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J Philips

Publications and source records attributed to J Philips.

At least 55 records · Page 3Linked to original sources

Features of squamous and adenocarcinoma in the same cell in a xenografted human transitional cell carcinoma: evidence of a common histogenesis?

Ultrastructural features of squamous differentiation have been found in adenocarcinomatous cells in a xenografted line (UCRU-BL-17) established in nude mice from a primary human bladder transitional cell carcinoma (grade III, stage T4) with a tetraploid DNA component. The line has been characterized by light and electron microscopy, flow cytometry and immunocytochemistry. The initial xenograft showed predominantly adenocarcinomatous differentiation with mucin secretion, whilst the subsequent passages also contained cells showing squamous differentiation. A xenograft subline established from a cell culture of the initial xenograft shows the emergence of a population of cells with near triploid DNA, which are less differentiated, grow more quickly, show decreased expression of carcinoembryonic antigen, and a change in the distribution of staining with peanut lectin from cell surface to cytoplasm. These lines offer an unusual opportunity to study the histogenetic relationships between the histological subtypes of bladder cancer.

Adenocarcinoma↗

Stability of lectin binding properties expressed by human bladder carcinoma cell lines passaged in vitro or in nude mice.

Binding of a panel of lectins by sublines of two human bladder carcinoma cell lines, UCRU-BL-17 CL and UCRU-BL-13 CL, assessed flow cytometrically following passage of the cells in vitro and in nude mice, was compared with that of human leukaemic cell lines, K562 and HL60, and found to be different. Marked glycosylation of sublines of both bladder cancer cell lines was found compared with normal human bladder transitional epithelium (assessed cytochemically). Neuraminidase pretreatment increased the binding of some lectins indicating that some galactose and N-acetylgalactosamine residues were sialylated. Lectin binding by UCRU-BL-17 CL sublines was remarkably constant on prolonged passage in vitro even though the lines underwent changes in physical characteristics and ploidy when grown in nude mice. This suggests that glycosylation of the tumour cell surface may represent an intrinsic feature of this bladder tumour.

Animals↗

Applications of the xenograft as a model of invasive transitional cell carcinoma of the bladder.

We have established a series of serially-transplantable xenografts of human bladder cancer which encompass the broad range of histological subtypes of this disease. Substantial heterogeneity has been demonstrated with respect to the ultrastructural and functional characteristics of these lines. We have used this model to explore the histogenesis of the different subtypes of bladder cancer as well as for preliminary studies of novel anti-cancer drugs for this disease. Future studies will characterise further the differences between superficial and invasive tumours and may reveal predictors of their natural history and metastatic potential.

Adenocarcinoma↗

Electron microscopy in the diagnosis of percutaneous fine needle aspiration specimens.

Five years experience in the application of electron microscopy to fine needle aspiration biopsy specimens is reviewed. In an initial evaluation, 200 consecutive unselected specimens were examined; 89 proved diagnostic and, in a third of these, electron microscopy gave additional information that was often essential to diagnosis. Negative specimens resulted almost entirely from failure to obtain an adequate amount of material. Results were improved by the adoption of a preparation technique involving concentration of the cells in bovine serum albumin and by the inspection of a rapidly stained smear at the time of the aspiration procedure, with a further needle pass for electron microscopy being performed if necessary. Despite the small size of specimens, adequate examination was usually possible and electron microscopy has proved of value in the diagnosis of tumor samples acquired by fine needle aspiration in the same way as has been established with the larger sized specimens obtained by conventional biopsy and surgical resection.

Adenocarcinoma↗

Diagnosis of renal allograft rejection by analysis of fine-needle aspiration biopsy specimens with immunostains and simple cytology.

Fine-needle aspiration biopsy specimens of renal transplants were analysed by means of commercially available monoclonal antibodies and an immunoperoxidase stain. Three cellular features associated with acute cellular rejection were identified--heavy infiltrates of activated T cells or large mononuclear cells strongly expressing HLA-DR antigens, and HLA-DR expression by renal tubular cells. A combination of semiquantitative scores for these features correctly identified rejection in 32 of 34 cases, with no false positives in cases of cyclosporin nephrotoxicity or stable graft function.

Antibodies, Monoclonal↗

Extraskeletal Ewing's sarcoma: a clinical, morphological and ultrastructural analysis of five cases with a review of the literature.

In 1969 it was recognised that tumors with light microscopic appearances indistinguishable from Ewing's sarcoma of bone may arise in extraskeletal sites (extraskeletal Ewing's sarcoma). Here, we review the available literature and report five new cases. All five received combined modality therapy with combination chemotherapy and radiotherapy to the primary site followed by surgical excision in two. All attained complete remission; after a median follow-up of 26 months, three remain disease-free but two have relapsed and died. Our experience, in accord with previous series, suggests that extraskeletal Ewing's sarcoma compared with its bony counterpart tends to occur in older subjects, has a similar incidence in males and females, usually presents with a painless mass and readily responds to combined modality therapy. We detected no light or electron microscopic features to denote a histogenetic origin. However, we suspect extraskeletal Ewing's sarcoma may occur more frequently than previously supposed.

Adult↗

Effect of application pressure and gestational age on transfontanel pressure in healthy neonates.

We developed and evaluated a transducer holder and calibrated, spring-loaded applicator for the Ladd intracranial pressure monitor. The transducer holder/applicator combination allows reproducibility of application pressure and assures coplanarity of the transducer and the skin of the anterior fontanel. Measured transfontanel pressure (TFP) increased with increasing application pressure. Mean TFP was 9.1 +/- (SD) 2.6 cm H2O with an application pressure of about 10 g/cm2 in a group of healthy preterm and term infants at 6 h postnatal age. Birth weight, gestational age and mode of delivery did not affect TFP, allowing use of a single normative value and set of confidence limits in all infants at 6 h of postnatal age.

Birth Weight↗

Bladder cancer xenografts: a model of tumor cell heterogeneity.

Twenty bladder biopsies from patients with primary transitional cell carcinoma were inoculated into nude mice. To date, eleven of these have grown as primary implants and three serially transplantable xenograft lines (UCRU-BL-12, UCRU-BL-13, UCRU-BL-14) have been established. The histological and ultrastructural features of human transitional cell carcinoma have been maintained in each line. Despite a relatively uniform histological appearance, several indices of occult tumor heterogeneity have been revealed. Immunocytochemical staining was negative for beta-subunit human chorionic gonadotrophin but positive for carcinoembryonic antigen only in areas of squamous differentiation. All three tumors bound peanut lectin. Flow cytometric DNA analysis of UCRU-BL-13 showed multiple aneuploid peaks, separate populations being demonstrated in different xenografts of the same generation. However, the morphologies of these tumors remained identical. On initial implantation UCRU-BL-12 and UCRU-BL-14 were near diploid but aneuploid populations became apparent with increasing passage number. Each xenograft line caused cachexia in the host mice. Treatment with the cisplatin analogue, isopropyl platinum, ameliorated the cachexia displayed by mice carrying UCRU-BL-14 but did not cause tumor regression. UCRU-BL-12, when tested with cisplatin, isopropyl platinum, and carboplatin, showed equivalent growth retardation with each drug. These xenografted human bladder cancers may be useful models for the study of heterogeneity of the tumor populations in bladder cancer and for the evaluation of new approaches to treatment.

Adult↗

Increased expression of HLA-DR antigens on renal tubular cells in renal transplants: relevance to the rejection response.

Whether the expression of DR antigens is altered in cadaver renal transplants was examined by the use of monoclonal antibodies to the non-polymorphic region of the DR molecule and an indirect immunoperoxidase stain. Expression of DR antigens increased considerably on renal tubular cells in all 25 biopsy specimens which showed severe cellular rejection, but in only 4 of 14 biopsy specimens with no or minimum evidence of rejection. 2 of these 4 specimens were from patients recently treated for severe rejection and the other 2 subsequently lost their grafts from chronic rejection. DR antigens were also expressed on the cell surface of isolated tubular cells aspirated from transplanted kidneys with acute cellular rejection but not on tubular cells in normal kidneys or aspirates from kidneys without rejection. Biopsy specimens with increased DR expression in tubules usually had an interstitial T cell infiltrate. Expression of DR antigens on tubular cells was not related to HLA-DR incompatibility between donor and host, or to the type of immunosuppressive therapy given. The expression of DR antigens on renal tubular cells may be induced by the infiltrating activated T cells or be a consequence of tubular regeneration following rejection or ischaemic damage. The increased expression of DR antigens on renal tubular cells during rejection makes these cells potential targets for delayed type hypersensitivity responses, which are only effective against DR antigen bearing cells.

Adult↗

Measurement of cellular DNA content as an adjunct to diagnostic cytology in malignant effusions.

We reviewed the final diagnosis and outcome of 119 patients who developed serous effusions. In addition to routine cytological examination, the cellular DNA content of fluid samples aspirated from the effusions was measured using flow cytometry in order to determine whether the detection of aneuploid cells could aid in diagnosis or serve as a guide to prognosis. The final diagnosis of 35 patients was non-malignant and a further 40 patients with biopsy-proven cancer had cytologically negative effusions. In all of these cases flow cytometry revealed the presence of diploid cells only. The effusions from 36 cancer patients were reported by cytology to contain a variable proportion of malignant cells, and aneuploid cells were detected in 23 of these samples, the remainder containing only diploid cells. Of 8 effusions where cytology was equivocal, one contained aneuploid cells and clinical outcome subsequently showed that all 8 were malignant. Median survival of patients with cancer was 3 months, and a positive cytology had no influence on survival. However, of the patients with positive cytology, those whose effusions contained aneuploid cells had a poorer short-term prognosis than those cases where only diploid cells could be detected (median survival 1.5 vs 4 months). Measurement of cellular DNA content using flow cytometry can occasionally confirm cancer in a cytologically equivocal effusion, but the negative results in 13 out of 36 (36.1%) effusions where cytology was reported as positive suggests that it has only a limited role in this clinical setting, using currently available techniques.

Aneuploidy↗

Radiologically-guided percutaneous fine needle aspiration biopsies of abdominal and osseous lesions.

The inductions, technique, complications and results of radiologically-guided percutaneous fine needle aspiration biopsy (FNAB) of abdominal and osseous sites performed over a four and a half year period at an Australian tertiary referral hospital are presented. FNAB provided a positive tissue diagnosis for malignancy in 79% of osseous and 78% of abdominal lesions with no false positive diagnoses in either series. Particular problems encountered and the methods employed to overcome them are discussed.

Abdominal Neoplasms↗

Radionuclide angiography in the evaluation of ductal shunts in preterm infants.

Radionuclide angiograms were compared with radiographic and physical findings and with echocardiographic left atrial to aortic ratios in 30 neonates clinically suspected of having a persistent ductus arteriosus. In three infants without clinical signs and with normal LA/Ao ratios (10%), radionuclide angiograms provided evidence of a large left-to-right shunt, which was confirmed by the finding of a large ducts arteriosus at surgery. Whereas routine physical, radiographic, and echocardiographic criteria fail to identify some neonates with large PDA's, the present study suggests that radionuclide angiography can be performed in a neonatal intensive care unit setting and may be a valuable addition to currently employed diagnostic techniques.

Angiography↗

Percutaneous thoracic aspiration needle biopsies.

The results of percutaneous thoracic aspiration needle biopsies in 221 patients performed over a 9-yr study period are presented. Indication for aspiration was a presumptive clinical diagnosis of primary or metastatic carcinoma of the lung or mediastinum. Of the 221 cases, 135 aspirates were reported as positive for malignancy, 26 were suspicious and 60 were diagnosed as negative or unsatisfactory. Follow-up data revealed 140 histologically and/or clinically confirmed cases of malignancy; of these 102 had aspirates diagnosed as positive, 15 as suspicious and 23 as negative. This represents a positive tissue diagnosis for malignancy of 73% from a minimally invasive technique within the study period. No false positive diagnoses were made.

Adenocarcinoma↗

Effects of prostaglandin D2 on perinatal circulation.

Prostaglandin D2 (PGD2) is a powerful antiaggregatory agent and contracts various types of smooth muscle preparations, including isolated canine and bovine pulmonary vessels. Pulmonary vascular responses of anesthetized fetal and adult goats and newborn lambs to PGD2 were evaluated in situ by means of an isolated perfused lower left lobe preparation. These experiments indicate that PGD2 is a pulmonary vasodilator in fetal goats, both a pulmonary vasodilator and vasoconstrictor in newborn lambs depending on the dose used, and a pulmonary vasoconstrictor in adult goats. Evidence is presented of an age-related change in pulmonary vascular response to prostaglandins. The responses of the pulmonary vasculature are dose dependent; however, there is not a significant dose-dependent relationship for systemic arterial pressure or heart rate with intrapulmonary infusions of PGD2. The inhibition of prostaglandin synthesis potentiates the pulmonary response to PGD2 in fetal goats. In contrast with other prostaglandins, PGI2, PGE2, and PGE1, which dilate both the fetal pulmonary and systemic circulations, PGD2 has minimal action on the systemic circulation over a wide range of doses.

Aging↗

Effects of prostacyclin on the fetal pulmonary circulation.

The effects of prostacyclin (PGI2) and its metabolite, 6-keto-PGF1 alpha, on pulmonary and systemic circulations of anesthetized, unventilated fetal goats and sheep were evaluated in situ using an isolated perfused lower left lobe preparation. Results from infusions of PGI2 into the left pulmonary artery suggested dose-dependent decreases in pulmonary vascular resistance (PVR) and mean systemic arterial pressure (SAP). Two-minute infusions produced more pronounced reductions in PVR than 1-minute infusions, and fetal goats exhibited greater depressor responses to PGI2 (2-minute infusions) than fetal lambs. For every 10% decrease in mean pulmonary arterial pressure (PAP), SAP decreased by 3% in sheep receiving 1-minute infusions of PGI2. Systemic hypotensive responses and increases in heart rate were similar in both species. PGI2 appears to be a more powerful dilator of the fetal pulmonary circulation than PGE1 or PGE2; also, intrapulmonary infusions of PGI2 resulted in greater and more sustained systemic hypotensive effects than similar infusions of PGE1 and PGE2. The stable metabolite of PGI2, 6-keto-PGF1 alpha, produced attenuated pulmonary vasodilation. Since PGI2 may produce systemic hypotension, the use of this agent in treatment of persistent pulmonary hypertension should be considered with caution.

6-Ketoprostaglandin F1 alpha↗