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T Colby

Publications and source records attributed to T Colby.

15 recordsLinked to original sources
PubMed2006

Acute exacerbation of idiopathic pulmonary fibrosis: frequency and clinical features.

Although acute exacerbations of idiopathic pulmonary fibrosis are well recognised, there are no studies documenting their prevalence or identifying pre-existing risk factors. This study analysed the clinical, radiological and pathological data of 11 patients who satisfied the criteria for acute exacerbation among 147 patients with biopsy-proven idiopathic pulmonary fibrosis. There were five additional patients who had similar demographics, radiology and surgical lung biopsy pathology, but had clinically less severe disease, and so were not included. The 2-yr frequency of acute exacerbation was 9.6% after the diagnosis. Most exacerbations were idiopathic, although two cases presented after surgical lung biopsy and one after bronchoalveolar lavage. No significant risk factor was found by univariate proportional hazard analysis. Imaging revealed diffuse bilateral ground-glass opacification superimposed on subpleural reticular and honeycombing densities. The biopsies of four patients taken during acute exacerbation exhibited diffuse alveolar damage superimposed upon usual interstitial pneumonia. The findings of this study demonstrate that acute exacerbation of idiopathic pulmonary fibrosis is rather common and this exacerbation is likely to have a spectrum of severity.

Acute Disease↗
PubMed2001

Utility of a lung biopsy for the diagnosis of idiopathic pulmonary fibrosis.

It is not known if a surgical lung biopsy is necessary in all patients for the diagnosis of idiopathic pulmonary fibrosis (IPF). We conducted a blinded, prospective study at eight referring centers. Initially, cases were evaluated by clinical history and examination, transbronchial biopsy, and high-resolution lung computed tomography scans. Pulmonologists at the referring centers then assessed their certainty of the diagnosis of IPF and provided an overall diagnosis, before surgical lung biopsy. The lung biopsies were reviewed by a pathology core and 54 of 91 patients received a pathologic diagnosis of IPF. The positive predictive value of a confident (certain) clinical diagnosis of IPF by the referring centers was 80%. The positive predictive value of a confident clinical diagnosis was higher, when the cases were reviewed by a core of pulmonologists (87%) or radiologists (96%). Lung biopsy was most important for diagnosis in those patients with an uncertain diagnosis and those thought unlikely to have IPF. These studies suggest that clinical and radiologic data that result in a confident diagnosis of IPF by an experienced pulmonologist or radiologist are sufficient to obviate the need for a lung biopsy. Lung biopsy is most helpful when clinical and radiologic data result in an uncertain diagnosis or when patients are thought not to have IPF.

Biopsy↗
PubMed2001

Extracutaneous angiosarcomas metastatic to the lungs: clinical and pathologic features of twenty-one cases.

Angiosarcomas are rare malignant vascular tumors with a high rate of metastasis involving lungs (most commonly), liver, regional lymph nodes, bone, and other sites. In this study, we have reviewed the clinical presentation and histopathology of 21 cases of extracutaneous angiosarcoma metastatic to the lungs. Tumors with exclusively pleural involvement were excluded. Patients presented with dyspnea, chest pain, and/or hemoptysis lasting a few weeks to months. Radiologically, the most common finding comprised multiple peripheral lung nodules (57%), often accompanied by infiltrates. For 11 cases (52%), the primary tumor was not identified at the time of presentation. Vasoformative areas were identified in 15 cases (71%). Nine cases comprised spindle cells (43%), two contained epithelioid cells (9.5%), and 10 consisted of both spindle and epithelioid cells (48%). Nuclear pleomorphism was at least moderate in all cases. However, five tumors contained regions of minimal nuclear atypia. Hemorrhage, siderophages, and fibrosis were commonly present. Immunohistochemical staining (IHS) was performed on 14 cases. Thirteen tumors showed reactivity for vascular markers. Tumor cells reacted for Von Willebrand factor in 13 of 14 cases, and CD31 and CD34 were each positive in 2/2 cases. Two cases (of nine examined) also expressed cytokeratins. Because the tumor often first presented in the lungs before the primary sarcoma was identified, the clinical impression included both benign and malignant entities. For patients with primary cardiac tumors, symptoms referable to the primary tumor complicated the clinical presentation, and radiologic evaluation supported a clinical diagnostic impression of non-neoplastic pericarditis. Thus, angiosarcoma in the lung may elude diagnosis until histopathologic evaluation of the lung biopsy.

Adult↗
PubMed2000

Histopathologic features of Burkholderia cepacia pneumonia in patients without cystic fibrosis.

We present the histopathologic features of fatal Burkholderia cepacia pneumonia in three adults (one man [age 44 years] and two women [aged 40 and 43 years]). In all patients, the pulmonary infiltrates initially were localized (right middle lobe, left upper lobe, and right middle lobe) but rapidly progressed. Two open-lung biopsies and one pneumonectomy specimen showed necrotizing granulomatous inflammation merging with areas of more conventional necrotizing bronchopneumonia In one patient, a mediastinal lymph node also showed stellate necrotizing granulomas. Vasculitis was absent. B. cepacia was cultured from the open-lung biopsies and bronchial wash specimens in two patients and from postmortem cultures of lung, subcarinal lymph nodes, and blood in the third. The histopathology in these patients resembles that of melioidosis, which is caused by a related organism, Burkholderia pseudomallei. B. cepacia needs to be considered in the differential diagnosis of necrotizing granulomatous inflammation. In addition, given the rarity with which B. cepacia is identified as a cause of pneumonia in the immunocompetent host, isolation of B. cepacia should trigger a workup for underlying immunodeficiency or lead to an investigation to exclude the possibility of a nosocomial infection.

Adult↗
PubMed1999

11q13 allelic imbalance discriminates pulmonary carcinoids from tumorlets. A microdissection-based genotyping approach useful in clinical practice.

Pulmonary tumorlets are minute neuroendocrine cell proliferations believed to be precursor lesions to pulmonary carcinoids. Little is known of their molecular pathogenesis because of their small size. Using tissue microdissection, we evaluated 11q13 region allelic imbalance in the pathogenesis of pulmonary tumorlet/carcinoid lesions. The int-2 gene was selected because of its chromosomal location at 11q13 in close proximity to MEN1, a tumor suppressor gene frequently mutated in familial forms of neuroendocrine cancer. Three cohorts of patients were studied: subjects with typical carcinoid tumors and coexisting tumorlets (n = 5), typical carcinoids without tumorlets (n = 6), and tumorlets alone without carcinoid lesions (n = 5). A total of 11 carcinoids and 11 tumorlets were microdissected from 4-micrometer-thick histological sections. Genotyping was designed to detect allelic imbalance of the int-2 gene and involved DNA sequencing of two closely spaced deoxynucleotide polymorphisms. Subjects shown to be informative were evaluated for allelic imbalance in tumorlet/carcinoid tissue. Eight of 11 (73%) carcinoids manifested allelic, in contrast to only one of 11 (9%) of tumorlets. Int-2 allelic imbalance was significantly associated with carcinoid tumor formation (P < 0.01). In patients having both carcinoid tumors and tumorlets, the latter showed allelic balance and were thus discordant in genotype with coexisting carcinoid excluding pathogenesis of tumorlets from intramucosal spread from carcinoid tumors. Int-2 allelic imbalance was shown to be an early event in carcinoid tumor formation by virtue of the absence of allelic imbalance for other common cancer-related gene disturbances involving 11p13 (Wilms' tumor), 3p25 (von-Hippel-Lindau), and 17p13 (p53). Demonstration of 11q13 allelic imbalance by microdissection/genotyping may be a useful discriminatory marker for pulmonary neuroendocrine neoplasia.

Alleles↗
PubMed1996

Malignant vascular tumors of the serous membranes mimicking mesothelioma. A report of 14 cases.

Malignant endothelial neoplasms involving the serous membranes are rare, and only a few cases have been documented. We report 14 patients with epithelioid hemangioendothelioma (EHE) or epithelioid angiosarcoma (EA) diffusely involving the pleural, peritoneal, or pericardial cavities, resulting in a picture closely resembling mesothelioma. The mean age at diagnosis was 52 (range, 34-85). The patients included two women and one man with peritoneal tumors, eight men with pleural tumors, and three men with pericardial tumors. A shared histological appearance was a diffuse sheet-like and clustered pattern of tumor growth with variable degrees of vascular differentiation. A tubulopapillary growth pattern, often seen in mesothelioma, was prominent in four cases. Nine cases showed a variable number of spindle cells, some neoplastic, others reactive, focally producing a biphasic growth pattern, further suggesting mesothelioma. Initial interpretations included mesothelioma, adenocarcinoma, and, in one case with prominent spindle-cell components, leiomyosarcoma. Immunohistochemically, strong vimentin staining and negative or weak to moderate cytokeratin staining were observed in all 14 cases. The tumor cells coexpressed at least two of the four endothelial markers used in the study (CD31, CD34, von Willebrand factor, and Ulex europaeus agglutinin-I [UEA-I)]. Detection of abortive vessel formation was facilitated by staining for collagen type IV. Markers of mesothelial, epithelial, muscular, and neuronal differentiation were all negative in the subset of cases studied. As a control group, 39 mesotheliomas and more than 60 adenocarcinomas of various origins were studied using the same antibody panel. This group revealed strong keratin staining, moderate or negative vimentin staining, and no expression of any of the endothelial-lineage markers, with the exception of positive staining for UEA-I in occasional adenocarcinomas. Clinically, these endothelial tumors were highly aggressive; 12 patients presented with disseminated disease, and most died within months of the initial presentation. These findings indicate that, although uncommon, EHE/EA should be included in the differential diagnosis of serous membrane neoplasms with histological and clinical features of malignant mesothelioma. The diagnosis of an endothelial neoplasm can be suspected by the presence of abortive vessel formation and by the strong expression of vimentin, with absent or low-level expression of cytokeratin. The demonstration of immunoreactivity for two or more endothelial-associated markers is essential in confirming the diagnosis.

Adult↗
PubMed1993

1H assignment and secondary structure determination of human melanoma growth stimulating activity (MGSA) by NMR spectroscopy.

The solution structure of melanoma growth stimulating activity (MGSA) has been investigated using proton NMR spectroscopy. Sequential resonance assignments have been carried out, and elements of secondary structure have been identified on the basis of NOE, coupling constant, chemical shift, and amide proton exchange data. Long-range NOEs have established that MGSA is a dimer in solution. The secondary structure and dimer interface of MGSA appear to be similar to those found previously for the homologous chemokine interleukin-8 [Clore et al. (1990) Biochemistry 29, 1689-1696]. The MGSA monomer contains a three stranded anti-parallel beta-sheet arranged in a 'Greek-key' conformation, and a C-terminal alpha-helix (residues 58-69).

Amino Acid Sequence↗
PubMed1993

Partial functional mapping of the human interleukin-8 type A receptor. Identification of a major ligand binding domain.

We have previously demonstrated that a basic amino acid residue of interleukin (IL)-8, namely Arg-6, is critical for the binding of IL-8 to its receptor. We reasoned that this residue is likely to be poised to directly interact with a counterpart acidic residue on the receptor. To identify this key residue, we systematically mutated to Ala all acidic residues present on the ligand accessible surface of IL-8 receptor type A. Using this strategy, we demonstrate that two residues which are present in extracellular loop 3 of the receptor, namely Glu-275 and Arg-280, are critical for ligand binding. In addition, we show that although Asp-11 is critical for ligand binding, a conservative mutation of Asp-11 to Glu or a substitution of Asp-11 with Lys (the residue found at position 11 in IL-8 receptor type B) does not affect the Kd of the receptor/ligand interaction. These data suggest that Lys-11 recruits a new and favorable interaction with IL-8 (analogous to that of IL-8 receptor type B with IL-8) or that the cavity created by mutating Asp-11 to Ala is particularly deleterious. Finally, we discuss fluorescence-activated cell sorter staining data which support the hypothesis that the N-terminal region and the extracellular loop 3 of the receptor may lie in close proximity of one another and constitute a major binding domain for IL-8.

Alanine↗
PubMed1992

Axonal sprouting induced in the sciatic nerve by the amyloid precursor protein (APP) and other antiproteases.

Protease inhibition is the mechanism by which some trophic factors promote the extension of neurites. In the rat sciatic nerve, we assessed the ability to induce sprouts of the APP isoform that embodies the Kunitz antiprotease domain and other antiproteases. With the electron microscope, axonal sprouts were found when antiproteases were supplied but not after administration of inactive substances. We conclude that axons have a drive to sprout which can be released by the unbalance of an extracellular protease-antiprotease system. We propose that this system is involved in the pathogenesis of Alzheimer's disease.

Amyloid beta-Protein Precursor↗
PubMed1991

Open lung biopsy does not correlate with pulmonary function after the adult respiratory distress syndrome.

Abnormalities of pulmonary function occur following the adult respiratory distress syndrome (ARDS). To determine if open lung biopsy (OLB) during ARDS predicts late pulmonary function abnormalities, we examined nine survivors of ARDS who had OLB during ARDS. Open lung biopsy was performed within two weeks of the diagnosis of ARDS, and the following were scored by a pulmonary pathologist as to extent and severity: hyaline membranes (HM), interstitial fibrosis (IF), air space organization (AO), interstitial cellularity (IC), and type 2 cell proliferation (T2C). Pulmonary function tests performed at least one year after ARDS were also used for analysis. Percent predicted Dco, TLC, DL/VA, and FVC were regressed against extent, severity, and combined scores. No significant correlation was found despite impressive histologic abnormalities. These data suggest that the severity and extent of HM, IF, AO, T2C, or IC do not correlate with lung function following ARDS.

Female↗
PubMed1986

Pulmonary capillary hemangiomatosis.

Pulmonary capillary hemangiomatosis (PCH) is a rare cause of pulmonary hypertension; only three cases have been reported. Four additional cases are described in this report. All of the patients in this study presented with signs and symptoms of pulmonary hypertension, and in none was a correct morphologic diagnosis made during life. Histologically, the most striking feature was the presence of numerous cytologically benign thin-walled capillary-sized blood vessels proliferating diffusely through alveolar walls and in and around larger vessels and airways. Venous infiltration was associated with intimal fibrosis and secondary veno-occlusive disease (VOD). Because of the presence of hemorrhage, the apparent interstitial widening and inflammation, and the venous changes, the condition in these cases was initially misdiagnosed as interstitial fibrosis or VOD. However, the identification of proliferating and invasive capillaries, which are unique to PCH, led to the correct diagnosis. Although the nature of PCH is unknown, it behaves like a low-grade vascular neoplasm.

Adolescent↗
PubMed1986

Open lung biopsy in Mycoplasma pneumoniae pneumonia.

Pathologic descriptions of Mycoplasma pneumoniae pneumonia in humans are scarce, and most descriptions are from autopsy studies. We studied open lung biopsy specimens from six patients with proved or probable M pneumoniae pneumonia and reviewed the findings on M pneumoniae pneumonia that have been reported in the literature, as well as the electron microscopic characteristics of the organism, to document the morphologic spectrum. Five of our six cases showed a typical but nonspecific polymorphonuclear leukocyte-rich exudate in the bronchiolar lumina, metaplastic cells that lined the bronchioles, a lymphoplasmacytic bronchiolar wall infiltrate, peribronchiolar septal widening, and adjacent hyperplasia of type II pneumocytes. In one patient, diffuse alveolar damage was superimposed on the above bronchiolar lesion, and the sixth patient had a nonspecific organizing pneumonia.

Adolescent↗
PubMed1981

Delayed ontogenic development in the bypassed ileum of the infant rat.

Ontogenic development continues after birth in mammalian enteric epithelium as an adaptive mechanism to extrauterine life. In the rat, particularly significant developmental changes in enteric structure, function, and cytokinetic properties occur over a short critical period (usually between 16 and 20 days of age), preparatory to dietary change with weaning. Surgical bypass of ileal segments was performed on suckling rats of 12-14 days of age, and the effect on subsequent intestinal development was studied in both the bypassed and the shortened segment remaining in continuity. The bypassed segment, although achieving normal maturational patterns of active sucrase appearance and maltase accumulation, continued to maintain coincident immature patterns of high lactose activity and low cell turnover times. The intestine in continuity showed precocious appearance of active sucrase and accumulation along with maltase to greater than control levels, accompanied by a normal coincident decline in lactase activity and enterocyte life-span. Involvement of intraluminal influences on various parameters of enteric ontogenic development is thus indicated with the effects expressed by a delay in the excluded (bypassed) segment and by stimulation in the shortened segment in continuity. Data are presented in further support of the hypothesis that the life-span of the enterocyte serves postnatally as a primary determinant of enteric lactase levels.

Animal Population Groups↗
PubMed1976

Bacterial endocarditis after cardiac catheterization.

Bacterial endocarditis is a rare complication of cardiac catheterization. We present the history of a patient who developed fatal, acute bacterial endocarditis following diagnostic cardiac catheterization. The implications regarding antibiotic prophylaxis and catheterization technique are discussed.

Cardiac Catheterization↗