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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

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↗

Circulating fibrocytes define a new leukocyte subpopulation that mediates tissue repair.

BACKGROUND: The host response to tissue injury requires a complex interplay of diverse cellular, humoral, and connective tissue elements. Fibroblasts participate in this process by proliferating within injured sites and contributing to scar formation and the longterm remodeling of damaged tissue. Fibroblasts present in areas of tissue injury generally have been regarded to arise by recruitment from surrounding connective tissue; however this may not be the only source of these cells. MATERIALS AND METHODS: Long-term culture of adherent, human, and murine leukocyte subpopulations was combined with a variety of immunofluorescence and functional analyses to identify a blood-borne cell type with fibroblast-like properties. RESULTS: We describe for the first time a population of circulating cells with fibroblast properties that specifically enter sites of tissue injury. This novel cell type, termed a "fibrocyte," was characterized by its distinctive phenotype (collagen+/vimentin+/CD34+), by its rapid entry from blood into subcutaneously implanted wound chambers, and by its presence in connective tissue scars. CONCLUSIONS: Blood-borne fibrocytes contribute to scar formation and may play an important role both in normal wound repair and in pathological fibrotic responses.

Animals↗

Volumetric analysis of small bowel displacement from radiation portals with the use of a pelvic tissue expander.

PURPOSE: Many techniques and devices have been used in an attempt to minimize gastrointestinal morbidity of pelvic irradiation. The value of a temporary intrapelvic tissue expander to displace small bowel from pelvic radiotherapy fields was analyzed by comparing volumetric treatment parameters of patients with and without such a device. METHODS AND MATERIALS: Between 1983 and 1991, 77 patients with a diagnosis of endometrial (n = 35), colorectal (n = 41), or anal carcinoma (n = 1) received adjuvant postoperative radiotherapy after undergoing treatment planning simulation with the use of small bowel oral contrast medium. Fourteen of these patients underwent surgical placement of a temporary intrapelvic tissue expander prior to radiotherapy, and 63 patients did not. Small bowel volume within the treatment portals was measured for both initial pelvic and conedown fields for all cases, and compared between the two patient groups. RESULTS: The volume of small bowel within the initial pelvic fields receiving full dose irradiation was significantly less among patients with a tissue expander. For patients with a tissue expander, mean volume receiving full dose irradiation was 25 cm3 (median 0 cm3, range 0-297 cm3), whereas the corresponding volume was 239 cm3 (median 181 cm3, range 0-943 cm3) without a tissue expander (p < .0001). A similar reduction of irradiated small bowel volume was noted in the conedown fields with the use of a tissue expander (p = .07). Volumes receiving less than full dose irradiation were also less within the initial pelvic (p = .0001) and conedown (p = .002) fields with a tissue expander. Multivariate analysis of patient and treatment-related parameters showed the use of a tissue expander to be the only factor correlated with decreased small bowel volume within the treatment field (p = .003). Morbidity related to placement and removal of the tissue expander was acceptable. Acute radiation-related morbidity was significantly less in patients irradiated with a tissue expander in place (p < .001). CONCLUSIONS: Placement of an intrapelvic tissue expander was correlated with decreased small bowel volume within the radiotherapy treatment field. Diminished radiation-induced acute gastrointestinal morbidity was noted with use of a tissue expander.

Aged↗

Intraperitoneal cisplatin and etoposide in peritoneal mesothelioma: favorable outcome with a multimodality approach.

Ten patients with histologically documented peritoneal mesothelioma were treated with intraperitoneal cisplatin 200 mg/m2, sodium thiosulfate rescue and etoposide 65-290 mg/m2 every 4 weeks for a maximum of six cycles. All had epithelial or mixed epithelial-fibrous histology. Toxicity was tolerable, with 50% sustaining grade 3 or 4 granulocytopenia. There was one episode of neutropenic fever. Grade 2 peripheral neuropathy occurred in one patient, grade 1 in five patients. Complete remission occurred in one of five patients with measurable disease. Median survival for patients whose tumors were surgically debulked to < 2 cm residua prior to treatment was 22 months, while it was 5 months for those with measurable, surgically inaccessible disease (P = 0.0731 by Cox regression proportional hazard model). These data suggest that patients who present with resectable disease may benefit from an aggressive adjuvant approach. This possibility warrants prospective testing in a randomized clinical trial.

Adult↗

Regulation of phosphatidylcholine synthesis in fetal type II cells by CTP:phosphocholine cytidylyltransferase.

Phosphatidylcholine synthesis increases in fetal rat type II cells during late gestation, as demonstrated by an increased incorporation of radiolabeled palmitate, glycerol, acetate, and choline into phosphatidylcholine. However, the percentage of phosphatidylcholine present in the saturated form remains essentially constant. The developmental profile of the enzymes of the CDP-choline pathway suggests that CTP:choline-phosphate cytidylyltransferase catalyses a rate regulatory step in de novo phosphatidylcholine synthesis by fetal type II cells. When cytidylyltransferase activity is assayed in different subcellular fractions, the greatest increase, as a function of development, is found in microsomes. This developmental increase is accompanied by a shift in subcellular distribution of cytidylyltransferase activity from cytosol to microsomes in fetal type II cells during late gestation. This shift is evident even when cytidylyltransferase activity is assayed in the presence of 0.5 mM phosphatidylcholine/oleic acid (1/1 molar ratio) vesicles. We speculate that either a subcellular translocation of CTP:phosphocholine cytidylyltransferase from cytosol to microsomes or an increase in cytidylyltransferase gene expression are responsible for the developmental increase of de novo phosphatidylcholine synthesis by fetal type II cells.

Animals↗

Advanced glycosylation endproducts block the antiproliferative effect of nitric oxide. Role in the vascular and renal complications of diabetes mellitus.

Advanced glycosylation endproducts (AGEs) accumulate on long-lived tissue proteins such as basement membrane collagen and have been implicated in many of the long-term complications of diabetes mellitus. These products originate from glucose-derived Schiff base and Amadori products but undergo a series of complex rearrangement reactions to form ultimately protein-bound, fluorescent heterocycles. AGEs can react with and chemically inactivate nitric oxide (NO), a potent endothelial cell-derived vasodilator and antiproliferative factor. Since mesenchymal cell proliferation is an early and characteristic lesion of diabetic vasculopathy and glomerulopathy, we investigated the possibility that collagen-bound AGEs functionally inactivate the antiproliferative effect of NO. In model cell culture systems, AGEs were found to block the cytostatic effect of NO on aortic smooth muscle and renal mesangial cells. The inactivation of endothelial cell-derived NO by basement membrane AGEs may represent a common pathway in the development of the accelerated vascular and renal disease that accompany long-term diabetes mellitus.

Animals↗