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Biomedical subjects

J H Hughes

Publications and source records attributed to J H Hughes.

At least 19 recordsLinked to original sources
PubMed1999

Urinary nuclear matrix protein 22 (NMP22): a diagnostic adjunct to urine cytologic examination for the detection of recurrent transitional-cell carcinoma of the bladder.

This study compares urine nuclear matrix protein 22 (NMP22) immunoassay and conventional urine cytologic examination for detecting recurrent transitional-cell carcinoma (TCC) of the urinary bladder. One hundred twenty-eight urine specimens from 107 patients with a history of TCC of the urinary bladder were studied. NMP22 immunoassay and conventional cytologic examination were performed on each specimen. The NMP22 and cytology results were then compared with the results of subsequent cystoscopies/surgical biopsies performed over a 6-mo follow-up period. The sensitivity of urine cytologic study for predicting recurrent TCC was 60%, while the sensitivity of NMP22 assay was 47%. When both NMP22 assay results and the cytologic interpretation were positive for TCC, the positive predictive value of the combined tests was 74%. When both tests showed negative results, the negative predictive power was 81%. Our findings suggest that urine NMP22 assay may represent a useful diagnostic adjunct to conventional urine cytologic examination for the detection of recurrent TCC of the urinary bladder.

Adult↗
PubMed1999

Nuclear matrix proteins and their potential applications to diagnostic pathology.

The nuclear matrix is the nonchromatin scaffolding of the cell nucleus that confers nuclear shape, organizes the nuclear chromatin, and regulates many important intranuclear biochemical events. Although our understanding of the nuclear matrix and its proteins is still evolving, it is clear that nuclear matrix proteins (NMPs) hold considerable promise as diagnostic tools for pathologists. Early evidence suggests that NMPs may be useful biomarkers of neoplastic disease in serum, body fluids, and tissues. NMPs are also potential candidates for use as tumor prognostic factors and targets of anticancer drugs. Moreover, NMPs may hold the key to understanding important cellular events, such as neoplastic transformation, steroid hormone binding, and apoptosis. Despite impressive gains made by cellular biologists and biochemists toward understanding the structure and function of the nuclear matrix, many of the potential applications of NMPs to diagnostic pathology are largely unexplored. Thus, NMPs should prove an exciting and fruitful area of investigation for experimental and clinical pathologists who are interested in developing diagnostic tests for detecting, quantitating, and characterizing these proteins in human tissues and body fluids and translating these applications into the clinical pathology laboratory.

Antigens, Nuclear↗
PubMed1998

Cytologic criteria for the brush diagnosis of gastric adenocarcinoma.

BACKGROUND: The cytologic diagnosis of gastric adenocarcinoma often is difficult, and the role of gastric brushing in the detection of gastric malignancy is controversial. The purpose of this study was to identify the key cytologic criteria that are most useful for establishing a diagnosis of adenocarcinoma in gastric brushing specimens. METHODS: One hundred gastric brushings were reviewed retrospectively. Fifty of the specimens were obtained from patients with histologically confirmed benign lesions. The other 50 specimens were obtained from patients with histologically confirmed gastric adenocarcinoma. All 100 brushing specimens were reviewed without knowledge of the histologic diagnosis. Each specimen was assessed for the presence or absence of 16 different cytologic features that have been identified in the published literature as being useful for separating benign conditions from malignancy. A multiple logistic linear regression analysis was performed to determine which combination of criteria was the most useful for diagnosing gastric adenocarcinoma. RESULTS: Three key cytologic criteria were identified as being the most useful for diagnosing gastric adenocarcinoma: single atypical cells with intact cytoplasm, eccentric nuclei, and atypical naked nuclei. When at least 2 of these cytologic criteria were present, the sensitivity and specificity for detecting adenocarcinoma were 88% and 100%, respectively. Two minor cytologic criteria also were identified: nuclear hyperchromasia and nuclear molding. CONCLUSIONS: Our statistical analysis demonstrates that gastric adenocarcinoma can be diagnosed with a high degree of accuracy using gastric brushing specimens when specific cytologic criteria are applied.

Adenocarcinoma↗
PubMed1998

The human DEVH-box protein Ski2w from the HLA is localized in nucleoli and ribosomes.

The human helicase gene SKI2W is located between RD and RP1 in the class III region of the major histocompatibility complex. Transcripts of SKI2W are detectable in RNA samples isolated from multiple tissues. The protein product Ski2w shares striking amino acid sequence similarities to the yeast antiviral protein Ski2p that controls the translation of mRNAs, probably based on the mRNA structural integrity. Whether this translational regulation mechanism for cellular and viral RNAs exists in mammals is under investigation. Antisera against human Ski2w were generated using fusion proteins produced in bacteria or insect cells. Western blot analysis showed that the endogenous Ski2w protein is approximately 140 kDa in size and is enriched in polysomal fractions of cytoplasmic extracts from HeLa cells. Ribosomal profile studies revealed that Ski2w distributed throughout the entire sucrose gradient in the presence of Mg2+, but co-sedimented with the 18S rRNA-containing 40S subunit and the small ribosomal subunit protein S27a in the presence of EDTA. The co-sedimentation of Ski2w with the 40S subunit is not affected by RNase A treatment of the cell extract, or the addition of KCl to 0.5 M, suggesting that Ski2w is associated with the 40S ribosomal subunit. Indirect immunofluorescence experiments showed that human Ski2w is localized in the nucleoli and in the cytoplasm. In essence, human Ski2w is present at the sites of ribosome biogenesis and protein synthesis.

Amino Acid Sequence↗
PubMed1998

Blastic variant of mantle-cell lymphoma: cytomorphologic, immunocytochemical, and molecular genetic features of tissue obtained by fine-needle aspiration biopsy.

Mantel-cell lymphoma (MCL) is a rare type of non-Hodgkin's lymphoma that has a moderately aggressive clinical course, generally between that a low-grade and intermediate-grade lymphomas. However, a small subset of MCLs, the so-called "blastic" variant, exhibits a poor prognosis and an aggressive clinical course. We describe a case of blastic MCL that occurred in a 64-yr-old man and that was diagnosed and accurately subclassified as blastic MCL on the basis of an fine-needle aspiration (FNA) biopsy. The aspirate smears showed a monotonous population of intermediate-sized lymphocytes with irregular nuclear contours, finely dispersed nuclear chromatin, and inconspicuous nucleoli. Material was obtained by FNA for ancillary studies (immunocytochemical stains, flow cytometry, cytogenetics, image analysis, and molecular studies) that supported the diagnosis of blastic MCL. Surgical biopsy confirmed the diagnosis. These findings underscore the utility of FNA in diagnosing lymphomas, particularly when the cytomorphologic examination is combined with appropriate ancillary studies.

Biopsy, Needle↗
PubMed1998

Fine-needle aspiration cytology of mediastinal non-Hodgkin's nonlymphoblastic lymphoma.

BACKGROUND: The histologic features of primary mediastinal non-Hodgkin's nonlymphoblastic lymphoma (NHL) are well described in the surgical pathology literature. However, the fine-needle aspiration (FNA) cytology of these lesions has not been characterized thoroughly. METHODS: FNA material from 12 patients with primary mediastinal NHL was reviewed. The series was comprised of 7 men and 5 women with a mean age of 42 years (age range, 26-65 years). All 12 patients underwent a mediastinal FNA as the initial step in their diagnostic evaluation. In some cases, flow cytometry or immunocytochemical studies were performed on the FNA material to render a definitive diagnosis. RESULTS: On the basis of the cytomorphologic findings and ancillary studies performed on the FNA material, a diagnosis of malignant lymphoma (five cases), consistent with/suspicious for malignant lymphoma (four cases), or nondiagnostic/negative for lymphoma (three cases) was rendered for each case. In general, a definitive diagnosis of malignancy was established when there was cytomorphologic evidence of lymphoma and a monoclonal lymphoid population could be demonstrated by immunocytochemistry. Eleven of the 12 primary mediastinal non-Hodgkin's lymphomas were large cell lymphomas (LCL), and 1 was a composite lymphoma (LCL and Hodgkin's disease). In three of the LCL cases the neoplastic cells exhibited prominent nuclear hyperlobation in association with sclerosis. CONCLUSIONS: A diagnosis of primary mediastinal NHL can be established with a high degree of accuracy on the basis of FNA cytology. The FNA cytomorphology of primary mediastinal NHL correlates with the spectrum of morphologic diversity associated with this entity in the surgical pathology literature.

Adult↗
PubMed1998

Is the cytologic diagnosis of esophageal glandular dysplasia feasible?

Barrett's esophagus is a premalignant condition in which the normal stratified squamous epithelium of the esophagus is replaced by metaplastic glandular epithelium. Patients with Barrett's esophagus are at increased risk for the development of esophageal adenocarcinoma. Because dysplasia precedes the development of frank adenocarcinoma, the cytologic detection of esophageal glandular dysplasia represents a potentially inexpensive and efficient means of monitoring disease progression to adenocarcinoma and identifying high-risk patients. This article discusses the current status of exfoliative cytology as a screening test for glandular dysplasia of the esophagus.

Barrett Esophagus↗
PubMed1998

Rhinovirus replication in HeLa cells cultured under conditions of simulated microgravity.

BACKGROUND: Rotating-wall vessels (RWVs) allow for the growth of cells under conditions of simulated microgravity. Information about the replication of viruses in simulated microgravity using RWVs has not been reported. Cells grown in RWVs are subjected to low shear motion, and the replication of certain viruses such as rhinoviruses has been reported to be enhanced by motion. HYPOTHESIS: Our research was based on the hypothesis that rhinovirus replication would be enhanced under conditions of simulated microgravity. METHODS: HeLa cells were cultured in three-dimensional cultures on microcarrier beads in simulated microgravity using RWVs and in sealed Teflon roller bottles. Two-dimensional cultures of HeLa cells were also grown in tissue culture flasks (T-150s). Viral infections for all cultures were carried out under standardized conditions at 1 x g. The amount of new virus released during the first viral replication cycle and the total viral yields obtained from multiple viral replication cycles were determined. RESULTS: Viral quantitation during the first viral replication cycle showed that after 10-13 h RWV and Teflon roller bottle supernatants contained significantly more virus than the supernatants from T-150 cultures. After multiple viral replication cycles (at 24, 48, 72, and 96 h following infection), total viral samples (both free and cell-associated virus) from RWV cultures contained significantly more virus than Teflon roller bottle cultures. CONCLUSIONS: The rhinovirus replication cycle was enhanced in cultures grown in the presence of motion (Teflon roller bottle cultures and RWV cultures). Additionally, multiple rounds of rhinovirus replication yielded more virus in simulated microgravity conditions. Viral transmission in cell cultures in RWVs was efficient and was similar to or better than what occurred in the Teflon roller bottles. The cultivation of cells in simulated microgravity possibly affected the rate of viral adsorption/uptake, the viral replication cycle, and/or the viral yield. RWVs provide an effective means for culturing human rhinoviruses.

Cell Culture Techniques↗
PubMed1997

Primary intrathyroidal paraganglioma with metachronous carotid body tumor: report of a case and review of the literature.

A case of primary intrathyroidal paraganglioma is reported, and the light microscopic and immunohistochemical findings are described. Primary paragangliomas of the thyroid region are extremely uncommon and are therefore often confused clinically and histopathologically with more common intrathyroidal mass lesions. The diagnostic difficulties are underscored by the present case, which was misdiagnosed twice, firstly as a medullary thyroid carcinoma and secondly as a follicular thyroid carcinoma. Immunohistochemistry may be very helpful in arriving at the correct diagnosis. The case was further complicated by a second neck mass contralateral to the original thyroid nodule, which was interpreted as consistent with metastasis. The second lesions was proved angiographically and histologically to be a carotid body paraganglioma.

Adult↗
PubMed1997

Sensitivity and cost-effectiveness of fine-needle aspiration with immunocytochemistry in the evaluation of patients with a pulmonary malignancy and a history of cancer.

OBJECTIVE: To determine the sensitivity and cost-effectiveness of transthoracic fine-needle aspiration in the separation of primary from metastatic malignancy. MATERIALS AND METHODS: Eighty-nine malignant pulmonary fine-needle aspirations in patients with a history of cancer were classified retrospectively by light microscopy, comparison with previous material, and immunocytochemistry. Decision analysis compared the cost-effectiveness of fine-needle aspiration, bronchoscopy, and thoracoscopy. RESULTS: Fine-needle aspiration classified 87% of the malignancies as primary (n = 7) or metastatic (n = 70) and 13% as indeterminate. By immunocytochemistry alone, 14 of 18 malignancies were subclassified. Decision analysis showed that pulmonary fine-needle aspiration with select use of thoracoscopy was more cost-effective than either bronchoscopy or thoracoscopy alone in many common clinical scenarios. CONCLUSIONS: Pulmonary fine-needle aspiration with immunocytochemistry is sensitive and cost-effective in subclassifying malignancies in patients with a history of cancer.

Adult↗
PubMed1996

Multicystic nephroma: report of a case with fine-needle aspiration findings.

This report presents the fine-needle aspiration biopsy (FNAB) findings of a multicystic renal tumor in a 52-yr-old woman. The aspirate smears contained clusters of cells with large, irregular nuclei and cytoplasmic vacuoles. Subsequent nephrectomy revealed a multicystic nephroma (MCN). Although most common in childhood, MCN should always be considered in the FNAB differential diagnosis of a multicystic renal mass in adult patients. Even in cases where the diagnosis of MCN is considered, it may be difficult to distinguish from cystic renal cell carcinoma on the basis of radiographic and FNAB findings.

Biopsy, Needle↗
PubMed1996

Adenosquamous carcinoma of the bile duct: cytologic features of brush specimens from two cases.

Cytologic brushing is a safe and specific procedure for diagnosing carcinoma of the distal bile duct and proximal pancreatic duct. The vast majority of these lesions are pure adenocarcinomas. Occasionally, however, other morphologic subtypes may be encountered. We report our experience with two adenosquamous carcinomas of the bile duct diagnosed by cytologic brushing. Both patients presented clinically with jaundice and were found to have mass lesions obstructing the bile duct. The brush specimens were cellular and contained a mixture of glandular and squamous elements. The glandular component was characterized by cohesive aggregates of cells with hyperchromatic, overlapping nuclei. The squamous component contained clusters and individual cells with hyperchromatic oval-to-spindled nuclei and orangeophilic cytoplasm. Focally, the squamous elements appeared to gradually merge into the glandular component, and there were clusters of hybrid cells which were difficult to classify as squamous or glandular. Although uncommon, these 2 cases demonstrate that the cytologic features of adenosquamous carcinoma can be appreciated on cytologic brushing specimens.

Aged↗
PubMed1996

Fine-needle aspiration of the pancreas.

In patients with a palpable or radiographically identified pancreatic lesion, FNA is a safe and accurate procedure for procuring diagnostic tissue. Complications of the procedure are rare, and the morbidity and mortality are considerably less than that associated with open laparotomy and wedge biopsy. The most common complication associated with pancreatic FNA is acute pancreatitis. Contraindications to FNA include an uncorrectable bleeding diathesis, marked ascites, and suspected hydatid cyst. The accuracy of FNA for diagnosing pancreatic adenocarcinoma is about 80%, and the overall sensitivity can be increased by multiple needle passes. Close communication and collaboration among the clinician, radiologist, and pathologist can help assure that suitable tissue is obtained and maximize the diagnostic yield of the procedure. To this end, the presence of the pathologist or a cytotechnologist at the FNA procedure is desirable to assess the tissue as it is procured. The vast majority of malignant pancreatic neoplasms are ductal adenocarcinomas. Thus, the primary diagnostic problem facing the pathologist is differentiating adenocarcinoma from benign and/or inflammatory processes. The three key cytologic features that aid in this distinction are anisonucleosis, increased nuclear size, and nuclear molding. When all three of these features are present, the sensitivity of the procedure approaches 98%, and its specificity approaches 100%.

Biopsy, Needle↗
PubMed1995

Topical anaesthesia for the insertion of nasogastric tubes.

The effect of topical anaesthesia on the discomfort caused by insertion of nasogastric tubes in conscious patients was assessed. An intra-nasal spray of 4% lignocaine significantly reduced the distress experienced without any increase in difficulty (P < 0.01).

Administration, Intranasal↗
PubMed1995

p53 immunoreactivity in primary and metastatic prostatic adenocarcinoma.

p53 is a tumor suppressor protein that is overexpressed in a variety of human neoplasms, including prostatic adenocarcinoma. Recent studies have demonstrated a significant positive correlation between extent of p53 overexpression and tumor grade in prostatic adenocarcinoma. Because it appears that mutations of p53 might play a role in the pathogenesis of a subset of biologically aggressive prostatic neoplasms, we sought to examine the frequency of p53 overexpression in primary and metastatic prostatic adenocarcinoma. Using a monoclonal antibody (D07) directed against both the wild-type and mutant forms of p53, we examined p53 immunoreactivity in 36 cases of primary prostatic adenocarcinoma, 17 cases of metastatic prostatic adenocarcinoma involving lymph nodes and 15 cases of metastatic prostatic adenocarcinoma involving bone. Twenty-eight percent (10/36) of the primary tumors displayed nuclear staining for p53. Increased p53 immunoreactivity was observed in only 6% (1/16) of prostatic adenocarcinomas with a total Gleason score of 6 or less, as compared with 45% (9/20) of those adenocarcinomas with a Gleason score of 7 or more. Fifty-nine percent (10/17) of the lymph node metastases and 43% (6/14) of the bone metastases displayed nuclear immunoreactivity for p53. Our results indicate that increased p53 expression is positively correlated with increased histologic grade and with the presence of metastatic disease in patients with prostatic adenocarcinoma, and they suggest that mutations of the p53 gene may play a role in mediating the behavior of a biologically aggressive subset of this common neoplasm.

Adenocarcinoma↗
PubMed1995

p53 expression in Bowen's disease and in microinvasive squamous cell carcinoma of the skin.

p53 is a tumor suppressor gene whose protein product is overexpressed in several human tumors. In this study we used a monoclonal antibody (DO7) direct against p53 and a previously described antigen retrieval methodology to examine p53 expression in 27 cases of microinvasive squamous cell carcinoma of the skin and in 10 cases of Bowen's disease. Immunohistochemical studies were performed on formalin-fixed, paraffin-embedded tissue sections that had been microwave-heated to improve antigenicity. Positive nuclear staining for p53 was observed in 23 of 27 (85%) cases of microinvasive squamous cell carcinoma and in five of 10 (50%) cases Bowen's disease. With the exception of occasional focal positive staining of basal layer cells, no p53 immunoreactivity was observed in normal skin. Our results demonstrate that increased expression of the p53 protein is a common finding in both in situ and microinvasive squamous cell carcinoma of the skin, and they suggest that loss of normal p53 tumor suppressor activity may be an important mechanism of oncogenesis in these neoplasms.

Bowen's Disease↗