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Biomedical subjects

H Paul

Publications and source records attributed to H Paul.

16 recordsLinked to original sources

Analysis of the DNA binding proteins interacting with specific upstream sequences of the S. purpuratus CyI actin gene.

The CyI actin gene of the sea urchin, Strongylocentrotus purpuratus, is regulated temporally and spatially within the cells of the early embryo. In an effort to understand the molecular basis for the CyI actin pattern of expression, we have begun analyzing the protein-DNA interactions within regions previously shown to be of potential functional importance (Katula et al., 1987). Using DNase I footprinting, 10 protected regions were identified containing both conserved and apparently novel protein binding sites. Gel mobility shift competition assays confirmed the presence of multiple protein factors which specifically recognize CyI actin upstream sequences. Determination of a relative affinity constant value (Kr) indicated that most of the protein factors preferred their respective oligonucleotide sequences vs. a synthetic competitor DNA in a range of 10(4). The highest affinity binding was observed for proteins binding to the oligonucleotide probe containing the octamer element (Kr approximately 10(6)). Heterologous gel shift competition assays were carried out to investigate the interrelatedness of the protein factors. These studies, combined with other data, indicate there are both unique and redundant protein-DNA interactions in the region being examined. Possible alterations in CyI actin DNA binding proteins were investigated during the period of CyI transcriptional activation by gel mobility shift analysis. An increase in binding activity was observed for most of the factors, indicating that early transcriptional activity of CyI actin may involve a general increase in the amount or activity of specific transcription factors. In addition, qualitative changes, as seen by alterations in the shift patterns, were observed for some of the oligonucleotide probes.

Actins

Possible risk considerations for toxic risk assessment.

The concepts of 'negligible', 'tolerable' and 'unacceptable' risk are considered in the context of 'voluntary' and 'involuntary' risks. Levels of risk for different ill health consequences are examined in relation to the various types of risk associated with standard setting and, in particular, for standards relevant to workplace ill-health.

Dose-Response Relationship, Drug

Pathologic anatomy.

The typical case shows one or more thickened bands overlying the flexor tendons in the palm that connect with one another via the transverse palmar fascia. Vertical septae fix the bands securely to the underlying fascia and transverse metacarpal ligaments. These septae pass deep between the tendon and neurovascular tunnel. Bands running into the fingers represent thickening and fibrosis of the natatory ligaments. Typically, a central band continues into the finger, forks, and dissipates just distal to the PIP joint. This dissipation occurs with bifurcation of the central band into two thickened bundles that pass deep to the neurovascular bundle and attach to the flexor sheath of the middle phalanx. There are also thickenings of Grayson's ligaments that run from the central cord laterally and dorsally. Understanding the anatomy of the palmar aponeurosis is essential to the effective treatment of Dupuytren's contracture. Because the cause is unknown, treatment is best directed at anatomic deformities. Although not systemic or lethal, poorly treated Dupuytren's contracture can lead to significant morbidity and long-term disability. The palmar aponeurosis and its substructures are more than just passive barriers. They integrate hand parts and when pathologically fibrosed can contract joints, deform skin, and deviate neurovascular structures. The best treatments are recognition of the contracture, meticulous dissection, and local radical fasciectomy. Special attention is directed toward protecting spiralling neurovascular bundles. Difficult releases are enhanced by judicious release of checkreins, tendon sheath attachments, and disease on the radial side of the hand.

Dupuytren Contracture

Crohn's disease in black patients.

Crohn's disease is less prevalent in blacks than in whites. However, when it does occur, it is associated with a high degree of morbidity and is frequently unrecognized at initial presentation. Forty-three patients with Crohn's disease presented to Howard University Hospital between 1965 and 1987. There were 156 hospital admissions, 47 emergency room visits, and 76 clinic visits over this 22-year period. Twenty-eight patients were female and 15 were male. The age of presentation for males ranged from 18 to 63 years and for females, 12 to 74 years. Crohn's disease should be considered in black patients who present with chronic abdominal pain and diarrhea. With correct diagnosis and appropriate medical therapy, patients should have an enhanced quality of life with less morbidity.

Adolescent

DNA polymorphic patterns and haplotype arrangements of the apo A-1, apo C-III, apo A-IV gene cluster in different ethnic groups.

The allelic frequency of five different restriction fragment length polymorphisms (RFLPs) in the A-1, C-III, A-IV gene region has been determined in Caucasians, Negroes, Indian Asians, and Japanese. The polymorphic sites are with Taq-1 at the 5' end of the A-1 gene, with Msp-1 in the third intron of the A-1 gene, with Pst-1 in the intergenic sequence between the A-1 and C-III genes, with Sst-1 in the 3' non-coding region of the C-III gene, and with Pvu-II in the third intron of the C-III gene. The alleles identified by three of the RFLPs showed large differences in frequency amongst the races, especially between Caucasians and non-Caucasians. Alleles of the Msp-1 polymorphism and Sst-1 polymorphism, which were rare in Caucasians (frequencies 0.03 and 0.01), were more common in Japanese (frequencies 0.37 and 0.35), Indian Asians (frequencies 0.37 and 0.26), and Negroes (frequencies 0.31 and 0.31). In contrast with a Pvu-II polymorphism one allele was rare in Japanese and in Indian Asians (frequency 0.01) but more common in Caucasians (frequency 0.11). Linkage disequilibrium was evident between some of the alleles and a total of seven haplotypes were identified among the different races.

Alleles

Infectiousness for humans of Ixodes ricinus containing Borrelia burgdorferi.

We studied the rate of transmission of Borrelia burgdorferi from ticks (Ixodes ricinus) to man under field conditions in a case control study. At a holiday camp in southern Germany 384 ticks were removed from 272 persons. Information on symptoms possibly related to Borrelia infection were obtained by a questionnaire to be sent back six weeks after the tick bite. Ticks were examined by immunofluorescence microscopy (IFT) for Borrelia and 49 (12.8%) were found positive. Blood was obtained from 41 persons bitten by Borrelia positive and 41 age and sex matched persons bitten by Borrelia negative ticks. Sera from age and sex matched patients of local hospitals and clinics served as additional controls. Antibody titers were obtained by indirect IFT about 13 weeks after tick bite. Titers 1 : greater than 32 suggested recent infection and 1 : 32 immunity. In the exposed group there were about half as many persons with titers 1 : less than 32 (n = 14) than in the control group (n = 27) suggesting that either part of the infected ticks was in a non-infectious state or the hosts were immune. In the exposed group there were 46.4% (n = 19) and in the control group, bitten by Borrelia negative ticks, 14.7% (n = 6) persons with titers 1 : greater than 32, but 5/6 of these persons in the control group recalled additional tick bites in 1984. Only one child (in the exposed group) developed an Erythema chronicum migrans, and no other Borrelia related manifestations were reported. The manifestation rate of the Borrelia-related disease was 4%.

Adolescent

A DNA polymorphism of the apoprotein AII gene in hypertriglyceridaemia.

A polymorphism of the apolipoprotein AII gene (on chromosome 1) was investigated using genomic hybridisation analysis. The two common alleles at this locus were defined by MspI restriction fragments of 3.0 kilobase pairs (M3.0) and 3.7 kilobase pairs (M3.7) respectively. The M3.7 allele was significantly more common (P less than 0.02) in Caucasian subjects who were normo-lipaemic (34%, 20/59) than in those who were hypertriglyceridaemic (16%, 16/98). Serum triglyceride levels were measured in 126 Caucasian subjects with different combinations of disease-associated alleles at the ApoAII and ApoCIII gene loci. Mean serum triglyceride levels were found to be significantly higher (P less than 0.05) in subjects with disease-associated alleles of both the ApoCIII and ApoAII genes, compared with subjects with a disease-associated allele of one or neither locus.

Alleles

Haplotypes identified by DNA polymorphisms at the apolipoprotein A-1 and C-III loci and hypertriglyceridaemia. A study in a Japanese population.

A Japanese group comprising 40 hypertriglyceridaemic and 35 normolipidaemic subjects were genotyped for two intragenic DNA restriction fragment length polymorphisms (RFLPs) at the A-1 and C-III gene loci. An Sst-1 polymorphism is located at the 3' end of the C-III gene and a Msp-1 polymorphism in the third intron of the A-1 gene. The polymorphic restriction sites are 3.8kb apart. The polymorphism with Sst-1 was present at allelic frequencies of 0.67 (S1 allele) and 0.33 (S2 allele), and the polymorphism with Msp-1 was present at allelic frequencies of 0.55 (M1 allele) and 0.45 (M2 allele). The alleles S1, S2, M1, and M2 are in linkage disequilibrium and three haplotypes were identified S1-M1, S1-M2, and S2-M2. Unlike the previously reported association of the S2 allele with hypertriglyceridaemia found in Caucasians there was no difference in the frequency of S2 allele between normolipidaemic and hyperlipidaemic Japanese. However one of the haplotypes S1-M2 was significantly increased in the hypertriglyceridaemic subjects (32% versus 11% P less than 0.025). Thus in Japanese there is an association with genotypes at this locus and hypertriglyceridaemia but with a different haplotype than in Caucasians.

Alleles

Myoglobinemia following acute myocardial infarction.

Myoglobin was identified in the serum of 11 of 21 patients after myocardial infarction by a sensitive specific complement fixation technic. This method allowed detection of as little as 0.03 mug of myoglobin. The assay tended to underestimate small concentrations of myoglobin due to serum interference. Myoglobinuria occurred with myoglobinemia but did not reflect the level of myoglobinemia or the duration of elevated serum levels. Larger amounts of myoglobin, 0.4 mug/ml or greater, were found in patients with severe infarctions, three of four of whom died as a result of this illness.

Animals

Pentobarbital inhibits the billiary excretion of organic acids: a study with succinysulfathiazole in the rat.

The present study was undertaken to determine whether the use of pentobarbital as an anesthetic reduces the biliary excretion of acidic drugs in rats. The drug chosen for the experiment was succinylsulfathiazole, a compound excreted unmetabolized in the bile. Animals anesthetized with urethane excreted 22.1% of the dose in the bile as compared to only 8.4% for the same time period in pentobarbital anesthetized animals. The choice of anesthetic did not affec the bile flow but did influence the bile/liver concentration gradient of succinylsulfathiazole, with the pentobarbital treated rats demonstrating a significantly lower value. Despite the higher biliary excretion of succinylsulfathiazole in the urethane treated rats, the total amount in the bile plus urine was 60% of the dose in the urethane anesthetized animals as compared with 62% in the pentobarbital treated rats. These results suggest that pentobarbital reduced the hepatic transport of succiylsulfathiazole into the bile. The question whether urethane is a preferred anesthetic for biliary excretion studies warrants further investigation.

Animals

The effects of sulphydryl reagents on the binding and mixed function oxidation of hexobarbital in rat hepatic microsomes.

1. The effects of the sulphydryl reagents p-chloromercuribenzoate, N-ethylmaleimide and iodoacetamide on the binding spectrum, oxygen consumption and formation of a suspected substrate-cytochrome P-450-oxygen complex for hexobarbital in rat liver microsomes were investigated. 2. The oxygen consumption caused by hexobarbital oxidation was inhibited non-competitively by all three agents, with 50% inhibition at 4 times 10(-5) M for p-chloromercuribenzoate, 3-7 times 10(-4) M for N-ethylmaleimide and 1-9 times 10(-3) M for iodoacetamide. Cysteamine protected and at least partially reversed this inhibition. 3. p-chloromercuribenzoate inhibited the formation of the cytochrome P-450-substrate-oxygen complex, while N-ethylmaleimide and iodoacetamide also inhibited the formation of this complex but to a lesser extent. The p-chloromercuribenzoate inhibition was protected against and reversed by cysteamine. 4. p-Chloromercuribenzoate and N-ethylmaleimide caused a 50% reduction in the magnitude of the hexobarbital-induced binding spectrum, and this was paralleled by the conversion of cytochrome P-450 to cytochrome P-420. Cysteamine protected against this effect but could not reverse it. Iodoacetamide had no effect on the binding spectrum of hexobarbital and failed to convert cytochrome P-450 to cytochrome P-420. 5. Points of attack within the reaction sequence of drug oxidation are tentatively ascribed to the sulphydryl reagents used in this study.

Animals