Effect of levamisole on malignant experimental neurinoma grown subcutaneously in a young rat: brief communication.

Levamisole, a drug that stimulates the immunologic defenses of the host, was tested on the experimental malignant neurinoma grown subcutaneously in young female inbred CDF rats in 3-month trial. The drug resulted in prevention of tumor growth in 80% of the treated animals, whereas tumors grew in 100% of the controls. After discontinuation of the drug, none of the animals in the treated group showed evidence of tumor growth upon clinical and pathologic examination 1 month after drug treatment was terminated. Treated animals failed to show any side effects related to levamisole upon clinical and pathologic examination.

Effect of levamisole on malignant experimental neurinoma grown subcutaneously in a young rat: brief communication.

Levamisole, a drug that stimulates the immunologic defenses of the host, was tested on the experimental malignant neurinoma grown subcutaneously in young female inbred CDF rats in a 3-month trial. The drug resulted in prevention of tumor growth in 80% of the treated animals, whereas tumors grew in 100% of the controls. After discontinuation of the drug, none of the animals in the treated group showed evidence of tumor growth upon clinical and pathologic examination 1 month after drug treatment was terminated. Treated animals failed to show any side effects related to levamisole upon clinical and pathologic examination.

Subarachnoid dissemination of thoracic chordoma.

Chordoma at the T-9 level, originally manifested by lumbosacral radiculopathy, developed in a 50-year-old man. The patient underwent three operations and radiation therapy for this condition, but ten years later, thoracic myelopathy developed, followed by left facial weakness. On autopsy, extensive dissemination of chordoma was found along the base of the brain and in the leptomeninges of the spinal cord.

Congenital ophthalmoplegia in oculoauriculovertebral dysplasia-hemifacial microsomia (Goldenhar-Gorlin syndrome). A clinicopathologic study and review of the literature.

Two patients with Goldenhar-Gorlin syndrome showed paralysis of one or more extraocular eye movements on neurologic examination. At autopsy, a third patient showed unilateral agenesis of trochlear and abducens nerves and corresponding brain stem nuclei. Congenital ophthalmoplegia is not infrequent in Goldenhar-Gorlin syndrome and may be due to hypoplasia or agenesis, or both, of extraocular muscles, extraocular nerves, and brain stem nuclei.

Melanotic ependymoma and subependymoma.

We report two examples of melanin production by human gliomas. One was a grossly pigmented, well-differentiated ependymoma resected from the left frontoparietal region of a 13-year-old girl. The patient received radiotherapy and was free of tumor 12 years after operation. The second example was a pigmented subependymoma incidentally discovered at the autopsy of a 52-year-old man. Neoplastic cells containing an intracytoplasmic pigment satisfying histochemical criteria for melanin were present in both cases. Electron microscopic study of the melanotic ependymoma revealed electron-dense granules in the cytoplasm of cells forming rosettes. Premelanosomes were not detected. While the mechanism of melanogenesis in these cases is obscure, they support the potential of glial derivatives to produce melanin and indicate that melanogenesis in such neoplasms may have no adverse prognostic import.

In vivo labeling of endothelin receptors with [(11)C]L-753,037: studies in mice and a dog.

UNLABELLED: Endothelin (ET) is a potent mammalian vasoconstrictive peptide and a pressor agent. Its 3 isoforms, ET-1, ET-2, and ET-3, mediate several physiologic actions in several organ systems, binding to 2 major receptor subtypes: ET(A) and ET(B). This study was undertaken to evaluate [(11)C]L-753,037 [(+)-(5S,6R,7R)-2-butyl-7-[2-((2S)-2-carboxy-propyl)-4-methoxyphenyl]-5-(3,4-methylenedioxyphenyl)cyclopenteno [1,2-beta]pyridine-6-carboxylate), a new mixed ET receptor A and B antagonist, as a tracer for in vivo labeling of ET receptors in mice and a dog. METHODS: [(11)C]L-753,037 was synthesized, purified, and formulated from a normethyl precursor, L-843,974, and [(11)C]H(3)I. The tracer was studied for its in vivo kinetics, biodistribution, and ET receptor binding characteristics in mice. In the dog, PET imaging was performed to evaluate binding of [(11)C]L-753,037 to ET receptors in the heart. Specificity of binding was studied in the heart with the selective ET(A) antagonist L-753,164. RESULTS: Kinetic studies in mice showed highest tracer uptake at 5 min after injection in liver (25.0 percentage injected dose per gram [%ID/g]), kidneys (18.7 %ID/g), lungs (15.2 %ID/g), and heart (5.6 %ID/g). Initial high uptake in liver, lungs, and kidneys was followed by rapid washout during the next 10 min and a very slow clearance during the time of observation (2 h after injection). By contrast, the radioactivity in the heart remained constant over 2 h. Administration of both ET(A) (L-753,164) and mixed ET(A)/ET(B) (L-753,137) receptor antagonists resulted in dose-dependent inhibition of [(11)C]L-753,037 binding in mouse heart, lungs, and kidneys but not in the liver. Radioactivity in the brain was very low, indicating that the tracer does not cross the blood-brain barrier. In the dog, a dynamic PET study of the heart showed high tracer accumulation at 55-95 min after injection. Injection of L-753,164 at 30 min before [(11)C]L-753,037 administration led to a significant reduction in tracer binding. [(11)C]methyl triphenyl phosphonium was used as a tracer for reference images of the dog heart muscle. CONCLUSION: The results suggest that [(11)C]L-753,037 binds to ET receptors in vivo and is, therefore, a promising candidate for investigation of these receptors and their occupancy by ET receptor antagonists using PET.

Lack of the alpha-1,2-linked N-acetyl-D-glucosamine epitope in the outer core structures of lipopolysaccharides from certain O serogroups and subspecies of Salmonella enterica.

A total of 176 strains of Salmonella enterica representing 116 serotypes were tested for the presence of the T6 epitope of the alpha-1,2-linked N-acetyl-D-glucosamine residue by reaction with a murine monoclonal antibody T6 specific for this structure in the Salmonella Ra core lipopolysaccharide (LPS). All 20 serotypes (70 strains) belonging to serogroups A to E were positive for the T6 epitope while 29% of the 96 serotypes (106 strains) belonging to O serogroups F to 67 were negative; 12 serotypes (12 strains) of subspecies IIIb Salmonella were positive for the T6 epitope, but 10 serotypes (11 strains) of subspecies IIIa Salmonella were found to lack this epitope. In T6-positive strains, the epitope was accessible to antibody binding in both the unsubstituted free rough core LPS and in the rough core LPS substituted with a few repeating units of O side chains. The presence or absence of the T6 epitope in Salmonella strains was not affected by culture conditions, the source of the isolate, the age of the culture or the presence of fimbriae antigens.

Intracranial extension and bone destruction in orbital pseudotumor.

Three cases of surgically proved pseudotumor of the orbital apex with intracranial extension occurred. All demonstrated bony destruction. Varying degrees of ophthalmoplegia and visual loss were present in all three. Previous computed tomographic descriptions of the patterns of orbital pseudotumor have not included bone destruction. Further, intracranial extension has been reported in only one patient. These three cases are reported to emphasize the fact that while these manifestations may be rare, it is appropriate to include orbital pseudotumor in the differential diagnosis of orbital apex lesions that are associated with both bone destruction and/or intracranial extension.

Characterization and specificity controls of murine monoclonal antibodies against serogroup C1 Salmonella.

Two IgG3 murine monoclonal antibodies, Cl-1 and Cl-2, that showed serologic specificities for the O antigens of serogroup C1 (0:6,7) Salmonella were established. The epitopes for the antibodies were found to reside on the repeating units of the serogroup C1 Salmonella lipopolysaccharide and were labile to sodium metaperiodate oxidation. Serologic reactivities of Cl-1 and Cl-2 were not inhibited by commercial monospecific antiserum to O antigen 7, but were inhibited to various degrees by anti-[O:6,7] serum. Both antibodies reacted strongly with all strains of serogroup C1 Salmonella that have either O:6(1),7, O:6(2),7, or O:6(1,2),7 antigens. Reactivities of Cl-1 and Cl-2 with the phage-14 lysogenized C1 strains that bear the phage-modified O antigen (O:6,7----O:6,7,14) were detected by slide agglutination method only and not by whole-cell enzyme-linked immunosorbent assay. Both Cl-1 and Cl-2 antibodies did not react with other O serogroups of salmonellae, nor with other Gram-negative or Gram-positive bacteria. The diagnostic value of these monoclonal antibodies together with a previously described monoclonal antibody against the serogroup C2 Salmonella was demonstrated using the slide agglutination method with monoclonal antibodies ascitic fluids.

Characterisation of pathogenic Yersinia enterocolitica serogroups by pulsed-field gel electrophoresis of genomic NotI restriction fragments.

Enteropathogenic Yersinia enterocolitica is an important cause of human and animal disease. Phenotypic and genotypic characteristics currently used to identify Y. enterocolitica are not necessarily sufficient to differentiate pathogenic from non-pathogenic strains or to analyse the epidemiology of yersiniae at a molecular level. To improve the characterisation of Yersinia isolates, NotI restriction fragment length polymorphisms (RFLPs) of chromosomal DNA of more than 100 clinical, animal and environmental isolates were analysed in pulsed-field gel electrophoresis. Highly conserved RFLP patterns with fragments ranging from 15 to 400 kb were detected within each of 10 Y. enterocolitica serogroups tested. Determination of RFLP types makes it possible to discriminate between isolates of different Y. enterocolitica serogroups and other Yersinia spp. Moreover, NotI restriction endonuclease analysis allows even subtyping of strains belonging to a unique serogroup-biotype. Identification of NotI fragments hybridising with inv- or ail-homologous sequences was used as an additional discriminating marker. The results indicate that NotI RFLP typing can provide a powerful new tool for the differentiation of clinical Y. enterocolitica isolates.

Intractable facial pain associated with a ganglioglioma of the cervicomedullary junction: report of a case.

A 6-year-old child with a brain stem tumor presented with the unusual complaint of intractable facial pain resembling trigeminal neuralgia in the absence of other symptoms or signs referable to the 5th cranial nerve. The radiological evaluation included a computed tomographic scan with intravenous contrast administration, which demonstrated an enhancing intramedullary lesion extending from the obex to C-4. After radiation and chemotherapy had failed to achieve symptomatic relief, the tumor, later proven to be a ganglioglioma, was radically removed with the ultrasonic aspirator. Postoperatively the patient experienced full pain relief.

Inflammatory reaction to synthetic dural substitute. Case report.

The authors report an unusual complication related to a dural substitute. An inflammatory response to a Marlex mesh duraplasty simulated a recurrent convexity meningioma 20 years after the initial surgery.

Identification of Yersinia enterocolitica within the genus Yersinia.

In this report we describe a PCR strategy for the unambigous identification of biochemically presumptive typed Yersinia (Y.) enterocolitica. A total of 269 isolates belonging to ten species of the genus Yersinia were investigated. In a first PCR only isolates classified as Y. enterocolitica (n = 113) gave rise to a specific amplification resulting in a sensitivity and a specificity of 100%. By sequencing the 269 amplicons of a second pan-Yersinia PCR spanning a distinct 16S rRNA gene region, 20 different sequence clusters could be identified within the genus. By this, Y. enterocolitica isolates of American and European origin could be distinguished safely and already described sequence clusters of the species Y. frederiksenii were confirmed. New 16S rRNA gene sequence clusters were detected for the species Y. frederiksenii, Y. intermedia, Y. mollaretii, Y. aldovae, Y. kristensenii, and Y. rohdei.

A highly specific one-step PCR - assay for the rapid discrimination of enteropathogenic Yersinia enterocolitica from pathogenic Yersinia pseudotuberculosis and Yersinia pestis.

Based on differences within the yopT-coding region of Yersinia. enterocolitica, Y pseudotuberculosis and Y pestis, a rapid and sensitive one-step polymerase chain reaction assay with high specificity for pathogenic Y enterocolitica was developed. By this method pathogenic isolates of Y enterocolitica can be easily identified and discriminated from other members of this genus. The entire coding sequence of the yopT effector gene of Y. pseudotuberculosis Y36 was determined.

Evaluation of a Yersinia adhesion gene (yadA) specific PCR for the identification of enteropathogenic Yersinia enterocolitica.

A total of 101 Yersinia enterocolitica strains was investigated with a PCR assay [Blais and Phillipe, Food Control, 6 (1995) 211-214] targeting the Yersinia adhesin gene (yadA) responsible for autoagglutination. Compared to the autoagglutination test the PCR assay has a specificity of 100% but a sensitivity of only 70%. This failure might be caused by the sequence heterogeneity of yadA.

Specific detection of plasmid bearing Yersinia isolates by PCR.

A total of 210 isolates belonging to 9 different species of the genus Yersinia (Y.) was investigated with three different PCR assays targeting two plasmoidal genes, the Yersinia adhesin gene (yadA) and the V-antigen gene. The yadA PCR assay described in 1995 by Blais and Phillipe, targeting a Y. enterocolitica specific gene region and a newly designed assay targeting the gene region functionally responsible for autoagglutination, were compared. Both assays identified the same Y. enterocolitica strains. To exclude the possibility that false negative results were obtained due to mutations that had occurred in parallel in both gene regions, a third PCR assay by Neubauer et al. (2000) targeting a conserved region of the V-antigen gene was used as control. Again, DNA of the same Y. enterocolitica strains was amplified. In contrast to the yadA PCR assay described by Blais and Phillipe, the newly established yadA and the V-antigen PCR assays amplified DNA from Y. pseudotuberculosis strains. Therefore, by using the PCR technique as a molecular tool spontaneous mutations could be excluded as the cause of anomalous reactions in PCR assays targeting genes of the Yersinia virulence plasmid. Based on these results, it can be assumed that all presumptive pathogenic Yersinia isolates can be identified on the basis of PCR analysis. These molecular assays may also produce fewer false positive reactions in comparison to phenotypic tests such as the autoagglutination test which depend heavily on the handler's experience. It has to be stressed that the PCR assays used in this study have not been evaluated for routine use. Therefore, standardization of the PCR methodology including sample preparation, primer target sequences and PCR reagents is needed for the reliable and safe diagnosis of pathogenic Yersinia spp. in future.

A miniaturised semiautomated system for the identification of Yersinia species within the genus Yersinia.

Commercially available identification systems based on biochemical reactions of bacteria are not suited for typing the species of the genus Yersinia (Y.) or the biovars (BV) of the species Y. enterocolitica. This failure is caused by the limited number of biochemical reactions applied, resulting in the absence of important discriminatory key reactions. The MICRONAUT identification system (Merlin, Bornheim-Hersel) makes use of dried substrates/enzymes reactions in the wells of a 96-well microtitration plate, reading of the results by a scanner device and typing of the isolate by the calculation of probabilities according to a data base. For this study a special identification panel was designed on which 38 substrates and enzyme reactions were configurated including 20 reactions for the identification of the species of the genus and the Y. enterocolitica biovars. The database was calculated using the results obtained from a total of 250 Yersinia strains of the eleven species of the genus. Reevaluation of the results of these strains revealed an overall sensitivity of 98%, as only four strains were not identified satisfactorily. Considering also questionable results the sensitivity was still 85%. The system was also used to identify Y. pestis isolates, but in this case reading was done visually. The printouts usually cite species designation, identification quality and probabilities. The sealing of the plates in an aluminium bag guarantees long life and long lasting quality. However, an evaluation of the system with a considerable number of strains has to be done in a next step. The 'Yersinia identification set' can replace time-consuming tube testing in the future and is a big step forward towards a sensitive identification of Yersinia isolates in the routine laboratory.

Iniencephaly: a neuropathologic study.

Five cases of iniencephaly are reviewed. Numerous central nervous system malformations were found at all levels, including microencephaly, polymicrogyria, heterotopic glial tissue in the leptomeninges, atresia of the ventricular system, marked disorganization of the brain stem, vermian agenesis, large cerebellar cyst, and disorganization of the spinal cord tissue. The cerebellum was normal in one case. Numerous skeletal anomalies were found as well as marked retroflexion of the craniocervical junction. We concluded that cerebral anomalies, although severe, are not specific for iniencephaly. Cerebellar anomalies, on the other hand, were considered to share some morphologic features between Dandy-Walker and Arnold-Chiari, i.e., Chiari type II and Chiari type III, malformations.

SPET brain perfusion imaging in mild traumatic brain injury without loss of consciousness and normal computed tomography.

We present SPET brain perfusion findings in 32 patients who suffered mild traumatic brain injury without loss of consciousness and normal computed tomography. None of the patients had previous traumatic brain injury, CVA, HIV, psychiatric disorders or a history of alcohol or drug abuse. Their ages ranged from 11 to 61 years (mean = 42). The study was performed in 20 patients (62%) within 3 months of the date of injury and in 12 (38%) patients more than 3 months post-injury. Nineteen patients (60%) were involved in a motor vehicle accident, 10 patients (31%) sustained a fall and three patients (9%) received a blow to the head. The most common complaints were headaches in 26 patients (81%), memory deficits in 15 (47%), dizziness in 13 (41%) and sleep disorders in eight (25%). The studies were acquired approximately 2 h after an intravenous injection of 740 MBq (20.0 mCi) of 99Tcm-HMPAO. All images were acquired on a triple-headed gamma camera. The data were displayed on a 10-grade colour scale, with 2-pixel thickness (7.4 mm), and were reviewed blind to the patient's history of symptoms. The cerebellum was used as the reference site (100% maximum value). Any decrease in cerebral perfusion in the cortex or basal ganglia less than 70%, or less than 50% in the medial temporal lobe, compared to the cerebellar reference was considered abnormal. The results show that 13 (41%) had normal studies and 19 (59%) were abnormal (13 studies performed within 3 months of the date of injury and six studies performed more than 3 months post-injury). Analysis of the abnormal studies revealed that 17 showed 48 focal lesions and two showed diffuse supratentorial hypoperfusion (one from each of the early and delayed imaging groups). The 12 abnormal studies performed early had 37 focal lesions and averaged 3.1 lesions per patient, whereas there was a reduction to--an average of 2.2 lesions per patient in the five studies (total 11 lesions) performed more than 3 months post-injury. In the 17 abnormal studies with focal lesions, the following regions were involved in descending frequency: frontal lobes 58%, basal ganglia and thalami 47%, temporal lobes 26% and parietal lobes 16%. We conclude that: (1) SPET brain perfusion imaging is valuable and sensitive for the evaluation of cerebral perfusion changes following mild traumatic brain injury; (2) these changes can occur without loss of consciousness; (3) SPET brain perfusion imaging is more sensitive than computed tomography in detecting brain lesions; and (4) the changes may explain a neurological component of the patient's symptoms in the absence of morphological abnormalities using other imaging modalities.

Flow cytometric analysis of T8 lymphocytes in patients with ovarian carcinoma in relation to clinical response.

The objective of this study was to examine variations of T8 lymphocytes in the peripheral blood of patients with ovarian carcinoma after surgical treatment and chemotherapy in relation to clinical response. In a prospective randomized study 30 women with ovarian carcinoma were studied. In the control group 30 patients had benign tumors of ovary. We examined the distribution of T8 lymphocytes in the peripheral blood of women with ovarian carcinoma preoperatively, during chemotherapy and 1 and 3 months postoperatively as well as in the control group. Quantification of suppressor/cytotoxic lymphocytes in peripheral blood was performed using specific monoclonal antibody (anti-T8) and flow cytometry. Values of T8 lymphocytes in the group of patients with complete response, 1 month after operation, were higher (0.67 +/- 0.3) compared to the control group (0.53 +/- 0.24), but lower in patients with partial response (0.45 +/- 0.20) and no effect (0.35 +/- 0.1). Three months after the operation, we recorded a decreased number of peripheral T8 lymphocytes in all patients of the examined group, compared to the values after 1 month.