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Biomedical subjects

J M Rowland

Publications and source records attributed to J M Rowland.

At least 19 recordsLinked to original sources

Syntheses, structures, and reactivity of low spin iron(III) complexes containing a single carboxamido nitrogen in a [FeN5L] chromophore.

A new pentacoordinate ligand based on TPA (tris-(2-pyridylmethyl)amine), namely, N,N-bis(2-pyridylmethyl)amine-N-ethyl-2-pyridine-2-carboxamide (PaPy(3)H), has been synthesized. The iron(III) complexes of this ligand, namely, [Fe(PaPy(3))(CH(3)CN)](ClO(4))(2) (1), [Fe(PaPy(3))(Cl)]ClO(4) (2), [Fe(PaPy(3))(CN)]ClO(4) (3), and [Fe(PaPy(3))(N(3))]ClO(4) (4), have been isolated and complexes 1-3 have been structurally characterized. These complexes are the first examples of monomeric iron(III) complexes with one carboxamido nitrogen in the first coordination sphere. All four complexes are low spin and exhibit rhombic EPR signals around g = 2. The solvent bound species [Fe(PaPy(3))(CH(3)CN)](ClO(4))(2) reacts with H(2)O(2) in acetonitrile at low temperature to afford [Fe(PaPy(3))(OOH)](+) (g = 2.24, 2.14, 1.96). When cyclohexene is allowed to react with 1/H(2)O(2) at room temperature, a significant amount of cyclohexene oxide is produced along with the allylic oxidation products. Analysis of the oxidation products indicates that the allylic oxidation products arise from a radical-driven autoxidation process while the epoxidation is carried out by a distinctly different oxidant. No epoxidation of cyclohexene is observed with 1/TBHP.

Amides↗

Rhabdomyomatous mesenchymal hamartoma of the eyelid: report of a case and literature review.

PURPOSE: To report a rare case of rhabdomyomatous mesenchymal hamartoma and to compare its features with those cases previously reported. DESIGN: Interventional case report and literature review. INTERVENTION: Complete ophthalmologic and systemic examinations followed by excisional biopsy and histopathologic examination. MAIN OUTCOME MEASURES: Clinical examination features and histopathologic findings. RESULTS: A 6-month-old Latino male presented with a congenital, elevated, smooth, flesh-colored right lower eyelid lesion. An ipsilateral right limbal dermoid and an upper eyelid coloboma were also present. Excisional biopsy of the eyelid lesion revealed randomly oriented mature striated muscle tissue with associated adipose tissue, blood vessels, pilosebaceous units, and peripheral nerves, findings consistent with rhabdomyomatous mesenchymal hamartoma. Of the 24 reported cases (including the current case), eight had associated congenital anomalies. CONCLUSIONS: Although rhabdomyomatous mesenchymal hamartomas are rare and benign, they may be associated with other congenital anomalies and anomaly syndromes. As a result, we recommend systemic evaluation of patients diagnosed with this entity.

Biopsy↗

Monomeric and dimeric copper(II) complexes of a novel tripodal peptide ligand: structures stabilized via hydrogen bonding or ligand sharing.

The novel tripodal ligand N-(bis(2-pyridyl)methyl)-2-pyridinecarboxamide (Py3AH) affords monomeric and dimeric copper(II) complexes with coordinated carboxamido nitrogens. Although many chloro-bridged dimeric copper(II) complexes are known, [Cu(Py3A)(Cl)] (1) remains monomeric and planar with a pendant pyridine and does not form either a chloro-bridged dimer or the ligand-shared dimeric complex [Cu(Py3A)(Cl)]2 (4) in solvents such as CH3CN. When 1 is dissolved in alcohols, square pyramidal alcohol adducts [Cu(Py3A)(Cl)(CH3OH)] (2) and [Cu(Py3A)(Cl)(C2H5OH)] (3) are readily formed. In 2 and 3, the ROH molecules are bound at axial site of copper(II) and the weak axial binding of the ROH molecule is strengthened by intramolecular hydrogen bonding between ROH and the pendant pyridine nitrogen. Two ligand-shared dimeric species [Cu(Py3A)(Cl)]2 (4) and [Cu(Py3A)]2(ClO4)2 (5) have also been synthesized in which the pendant pyridine of one [Cu(Py3A)] unit completes the coordination sphere of the other [Cu(Py3A)] neighbor. These ligand-shared dimers are obtained in aqueous solutions or in complete absence of chloride in the reaction mixtures.

Copper↗

Comparison of outcomes between living donor and cadaveric lung transplantation in children.

BACKGROUND: Long-term survival in lung transplant is limited by bronchiolitis obliterans (BOS). We compared outcomes in pediatric living donor bilateral lobar (LL) vs cadaveric lung transplant (CL). METHODS: Children were studied who had LL or CL with at least 1 year follow-up. Data collected included acute rejection episodes, pulmonary function tests (PFT), BOS, and survival. Mean age was 13.36+/-3.16 years in LL and 12.00+/-4.19 years in CL patients (p = 0.37, ns). RESULTS: There was no difference in rejection (p = 0.41, ns). CL had rejection earlier (2.48+/-3.84 months) than LL (13.60+/-10.74 months; p = 0.02). There was no difference in 12 month PFT. But at 24 months, LL had greater forced expiratory volume in 1 second (FEV1) (p = 0.001) and FEF25-71% (p = 0.01) than CL. BOS was found in 0/14 LL vs 9/11 (82%) CL after 1 year (p = 0.04). After 2 years, 0/8 LL and 6/7 (86%) CL had BOS (p < 0.05). LL had 85% survival vs 79% for CL at 12 months. At 24 months, LL survival was 77% vs 67% for CL. CONCLUSIONS: Pediatric LL had less BOS and better pulmonary function than CL. As BOS is a determinant of long-term outcome, we believe LL is the preferred lung transplant method for children.

Adolescent↗

Documentation of EWS gene rearrangements by fluorescence in-situ hybridization (FISH) in frozen sections of Ewing's sarcoma-peripheral primitive neuroectodermal tumor.

Prompt and accurate diagnosis of small round cell tumors warrants ancillary studies. Recently, two-color fluorescence in-situ hybridization (FISH) using probes for specific gene rearrangements has gained wide acceptance. EWS gene rearrangements, present in essentially 100% of Ewing's Sarcoma/peripheral primitive neuroectodermal tumor, were evaluated by FISH on frozen sections (FS) of tumor biopsies from 10 patients, plus a negative control, and in seven other malignant neoplasms of childhood. 4mu FS were hybridized overnight, using a single EWS gene-specific probe spanning the EWS breakpoint. We identified EWS rearrangements in 8 of 10 cases (80%) of Ewing's Sarcoma/pPNET. There are no known false positives in diploid or near-diploid tumors, or in any of the non-EWS tumors tested; the uncommon false negative can be confirmed by RT-PCR. Hyperdiploid cases with multiple copies of chromosome 22 may be better evaluated by two-color FISH. This is the first use on FS biopsy material of a single probe for EWS, capable of detecting all known EWS rearrangements, in ES and other tumors. Utilization of this ancillary technique on FS for ES/pPNET and other tumors with distinctive chromosomal translocation is highly specific, reliable, expeditious (24-36 hours) and cost-effective.

Chromosomes, Human, Pair 11↗

Gastric duplication-colonic fistula with colonic ulceration and bleeding.

An 11-month-old girl had massive rectal bleeding. A midabdominal mass was palpated. Ultrasound scan showed a large cystic mass with diffusely echogenic contents; Tc-99M radionuclide scan confirmed a duplication. Exploratory surgery and pathology examination showed a gastric duplication with formation of a fistula into the transverse colon with a colonic ulcer and hemorrhage. This combination of findings is presented as a rare cause of lower gastrointestinal hemorrhage in infancy.

Colonic Diseases↗

Systemic mast cell disease associated with primary ovarian mixed malignant germ cell tumor.

A 12-year-old girl with a mixed malignant germ cell tumor of the ovary, treated by surgery and chemotherapy, developed systemic mast cell disease (SMCD) approximately 3 months after chemotherapy. Hematologic malignancies have previously been noted in patients with mediastinal germ cell tumors but this is the first report of a primary ovarian germ cell neoplasm associated with SMCD.

Child↗

Living donor lobar lung transplantation: the pediatric experience.

Living donor (LD) lobar lung transplantation is now an accepted alternative to cadaveric lung transplantation in selected patients with end-stage lung disease. This study reviews the Childrens Hospital Los Angeles LD experience of 17 patients (mean 13.2 +/- 2.7 yrs; range 9.3-18.5 yrs). 12 LD patients had end-stage cystic fibrosis, 4 had primary pulmonary hypertension, and 1 child had bronchiolitis obliterans. LD candidates must meet the same criteria as for cadaveric lung transplant candidates. Donor candidates are rigorously screened (physically and psychologically) prior to acceptance for lobectomy. LD patients receive the same triple immunosuppression regimen as our cadaveric recipients (prednisone, cyclosporine/FK506, and azathioprine/mycophenolate). Comparison of rejection episodes, incidence of bronchiolitis obliterans, pulmonary function tests, exercise stress tests, and cardiac catheterization data was made between LD and cadaveric lung transplantation (CL) pediatric recipients. Donor outcomes were also reviewed. In our pediatric program, the 1-year survival rate for LD recipients is currently 81%, which compares favorably with the ISHLT average of 70% for pediatric transplant patients. The incidence of rejection is about the same for LD and CL recipients, but the episodes are less severe for pediatric LD patients. There have been no histological cases of bronchiolitis obliterans syndrome in our LD recipients. Although there have been questions as to whether transplanted lobes can supply comparable pulmonary reserve to whole cadaveric lungs, the lung volumes (TLC and VC), expiratory flow rates, maximal exercise stress tests, and pulmonary artery pressures (no evidence of pulmonary hypertension) in LD patients are not significantly different to CL recipients in our institution. Besides pain from the thoracotomy, the donors have a decrease of 16% (right lower lobe donor) and 18% (left lower lobe donor) in their vital capacity. Otherwise, there have been no major complications to the donors and most have resumed their usual activities. Based on outcomes, pulmonary function tests, exercise stress tests, and hemodynamic studies as well as low donor morbidity, living donor double lobar lung transplantation is a viable alternative to cadaveric lung transplantation in selected pediatric patients with end-stage lung disease.

Adolescent↗

Increased submucosal nerve trunk caliber in aganglionosis: a "positive" and objective finding in suction biopsies and segmental resections in Hirschsprung's disease.

OBJECTIVE: To establish the diagnostic usefulness of submucosal hypertrophic nerve trunk morphology in Hirschsprung's disease as a quantifiable parameter supportive of aganglionosis on hematoxylin-eosin-stained sections. DESIGN: We retrospectively evaluated size and density of submucosal nerves on hematoxylin-eosin-stained sections and S100 protein-stained sections of resected segments from 13 patients with Hirschsprung's disease, and in sections of 20 aganglionic and 50 ganglionic rectal suction biopsies. SETTING: All patients were seen at Childrens Hospital Los Angeles (Calif), a tertiary-care pediatric center; the age of patients at diagnosis or resection ranged between 2 days and 3 years. RESULTS: Aganglionic segments contain many distinct nerve trunks greater than 40 microm in diameter. Ganglionic segments/biopsies showed no nerve trunk larger than this threshold value (P approximately .0000). Nerve trunks of such caliber are rarely encountered in pathologic transition zones and sites of colostomy. CONCLUSIONS: Submucosal nerve trunks that are 40 microm or greater in diameter strongly correlate with abnormal innervation/aganglionosis. Use of this objective parameter in evaluating suction biopsies should be helpful in the morphologic diagnosis of Hirschsprung's disease in infancy and early childhood.

Biopsy, Needle↗

Distinct pattern of ret oncogene rearrangements in morphological variants of radiation-induced and sporadic thyroid papillary carcinomas in children.

In this study, we compare the morphological and genetic characteristics of 38 post-Chernobyl thyroid papillary carcinomas from Belarussian children 5-18 years old with those of 23 sporadic papillary carcinomas from the same age children without history of radiation exposure from Los Angeles and Cincinnati. Among radiation-induced tumors, solid variant of papillary carcinoma was found in 37%, follicular in 29%, typical papillary in 18%, and mixed and diffuse sclerosing variants in 8% each. In the sporadic group, a typical papillary pattern was prevalent in 70%, follicular in 17%, diffuse sclerosing variant in 9%, and solid in 4%. In both groups, the prevalence of ret rearrangements was high, but the frequency of specific types of rearrangement was significantly different. Among radiation-induced tumors, ret/PTC3 was found in 58%, ret/PTC1 in 16%, and ret/PTC2 in 3%, whereas among sporadic tumors, ret/PTC1 was found in 47% (P < 0.05), and ret/PTC3 was found in 18% (P = 0.01). The morphological variants of papillary carcinoma showed different prevalence of the specific types of ret rearrangement. Seventy-nine % of solid variant tumors had ret/PTC3, whereas only 7% had ret/PTC1 (P = 0.0007). Among typical papillary tumors, ret/PTC1 was found in 38%, ret/PTC3 in 19%, and ret/PTC2 in 5%. Thus, ret rearrangements are highly prevalent in pediatric papillary carcinomas from children exposed to radiation and in those occurring sporadically. However, the types of ret/PTC vary between these two populations, with ret/PTC3 present more commonly in post-Chernobyl tumors. Furthermore, solid variants have a high prevalence of ret/PTC3, whereas typical papillary carcinomas do not, suggesting that the different types of ret rearrangement confer neoplastic thyroid cells with distinct phenotypic properties.

Adolescent↗

Antibody to capsular polysaccharides of Streptococcus pneumoniae: prevalence, persistence, and response to revaccination.

The prevalence of immunity to Streptococcus pneumoniae in the adult population of the United States is unknown. In the study described herein, military recruits had anticapsular IgG antibody to only 15% of common pneumococcal serotypes, whereas working men and elderly men had IgG antibody to 33% and 34% of the common serotypes, respectively (P < .001). Among eight elderly subjects, the prevalence of IgG antibody to capsular polysaccharides increased from 30% to 78% after pneumococcal vaccination; 6 years thereafter, the rate of positive reactions had declined to 58% and IgG levels had declined substantially. With revaccination, IgG levels returned to within (+/-) 40% of the original postvaccination levels. IgM and IgG antibody appeared or began to increase in titer 6 days after vaccination; the rate and degree of response were the same after the first and second exposures. Since most individuals rapidly develop IgG antibody after colonization by S. pneumoniae and since IgG confers immunity, these data suggest that pneumonia is infrequent among healthy adults not because preexisting immunity is widespread but because--with colonization--an immune response develops rapidly, preceding specific events that might lead to infection. Our findings support recommended vaccination procedures and suggest that wider application in subsets of healthy younger adults should be considered.

Adolescent↗

Reverse transcriptase PCR amplification of EWS/FLI-1 fusion transcripts as a diagnostic test for peripheral primitive neuroectodermal tumors of childhood.

The peripheral primitive neuroectodermal tumors (pPNETs) of childhood, including Ewing's sarcoma, peripheral neuroepithelioma, and Askin's tumor, often present significant diagnostic challenges for the anatomic pathologist. One consistent feature of these tumors is the presence of the t(11;22)(q24;q12) in tumor cells, and this translocation has been useful as a marker for this group of tumors. The recent cloning of the t(11;22) breakpoint has revealed the fusion of the human FLI-1 gene on chromosome 11q24 with a gene of unknown function called EWS on 22q12, and fusion transcripts have been detected. These findings have raised the possibility of using molecular genetic analysis as a tool to diagnose pPNETs. To this end, we have tested pPNETs for the presence of EWS/FLI-1 fusion transcripts by reverse transcriptase-polymerase chain reaction (RT-PCR) using EWS and FLI-1 specific primers. Eight (80%) of 10 pPNET cell lines were positive for amplified products using this technique. These results were confirmed by Southern analysis, which revealed rearrangements of EWS using genomic EWS probes in all eight positive cell lines. We then tested 20 primary pPNET tumors, and identified fusion transcripts by RT-PCR in 18 (90%) of these cases. Cloning and sequencing of PCR products confirmed the presence of EWS and FLI-1 sequences in these products. Furthermore, fusion transcripts were not detected by this technique in a series of non-pPNET pediatric solid tumors. Detection of EWS/FLI-1 fusion transcripts by RT-PCR therefore provides a novel adjunctive tool in the diagnosis of pPNETs.

Adolescent↗

Prolonged course of illness in a child with malignant lymphoma mimicking sarcoidosis.

We describe a case of malignant lymphoma mimicking the rheumatic presentation of sarcoidosis in an adolescent with a 3-year history of febrile illness. Final diagnosis was established by tissue biopsy after multiple studies failed to provide histological evidence of granulomas consistent with sarcoidosis. We discuss the limited diagnostic specificity of serum angiotensin converting enzyme in sarcoidosis and emphasize the need for aggressive diagnostic evaluation of a patient whose clinical presentation is not fully explained by a known rheumatologic illness.

Adolescent↗

Age-related marrow changes in the pelvis: MR and anatomic findings.

Short repetition time magnetic resonance images of the pelvis in 70 subjects (aged 1 day to 24 years) without history of bone marrow disease were retrospectively analyzed for the distribution and appearance of red and yellow marrow. The signal intensity and degree of mottling of marrow in six anatomic regions of the pelvis were observed and were assigned a grade. Anatomic correlation was provided with gross and microscopic examination of bone marrow biopsy specimens taken from selected pelvic sites in cadavers of children. Marrow signal intensity increased in all pelvic regions except the acetabulum from birth to age 24 years. Marrow heterogeneity was most prominent in the acetabulum at all ages. Patterns of bone marrow signal intensity and heterogeneity are recognized for four age groups: the infant, child, adolescent, and young adult. Regional and age-related differences in the signal intensity of pelvic marrow correlate with the percentage of fat seen microscopically in marrow.

Adolescent↗

Differential inhibition of HIV-1 cell binding and HIV-1-induced syncytium formation by low molecular weight sulphated polysaccharides.

Dextran sulphate (MW 5000 and 8000) and a polysulphated glycosaminoglycan (MW 10,000), at concentrations that provided complete protection in a homologous infection assay, failed to block syncytium formation and the resulting cytopathic effect when MT-2 cells were mixed with H9/HIV-1 cells. These substances also had no antiviral activity when added to cells, after virus challenge, at a time when binding and entry were complete. However, a high molecular weight (500,000) dextran sulphate blocked HIV-1 infection at both stages. Thus, the gp120-CD4 interactions mediating HIV-1 binding and HIV-1-induced syncytium formation are differentially affected by this class of polyanionic substances. Furthermore, size may be a determining factor in their potential application as anti-HIV treatment.

Antiviral Agents↗

Antifusion activity in sera from persons infected with human immunodeficiency virus type 1.

Cell-to-cell fusion plays an important role in the pathogenesis of human immunodeficiency virus type 1 (HIV-1) infections. An assay to measure the antifusion activity of serum has been developed by using the fusion event that occurs between H9 cells chronically infected with HIV-1 (H9IIIB) and fusion-susceptible MT-2 cells. The endpoint is determined by measuring neutral red uptake in cells after syncytium formation is allowed to occur in the presence of various serum dilutions. The assessment of antifusion activity in serum by neutral red uptake has been shown to correlate with syncytium reduction as determined by direct counting. The optimal number and ratio of cells in the suspension for efficiency and speed of the assay have been determined. With this assay it was shown that 50% of 36 serum specimens capable of neutralizing cell-free virions failed to inhibit syncytium formation. The assay can thus measure a distinct activity in HIV-1-immune human sera which is a subset of neutralization activity. Because of the potential role of this activity in the rate of disease progression and protective immune responses, the antifusion assay will be an important tool for the investigation of disease pathogenesis and for acquired immunodeficiency syndrome vaccine development. The assay can also be applied to the investigation of the pathogenesis of the fusion event at the cellular level. The ability to use absorbance measurements rather than syncytium counts as the endpoint facilitates direct computer-assisted data analysis, which expedites the performance of the assay.

Cell Fusion↗