CGS 10746B was tested against maximally effective doses of the psychomotor stimulants. Although CGS 10746B completely blocked the locomotor stimulant effects of cocaine and methamphetamine, it also decreased spontaneous activity in mice over the same dose range. Rats were trained to discriminate 10 mg/kg cocaine or 1 mg/kg methamphetamine from saline. The discriminative stimulus effects of cocaine or methamphetamine were not blocked by CGS 10746B. Thus, in contrast to other potential atypical antipsychotic compounds (e.g., D1 receptor antagonists), CGS 10746B does not appear to produce selective blockade of these behavioral effects of psychomotor stimulant compounds.

Animals↗
PubMed1993

Behavioral correlates of individual differences in road-traffic crash risk: an examination method and findings.

This article considers methodological issues relevant to the study of differential crash involvement and reviews the findings of research in this area. Aspects of both driving skill and driving style appear to contribute to crash risk. Of the former, hazard-perception latency appears to play an important role, and this may be attributable to generalized abilities to identify visual targets in a complex background and to switch attention rapidly. Of the latter, faster driving speed and willingness to commit driving violations increase crash risk, and these factors may be explicable in terms of personality and antisocial motivation. The article concludes with an examination of the practical implications and of the ways in which research in this area might usefully proceed.

Accidents, Traffic↗
PubMed1993

Direct observation of driving, self reports of driver behaviour, and accident involvement.

Forty-eight drivers answered a set of written questions about their driving style and drove a pre-defined, mixed urban and motorway route under observation. For 20 drivers there was a second observer in the car to check on inter-observer reliability. Relationships were examined between self-reports of driver behaviour and observers' reports, and between both of these and the number of accidents in which the drivers had been involved in the past three years. The results indicated that there was good inter-observer agreement on a number of important variables including speed, calmness, and attentiveness. Inter-observer reliability for other variables was less good; among these were preferred distance to car in front, use of indicators, and aggressiveness. Observers also showed good agreement on overall ratings of driver skill and safety. Observed speed on the motorway correlated well with drivers' self reports of normal driving speed. Observer ratings of calmness correlated significantly with self-reports of calmness. Also observer ratings of attentiveness and carefulness correlated significantly with self-reports of deviant driving behaviour. Observed speed on the motorway showed a clear positive correlation with self-reported accident involvement. The results indicate that self-reports of certain aspects of driver behaviour can be used as surrogates for observational measures, thus providing a convenient extension to the researcher's methodological armoury. One such aspect is speed which appears to play an important role in accident involvement.

Accidents, Traffic↗
PubMed1993

Effect of low and moderate doses of alcohol on driving hazard perception latency and driving speed.

Both driving speed and speed of detection of potentially hazardous events while driving have been found to correlate positively with accident rates across individuals. Alcohol ingestion is also known to increase risk of a traffic accident. This paper reports two double-blind, placebo-controlled studies: one on the effect of alcohol on driving speed and the other on the effect of alcohol on time taken to detect potential traffic hazards. Moderate drinkers aged between 30 and 55 took part. Each subject underwent three experimental conditions on separate days: no alcohol, low alcohol (0.025% BAC) and moderate alcohol (0.05% BAC). The order of conditions was counterbalanced. The moderate alcohol dose increased mean time taken to respond to hazards (2.5 s in no alcohol condition compared with 3.2 s in moderate alcohol condition) but did not affect mean driving speed (indexed by time taken to travel sections of a fixed route; 19.3 s in no alcohol compared with 19.0 s in moderate alcohol). The results support the view that at least part of the excess risk of accident associated with alcohol ingestion is attributable to an increase in the time taken to respond to traffic hazards.

Adult↗
PubMed1993

Mild social deviance, Type-A behaviour pattern and decision-making style as predictors of self-reported driving style and traffic accident risk.

A 10-item self-report scale for mild social deviance (the Social Motivation Questionnaire) was developed and used in a study examining the role of social deviance in traffic accident risk. The scale focused on self-serving behaviours which might directly or indirectly harm the interests of others. Data were obtained from 108 drivers taking part in a research programme examining a range of factors underlying traffic accident risk. Apart from social deviance scores, measures were taken of Type-A behaviour pattern, decision-making style, self-reported driving style, age, sex, annual mileage, and accidents over a three-year period. The results indicated that the social deviance scale yielded a good spread of values and had adequate intra-scale reliability. Social deviance was positively correlated with accident rates independently of age, sex and annual mileage. The association between social deviance and accident rates appeared to be partly mediated by faster driving speed. The results indicate that, even within the general population, social deviance can show measurable variation and that this variation is predictive of traffic accident risk.

Accidents, Traffic↗
PubMed1992

Healing rituals and sacred serpents.

Votive tablets found during the excavation of shrines of the Graeco-Roman god of medicine (Asklepios or Aesculapius) associate the healing of superficial lesions with contact with the oral cavity of non-poisonous serpents. We suggest that this may have been the empirical exploitation of the healing properties of salivary growth factors. By immunohistochemistry and immunoblotting we demonstrate the expression of the epidermal growth factor and its receptor in the oral, upper digestive, and salivary epithelia of Elaphe quatuorlineata, a species probably used in healing rituals.

Animals↗
PubMed1992

The interaction between exogenous DNA and sperm cells.

Epididymal sperm cells, incubated with plasmid DNA, showed a spontaneous tendency to interact with the exogenous nucleic acid. We have investigated the molecular basis of such interaction. Exogenous DNA is taken up by sperm cells over a 15- to 20-min period and is specifically localized on the nuclear area of the sperm head. DNA was reversibly bound to spermatozoa since it can be competed out by excess of cold competitor DNA or by other polyanions as heparin and dextran sulphate. By contrast, poly-L-lysine, a polycation, favours the uptake. DNA molecules of large size (7 kb) were preferentially taken up as compared to smaller ones (150-750 bp). Acidic proteins were also taken up and concentrated, as for DNA, at the nuclear level. These data strongly suggested that ionic interactions may occur between foreign molecules and a substrate located in the sperm head. On the basis of Southwestern analysis, a sperm head protein(s) of 30-35 KD is identified as potential substrate for exogenous DNA binding. Moreover, we have found that seminal plasma contains factor(s) which abolish sperm permeability, exerting a powerful inhibitor effect on DNA uptake. The presence of a specific binding protein for the DNA and of a factor inhibiting such interaction support the existence of a mechanism controlling, through specific factors, the sperm-DNA interaction.

Animals↗
PubMed1991

Regional heterogeneity and complementation in the expression of the tumor-associated glycoprotein 72 epitopes in colorectal cancer.

We analyzed the immunohistochemical expression of three epitopes of the tumor-associated glycoprotein 72 (TAG-72) in whole cross-sections of primary colorectal carcinomas and in regional lymph node metastases using monoclonal antibodies (MAbs) B72.3, CC-49, and CC-83, which recognize distinct carbohydrate antigenic determinants. B72.3, CC-49, and CC-83 reacted with 13 of 27 (48%), 25 of 27 (92%), and 21 of 27 (77%) carcinomas, respectively. The immunoreactivity with lymph node metastases followed a similar pattern; MAb CC-49 was again the most reactive of the three antibodies, since it labeled 13 of 15 metastatic lesions. Positive reactions of the MAbs with the primary tumors were not always predictive of the immunorecognition of their metastases. Distinct areas within whole cross-sections of TAG-72-positive primary carcinomas demonstrated marked differences in the expression of the three epitopes. CC-49 tended to react with the highest number of areas and with the highest percentages of carcinoma cells within each area. In no instances did B72.3 demonstrate reactivity superior to that of either CC-49 or CC-83. Tumors negative for the CC-49 epitope in any area also did not express the other two TAG-72 epitopes. However, the comparison of the immunostaining obtained with each MAb in TAG-72-positive primary lesions revealed areas where CC-83 was clearly more reactive than CC-49. Moreover, one lymph node metastasis, negative for CC-49, was recognized by CC-83. Thus, the combined use of MAbs CC-49 and CC-83 resulted in additive immunostaining of primary and metastatic colorectal carcinoma cells. The study provides evidence of intratumoral heterogeneity in the glycosylation pattern of the TAG-72 antigen in colorectal cancer and emphasizes the advantages of cocktails of anti-tumor-associated antigen MAbs in the immunodetection of colorectal tumor cells.

Antibodies, Monoclonal↗
PubMed1991

Amplifications of multiple regions of the HTLV-I genome from DNA of an Italian spastic paraparesis patient but not from DNA of multiple sclerosis patients.

We searched for evidence of infection by the human T-cell lymphoma/leukemia virus type I (HTLV-I) in patients with multiple sclerosis (40 cases); brainstem encephalitis (1 case); Friedreich's ataxia (1 case); spastic paraparesis of unknown etiology (1 case). All patients were from the region of Abruzzo, Italy. Sera were all negative for anti-HTLV-I reactivity by the Western blotting (WB) analysis. DNAs from peripheral blood mononuclear cells were amplified using the polymerase chain reaction (PCR) technique with primers specific for the HTLV-I gag, pol, and env proviral regions. HTLV-I sequences were amplified only in the patient with spastic paraparesis of unknown etiology. In this case, HTLV-I infection might have been related to blood transfusions received 2 years prior to the onset of the neurologic symptoms. Members of the patient's family were negative for HTLV-I by PCR and WB. These data indicate that HTLV-I associated myelopathy is present also in Italy, but fail to substantiate an association of HTLV-I with multiple sclerosis.

Adolescent↗
PubMed1991

HTLV-1-associated myeloneuropathy in an Italian.

A 58-year old man presented with slowly progressive spastic paraparesis, ataxia, absent ankle jerks, bladder disturbances, impairment of vibration sense and mental deterioration. Electrophysiological studies documented axonal sensory neuropathy, posterior column and optic nerve involvement. Serum tests for anti-HTLV-1 antibodies were negative but HTLV-1 proviral sequences were consistently demonstrated in white blood cell genomic DNA using the polymerase chain reaction technique. Western blot and polymerase chain reaction assays of sera and DNA from family members were negative for HTLV-1. The most likely cause of infection in this patient was a blood transfusion received 2 years before onset of symptoms. This is the second Italian case of HTLV-1 associated myelopathy and the fourth reported in white subjects living in Europe.

Amino Acid Sequence↗