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Biomedical subjects

P Shaw

Publications and source records attributed to P Shaw.

At least 19 recordsLinked to original sources
PubMed1992

Induction of apoptosis by wild-type p53 in a human colon tumor-derived cell line.

A wild-type p53 gene under control of the metallothionein MT-1 promoter was stably transfected into human colon tumor-derived cell line EB. Repeated inductions of the metallothionein wild-type p53 gene with zinc chloride results in progressive detachment of wild-type p53 cells grown on culture dishes. Examination at both the light and electron microscopic level revealed that cells expressing wild-type p53 developed morphological features of apoptosis. DNA from both attached and detached cells was degraded into a ladder of nucleosomal-sized fragments. Expression of wild-type p53 inhibited colony formation in soft agar and tumor formation in nude mice. Furthermore, established tumors in nude mice underwent regression if wild-type p53 expression was subsequently induced. Regressing tumors showed histological features of apoptosis. Thus, regression of these tumors was the result of apoptosis occurring in vivo. Apoptosis may be a normal part of the terminal differentiation program of colonic epithelial cells. Our results suggest that wild-type p53 could play a critical role in this process.

Base Sequence↗
PubMed1992

Intraperitoneal therapy of malignant ascites associated with carcinoma of ovary and breast using radioiodinated monoclonal antibody 2G3.

A phase I/II study of intraperitoneal (ip) radioimmunotherapy was conducted in ovarian or breast cancer patients with symptomatic chemotherapy-resistant ascites using a novel anti-mucin monoclonal antibody (mAb) 2G3 labeled with 131I. Tracer doses of 2 mCi [131I]2G3 were given by ip injection to 11 patients, followed by increasing therapeutic doses up to 150 mCi (cumulative) in 9 patients. There was no serious toxicity. Temporary palliation of ascites was observed in 3 of 4 patients who received doses greater than 50 mCi. Total body elimination half-life of the radiolabeled antibody assessed by gamma scintigraphy ranged from 95 to 250 hr, longer than data previously reported in patients without ascites treated with ip administered radiolabeled antibodies. However, uptake of radiolabel by tumor nodules was small and variable (2 x 10(-4) - 2 x 10(-2) % ID/g), and preferential uptake by tumor compared to normal peritoneum was observed in only 2 of 5 patients in whom biopsies were obtained. These results suggest that the observed palliation of ascites is due to prolonged retention of radiolabeled antibody in the peritoneal cavity even in the absence of specific targeting.

Adult↗
PubMed1992

The value of CT scanning and percutaneous fine needle aspiration of adrenal masses in biopsy-proven lung cancer.

Pre-operative CT scans of 546 patients with biopsy-proven primary bronchial carcinoma were reviewed. Twenty-two patients had a solid adrenal tumour (2 bilateral). Sixteen underwent percutaneous fine needle aspiration (FNA). Malignant cells were aspirated in five, eight revealed benign cells and in three cases there was insufficient material for diagnostic purposes. Six patients did not undergo FNA, four of these were considered to have benign adenomas on CT. This was confirmed by the unchanged CT image at more than 21 months follow-up. The five subjects with FNA-proven metastases died at a median of 14 months (range 3-24 months). All five would have been regarded as operable on their staging chest CT scan. Five patients with a negative biopsy underwent surgery, two died of metastases at 6 and 11 months respectively and one died of post-operative complications. The other two have unchanged adrenal lesions on CT at 9 months and 25 months. The CT appearances of these lesions were analysed. Well defined, low attenuation lesions which had a smooth attenuation rim or only involved part of the gland were benign and the survivors had unchanged CT appearances at follow-up (six lesions in five patients). Of these four lesions were less than or equal to 2 cm in diameter. Low attenuation lesions without a rim were malignant (n = 2). These latter both measured more than 2 cm in diameter. The CT appearances of many adrenal lesions were insufficiently distinctive to exclude malignancy and biopsy was necessary to establish a diagnosis.

Adrenal Gland Neoplasms↗
PubMed1992

Self-reported sleep quality in college students: a repeated measures approach.

A longitudinal assessment of sleep quality is presented. Undergraduates provided two levels of repeated measures data. Sleep log information was gathered across the 7 days of the week, in three replications, over a semester. There were several new findings. Across the week, students spent significantly more time in bed on weekend days as compared with weekdays. Further, a new measure for quality of sleep covaried with the amount of time spent in bed during the week. The students enjoyed their sleep more on the weekends. Finally, both the amount of time in bed and the number of awakenings reported dropped significantly as the semester progressed.

Adolescent↗
PubMed1991

Occurrence of Ki-ras and p53 mutations in primary colorectal tumors.

Twenty-four colorectal tumors and their paired mucosa were examined for allele loss on chromosomes 5 and 17, using polymerase chain reaction-amplified DNA, and for mutations in the Ki-ras and p53 genes. In addition, 19 benign polyps were analysed for mutations in the p53 gene. RFLP analysis of the long arm of chromosome 5 indicated an allele loss frequency of 47% for malignant tumors, a value somewhat higher than previously observed. Examination of the short arm of chromosome 17 indicated an allele loss of 60%. Sequence analysis of the p53 gene in colorectal tumors indicated that 64% contained a mutation. All tumors showing allele loss on chromosome 17 were mutant for p53, suggesting that mutation of one p53 allele precedes the hemizygotic loss of the wild-type allele. Sequence analysis of the p53 gene in 19 benign polyps, devoid of severe dysplasia, did not reveal any mutants, suggesting that the mutation of one p53 allele is an event that takes place after polyp formation. Ki-ras mutations were observed in 48% of the tumors examined. All tumors which were mutant for Ki-ras, except for one, were also mutant for p53.

Blotting, Northern↗
PubMed1990

Detection of Epstein-Barr virus DNA by polymerase chain reaction in lymph node biopsies from patients with angioimmunoblastic lymphadenopathy.

Epstein-Barr virus DNA was detected by the polymerase chain reaction (PCR) in five lymph node biopsies from eight patients with diagnosis of angioimmunoblastic lymphadenopathy (AILD). Three pairs of specific primers detected EBV DNA sequences near the 5' end (Bam W region), the middle (BMRF 1 region) and the 3' end (Eco RI D region) of the viral genome with equal accuracy when 1 microgram of DNA and 30 amplification cycles were used. When only 100 ng of DNA were screened with the BMRF 1 set of primers, a specific amplification product was still identifiable. The 593 base pair amplification product obtained using the Eco RI D set of primers was shown to contain an expected Sma I site at position 215, confirming the viral origin of the amplified sequence [corrected]. Our findings indicate that lymph nodes of AILD patients frequently harbour the entire EBV genome at a high percentage of at least 1 viral copy per 15,000 human cells.

Base Sequence↗
PubMed1990

Ascitic fluid from human ovarian cancer patients contains growth factors necessary for intraperitoneal growth of human ovarian adenocarcinoma cells.

Human ovarian cancer, the leading cause of death from gynecologic malignancy, tends to remain localized to the peritoneal cavity until late in the disease. In established disease, ascitic fluid accumulates in the peritoneal cavity. We have previously demonstrated that this ascitic fluid is a potent source of in vitro mitogenic activity including at least one unique growth factor. We now report that the human ovarian adenocarcinoma line, HEY, can be induced to grow intraperitoneally in immunodeficient nude mice in the presence (23/28 mice), but not absence (0/21 mice) of ascitic fluid from ovarian cancer patients. Ascitic fluid from patients with benign disease did not have similar effects on intraperitoneal growth of HEY cells (1/15 mice). Once tumors were established by injections of exogenous ascitic fluid, they could progress in the absence of additional injections of ascitic fluid. The mice eventually developed ascitic fluid which contained potent growth factor activity, suggesting that the tumors eventually produced autologous growth factors. This nude mouse model provides a system to study the action of ovarian cancer growth factors on tumor growth in vivo and to evaluate preclinically, therapeutic approaches designed to counteract the activity of these growth factors.

Animals↗
PubMed1990

Comparison of 99Tcm dimercaptosuccinic acid scans and intravenous urography in children.

A retrospective comparison of 99Tcm dimercaptosuccinic acid (DMSA) scans and intravenous urograms (IVUs) was performed on a large, unselected paediatric population to assess critically the relative merits of these two techniques. A total of 205 children were studied, providing 388 kidneys for comparison. The studies agreed in 81%, both being normal in 39%, and both abnormal in 42%. In 28 kidneys (7%), the IVU was abnormal when the 99Tcm DMSA was normal. There was a collecting system abnormality in 27 kidneys, but 10 kidneys also showed a parenchymal abnormality. In all these the parenchymal abnormality was global thinning on the IVU, and the contralateral kidney was small. In 40 kidneys (10%) the 99Tcm DMSA was abnormal when the IVU was normal: the abnormalities demonstrated were predominantly focal defects. After excluding IVUs of poor diagnostic quality, only 14 kidneys (3.6%) showed this disparity. The important clinical subgroups are infection, with or without reflux (27 kidneys), hypertension (4) and neonates with poor renal function (2). The one false positive 99Tcm DMSA was a result of an anatomical variant. Global thinning in a "normal" kidney on a 99Tcm DMSA scan may be overlooked when the contralateral kidney is poorly functioning and small.

Adolescent↗
PubMed1989

Laser angioplasty with a pulsed NdYAG laser: early clinical experience.

Since December 1986, 40 laser angioplasty procedures have been performed using the energy from a pulsed NdYAG laser, delivering near infrared light (1064 nm) in 100-microseconds pulses of approximately 300 mJ per pulse, directly through a transparent sapphire tipped device. All patients had total occlusion of the superficial femoral artery and symptoms severe enough to warrant surgery, with ulceration or gangrene in eight, rest pain in 14 and severe claudication interfering with life-style in the others. The device was introduced through an antegrade puncture of the superficial or common femoral artery and laser recanalization was followed by attempted balloon angioplasty in all cases. Occlusions were a median length of 15 cm (range 2-35 cm); ten patients had previously undergone failed attempts at conventional balloon angioplasty and four had occluded femoropopliteal grafts. Thirty-seven legs of 34 patients were treated with an average of 60 J (range 10-235 J) with successful recanalization in 27 and immediate reocclusion in seven. The 20 successful recanalizations have been followed up for up to 24 months (median 7 months) with only one late occlusion at 5 months. Failed recanalization was due to poor transmission by the delivery device in the early part of the series (five cases), repeated passage of the device down a collateral branch (four cases), dissection at the site of previous surgery (two cases) or no apparent reason (two cases). Immediate reocclusion was due to very poor run off in patients with severely ischaemic limbs (three cases) or technical difficulties with balloon dilatation (two cases). Complete symptomatic relief was obtained in all the cases of radiologically successful laser angioplasty. Early surgery was required in one case following reocclusion of the artery when an angioplasty balloon failed to deflate, and one patient suffered a skin reaction thought to be due to inadequate removal of the sterilizing solution. A different sterilizing procedure is now followed. Laser angioplasty can reduce the number of patients requiring bypass surgery and improvements in the device and access methods may reduce the number of untreatable cases.

Adult↗
PubMed1989

Diagnostic fine needle core biopsy of deep lymph nodes for the diagnosis of lymphoma in patients unfit for surgery.

The use of a technique for safe percutaneous fine needle biopsy of inaccessible lymph nodes is described. In a prospective study of 24 patients, including five cases positive for the human immunodeficiency virus (HIV), this technique was used to provide diagnostic material. A firm diagnosis was made in 21 cases; four cases of Hodgkin's disease, 14 non-Hodgkin's lymphomas, one case of Kaposi's sarcoma, one case of mycobacterial infection, and one which showed the features of persistent generalized lymphadenopathy (PGL). In the cases of lymphoma, available serial sections allowed characterization of the tumour with immunocytochemistry. In three cases, no diagnosis could be made, with one of these requiring a subsequent open biopsy. Percutaneous fine needle biospy is ideal for patients unfit or unsuitable for general anaesthesia or surgery. The biopsy obtained gives the pathologist sufficient tissue for an accurate diagnosis in the majority of cases. The preservation of architecture and multiple sections available are advantages over fine needle aspiration.

Adult↗
PubMed1989

Fluorescence microscopy in three dimensions.

The combination of the specificity provided by fluorescence microscopy and the ability to quantitatively analyze specimens in three dimensions allows the fundamental organization of cells to be probed as never before. Key features in this emergent technology have been the development of a wide variety of fluorescent dyes or fluorescently labeled probes to provide the requisite specificity. High-quality, cooled charge-coupled devices have recently become available. Functioning as nearly ideal imagers or "electronic film," they are more sensitive than photomultipliers and provide extraordinarily accurate direct digital readout from the microscope. Not only is this precision crucial for accurate quantitative imaging such as that required for the ratioing necessary to determine intracellular ion concentrations, but it also opens the way for sophisticated image processing. It is important to realize that image processing isn't simply a means to improve image aesthetics, but can directly provide new, biologically important information. The impact of modern video microscopy techniques (Allen, 1985; Inoué, 1986) attests to the fact that many biologically relevant phenomena take place at the limits of conventional microscopy. Image processing can be used to substantially enhance the resolution and contrast obtainable in two dimensions, enabling the invisible to be seen and quantitated. Cells are intrinsically three-dimensional. This can simply be a nuisance because of limited depth of focus of the microscope or it could be a fundamental aspect of the problem being studied. In either case, image processing techniques can be used to rapidly provide the desired representation of the data. In this chapter we have discussed the nature of image formation in three dimensions and dealt with several means to remove contaminating out-of-focus information. The most straightforward of these methods uses only information from adjacent focal planes to correct the central one. This approach can be readily applied to virtually any problem and with most commonly available image processing hardware to provide a substantially deblurred image in almost real time. In addition to covering more sophisticated algorithms where the utmost in three-dimensional imaging is required, we have developed a method for extremely rapidly and accurately producing an in-focus, high-resolution "synthetic projection" image from a thick specimen. This is equivalent to that produced by a microscope having the impossible combination of a high-NA objective lens and an infinite depth of focus. A variation on this method allows efficient calculation of stereo pairs.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

51Cr-EDTA/99Tcm-MDP ratio: a simple non-invasive method for assessing renal osteodystrophy.

We have used 99Tcm-MDP to develop a measure of overall skeletal activity for use in renal disease. The method utilizes the relative clearances of 99Tcm-MDP and 51Cr-EDTA from the blood after simultaneous injection. This is expressed as a ratio and the upper limit in normals is 1.4. This ratio has been evaluated in 42 patients with chronic renal failure and compared with appearances of left-hand radiographs. The ratio was elevated in these patients and the level corresponded to the degree of severity of the subperiosteal resorption. Similarly, there was a close correlation between the ratio values and the serum alkaline phosphatase measurements and parathyroid hormone values. Thirty-three patients had sequential studies performed at intervals of up to 2 years. Twenty-one patients showed no change on clinical, biochemical or bone scan evaluation. Of these, only one patient showed a change in ratio value of greater than 20%. Twelve patients showed evidence of change based either on clinical, biochemical or bone scan alteration and all 12 patients showed changes in ratio values greater than 20%. The 51Cr-EDTA/99Tcm-MDP ratio appears to offer not only a single plasma sample method for the detection and evaluation of renal bone disease, but our results also suggest that it may be valuable in the follow-up of these patients.

Chromium Radioisotopes↗
PubMed1988

The use of antipyrine clearance to measure liver damage in psoriatic patients receiving methotrexate.

Salivary antipyrine clearance was measured in 15 patients with psoriasis receiving methotrexate and related to liver biopsy changes and routine liver function tests, to determine whether antipyrine clearance could be used as a non-invasive method for monitoring liver function. Comparison of the salivary antipyrine clearance in the methotrexate group (mean 0.51 ml/min/kg, range 0.26-0.81) with 15 matched psoriatic controls (mean 0.54 ml/min/kg, range 0.34-0.99) showed no significant difference. Liver biopsy changes were scored for fatty change, fibrosis, liver cell necrosis and portal tract infiltrate. Total liver biopsy scores correlated significantly with antipyrine clearance/kg body weight (r = -0.72, P less than 0.05). There was no significant correlation of total liver biopsy scores with the other liver function tests. Correlation of the individual liver biopsy changes and antipyrine clearance showed a significant correlation with fatty change (r = -0.75, P less than 0.01), but not with fibrosis (r = -0.53), liver cell necrosis (r = -0.54) or infiltrate (r = -0.41).

Adult↗
PubMed1988

Reactivity of tumor cells in malignant effusions with a panel of monoclonal and polyclonal antibodies.

A panel of 13 mouse monoclonal antibodies (mAb) and 1 rabbit polyclonal antibody was tested for reactivity with tumor cells in 26 effusions obtained from patients with carcinoma of ovary, breast, or mesothelioma, using an immunoperoxidase staining reaction. Specific staining of tumor cells but not reactive mesothelial cells was demonstrated with some of the mAb in the panel. In 4 of 26 effusions no evidence of malignancy was obtained after routine cytological staining, but this was reversed on the basis of immunoperoxidase staining of tumor cells with the mAb in the panel. Serial effusions were evaluated in 4 patients during the course of chemotherapy, allowing an assessment of effect of therapy on the antigenic characteristics of the tumor cells. In another 4 patients, the results of immunoperoxidase staining of effusions were compared with those obtained by applying the same antibody panel to solid tumor nodules. There was a tendency to develop changes in the pattern of reactivity during therapy, and the pattern of reactivity was more restricted in tumor nodules than in effusions. One of the mAb in our panel (2G3) was consistently shown to produce strong staining of a high proportion of tumor cells in effusions and tumor nodules from patients with ovarian or breast cancer and may be of value in immunocytochemical diagnosis and therapy of epithelial malignancies.

Animals↗