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Biomedical subjects

M Hogan

Publications and source records attributed to M Hogan.

At least 37 records · Page 2Linked to original sources

Evidence from cultured rat cortical neurons of differences in the mechanism of ischemic preconditioning of brain and heart.

Ca2+ influx and activation of protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) during nonlethal ischemic preconditioning have been implicated in the protection of the heart against subsequent lethal ischemic injury. Thus, we determined if Ca2+ influx, PKC and MAPK also mediate ischemic preconditioning-induced protection in neurons. Preconditioning by exposure of E18 rat cortical cultures to 90 min of nonlethal oxygen-glucose deprivation (OGD) 24 h prior to 180-240 min of lethal OGD was neuroprotective. Exposure to nominally free Ca2+, or blockade of the alpha-amino-hydroxy-5-methyl-isoxazolepropionate (AMPA) receptor with CNQX did not eliminate protection. MAPK activity did not change and PKC activity decreased by 50% relative to normal baseline levels at 0 and 24 h following preconditioning. The sustained decrease in PKC activity was not due to a loss of enzyme as determined from immunoblots using pan and epsilon-, beta- and zeta-specific PKC antibodies. Neuroprotection was maintained with pharmacological inhibition of PKC activity by staurosporine, chelerythrine and calphostin C and MAPK activity by PD 98059 during preconditioning, indicating that activation of these enzymes during preconditioning was not necessary for protection. Therefore, in contrast to cardiac tissue, ischemic preconditioning of neurons does not require activation of PKC and MAP kinase, and protection is maintained with substantial removal of extracellular Ca2+ or blockade of the AMPA receptor.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Abnormal prenatal sonographic findings in the posterior cranial fossa: a case of Joubert's syndrome.

Joubert's syndrome is a well-documented but rare disorder characterized by a variable combination of central nervous system, respiratory, renal and eye anomalies. The most significant and constant neuropathological finding is partial or complete agenesis of the cerebellar vermis. The syndrome was first described by Joubert and colleagues as a familial agenesis of the cerebellar vermis and appears to be inherited as an autosomal recessive trait. A case of Joubert's syndrome is described in which second-trimester ultrasonography demonstrated abnormal findings in the fetal posterior fossa with associated renal abnormalities. However, postnatal sonography of the posterior fossa could not confirm the prenatal findings, and the diagnosis of Joubert's syndrome was only later established by computed tomography of the neonatal brain in the knowledge of the characteristic clinical picture.

Abnormalities, Multiple↗

Strategic planning. Implementing a foundation.

An interdisciplinary continuum-of-care process achieves a unit's mission and enhances team excellence. Quality of patient care improves, costs decrease, staff satisfaction and morale increase, and a sense of team integration emerges. Strategic planning is an effective tool to actualize this process.

Continuity of Patient Care↗

Detection of DNA gains and losses in primary endometrial carcinomas by comparative genomic hybridization.

Comparative genomic hybridization (CGH) was used in a retrospective analysis of chromosomal imbalances in frozen primary tumor specimens from 14 endometrial carcinoma patients. Chromosome changes were detected in nine cases (64%), and tumor stage and grade tended to parallel the degree of genomic imbalances. Gain of the entire long arm of chromosome 1 was observed in six cases (43%), three of which displayed only this chromosome change. Other common sites of copy number increases included 8q21-->qter (4 cases), 10p15 (4 cases), 10q11-->q24 (3 cases), and 13q21-->qter (3 cases, each with stage III disease). Two of the tumors with gains of chromosome 10 involved the whole chromosome, and this was the sole abnormality in one case. DNA amplification at 5p14-->p15 was identified in one specimen, a stage III tumor having numerous imbalances. DNA microsatellite analysis revealed multiple replication errors (RER), indicative of the RER+ phenotype, in four of 13 (31%) cases evaluated. The RER+ phenotype was observed in four of six stage la tumors but in none of seven stage Ib or stage III tumors. Multiple genomic imbalances detected by CGH were not observed in RER+ tumors but were detected in five of nine tumors without the RER+ phenotype. These investigations demonstrate the feasibility of CGH for the retrospective assessment of chromosomal changes in endometrial carcinoma specimens. Moreover, these data suggest that the etiologies in tumors with and without the RER+ phenotype may differ.

Aged↗

Adolescent sexual aggression: risk and protective factors.

OBJECTIVE: Little research addresses the correlates of sexual aggression in nonclinical populations of adolescents. The purpose of this study was to identify risk and protective factors associated with sexual violence among male and female adolescents. METHODS: We analyzed data on 71,594 students in the 9th and 12th grades responding to the 1992 Minnesota Student Survey, an anonymous, self-report survey examining an array of risk environments, health-compromising behaviors, and protective factors. The responses of students reporting a history of forcing someone into a sexual act were compared with those who reported that they had never forced someone into a sexual act. Separate analyses were conducted for males and females. RESULTS: A history of sexual violence perpetration was reported by 4.8% of male and 1.3% of female adolescents. Using a logistic regression model, sexual aggression was associated with experiencing intrafamilial or extrafamilial sexual abuse, witnessing family violence, frequent use of illegal drugs, anabolic steroid use, daily alcohol use, gang membership, high levels of suicide risk behavior, and excessive time spent "hanging out." Emotional health and connectedness with friends and adults in the community were protective factors for male adolescents against sexually aggressive behavior, and academic achievement was a protective factor for female adolescents. CONCLUSIONS: A history of forcing someone into a sexual act was associated with several risk and protective factors. Efforts to prevent adolescent sexual violence should target individuals at increased risk. Through their psychosocial assessment of young people, health care professionals can play a role in identifying, counseling, and making appropriate referrals for adolescents at risk for sexually aggressive behavior.

Adolescent↗

Regulation of phosphatidylcholine synthesis in maturing type II cells: increased mRNA stability of CTP:phosphocholine cytidylyltransferase.

Pulmonary surfactant phosphatidylcholine synthesis increases in fetal lung type II cells with advancing gestation. This increase is accompanied by an increase in gene and protein expression of CTP:phosphocholine cytidylyltransferase (CT; EC 2.7.7.15), which catalyses a regulatory step in de novo phosphatidylcholine synthesis by fetal type II cells. In the present study we investigated the role of transcriptional and post-transcriptional mechanisms in the developmental induction of CT mRNA in maturing type II cells. We found that CT mRNA increased 2-fold from days 18 to 21 of fetal rat gestation (term 22 d). This increase in CT mRNA was not accompanied by a developmental increase in CT gene transcription. However, CT mRNA was more stable on day 21 (t1/2 48 h) compared with that on day 18 (t1/2 17 h). Glucocorticoids have been shown to enhance surfactant phosphatidylcholine synthesis in fetal type II cells. Therefore we also examined the effect of maternal glucocorticoid administration to pregnant rats at 19 d of gestation on CT mRNA expression in fetal type II cells isolated 24 h later. Glucocorticoid treatment did not increase type II cell CT mRNA. As reported previously, however, glucocorticoids increased CT activity in the microsomal membrane fraction of fetal type II cells, whereas no differences in cytosolic CT activity were observed. We conclude that the developmental increase in CT mRNA in fetal type II cells is due to a decreased breakdown of the CT transcript and that glucocorticoids regulate fetal type II cell CT activity at a post-translational level.

Animals↗

Multipolypoid intussusceptum: a distinctive appearance of ileoileocolic intussusception at the ileocecal valve.

Objective. To determine whether ileoileocolic intussusception can be diagnosed by a distinctive appearance during pneumatic reduction. Materials and methods. We reviewed the clinical, pathologic, and imaging findings of 11 patients with ileoileocolic intussusceptions seen in our hospital between January 1989 and July 1994. The patients ranged in age from 4 months to 4 years and 2 months. We specifically evaluated the appearance of these intussusceptions on air enemas performed in nine of these patients. Another 22 air enemas of all patients with surgically proven ileocolic intussusception seen during the same time period were also reviewed for comparison. Results. In seven of the nine patients with ileoileocolic intussusception who had air enemas, the intussusceptum clearly had two or more separate polypoid components once it was reduced to the cecum. This distinctive appearance was not seen until the intussusceptum was tethered at the ileocecal valve. The intussusceptum was also reduced to the cecum in 19 patients from the control group with ileocolic intussusception. In contrast to the ileoileocolic intussusceptums, these intussusceptums were either smoothly marginated (16 patients) or slightly lobular (three patients). Conclusion. In most patients with ileoileocolic intussusception, the intussusceptum has two or more polypoid components at the level of the ileocecal valve which are easily distinguished from the smoothly marginated or slightly lobular intussusceptum seen with ileocolic intussusception.

Air↗

The clinical effects of intensive, specific exercise on chronic low back pain: a controlled study of 895 consecutive patients with 1-year follow up.

Eight hundred ninety-five consecutive chronic low back pain patients were evaluated. Six hundred twenty-seven completed the program. One hundred sixty-one began, but dropped out, and 107 were recommended for treatment but did not undergo treatment for various reasons. Average duration of symptoms prior to evaluation was 26 months. Forty-seven percent of patients were workers' compensation patients. The primary treatment was intensive, specific exercise using firm pelvic stabilization to isolate and rehabilitate the lumbar spine musculature. Patients were encouraged to work hard to achieve specific goals. Seventy-six percent of patients completing the program had excellent or good results. At 1-year follow up 94% of patients with good or excellent results reported maintaining their improvement. Results in the control group were significantly poorer in all areas surveyed except employment.

Adolescent↗

Access to physicians.

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Appointments and Schedules↗

T.C.G triplet in an antiparallel purine.purine.pyrimidine DNA triplex. Conformational studies by NMR.

The antiparallel purine.purine.pyrimidine DNA triplex, RRY6, which contains a T.C.G inverted triplet in the center of the sequence, was examined by proton and phosphorous two-dimensional NMR spectroscopy. The local conformation of the T.C.G triplet (T4.C11.G18) and the effect of this triplet on the global helical structure were analyzed in detail. The formation of the T.C.G triplet is confirmed by a set of cross-strand NOEs, including unusual cross-strand NOEs between the third strand and the pyrimidine strand as opposed to the purine strand of the duplex. NMR data suggest that the T.C.G triplet may be present in an equilibrium between a non-hydrogen-bonded form and a T(O4)-C(NH2) hydrogen-bonded form and that there is a distortion of the in-plane alignment of the three bases. The flanking G.G.C base triplets are well-defined on the 5'-side of T4, but somewhat interrupted on the 3'-side of T4. The effect of the third strand binding on the Watson-Crick duplex was probed by an NMR study of the free duplex RY6. NMR parameters are affected mostly around the T.C.G inversion site. The perturbations extend to at least two adjacent base triplets on either side. The binding of the third purine strand and the accommodation of a central T.C.G inversion in RRY6 does not require a readjustment in sugar pucker, which remains in the range of C2'-endo. 31P resonances of RRY6 distribute over a range of 2.2 ppm. The H-P coupling patterns of the third strand differ from those of the duplex. General spectral patterns defined by the marker protons of the RRY and YRY triplexes are compared.

Base Sequence↗

Differential expression of the small inducible cytokines GRO alpha and GRO beta by synovial fibroblasts in chronic arthritis: possible role in growth regulation.

Synovial pannus represents a hypertrophic and locally invasive connective tissue response to chronic inflammation that accounts in large part for the periarticular destruction of rheumatoid arthritis. Synovial fibroblasts cultured from rheumatoid synovia have been found to display an increased rate of proliferation and the constitutive expression of collagenases, growth factors, and inflammatory cytokines. The existence in rheumatoid synovium of both a pro-inflammatory state and growth dysregulation led us to investigate the expression by synovial fibroblasts of the closely homologous cytokines GRO alpha (gro/MGSA), GRO beta (MIP-2 alpha), and GRO gamma (MIP-2 beta). These cytokines are released by a variety of cell types and display overlapping growth regulatory and pro-inflammatory activities. In contrast to expectations, the majority of synovial fibroblast cell lines derived from osteoarthritic or non-inflammatory synovia showed a relative increase in the constitutive expression of GRO alpha and GRO beta when compared to synovial fibroblasts obtained from rheumatoid synovia. Considered together with evidence that GRO alpha is a growth regulator that modulates the expression of metalloproteinase activity, these findings provide evidence for a differential pathway of cytokine activation that may downregulate the proliferative and erosive response to chronic arthritis.

Actins↗

Increased expression of CTP:phosphocholine cytidylyltransferase in maturing type II cells.

We previously reported that phosphatidylcholine synthesis increased in fetal rat lung type II cells with advancing gestation. This increase was accompanied by an increase in CTP:phosphocholine cytidylyltransferase activity, which catalyses a rate regulatory step in de novo phosphatidylcholine synthesis by fetal type II cells. To determine whether this increase in cytidylyltransferase activity is due to an increase in cytidylyltransferase protein levels, the gene and protein expression of cytidylyltransferase was investigated in maturing type II cells. The cytidylyltransferase cDNA was cloned from fetal rat type II cells and showed 99% sequence homology with rat liver cDNA. The cDNA detected two mRNA transcripts (1.8 and 7.5 kb) in fetal rat lung. By reverse-transcriptase polymerase chain reaction (RT-PCR) analysis, cytidyltransferase mRNA content increased three-fold in fetal type II cells with advancing gestation, whereas cytidylyltransferase mRNA levels in fibroblasts remained constant. An antibody against rat liver cytidylyltransferase was used to assess cytidylyltransferase protein. Western blotting revealed that cytidylyltransferase protein content increased threefold in the microsomal fraction of type II cells with advancing gestation. The enzyme protein levels in the cytosolic fraction did not significantly change with development. Enzyme activity studies confirmed these latter observations. We conclude that the increase in surfactant phosphatidylcholine synthesis by type II cells at late fetal gestation is due in part to an increase in the amount of cytidylyltransferase protein.

Animals↗

A microchip for quantitative detection of molecules utilizing luminescent and radioisotope reporter groups.

Through the marriage of microelectronics and molecular biology, a miniaturized device is presented for ultrasensitive detection of labeled molecules. The novelty of the approach is the direct integration of a charge-coupled device (CCD) and a probe-based assay. Specifically, a CCD detector serves as an active solid support that quantitatively detects and images the distribution of labeled target molecules near the spatially addressable pixels. The device exploits the inherent characteristics of microelectronics that accommodate highly parallel assays, ultrasensitive detection, high throughput, integrated data acquisition and computation. Hence, the technology presented offers substantial practical utility to both research and clinical diagnostic applications that require quantitative analysis of bound molecules. Specifically for probe-based assays such as reverse dot blots, hybridization of radiolabeled or fluorescently labeled, target DNA can be quantitatively assessed within seconds due to the high sensitivity and direct coupling employed.

DNA Probes↗