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Detection of Epstein-Barr virus-infected mucosal lymphocytes in nasal polyps.

Primary nasal lymphomas of T or NK cell origin are known to be associated with Epstein-Barr virus (EBV). However, it is not known whether EBV is normally present in nasal mucosa as distinct to nasopharyngeal tissue. This study investigates the prevalence of EBV infection in 13 cases of nasal polyps. EBV DNA was detected in 2 of 13 (15%) by Southern blot hybridization and in 9 of 13 (69%) by polymerase chain reaction. In situ hybridization for EBV-encoded small nuclear RNAs (EBER) was positive in 11 of 13 (85%) cases; the virus was present in stromal lymphocytes only and not in the epithelial cells. Immunohistochemistry for EBV proteins in 7 cases revealed EBV nuclear antigen (EBNA)-2, latent membrane protein (LMP)-1, and ZEBRA (the switch protein encoded by gene BZLF1) expression in rare isolated stromal lymphocytes in 3 cases. Double immunostaining in 1 case showed that the LMP-1+ cells were B or T cells. Immunohistochemistry for EBV lytic proteins showed very rare viral capsid antigen (VCA)+ and membrane antigen (MA)+ cells in 1 case and very rare diffuse early antigen (EA-D)+ and VCA+ cells in 1 other case. The expression of ZEBRA, EA-D, VCA, and MA suggested a disruption of latency in very rare stromal lymphocytes leading to a productive cycle. Although the incidence of EBV positivity in nasal polyps in our population is high (85%), very low numbers of EBV+ cells are found in each case. Nevertheless, they indicate that nasal mucosa could be one of the sites of EBV persistence through a low level of infection of the resident lymphocytes and thereby provide a possible setting for the emergence of virally associated tumors in this site.

Adult↗

Phenotypic heterogeneity in cultured skin fibroblasts from patients with disorders of peroxisome biogenesis belonging to the same complementation group.

We have studied fibroblast cell lines derived from a control subject (cell line 85AD5035F) and three patients clinically described as having the Zellweger syndrome (cell line W78/515), the infantile form of Refsum disease (cell line BOV84AD) and hyperpipecolic acidaemia (cell line GM3605), respectively. The mutant cell lines belonged to the same complementation group. The fibroblasts were cultured under identical conditions and were harvested at different time intervals after reaching confluence. Several peroxisomal parameters were determined. In agreement with previous reports, a lowered enzymic activity of acyl-CoA: dihydroxyacetonephosphate acyltransferase and a decrease in latent catalase clearly distinguished the patient cell lines from the control cell line. However, the cell lines exhibited a phenotypic heterogeneity. This was most strikingly encountered when cells were processed for indirect immunofluorescence microscopy and stained with anti-(catalase). The control cells exhibited a punctate fluorescence, which is indicative of the presence of catalase in peroxisomes. In the mutant cell line W78/515 a diffuse fluorescence was observed, indicative of the presence of catalase in the cytosol. In the other two mutant cell lines a punctate fluorescence was observed in some of the cells. Moreover, clear differences in the extent of proteolytic processing of acyl-CoA oxidase were detected. The mutant cell line BOV84AD displayed a control-like pattern with all molecular forms of acyl-CoA oxidase (72, 52 and 20 kDa) present, whereas in the W78/515 cell line only the 72 kDa component could be visualised. The GM3605 cell line was intermediate in this respect.

Acetyl-CoA C-Acetyltransferase↗

Critical evaluation of models developed for monitoring an industrial submerged bioprocess for antibiotic production using near-infrared spectroscopy.

Near-infrared spectroscopy (NIRS) is known to have potential for cost-effective monitoring of bioprocesses. Although this has been demonstrated in many instances and several models have been reported, information regarding the complexity of models required and their utility over extended periods of time is lacking. In the present study, the complexity of the models required for the NIRS prediction of substrate (oil) and product (tylosin) concentration in an industrial bioprocess that employs a physicochemically heterogeneous medium for antibiotic production was assessed. Measurements made by both the diffuse reflectance and transmittance modes were investigated. SEP values for the prediction of the analytes averaged 5% or less, for the successful models, when evaluated using an external validation set, 2 years after the initial model development exercise. Diffuse reflectance measurements showed poorer results, compared to transmittance measurements, especially for monitoring tylosin. In general, this investigation provides evidence to support the fact that models built for the prediction of analytes in a commercial bioprocess that employs a physicochemically complex production medium can be robust in performance over an extended period of time and that simple models based on fewer terms or latent variables can perform well, even in the context of matrices that are relatively complex. It also indicates that sample presentation is likely to be a critical factor in the successful application of NIRS in bioprocess monitoring, which merits further detailed investigation.

Anti-Bacterial Agents↗

Reticulo-endothelial sarcoma arising in the nose and palate (granuloma gangrenescens).

Granuloma of the nose which does not heal is a tripartite disease, including classical malignant granuloma, Wegener's granulomatosis, and a third group with neoplastic characteristics (granuloma gangrenescens). Five cases of this third type are described and 20 others from the literature are tabulated. The primary lesion is in the nasal or palatal region; after a latent period, metastases develop in many organs. The histological features are those of malignancy. Reasons are given for regarding the condition as a sarcoma of the reticulo endothelial system.

Granuloma↗

Serum precipitin reactions in Hashimoto's thyroiditis.

Sera from certain patients with Hashimoto's disease or a related condition contain a non-precipitating antithyroglobulin which produces in double-diffusion tests with thyroglobulin a line of clearing in the agar. Two such sera are described. Other sera from examples of the disease give negative precipitin tests with thyroglobulin but combine with sera containing ;clear line', non-precipitating antithyroglobulin to give a positive precipitin test. The serum from 15 out of 26 precipitin-negative cases of Hashimoto's disease showed this latent property. Eight of the 15 were tested by the tanned red cell technique and showed substantial titres of antithyroglobulin.

Autoantibodies↗

Epstein-Barr virus and gastrointestinal lymphomas in Korea.

To analyze the association of Epstein-Barr virus (EBV) with gastrointestinal non-Hodgkin's lymphomas arising in immunocompetent patients, 56 consecutive cases of gastrointestinal lymphomas (B-cell: 52-cases, T-cell: 3 cases, T/NK-cell: 1 case) occurring in the stomach (33 cases), intestine (22 cases) and esophagus (1 case) were investigated for the presence of EBV using polymerase chain reaction analysis as a screening method followed by EBER-1 RNA and DNA in situ hybridization (ISH) and immunohistochemistry for the expression of latent membrane protein 1 (LMP-1). Forty-seven cases demonstrated extractable DNA and EBV DNA was detected only in 4 cases. Among the, RNA (EBER-1) and DNA ISH analysis confirmed the presence of the EBV genome in tumor cells in 3 cases (T/NK-cell lymphoma of ileum, gastric high-grade B-cell lymphoma of mucosa-associated lymphoid tissue, gastric diffuse large B-cell lymphoma). Only the T/NK cell lymphoma showed diffuse positivity of tumor cells while 2 gastric B-cell lymphomas demonstrated a scattered positive reaction and no cases expressed LMP-1. Nine cases without extractable DNA by the PCR method showed no nuclear signal by EBER-1 ISH. These findings suggest that most sporadic primary gastrointestinal lymphomas in Korea are not associated with EBV.

Gastrointestinal Neoplasms↗

"Postpolio" sequelae and sleep-related disordered breathing.

OBJECTIVE: To analyze the clinical manifestations and various types of sleep-related disordered breathing (SRDB) in patients with a history of poliomyelitis and with current "postpolio" sequelae (PPS). MATERIAL AND METHOD: We retrospectively reviewed the medical records of 108 consecutive patients with PPS and sleep disturbances encountered during an 11-year period at Mayo Clinic Rochester and abstracted the features of acute polio, PPS, and results of sleep evaluation (overnight oximetry or polysomnography). Only those patients who were not receiving ventilatory support were included in the study. RESULTS: The features of PPS were dyspnea, fatigue, new weakness, and musculoskeletal pain. Of the 108 patients, 35 fulfilled the inclusion criteria. Sleep evaluations revealed three general types of disturbances: obstructive sleep apnea (group O, N = 19); hypoventilation (group H, N = 7); and both (group OH, N = 9). The mean apnea/hypopnea index was 37, 4, and 16 per hour in patients in groups O, H, and OH, respectively (P < 0.05), and the mean arterial carbon dioxide tension was 39, 60, and 55 mm Hg in these respective study groups (P < 0.05). The overall mean age at onset of symptoms of SRDB was 47 years, and the mean latent period after acute polio was 37 years. Hypersomnolence was the commonest SRDB symptom, present in 32 of the 35 patients. Snoring was noted in 100% of patients in group O, 0% in group H, and 67% in group OH. Patients in group O were obese and had normal lung function. Patients in group H tended to have normal weights and a history of diffuse neurologic deficits involving the trunk during the acute episode of polio. Scoliosis, restricted lung function, cor pulmonale, and decreased maximal respiratory pressures were common in patients in group H. Patients in group OH had overlapping features of those in groups O and H. CONCLUSION: In patients with PPS, we identified three patterns of sleep disturbances--obstructive sleep apnea, hypoventilation, and a combination of both. These groups are characterized by clinical features and by results of arterial blood gas determinations, overnight oximetry, and polysomnography. SRDB is a late sequela of poliomyelitis, and clinical evaluation should include information about sleep.

Carbon Dioxide↗

Rapid and quantitative detection of the microbial spoilage in chicken meat by diffuse reflectance spectroscopy (600-1100 nm).

AIMS: To evaluate the feasibility of visible and short-wavelength near-infrared (SW-NIR) diffuse reflectance spectroscopy (600-1100 nm) to quantify the microbial loads in chicken meat and to develop a rapid methodology for monitoring the onset of spoilage. METHODS AND RESULTS: Twenty-four prepackaged fresh chicken breast muscle samples were prepared and stored at 21 degrees C for 24 h. Visible and SW-NIR was used to detect and quantify the microbial loads in chicken breast muscle at time intervals of 0, 2, 4, 6, 8, 10, 12 and 24 h. Spectra were collected in the diffuse reflectance mode (600-1100 nm). Total aerobic plate count (APC) of each sample was determined by the spread plate method at 32 degrees C for 48 h. Principal component analysis (PCA) and partial least squares (PLS) based prediction models were developed. PCA analysis showed clear segregation of samples held 8 h or longer compared with 0-h control. An optimum PLS model required eight latent variables for chicken muscle (R = 0.91, SEP = 0.48 log CFU g(-1)). CONCLUSIONS: Visible and SW-NIR combined with PCA is capable of perceiving the change of the microbial loads in chicken muscle once the APC increases slightly above 1 log cycle. Accurate quantification of the bacterial loads in chicken muscle can be calculated from the PLS-based prediction method. SIGNIFICANCE AND THE IMPACT OF THE STUDY: Visible and SW-NIR spectroscopy is a technique with a considerable potential for monitoring food safety and food spoilage. Visible and SW-NIR can acquire a metabolic snapshot and quantify the microbial loads of food samples rapidly, accurately, and noninvasively. This method would allow for more expeditious applications of quality control in food industries.

Food Microbiology↗

[Function of external respiration in patients with systemic scleroderma (according to roentgenopneumopolygraphic data)].

External respiratory function was investigated in 33 patients with systemic scleroderma+ using roentgenopneumopolygraphy (RPPG). Respiratory changes consisted in diffuse and regional ventilation disturbance (after emphysematous, hypoventilation or mixed type), disorders of respiratory kinetics of the diaphragm, ribs and mediastinum. External respiratory functional disturbance showed direct correlation with the patients' age, period of disease and a degree of pathological activity. The type of external respiratory functional disturbance was unchanged during observation over time. The use of exercise testing showed the presence of signs of latent ventilation insufficiency in most of the patients.

Adult↗

[Clinico-laboratory pattern and effectiveness of glucocorticoid therapy of patients with primary diffuse mesangioproliferative glomerulonephritis].

The paper is concerned with clinico-laboratory correlations and assessment of short- and long-term results of glucocorticoid therapy (GCT) in 137 patients with diffuse mesangioproliferative glomerulonephritis (DMPGN). It may have different clinical variants and is characterized by a relatively favorable course in the first 10 yrs. A good clinical effect of GCT was observed only in some patients with the nephrotic variant of DMPGN in the absence or presence of insignificant fibroplastic changes, and in the absence or presence of the moderate tubulointerstitial component. In patients with a latent variant of DMPGN GCT made no considerable effect on the clinical symptoms of disease. The 15-year survival in patients on GCT was slightly higher (insignificant statistical difference) than that in patients receiving symptomatic treatment only.

Adolescent↗

[Neuropathy with contractures evoking the stiff-man syndrome. Latent solitary plasmacytoma].

A further case of apparently primary sensorimotor neuropathy is reported. The patient, a 31-year-old man, developed the syndrome after a 4-year history of a solitary vertebral plasmocytoma revealed by post mortem examination. Circulating monoclonal immunoglobulin and specific anomalies on nerve biopsy were absent. The condition became progressively worse, with initial and predominant autonomic nervous system anomalies. After 3 years, contractures of the limbs and paravertebral muscles, with painful paroxysmal attacks suggestive of the stiff-man syndrome appeared. Pathology confirmed the severity of the root lesions with diffusion to the cranial nerves. Reflex tests could not be conducted but the semiologic characteristics and the efficacity of baclofen were distinctive of continuous muscle fiber activities reported in some peripheral neuropathies. This case was comparable to some reported ones of interneuron rigidity.

Adult↗

In three types of interface dermatitis, different patterns of expression of intercellular adhesion molecule-1 (ICAM-1) indicate different triggers of disease.

We found distinct patterns of intercellular adhesion molecule-1 (ICAM-1) expression in three diseases characterized by interface dermatitis with mononuclear infiltrates and keratinocyte cytotoxicity: lichen planus (LP), subacute cutaneous lupus erythematosus (SCLE), and erythema multiforme (EM). In LP, basal keratinocytes show strong ICAM-1 expression associated with a dermal infiltrate, but ICAM-1 expression in the rest of the epidermis is minimal. In SCLE, there is diffuse epidermal ICAM-1 expression, sometimes with accentuation on the cell surface of basal cells. In EM, there is strong basal cell expression of ICAM-1 with evident cell surface accentuation, and also pockets of suprabasal expression with cell surface accentuation. These patterns are associated with different factors that trigger cytokine release in different locations. Both tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) produce greater relative ICAM-1 expression in basal keratinocytes than in more differentiated keratinocytes. In LP, the pure basal keratinocyte expression of ICAM-1 appears to be caused by cytokines, predominantly IFN-gamma, released by dermal lymphocytes. The pattern of ICAM-1 in SCLE corresponds to the pattern induced by ultraviolet radiation (UVR): diffuse epidermal ICAM-1 expression, sometimes with basal accentuation. Some individuals are "responders" to TNF-alpha or UVR, showing high levels of ICAM-1 expression following UVR or TNF-alpha stimulation in vitro or UVR stimulation in vivo. We propose that the pattern of ICAM-1 induction in SCLE is dependent on UVR-induced TNF-alpha release. EM is associated with apparent latent Herpes simplex virus, and Herpes simplex virus (HSV)-infected keratinocytes show enhanced ICAM-1 expression. We propose that in EM suprabasal ICAM-1 expression may be induced directly by HSV infection or indirectly through TNF-alpha release induced by HSV reactivation. Induction of ICAM-1 within the epidermis is stratified and individually variable. Basal keratinocytes show maximal induction of ICAM-1 expression due to innate sensitivity to TNF and IFN-gamma stimulation, and to location adjacent to dermal sources of cytokines. Suprabasal ICAM-1 can be induced by UVR and epidermal TNF-alpha release, and by factors such as viral infection. Different triggers of cytokine release and adhesion molecule induction may influence the different patterns of inflammation seen in diverse inflammatory skin diseases.

Erythema Multiforme↗

Characterization of a thermophilic bacteriophage for Bacillus stearothermophilus.

Saunders, Grady F. (University of Illinois, Urbana), and L. Leon Campbell. Characterization of a thermophilic bacteriophage for Bacillus stearothermophilus. J. Bacteriol. 91:340-348. 1965.-The biological and physical-chemical properties of the thermophilic bacteriophage TP-84 were investigated. TP-84 was shown to be lytic for 3 of 24 strains of Bacillus stearothermophilus tested over the temperature range of 43 to 76 C. The latent period of TP-84 on B. stearothermophilus strain 10 was 22 to 24 min. TP-84 has a hexagonal head, 53 mmu in diameter and 30 mmu on a side; its tail is 130 mmu long and 3 to 5 mmu wide. The phage has an S(50) (20,w) of 436, and bands at a density of 1.508 g/cc in CsCl (pH 8.5). The diffusion coefficient of TP-84 was calculated to be 6.19 x 10(-8) cm(2)/sec. From the sedimentation and diffusion data, a particle molecular weight of 50 million daltons was calculated for TP-84. The phage DNA has a base composition of 42% guanine + cytosine, deduced from buoyant density and melting temperature measurements.

Amino Acids↗

Enhancement of chronic Trypanosoma cruzi myocarditis in dogs treated with low doses of cyclophosphamide.

An enhancement of chronic myocarditis was obtained in dogs chronically infected with Trypanosoma cruzi protozoa soon after they were submitted to treatment with low doses of cyclophosphamide (50 mg/sq m bs three times a week for 3 weeks). Such treatment did not cause immunodepression. Myocarditis varied in intensity, but was quite severe and diffuse in some animals, with focal fibrinoid, coagulative, and lytic necrosis and invasion of disintegrating myocardial fibers by the mononuclear inflammatory cells. Untreated infected controls exhibited mild focal myocarditis, usually represented by accumulation of lymphocytes in the interstitial connective tissue. It is suggested that the administration of low doses of cyclophosphamide interfered with the immunologic suppressor network that is thought to maintain the chronic indeterminate (or latent) phase of T cruzi infection.

Animals↗

[Functional reserves of the thyroid gland in thyrotoxicosis remission].

A test with intramuscular injection of 5 or 10 U of TTH was carried out in 47 patients suffering from diffuse toxic goiter, including 34 cases at the stage of thyrotoxicosis remission. Results of this test were evaluated by the changes of I131 absorption by the thyroid gland and of the blood protein-bound iodine level. The thyroid gland TTH sensitivity was found to be diminished in 16 patients with thyrotoxicosis remission. The reaction was absent most regularly in patients with ophthalmopathy. This denotes a latent form of thyroid insufficiency and suggest that the patients with the negative response to the exogenous TTH are in the "risk group" in respect to the development of manifest hypothyroidism.

Adult↗

BHRF1, the Epstein-Barr virus (EBV) homologue of the BCL-2 protooncogene, is transcribed in EBV-associated B-cell lymphomas and in reactive lymphocytes.

BHRF1, one of many Epstein-Barr virus (EBV)-encoded proteins, shows strong functional homology to the human bcl-2 proto-oncogene product, a protein involved in the pathogenesis of a subset of B-cell lymphomas, ie, follicle center cell lymphomas (FCCL). We have investigated the presence of possible latent and lytic transcripts of BHRF1 using a reverse transcriptase-polymerase chain reaction (RT-PCR)-based assay in a group of EBV-associated B-cell lymphomas in patients with (N = 5) or without overt immunodeficiency (N = 4), in T-cell lymphomas (N = 9), and in cases of Hodgkin's disease (N = 6). BHRF1 transcription was found consistently in EBV-associated (ie, diffuse EBER 1/2-positive) B-cell lymphomas in patients with or without immune deficiency, whereas in EBV-associated T-cell lymphomas or in EBV-associated Hodgkin's disease, BHRF1 transcription was only detected in two T-cell lymphomas and one case of Hodgkin's disease, which also harbored EBER 1/2-positive reactive cells. Moreover, weak BHRF1 signals were found in two T-cell lymphomas where EBER 1/2 expression was detected mainly in sporadic reactive lymphocytes and in one reactive tonsil with sporadic EBER 1/2-positive lymphocytes. BHRF1 transcripts were found to be generated by the C or W promoter (associated with viral latency) and/or by the H promoter (associated with the virus lytic cycle). In all cases with H promoter-derived BHRF1 transcripts, transcripts encoding ZEBRA were also detected, suggesting a reactivation of the virus lytic cycle. Analysis of other EBV genes revealed transcription of BARFO in all tested EBV-harboring tissues. Transcription of EBNA1 and LMP1 was usually detected, whereas EBNA2 transcription was found exclusively in B-cell lymphomas in immunocompromised patients. These data demonstrate that BHRF1 transcripts are exclusively found in EBV-associated B-cell lymphomas. When BHRF1 transcripts are detected in T-cell lymphomas or in Hodgkin's disease, it is probably due to the presence of reactive EBER 1/2-positive lymphocytes. The consistent transcription of BHRF1 in EBV-associated B-cell lymphomas suggests a possible pathogenic role for this gene product in EBV-positive B-cell lymphomas analogous to bcl-2.

Base Sequence↗

Squamous carcinoma of the stomach after luetic linitis plastica.

This report illustrates many of the long term complicatio of syphilis involving the stomach. A 49-year-old woman with diffuse squamous metaplasia of the gastric mucosa developed invasive pure squamous cell carcinoma. The literature is reviewed and the probable pathophysiology is discussed.

Adenocarcinoma, Scirrhous↗

Changes in tonsils and adenoids in children with posttransplant lymphoproliferative disorder: report of three cases with early involvement of Waldeyer's ring.

Posttransplant lymphoproliferative disorder (PTLD) is an infrequent complication of transplantation in children, and this report emphasizes the value of tonsil and adenoid biopsy in the early management of this potentially life threatening condition. In all three cases biopsy specimens of tonsils and adenoids were diagnostic of polymorphic diffuse B-cell hyperplasia (PBCH). Immunophenotyping showed no immunoglobulin (Ig) light chain restriction, although immunoglobulin heavy chain (IgH) gene rearrangement was monoclonal in two cases. Despite an absence of serological evidence for acute Epstein-Barr virus (EBV) infection, EBV was detected in all cases by semiquantitative polymerase chain reaction (PCR) for EBV DNA, by in situ hybridization for EBV mRNA (EBER), and by immunoperoxidase for EBV latent membrane protein (LMP). All three patients were treated with reduced immunosuppression and acyclovir and are well (19, 28, and 28 months' follow-up) with no recurrence. Children without previous EBV exposure may develop PTLD localized to the tonsils/adenoids, and biopsy specimens of these tissues may permit early diagnosis and clinical intervention. Despite monoclonal gene rearrangement in two cases, overall features were not indicative of malignancy. Strong association with EBV is helpful in confirming the diagnosis of PTLD and is consistent with initial presentation in the tonsils/adenoids.

Adenoids↗