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Biomedical subjects

J McMahon

Publications and source records attributed to J McMahon.

At least 73 records · Page 4Linked to original sources
PubMed1991

Characterization of new members of the pregnancy-specific beta 1-glycoprotein family.

Three cDNAs encoding members of the pregnancy-specific beta 1-glycoprotein (PSG) family were isolated from human term placental cDNA library. All three cDNAs encode proteins with similar domain structure. There is a leader sequence of 34 amino acids followed by an N-domain of 109 amino acids. Immediately after the N-domain are one or two copies of a repeating A-domain of 93 amino acids, a B-domain of 85 amino acids and a C-domain of variable size. The proteins are highly hydrophilic. However, one of them has an 81-amino acid C-domain which is very hydrophobic and could potentially serve as a membrane attachment site. The putative cell-cell recognition tripeptide, Arg-Gly-Asp, is present in the N-domain of two of the proteins. Partial sequence of one of the cDNAs has been found in HeLa cells while cDNAs highly homologous to two of the cDNAs have been found in the fetal liver. Functional roles of the PSG proteins basing on their structure are proposed.

Amino Acid Sequence↗
PubMed1991

Sublingual captopril--a pharmacokinetic and pharmacodynamic evaluation.

In this study we compared the pharmacokinetics and pharmacodynamics of captopril after sublingual and peroral administration. Single 25 mg doses of captopril were administered sublingually and perorally on two different occasions in a randomised cross-over fashion to eight healthy volunteers aged 22-35 years. The kinetics of unchanged captopril, plasma renin activity (PRA). BP and heart rate were studied over three hours after both peroral and sublingual administration of captopril. Mean pharmacokinetic parameters for unchanged captopril after sublingual administration were: Cmax, 234 ng.ml-1; tmax, 45 min; AUC (0-3 h), 15.1 micrograms.ml-1.min. Mean pharmacokinetic parameters for unchanged captopril after peroral administration were; Cmax, 228 ng.ml-1; tmax, 75 min; AUC (0-3 h), 17.0 micrograms.ml-1.min.tmax was significantly shorter when captopril was administered sublingually; all other pharmacokinetic parameters were equivalent. The plasma captopril concentrations achieved post drug administration led to increases in PRA and reductions in BP.tmax for PRA was 86 min for sublingual captopril and 113 min for perorally administered drug. Peak PRA values were, however, not significantly different. BP, as expected, was not reduced dramatically in these healthy volunteer subjects, however, in systolic BP vs time profiles, BP was significantly lower after volunteers received sublingual captopril. Heart rate increased slightly after captopril administration; there were no differences between the two routes of administration. Administration of captopril sublingually, therefore led to a more rapid attainment of plasma captopril concentrations and had a more rapid onset of pharmacological effect when compared with peroral administration.

Administration, Oral↗
PubMed1991

A genetic linkage map of human chromosome 5 with 60 RFLP loci.

A genetic map of human chromosome 5 that contains 60 restriction fragment length polymorphism (RFLP) loci in one linkage group has been constructed. Segregation data using these markers and 40 large multigenerational families supplied by the Centre d'Etude du Polymorphisme Humain have been collected. Linkage analyses were performed with the program package CRI-MAP; using odds greater than 1000:1, 30 RFLP loci could be placed on the map. This genetic map spans 289 cM sex-equal, 353 cM in females, and 244 cM in males. While the relative rate of recombination for female meioses is nearly twice that of males over much of the chromosome, several instances of statistically significant excess male recombination were observed. The order of probes on the genetic map has been confirmed by their physical order as determined by somatic cell hybrid lines containing deletions of normal chromosome 5. There is concordance between the physical positions of markers and their genetic positions. Our most distal probes on the genetic map are cytologically localized to the most distal portions of the chromosome. This suggests that our genetic map spans most of chromosome 5.

Blotting, Southern↗
PubMed1990

Feasibility of cellular microencapsulation technology for evaluation of anti-human immunodeficiency virus drugs in vivo.

We investigated the feasibility of micro-encapsulation technology for the evaluation of anti-human immunodeficiency virus (HIV) drugs in vivo. The ability to place human cells in microcapsules with semipermeable membranes for implantation into test animals led to the development of this assay. The anti-HIV activity assay involves microencapsulating human T-lymphoblastoid cells sensitive to the cytopathic effects of HIV; the encapsulated cells are then implanted into athymic nude mice and recovered after drug treatment in vivo. A positive antiviral effect of the test substance is indicated by growth or survival of the virus-infected cells in the microcapsules. Several HIV-sensitive cell lines of T-lymphocyte, monocyte, and nonlymphocyte origin were examined for growth in microcapsules in vitro and in vivo. Light and electron microscopic analysis of the capsules and the human cells contained therein revealed the invasion of mouse immune cells and other adverse effects that could not be overcome by any of numerous technical modifications attempted. We conclude that cellular microencapsulation technology is not feasible for in vivo drug-testing protocols because of immunogenic reactions.

Animals↗
PubMed1990

New colorimetric cytotoxicity assay for anticancer-drug screening.

We have developed a rapid, sensitive, and inexpensive method for measuring the cellular protein content of adherent and suspension cultures in 96-well microtiter plates. The method is suitable for ordinary laboratory purposes and for very large-scale applications, such as the National Cancer Institute's disease-oriented in vitro anticancer-drug discovery screen, which requires the use of several million culture wells per year. Cultures fixed with trichloroacetic acid were stained for 30 minutes with 0.4% (wt/vol) sulforhodamine B (SRB) dissolved in 1% acetic acid. Unbound dye was removed by four washes with 1% acetic acid, and protein-bound dye was extracted with 10 mM unbuffered Tris base [tris (hydroxymethyl)aminomethane] for determination of optical density in a computer-interfaced, 96-well microtiter plate reader. The SRB assay results were linear with the number of cells and with values for cellular protein measured by both the Lowry and Bradford assays at densities ranging from sparse subconfluence to multilayered supraconfluence. The signal-to-noise ratio at 564 nm was approximately 1.5 with 1,000 cells per well. The sensitivity of the SRB assay compared favorably with sensitivities of several fluorescence assays and was superior to those of both the Lowry and Bradford assays and to those of 20 other visible dyes. The SRB assay provides a colorimetric end point that is nondestructive, indefinitely stable, and visible to the naked eye. It provides a sensitive measure of drug-induced cytotoxicity, is useful in quantitating clonogenicity, and is well suited to high-volume, automated drug screening. SRB fluoresces strongly with laser excitation at 488 nm and can be measured quantitatively at the single-cell level by static fluorescence cytometry.

Adenocarcinoma↗
PubMed1990

Parental origin of chromosome 5 deletions in the cri-du-chat syndrome.

The parental origin of de novo deletions leading to the cri-du-chat syndrome has been investigated. Since the cri-du-chat syndrome is correlated with deletions involving the short arm of chromosome 5 (5p), DNA fragments known to detect restriction fragment length polymorphisms (RFLPs) along 5p were used to establish whether the paternal or the maternal chromosome had suffered the deletion. In cases where only one parent was available, somatic cell hybrids were used in conjunction with RFLP analysis to determine the origin of the deleted chromosome. The deleted chromosome 5 was of paternal origin in 20/25 cases.

Chromosome Deletion↗
PubMed1990

Ultrastructural evidence that insoluble microtubules are components of the neurofibrillary tangle.

The ultrastructure of Alzheimer's neurofibrillary tangles is heterogeneous and includes abnormal paired helical filaments (PHF) and various other insoluble structures. Insoluble non-PHF components isolated from neurofibrillary tangles were examined by electron microscopy. Comparison of these fractions with normal assembled neurofilaments and normal brain microtubules revealed scattered profiles which were morphologically (not chemically) identical to structures present in the microtubule, but not in the neurofilament preparations. These results support the notion that insoluble microtubules contribute to the make up of the neurofibrillary tangle. Based on these findings, preliminary experiments were conducted which suggest that non-enzymatic glycosylation may be a pathway leading to insolubility of the microtubules.

Aged↗
PubMed1989

Adolescent third-trimester enrollment in prenatal care.

This study reports the demographic and reproductive characteristics of 87 adolescents (11-19 years of age) who entered prenatal care during the third trimester of pregnancy at a publicly funded program during a 6-month period of 1987-1988, as well as their self-reported reasons for delayed prenatal care. The findings suggest that concealment of the pregnancy was the primary reason for younger adolescents (11-17 years), while poor motivation to attend prenatal care was often cited by the older adolescents (18-19 years). Older adolescents appeared to be particularly at risk for poor pregnancy outcome: 63% were mothers; the identified pregnancy was the third child for 20%; 42% smoked during pregnancy; and 22% entered care during the period from 36 to 41 weeks of gestation. The apparently poor motivation to attend prenatal care and the closely spaced pregnancies of this age group suggest that the second and third children of adolescent mothers may be a particularly vulnerable pediatric population.

Adolescent↗
PubMed1989

Status of trauma center designation.

1) In 1986 20 states are designating trauma centers. 2) ACS guidelines appear to be the accepted standard. 3) Almost all of the states providing designation retain the power of final designation but allow individual hospitals to initiate the process. 4) Designation is usually based on actual capability and frequently requires a site visit team in which surgeons and emergency medicine physicians play a prominent role. 5) Designation appears to be for a finite period of time but half of the states do not provide for de-designation. 6) A national mandate is necessary for timely and uniform implementation of trauma center designation.

General Surgery↗
PubMed1989

Prenatal diagnosis and carrier detection of a cryptic translocation by using DNA markers from the short arm of chromosome 5.

DNA markers from the short arm of chromosome 5 were used to examine a large family in which a microscopically undetectable translocation was segregating. In addition to confirming that three retarded children were hemizygous for loci distal to 5p14, these analyses identified five individuals as being carriers of the balanced translocation. The use of molecular probes provided informed genetic counseling to the family for the first time. With the DNA markers from 5p, prenatal diagnosis was performed on two fetal chorionic villus samples, both of which were found to have unbalanced karyotypes. The identification of translocation carriers was complicated by recombination between the small translocated segment of 5p and the corresponding region on the normal homologue, which changed the haplotype of the translocated 5p segment.

Animals↗
PubMed1988

Foreign-body granuloma following bilateral facial reconstruction with an omental flap.

Bilateral facial reconstruction using an omental free-flap transfer for soft-tissue augmentation was performed on a 23-year-old man who had undergone previous surgical resection of an embryonal-cell rhabdomyosarcoma followed by radiation and chemotherapy. Eight weeks following surgery, the patient presented with pain and edema from a foreign-body reaction documented by electron microscopy. This was successfully managed with a course of steroid administration. The patient has remained symptom-free for 5 years.

Adult↗
PubMed1988

The induction of Friend erythroleukaemia differentiation is markedly affected by expression of a transfected c-myb cDNA.

A minigene containing a cDNA encoding the normal mouse p80c-myb protein under strong promoter control was used to transfect Friend erythroleukaemia cells. Expression of the transfected gene was found to result in elevated levels of p80c-myb which were not subject to rapid down-modulation by inducers of Friend cell differentiation as was the product of the endogenous c-myb gene. Continued synthesis of p80c-myb was found to be associated with a marked decrease in differentiation of Friend cells and we concluded that normal down-regulation of c-myb expression may be a necessary event in differentiation of these cells.

Animals↗
PubMed1987

Multiple c-myb transcript cap sites are variously utilized in cells of mouse haemopoietic origin.

Mouse c-myb gene transcripts in various cells of haemopoietic origin were analysed using S1 nuclease and RNase mapping techniques and by Northern blotting. It was found that the prevalent 3.8-kb c-myb mRNA present in thymocytes, T cell leukaemias, myelomonocytic leukaemias, erythroleukaemias and myeloid stem cells was initiated at several cap sites mapping within a region 97-244 bp upstream from the protein coding sequence. Utilization of additional cap sites mapping further upstream was also observed in certain cells, most notably thymocytes, and this gave rise to RNA species (4.3-5.6 kb) larger than the presumptive mRNA. In contrast, myeloma cell c-myb transcripts, which are much less abundant than those in more immature haemopoietic cells, were found to be initiated at a restricted set of cap sites mapping 244-277 bp upstream of the coding sequence. Hence, these data suggest that the abundance of the c-myb mRNA may be regulated by a process involving selective utilization of mRNA cap sites. Sites hypersensitive to DNase I were associated with mRNA cap sites in cells that expressed c-myb.

Animals↗
PubMed1987

Characterization of a mutant polyoma that expresses in F9 embryonal carcinoma cells: morphology, tumorigenicity, and restriction enzyme analysis.

A mutant polyoma virus (TT340), which replicates in F9 embryonal carcinoma (EC) cells and contains 2500 base pairs (bp) of additional DNA located in the early noncoding region of the genome, was analyzed to determined the DNA origin of the mutant insertion. Two fragments, representing repeated units of the 2500-bp insert, were isolated from TT340, labeled, and hybridized to the parental wild-type viral DNA. A BglI 500-bp unit, of which there are approximately five copies within the 2500-bp insert, contains sequences homologous to regions on the early and late side of the viral origin of replication. A HpaII 400-bp repeated fragment shows homology to sequences on the early side with little hybridization to the late side. Removal of the 2500-bp insert results in the loss of infectivity on F9 EC cells but not on 3T6 or mouse embryo fibroblasts. Insertion of the BglI 500-bp repeat element into wild-type DNA at the BglI site allows replication of the constructed virus in F9 cells. The mutant virions were tumorigenic in newborn Syrian hamsters and the morphology of the virus was that of wild-type as assayed by electron microscopy.

Animals↗
PubMed1987

Observations on the treatment of mediastinal masses in Hodgkin's disease emphasizing site of failure.

Of 244 patients with Hodgkin's disease, 126 (52%) had an abnormal mediastinum. Sixty-four patients were treated with radiation, 36 with radiation and chemotherapy, and 25 with chemotherapy alone as an initial treatment. Twenty of 52 (38%) with stage I or II who received initially radiation alone relapsed, and 70% (14 of 20) of them were salvaged with chemotherapy. Therefore, the ultimate failure rate was 12% (6 of 52). Forty percent (8 of 20) of these patients failed within or at the margin of the radiation portal, and 60% failed predominantly outside of the radiation field. Even though we did not treat the whole lung prophylactically, there was only one true peripheral lung recurrence. Nine of 20 (45%) recurred in more than one site. Of 36 patients treated with combined radiation and chemotherapy, 21 patients had stage I, II, or IIIA disease. Of these, two patients relapsed. Of 86 patients with accessible x-ray films, 30 patients had large masses with a ratio of mass to transverse diameter greater than .33 at the broadest level. Fifty-six patients had small masses. Survival at 96 months in patients with stages I-IIIA with either large or small masses is 94% (p = 0.80). Their relapse-free survival at 96 months is 79% for large masses and 95% for small masses (p = 0.18). The site of relapse is discussed in detail in the text. There were five treatment-related deaths; three patients died of acute myelogenous leukemia. Our data do not support the role of whole-lung prophylactic irradiation or initial combined radiotherapy and chemotherapy in patients with large mediastinal masses.

Adolescent↗
PubMed1987

Revised post-mortem inspection procedures for cattle and pigs slaughtered at Australian abattoirs.

Revised procedures for the post-mortem inspection of cattle and pigs at Australian abattoirs were developed as minimum national requirements. Comparative trials of current and revised procedures were conducted at 3 and 4 Australian abattoirs for pigs and cattle respectively. Residual pathological changes after inspection and removal of lesions from heads, carcases or viscera were recorded by an evaluation team with the data used to determine relative effectiveness. For cattle, there was no significant difference between current and revised procedures. Although it had been proposed to eliminate routine incision of cervical lymph nodes for pigs, it was found necessary to retain this procedure. The data also revealed a significant variation in detection of pathology between abattoirs for both species. Parasitic conditions accounted for the greatest proportion of undetected lesions in both species for both current and revised procedures. These comprised mainly fascioliasis in cattle and ascariasis in pigs. The former was associated with the study being conducted in eastern Australia. Chronic interstitial nephritis was also a common undetected lesion, reinforcing the need for intensified inspection of kidneys. However, such residual pathology was considered to be of only limited significance to human health. The revised procedures and findings are discussed in the context of animal and human health and of the importance of the meat industry to Australian exports. Some attention has been given to specific conditions likely to be affected by the proposals including tuberculosis, bovine cysticercosis, fascioliasis, porcine arthritis and salmonellosis. The role of meat inspection in monitoring for specific diseases is discussed.(ABSTRACT TRUNCATED AT 250 WORDS)

Abattoirs↗