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Biomedical subjects

T Krausz

Publications and source records attributed to T Krausz.

At least 55 records · Page 3Linked to original sources

Streptococcal pyrogenic exotoxin A release, distribution, and role in a murine model of fasciitis and multiorgan failure due to Streptococcus pyogenes.

The role of streptococcal pyrogenic exotoxin A (SPEA) was evaluated in a murine model of fasciitis and multiorgan failure due to a toxigenic strain of Streptococcus pyogenes. Increased serum levels of SPEA at 15 and 21 h were associated with a survival time of <24 h. Levels of SPEA correlated with interleukin-6 levels. Immunostaining showed SPEA localized to renal and hepatic cells. Neutralizing rabbit antibody to SPEA was administered to mice challenged with S. pyogenes, but no effect on survival was observed. Vaccination of mice with recombinant SPEA enhanced mortality due to streptococcal infection, despite the development of neutralizing immunity to the toxin prior to infection. Hence, SPEA is produced systemically during S. pyogenes soft-tissue infection, and increased levels are associated with reduced survival. In this model, however, SPEA did not appear to play a dominant role in pathogenesis; passive immunization against SPEA was not protective, and active immunization enhanced mortality.

Animals↗

Cryopreservation of human ovarian tissue using dimethylsulphoxide and propanediol-sucrose as cryoprotectants.

Pieces of ovarian cortical tissue (0.3-2 mm in diameter) were obtained during gynaecological operations by biopsy or as a result of oophorectomy from 19 women aged 19-44 years. The tissue was frozen in a programmable freezer using one of two different cryoprotectants, either 1.5 M dimethylsulphoxide (DMSO), or a combination of 1,2-propanediol (1.5 M) and sucrose (0.1 M). After cryopreservation lasting from 24 h to 5 weeks, the ovarian pieces were thawed and studied histologically. Specimens taken before and after cryopreservation with either protectant showed no signs of tissue necrosis. Follicles at similar developmental stages were found before and after freezing. The proportions of follicles showing signs of atresia, 27% in the non-frozen tissue and 19% in the frozen-thawed tissue, were not significantly different. Oocytes, too, had the same appearance after freezing and thawing with both cryoprotectants as was seen in the specimens taken before freezing. These results suggest that cryopreservation of human ovarian tissue is feasible. However, the normality of the oocytes taken from tissue which has been frozen still needs to be established. Cryopreservation of ovarian tissue would be potentially an excellent method for storage of human oocytes once methods for their maturation in vitro have been developed.

Adult↗

Reduced beta adrenoceptor density in vivo in human lung tumours: a preliminary study with positron emission tomography.

BACKGROUND: Reduced beta adrenergic receptor density in tumours has been reported in previous in vitro studies. The aim of the present study was to assess whether this occurs in vivo. METHODS: Pulmonary beta adrenoceptors were imaged and quantified in vivo using positron emission tomography (PET) and the beta antagonist radioligand (S)-[11C]CGP-12177 in five men with lung tumours of mean age 58 years (range 42-68). The histology of the tumours was squamous cell carcinoma in two cases, adenocarcinoma in one, carcinoid tumour in one, and large cell carcinoma in one. The regional blood volume and extravascular tissue density were also measured using PET. Regions of interest were drawn for both non-tumour and tumour lung tissue. RESULTS: The mean (SD) blood volume was 0.142 (0.025) ml/ml in tumour regions and 0.108 (0.010) ml/ml in normal lung regions--a difference of 31%. Mean (SD) extravascular tissue density was 0.653 (0.133) g/ml in tumour regions, substantially higher than in normal lung regions (0.157 (0.021) g/ml). On the contrary, beta receptor density was 5.1 (1.8) pmol/g in tumour regions, lower than the value of 9.9 (1.6) pmol/g found in adjacent normal lung--a difference of 48%. CONCLUSIONS: In vivo beta adrenoceptor density is reduced in human lung tumours.

Adrenergic beta-Antagonists↗

Human endometrial fibroblasts immortalized by simian virus 40 large T antigen differentiate in response to a decidualization stimulus.

Human endometrial fibroblasts have been immortalized by infection with simian virus 40 large T antigen and established as a permanent cell line, St-2. Biochemical differentiation of this cell line has been demonstrated by the ability of a decidualizing stimulus, 8-bromo-cAMP plus medroxyprogesterone acetate (MPA), to induce PRL secretion and increase the enzymatic activity of estrone sulfatase. MPA, alone or in combination with estradiol, was unable to elicit this response, but potentiated the effect of 8-bromo-cAMP on PRL production and estrone sulfatase activity. The increase in PRL protein was accompanied by an increase in PRL messenger RNA and increased expression of the insulin-like growth factor-binding protein-1 messenger RNA. The St-2 cell PRL transcript was larger than the pituitary PRL transcript, suggesting its initiation from the distal, nonpituitary, PRL promoter. This was confirmed by reverse transcription-PCR analysis of PRL transcripts using primers specific for the additional sequences present only in the 5'-untranslated region of RNA initiated from the distal promoter. Transient transfection of a reporter construct containing 3000 bp of DNA 5' to the decidual-specific promoter of the human PRL gene demonstrated that cAMP was capable of activating this distal promoter in St-2 cells. In conclusion, this novel cell line provides an interesting new model in which to pursue aspects of biochemical differentiation of human endometrium in vitro.

8-Bromo Cyclic Adenosine Monophosphate↗

High-resolution MR imaging of stage I cervical neoplasia with a dedicated transvaginal coil: MR features and correlation of imaging and pathologic findings.

OBJECTIVE: The purposes of this study were to assess the appearance of stage 1 neoplasia of the cervix by high-resolution MR imaging with an enveloping transvaginal receiver coil and to correlate the imaging findings with the pathologic findings. SUBJECTS AND METHODS: Fifteen patients (25-73 years old; mean, 40 years old) with clinical stage I disease were examined with a 37-mm-diameter ring-design solenoid receiver coil placed around the cervix. Axial 2.5-mm contiguous slices were obtained with a field of view of 10-15 cm on a 1.0-T HPQ Vista scanner with T1-weighted (660/20 msec [TR/TE]) and T2- weighted (2500/80 msec) spin-echo sequences and dynamic gradient-echo sequences during injection of gadopentetate dimeglumine (0.1 mmol/kg). Ten patients subsequently underwent Wertheim's hysterectomy, two underwent radiotherapy, two underwent extended cone biopsy for microinvasive disease, and one underwent a punch biopsy. For seven of 10 patients who had a hysterectomy, the widths of the tumor and the residual stroma were measured at eight radial points on the transverse images and at corresponding points on the histologic specimens at 5, 10, 15, 20, and 25 mm from the ectocervix. We then compared the widths of the tumor and the stroma on images and histologic specimens at each of these 40 points. Tumor volumes were calculated from the MR imaging and pathologic data and compared. For the other three patients, detailed MR imaging-pathology correlation was not possible because of multifocal tumor distribution (two patients) and insufficient detailed pathologic data (one patient). RESULTS: Three carcinoma types were recognized. Squamous carcinoma (nine cases) was seen as a centrally expanding intermediate-signal-intensity mass, whereas oat (small)-cell carcinoma (one case) and clear-cell carcinoma (one case) showed a multifocal distribution. For patients who had a radical hysterectomy, we noted good agreement between the widths of the tumor and the stroma determined by MR imaging and histology. Tumor volumes were determined to be 0-28.2 cm3 by MR imaging and 0-18.4 cm3 by pathology. We observed tumor extension into the immediate parametrium in four patients by MR imaging; one of these cases was not confirmed at surgery. Parametrial extension was not underestimated by MR imaging in any case. CONCLUSION: High-resolution imaging of the cervix with a transvaginal coil provides accurate assessment of the intra- and extracervical extents of tumors in clinical stage 1 cervical neoplasia.

Adenocarcinoma, Clear Cell↗

MR imaging of the anal sphincter in multiparous women using an endoanal coil: correlation with in vitro anatomy and appearances in fecal incontinence.

OBJECTIVE: The aim of this study was to correlate the components of the normal female anal sphincter seen on high-resolution MR images with the in vitro anatomy and to describe the change in appearances of these components in multiparous women with fecal incontinence. SUBJECTS AND METHODS: Ten asymptomatic female volunteers (32-72 years old; mean, 54 years old) and 22 women with fecal incontinence were studied. In six patients (26-68 years old; mean, 49 years old) fecal incontinence began immediately after childbirth; in the remaining 16 patients (45-77 years old; mean, 58 years old) fecal incontinence developed 15- 30 years after childbirth. In the latter group of patients, terminal motor latencies of the pudendal nerve were measured. Imaging was done on a 0.5-T Picker Asset unit and on a 1.0-T Picker HPQ unit. A saddle geometry endoanal receiver coil was used for all imaging. T1-weighted spin-echo (720-820/20 [range of TR/TE]), T2-weighted spin-echo (2500/80 [TR/TE]), fast spin-echo (4500/96 [TR/ effective TE]), and short inversion time inversion recovery (2500/80 [TR/TE]; inversion time, 107 msec) MR images were obtained in transverse, coronal oblique, and sagittal planes. Images were assessed for integrity of the sphincter components. A nonpaired separate-variance t test was used to compare thickness of individual muscle components between patients with delayed-onset fecal incontinence and asymptomatic age-matched volunteers. Degree of muscle atrophy was correlated with degree of delay in the terminal motor latency of the pudendal nerve. RESULTS: The high resolution obtained with an endoanal coil allowed differentiation of the various muscle components of the anal sphincter complex. The internal sphincter was seen as a ring of homogeneously high signal intensity with a low-signal-intensity rim that was rich in collagen and contained neurovascular bundles. The external anal sphincter, which had low signal intensity on T1- and T2-weighted images, was shown as three components: subcutaneous, superficial, and deep. In six patients who had fecal incontinence that began immediately after childbirth, endoanal MR imaging revealed the site and extent of a tear. All tears were confirmed at surgery. In the 16 patients who had fecal incontinence that began several years after childbirth, atrophy of the external sphincter was revealed in all cases in the superficial and deep components. The internal sphincter remained normal. However, we found that the degree of atrophy of individual components of the external sphincter did not correlate with the degree of delay in pudendal nerve conduction. CONCLUSION: MR imaging with an endoanal coil reveals the integrity and bulk of individual muscle components of the anal sphincter in multiparous women with fecal incontinence.

Adult↗

Oncogenic osteomalacia associated with a meningeal phosphaturic mesenchymal tumor. Case report.

A 60-year-old woman suffered from hypophosphatemic osteomalacia secondary to a frontal intracranial tumor. Oral administration of phosphate and 1-alpha-hydroxyvitamin D3 provided only temporary symptomatic relief. A computerized tomography (CT) scan of the patient's head revealed a large subfrontal tumor attached to the dura. Following removal of the tumor, the patient's hypophosphatemia subsided; her level of 1,25-dihydroxyvitamin D3, which was undetectable preoperatively, returned to normal, and she had symptomatic improvement. Three years later, decreasing levels of phosphate and 1,25-dihydroxyvitamin D3 indicated tumor recurrence, before it was detected by CT scan. Histological examination of the tumor provided the diagnosis of "mixed connective tissue variant of phosphaturic mesenchymal tumor." The characteristic histological features of this relatively rare entity are discussed. This is the first report of a surgically treated intracranial phosphaturic mesenchymal tumor that caused oncogenic osteomalacia.

Craniotomy↗

In vivo quantification of human pulmonary beta-adrenoceptor density using PET: comparison with in vitro radioligand binding.

UNLABELLED: A new method has recently been developed to quantify pulmonary beta-adrenergic receptors in vivo using PET. This study used in vitro radioligand binding assay (RLBA) as the gold standard to validate in vivo PET measurements. METHODS: Five male patients with lung cancer aged 57 yr (range 42-67 yr) were studied. PET scanning was performed the day before thoracotomy to determine regional pulmonary beta-receptor density. RLBA was carried out on cell membranes prepared from specimens of lung tissue obtained at the thoracotomy to measure beta-receptor density in vitro. In both cases, the hydrophilic nonselective beta-antagonist radioligand (S)-CGP-12177 was used. For PET studies, this was labeled with 11C and for RLBA with 3H. RESULTS: In the PET study, beta-receptor density (Bmax) was 9.43 +/- 1.32 pmole g-1 tissue. In the RLBA study, Bmax was 99.0 +/- 15.5 fmole mg-1 protein, equivalent to 9.90 +/- 1.55 pmole mg-1 tissue. These values are in good agreement with previously reported in vitro measurements on human lung membranes using 125I-iodocyanopindolol. A correlation was found between beta-adrenergic density obtained using PET and beta-adrenergic density obtained using RLBA (r = 0.92; p < 0.05). CONCLUSION: The results support the use of PET as a new method for imaging and the way for studies of physiological and pharmacological regulation of beta-adrenergic receptors through noninvasive serial measurements.

Adrenergic beta-Antagonists↗

E-cadherin expression in bladder cancer using formalin-fixed, paraffin-embedded tissues: correlation with histopathological grade, tumour stage and survival.

To determine the potential prognostic value of epithelial cadherin (E-cadherin), a Ca(2+)-dependent cell-cell adhesion molecule, we have analysed its immunoreactivity and cellular localisation in 67 transitional cell carcinomas (TCC) using an avidin-biotin immunoperoxidase technique on formalin-fixed, paraffin-embedded tissues. These results were correlated with histopathological grade, tumour stage, presence of metastases and survival. In addition, 10 cystitis and 11 normal bladder biopsies were evaluated as controls. E-cadherin was expressed in a normal membranous pattern in all normal and 7 of 10 cystitis biopsies. Loss of normal surface E-cadherin expression was found in 3 of 15 superficial tumours and in 48 of 52 invasive cancers. Abnormal immunoreactivity was strictly related to tumour differentiation and stage. Fifteen of 20 well-differentiated (grade I) tumours showed preserved membranous E-cadherin immunoreactivity, while 46 of 47 moderate and poorly differentiated tumours (grades II and III) demonstrated abnormal staining patterns. Loss of membranous E-cadherin immunoreactivity was also associated with advanced tumour stage. There was a significantly higher 5-year survival rate for patients with preserved membranous staining compared with patients with abnormal staining.

Cadherins↗

A rare mediastinal tumour presenting with systemic effects due to IL-6 and tumour necrosis factor (TNF) production.

Patients presenting with prolonged systemic illnesses with no specific clinical or serological defining features may be diagnosed as having atypical systemic vasculitides, but often turn out to have occult malignancies. Cytokines have been implicated in causing many of the systemic effects in such cases. In this study we describe a patient presenting after 2 years of a severe systemic illness with a marked acute phase response, due to an occult mediastinal angiomatoid malignant fibrous histiocytoma. Tumour resection was curative. We evaluated in detail the local and systemic production of cytokines induced by this tumour. Blood samples were taken pre- and post-operatively for cytokine studies. In vitro production of IL-2, IL-2R, IL-1 beta, IL-6 and TNF-alpha by cultured monocytes from the patient, as well as plasma cytokine levels, were measured by ELISA. Tumour cytokine production was also evaluated immunocytochemically, and by in situ hybridization with specific cDNA probes. Plasma IL-2R and IL-6, and IL-6 and TNF-alpha production by peripheral blood monocytes were markedly elevated before tumour resection, normalizing post-operatively. Most tumour cells and infiltrating lymphocytes stained with antibodies to IL-6, IL-6R and TNF-alpha, and expressed HLA class II. IL-6 and TNF-alpha mRNA production in the tumour was confirmed by in situ hybridization studies. We have described the first case of an occult angiomatoid malignant fibrous histiocytoma in the mediastinum. Studies of cytokine expression suggested that chronic TNF, IL-6, and IL-2 production by leucocytes and tumour cells in this patient was responsible for the severe systemic illness with which she presented.

Adult↗

Female adnexal tumour of probable Wolffian origin: a clinicopathological and immunohistochemical study of three cases.

The clinical and pathological features of three adnexal tumours of probable Wolffian origin are reported. One case was an incidental finding in a patient who died from ovarian carcinoma; in the other two cases the patients presented with lower abdominal pain. The three tumours were well-circumscribed, solid masses arising in the leaves of the broad ligament and histological examination showed bland epithelial cells forming tubular, solid and microcystic patterns. The immunohistochemical profile of the tumours was similar to that of Wolffian duct remnants. They co-expressed cytokeratin and vimentin and lacked epithelial membrane antigen (EMA) reactivity, in contrast to tumours of Müllerian origin which usually express EMA. The differential diagnosis of female adnexal tumours is discussed.

Adenoma↗

Abnormal intraepithelial airway nerves in persistent unexplained cough?

Idiopathic persistent nonproductive cough (PNPC) is characterized by enhanced cough sensitivity to inhaled capsaicin, suggesting that capsaicin-sensitive afferent airway nerves are either present in increased numbers or functionally upregulated. In 16 patients with idiopathic PNPC and eight healthy control subjects, we measured cough sensitivity to inhaled capsaicin and the anatomic density in bronchial epithelium of nerves immunoreactive for the general nerve-marker protein gene product (PGP)-9.5 and the sensory neuropeptides calcitonin-gene-related-peptide (CGRP) and substance-P (SP). The log concentrations of capsaicin required to elicit at least two (C2) and five (C5) coughs were significantly lower in patients (P) than in control subjects (C) (median [range] log C2, P = 0.3 [-0.3 to 1.2] microM; C = 1.5 [0.9 to 2.1], p < 0.0005; log C5, P = 0.8 [-0.3 to 2.1]; C = 2.6 [1.8 to 3.0], p < 0.0005). In bronchial epithelium taken from the carina of the right upper lobe (RUL) and a subsegmental carina of the right lower lobe (RLL), total nerve density (PGP-9.5 immunoreactivity) was greater in P than C, although this was not significant. CGRP-immunoreactive nerve density was significantly higher in P than in C in the RUL (median [range] P = 1.05% [0.13 to 5.08]; C = 0.02% [0 to 0.24], p = 0.001) and RLL (P = 0.59% [0.04 to 3.14]; C = 0% [0 to 0.50], p < 0.02). SP-immunoreactive nerves were not significantly different in the two groups. Abnormal intraepithelial airway nerves containing increased quantities of CGRP are present in patients with idiopathic PNPC.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Idiopathic eosinophilic myositis.

Eosinophilic myositis is a rare entity accompanying parasitic infection or other inflammatory disorders. Two cases are reported in which myalgia and eosinophilic infiltration of muscle occurred in the absence of associated disease, and twelve previously published cases of idiopathic eosinophilic myositis are reviewed. A classification system for idiopathic eosinophilic muscle disease is proposed, describing three distinct groups. Comparisons are drawn between these and other causes of eosinophilic muscle disease, outlining the differential diagnoses for each group.

Adult↗

Combined choriocarcinoma and yolk sac tumor arising in Barrett's esophagus.

A patient with primary adenocarcinoma with yolk sac and trophoblastic differentiation occurring in Barrett's esophagus is reported. Yolk sac differentiation at this site has not been described previously. The diagnosis of germ cell differentiation initially was suggested by the finding of elevated serum tumor marker levels. The patient experienced disease remission after cytotoxic chemotherapy. Germ cell differentiation may be difficult to identify in small biopsy samples, which may not be representative of the tumor as a whole. The finding of germ cell differentiation defines therapy and predicates for a relatively good prognosis, which is contrast to adenocarcinoma. Because of the significance of germ cell differentiation in the selection of appropriate therapy, immunostaining for germ cell tumor markers is suggested in all patients with adenocarcinoma who are younger than 50 years.

Adenocarcinoma↗

Squamous cell carcinoma of the feline thymus with widespread apoptosis.

The present report documents a case of squamous cell carcinoma originating from the thymus of a 12-year-old short-haired male cat. The tumour had metastasised to the sternal lymphoid tissue and to the left lung. To the authors' knowledge, thymic carcinoma has not been reported in domestic animals. Furthermore, extensive apoptosis was observed in the tumour mass.

Animals↗

Non-invasive assessment of bronchial inflammation in asthma: no correlation between eosinophilia of induced sputum and bronchial responsiveness to inhaled hypertonic saline.

Bronchial inflammation in mild asthma has been investigated using bronchoscopical techniques. The safety of bronchoscopy in patients with more severe asthma has been questioned. We have used the non-invasive technique of hypertonic saline (HS) inhalation to induced sputum samples for cellular analysis whilst simultaneously yielding a measure of bronchial responsiveness. Ten normal subjects and a heterogenous group of 24 asthmatic patients (range % predicted FEV1 43.3-111.5) underwent HS challenge. Sputum samples induced were analysed. Total and differential cell counts between the two groups were compared. The association between bronchial responsiveness to HS and sputum cell counts was examined in the asthma group. Mean maximum fall in FEV1 for normal subjects was 4.0 (2.1-5.9, 95% CI)% after saline. Geometric mean PD20HS for asthma patients was 7.7 (range 0.68-40.92)ml. Adequate sputum samples were obtained from 9/10 normals and 23/24 asthmatic patients. Sputum from normal subjects contained a median of 3.8 (2.8-8.1, interquartile range)% eosinophils compared with 17.6 (8.9-34.1)% in sputum from asthma patients (P < 0.001). Sputum from asthma patients contained fewer of all other cell types compared with normals, with the difference in macrophages reaching significance. There was no correlation between PD20HS and cell count for any cell type in asthma subjects. Analysis of induced sputum represents a simple, safe, non-invasive and well-tolerated method of assessment of bronchial inflammation, suitable for use in patients with a range of asthma severity. There was no relationship between inflammation, as assessed by sputum cell counts and a measure of 'indirect' bronchial responsiveness.

Asthma↗

Aspiration cytodiagnosis of pancreatic endocrine tumours.

We have reviewed fine needle aspirates from 11 patients with pancreatic endocrine tumours and evaluated the diagnostic criteria as well as those proposed in the literature in an attempt to formulate reliable criteria for the cytological diagnosis of these tumours. As expected, no single criterion was reliable for diagnosis: however, cells with rounded or polygonal rather than a columnar shape, cytoplasmic granularity, and eccentricity of round or oval nuclei with a finely stippled, evenly distributed chromatin pattern were features which, taken together, usually enabled one to make a reliable diagnosis. A striking feature of the smears was the cellular monotony and absence of pleomorphism of the tumour cells. Immunocytochemistry and electron microscopy identified tumour products and confirmed the diagnosis.

Adenoma, Islet Cell↗