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Biomedical subjects

C Moran

Publications and source records attributed to C Moran.

At least 19 recordsLinked to original sources

Phylogenetic relationships of Asian and European pig breeds determined by mitochondrial DNA D-loop sequence polymorphism.

Phylogenetic relationships among Asian and European pig breeds were assessed using 1036 bp of mitochondrial DNA (mtDNA) D-loop sequences. An unweighted pair-group method with arithmetic mean (UPGMA) tree was constructed on the basis of maximum likelihood distances using sequences determined for three Cheju (Korea), 11 Chinese, one Westran (Australian feral origin) and two European pigs (Berkshire and Welsh), and also published sequences for four Japanese (including two Wild Boars), one Yucatan miniature, five European (including Large White, Landrace, Duroc, Swedish and Wild Boar) and two Meishan pigs. The Colombian collared peccary (Tayassu tajacu) sequence was also determined and used as an outgroup. The maximum parsimony with heuristic search method was used to determine bootstrap support values. Asian-type pigs clustered together (bootstrap support 33%), but were separate from European-type pigs that also clustered together (93%). The Westran pig, derived from the feral descendants of pigs inhabiting Kangaroo Island of South Australia, clustered with Asian pigs, demonstrating Asian origin of their mitochondria. Berkshire and Large White clustered with Asian pigs, indicating that Asian pigs were involved in the development of these breeds. Our findings clearly demonstrate that pigs indigenous to China, Korea and Japan are only recently diverged from each other and distinctly different from European-type pigs. European pig breeds consist of pigs with mitochondria of Asian and non-Asian type, some of which were formed from closely related maternal ancestors, if not from a single ancestor.

Animals↗

Altered autophosphorylation of the insulin receptor in the ovary of a woman with polycystic ovary syndrome.

OBJECTIVE: To determine whether the tyrosine autophosphorylation of the insulin receptor (IR) in the ovary of a woman with polycystic ovary syndrome (PCOS) was reduced compared to normal. DESIGN: Experimental study. SETTING: Tertiary care medical center. PATIENT(S): One woman with PCOS and one healthy control, both of whom underwent a hysterectomy and bilateral salpingo-oophorectomy. INTERVENTION(S): Plasma membrane fraction of ovarian tissue was isolated, and the IR was purified and concentrated. MAIN OUTCOME MEASURE(S): Western blots of the IR, which had been incubated with and without insulin, were prepared. Colorimetric and chemiluminescent methods were used to detect the presence of the IR beta-subunit and IR tyrosine autophosphorylation, respectively. RESULT(S): The presence of the beta-subunit of the IR was identified in both ovarian samples. The degree of insulin-stimulated IR tyrosine autophosphorylation, reflected by the mean (+/-SD) relative optical density of the 95 kd band, was 4.3-fold higher in the normal ovary compared to the PCOS ovary (0.56 +/- 0.18 optical density vs. 0.13 +/- 0.10 optical density, respectively). CONCLUSION(S): Tyrosine autophosphorylation of the IR may be decreased in the ovaries of women with PCOS, similar to the findings in other tissues. The mechanisms through which insulin acts to produce an excess in ovarian androgen production in the face of a decrease in ovarian IR autophosphorylation remain to be determined.

Adult↗

Hyperandrogenemia in patients presenting with acne.

OBJECTIVE: To determine whether acne is associated with hyperandrogenemia, regardless of age of presentation. DESIGN: Prospective controlled study. SETTING: Tertiary-care medical center. PATIENT(S): Thirty consecutive unselected women presenting with acne and no hirsutism and 24 eumenorrheic healthy controls. INTERVENTION(S): Serum samples was taken in all patients, and an acute 60-minute ACTH-(1-24) test was performed in 19 patients. MAIN OUTCOME MEASURE(S): Total and free T, sex hormone-binding globulin (SHBG), and DHEAS levels in basal samples, and ACTH-stimulated 17-hydroxyprogesterone (17-HP) response to exclude 21-hydroxylase (21-OH)-deficient nonclassic adrenal hyperplasia (NCAH) were determined. RESULT(S): Nonhirsute patients with acne demonstrated significantly lower levels of SHBG and higher free-T and DHEAS levels than controls. Nineteen (63%) acneic patients had at least one androgen value above the 95% of controls. In patients aged 12-18 years, 7/8 (88%) had at least one increased androgen value, compared with 12/22 (55%) patients aged 19-43 years. One patient (5.3%) was found to have 21-OH-deficient NCAH. CONCLUSION(S): Hyperandrogenemia was evident in a majority of nonhirsute acneic patients studied, regardless of age. These data suggest that androgen suppression may be useful in treating acne in many of these patients.

17-alpha-Hydroxyprogesterone↗

The role of the adrenal cortex in polycystic ovary syndrome.

Adrenal androgen excess affects approximately 25% of PCOS patients. The exact etiology of this excess in PCOS patients is unclear. Some evidence that adrenal androgen excess may be a genetic trait. The adrenal androgen response to ACTH is highly individualized, and the relative response seems to be constant over time. In addition, there is a strong familial component to adrenal androgen levels in normal individuals and PCOS patients. It is possible that the tendency to overproduce adrenal androgens is an inherited risk factor for the development of PCOS. Overall, few hyperandrogenic patients actually have isolated deficiencies of 3 beta-hydroxysteroid dehydrogenase, 21-hydroxylase, and 11-hydroxylase. The ovarian hormonal secretion in PCOS can affect adrenal androgen secretion and metabolism, although this factor accounts for only part of this abnormality. More likely, the adrenal androgen excess results from a generalized hyperresponsiveness of the adrenal cortex to ACTH, but without an increase in CRH or ACTH sensitivity. Although glucocorticoid administration may improve the ovulatory function of these patients, the results are modest and cannot be predicted by the circulating androgen levels.

Adrenal Cortex Diseases↗

Myocardial ischaemia in normal patients undergoing elective Caesarean section: a peripartum assessment.

Incidence rates of electrocardiographic changes during Caesarean section vary from 25 to 60%. To date, no investigator has identified myocardial ischaemia resulting from these changes. We investigated patients undergoing elective Caesarean section using peripartum Holter monitoring and serum analysis of cardiac troponin I (cTnI). Twenty-six patients presenting for elective Caesarean section were studied. Peroperative Holter monitoring continued for 12 h postoperatively, at which time blood samples for cTnI levels were taken. Significant ST changes were recorded in 42% of patients peroperatively and 38.5% of patients postoperatively. Forty-two per cent of patients experienced peroperative chest pain requiring opioid analgesia. Chest pain was significantly associated with abnormal electrocardiogram (ECG) findings. Ischaemic levels of cTnI were recorded in two patients. This study reports, for the first time, myocardial ischaemia (7.69% of patients) arising in conjunction with the ECG changes seen during elective Caesarean section. We also report episodes of significant postoperative ST-segment changes.

Adult↗

Comparative porcine gene mapping relative to human chromosomes 9, 10, 20 and 22.

Comparative anchor tagged sequence (CATS) consensus primers from loci mapped to human chromosomes 9, 10, 20, and 22 have been used to amplify homologous loci in pigs. Of 53, CATS primers tested in pigs, only 23 yielded products homologous to the human locus (42% success). Ten loci were physically mapped (43% success rate for verified products, but only 19% for primers tested). Due to lack of polymorphism, linkage mapping was possible only for AMBP. Map locations were consistent with human/pig ZOO-FISH, except for ADRA1A, whose position is still equivocal in humans. These CATS primers have made very limited contributions to pig/human comparative gene mapping because of low efficiency of amplification of orthologous porcine product, frequent amplification from rodent template in a somatic hybrid panel and low level of polymorphism.

Animals↗

An audit of perioperative management of autistic children.

BACKGROUND: Autistic children are very difficult to manage in the hospital setting because they react badly to any change in routine. METHODS: We have developed a unique management program for autistic children admitted for medical and surgical procedures requiring a general anaesthetic. Details of each patient managed according to this program have been prospectively entered into an Autistic Register. RESULTS: An audit of this database shows that we have administered anaesthesia on 87 occasions for 59 autistic children over 4 years. CONCLUSIONS: There is great variation in the severity of autism and hospital needs of these children. The focus is on early communication with the patient's families, flexibility to individualize the admission process and anaesthetic plan with admission and early discharge on the day of surgery whenever possible. Oral midazolam is an effective premedication for the milder cases and oral ketamine is the most reliable for moderate and severe cases. Comparison of oral midazolam and ketamine shows no significant different postoperative recovery and hospital discharge times. Routine intravenous fluids and antiemesis prophylaxis with removal of the i.v. cannula before return to the ward are also seen as important steps to decrease stress and smooth the postoperative phase. This program has also successfully been extended to the management of problem children due to other causes.

Adolescent↗

Facial and abdominal hair growth in hirsutism: a computerized evaluation.

Methods of objectively assessing the growth rate of hairs in hirsute women have generally required some form of shaving and have focused on studying hairs affecting the face, which has reduced the number of patients willing or able to participate in such studies. A possible solution is to assess the terminal hairs on the lower abdomen (ie, the male escutcheon) because these two body areas are the most frequently affected with excess hair growth in hirsute patients. Nonetheless, it is unclear how the growth characteristics (density, diameter, and growth rate) of the hairs on the abdomen and face differ in these patients. We hypothesize that the growth characteristics of terminal hairs on the abdomen and face are similar and that evaluation of either area may be sufficient in assessing the hair growth rate of these patients. To objectively evaluate hair growth in the face and abdomen in hirsute patients, we developed a computer-aided image analysis system capable of measuring several growth parameters. Twenty hirsute women (12 white and 8 black), aged 31.2 +/- 6.1 years, were studied. Facial and abdominal skin areas were shaved, and 3 to 5 days later the areas were photographed through a calibrated glass plate and 5 terminal hairs were plucked from each area. The daily hair growth rate (assessed by photography and by direct measurement of the plucked hair), the density of hairs (number of hairs per surface area assessed by photography), and hair diameter (of the plucked hairs) were determined. The extent of hirsutism was also measured, albeit subjectively, by a modification of the Ferriman-Gallwey method, with each area given a score of 0 (no terminal hairs seen) to 4 (terminal hairs in a pattern similar to that of a very hirsute man). Facial, abdominal, and total Ferriman-Gallwey scores were 1.3 +/- 0.6, 1.8 +/- 0.9, and 12.5 +/- 5.4, respectively. Our results indicated that facial hairs were distributed in greater density and had a greater diameter than abdominal hairs (15.6 +/- 14.2 hairs/cm(2) vs 5.4 +/- 1.9 hairs/cm(2), and 84.5 +/- 19.5 microm and 66.2 +/- 17.5 microm, respectively, P <.005). Alternatively, the growth rates of facial and abdominal hairs were similar, whether determined photographically (0.36 +/- 0.18 mm/day vs 0.43 +/- 0.19 mm/day, respectively) or from plucked hairs (1.2 +/- +0.2 mm/d vs 1.4 + 0.4 mm/d, respectively). We conclude that although the density and diameter of facial hairs are greater than that of lower abdominal hairs, these areas have very similar growth rates. Hence evaluation of either of the body areas, using an objective method of assessing hair growth, should provide equivalent results.

Abdomen↗

Comparison of continuity in a resident versus private practice.

BACKGROUND: There is widespread agreement among pediatric educators that continuity (following a panel of patients on a first contact basis for all their health care) is an important part of the education of pediatricians. OBJECTIVE: To measure continuity in a pediatric residency practice and to compare this continuity with 2 nearby private general pediatric group practices. We also examined measures of continuity suggested in the literature. DESIGN: Visit data were obtained from the practice billing system for a resident continuity practice and 2 nearby private practices for the 3-year period from July 1, 1992, to June 30, 1995. Visit data used were restricted to patients seen in the office of the practices during regular office hours. Continuity was measured using 5 different indices: 1) the usual provider of care index, visits by the usual clinician/total visits, 2) continuity for patient, the average proportion of visits that an individual patient was seen by his or her own physician, 3) continuity for physician (PHY), the average proportion of visits that an individual physician saw his or her own patients, 4) Continuity of Care Index (COC), and 5) the Modified, Modified Continuity Index. During the period examined, pediatric residents were present in the continuity practice for 1 half-day each week. The resident continuity practice (RCP) had 57 residents and saw 3386 patients for 18 955 visits. Private practice 1 (PP1) had 4 pediatricians who saw 4968 patients for 33 537 visits. Private practice 2 (PP2) had 5 pediatricians who saw 11 953 patients for 75 778 visits. RESULTS: For all visit types, continuity in the RCP was not as high as in the private practices, PHY-RCP versus PP1, PP2; 53% versus 70%, 77%. However, continuity in RCP was greater than 50% for all measures except the COC index, which precipitously decreases as the number of clinicians seen increases. Examining continuity for health maintenance visits (PHY-RCP, PP2 vs PP1; 96%, 96% vs 82%) RCP was equal to the best of the private practices. The percentage of patients not seen for a health maintenance visit during the study period was lowest in the resident practice (RCP/PP1/PP2, 15/22/30). CONCLUSIONS: Although continuity for all visits in this RCP was less than in private practice, it was surprisingly high, considering the limited time residents spend in clinic. In a particularly important area for continuity, health maintenance visits, continuity was identical to one and superior to the other private practice.

Continuity of Patient Care↗

Mapping dispersed repetitive loci using semi-specific PCR cloning and somatic cell hybrid mapping.

A simple and effective method based upon semi-specific PCR followed by cloning has been developed. Chromosomal mapping of the generated fragment on a somatic cell hybrid panel identifies the chromosomal position, and yields a unique sequence tag for the site. Using this method, the chromosomal location of one porcine endogenous retrovirus (PERV) was determined. The porcine genomic sequences were first amplified by PCR using a PERV-specific primer and a porcine short interspersed nuclear element (SINE)-specific primer. PCR products were cloned, and those sequences that contained PERV plus flanking regions were selected using a second round of PCR and cloning. Sequences flanking the PERV were determined and a PERV-B was physically mapped on porcine chromosome 17 using a somatic hybrid panel. The general utility of the method was subsequently demonstrated by locating PERVs in the genome of PERV infected human 293 cells. This method obviates the need for individual library construction or linker/adaptor ligation, and can be used to quickly locate individual sites of moderately repeated, dispersed DNA sequences in any genome.

Animals↗

SMARCAD1, a novel human helicase family-defining member associated with genetic instability: cloning, expression, and mapping to 4q22-q23, a band rich in breakpoints and deletion mutants involved in several human diseases.

Members of the DEAD/H box-containing helicase superfamily include proteins essential to genome replication, repair, and expression. We report here the cloning and initial characterization of a novel human member of this protein family, designated hHel1 (human helicase 1), now designated SMARCAD1 by HUGO. This DEAD/H box-containing molecule has seven highly conserved sequence regions that allow us to place it in the SNF2 family of the helicase superfamily. Uniquely, though, hHel1 contains two DEAD/H box motifs, a property not reported to be shared by any other SNF2 family members. This defines a new subfamily consisting of hHel1 and its homologues. In addition to these DEAD/H box/ATP-binding motifs, hHel1 has a putative nuclear localization signal and several regions that may mediate protein-protein interactions. Expression analysis indicates that hHel1 transcripts are ubiquitous, with particularly high levels in endocrine tissue. We have mapped the gene for hHel1 to human chromosome 4q22-q23; this region is rich in breakpoints and deletion mutants of genes involved in several human diseases, notably soft tissue leiomyosarcoma, hepatocellular carcinoma, and hematologic malignancies. Our observation that human Hel1 gene overexpression is present in an E1A-expressing cell line with increased capacity for gene reactivation events by genomic rearrangement suggests that human Hel1 may play a role in genetic instability development.

Adenovirus E1A Proteins↗

Duplicated downstream enhancers control expression of the human apolipoprotein E gene in macrophages and adipose tissue.

Two distal enhancers that specify apolipoprotein (apo) E gene expression in isolated macrophages and adipose tissue were identified in transgenic mice that were generated with constructs of the human apoE/C-I/C-I'/C-IV/C-II gene cluster. One of these enhancers, multienhancer 1, consists of a 620-nucleotide sequence located 3.3 kilobases (kb) downstream of the apoE gene. The second enhancer, multienhancer 2, is a 619-nucleotide sequence located 15.9 kb downstream of the apoE gene and 5.9 kb downstream of the apoC-I gene. The two enhancers are 95% identical in sequence, and they are likely to have arisen as a consequence of the gene duplication event that yielded the apoC-I gene and the apoC-I' pseudogene. Both enhancer sequences appear to have equivalent activity in directing apoE gene expression in peritoneal macrophages and in adipocytes, suggesting that their activity in specific cell types may be determined by common regulatory elements.

Adipose Tissue↗

The bovine alpha-glucosidase gene: coding region, genomic structure, and mutations that cause bovine generalized glycogenosis.

We report here cDNA and genomic sequence of the bovine acidic alpha-glucosidase gene, from the initiation codon to the most 3' polyadenylation signal. The 2814-bp coding sequence predicts a 937-amino acid protein, which is highly conserved compared with the human alpha-glucosidase gene (86% and 83% identity respectively). The intron/exon boundaries are also conserved between the two species. Two mutations have been identified in Brahmans, and one in Shorthorns, that lead to generalized glycogenosis. All three mutations result in premature termination of translation. Evidence is also presented for a missense mutation segregating with the Brahman population, which is responsible for a 70-80% reduction in alpha-glucosidase activity.

Amino Acid Substitution↗

Prevalence of 21-hydroxylase-deficient nonclassic adrenal hyperplasia and insulin resistance among hirsute women from Puerto Rico.

OBJECTIVE: To determine the prevalence of 21-hydroxylase (21-OH)-deficient nonclassic adrenal hyperplasia (NCAH) and insulin resistance in hirsute women from Puerto Rico. DESIGN: Cross-sectional prospective study. SETTING: Clinical research center. PATIENT(S): 100 consecutive untreated hirsute women. MAIN OUTCOME MEASURE(S): Fasting total T, free T, DHEAS, insulin, and glucose were measured, and a 60-minute acute ACTH-(1-24) stimulation for 17-hydroxyprogesterone (17-HP) was performed. A diagnosis of 21-OH-deficient NCAH was considered when the stimulated 17-HP level was >30.3 nmol/L. The glucose/insulin ratio was calculated as a measure of insulin resistance (normal value, > or =4.5). RESULT(S): Patients had a mean (+/-SD) age of 26.8+/-6.6 years; 82 were oligomenorrheic. Overall, 12%, 8%, and 60% of patients had elevated levels of DHEAS, total T, or free T, respectively. One patient was identified as having 21-OH-deficient NCAH. Eight women, none of whom had NCAH, were found to be hyperglycemic; four of these women had type 2 diabetes mellitus. Excluding hyperglycemic patients, a glucose/insulin ratio of <4.5, consistent with IR, was found in 51.7%. CONCLUSION(S): The prevalence of 21-OH-deficient NCAH among patients from Puerto Rico does not differ significantly from that reported for other non-Jewish, non-Hispanic white populations.

Adrenal Hyperplasia, Congenital↗

Analysis of diversity and genetic relationships between four Chinese indigenous pig breeds and one Australian commercial pig breed.

The genetic diversities and relationships of four Chinese indigenous pig breeds and one Australian commercial pig breed have been evaluated using 27 microsatellites recommended by the International Society of Animal Genetics (ISAG) and the Food and Agriculture Organization (FAO). The allele frequencies, effective numbers of alleles and the polymorphic information content have been calculated. Nei's standard genetic distances have been used to construct a UPGMA dendrogram, which has been evaluated by the Bootstrap test. The utility of microsatellites for evaluating genetic diversity of pigs is discussed.

Alleles↗