Positron emission tomography of 18FDG uptake in localized pulmonary inflammation.
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Animals↗
Biomedical subjects
T Krausz
Publications and source records attributed to T Krausz.
The partial purification and characterization of GnRH-like activity from prostatic biopsy specimens and prostatic cancer cell lines.
We have investigated the possibility of the secretion of gonadotrophin-releasing-hormone (GnRH)-like peptides by prostatic cancer cells in culture and their presence in cytosolic preparations from human prostatic biopsy specimens. A GnRH-specific radioimmunoassay showed GnRH-like activity in concentrated cytosolic preparations and conditioned media from DU 145, an androgen-insensitive human prostatic cell line and from LNCaP, an androgen-responsive prostatic cancer cell line. GnRH immunoreactivity in culture media correlated directly with cell numbers. HPLC demonstrated that this GnRH-like material co-migrated with synthetic GnRH. This homology between synthetic GnRH and partially purified prostatic GnRH was confirmed following V8 protease and trypsin digestion which resulted in similar alterations in HPLC characteristics. The mean content of GnRH-like activity/g specimen tissue was significantly more in malignant tissue (88.5 +/- 80.5 fmol) than in benign (29.6 +/- 22 fmol), though more specimens of benign tissue were positive (37/54) than malignant tissue (6/22). This observation, taken with an earlier finding of GnRH-specific receptors in a hormone-sensitive cell line and human cancer specimens provides supportive evidence for the autocrine hypothesis of cell regulation.
Gonadotropin-Releasing Hormone↗
Type IV collagen in developing human lung: a comparison between normal and hypoplastic fetal lungs.
Human lung tissue obtained from 24 aborted fetuses of varying gestational ages (beyond 24 weeks) was examined for immunolocalisation of type IV collagen, using monoclonal antibody. Twelve cases of lung hypoplasia associated with oligohydramnios were compared with 12 normally developed lungs over the same gestational age range acting as control. Type IV collagen was located in alveolar septa and subepithelial basement membranes in all the lungs examined but showed less prominently in hypoplastic lungs than in control lungs of a similar gestational age. The findings suggest a potential role of type IV collagen in maturation of the developing human lung.
Amniotic Fluid↗
Evaluation of fine needle aspiration of the male breast for the diagnosis of gynaecomastia.
Fine needle aspiration of the male breast can present problems of diagnosis because the cytological presentation of gynaecomastia can be confused with that of adenocarcinoma. We reviewed breast aspirates from 24 male patients in order to determine the accuracy of cytology as a method of diagnosing gynaecomastia. Discrepancies were observed between the original cytology reports on one hand and the review cytology and biopsies on the other. Of the 24 aspirates from the male breast, the cytology was reported as negative in 16 cases, suspicious in three cases and malignant in five. In four cases of the negative group, a specific diagnosis of gynaecomastia was made. In two of the negative cases the subsequent biopsies revealed adenocarcinoma. Of the five cases reported on the original cytology as adenocarcinoma, two on review showed the features of florid gynaecomastia and this was confirmed on biopsy and three confirmed the initial diagnosis of adenocarcinoma. The cytological features of gynaecomastia which distinguish it from adenocarcinoma are discussed.
Adenocarcinoma↗
Reliability of colposcopy and directed punch biopsy.
A group of 118 women underwent laser cone biopsy. Data were collected routinely on proforma case notes and entered into a computerized database. The histology of the cone biopsies was compared with that of previous, colposcopically directed punch biopsies, with the cytology of smears taken in the clinic and with the colposcopic diagnosis. The punch biopsy had a 54% false negative rate and neither of the two microinvasive carcinomas biopsied in this way were detected by the biopsy. Ten of 24 women with negative punch biopsies had CIN III in the cone. When the punch biopsy showed CIN II or worse, the cone biopsy confirmed the presence of CIN in 86%. There was some evidence of false negative cone biopsies. The data suggest that management should not be based solely upon the punch biopsy result but should include consideration of the cytology and colposcopy findings. Excisional methods of treatment are more likely to reveal early invasion and adenocarcinoma-in-situ.
Biopsy↗
Persistence of intrinsic neurones and possible phenotypic changes after extrinsic denervation of human respiratory tract by heart-lung transplantation.
Respiratory tract nerves have cell bodies outside (sensory, sympathetic) and inside (parasympathetic) the organ and contain bioactive peptides. These include calcitonin gene-related peptide and tachykinins (sensory nerves), vasoactive intestinal polypeptide (parasympathetic nerves), and neuropeptide with tyrosine (sympathetic nerves). Because transplantation interrupts the extrinsic nerve supply to the tissues, we have examined transplanted human respiratory tracts (n = 11) removed at retransplantation 2 to 42 months after the primary transplant in order to determine whether any nerves and peptide synthesis persist. As controls to establish nerve distribution in human respiratory tract, tissues were obtained from 10 lung resections and five autopsies. Cryostat sections were immunostained to demonstrate the general neural marker PGP 9.5, neuropeptides, and the catecholamine-synthesizing enzyme tyrosine hydroxylase. Nerves immunoreactive for PGP 9.5 were detected in all transplanted tissues. They were fewer in number overall than in control tissue, significantly so in epithelium of trachea and bronchus where they were present sparsely in only three cases. Nerves immunoreactive for tyrosine hydroxylase were significantly fewer in the transplants. Peptide-immunoreactive nerves were also reduced in number in the transplants, except for vasoactive intestinal polypeptide, which was only significantly changed in blood vessels in the lung. Ganglion cells immunoreactive for tyrosine hydroxylase and neuropeptide with tyrosine were seen in the transplanted tissues in five cases, but never in the control tissues. We conclude that whereas some nerves and neuropeptide synthesis persist after extrinsic pulmonary denervation, potentially significant changes also occur, including the appearance in intrinsic parasympathetic neurones of immunoreactivity for a catecholamine-synthesizing enzyme and a peptide normally found in sympathetic nerves.
Adult↗
Effect of polarity and differentiation on antibody localization in multicellular tumour spheroid and xenograft models and its potential importance for in vivo immunotargeting.
Two monoclonal antibodies (MAbs) AUAI and HMFGI recognize antigens located on different membrane domains of polarized epithelial cells. We have assessed the accessibility of these antigens in multicellular tumour spheroids produced in culture using a well-polarized (HRA-19) and a non-polarized cell line (LoVo) of human large-bowel carcinoma origin. Multicellular spheroids of HRA-19 cells develop polarity, so that the membrane which is in contact with the culture medium (apical) becomes antigenically distinct from the membrane facing the centre of the spheroids (basolateral). This was confirmed by immunostaining sections of spheroids with 2 MAbs, AUAI and HMFGI. AUAI recognizes an antigen located exclusively on the basolateral membranes of polarized epithelial cells, and stained only internal membranes in spheroid sections. Conversely HMFGI, which recognizes an antigen located on the apical membranes, stained only the periphery of the spheroids. These 2MAbs were then radiolabelled with 125I and incubated with live spheroids for 4 hr at 37 degrees C. Autoradiographs of spheroid sections showed a marked difference between the 2 MAbs. 125I-HMFGI-radioantibody localized exclusively on the spheroid surface in a pattern identical to the in vitro immunostaining pattern, while 125I-AUAI radioantibody showed no binding in spite of the uniform presence of antigen on all tumour cells basolaterally. This appeared to be the result of the inaccessibility of basolateral antigenic sites in well-polarized epithelial cells because of the tight junctions connecting these cells at their apical surfaces. In contrast to the HRA-19 cell line LoVo, spheroids do not develop polarity; as a result, when stained with AUAI, variable antigenic expression all over the cell surface was seen. Autoradiographs of these spheroids showed 125I-AUAI binding with a penetration to a depth of about 1-3 cells, while HMFGI which shows no reactivity with this cell line in vitro, did not bind. This phenomenon was further investigated in xenografts of the HRA-19 cell line. It was shown that in a well-differentiated adenocarcinoma where the tumour cells forming acini are arranged in a polarized fashion, the luminal antigenic sites may be inaccessible to the injected MAb. The striking differences in binding of MAbs on polarized and unpolarized tumours indicate the importance of cell polarization and exact location of antigenic sites for in vivo immunotargeting.
Adenocarcinoma↗
Formation of endothelin by cultured airway epithelial cells.
Immunoreactivity to endothelin was detected in conditioned culture medium from both canine and porcine tracheal epithelial cells. Gel permeation chromatography and fast protein liquid chromatography were used to confirm the identity of the endothelin. The two peaks demonstrated on fast protein liquid chromatography co-eluted with endothelin 1 and endothelin 3 respectively.
Animals↗
Diazepam binding inhibitor-like immunoreactivity(51-70): distribution in human brain, spinal cord and peripheral tissues.
We have used a specific radioimmunoassay to describe the distribution of diazepam binding inhibitor-like immunoreactivity (DBI-IR(51-70) in human post-mortem tissues. In brain, highest concentrations were found in the cerebellum, amygdala, hippocampus, hypothalamus and substantia nigra. In the spinal cord, DBI-IR(51-70) was evenly distributed. In peripheral tissues, highest concentrations were found in the liver and kidney. Chromatographic analysis revealed several molecular forms of DBI-IR(51-70) the major form being of greater molecular weight and hydrophobicity than the synthetic fragment peptide. In peripheral tissues, but not in the CNS, a small peak of immunoreactivity was indistinguishable from the synthetic peptide. DBI-IR(51-70) is therefore widespread, but tissue processing may be different.
Aged↗
Atrial natriuretic peptide levels in plasma and in cardiac tissues after chronic hypoxia in rats.
1. Atrial natriuretic peptide (ANP) levels were measured in cardiac tissues and in plasma from adult rats exposed to chronic alveolar hypoxia for periods of 2 h, 24 h and 7 days. Levels were also measured in rats that were maintained in hypoxia for 7 days and then returned to air for 24 h. 2. Plasma ANP was not altered at 2 h but was significantly increased at both 24 h and at 7 days. Plasma ANP in animals exposed to hypoxia for 7 days was normal 24 h after returning to air breathing, despite the persistence of indices of pulmonary hypertension. 3. No significant right atrial hypertrophy was observed under these conditions of chronic hypoxia. A reduction in right atrial ANP content was found at 24 h and was accompanied by a decrease in the number of electrondense granules per right atrial muscle cell. After exposure to hypoxia for 7 days, right atrial ANP and granule number was not different from control, and no alteration was found in right atrial ANP level after removal from the hypoxic environment. 4. No significant right ventricular hypertrophy was produced by exposure to hypoxia for 2 or 24 h. In the former group ventricular ANP had decreased significantly compared with control. Right ventricular hypertrophy was found in both the hypoxic groups after exposure for 7 days, when selective increases in right ventricular ANP content were found. 5. These findings are consistent with the hypothesis that ANP release occurs on exposure to chronic hypoxia and is independent of the associated cardiac hypertrophy and pulmonary vascular remodelling. The findings may have relevance to the natriuresis and reported changes in the renin-angiotensin-aldosterone axis under hypoxic conditions.
Animals↗
Invasive aspergillosis: clinical and pathological features of a new animal model.
A new animal model of invasive aspergillosis is described in which female New Zealand White rabbits were immunosuppressed with corticosteroids and cyclophosphamide and were given an intratracheal inoculation of 4 x 10(4) conidia of Aspergillus fumigatus. Thirteen of 15 animals survived during a 10-day-period of observation. Most had clinical signs of a respiratory infection (dyspnoea) and at autopsy there was macroscopic and microscopic evidence of invasive pulmonary aspergillosis. Six control animals (infected but not immunosuppressed) showed no such signs. The extent of hyphal invasion was assessed histologically and quantified by calculating the number of colony forming units (c.f.u.) g-1 of tissue: in the experimental group the mean c.f.u. value for the lungs was 1.25 x 10(3) compared to 73.3 c.f.u. g-1 of lung for the control group (P = 0.003). The infection was also quantified by a whole lung chitin assay: in the experimental group the mean chitin content (expressed as a glucosamine equivalent) was 3.05 micrograms g-1 lung tissue compared to a 0.53 micrograms g-1 lung tissue for the control group (P = 0.01). We conclude that this model of invasive aspergillosis in rabbits reflects closely the pathological features of the disease in man and that it may prove useful for studies of the pathogenesis and the treatment of invasive aspergillosis.
Animals↗
Secretory carcinoma of the breast in adults: emphasis on late recurrence and metastasis.
Secretory (so-called juvenile) carcinoma of the breast, first described in children, occurs also in adult women, predominantly in the third decade. Less commonly it is seen in older age groups, up to the eighth decade. We report five patients with this tumour; one, a female aged 73, is the oldest age at which the tumour has been recorded, and one is the first report in an adult male in whom the disease recurred after 20 years, only the second recorded death attributable to this tumour type. Secretory carcinoma in adults is potentially more aggressive than in childhood. Nodal metastases are more frequent and sometimes more extensive. Recurrence of tumour after surgery developed in four of our five patients at 3, 8, 15 and 20 years. Slow growth and delayed recurrence are characteristic of many of these tumours. Death from systemic metastases is rare, but may ensue either rapidly or following a long latent period after treatment. Prolonged follow-up is needed to assess accurately the biological behaviour of this tumour.
Adult↗
Laser vaporization versus laser excision conization in the treatment of cervical intraepithelial neoplasia.
One hundred patients with histologically confirmed cervical intraepithelial neoplasia suitable for ablative therapy were randomly allocated to treatment by either laser vaporization or laser excision conization under local anesthesia in the outpatient colposcopy clinic. The two methods were compared with respect to the immediate surgical complications, ease of performance, and long-term complications. They were comparable in most respects, and both were well accepted by the patients. Laser excision had the added advantage of providing further material for histologic examination to confirm the absence of invasion and the completeness of excision of the lesion.
Adolescent↗
Localization of monoclonal antibody AUA1 and its F(ab')2 fragments in human tumour xenografts: an autoradiographic and immunohistochemical study.
The mouse monoclonal antibody (MAb) AUA1, when applied on LoVo tumour sections, reacts by staining all tumour cells, on their cell surfaces. To investigate the accessibility of these sites to antibody when the tumour is present as a solid mass in vivo, subcutaneous xenografts of LoVo were first prepared in nude mice. The mice were then injected intravenously with either 125I-labelled AUA1, 125I AUA1 F(ab')2 or with 125I-labelled HMFG2 (negative control antibody). Animals were killed at various time intervals. Gross and micro-autoradiography as well as immunohistochemistry were performed on tissue samples of tumour and control organs. The in vivo injected antibody, in contrast to that studied in vitro, was localized only, as detected by autoradiography, on a thin layer of tumour cells adjacent to the vascularized stroma. On microscopically small tumour islands the antibody penetration was complete. Most of the radioactivity was on the cell surfaces, as seen on in vitro immunostaining. With intact antibody, similar autoradiographic results were obtained at days 1, 3 and 6. With F(ab')2 fragments there was deeper penetration into the tumour at days 1 and 3, though less radioactivity was found; by day 6 the activity had greatly decreased. Radioactivity in the control organs was limited to the blood pool. Negative control antibody HMFG2 showed no localization on the tumour cells. These results were not due to differences in antigenic expression of the tumour cells but reflect the problem of accessibility of antigenic sites in vivo.
Animals↗
Localization of biotinylated monoclonal antibody in nude mice bearing subcutaneous and intraperitoneal human tumour xenografts.
To demonstrate the precise distribution and binding of in vivo injected monoclonal antibodies on histological tumour sections, we have biotinylated our primary antibody AUA1. Biotinylated antibody was injected into nude mice bearing simultaneous subcutaneous and intraperitoneal xenografts of the human tumour LoVo. Twenty-four hours after injection, the animals were killed, tumours and control organs were removed. Antibody was demonstrated on frozen sections by incubating sections with avidin biotin peroxidase complex. We compared the in vivo penetration and binding of this antibody on intraperitoneal and subcutaneous xenografts. The antibody penetration was mainly restricted to a thin layer of tumour cells adjacent to the vascularized stroma in large solid subcutaneous and intraperitoneal tumours, whereas in very small intraperitoneal tumours, antibody penetration was complete. These findings were similar to our autoradiographic results. This study demonstrates that employing the biotinylated antibodies for in vivo localization studies provides superior resolution of antibody binding for morphological assessment compared to autoradiography. Localization of a biotin label is more precise and will permit ultra-structural studies.
Animals↗
Pigmented dermatofibrosarcoma protuberans (Bednar tumour): melanocytic colonization or neuroectodermal differentiation? A clinicopathological and immunohistochemical study.
Approximately 5% of cases of dermatofibrosarcoma protuberans contain dendritic melanocytes; such lesions are often known as Bednar tumours. These neoplasms have received little attention in the literature but seem to show no great clinicopathological differences from conventional dermatofibrosarcoma protuberans except for the presence of melanocytes. The existence of such tumours, combined with ultrastructural evidence, has led some leading authors to regard them all as being of neuroectodermal origin. Seven examples of the pigmented variant are presented herein, of which six have been studied immunohistochemically and one has been examined ultrastructurally. Except for the presence of melanocytes in each tumour, no evidence of neuroectodermal (in particular perineural fibroblastic) differentiation has been demonstrated. The histogenesis of dermatofibrosarcoma protuberans and its pigmented variant is discussed. The possibility that the pigmentation may simply reflect secondary melanocyte colonization from the epidermis should be considered.
Adolescent↗
Clonal rearrangement of the T-cell receptor gamma gene associated with a bizarre lymphoproliferative syndrome.
Investigations in an unusual patient with prolonged fever, fat necrosis and haemorrhagic tendency showed widespread histiocytic phagocytosis in fat and liver biopsy specimens. Lymph nodes were also infiltrated by morphologically normal T lymphocytes predominantly expressing the OKT4 antigen. Analysis of lymph node DNA using immunoglobulin and T-cell receptor (TCR) probes showed rearrangement restricted to the gamma TCR gene combined with polyclonal beta TCR gene rearrangements, thus providing evidence of a unique lymphoproliferative disorder of T cells. The patient displayed a striking response to cytotoxic chemotherapy.
DNA↗
Cartilaginous tumours of soft tissue.
Tumours of soft tissue may manifest cartilaginous differentiation as a primary phenomenon (as in chondromas or extraskeletal myxoid and mesenchymal chondrosarcomas) or as a secondary metaplastic feature (most notably in extraskeletal osteosarcomas or malignant nerve sheath tumours). The literature regarding primary cartilaginous tumours is reviewed and their differential diagnosis discussed. Soft tissue chondromas are noteworthy for their tendency to show significant nuclear pleomorphism. Extraskeletal chondrosarcoma is much rarer than its osseous counterpart, accounting for only 1-2% of soft tissue sarcomas. Virtually all such sarcomas can be classified into the myxoid or mesenchymal subtypes, of which myxoid carries a better prognosis. Soft tissue neoplasms which may show focal cartilaginous metaplasia are covered more briefly.
Cartilage↗