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Biomedical subjects

D N Howell

Publications and source records attributed to D N Howell.

At least 37 records · Page 2Linked to original sources
PubMed1999

Trichodysplasia spinulosa--a newly described folliculocentric viral infection in an immunocompromised host.

This is a case report of an immunocompromised individual who presented with progressive alopecia, friable follicular spinous processes, and erythematous, indurated papules. Examination of skin biopsies using light microscopy and immunohistochemistry revealed pathologic changes of the follicular inner root sheath epithelium with dystrophic trichohyaline granules. Electron microscopy of thin sections of tissue revealed intracellular viral particles with a size and appearance consistent with those in the Papovaviridae family. Electron microscopy of negatively stained extract from a homogenized lesion also demonstrated icosahedral viruses with papovavirus morphology. We believe this is a previously unreported folliculocentric viral infection in an immunosuppressed human host and have termed this entity "trichodysplasia spinulosa".

Adult↗
PubMed1999

Clinical and genetic heterogeneity in familial focal segmental glomerulosclerosis. International Collaborative Group for the Study of Familial Focal Segmental Glomerulosclerosis.

BACKGROUND: Familial forms of focal segmental glomerulosclerosis (FFSGS) that exhibit autosomal dominant or recessive patterns of inheritance have been described. The genetic basis of these hereditary forms of FSGS is unknown. One recent study of a kindred from Oklahoma with an autosomal dominant form of FSGS linked this disease to a region of chromosome 19q. In addition, polymorphisms in a gene in this region on chromosome 19q13 have been linked to congenital nephrotic syndrome of the Finnish type. We have ascertained and characterized a large family with autosomal dominant FFSGS (Duke 6530). METHODS: Families were compared for clinical and genetic heterogeneity. To test for linkage of our family to this portion of chromosome 19, genomic DNA was isolated from 102 family members, and polymerase chain reaction was performed using eight microsatellite markers that spanned the area of interest on chromosome 19. Data were evaluated using two-point linkage analysis, multipoint analysis, and an admixture test. RESULTS: Linkage was excluded at a distance of +/- 5 to 10 CM for all markers tested with two-point log10 of the odds of linkage (LOD) scores and from an approximate 60 CM interval in this area of chromosome 19q via multipoint analysis. CONCLUSIONS: FSGS has been called the "final common pathway" of glomerular injury, as it is a frequent pathological manifestation with diverse etiologies. This diversity likely correlates with the genetic heterogeneity that we have established. Thus, our data demonstrate that there are at least two genes responsible for this disease, and there is genetic as well as clinical heterogeneity in autosomal dominant FSGS.

Adolescent↗
PubMed1999

Spectrum of disease in familial focal and segmental glomerulosclerosis.

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is the underlying pathologic entity in 5% of adults and 20% of children with end-stage renal disease (ESRD). FSGS is generally considered to be sporadic in origin. METHODS: Recently, we identified 60 families involving 190 individuals with familial FSGS, providing evidence for a subset of families in which a genetic form is segregating. Each family had at least one member with renal biopsy-confirmed FSGS and at least one other member with either renal biopsy-confirmed FSGS or ESRD. RESULTS: Twenty-six families had individuals affected in more than one generation [multigeneration (MG)], and the remaining 34 families had only a single generation (SG) affected. There was equal representation of males and females among affected individuals. Ten percent of MG families were African American, and 52% of SG families were African American. The mean age of presentation was significantly higher in the MG families (32.5 +/- 14.6 years) compared with the SG families (20.1 +/- 12.1 years, P = 0.0001). SG cases had higher levels of proteinuria at presentation (7.0 +/- 5.6 g/24 hr, compared with 3.8 +/- 3.4 g/24 hr, for the MG families, P = 0.002). On renal biopsy, tubulointerstitial damage was more severe in patients in the SG families than in the MG families; however, the level of glomerular damage did not differ between these groups. Fifty percent of the patients had progressed to ESRD by the age of 30 years. Variables measured at presentation that were independently associated with poor renal survival were decreased age, increased serum creatinine, and increased urinary protein excretion. Forty-one patients underwent successful renal transplantation, with a 10-year graft survival rate of 62%. One patient developed clinical and biopsy evidence of recurrence of FSGS in the allograft. CONCLUSION: These data confirm the existence of a non-Alport's form of hereditary glomerulonephritis, which has a morphological pattern of FSGS.

Adult↗
PubMed1999

Electron microscopic diagnosis of human flavivirus encephalitis: use of confocal microscopy as an aid.

The distinction between intracranial viral infections and inflammatory conditions requiring immunosuppression is important. Although specific laboratory reagents are readily available for some viruses, diagnosis of arbovirus infection is more difficult. Transmission electron microscopy (TEM) theoretically allows identification of viral particles independent of reagent availability, but it has limited sensitivity. We report two cases of human flavivirus encephalitis diagnosed by TEM. Laser scanning confocal microscopy (LSCM) was used in one case to survey unembedded tissue slices for focal abnormalities, from which fragments smaller than 1 mm2 were excised for epoxy embedding. This facilitated TEM identification of intracytoplasmic, budding, 35-40 nm spherical virus particles, confirmed by serology as St. Louis encephalitis. In contrast to mosquitoes and newborn mice, in which high viral loads are associated with minimal tissue responses, these biopsies showed florid angiodestructive inflammation and microgliosis, with rare virions in necrotic perivascular cells and astrocytes. To our knowledge, this represents the first ultrastructural study of St. Louis encephalitis in humans, indicating the potential value of LSCM-aided TEM.

Adult↗
PubMed1999

Respiratory viral infections in lung transplant recipients: radiologic findings with clinical correlation.

PURPOSE: To evaluate radiologic finding of respiratory viral infection in lung transplant recipients with clinical correlation. MATERIALS AND METHODS: Over 5 years, 21 episodes of respiratory viral infection (parainfluenza [n = 9], respiratory syncytial virus [n = 8], adenovirus [n = 5], influenza [n = 2]) were diagnosed 6-727 days (mean, 270 days) after lung transplantation in 20 recipients. Chest radiographs, computed tomographic (CT) images, and clinical records were reviewed. RESULTS: Sixteen episodes of respiratory viral infection were diagnosed in patients with symptoms of lower respiratory tract infection or acute allograft dysfunction; five were diagnosed in asymptomatic patients. Chest radiographs were abnormal in 11 (52%) episodes; findings included heterogeneous or homogeneous opacities and masslike consolidation. All patients with radiographic abnormalities were symptomatic. Chest radiographs were unchanged from baseline in 10 (48%) episodes; in one, CT revealed findings not depicted at radiography. Adenoviral infection (n = 5) was typically symptomatic, was associated with new radiographic abnormalities, and was rapidly lethal (n = 4). Infection with parainfluenza and/or respiratory syncytial virus was commonly asymptomatic and was not associated with radiographic abnormalities; affected patients had good outcomes. CONCLUSION: Respiratory viral infections are important causes of morbidity and mortality in lung transplant recipients. Radiographic abnormalities in patients with respiratory viral infections were usually accompanied by symptoms of lower respiratory tract infection. Adenoviral infection was frequently accompanied by progressive pulmonary opacity and fatal outcome.

Adenovirus Infections, Human↗
PubMed1998

Expression of a copper-containing amine oxidase by human ciliary body.

PURPOSE: To examine the molecular structure and ultrastructural distribution of a novel amine oxidase in human ciliary body. METHODS: Human ciliary bodies were solubilized with a nonionic detergent. The solubilized material was subjected to affinity chromatography with 2B4.14.1, a monoclonal antibody which recognizes a family of ciliary body glycoproteins. Proteins eluted from the affinity column were further separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Peptides produced from a 2B4.14. 1-reactive protein with an approximate molecular weight of 100 kDa were analyzed by Edman degradation. The protein thus identified was further examined by Western blotting and immunoelectron microscopy with anti-peptide antisera. RESULTS: Peptide sequences from the 100 kDa ciliary body protein were identical to the predicted protein sequence of an amine oxidase identified recently in a human placental cDNA library. The identity of the ciliary body protein was confirmed by Western blotting with rabbit antiserum generated against the predicted carboxy-terminal peptide of human placenta amine oxidase. Western blotting under nonreducing conditions and following glycosidase digestion indicated that the native enzyme is a disulfide-linked homodimer with multiple N-linked oligosaccharide side chains. By immunoelectron microscopy, the ciliary body amine oxidase was localized to the plasma membranes of inner epithelial cells. CONCLUSIONS: Human placenta amine oxidase is present on the plasma membranes of ciliary body inner epithelial cells. This finding provides a potential explanation for amine oxidase enzyme activity detected in previous studies of anterior segment tissues. Though the functional role of human placenta amine oxidase in the eye is unclear, it may contribute to the production of H2O2 in aqueous humor.

Aged↗
PubMed1998

Special techniques in diagnostic electron microscopy.

The power of electron microscopy as a diagnostic tool can be amplified considerably by the application of ancillary preparative and analytic methods. Subcellular chemistry and structure can be examined by various forms of microprobe analysis and by special staining methods, including cytochemical, immunocytochemical, and negative staining. Qualitative ultrastructural examination can be augmented by morphometric analysis. Correlative microscopic survey methods can be used as a means of targeting ultrastructural investigations. This article provides an overview of the use of these special techniques in the diagnosis and classification of tumors and other selected pathologic processes.

Diagnosis, Differential↗
PubMed1998

Morphologic criteria for the preliminary identification of Fusarium, Paecilomyces, and Acremonium species by histopathology.

Nontraditional human pathogenic fungi, including Fusarium, Paecilomyces, and Acremonium species, have been increasingly documented as agents of infection in immunocompromised patients and, occasionally, in normal hosts. Although definitive identification of these fungi requires culture, they often can be identified provisionally in tissue sections by a combination of histologic features, including hyaline septate hyphae and characteristic reproductive structures known as phialides and phialoconidia. These morphologic characteristics, although familiar to mycologists, are easily overlooked by histopathologists; as a result, Fusarium species and Paecilomyces lilacinus are frequently misidentified in tissue sections as Aspergillus or Candida species. We identified 19 culture-proved cases of infection with species of Fusarium, Paecilomyces, or Acremonium; retrospectively reviewed histologic specimens stained by routine hematoxylin and eosin, Gomori methenamine silver, and/or periodic acid-Schiff stains; and delineated morphologic criteria that will help pathologists make a preliminary identification of these fungi by histopathology. Adventitious sporulation was found in 9 of 9 infections caused by Paecilomyces species, 7 of 10 infections caused by Fusarium species, and in the single case of infection caused by Acremonium strictum. Histologic recognition of these morphologies may help clinicians select appropriate initial antifungal treatment and manage the infection.

Acremonium↗
PubMed1998

L-selectin and ICAM-1 mediate reperfusion injury and neutrophil adhesion in the warm ischemic mouse liver.

Leukocytes recruited during ischemia-reperfusion to the liver are important mediators of injury. However, the mechanisms of leukocyte adhesion and the role of adhesion receptors in hepatic vasculature remain elusive. L-selectin may critically contribute to injury, priming adhesion for later action of intercellular adhesion molecule-1 (ICAM-1). Paired experiments were performed using mutant mice (L-selectin -/-, ICAM-1 -/-, and L-selectin/ICAM-1 -/-) and wild-type mice (C57BL/6) to investigate leukocyte adhesion in the ischemic liver. Leukocyte adhesion and infiltration were assessed histologically. Aspartate aminotransferase levels were significantly reduced (2- to 3-fold) in mutant vs. wild-type mice in most groups but most significantly after 90 min of partial hepatic ischemia. Leukocyte adhesion was significantly reduced in all mutant mice. Areas of microcirculatory failure, visualized by intravital microscopy, were prevalent in wild-type but virtually absent in L-selectin-deficient mice. After total hepatic ischemia for 75 or 90 min, survival was better in mutant L-selectin and L-selectin/ICAM-1 mice vs. wild-type mice and ICAM-1 mutants. In conclusion, L-selectin is critical in the pathogenesis of hepatic ischemia-reperfusion injury. Poor sinusoidal perfusion due to leukocyte adhesion and clot formation is a factor of injury and appears to involve L-selectin and ICAM-1 receptors.

Animals↗
PubMed1998

Community respiratory viral infection in adult lung transplant recipients.

STUDY OBJECTIVE: To define the epidemiology, clinical manifestations, and long-term complications of respiratory viral infections in adult lung transplant recipients. DESIGN: Retrospective review of the records of 122 adult lung transplant recipients over a 5-year period at one institution. RESULTS: Ten episodes of infection with respiratory syncytial virus, parainfluenza, influenza, or adenovirus were identified. All patients presented with symptoms of respiratory tract infection. Two patients died acutely and four patients subsequently had development of obliterative bronchiolitis (OB). CONCLUSIONS: These data suggest community respiratory viral infections cause significant morbidity and mortality in lung transplant recipients. Further prospective studies are warranted to clarify the relationship between respiratory viral infection and OB and to define the optimal therapy for these viral infections.

Adult↗
PubMed1998

Isolation, culture, and characterization of endothelial cells from Schlemm's canal.

PURPOSE: An important goal in glaucoma research has been to understand the functional contribution of trabecular meshwork (TM) and Schlemm's canal (SC) endothelia to aqueous humor outflow resistance. To date, TM cells are routinely cultured and used as a model by several laboratories. However, there has been only limited success in isolating SC cells. The current objective was to develop a technique for selective isolation and culture of endothelial cells from human SC. METHODS: The anterior chamber of human cadaveric eyes was cut into eight equal and radially symmetric wedge-shaped pieces. Using a dissecting microscope, a gelatin-coated suture (6-0 sterile nylon monofilament) was gently inserted into the lumen of SC and advanced into the canal. The cannulated pieces of tissue were placed in culture medium and maintained for 3 weeks. Sutures were removed from SC and cells seeded onto 3-cm culture plates. Morphology, growth characteristics, and expression of endothelial surface antigens and other cellular markers were evaluated. RESULTS: Of the 20 pairs of eyes that were cannulated, primary cells were obtained from 13. All SC cell isolates had a fusiform morphology; formed nonoverlapping, linearly arranged monolayers; and were contact inhibited. Schlemm's canal cell isolates reacted with antibodies specific for CD44 (hyaluron receptor), CD54 (intercellular adhesion molecule-1, ICAM-1), tissue-type plasminogen activator, and TM-inducible glucocorticoid-responsive protein-myocilin (TIGR-MYOC). Unlike TM cells, however, TIGR-MYOC protein was not induced in SC cells after long-term dexamethasone treatment. Schlemm's canal cells endocytosed low-density lipoprotein and acetylated low-density lipoprotein, and in the presence of Matrigel organized into multicellular tubelike structures. CONCLUSIONS: Cannulation of SC with gelatin-coated suture material is an effective method for the isolation of human SC cells and provides a cellular model to study the potential role of SC cells in aqueous humor outflow function.

Adult↗
PubMed1998

Candidal anastomotic infection in lung transplant recipients: successful treatment with a combination of systemic and inhaled antifungal agents.

Anastomotic infection is an uncommon but potentially life-threatening complication after lung transplantation. We recently encountered three lung transplant recipients with invasive candidal anastomotic infection. Two patients were admitted with dyspnea and fever, and one asymptomatic infection was detected on surveillance bronchoscopy. All three patients were treated similarly with a combination of intravenous amphotericin B, inhaled amphotericin B, and oral fluconazole. The combination of systemic and inhaled antifungal agents successfully treated all three cases of anastomotic infection.

Administration, Inhalation↗
PubMed1997

Appearance of immune complex glomerulonephritis following the onset of type I diabetes mellitus in a child.

Renal disease is a frequent late complication of type I diabetes mellitus, occurring almost entirely in adult patients. Typical diabetic nephropathy is characterized by proteinuria, and by the histological lesions of mesangial expansion and basement membrane thickening. We report an interesting case of a 3-year-old boy who developed immune complex glomerulonephritis with nephrotic syndrome 2 months after the onset of insulin-dependent diabetes mellitus.

Biopsy↗
PubMed1997

Extrusion of abnormal endothelium into the posterior corneal stroma in a patient with posterior polymorphous dystrophy.

PURPOSE: To report the presence of abnormal endothelium that extruded into the posterior corneal stroma in a patient with posterior polymorphous dystrophy. METHODS: The corneal button of a man who underwent penetrating keratoplasty for posterior polymorphous dystrophy was examined by light and electron microscopy. Immunoperoxidase staining for cytokeratins, vimentin, and the endothelial antigen recognized by monoclonal antibody 2B4.14.1 antigen was performed. Two-color immunofluorescence staining for simultaneous detection of cytokeratins and 2B4.14.1 antigen was also done. RESULTS: Much of the endothelium had characteristic features of epithelium-like cells, and abnormalities in Descemet's membrane were present. Curious oval and slit-like spaces in the posterior stroma were lined by epithelium-like endothelial cells and were continuous with the anterior chamber through defects in Descemet's membrane. CONCLUSION: These abnormalities in the posterior stroma have not previously been described in histopathologic reports of posterior polymorphous corneal dystrophy and are likely an unusual variation in the spectrum of this hereditary disorder.

Adolescent↗
PubMed1997

Immunoperoxidase and immunofluorescent staining of Rickettsia rickettsii in skin biopsies. A comparative study.

OBJECTIVE: To compare immunofluorescent and immunoperoxidase staining of Rickettsia rickettsii in skin biopsies of patients suspected of having Rocky Mountain spotted fever (RMSF). DESIGN: Immunofluorescent staining results for R rickettsii from skin biopsies of patients suspected of having RMSF were obtained by computer and chart review. Immunoperoxidase staining for R rickettsii was performed on formalin-fixed, paraffin-embedded skin biopsies from the same patient population. PATIENTS: Twenty-six patients who were clinically suspected of having RMSF were included in this study. Skin biopsies of these patients were examined for evidence of RMSF by immunofluorescence and routine histology. MAIN OUTCOME MEASURES: The sensitivity and specificity of both immunofluorescent and immunoperoxidase staining techniques were calculated. The chi 2 method was used to assess significance. RESULTS: Both tests were highly significant for the detection of R rickettsii (P < .01). The sensitivity and specificity of the immunofluorescent and immunoperoxidase staining techniques for the identification of RMSF were identical. No significant difference between these tests was identified (P > .05). CONCLUSION: The sensitivity and specificity of immunofluorescent and immunoperoxidase staining of R rickettsii in routinely processed, paraffin-embedded skin biopsies of patients suspected of having RMSF are identical. Although not as rapid as the immunofluorescent technique, immunoperoxidase staining of R rickettsii has advantages over the immunofluorescent technique; these include easier antigen localization and concomitant viewing of the corresponding histopathology.

Biopsy↗
PubMed1997

Endothelial metaplasia in the iridocorneal endothelial syndrome.

PURPOSE: To test the hypothesis that the aberrant, cytokeratin-expressing cells that replace endothelium in the iridocorneal endothelial (ICE) syndrome are of endothelial origin. METHODS: Corneas from four patients with Chandler's syndrome and three with essential iris atrophy were examined by two-color immunofluorescence for simultaneous expression of cytokeratins and two markers of endothelial lineage: vimentin and the antigen recognized by the antiendothelial monoclonal antibody 2B4.14.1. RESULTS: In six corneas, unequivocal endothelial staining for cytokeratins was present; in each of these, cells coexpressing cytokeratins and the two endothelial markers were clearly identifiable. In the remaining cornea, weak cytokeratin staining that colocalized with vimentin was present. CONCLUSIONS: These results lend strong support to the hypothesis that the "epithelial-like" endothelial cells in ICE syndrome are cells of endothelial lineage rather than heterotopia of epithelial cells; these cells probably arise via a metaplastic transformation of preexisting endothelium.

Adult↗
PubMed1996

Diagnostic yield of bronchoscopies after isolated lung transplantation.

Lung transplantation has become an acceptable therapeutic option for end-stage pulmonary diseases. The most common causes of long-term mortality after transplantation are infections and obliterative bronchiolitis (OB). While acute rejection has been shown to be associated with an increased risk of development of OB, cytomegalovirus (CMV) pneumonitis is more controversial as a risk factor for OB. Surveillance bronchoscopies are therefore advocated as a method of detecting silent episodes of CMV pneumonitis or acute rejection. We performed 226 bronchoscopies in 43 lung transplant recipients over 34 months. One hundred fifty-seven of the 226 bronchoscopies were performed according to a surveillance protocol. Acute rejection was diagnosed if lung histologic study revealed grade 2 to 4 rejection or if prompt reversal of clinical deterioration occurred after initiation of pulse steroid therapy. CMV pneumonitis was diagnosed when transbronchial biopsy histologic specimens revealed evidence of CMV inclusion bodies, or when CMV was recovered on BAL fluid in the presence of allograft deterioration. The proportion of patients who were free from any episode of acute rejection or CMV pneumonitis after transplantation was determined by Kaplan-Meier analysis. Twenty-one percent of our transplant recipients were free from acute rejection or CMV pneumonitis after a mean follow-up of 13 months. All patients who had acute rejection or CMV pneumonitis had the initial episode in the first 4 months after transplantation. Patients free of acute rejection or CMV pneumonitis 4 months after transplantation continued to be event free for the duration of follow-up. Our data suggest that surveillance bronchoscopy can be aborted in patients who are free from acute rejection or CMV pneumonitis by 4 months after transplantation. The role of surveillance bronchoscopy in decreasing the incidence of OB or improving survival can be determined only by future randomized prospective trials.

Acute Disease↗