bluuebunny/crossref_metadata_2025 huggingface dataset:
Nystagmus Findings in Healthy Subjects Examined with Infrared Videonystagmoscopy
Authors: Geisler Christian , Bergenius Johan , Brantberg Krister
Published: April 2003

The increased use of videosystems for the detection of nystagmus is a new diagnostic tool in the diagnosis of patients with vestibular disorders. Small video cameras mounted in a light sealed mask visualize the eyes which are illuminated with infrared light. Compared to the well-established use of Frenzel glasses the patient has no visual references at all. This new technique requires standards for normal limits. Thirty subjects between 20 and 78 years of age with no history of vestibular disorders were examined with infrared video-oculoscopy with the gaze in primary position, after head-shake and in supine position with head torsion and Dix-Hallpike positions backward and forward according to a standardized procedure at our department. Two subjects had spontaneous nystagmus, but nystagmus after head-shake was not found in any. No subject had torsional nystagmus in the Dix-Hallpike positions. In the elderly subjects horizontal nystagmus in head hanging position was a frequent finding.
Lymphoma in the Ear
Authors: Merkus P. , Copper M.P. , van Oers M.H.J. , Schouwenburg P.F.
Published: April 2003

Background: Malignant tumors of the ear are rare. The most common malignant tumors are squamous cell carcinomas and adenocarcinomas. Lymphoma in the ear is rare. Methods: We report 2 cases of a primary presentation of a lymphoma of the ear. The literature since 1947 is reviewed. Results: An 83-year-old woman with an anaplastic large cell lymphoma of the skin of the external auditory meatus and a 75-year-old man with a B-cell non-Hodgkin’s lymphoma of the mastoid process are presented. The literature review shows that only 16 cases of lymphomas of the ear have been reported so far. Conclusions: In a case of therapy-resistant otitis and/or peripheral facial paralysis malignancy should be excluded by computer tomography of the mastoid. For histopathological diagnosis unfixed specimens are preferable. Uniform treatment of lymphomas of the ear has not been established.
Bilateral Parotid Gland Basal Cell Adenomas
Authors: Suzuki Shigenori , Okamura Hiro-oki , Ohtani Iwao
Published: April 2003

We report a 65-year-old female with basal cell adenomas arising in the left and right parotid glands and review the literature. Diagnosis was based on clinical features, ultrasonographic and CT findings as well as histopathological examination. Parotid tumours usually arise on one side and bilateral occurrence is rare, accounting for 1–3% of all parotid tumours. Most bilateral parotid tumours are Warthin’s tumours and pleomorphic adenomas, and bilateral basal cell adenomas of the parotid glands are very rare and only 5 cases including ours have been reported. The exact mechanisms contributing to the development of bilateral parotid tumours remain unknown. We speculate on the involvement of environmental and genetic factors since the histological features of both parotid tumours are identical in most cases.
Antrolithiasis in the Frontal Sinus
Authors: Mori Shigehito , Lee Kotetsu , Fujieda Shigeharu , Kojima Akihiro , Saito Hitoshi
Published: April 2003

A very rare case of sinusitis with antrolithiasis in the left frontal sinus of a 63-year-old male patient is reported. Various conservative treatments had no effect on the decrease of his left frontal pain and of postnasal drip. Neither bacteria nor fungus were detected in the discharge. Computed tomographic scanning revealed several high-dense spots in an isodense shadow in the left frontal sinus. At first, endoscopic sinus surgery (ESS) was employed and a stony mass was detected in the nasofrontal duct and sinus. Patency of the nasofrontal duct was insured and a sticky paste and small masses were removed as well as possible. However, the flow of discharge from the frontal duct continued after surgery. We performed a second operation with extranasal approach and additional stones in the sinus were successfully removed. Most cases of antrolithiasis are caused by a foreign body or caseous sinusitis with fungus. The maxillary sinus is the most common site of disease in antrolithiasis. It is unknown why the present case of antrolithiasis was in the frontal sinus. In such cases of antrolithiasis or cases having pastelike contents in the frontal sinuses, we conclude that ESS may be an unsuccessful treatment and a classical surgical approach may be required.
Benign and Malignant Oncocytoma of the Salivary Glands with an Immunohistochemical Evaluation of Ki-67
Authors: Ito Keiko , Tsukuda Mamoru , Kawabe Ryoichi , Nakagawa Chihiro , Matsushita Kazuhiko , Kubota Akira , Furukawa Madoka , Kameda Yoichi , Ito Takaaki
Published: April 2003

We present two cases of benign oncocytoma derived from the parotid gland and minor salivary gland and one case of malignant oncocytoma from the parotid gland. The proliferative activity of the tumor cells was evaluated immunohistochemically for Ki-67. The average frequency of Ki-67-positive cells was 3.3% in the benign oncocytomas and 6.5% in the malignant oncocytoma. The higher frequency of Ki-67-positive cells in the malignant oncocytoma might reflect active cell proliferation. Ki-67 immunostaining may be useful in distinguishing a benign oncocytoma from a malignant oncocytoma.
Stereoscopic Display of a Three-Dimensional Image of the Larynx Using High-Speed Helical Scanning
Authors: Sakakura Atsushi , Yamamoto Yuzo , Uesugi Yasuo , Nakai Ken , Hayashi Ibuki , Makimoto Kazuo , Takenaka Hiroshi , Narabayashi Isamu
Published: April 2003

To evaluate the usefulness of stereoscopic images of larynges using helical CT in stereo mode, a retrospective review of the characteristics of stereoscopic viewing of larynges was made. The subjects were 3 patients with laryngeal cancer, 1 patient with laryngeal leiomyosarcoma and 1 patient with an advanced tongue carcinoma whose formalin-fixed larynx was extirpated. The larynges were scanned by high-speed helical CT using 1- to 2-mm slices. The reproduction of stereographic images was performed by the manipulation and rotation of three-dimensional structures around the y-axis on the computer display. The three-dimensional images of the complex structures, such as the arytenoid cartilage, aryepiglottic fold and pyriform sinus, were better observed by binocular images (stereograms) than by monocular images. Stereoscopic views of the larynx are useful in producing three-dimensional images of the unseen inner surface of the human body.
Efficacy of Inhalation Form of Furosemide to Prevent Postsurgical Relapses of Rhinosinusal Polyposis
Authors: Passàli D. , Mezzedimi C. , Passàli G.C. , Bellussi L.
Published: April 2003

The aim of the work is to demonstrate the efficacy of furosemide to prevent relapses of rhinosinusal polyps after surgical treatment. Two groups of people with rhinosinusal polyposis were enrolled: the study group consisted of 64 patients and the control group of 40 subjects. After surgical treatment, the study group started the therapy with topical furosemide; the control group had no treatment administered after the operation. Six years after the operation only 4 cases of relapse were noticed in the study group (10%), while there were 12 relapses, 4 slight (6.4%) and 8 severe (20%), in the control group. In conclusion, furosemide could represent a valid therapeutic aid in the prevention of nasosinusal polyps.
The Relationship between Traumatic Tympanic Membrane Perforations and Pneumatization of the Mastoid
Authors: Aktaş Davut , Kutlu Ramazan
Published: April 2003

We evaluated the possible relationship between tympanic membrane perforations resulting from blast trauma or slap and pneumatization of the mastoid cells. A total of 25 male patients with tympanic membrane perforations resulting from blast injury (n = 7), slap (n = 17), and football hit (n = 1) and 20 healthy male volunteers without any ear problem had temporal bone computed tomographic scans in the axial plane, parallel to the infraorbitomeatal line, with 2 mm slice thickness and 2-mm intervals using bone algorithm with a ProSpeed Spiral tomography machine. The area of air cells in each slice was measured using trace and area measurement functions of the tomography machine, and by multiplying the resulting area by slice thickness, the volume of each slice was calculated. For each ear, the total of volumes of air cells was calculated by adding the volumes of each slice containing air cells. The calculated volumes of mastoid cells were evaluated by comparing microscopic findings. Both patient and control groups consisted of males, and their ages ranged from 17 to 32 (mean 24.5) years. Microscopic examinations revealed that perforations were frequently located in the lower quadrants and that most of them were less than 3 mm. There were no pars flaccida and marginal perforations. Ossicular chain destruction was noted neither in temporal bone tomographic nor during intraoperative examinations. The mean (± SD) volumes of right and left ear mastoid air cells in patient and control groups were 6.92 ± 2.45 vs. 7.00 ± 2.59 cm3 and 9.04 ± 4.55 vs. 8.95 ± 4.53 cm3, respectively, and the differences were not statistically significant. It was found that the level of mastoid pneumatization has no statistically significant effect on tympanic membrane pathologies due to blast or other injuries.
Update on the Pathology and Management of Benign Paroxysmal Positional Vertigo
Authors: Gacek Richard R. , Gacek Mark R.
Published: April 2003

Objective: To describe the otopathology in benign paroxysmal positional vertigo (BPV) and report our experience with singular neurectomy (SN) over a 24-year period. Materials: (I) The temporal bones (TB) of 3 patients who demonstrated BPV before death were acquired and prepared for examination by light microscopy. (II) A clinical series of patients who underwent SN for chronic disabling BPV has been updated to December 1998. Results: (I) In each of the 3 TB representing the downmost ear in the Hallpike maneuver, two pathologic changes were observed: (1) scattered degenerative neurons were found in the facial nerve meatal ganglion (MG); (2) focal axonal degeneration of vestibular axons (2 TB) or degenerated ganglion cells (1 TB) were observed in the inferior vestibular division. (II) From 1974 to 1998, SN was performed unilaterally in 177 patients and bilaterally (sequential) in 10 patients (n = 197). The age, sex and etiologic factors in the series were consistent with the literature. In 189 patients (96%), BPV was completely relieved by SN, while 3 patients (1.5%) experienced partial relief and 5 patients (2.5%) failed to benefit from SN. Sensorineural hearing loss followed SN in 5 patients (2.5%). Conclusions: The focal degeneration in the inferior vestibular nerve or ganglion may result from reactivation of a latent neurotropic virus in inferior vestibular ganglion cells as a result of various stressors (upper respiratory infection, trauma, surgery, general anesthesia, pregnancy). The portal of entry of the virus is likely from the nose and oral cavity to the MG of the facial nerve where latency is assumed and spread to the vestibular ganglion develops. The series of 197 SN over a 24-year period demonstrates that SN is a safe, effective surgical maneuver to selectively ablate function of the posterior semicircular canal crista.
Bilaterale chronische Parotitis bei unerkanntem Münchhausen-Syndrom
Authors: Biermann E. , Schultz K.-D. , Morgenstern C.
Published: April 2003

Es wird ein über 8 Jahre verkanntes Münchhausen-Syndrom mit fast letalem Ausgang beschrieben, bei dem eine chronische Parotitis mit Abszedierung durch Autoinjektionen unterhalten wurde. Die Patientin wurde beidseitig parotidektomiert. Die Gründe für die Fehldiagnose werden diskutiert.
Sudden Deafness – A Critical Evaluation of Pathogenesis and ‘Cure’
Authors: Hultcrantz Elisabeth
Published: April 2003

Objective: To discuss the possible etiology, pathogenesis and ‘cure’ of idiopathic sudden deafness (SD). Method: A review was made of different methods for the study of inner-ear physiology, especially its microcirculation, relating them to clinical evaluation and praxis for SD. Results: Cochlear blood flow (CBF) can be measured quantitatively with the microsphere method in animals. Direct qualitative measurements can be performed using the laser Doppler method. The CBF is partly autoregulated, but to a lesser degree than cerebral blood flow. Sympathetic stimulation decreases CBF up to 25%. Noise does not influence total CBF but seems to reduce blood flow in the lateral wall. Nicotinic acid, hemodilution and osmotic drugs increase the CBF proportionally. Carbogen increases the CBF but also creates acidosis. Treating patients with SD in accordance with these findings does not show any convincing effect compared to no treatment. Conclusion: More and more diseases have been identified which can have SD as a symptom. It is important to investigate to identify these treatable cases. Idiopathic cases should not be exposed to hazardous systemic medication or surgery. Local treatment through the round window will be the treatment modality for the future, but more basic research is necessary.
Keimbesiedlung bei Komplikationen akuter und chronischer Sinusitiden
Authors: Mertens Jürgen , Maune Steffen , Rudert Heinrich , Ullmann Uwe
Published: April 2003

Fragestellung: Komplikationen von Nasennebenhöhlenentzündungen (orbitale und zerebrale Komplikationen, Stirnbeinosteomyelitiden) erfordern neben der notfallmässigen operativen Sanierung eine hochdosierte antibiotische Behandlung. Diese muss das für die Komplikationen zu erwartende verantwortliche Keimspektrum abdecken. Das Ziel der vorliegenden Untersuchung war es, die Keimspektren bei Komplikationen akuter und chronischer Nasennebenhöhlenentzündungen zu ermitteln und, da das Ergebnis der Abstrichuntersuchung nicht abgewartet werden kann, ein adäquates Behandlungsschema zu entwerfen. Patienten und Methoden: Es wurden die Abstrichergebnisse von 58 Patienten mit Komplikationen bei Sinusitis ausgewertet und daraus die Keimbesiedlung ermittelt. Es handelte sich dabei um Fälle mit akuter und chronischer Sinusitis. In allen Abstrichen wurden pathogene Keime gefunden. Ergebnisse: Bei den 21 Patienten mit akuten Sinusitiden wurden ausschliesslich Streptokokken, Staphylokokken und Anaerobier nachgewiesen. Bei den 37 Patienten mit chronischen Sinusitiden war mit 43% der hohe Anteil der sogenannten Problemkeime – Pseudomonas aeruginosa und Enterobakterien – auffällig. Die Beteilung von Anaerobiern war bei den chronischen Sinusitiden mit 13,5% deutlich niedriger als bei den akuten Sinusitiden mit 38%. In beiden Gruppen lag ein hoher Anteil von Mischinfektionen vor. Er war bei den chronischen Nasennebenhöhlenentzündungen mit 64,8% deutlich höher als bei denen der akuten Sinusitiden mit 42,8%. Schlussfolgerungen: Für die Antibiotikabehandlungen der Komplikationen akuter Sinusitiden mit dem geringen Keimspektrum lauten unsere Antibiotikaempfehlungen: Amoxycillin + Clavulansäure oder Sulfamicillin oder Oralcephalosporine (z.B. Cephaclor, Cefuroximaxetil, Cefpodoximproxetil) in Kombination mit Clindamycin. Für die Antibiotikabehandlungen von Komplikationen chronischer Sinusitiden sollten nur Kombinationstherapien eingesetzt werden. Fluorchinolone + Metronidazol/Clindamycin sind hier die Mittel der Wahl.
Difficultés liées au développement d’une échelle de handicap vestibulaire
Authors: Erni Corinne , Guyot Jean-Philippe
Published: April 2003

Le concept de «qualité de vie» est un indicateur de plus en plus utilisé pour évaluer l’impact d’une maladie dans la vie quotidienne d’un individu. Il implique l’exploration de dimensions physiques, psychiques, de dépendance, de relations sociales et de relations à l’environnement. Toutes sortes d’outils ont été élaborés pour évaluer la qualité de vie, dans diverses affections. Pour évaluer le handicap résultant d’affections vestibulaires, Jacobson et Newmann ont développé un questionnaire, aujourd’hui cité en référence dans de nombreuses publications traitant d’affections otoneurologiques. Nous l’avons traduit en français et utilisé chez 45 patients. Bien que la traduction ait été faite selon des modalités très strictes pour garder au texte tout son sens, certaines questions ont dû être modifiées pour être comprises d’une population de langue et de culture françaises. Une fois les modifications apportées, les patients ont estimé que les questions reflétaient correctement leurs préoccupations. La version française de ce questionnaire devra encore être validée avant d’être utilisée de routine sur une large échelle.
Differential Regulation of the Expression of Cytokine-Induced Neutrophil Chemoattractant by Mouse Macrophages
Authors: Crippen Tawni L. , Riches David W.H. , Hyde Dallas M.
Published: April 2003

The production of cytokine-induced neutrophil chemoattractant (CINC) by functionally diverse mouse bone-marrow-derived macrophages was determined. Studies showed that β1,3-glucan, IL-1β, TNFα and IFNγ/TNFα induced expression and production of CINC in macrophages while neither IFNγ nor TGFβ alone induced detectable CINC expression. Pretreatment or simultaneous treatment of macrophages with TGFβ resulted in suppression of CINC protein production. These studies demonstrate that IFNγ and TNFα, found early during the inflammatory response, induce production of CINC, as well as induce macrophages into a cytocidal state that are capable of killing transformed cells, parasites and bacteria, and recruiting neutrophils. In contrast, TGFβ, found during reparative stages of the inflammatory response, suppressed production of CINC, while inducing the development of inflammatory macrophages that are capable of producing lysosomal enzymes, enhanced endocytosis and ingestion of particulate matter and function to scavenge debris, debride tissue and stimulate repair.
Choline Deficiency Induces Apoptosis and Decreases the Number of Eosinophilic Preneoplastic Foci in the Liver of OXYS Rats
Authors: Albright Craig D. , Zeisel Steven H. , Salganik Rudolf I.
Published: April 2003

Choline deficiency (CD) was previously shown to trigger apoptosis in rat hepatocytes in culture and in vivo. In the present study we investigated the effects of short-term withdrawal of choline from the diet on the expression of putative preneoplastic foci in OXYS rats, an inbred strain with an inherited overproduction of free radicals. Animals were fed a defined, choline-sufficient (CS, control) or choline-deficient (CD) diet for 6 weeks. Eosinophilic, glutathione S-transferase (π class) (+) preneoplastic foci were found in histologic sections of control OXYS rat liver. CD caused a 60% decrease in the number of eosinophilic foci per liver section (27.0 ± 6.1 vs. 10.6 ± 4.6 foci/section) compared to CS controls. Apoptotic bodies were detected in 0.18 ± 0.03% of hepatocytes in CD livers compared to 0.05 ± 0.009% of hepatocytes in controls. Cells which exhibited an apoptotic morphology in hematoxylin and eosin-stained sections were TUNEL-positive, confirming the induction of apoptosis. Also in CD animals compared to controls, there was an increased expression of p27Kip1 protein, and a reduction in PCNA nuclear labeling and the number of mitotic figures, consistent with an inhibition of cell proliferation in the livers of CD animals. This study shows that the liver of OXYS rats with an inherited overgeneration of free radicals retains sensitivity to CD, and that this p53-independent trigger of apoptosis can decrease the number of eosinophilic foci in the livers of these animals.
Chemoattractant Factors and the Control of Human Immunodeficiency Virus Replication
Authors: Baier Michael , Bannert Norbert , Werner Albrecht , Adler Henric S. , Otteken Ahlert , Beer Brigitte , Norley Steve , Kurth Reinhard
Published: April 2003

Factors secreted by CD8(+) T cells have been described to suppress immunodeficiency virus replication. The research efforts to identify these factors led to the proposal of some candidate proteins as being responsible for the antiviral effects. Chemokines and IL-16 are secreted by CD8(+) T cells and inhibit HIV replication through different mechanisms. However, their antiviral properties cannot fully explain the inhibitory activities found in cell culture supernatants from CD8(+) T cells.
M Cells as Portals of Entry for HIV
Authors: Owen Robert L.
Published: April 2003

Accumulating evidence points toward active uptake by mucosal antigen sampling cells as the mechanism for rectal HIV acquisition. Organized lymphoid tissue in the intestine consists of lymphoid follicles with an epithelium containing M cells specialized for uptake and transport of microorganisms, bringing them into contact with lymphoid cells. M cells have been found in the human colon and rectum, and adherence and uptake of HIV by M cells in mouse and rabbit Peyer’s patches has been demonstrated in vitro. In an in vivo mouse model of viral acquisition, reovirus is actively taken up by M cells into rectal lymphoid tissue containing CD4 lymphocytes and macrophages, which are targets and replication sites for HIV. Immunization strategies for prevention of HIV transmission should include a mucosal component to prevent initial entry, since elimination from cellular sanctuaries remains an elusive goal.
Gastrointestinal Pathology in Rhesus Monkeys with Experimental SIV Infection
Authors: Kaup F.-J. , Mätz-Rensing K. , Kuhn E.-M. , Hünerbein P. , Stahl-Hennig C. , Hunsmann G.
Published: April 2003

The updated results of current pathomorphological investigations in SIV-infected rhesus monkeys (Macaca mulatta) are summarized. After experimental infection with several SIVmac251 subtypes and various vaccination trails, 147 rhesus monkeys were morphologically examined until now. The pathology of the gastrointestinal tract in SIV-infected animals resembled those of human cases with HIV and AIDS. Alterations were considered to be primary SIV-induced (SIV enteropathy, giant cell disease) or secondary caused by opportunistic agents. Typical secondary gastrointestinal opportunistic infectious agents were parasites (Cryptosporidium sp., Trichuris sp., Trichomonas sp., Spironucleus sp.), viruses (cytomegalovirus, adenovirus) and bacteria (Mycobacterium simiae). Five animals developed malignant lymphomas involving the intestinal tract. The present observations revealed that SIV infection of rhesus monkeys provide an excellent model for studies on the pathogenesis of HIV in man.
High-Risk Human Papillomavirus Infection and E6 Protein Expression in Lesions of the Uterine Cervix
Authors: Pillai M. Radhakrishna , Lakshmi S. , Sreekala S. , Devi T. Ganga , Jayaprakash P.G. , Rajalakshmi T.N. , Devi C.G. Chandrika , Nair M. Krishnan , Nair M. Balaraman
Published: April 2003

Pathologic and epidemiologic investigations carried out over the past several years have provided evidence that carcinogenesis in the uterine cervix is a multi-step process involving discreet preinvasive stages. Molecular epidemiologic data also indicate that human papillomavirus (HPV) infection is a critical factor in the tumor progression process. In vitro studies have shown that for the initiation and maintenance of the malignant phenotype, the expression of the HPV-transforming protein E6 is required. The E6 protein produced by the high-risk HPV types 16 and 18 can bind to and inactivate the tumor suppressor protein p53 leading to deregulated proliferation and defective apoptosis, thus facilitating tumor progression. Therefore, determination of the HPV genotype alone may not be sufficient in assessing tumor progression in the uterine cervix. In the present study, a total of 623 cervical tissue samples at various phases of tumor progression were assessed for HPV infection by nonisotopic in situ hybridization (NISH) and for HPV 16/18 E6 protein expression by immunocytochemistry. There was significant correlation between the extent of histological abnormality and HPV infection. Significant correlation (r = 0.707, p = 0.000) was observed between the presence of HPV 16 and high-grade squamous intraepithelial lesions (SILs) and invasive cancer. The odds ratio of a cervical tissue infected with HPV 16 falling into these two categories was 44.57 (95% CI: 27.10, 73.30). The E6 protein also was mostly detected in high-grade SILs and cervical cancer tissue expressing either HPV 16 or 18. It was less frequent in low-grade SILs infected with HPV 16/18 and was absent in benign cervical tissue infected with HPV 16. The odds ratio of an HPV-16/18-infected cervical tissue positive for E6 being a high-grade SIL or invasive cancer was 16.20 (95% CI: 6.06, 43.33). These results thus show the clinical utility of HPV characterization along with the analysis of the transforming protein E6 in the assessment of tumor progression in the uterine cervix.
Regulation of Vascular Endothelial Growth Factor Receptor KDR in vitro by a Soluble Factor in Confluent Endothelial Cells
Authors: Liu Wenbiao , Ellis Lee M.
Published: April 2003

Hypoxia regulates the expression of both vascular endothelial growth factor (VEGF) and its receptor (KDR). We have shown that cell density regulates VEGF expression in colon cancer and hypothesized that a similar mechanism regulates KDR in endothelial cells. Human umbilical vein endothelial cells were grown as sparse and confluent monolayers. Northern blot analysis revealed that KDR and VEGF mRNA expression in confluent cells was more than two-fold greater than in sparse cells. In contrast, flt-1 expression increased only slightly in cells grown to confluence. Cells were then plated at various concentrations and subjected to semi-quantitative PCR; KDR mRNA expression increased as cell density increased. Serum-free conditioned medium from cells grown to confluency for 48 h was added to sparsely plated cells, and KDR expression in the sparse cells increased twofold. We conclude that cell density regulates KDR endothelial cell expression via an unidentified soluble factor.
Human Psoriatic Skin in Organ Culture: Comparison with Normal Skin Exposed to Exogenous Growth Factors and Effects of an Antibody to the EGF Receptor
Authors: Varani James , Kang Sewon , Stoll Stefan , Elder James T.
Published: April 2003

Organ cultures were established from psoriatic lesional skin of 24 different individuals and maintained for 8 days under serum-free, growth-factor-free conditions. Nonlesional skin from 14 of the same individuals and normal skin from another 12 individuals were also maintained in organ culture. At the end of the incubation period, the tissues were fixed in formalin and examined histologically. Lesional skin continued to express features of psoriatic plaque, which included irregularly shaped epithelial cells arranged in a disorganized fashion, and elongation of the rete ridges with a thickening in their lower portion. Abnormal epidermal differentiation and separation of the upper epidermal layers from the lower layers was also a consistent feature. In contrast, nonlesional skin from psoriatic patients exhibited a histological appearance which resembled that of site-matched normal skin. When normal skin was exposed to a growth-factor-enriched culture medium during the 8-day incubation period, it exhibited a histological appearance similar to that of psoriatic skin. In addition to abnormal histological features, the psoriatic skin in organ culture released higher amounts of matrix metalloproteinase-9 (MMP-9; 92-kD gelatinase B/type IV collagenase) into the culture fluid than either nonlesional skin or normal skin. Organ cultures of psoriatic lesional skin from 6 individuals were maintained for 8 days in the presence of an antibody to the human epidermal growth-factor (EGF) receptor. The abnormal histological features of the psoriatic tissue were partially ameliorated in the presence of the antibody. These data suggest that growth factors which act through the EGF receptor help to maintain the psoriatic phenotype in organ culture. They also suggest that organ culture may provide a useful tool with which to elucidate the pathophysiological mechanisms of altered keratinocyte proliferation and differentiation in psoriasis.
Loss of Heterozygosity on the Short Arm of Chromosome 3 in Cervical Intra-Epithelial Neoplasia without Concomitant Cervical Carcinoma
Authors: Fouret Pierre J. , Dabit Dominique , Mergui Jean-Luc , Uzan Serge
Published: April 2003

Losses of heterozygosity on the short arm of chromosome 3p are common in cervical carcinomas in the 3p13-3p21 region, and can be observed in intra-epipthelial lesions accompanying cervical cancers. As a preliminary attempt to determine whether these losses can be observed in intra-epithelial cervical lesions without concomitant invasive carcinoma, we have used two microsatellite markers located at the two most frequently deleted segments of the 3p13-3p21 region. We have studied 36 cases of grade II and grade III cervical intra-epithelial neoplasias obtained by conisation biopsies and 30 cases of cervical carcinoma including 3 micro-invasive squamous cell carcinomas. We found loss of heterozygosity or microsatellite instability in 6 of 16 (38%) and 9 of 23 (39%) informative cases of cervical carcinoma at 3p13 and 3p21, respectively. Four of 27 (15%) cases of cervical intra-epithelial neoplasia showed loss of heterozygosity at 3p13, whereas loss of heterozygosity or microsatellite instability at 3p21 was found in 5 of 19 cases (26%). No relationship was found between 3p loss of heterozygosity and human papillomavirus infection. In conclusion, losses of heterozygosity at 3p13 and 3p21 occur in premalignant lesions without concomitant invasive lesions. The prevalence and precise extent of these losses should be established by a more extensive analysis.
T Cells Mediate Treatment of Six-Day-Old Cytokine-Gene-Transfected Mouse Mammary Tumor
Authors: Matory Yvedt L. , Dorfman David M. , Chen Man , Wu Lei , Spanjaard Remco A. , Goedegebuure Peter S. , Eberlein Timothy J.
Published: April 2003

We have previously shown that immunologically different mouse mammary cancer cell lines induce antitumor responses after IL2 or IL4 gene transfection. We now report the ability of cytokine-transfected tumors to induce eradication of established wild-type tumor. Animals with 6-day-old tumor treated with IL2-transfected cells also had significantly smaller tumors 2.8 and 1.7 cm2 (EMT6 and 410.4). Findings were similar for IL4-transfected cells. Tumor infiltrating lymphocytes or cells from draining lymph nodes demonstrated tumor-specific in vitro cytotoxicity. Immunohistochemical studies revealed T cell infiltrates in transfected tumors.
Role of Interleukin-8 in Tumor Growth and Metastasis of Human Melanoma
Authors: Bar-Eli Menashe
Published: April 2003

Expression of interleukin-8 (IL-8) by human melanoma cells correlates with their metastatic potential in vivo. Moreover, UVB irradiation of primary cutaneous melanoma induces IL-8 mRNA and protein production and increases both tumor growth and metastasis in nude mice. Although IL-8 has been shown to be an angiogenic factor, the biological consequences of increased IL-8 production by melanoma cells and the role of IL-8 in the metastatic process remains unclear. The purpose of this review is to determine the role of IL-8 in tumor growth and metastasis of human melanoma. Transfection of nonmetastatic and IL-8-negative melanoma cells with the IL-8 gene rendered them highly tumorigenic and increased their metastatic potential in nude mice. The IL-8-transfected cells displayed upregulation of MMP-2 expression and activity and increased invasiveness through Matrigel-coated filters. Activation of MMP-2 by IL-8 can enhance the invasion of host stroma by the tumor cells and increase angiogenesis and, hence, metastasis. In addition to UVB, IL-8 can also be upregulated by hypoxia conditions, suggesting that the environment plays a major role in regulating IL-8 expression and metastasis. The studies summarized in this review suggest that in melanoma, IL-8 may serve as the angiogenic factor distinguishing benign from malignant cells.
Stereology and Immunohistochemistry of the Myocardium in Experimental Hypertension: Long-Term and Low-Dosage Administration of Inhibitor of the Nitric Oxide Synthesis
Authors: Gomes Pessanha Mônica , Mandarim-de-Lacerda Carlos Alberto , Dumas Hahn Myriam
Published: April 2003

Morphological changes in the myocardium after left ventricular hypertrophy, due to chronic experimental hypertension, require an understanding of the quantitative relationship between myocyte and nonmyocyte compartments forming the structural framework of the myocardium. Hypertension was induced by long-term low-dosage inhibition of nitric oxide synthesis by NG-nitro-L-arginine methyl ester (L-NAME) in rats. L-NAME (12 mg/kg) was given to animals in water ad libitum during 15 weeks. After this period, systolic blood pressure increased almost 50% as compared with that in the control group. Morphological changes in control and L-NAME animals were investigated with stereology and immunohistochemistry. Comparing control and L-NAME animals, the surface density of myocytes decreased 73.7% while the mean cross-sectional area increased 97.6% in L-NAME rats. The volume density of myocytes decreased 45.9% and the volume density of the interstitium increased 71.7% in L-NAME rats. No stereological difference was found in blood vessels comparing the two groups. Remodeling of the cardiac interstitium occurred with increased deposition of both fibronectin and type III collagen. Fibronectin was seen in both early and latter responses to infarction while type III collagen was seen mainly in areas of incomplete healing among myocytes and around intramyocardial branches of the coronary arteries. The long-term low-dosage administration of an inhibitor of the NO synthase such as L-NAME causes myocyte hypertrophy and early interstitial and perivascular fibrosis without important quantitative changes in microcirculation.
Changes in Keratin and Filaggrin Expression in the Skin of Chronic Proliferative Dermatitis (cpdm) Mutant Mice
Authors: HogenEsch H. , Boggess D. , Sundberg J.P.
Published: April 2003

The expression of keratins and filaggrin by keratinocytes is a highly regulated process and depends on their state of differentiation and proliferation. As such, these proteins can be used as markers to determine if keratinocyte differentiation is normal. Mutant cpdm/cpdm mice develop a chronic skin disease characterized by epidermal hyperplasia and inflammation. Immunohistochemical staining for the basal keratins K5 and K14 revealed expression in the basal and suprabasal cell layers. The expression of K1 and K10 was reduced and limited to the outer layers of the stratum spinosum. Keratin 6 was expressed in the suprabasal layers of affected skin, and throughout all layers in severely affected skin. Filaggrin was present in the stratum granulosum which had variable thickness. These results indicate that the differentiation of keratinocytes in cpdm/cpdm mice was normal. The altered distribution and expression of keratins in comparison with the skin of control mice was the result of hyperproliferation.
Expression of Substance P Receptors in Normal and Psoriatic Skin
Authors: Staniek Véronique , Doutremepuich Jean-Daniel , Schmitt Daniel , Claudy Alain , Misery Laurent
Published: April 2003

Recently, sustance P receptors (SPR) have been detected in neonatal foreskin. Our purpose was to determine the expression of SPR in other localizations than neonatal foreskin. As SP has been implicated in the pathogenesis of inflammatory cutaneous lesions, we wondered whether SPR localization was modified in psoriatic lesions. In normal skin, SP binding sites were detected using biotinylated SP and abrogated by a specific NK1 antagonist (spantide) on blood vessels, sweat glands and hair follicles. In the normal epidermis, SPR were usually observed on granular layers but may also be observed on other cell layers. The SP binding processed on cultured keratinocytes demonstrated that SPR were expressed in the epidermis, except basal cell layers, confirming that keratinocytes constitutively express SPR. In skin lesions of psoriatic patients, SP binding sites were expressed on the uppermost keratinocytes which are not granular cells, and seem to be overexpressed. Our results raise the question of the role of SPR on psoriatic keratinocytes.
Cellular Reservoirs for Coronavirus Infection of the Brain in β2-Microglobulin Knockout Mice
Authors: Lavi Ehud , Das Sarma Jayasri , Weiss Susan R.
Published: April 2003

Mouse hepatitis virus (MHV) A59 infection which causes acute encephalitis, hepatitis, and chronic demyelination, is one of the experimental models for multiple sclerosis. Previous studies showed that lethal infection of β2-microglobulin ‘knockout’ (β2M(–/–)) mice required 500-fold less virus and viral clearance was delayed as compared to infection of immunocompetent C57Bl/6 (B6) mice. To investigate the mechanism of the increased susceptibility of β2M(–/–) mice to MHV-A59, we studied organ pathology and the distribution of viral antigen and RNA during acute and chronic infection. A59-infected β2M(–/–) mice were more susceptible to acute encephalitis and hepatitis, but did not have increased susceptibility to demyelination. Viral antigen and RNA distribution in the brain was increased in microglia, lymphocytes, and small vessel endothelial cells while the distribution in neurons and glia was similar in β2M(–/–) mice and B6 mice. Acute hepatitis and thymus cortical hypoplasia in β2M(–/–) mice were delayed in onset but pathologic changes in these organs were similar to those in B6 mice. The low rate of demyelination in β2M(–/–) mice was consistent with the low dose of the virus given. A less neurotropic virus MHV-2, caused increased parenchymal inflammation in β2M(–/–) mice, but without demyelination. Thus, CD8+ cells were important for viral clearance from endothelial cells, microglia and inflammatory cells, but not from neuronal and glial cells. In addition, CD8+ cells played a role in preventing the spread of encephalitis.
Role of Laminin Isoforms in Glomerular Structure
Authors: Hansen Kim , Abrass ChristineK.
Published: April 2003

Laminin along with collagen type IV, proteoglycans, and entactin are major components of basement membranes. Basement membrane components are synthesized at high levels during development. The formation of specialized basement membranes may play important roles in cell and tissue function by influencing cell proliferation, phenotype, migration and gene expression as well as tissue architecture. The growing diversity of laminin isoforms influences the formation of distinct basement membranes. Many of the laminin chains sequenced to date are expressed during glomerular development under strict temporal control. Also, some studies suggest that additional laminin chains exist and contribute to unique isoforms expressed within the renal glomerulus. This article will review the status of characterization of laminin isoforms expressed by glomerular cells, point out possible differences in isoforms expressed by different species, and discuss the implications of the complexity of glomerular laminins. In order to fully understand the nature of the glomerular laminins and their importance, information from studies of cells in culture, whole tissue, and those that use molecular and protein analysis must be integrated.
Trisomy 9 in a Patient with Secondary Acute Myelogenous Leukemia Detected by Fluorescent in situ Hybridization
Authors: Mark Hon Fong L. , Gray Yulia , Sotomayor Edgar , Joseph P.
Published: April 2003

Fluorescent in situ hybridization (FISH) is a molecular cytogenetic technique that is playing an increasingly important role for augmenting the findings of conventional cytogenetics. Here we present the case history of a patient with the clinical diagnosis of secondary acute myelogenous leukemia whose bone marrow cells were found to be hyperdiploid with an extra C group chromosome in a less than optimal preparation. By using FISH the extra chromosome was unequivocally determined to be a chromosome 9. The detection of trisomy 9 in this patient underscores the utility of FISH as an adjunct to GTG banding in the routine diagnosis and management of leukemic patients.
Baculovirus Expression, Purification and Evaluation of Recombinant Pneumococcal Surface Adhesin A of Streptococcus pneumoniae
Authors: De B.K. , Sampson J.S. , Ades E.W. , Johnson S.E. , Stinson A.R. , Crook J. , Tharpe J.A. , Huebner R.C. , Carlone G.M.
Published: April 2003

Pneumococcal surface adhesin A (PsaA), with a molecular mass of ∼37 kD by SDS-PAGE, is a common surface protein expressed by all 90 serotypes of Streptococcus pneumoniae. S. pneumoniae serotype 6B genomic DNA was amplified to generate a DNA fragment carrying the full-length psaA sequence and was cloned into a baculovirus expression system. We expressed either cell-associated or cell-free nonfusion PsaA polypeptides using two insect cell lines, Spodoptera frugiperda (Sf9) and Trichoplusia ni 5B1-4 (High-Five). Recombinant PsaA (rPsaA) polypeptides were partially purified by partitioning in PBS/Triton X-114 buffers and by weakly basic ion exchange filter chromatography. Membrane-bound ‘hydrophobic rPsaA’ (hrPsaA) expressed by either Sf9 or High-Five cells had a molecular mass of ∼38 kD by SDS-PAGE and partitioned in a Triton X-114 phase, it reacted with both rabbit polyclonal and five monoclonal anti-PsaA antibodies by dot blot or Western blot analysis. High-Five-cell-expressed ‘soluble rPsaA’ (srPsaA) with a molecular mass of ∼37 kD by SDS-PAGE, was isolated from the serum-free culture medium and did not partition in the Triton X-114 phase; it reacted with anti-PsaA rabbit polyclonal and mouse monoclonal antibodies by ELISA and Western blot analysis. Both rPsaA polypeptide forms were immunogenic in Swiss-Webster adult female mice. In an infant mouse model of bacteremia, survival rates for mice given mouse anti-rPsaA immune serum (from mice immunized with High-Five-expressed srPsaA; 20 µl, 1:50,000 titer) 24 h before bacteremic challenge were greater than for the control group (48 h postchallenge, 20 vs. 90% survival rates) when challenged with S. pneumoniae serotype 6B. These results indicate that rPsaA is immunogenic and elicits protective antibody in mice similar to native protein.
Alteration of Signal-Transducing Molecules and Phenotypical Characteristics in Peripheral Blood Lymphocytes from Gastric Carcinoma Patients
Authors: Kim Chul Woo , Choi Sang Hoon , Chung Eun Joo , Lee Min Jung , Byun Eun Kyung , Ryu Min Hee , Bang Yung-Jue
Published: April 2003

The mechanisms underlying the impaired immune response frequently observed in cancer patients are not fully understood. Alteration of T-cell-associated signal transduction molecules has recently been implicated in immune suppression in tumor-bearing hosts. Furthermore, T cells from tumor-bearing host, irrespective of the presence of the ζ-chain, showed a lack of proliferative activity and cytotoxic function. In the present study, we investigated the expression of the ζ-chain molecule and the p56lck and p59fyn protein tyrosine kinase (PTK) levels in peripheral blood T lymphocytes (T-PBL) from patients with advanced gastric carcinomas; for this, flow cytometric analysis and immunoblotting, respectively, were used. We also compared the results of flow cytometric analysis of PBL between stomach cancer patients and normal healthy volunteers. In T-PBL from 22 tumor-bearing hosts, significantly reduced ζ-chain expression (16/22, 73%) was observed. Moreover, the expression level of p56lck in T-PBL from patients was significantly lower than that of p59fyn. Flow cytometric analysis of T-PBL indicated a markedly increased CD8+28– cell population in T-PBL from 19 tumor-bearing hosts.
Reduced Expression of Cyclin-Dependent Kinase Inhibitor p27Kip1 in Oral Malignant Tumors
Authors: Ito Reiko , Yasui Wataru , Ogawa Yuzo , Toyosawa Satoru , Tahara Eiichi , Ijuhin Naokuni
Published: April 2003

p27Kip1, a cyclin-dependent kinase (CDK) inhibitor, blocks progression from the G1 to S phase by binding cyclin E-CDK2 and inhibiting their activities. We studied the expression of p27 in oral tumors by immunohistochemistry to determine whether lack of p27 plays a role in the development and progression of oral cancer. Reduced expression of p27 was detected in 86% of the squamous cell carcinomas and 95% of the mucoepidermoid carcinomas, respectively, while p27 expression was well preserved in the pleomorphic adenomas. The expression of p27 showed an inverse correlation with the expression of cyclin E in the squamous cell carcinomas and mucoepidermoid carcinomas. However, there was no relationship between clinicopathological parameters and p27 expression. These results suggest that the reduction of p27 protein may confer the development of oral squamous cell carcinoma and mucoepidermoid carcinoma partly through the increased expression of cyclin E.
Balanced Macrophage Activation Hypothesis: A Biological Model for Development of Drugs Targeted at Macrophage Functional States
Authors: McGrath Michael S. , Kodelja Vitam
Published: April 2003

Macrophages play a central role in the immune response and are major targets for chronic infection with viruses such as HIV. Recent studies on macrophage differentiation have shown the existence of classical activation and the counter-balancing anti-inflammatory alternative activation states. In the ‘balanced macrophage activation hypothesis’ we propose that macrophage activation is a cyclic process that balances these two states to achieve proper immunologic function. Dysregulation of this cycle would, therefore, be associated with various forms of chronic disease. This model has been utilized in the drug development of WF10, a novel macrophage-targeted drug, currently in advanced clinical testing for the treatment of HIV disease.
Supernatants of Virus-Infected Macrophages Prime Uninfected Macrophages for Lipopolysaccharide-Induced Apoptosis by Both an Interferon-Dependent and an Independent Mechanism
Authors: Jungi Thomas W. , Schweizer Matthias , Perler Lukas , Peterhans Ernst
Published: April 2003

Virus-infected macrophages (Mφ) release factors priming uninfected Mφ for LPS-induced apoptosis. This was shown for bovine Mφ infected with cytopathogenic bovine virus diarrhea (BVD) virus or with bovine herpes virus-1 (BHV-1) but not for Mφ infected with noncytopathogenic BVD virus. The former two viruses also induced interferon type I in Mφ, which also primes macrophages for LPS-induced apoptosis. However, several lines of evidence suggested that virus-infected Mφ produce IFN-independent factors priming for apoptosis. For example, a soluble IFN type I receptor abrogated the antiviral activity, but not the ability of supernatants to prime uninfected Mφ for LPS-induced apoptosis. It is suggested that the production of factors priming uninfected cells for apoptosis plays a part in virus-induced pathogenesis, e.g. in cattle afflicted with mucosal disease, or with infectious bovine rhinotracheitis, or in viral diseases inducing a marked lymphopenia.