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R F Clark

Publications and source records attributed to R F Clark.

At least 73 records · Page 4Linked to original sources
PubMed1995

A yeast artificial chromosome contig from human chromosome 14q24 spanning the Alzheimer's disease locus AD3.

Familial Alzheimer's disease has been previously linked to three genetic loci on chromosomes 21, 19 and 14. The AD3 locus on chromosome 14 has not been cloned and the molecular defect in chromosome 14-linked AD3 families has yet to be identified. Genetic linkage analysis has placed the AD3 locus in band 14q24 between the dinucleotide markers D14S61 and D14S289, a genetic distance of approximately 6.4 cM. We have constructed a yeast artificial chromosome (YAC) contig that covers the entire minimal region, encompassing all genetic markers that are non-recombinant for the disease in AD3-linked families. This contig, constructed by using a combination of YAC end sequence walking and sequence-tagged site (STS) mapping, consists of 63 YACs from three different libraries. The AD3 contig contains 12 polymorphic dinucleotide repeat markers from D14S61 to D14S251, as well as an additional 43 non-polymorphic STSs. This contiguous physical map of the region will allow the physical distances between the markers to be determined, as well as providing a framework for the identification of candidate genes.

Aged↗
PubMed1995

Genetic and physical characterization of the early-onset Alzheimer's disease AD3 locus on chromosome 14q24.3.

Genetic linkage studies have provided significant evidence that a major gene defect, AD3, for familial early-onset Alzheimer's disease (EOAD) is located at chromosome 14q24.3, between the short tandem repeat (STR) markers D14S52 and D14S53 defining a genetic size of 22.7 cM for the AD3 candidate region. We constructed a physical map of the AD3 region using yeast artificial chromosomes (YACs) selected from both the CEPH and megaCEPH YAC libraries using the AD3 linked STR markers as well as new sequence-tagged sites (STSs) designed based on YAC terminal sequences. The YAC map is contiguous in the region between D14S258 and D14S53, a region of 8.2 cM, and has an estimated physical size of 4-8 Mb. The YAC contig map was used as a framework to localize three known genes, a pseudogene and two brain expressed sequence tags (ESTs). Linkage analysis studies in two Belgian chromosome 14 EOAD families AD/A and AD/B, identified obligate recombinants in family AD/A with D14S289 and D14S61 reducing the genetic size of the candidate AD3 region substantially. The minimal AD3 candidate region measured 6.4 cM on the genetic map and is contained within six overlapping megaCEPH YACs that covered a physical distance estimated between 2 and 6 Mb. These YACs as well as other YACs in the YAC contig map are valuable resources in gene cloning efforts or genomic sequencing experiments aiming at isolating the AD3 gene.

Age of Onset↗
PubMed1995

Ciguatera fish poisoning. A southern California epidemic.

Ciguatera fish poisoning results from the bioconcentration of a variety of toxins produced by marine dinoflagellates. Signs and symptoms vary widely, but it usually presents as gastrointestinal and neurologic complaints beginning shortly after the ingestion of fish containing the toxins. Symptoms may persist for months and sometimes even years. Although cases have been reported throughout the United States, epidemics are most common along tropical and subtropical coasts and usually involve the ingestion of large carnivorous fish. We review the literature and report the first epidemic of 25 cases of ciguatera fish poisoning presenting to area hospitals in Southern California that were successfully tracked by the Department of Health Services and isolated to fish caught off the coast of Baja California, Mexico.

Adolescent↗
PubMed1994

Hyperthermia in psychostimulant overdose.

Psychostimulant drugs such as amphetamines, amphetamine derivatives, and cocaine produce a variety of potentially lethal effects, and an understanding of these toxic effects is important for emergency physicians. While some effects of psychostimulant poisonings such as cardiovascular compromise and seizures have been discussed extensively, other metabolic derangements such as hyperthermia are less well characterized. In fact, hyperthermia is a common feature of severe-to-lethal poisonings and may be the primary mode of demise in some patients. Animal studies confirm that drug-induced hyperthermia alone can be lethal in some species, although other toxic effects may predominate at different drug doses or rates of administration. In non-lethal poisonings, hyperthermia can produce rhabdomyolysis, leading to further morbidity. Clinical reports and animal studies indicate that hyperthermia is a primary effect of psychostimulant drugs and can occur independently of seizures or increased motor activity. Furthermore, activation of particular dopamine receptors in the central nervous system appears to mediate psychostimulant-induced hyperthermia. The literature suggests cooling and tranquilization of psychostimulant-poisoned patients after cardiovascular stabilization. Paralysis and mechanical ventilation may be required. The involvement of dopamine receptor activation in psychostimulant toxicity suggests that dopamine-blocking neuroleptic drugs may be a useful adjunct to current treatment regimens. However, further studies are required to assess this approach. In summary, hyperthermia is a potentially lethal but treatable manifestation of severe psychostimulant poisoning.

Amphetamines↗
PubMed1994

Sunlight and the plant: a toxic combination: severe phytophotodermatitis from Cneoridium dumosum.

A severe case of phytophotodermatitis occurred in a patient who had spent several hours walking through an area densely populated with Cneoridium dumosum. This patient's co-worker experienced a similar reaction after undergoing patch testing of an area of skin and exposing it to sunlight. Voluntary patch testing by one of the authors produced a reaction consistent with the other two cases. Approximately twenty other cases were described by a U.S. Fish and Wildlife Service ranger in students who came into contact with the plant during a field trip with him to Baja California, Mexico. Cneoridium dumosum is a common native bush that grows in the chaparral vegetation zone of southern California and Baja California, Mexico. In a search of Poisindex, Medline, Agris International, and Agricola databases, no previous reports of toxic exposures were found.

Arm↗
PubMed1993

Molecular genetics of Alzheimer's disease.

The part that genetics plays in the origin of Alzheimer's disease (AD) is a complex problem that is only now, in the last few years, beginning to be understood. Progress in the study of the epidemiology of AD, discovery of multiple AD loci, and interpreting how mutations affect and produce the AD phenotype have been the initial keys to unlocking the mysteries of this disease. We now know of the existence of at least three AD loci on chromosomes 14, 19, and 21 and are beginning to understand the role that one of these loci, APP, and its mutations plays in the progression of AD. On future studies using animal modeling and the positional cloning of the other AD loci, a definite model for AD should become evident within the next few years.

Aged↗
PubMed1993

Fractionation of human H1 subtypes and characterization of a subtype-specific antibody exhibiting non-uniform nuclear staining.

Four histone H1 subtypes and H1(0) were fractionated from human placental nuclei and purified to homogeneity by a combination of Bio-Rex 70 chromatography and reverse-phase high-performance liquid chromatography (RP-HPLC). Polyclonal antibodies were generated in rabbits against one of these subtypes designated H1-3. Antibodies reacted only against this subtype in enzyme-linked immunosorbent assays and Western assays; subtype specificity was documented further by Western blotting of cell and nuclear extracts. They crossreacted with monkey H1, but not with H1 from other vertebrates tested. The epitope(s) recognized were mapped by immunoblotting against peptides prepared by cleavage with N-bromosuccinimide (NBS) and alpha-chymotrypsin; it includes the variant amino-terminal tail of the protein as well as a portion of the globular domain. The antibody stains mitotic chromosomes weakly but uniformly and, unlike antibodies that recognize total H1 which show uniform nuclear staining after indirect immunofluorescence localization, anti-H1-3 exhibits preferential labelling of the nuclear periphery. This non-uniform staining suggests compartmentalization of this subtype which may have functional significance with respect to differential chromatin condensation.

Amino Acid Sequence↗
PubMed1993

The relationship of the incisive papilla to the maxillary central incisors and canine teeth in southern Chinese.

A photographic technique was used to measure anatomic landmarks located on dental casts. The relationship of the maxillary anterior teeth to the incisive papilla in a Southern Chinese population living in Hong Kong was studied. The distances from the labial surface of the central incisors to the midpoint and the posterior border of the incisive papilla were measured. The area on the incisive papilla where the intercanine line crossed was noted. The data obtained were compared with those from previous studies of Caucasians. Results show that there is little difference between the Southern Chinese in this study and most other ethnic groups. The guidelines that use the incisive papilla as a reference for the setting of artificial teeth in denture construction recommended for Caucasians can be applied to Southern Chinese patients.

Adult↗
PubMed1993

A multivariate analysis of disability and health, and its change over time in the National Channeling Demonstration data.

The Channeling Demonstration examined the effects of case management interventions on a variety of outcomes. In the study, longitudinal data were collected from interviews of cases and controls. A multivariate procedure applied to this data identified groups with specific health profiles. Six profiles described health variation over individuals, and time, according to likelihood ratio statistics. Six sets of life tables were calculated, one for each health profile, to estimate the average duration of service use and the "follow-up" services used. A number of differences, and changes, in service use between the six groups were significant.

Activities of Daily Living↗
PubMed1993

Ondansetron in the treatment of intractable nausea associated with theophylline toxicity.

OBJECTIVE: To report the efficacy of ondansetron in the treatment of a patient poisoned with theophylline. PATIENT: A 36-year-old man who ingested 6 g of sustained-release theophylline. INTERVENTION: Ondansetron 8 mg intravenously after clinical failure of other antiemetics. RESULTS: Subjective relief of nausea within minutes, enabling the patient to tolerate multiple doses of activated charcoal and whole bowel irrigation. CONCLUSIONS: Ondansetron may offer an alternative to present antiemetic therapy in the poisoned patient.

Adult↗
PubMed1993

Molecular cloning of a human homologue of Drosophila heterochromatin protein HP1 using anti-centromere autoantibodies with anti-chromo specificity.

We have identified a novel autoantibody specificity in scleroderma that we term anti-chromo. These antibodies recognize several chromosomal antigens with apparent molecular mass of between 23 and 25 kDa, as determined by immunoblots. Anti-chromo autoantibodies occur in 10-15% of sera from patients with anti-centromere antibodies (ACA). We used anti-chromo antibodies to screen a human expression library and obtained cDNA clones encoding a 25 kDa chromosomal autoantigen. DNA sequence analysis reveals this protein to be a human homologue of HP1, a heterochromatin protein of Drosophila melanogaster. We designate our cloned protein HP1Hs alpha. Epitope mapping experiments using both human and Drosophila HP1 reveal that anti-chromo antibodies target a region at the amino terminus of the protein. This region contains a conserved motif, the chromo domain (or HP1/Pc box), first recognized by comparison of Drosophila HP1 with the Polycomb gene product. Both proteins are thought to play a role in creating chromatin structures in which gene expression is suppressed. Anti-chromo thus defines a novel type of autoantibody that recognizes a conserved structural motif found on a number of chromosomal proteins.

Amino Acid Sequence↗
PubMed1993

Invasion of the 'killer' bees. Separating fact from fiction.

Even a single honeybee sting can lead to anaphylaxis in a susceptible person, but severe reactions can result from multiple stings, particularly if stings are from the fast-spreading Africanized honeybees, sometimes called "killer" bees. Signs and symptoms of multiple stings may include urticaria, nausea, vomiting, diarrhea, hypotension, confusion, seizures, and renal failure. Treatment is entirely supportive and requires special attention to airway patency, blood pressure, and renal function. Patients with more than 50 stings are at a higher risk of toxicity. Stingers should be removed by scraping gently to prevent further venom injection. Smoke or aerosolized deet (diethyl-toluamide) may thwart attacking bees, but avoidance is the best line of defense.

Adult↗
PubMed1992

Heterochromatin protein 1, a known suppressor of position-effect variegation, is highly conserved in Drosophila.

The Su(var)205 gene of Drosophila melanogaster encodes heterochromatin protein 1 (HP1), a protein located preferentially within beta-heterochromatin. Mutation of this gene has been associated with dominant suppression of position-effect variegation. We have cloned and sequenced the gene encoding HP1 from Drosophila virilis, a distantly related species. Comparison of the predicted amino acid sequence with Drosophila melanogaster HP1 shows two regions of strong homology, one near the N-terminus (57/61 amino acids identical) and the other near the C-terminus (62/68 amino acids identical) of the protein. Little homology is seen in the 5' and 3' untranslated portions of the gene, as well as in the intronic sequences, although intron/exon boundaries are generally conserved. A comparison of the deduced amino acid sequences of HP1-like proteins from other species shows that the cores of the N-terminal and C-terminal domains have been conserved from insects to mammals. The high degree of conservation suggests that these N- and C-terminal domains could interact with other macromolecules in the formation of the condensed structure of heterochromatin.

Amino Acid Sequence↗
PubMed1992

Optimal patient position for transport and initial management of toxic ingestions.

STUDY OBJECTIVES: Many factors influence the rate of gastric emptying and therefore the rate of drug absorption in the orally poisoned patient. Limited studies have evaluated the effect of body position on the rate of gastric emptying of radiographically marked foods and contrast media, but effects on drug absorption have not been studied previously. Our hypothesis was that body position would have an effect on the rate of drug absorption in an oral overdose model. DESIGN: A blinded, within-subjects (crossover) design. PARTICIPANTS: Six male and six female healthy, adult volunteer subjects with no concurrent drug use or medications affecting gastrointestinal function. INTERVENTIONS: Five body positions commonly used in prehospital and emergency department settings were examined: left lateral decubitus, right lateral decubitus, supine, prone, and sitting. All were performed by all subjects in random order with a three-day washout phase between trials. To simulate an acute overdose, fasted subjects ingested 80 mg/kg acetaminophen in the form of 160-mg pediatric tablets. Each subject then remained in the body position for that trial for two hours. Acetaminophen levels were obtained at 15-minute intervals, and a two-hour area under the curve (AUC) was calculated for each subject trial to represent total drug absorption during each study period. Investigators were blinded to all results until all trials were completed. MEASUREMENTS AND MAIN RESULTS: All subjects completed the study. Group mean drug absorption as represented by two-hour AUC (mg.L.min) was calculated for each body position. AUC for left lateral decubitus (6,006 +/- 2,614) was lowest but did not significantly differ from that for supine (6,649 +/- 2,761). Both were significantly less than those for prone (7,432 +/- 1,809), right lateral decubitus (8,950 +/- 1,405), and sitting (8,608 +/- 1,725) positions (P less than .05 by one-way analysis of variance and follow-up paired t tests). CONCLUSION: Initial drug absorption as determined by two-hour AUC was lowest in the left lateral decubitus position. Although the difference between the left lateral decubitus and supine positions did not reach statistical significance, both left lateral decubitus and supine were significantly lower than three other common patient body positions tested. Because the left lateral decubitus position has other advantages (eg, prevention of aspiration) in addition to minimizing drug absorption, we recommend that orally poisoned patients be placed in the left lateral decubitus position for prehospital and initial ED management.

Acetaminophen↗
PubMed1992

Massive diphenhydramine poisoning resulting in a wide-complex tachycardia: successful treatment with sodium bicarbonate.

Diphenhydramine poisoning is characterized most often by anticholinergic effects. Cardiotoxicity and circulatory collapse have rarely been reported after massive ingestions of diphenhydramine and other H1-receptor-blocking agents, although these substances have local anesthetic properties and have been studied as antiarrhythmics. We report the case of a patient who developed a wide-complex tachycardia as a complication of acute diphenhydramine poisoning that responded to IV sodium bicarbonate.

Adolescent↗