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Biomedical subjects

M Richardson

Publications and source records attributed to M Richardson.

At least 145 records · Page 8Linked to original sources
PubMed1996

Refined mapping and YAC contig construction of the X-linked cleft palate and ankyloglossia locus (CPX) including the proximal X-Y homology breakpoint within Xq21.3.

The gene for X-linked cleft palate (CPX) has previously been mapped in an Icelandic kindred between the unordered proximal markers DXS1002/DXS349/DXS95 and the distal marker DXYS1X, which maps to the proximal end of the X-Y homology region in Xq21.3. Using six sequence-tagged sites (STSs) within the region, a total of 91 yeast artificial chromosome (YAC) clones were isolated and overlapped in a single contig that spans approximately 3.1 Mb between DXS1002 and DXYS1X. The order of microsatellite and STS markers in this was established as DXS1002-DXS1168-DSX349-DXS95-DXS364-DXS 1196-DXS262-DXS110-DXS1066-(DXS1169, DXS1222)-DXS472-DXS1217-DXYS1X. A long-range restriction map of this region was created using eight nonchimeric, overlapping YAC clones. Analysis of newly positioned polymorphic markers in recombinant individuals from the Icelandic family has enabled us to identify DXS1196 and DXS1217 as the flanking markers for CPX. The maximum physical distance containing the CPX gene has been estimated to be 2.0 Mb, which is spanned by a minimum set of five nonchimeric YAC clones. In addition, YAC end clone and STS analyses have pinpointed the location of the proximal boundary of the X-Y homology region within the map.

Base Sequence↗
PubMed1996

Primary structure of a Kunitz-type trypsin inhibitor from Enterolobium contortisiliquum seeds.

A trypsin inhibitor was isolated from Enterolobium contortisiliquum seeds. Starting with a saline extract, ECTI (E. contortisiliquum trypsin inhibitor) was purified as a homogeneous protein by acetone precipitation, ion-exchange chromatography (DEAE-Sephadex A-50), gel filtration (Sephadex G-75 and Superose 12) and reversed phase HPLC (mu-Bondapak C-18). The amino acid sequence was determined by automatic degradation and by DABITC/PITC microsequence analysis of the reduced and carboxymethylated protein and also of purified peptides derived from the protein by cleavage with iodosobenzoic acid and by enzymic digestion with trypsin, chymotrypsin and Staphylococcus aureus V8 protease. ECTI contains 174 amino acid residues in two polypeptide chains, an alpha-chain consisting of 134 residues and a beta-chain made up of 40 residues. The inhibitor displays a high degree of sequence identity with other Kunitz-type proteinase inhibitors isolated from the Mimosoideae subfamily. The reactive site was identified (by homology) as the arginine-isoleucine peptide bond at position 64-65. ECTI inhibits trypsin and chymotrypsin in the stoichiometric ratio of 1:1 and also Factor XIIa, plasma kallikrein and plasmin, but not thrombin and Factor Xa.

Amino Acid Sequence↗
PubMed1996

Complete amino acid sequences of two trypsin inhibitors from buckwheat seed.

The major trypsin isoinhibitors from seed extracts of buckwheat (Fagopyrum esculentum Mönch) were purified by affinity chromatography, anion exchange chromatography, anion exchange HPLC and reversed-phase HPLC, and the complete amino acid sequences of two isoinhibitors, BTI-1 and BTI-2, were established by automated Edman degradation. Each isoinhibitor consists of a single polypeptide chain of 69 amino acids, including two Cys residues. The N-terminal sequence of a third isoform, BTI-3, was also determined. The buckwheat trypsin isoinhibitors exhibit clear sequence similarities with the potato chymotrypsin inhibitor I family of serine proteinase inhibitors.

Amino Acid Sequence↗
PubMed1996

alpha-Amylase inhibitors from wheat: amino acid sequences and patterns of inhibition of insect and human alpha-amylases.

Four alpha-amylase inhibitors, WRP24, WRP25, WRP26, and WRP27, were purified from wheat flour by preparative, reversed-phase high performance liquid chromatography. All have polypeptide molecular masses of about 14 kDa and are members of the cereal superfamily of protease and alpha-amylase inhibitors. Sedimentation velocity analysis indicated that WRP25 and WRP27 are monomeric proteins, whereas WRP24 is a dimer. WRP24 is identical in N-terminal amino acid sequence to the well characterized 0.19 dimeric inhibitor from wheat kernels. WRP25 and WRP26 differ in sequence from each other at only three positions and represent previously unseparated forms of the 0.28 wheat inhibitor. WRP27 is a previously uncharacterized inhibitor and is more similar in sequence to the 0.28 inhibitor than to the 0.19 inhibitor. WRP25 and WRP26 inhibited alpha-amylases from the rice weevil, red flour beetle, and the yellow meal worm, but did not inhibit human salivary alpha-amylase. WRP24 inhibited the human as well as the insect alpha-amylases, but inhibited one of the two rice weevil alpha-amylases much more strongly than the other. WRP27 was notable in that, of the enzymes tested, it strongly inhibited only the rice weevil alpha-amylases. We observed that the growth rate of red flour beetle larvae was slowed when purified WRP24 was included in the diet at a level of 10%. Addition of WRP24 to corn starch resulted in greater weight loss of red flour beetle adults than occurred on control diets. Our results support the hypothesis that these alpha-amylase inhibitors provide wheat seeds with a selective evolutionary advantage since the inhibitors can slow the growth of insect pests that attack cereal grains.

Amino Acid Sequence↗
PubMed1996

Childhood pleuropulmonary blastoma: caution against nonoperative management of congenital lung cysts.

Pulmonary blastoma is a rare and aggressive malignant tumor that affects children and adults. Recently a 3-year-old boy with a 2-year history of bilateral unilocular pulmonary cysts was transferred for evaluation of a cough and high spiking fever. A chest radiogram showed left pulmonary consolidation with pleural effusion, but thoracentesis was unsuccessful. Computerized tomography (CT) was suggestive of a pulmonary abscess, but CT-guided drainage did not yield any purulent fluid. Percutaneous biopsies were performed, and the cytology showed malignant cells. During thoracotomy, a large tumor involving the left lower lobe and pleural space was found, and a biopsy was performed. A frozen section showed blastemal and mesenchymal components devoid of neoplastic epithelium, consistent with the pleural variant of pulmonary blastoma. A left lower lobectomy, with tumor decortication of the pleural space, achieved total gross tumor removal. The child received aggressive multiagent chemotherapy, and midway through it he underwent elective excision of the opposite lung cyst. It has been 17 months since the lobectomy; he is off chemotherapy and has no evidence of disease. A review of the literature showed that a large number of pediatric pulmonary blastomas are associated with cystic lung disease. Because total tumor removal offers the only chance of a good long-term outcome, surgical excision or close follow-up of pulmonary cysts in children is strongly recommended.

Age of Onset↗
PubMed1996

Changes in the pattern of distribution of von Willebrand factor in rat aortic endothelial cells following thrombin generation in vivo.

The pattern of distribution of von Willebrand factor (VWF) in relatively large sheets of rat aortic endothelial cells (EC) obtained by the Häutchen technique were analysed by immunocytochemistry and light microscopy. EC were examined pre and post administration of a procoagulant mixture of factor Xa (F.Xa) and phosphotidylcholine/phosphotidylserine (PCPS) vesicles which was demonstrated to result in the selective loss of high molecular weight multimers (HMWM) of plasma VWF in the rat. In placebo animals the pattern was heterogenous both in overall distribution and in individual cells which showed both a diffuse and granular pattern. Groups of intensely stained EC were oriented parallel to the longitudinal axis of the aorta and staining was particularly prominent around the orifices of the intercostal arteries, implicating shear-stress as a possible factor in VWF expression by EC. Changes in the pattern of distribution of staining were observed at various time points post-infusion of F.Xa/PCPS, suggesting the immediate release of VWF from EC stores followed by the recruitment of EC to synthesize and store VWF. These changes are consistent with the decrease in EC Weibel-Palade Body (WPB) content observed by EM in previously reported studies using this model.

Animals↗
PubMed1996

Access to primary health care among persons with disabilities in rural areas: a summary of the literature.

Despite the prevalence of disabilities among persons living in rural areas, scarce data exist on their health care needs. While rural residents generally experience barriers to access to primary health care, these problems are further exacerbated for people with disabilities. This article summarizes findings from the published literature on access to primary health care among people with disabilities living in rural locations. A comprehensive computerized literature search turned up 86 articles meeting the study criteria, focused on the following rural populations affected by disabilities: children and adolescents, working-age adults, the elderly the mentally ill, and people with AIDS. For each of these populations, substantial problems in accessing appropriate health care have been documented. The literature consistently emphasizes the failure of local health care systems in nonmetropolitan areas to adequately address the complex medical and related needs of individuals with disabilities. In the absence of specialized expertise, facilities, and primary care providers trained specifically to care for disabled persons, local programs rely heavily on the use of indigenous paraprofessionals and alternative models of care. Further research is needed to identify and test the efficacy of innovative service delivery strategies to improve health care access for this population.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Genotyping of Mycobacterium tuberculosis with additional markers enhances accuracy in epidemiological studies.

Two highly polymorphic Mycobacterium tuberculosis genomic domains, characterized by hybridization to the oligonucleotide (GTG)5, were identified as potential DNA fingerprinting probes. These domains were cloned [pMTB484(1) and pMTB484(2K4), respectively] and shown to be useful for genotype analysis by Southern blotting. These probes were used to genotype geographically linked strains of M. tuberculosis previously shown to have identical IS6110 fingerprints. Subsequent DNA fingerprints generated with MTB484(1) and MTB484(2K4) showed a high degree of polymorphism, allowing subclassification of IS6110-defined clusters into composites of smaller clusters and unique strains. Correlation of the molecular data with patient interviews and clinical records confirmed the sensitivity of these probes, as contacts were established only within subclusters. These findings demonstrate the requirement for multiple probes to accurately classify M. tuberculosis strains, even those with high copy numbers of IS6110. The enhanced accuracy of strain typing should, in turn, further our understanding of the epidemiology of tuberculosis.

Bacterial Typing Techniques↗
PubMed1996

An increased uptake of prothrombin, antithrombin, and fibrinogen by the rabbit balloon-deendothelialized aorta surface in vivo is maintained until reendothelialization is complete.

The ability of the rabbit aorta intima-media (IM) layer to adsorb certain plasma proteins was measured for up to 20 months after a deendothelializing injury in vivo. Purified radioiodinated rabbit fibrinogen, antithrombin, or prothrombin was injected intravenously into either uninjured or sham-injured rabbits (controls) or rabbits at various times (5 minutes to 20 months) after a balloon-catheter injury to the aorta. After a 10-minute circulation time, a blood sample was taken, and the rabbit was exsanguinated rapidly (via a carotid cannula) and the aorta excised. Uptake of each radiolabeled protein was measured as bound radioactivity per square centimeter of platelet- or endothelium-free aorta IM and was compared with the radioactivity (ergo concentration) in blood at exsanguination. Fibrinogen adsorption by the IM was maximal at 5 minutes after injury (10.9 +/- 2.3 pmol/cm2 IM) and declined slowly to 4 to 6 pmol/cm2 at 12 months (controls: 0.8 +/- 0.1 pmol/cm2). Uptake of prothrombin (3.7 +/- 0.5 pmol/cm2 at 5 minutes) decreased to approximately 2 pmol/cm2 at 12 months (controls: 0.3 pmol/cm2). Antithrombin adsorption by the IM (3.3 +/- 0.4 pmol/cm2 at 5 minutes) paralleled that of prothrombin over 12 months (controls: 0.3 to 0.4 pmol/cm2), the molar ratio ranging from 0.8 to 1.2. At 20 months, the ballooned aorta had a significantly thickened intima and was approximately 90% reendothelialized. Injection of horseradish peroxidase (HRP) into rabbits at 1 or 12 months after balloon injury showed clearly that HRP activity was present throughout the entire depth of the deendothelialized, but not the reendothelialized, thickened intima. These results may indicate that an elevated turnover of hemostatic proteins continues within the deendothelialized intima after injury, conceivably until reendothelialization is complete.

Animals↗
PubMed1996

Unexpectedly high strain diversity of Mycobacterium tuberculosis in a high-incidence community.

OBJECTIVE: To characterise Mycobacterium tuberculosis strains present in a community experiencing an epidemic, in order to establish whether a high rate of transmission results in low strain diversity. DESIGN: Sputum specimens collected for 18 months; IS6110-based DNA fingerprinting. SETTING: The communities of Ravensmead and Uitsig, Cape Town, South Africa. PARTICIPANTS: Three hundred and thirty-four pulmonary tuberculosis patients attending the Local Authority Health Care Clinic. MAIN OUTCOME MEASURE: DNA fingerprinting. RESULTS: A total of 334 M. tuberculosis isolates were characterised by IS6110-based DNA fingerprinting; 209 strains were identified, 199 having 5 or more insertions. Forty of these strains were present in 2 or more patients (clustering--126 patients in total), which indicates a recent transmission rate of 30%. The 163 unique strains suggest reactivation of latent infections. Computer analysis showed a high degree of strain diversity, and a common progenitor could only be linked to 33% of the strains. Clustering was shown in 50% of drug-resistant isolates. CONCLUSIONS: The low rate of transmission (30%) and the high degree of strain diversity (209 strains) was unexpected and unexplained, given the high burden of disease in this community. The clustering of drug-resistant strains suggests that transmission, rather than lack of compliance, drives the spread of antibiotic resistance in this community. Preliminary indications are that BCG vaccination, while having little effect on the incidence of tuberculosis in this community, may have altered the strain dynamics.

Adolescent↗
PubMed1996

The biopsychosocial model of general practice: rhetoric or reality?

BACKGROUND: For more than 20 years, general practitioners have been encouraged to adopt a 'biopsychosocial' model of health care, that is, encompassing physical, psychological and social aspects. AIM: A study was undertaken to explore the extent to which general practitioners' views about the acceptable boundaries of their work are consistent with a biopsychosocial model. METHOD: A semi-structured postal questionnaire was sent to all 494 members of the Royal College of General Practitioners in Mersey Region who were general practitioner principals. The general practitioners were asked to list up to three topics presented by patients that they considered to be appropriate, and up to three topics that they considered to be inappropriate, to a general practitioner's knowledge and skills. The general practitioners were asked to rate, on a five-point scale of appropriateness, each of a list of 12 topics about which patients might have problems and present. Responses were analysed by sex and age of respondents. RESULTS: The response rate was 42%. Acute physical problems were most often listed appropriate by respondents, followed by chronic physical and psychological problems. The topics most often considered inappropriate were bureaucracy and social issues. Among the list of 12 specified topics, respondents considered terminal care and hypertension to be more appropriate than housing issues, spiritual worries, welfare rights or political issues. The sex of respondents did not relate to differences in results. Respondents aged 35 years and over generally considered topics presented by their patients to be more appropriate than did their younger colleagues. CONCLUSION: The general practitioner respondents in this study appeared to hold the view that general practitioners should work to a bio(psycho) rather than a biopsychosocial model of health care.

Attitude of Health Personnel↗
PubMed1996

Ecotoxicity monitoring--use of Vibrio fischeri.

The proliferation of chemical substances having the potential to pollute any environmental medium (air, land, water), or humans via occupational exposure, la considerable. Whilst chemical analytical techniques exist for the measurement of some of these chemicals, many of the methods involve costly techniques of considerable sophistication-quantification may be even more difficult. In less developed countries where sophisticated techniques may not be available or supplies of reagents, compressed gases or even electricity cannot be guaranteed, generic techniques have a great deal to offer. An emission of a chemical will cause adverse effects to organisms and hence there is an enormous advantage in measuring such effects on biological systems. One such technique is the reduction of light output In the presence of a toxicant to the marine bacteria Vibrio fischeri (formerly known as Photobacterium phosphoreum NRRL B-11177). A dark variant M-169 can also be used to obtain mutagenicity data. A chronic test whose results compare well with Ceriodaphnia dubia, has also been developed. The development of the principles of environmental toxicology assessment is reviewed together with the concept of toxic insult as a pragmatic tool in environmental risk assessment.

Environmental Monitoring↗
PubMed1995

A novel cytochrome P450 expressed primarily in brain.

hct-1 (hippocampal transcript) was detected in a differential screen of a rat hippocampal cDNA library. Expression of hct-1 was enriched in the formation but was also detected in rat liver and kidney, though at much lower levels; expression was barely detectable in testis, ovary, and adrenal. In liver, unlike brain, expression was sexually dimorphic; hepatic expression was greatly reduced in female rats. In mouse, brain expression was widespread, with the highest levels being detected in corpus callosum; only low levels were detected in liver. Sequence analysis of rat and mouse hct-1 cDNAs revealed extensive homologies with cytochrome P450s (CYPs), a diverse family of heme-binding monooxygenases that metabolize a range of substrates including steroids, fatty acids, and xenobiotics. Among the CYPs, hct-1 is most similar (39% at the amino acid sequence) to cholesterol 7 alpha-hydroxylase (CYP7) and contains a postulated steroidogenic domain present in other steroid-metabolizing CYPs but clearly represents a type of CYP not previously reported. Genomic Southern analysis suggests that a single gene corresponding to hct-1 is present in mouse, rat, and human. hct-1 is unusual in that, unlike all other CYPs described, the primary site of expression is in the brain. Similarity to CYP7 and other steroid-metabolizing CYPs may argue that hct-1 (CYP7B) plays a role in steroid metabolism in brain, notable because of the documented ability of brain-derived steroids (neurosteroids) to modulate cognitive function in vivo.

Amino Acid Sequence↗