Biomedical subjects

T Pham

Publications and source records attributed to T Pham.

At least 55 records · Page 3Linked to original sources

PubMed2000

Uveitis, an under-recognized adverse effect of pamidronate. Case report and literature review.

Ophthalmologic adverse effects of bisphosphonate therapy are infrequent and of unclear pathogenesis. The most common has been anterior uveitis, of which 18 cases have been reported. Onset was within 24 to 48 hours after infusion initiation, and both eyes were affected in most patients. The outcome was favorable within a few days after bisphosphonate discontinuation and topical glucocorticoid therapy, although rechallenge was frequently followed by a recurrence. Bisphosphonates are being used successfully in an increasingly broad range of disorders. We report a case of pamidronate-induced anterior uveitis and present a review of the relevant literature.

Anti-Inflammatory Agents↗

PubMed1999

Constitutional von Hippel-Lindau (VHL) gene deletions detected in VHL families by fluorescence in situ hybridization.

von Hippel-Lindau (VHL) disease is an autosomal dominantly inherited cancer syndrome predisposing to a variety of tumor types that include retinal hemangioblastomas, hemangioblastomas of the central nervous system, renal cell carcinomas, pancreatic cysts and tumors, pheochromocytomas, endolymphatic sac tumors, and epididymal cystadenomas [W. M. Linehan et al., J. Am. Med. Assoc., 273: 564-570, 1995; E. A. Maher and W. G. Kaelin, Jr., Medicine (Baltimore), 76: 381-391, 1997; W. M. Linehan and R. D. Klausner, In: B. Vogelstein and K. Kinzler (eds.), The Genetic Basis of Human Cancer, pp. 455-473, McGraw-Hill, 1998]. The VHL gene was localized to chromosome 3p25-26 and cloned [F. Latif et al., Science (Washington DC), 260: 1317-1320, 1993]. Germline mutations in the VHL gene have been detected in the majority of VHL kindreds. The reported frequency of detection of VHL germline mutations has varied from 39 to 80% (J. M. Whaley et al., Am. J. Hum. Genet., 55: 1092-1102, 1994; Clinical Research Group for Japan, Hum. Mol. Genet., 4: 2233-2237, 1995; F. Chen et al., Hum. Mutat., 5: 66-75, 1995; E. R. Maher et al., J. Med. Genet., 33: 328-332, 1996; B. Zbar, Cancer Surv., 25: 219-232, 1995). Recently a quantitative Southern blotting procedure was found to improve this frequency (C. Stolle et al., Hum. Mutat., 12: 417-423, 1998). In the present study, we report the use of fluorescence in situ hybridization (FISH) as a method to detect and characterize VHL germline deletions. We reexamined a group of VHL patients shown previously by single-strand conformation and sequencing analysis not to harbor point mutations in the VHL locus. We found constitutional deletions in 29 of 30 VHL patients in this group using cosmid and P1 probes that cover the VHL locus. We then tested six phenotypically normal offspring from four of these VHL families: two were found to carry the deletion and the other four were deletion-free. In addition, germline mosaicism of the VHL gene was identified in one family. In sum, FISH was found to be a simple and reliable method to detect VHL germline deletions and practically useful in cases where other methods of screening have failed to detect a VHL gene abnormality.

Chromosomes, Human, Pair 3↗

PubMed1999

Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) following treatment with deoxycoformycin in a patient with cutaneous T-cell lymphoma (Sezary syndrome): A case report.

We present a case of a patient who developed all manifestations of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) acutely following treatment of cutaneous T-cell lymphoma (CTCL, Sezary syndrome) with deoxycoformycin (pentostatin). Symptoms and signs included severe thrombocytopenia and microangiopathic hemolytic anemia; hallucinations, confusion and disorientation; oliguric acute renal failure requiring hemodialysis; and fever. No other etiology for these symptoms and signs was present. Complete recovery followed treatment for one month with plasma exchange and glucocorticoids. During the succeeding 20 months she has remained well and her CTCL remains stable on no further treatment. This case and two previously published cases suggest that acute and severe TTP-HUS may be a dose-dependent toxicity of deoxycoformycin (pentostatin).

Enzyme Inhibitors↗

PubMed1999

Molecular cytogenetic fingerprinting of esophageal squamous cell carcinoma by comparative genomic hybridization reveals a consistent pattern of chromosomal alterations.

Esophageal cancer is the third most prevalent gastrointestinal malignancy in the world. The tumor responds poorly to various therapeutic regimens and the genetic events underlying esophageal carcinogenesis are not well understood. To identify overall chromosomal aberrations in esophageal squamous cell carcinoma, we performed comparative genomic hybridization (CGH). All 17 tumor samples were found to exhibit multiple gains and losses involving different chromosomal regions. The frequency of chromosomal loss associated with this type of tumor was as follows: in 2q (100%), 3p (100%), 13q (100%), Xq (94%), 4 (82%), 5q (82%), 18q (76%), 9p (76%), 6q (70%), 12q (70%), 14q (65%), 11q (59%), and 1p (53%). Interstitial deletions on 1p, 3p, 5q, 6q, 11q, and 12q were detected also. Chromosomal gains were displayed by chromosomes and chromosome areas: 19 (100%), 20q (94%), 22 (94%), 16p (65%), 17 (59%), 12q (59%), 8q (53%), 9q (53%), and 3q (50%). Two sites showing apparent amplification were 11q (70%) and 5p15 (47%). To validate the CGH data, we isolated a BAC clone mapping to 18q12.1. This clone was used as a probe in interphase fluorescence in situ hybridization of tumor touch preparations and allelic loss was clearly revealed. This study represents the first whole-genome analysis in esophageal squamous cell carcinoma for associated chromosomal aberrations that may be involved in either the genesis or progression of this malignancy.

Carcinoma, Squamous Cell↗

PubMed1999

The absence of desmin leads to cardiomyocyte hypertrophy and cardiac dilation with compromised systolic function.

Desmin is the muscle-specific member of the intermediate filament family of cytoskeletal proteins, expressed both in striated and smooth muscle tissues. In mature striated muscle fibers, the desmin filament lattice surrounds the Z-discs, interconnects them to each other and links the entire contractile apparatus to the sarcolemmal cytoskeleton, cytoplasmic organelles and the nucleus. There have been increasing reports of human cardiomyopathies associated with abnormal accumulation and aggregation of desmin filaments. Recently identified desmin mutations in humans suffering from skeletal muscle myopathy and cardiomyopathy suggest that these diseases might arise as a consequence of impaired function of desmin filaments. Previous generation of desmin null mice in our laboratory demonstrated that the absence of desmin results in myocyte ultrastructural defects and myocyte cell death leading to fibrosis and calcification of the myocardium. However, the effects that these defects have on cardiac function were not addressed. To further our understanding of desmin function in vivo, and in order to address the direct involvement of desmin in cardiomyopathy, we investigated the effect of the absence of desmin on myocardial mass, myocyte size and shape, changes in gene expression and cardiac systolic and diastolic function in mice. Morphometric characterization of isolated cardiomyocytes demonstrated a 24% increase in cell volume in the desmin null mice, solely due to an increase in transverse section area, suggesting for the first time that mice lacking the intermediate filament protein desmin develop concentric cardiomyocyte hypertrophy. This type of hypertrophy was accompanied by induction of embryonic gene expression and later by ventricular dilatation, and compromised systolic function. These results demonstrate that desmin is essential for normal cardiac function, and they suggest that the absence of an intact desmin filament system, rather than accumulation of the protein, may be responsible for the pathology seen in some of the desmin associated cardiomyopathies.

Animals↗

PubMed1999

Expression of cholecystokinin A receptors in neurons innervating the rat stomach and intestine.

BACKGROUND & AIMS: Two distinct receptors, cholecystokinin (CCK)-A and CCK-B, mediate CCK effects in the digestive system. The aim of this study was to elucidate the cellular sites of expression of CCK-A receptor in the rat stomach and small intestine. METHODS: We developed and characterized an antibody to the N-terminal region (LDQPQPSKEWQSA) of rat CCK-A receptor and used it for localization studies with immunohistochemistry. RESULTS: Specificity of the antiserum was demonstrated by (1) detection of a broad band at 85-95 kilodaltons in Western blots of membranes from CCK-A receptor CHO-transfected cells; (2) cell surface staining of CCK-A receptor-transfected cells, (3) translocation of CCK-A receptor immunostaining in CCK-A receptor-transfected cells after exposure to CCK; and (4) abolition of tissue immunostaining by preadsorbtion of the antibody with the peptide used for immunization. CCK-A receptor immunoreactivity was localized to myenteric neurons and to fibers in the muscle and mucosa. In the stomach, myenteric neurons and mucosal fibers were abundant. Many CCK-A receptor myenteric neurons contained the inhibitory transmitter vasoactive intestinal polypeptide, and some were immunoreactive for the excitatory transmitter substance P. Subdiaphragmatic vagotomy reduced the density of CCK-A receptor fibers in the gastric mucosa by approximately 50%, whereas celiac/superior mesenteric ganglionectomy had no detectable effect on fiber density. CONCLUSIONS: CCK-A receptor is expressed in functionally distinct neurons of the gastrointestinal tract. CCK-A receptor may mediate reflexes stimulated by CCK through the release of other transmitters from neurons bearing the receptor.

Amino Acid Sequence↗

PubMed1999

Detection of loss of heterozygosity on chromosome 9q22.3 in microdissected sporadic basal cell carcinoma.

Identification of loss of heterozygosity (LOH) at specific genetic loci in cancer cells suggests the presence of a tumor suppressor gene within the deleted region. A basal cell carcinoma (BCC) susceptibility gene, human homolog of drosophila patched (PTC), has been recently cloned and localized on chromosome 9q22.3. Mutation and deletion of this region has been reported in BCCs using frozen tumor tissue. The objective of this study was to test whether LOH of human PTC on chromosome 9q22 could be detected in archival sporadic BCCs. We studied 20 randomly selected sporadic BCCs by microdissection and polymerase chain reaction using paraffin-embedded, formalin-fixed material on glass slides. In all cases, analysis was performed with the polymorphic markers D9S53, D9S15, D9S287, and D9S303. The LOH frequencies were 30%, 42%, 56%, and 75% with D9S15, D9S287, D9S53, and D9S303, respectively. LOH at 9q22 was identified in 12 of 20 cases (60%) with at least one marker. Seven cases showed LOH with two markers, two cases with three markers, and one case showed LOH with all four markers. The results indicate that BCC LOH can be frequently identified in paraffin-embedded BCC after routine processing.

Aged↗

PubMed1999

An indwelling brachytherapy balloon catheter: potential use as an intracranial light applicator for photodynamic therapy.

An indwelling balloon applicator developed for postoperative intracavity afterloading brachytherapy was evaluated for photodynamic therapy (PDT). Following tumor resection, the applicator is positioned in the center of the resultant cavity and the balloon is inflated with a scattering solution. The liquid-filled balloon stabilizes the resection cavity ensuring a constant and simple geometric shape during treatment. The catheter is brought out through the skin and adjusted so that 1-2 cm projects above the scalp surface. Measurements of light distribution in a phantom model surrounding the balloon catheter, show that it may be used to deliver sufficiently uniform light doses during PDT. The light distribution is uniform to within 5% when the balloon is filled with a scattering medium. Based on simple assumptions, it is shown that the applicator can be used to deliver a sufficient optical dose to brain tissue at a depth of 1 cm in less than 1 h. The applicator has already been used for brachytherapy in 72 patients with few complications. A new treatment protocol employing the combination of both fractionated intracavity brachytherapy and PDT is currently being planned.

Brachytherapy↗

PubMed1999

The unipolar Shigella surface protein IcsA is targeted directly to the bacterial old pole: IcsP cleavage of IcsA occurs over the entire bacterial surface.

Shigella flexneri is an intracellular pathogen that is able to move within the cytoplasm of infected cells by the continual assembly of actin onto one pole of the bacterium. IcsA, an outer membrane protein, is localized to the old pole of the bacterium and is both necessary and sufficient for actin assembly. IcsA is slowly cleaved from the bacterial surface by the protease IcsP (SopA). Absence of IcsP leads to an alteration in the distribution of surface IcsA, such that the polar cap is maintained and some IcsA is distributed along the lateral walls of the bacillus. The mechanism of unipolar localization of IcsA and the role of IcsP in its unipolar localization are incompletely understood. Here, we demonstrate that cleavage of IcsA occurs exclusively in the outer membrane and that IcsP is localized to the outer membrane. In addition, we show that IcsA at the old pole is susceptible to cleavage by IcsP and that native IcsP is active at the pole. Taken together, these data indicate that IcsP cleaves IcsA over the entire bacterial surface. Finally, we show that, immediately after induction from a tightly regulated promoter, IcsA is expressed exclusively at the old pole in both the icsP- icsA- and the icsA- background. These data demonstrate that unipolar localization of IcsA results from its direct targeting to the pole, followed by its diffusion laterally in the outer membrane.

Actins↗

PubMed1999

Reflectance measurements of layered media with diffuse photon-density waves: a potential tool for evaluating deep burns and subcutaneous lesions.

The basic principles of a non-contact, near-infrared technique for the mapping of layered tissues are discussed theoretically and verified experimentally. The propagation properties of diffuse photon-density waves in tissues depend on the optical properties of the tissue. When a layered medium is irradiated by amplitude modulated light, the difference in optical properties between the layers is evident in the phase and amplitude of the diffuse reflection coefficient, which is a result of the interference of the partial waves propagating in the different layers. Thus, diffuse photon-density waves are applicable to the analysis of the structure of layered tissue. The probing depth is determined by the modulation frequency of the incident light. For modulation frequencies between several hundred megahertz and a few gigahertz, this allows us to analyse the properties of muscle tissue of up to 4-8 mm below the surface. Experimental results based on chicken breast muscle are given. As an example, the technique might be of use for evaluating the depth of necrosis and the blood volume fraction in deep burns.

Animals↗

PubMed1999

Decay-accelerating factor and cytoskeleton redistribution pattern in HeLa cells infected with recombinant Escherichia coli strains expressing Dr family of adhesins.

Escherichia coli strains expressing Dr fimbriae are able to enter epithelial cells by interacting with a complement-regulatory protein, decay-accelerating factor. This model of bacterial internalization, with a well-characterized bacterial ligand and host receptor, provides a unique opportunity to investigate the early stages of invasion. We used immunofluorescence staining techniques to examine the distribution of receptor and cytoskeletal proteins in HeLa cells infected with E. coli recombinant strains that expressed Dr family of adhesins: Dr, Dr-II, F1845, AFA-I, and AFA-III. A major rearrangement of decay-accelerating factor was found at the adherence sites of recombinant strains expressing Dr, Dr-II, and F1845 adhesins. The changes in the distribution of receptor were significantly smaller on HeLa cells infected with E. coli bearing AFA-I or AFA-III afimbrial adhesins. Receptor aggregation was associated with the redistribution of cytoskeleton-associated proteins such as actin, alpha-actinin, ezrin, and occasionally tropomyosin. Purified Dr fimbriae coated on polystyrene beads were capable of triggering clustering of receptor and accumulating actin at the adhesion sites of beads to HeLa cells. Using scanning and transmission electron microscopic techniques, we have shown that beads coated with Dr fimbriae, as opposed to beads coated with bovine serum albumin, were enwrapped by cellular microvilli and ultimately internalized into HeLa cells. This indicates that interaction of Dr fimbriae with decay-accelerating factor is associated with redistribution of receptor and is sufficient to promote bacterial internalization.

Actins↗

PubMed1999

Anteroposterior atlantoaxial subluxation in cervical spine osteoarthritis: case reports and review of the literature.

Nontraumatic anteroposterior atlantoaxial subluxation (AAS) has been described in several rheumatic or inherited disorders, especially rheumatoid arthritis and to a lesser extent the inflammatory spondyloarthropathies. We describe AAS secondary to osteoarthritis (OA) of the cervical spine in a 76-year-old man and a 73-year-old woman with severe cervical OA, symptomatic C1-C2 facet joints, and signs of generalized OA. Only 6 similar cases exist in the literature. OA should be added to the causes of AAS, and conversely AAS should be assessed in cases with severe OA of the upper cervical spine.

Aged↗

PubMed1999

Fibrous dysplasia with intramuscular myxoma (Mazabraud's syndrome). Report of a case and review of the literature.

About 30 cases of fibrous dysplasia associated with one or more myxomas (Mazabraud's syndrome) have been reported since 1926. We report a new case in a woman with polyostotic fibrous dysplasia and a myxoma in the left femoral muscle. She also had a history of precocious sexual development and café au lait spots, two manifestations whose association with polyostotic fibrous dysplasia defines McCune-Albright syndrome.

Adult↗

PubMed1999

Painful swelling of the thigh in a diabetic patient: diabetic muscle infarction.

A 44-year-old woman with a 5-year history of poorly controlled Type 1 diabetes mellitus presented with a painful, firm and warm swelling in her right thigh. Pain was severe but the patient was not febrile, and had no history of trauma or abnormal exercise. Laboratory tests showed ketoacidosis, major inflammation (erythrocyte sedimentation rate (ESR) = 83 mm/h), normal white blood cell count and normal creatine kinase level. Plain radiographs were normal, and there were no signs of thrombophlebitis at Doppler ultrasound. Magnetic resonance imaging (MRI) showed diffuse enlargement and an oedematous pattern of the adductors, vastus medialis, vastus intermedius and sartorius of the right thigh. The patient's symptoms improved dramatically, making biopsy unnecessary, and a diagnosis of diabetic muscular infarction was reached. Idiopathic muscular infarction is a rare and specific complication of diabetes mellitus, typically presenting as a severely painful mass in a lower limb, with high ESR. The diabetes involved is generally poorly controlled longstanding Type 1 diabetes with established microangiopathy. Differential diagnoses include deep vein thrombosis, acute exertional compartment syndrome, muscle rupture, soft tissue abscess, haematoma, sarcoma, inflammatory or calcifying myositis and pyomyositis. In fact, physician awareness should allow early diagnosis on the basis of clinical presentation, routine laboratory tests and MRI, thereby avoiding biopsy and its potential complications as well as unnecessary investigations. Rest, symptomatic pain relief and adequate control of diabetes usually ensure progressive total recovery within a few weeks. Recurrences may occur in the same or contralateral limb.

Adult↗

PubMed1999

Instructional characteristics of online continuing education courses.

OBJECTIVE: The purpose of this study was to determine the instructional characteristics of online continuing dental education courses on the World Wide Web. METHOD AND MATERIALS: One hundred fifty-seven online courses offered by 32 providers were reviewed for 34 criteria. RESULTS: Courses of various types spanned a variety of topics. Approximately half of all courses offered continuing dental education credit. The relationship between credit hours and course length was quite variable. Most courses consisted of text and images. Very few courses used advanced media such as video clips. Measured against an index of instructional quality developed for this study, the instructional quality of the courses, in general, was poor. Most for-credit courses contained self-assessment questions, but only 28% of courses scored the questions online. Basic information that was missing on many courses included the authors' names (29%); the intended audience (81%); goals and objectives (77%); and references (85%). In 47% of the courses, there was no opportunity to provide feedback to either the author or the provider. CONCLUSION: The theoretical advantages of Web-based continuing dental education are numerous, but the currently available online resources are mostly of unacceptable quality.

Computer-Assisted Instruction↗

PubMed1998

Heterogeneity of Atlantic salmon troponin-I.

Three non-identical, full length troponin-I (Tn-I) clones were isolated from an Atlantic salmon myotomal (trunk) muscle cDNA library. The primary structures, which are predicted to range from 172 to 180 amino acids in length, exhibit similar percent identity scores when compared with fast, slow and cardiac specific Tn-Is from higher vertebrates. When the sequence data are considered along with the results of Western blotting it is evident that Tn-I is more heterogeneous in Atlantic salmon than has been previously shown in higher vertebrates.

Amino Acid Sequence↗

PubMed1998

Inflammatory breast carcinoma incidence and survival: the surveillance, epidemiology, and end results program of the National Cancer Institute, 1975-1992.

BACKGROUND: Little is known about the cause of inflammatory breast carcinoma (IBC), the most aggressive form of breast cancer. To the authors' knowledge, no studies have investigated whether IBC risk factors are different from those for breast carcinoma overall, and there has been only one report of IBC incidence and survival patterns. METHODS: The authors used data from the Surveillance, Epidemiology, and End Results program of the National Cancer Institute for the period 1975-1992 to calculate age-adjusted incidence and survival rates for 913 white and 121 African American women with IBC involving dermal invasion of lymphatic ducts and 166,375 white and 13,674 African American women with other types of breast carcinoma (non-IBC). RESULTS: Between 1975-1977 and 1990-1992, IBC incidence doubled, increasing among whites from 0.3 to 0.7 cases per 100,000 person-years and among African Americans from 0.6 to 1.1 cases. However, rates for African Americans varied due to the small numbers of IBC cases. The twofold increase in IBC incidence was higher than that observed for non-IBC during the same period (27% for African Americans and 25% for whites). IBC patients were significantly younger at diagnosis than non-IBC patients; and among both IBC and non-IBC patients, African Americans were younger than whites. Overall survival was significantly worse for IBC patients than for non-IBC patients and for African Americans than for whites. Among whites, 3-year survival improved more for IBC patients than for non-IBC patients between 1975-1979 and 1988-1992, increasing from 32% to 42% for IBC patients (P=0.0001) and from 80% to 85% for non-IBC patients (P=0.0001). CONCLUSIONS: The disparities observed in incidence trends and age at diagnosis, particularly according to race, highlight the need for further investigation of the differences between IBC and non-IBC incidence.

Adenocarcinoma↗

PubMed1998

LOH at 16p13 is a novel chromosomal alteration detected in benign and malignant microdissected papillary neoplasms of the breast.

Papillary carcinoma of the breast is a variant of predominantly intraductal carcinoma characterized by a papillary growth pattern with fibrovascular support. Loss of heterozygosity (LOH) was evaluated at multiple chromosomal loci (including loci reported to show frequent genetic alterations in breast cancer) to determine the frequency of genetic mutations in these tumors and their precursors. Thirty-three papillary lesions of the breast (6 papillary carcinomas, 12 carcinomas arising in a papilloma, and 15 intraductal papillomas with florid epithelial hyperplasia) were retrieved from the files of the Armed Forces Institute of Pathology (AFIP). Tumor cells and normal tissue were microdissected in each case and screened for LOH at INT-2 and p53 as well as several loci on chromosome 16p13 in the TSC2/PKD1 gene region (D16S423, D16S663, D16S665). LOH on chromosome 16p13 was present in 10 of 16 (63%) informative cases of either papillary carcinoma or carcinoma arising in a papilloma as well as in 6 of 10 (60%) informative cases of intraductal papilloma with florid epithelial hyperplasia (IDH). One case showed simultaneous LOH in both the florid IDH and carcinoma components of a papilloma. LOH was not observed at either INT-2 or p53 in any of the papillary carcinomas or papillomas with florid IDH. In conclusion, a high frequency of LOH at chromosome 16p13 (the TSC2/PKD1 gene region) is in both papillary carcinomas of the breast as well as in papillomas with florid IDH, including a case with LOH present simultaneously in both components. These findings suggest that chromosome 16p contains a tumor suppressor gene that frequently is mutated early in papillary neoplasia.

Biomarkers, Tumor↗