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Biomedical subjects

S L Su

Publications and source records attributed to S L Su.

At least 19 recordsLinked to original sources

Current evaluation of the tissue localization and diagnostic utility of prostate specific membrane antigen.

BACKGROUND: Current statistics indicate that prostate carcinoma is the most common form of cancer diagnosed in American men, resulting in the second highest cancer death rate. Early diagnosis and accurate staging are imperative given that there is little effective treatment for metastatic disease, especially after androgen deprivation therapy fails. Identification of new biochemical markers for disease progression will provide important tools for diagnosis and monitoring. One such potential marker is prostate specific membrane antigen (PSMA). METHODS: A review was conducted to identify reports concerning evaluation of diagnostic applications of PSMA. RESULTS: PSMA is a membrane-bound glycoprotein that is highly restricted to the prostate. Immunohistochemical findings indicate that PSMA is a marker of epithelial cells of the prostate. This expression is increased in association with prostate carcinoma, particularly in hormone-refractory disease. Given its membrane-bound character, PSMA has been exploited as a marker for tumor detection by immunoscintiscanning with the 111In-labeled anti-PSMA monoclonal antibody 7E11.C5. Increased concentrations of 7E11.C5-reactive antigen are present in the serum of prostate carcinoma patients compared with healthy individuals; also, hematogenous circulating prostate carcinoma cells are detectable with reverse transcriptase-polymerase chain reaction analysis with primers specific for PSMA. New monoclonal antibodies specific for extracellular portions of the PSMA molecule currently are being utilized in applied studies. CONCLUSIONS: PSMA is a widely used marker for prostate epithelial cells. Its up-regulation in association with cancer, particularly in advanced cancer, is ideal for application as a prognostic marker. A variety of promising clinical applications utilizing PSMA have been or are being developed. In the future, these promise to have an important impact on cancer diagnosis and patient treatment.

Antigens, Surface↗

Mapping, genomic organization and promoter analysis of the human prostate-specific membrane antigen gene.

Prostate-specific membrane antigen (PSMA) is a 100 kDa type II transmembrane protein with folate hydrolase and NAALAdase activity. PSMA is highly expressed in prostate cancer and the vasculature of most solid tumors, and is currently the target of a number of diagnostic and therapeutic strategies. PSMA is also expressed in the brain, and is involved in conversion of the major neurotransmitter NAAG (N-acetyl-aspartyl glutamate) to NAA and free glutamate, the levels of which are disrupted in several neurological disorders including multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's disease and schizophrenia. To facilitate analysis of the role of PSMA in carcinoma we have determined the structural organization of the gene. The gene consists of 19 exons spanning approximately 60 kb of genomic DNA. A 1244 nt portion of the 5' region of the PSMA gene was able to drive the firefly luciferase reporter gene in prostate but not breast-derived cell lines. We have mapped the gene encoding PSMA to 11p11-p12, however a gene homologous, but not identical, to PSMA exists on chromosome 11q14. Analysis of sequence differences between non-coding regions of the two genes suggests duplication and divergence occurred 22 million years ago.

Antigens, Surface↗

Evaluating neoadjuvant therapy effectiveness on systemic disease: use of a prostatic-specific membrane reverse transcription polymerase chain reaction.

OBJECTIVE: An on-going study at the Memorial Sloan-Kettering Cancer Center assessed the effectiveness of androgen deprivation therapy (ADT) prior to surgical removal of the prostate. In this report, we evaluate the effectiveness of ADT on systemic disease by monitoring the presence or absence of circulating prostatic epithelial cells using a reverse transcription polymerase chain reaction (RT-PCR) assay for prostatic-specific membrane antigen (PSM). METHODS: PSM RT-PCR was performed on a total of 38 prostate cancer patients. There were 12 pT2 patients in the ADT group and 10 patients in the control pT2 group and 5 pT3 patients in the ADT group and 11 pT3 patients in the control group. RESULTS: For pT2 patients, 2 of the 12 patients (17%) were positive for circulating prostatic cells during androgen deprivation therapy but before radical retroprostatectomy (RRP). Within a 6-month period after RRP, 3 of 12 patients (25%) were positive. For the period between the 7th and 12th month after RRP, 6 of 12 patients (50%) were positive. For the period 12-36 months after RRP, 2 of the 12 patients (17%) remained positive for circulating prostatic cells. In contrast, the pT2 control group had higher positive rates in comparable periods: 4 of 10 patients (40%) were positive prior to surgery; 6 of 10 patients (60%) were positive during the 6 months following surgery. For the period between the 7th and 12th month following surgery, 4 of 7 patients (57%) were positive for PSM. Finally, 3 of 6 patients (50%) were positive for the period longer than 12 months. Regarding patients who have extraprostatic disease (stage pT3), the ADT group had a lower rate of circulating PSM positive cells. Before RRP and during androgen deprivation therapy, 1 out of 5 patients (20%) in the ADT group were positive as compared to 4 out of 11 patients for the control group. Within a 6-month period after RRP, the ADT group had 4 out of 9 (44%) patients positive for PSM as compared to 9 of 11 (82%) for the control group. For the period between the 7th and 12th months postsurgery, 1 of 5 patients (20%) of the ADT group were positive as compared to 4 of 7 (57%) of the control patients. CONCLUSIONS: These results indicate that patients with pT2 and pT3 lesions who receive neoadjuvant ADT are less likely to have circulating tumor cells detected compared to a control group both prior to and after surgery. In addition, irrespective of ADT or control group, there were increases in the detection of circulating tumor cells in the period after RRP, and this rise gradually decreased, suggesting that surgical manipulation may cause hematogenous dissemination of tumor cells and that ADT reduces such dissemination of tumor cells. Overall, these results indicate that the use of neoadjuvant ADT decreases the number of circulating prostatic cells. These data represent the initial results of an on-going study. As additional patients are added to the studies, attempts to correlate PSM positivity and serum PSA values postoperatively, recurrence, and margin positivity will be made.

Androgen Antagonists↗

Localization and physical mapping of the prostate-specific membrane antigen (PSM) gene to human chromosome 11.

The prostate-specific membrane antigen (PSM) was identified by the monoclonal antibody 7E11-C5.3, which was raised against the human prostatic carcinoma cell line LNCaP (3). The PSM antigen is expressed by normal, neoplastic, and metastatic prostatic tissues. The 2.65-kb cDNA encoding the 100-kDa PSM glycoprotein was cloned from LNCaP cells (4). Studies have shown that the expression of PSM is tissue-specific (5). In the present study monochromosomal somatic cell hybrids were used to localize the PSM gene to human chromosome 11. Using this information, initial mapping studies identified two potential PSM gene loci at 11p11.1-p13 and 11q14. Further high-stringency analysis using cosmid probes identified the 11q14 region as the location of the PSM gene.

Antigens, Neoplasm↗

Alternatively spliced variants of prostate-specific membrane antigen RNA: ratio of expression as a potential measurement of progression.

We examined expression of prostate-specific membrane antigen (PSM) mRNA in normal prostate using reverse transcription-PCR and sequencing. An alternatively spliced variant, PSM', along with the previously described PSM form, was found in normal prostate. PSM' cDNA is shorter (2387 nucleotides) than PSM (2653 nucleotides). The cDNAs are identical except for a 266-nucleotide region near the 5' end of PSM cDNA (nucleotide 114-380) that is absent from PSM'. This deleted region includes the translation initiation codon and codons for the putative transmembrane domain of PSM. Thus, PSM' RNA codes for a protein that has no apparent signal sequence. We verified the existence of spliced mRNA variants in human primary tissue specimens by RNase protection assay. In LNCaP human prostatic cancer cells and in primary prostate tumors, PSM is the dominant form. In contrast, normal human prostate expressed more PSM' than PSM. Benign prostatic hypertrophy samples showed about equal expression of both variants. We quantified the relative expression of each variant by densitometry and compiled a tumor index, which is the ratio of PSM:PSM' level. LNCaP has an index ranging from 9-11, carcinoma of the prostate from 3-6, benign prostatic hypertrophy from 0.75-1.6, and normal prostate from 0.075-0.45. The index reflects the increased expression of PSM over PSM' following the progression from normal to tumor state. This tumor index may be a useful indicator for the measurement of tumor progression. PSM and PSM' may be functionally different proteins as a result of differences in structure or cellular location. We are investigating the prevalence of one form over the other and how it may influence tumor progression.

Alternative Splicing↗

Mayer-Rokitansky-Kuster-Hauser syndrome with immature teratoma of the ovary at age 4 years.

We describe a rare combination of Mayer-Rokitansky-Kuster-Hauser syndrome and immature teratoma of the ovary in a 4-year-old girl. The patient was admitted due to increased abdominal size. Sonagraphy and C-T scan revealed a heterogeneous mass with cystic, calcified, and solid parts. A right salpingo-oophorectomy was performed under the FIGO (International Federation of Gynecology and Obstetrics) staging of stage Ia. The diagnosis of immature teratoma, grade II, was confirmed by histopathologic examination. Agenesis of the upper third of the vagina and the uterus was also confirmed by the surgery.

Abnormalities, Multiple↗

Sensitive detection of prostatic hematogenous tumor cell dissemination using prostate specific antigen and prostate specific membrane-derived primers in the polymerase chain reaction.

We developed a polymerase chain reaction based assay enabling sensitive detection of hematogenous tumor cell dissemination in patients with prostate cancer. We performed "nested polymerase chain reaction," amplifying messenger ribonucleic acid sequences unique to prostate specific antigen (PSA) and to the prostate specific membrane antigen, and compared the respective results. Prostatic tumor cells were detected in 2 of 30 patients (6.7%) by polymerase chain reaction with PSA derived primers, while prostate specific membrane primers detected tumor cells in 19 (63.3%). All 16 negative controls had negative PSA and prostate specific membrane polymerase chain reaction. Assays were repeated to confirm results, and polymerase chain reaction products were verified by deoxyribonucleic acid sequencing and Southern analysis. Patients harboring circulating prostatic tumor cells as detected by prostate specific membrane and not by PSA polymerase chain reaction included 7 of 13 previously treated by radical prostatectomy who had nonmeasurable serum PSA levels at the time of this assay. The significance of these findings with respect to future disease recurrence and progression will be investigated.

Base Sequence↗

Prenatal diagnosis of Meckel-Gruber syndrome case reports.

Two cases of Meckel-Gruber syndrome are presented. In the first case, abdominal tumor and decreased amniotic fluid were initially suspected. In the second case, Omphalocele was diagnosed by local practitioners. Thorough obstetric sonographic studies revealed encephalocele, bilateral renal cystic dysplasia, polydactyly, microcephalus, intrauterine growth retardation (IUGR) and oligohydramnios. Chromosomal analysis by percutaneous umbilical cord blood sampling (PUBS) was normal with 46,XY in Case 1 and 46,XX in Case 2. The prenatal diagnoses were confirmed by autopsy. The pathologic reports revealed type I polycystic kidney, bile duct proliferation, fibrosis of the portal area, encephalocele and polydactyly. It is interesting to note that the two cases came from two different families without any family history of inherited disease.

Abnormalities, Multiple↗

Sensitive nested reverse transcription polymerase chain reaction detection of circulating prostatic tumor cells: comparison of prostate-specific membrane antigen and prostate-specific antigen-based assays.

A highly sensitive nested reverse transcriptase-PCR assay, with primers derived from the prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSM) cDNA sequences, has been used to detect occult hematogenous micrometastatic prostate cells. In 77 patients with prostate cancer, PSM and PSA primers detected circulating prostate cells in 48 (62.3%) and 7 (9.1%) patients, respectively. In treated stage D disease patients, PSM primers detected cells in 16 of 24 patients (66.7%), while PSA primers detected cells in 6 of 24 (25%). In post-radical prostectomy patients with negative serum PSA values, PSM primers detected metastases in 21 of 31 patients (67.7%), whereas PSA primers detected cells in only 1 of 33 (3.0%), indicating that micrometastatic spread may be a relatively early event in prostate cancer. The analysis of 40 individuals without known prostate cancer provides evidence that this assay is highly specific and suggests that PSM expression may predict the development of cancer in patients without clinically apparent prostate cancer. Using PSM primers, we detected micrometastases in 4 of 40 controls, 2 of whom had known benign prostatic hyperplasia and were later found to have previously undetected prostate cancer. The clinical significance of detection of hematogenous micrometastic prostate cells using PSM primers and potential applications of this molecular assay, as well as the assay for PSA, merit further study.

Antigens, Neoplasm↗

Fibroblast activation protein: purification, epitope mapping and induction by growth factors.

The human fibroblast activation protein (FAP) defined by monoclonal antibody (MAb) F19 is a cell surface antigen expressed in reactive stromal fibroblasts of breast, colorectal, lung and other epithelial cancers. In contrast to its stroma-specific localization in epithelial neoplasms, FAP is expressed in the malignant mesenchymal cells of bone and soft tissue sarcomas. FAP is transiently expressed in some fetal mesenchymal tissues but is absent or expressed at low levels in most adult tissues. FAP is induced in cultured fibroblasts and, in these cells, consists of a M(r) 95,000 subunit (FAP alpha) carrying the F19 epitope and a non-covalently bound M(r) 105,000 subunit (FAP beta) lacking the F19 epitope. Using MAb F19 and 5 newly derived MAbs, we identify 3 distinct epitopes on FAP alpha and tentatively assign one epitope to FAP beta. Analysis of detergent extracts of a FAP alpha high beta- sarcoma cell line by size exclusion-high performance liquid chromatography (HPLC) revealed that FAP alpha does not elute as a M(r) 95,000 species but as part of a high-molecular weight complex (M(r) > 400,000) that dissociates into M(r) 95,000 subunits in SDS gels. Immunoaffinity purification of FAP alpha followed by tryptic digestion, reversed-phase HPLC and microsequencing identified 3 unique FAP alpha peptides, with 2 showing sequence similarity (23/38 identical amino acids) to segments of CD26, a T-cell activation antigen. CD26 is a membrane-bound enzyme (dipeptidyl aminopeptidase IV), but immunopurified FAP alpha has little if any dipeptidase activity with typical CD26 substrates. Finally, studies with FAPlow leptomeningeal fibroblasts revealed that transforming growth factor-beta, 12-O-tetradecanoyl phorbol-13-acetate and retinoids can upregulate FAP expression, whereas serum and several other factors had no or little effect on FAP levels. FAP and CD26 may belong to a family of structurally related but functionally distinct activation proteins that are expressed on different cell types and show unique modes of regulation in normal and malignant cells.

Amino Acid Sequence↗

Evaluation of the cervical conditions with PGE2 in first and second trimester.

The PGE2 vaginal tablet has been introduced for use in term pregnancy. However, its effect in abortion and intrauterine fetal death (IUFD) is still uncertain. So we set up the following processes to research the efficacy of PGE2 in abortion and IUFD. We used PGE2 (3 mg) intravaginally for 12 hours in the patients of the first trimester. Consequently, the induction was achieved in a much shorter period. On the other hand, for patients in the second trimester, we used PGE2 (3 mg) in posterior fornix for 12 hours and PGE2 (1.5 mg) in extra-amnion successively. As a result, the cervical condition ripened more satisfactorily. The time of induction was about 14 to 18 hours in the second trimester, much shorter than the usual time needed. Besides, patients didn't complain of any special symptoms/signs such as nausea, vomiting, diarrhea, tachycardia, or hypertension. Therefore, we prefer to use this method for induction of the first & second trimester pregnancy including IUFD and abortion.

Abortion, Induced↗

Regulation and heteromeric structure of the fibroblast activation protein in normal and transformed cells of mesenchymal and neuroectodermal origin.

The human fibroblast activation protein (FAP), defined by monoclonal antibody F19, is expressed in vivo in reactive stromal fibroblasts of epithelial cancers, subsets of bone and soft tissue sarcomas, and granulation tissue of healing wounds. FAP is generally absent from the stroma of benign epithelial tumors and normal adult tissues. In vitro FAP induction is observed in proliferating cultured fibroblasts and in melanocytes grown with fibroblast growth factor and phorbol ester. In the present study, we show that fibroblast and melanocyte FAP is a cell surface protein comprising noncovalently linked M(r) 95,000 (p95) and M(r) 105,000 (p105) subunits. In contrast, cultured sarcoma and melanoma cell lines express only p95 or are FAP negative. Immunoblot experiments show that p95, but not p105, carries the epitope defined by monoclonal antibody F19. Furthermore, peptide maps of purified p95 and p105 differ, suggesting that they may be distinct gene products. Loss of FAP or a change from p95/p105 to p95 expression accompanies the acquisition of growth factor independence and tumorigenicity in several in vitro test systems, including simian virus 40 transformation of normal fibroblasts, Ha-ras transformation of normal melanocytes, supertransformation of osteosarcoma cells, and enhanced N-MYC expression in variant neuroblastoma cells, whereas serum-starved normal fibroblasts continue to express p95/p105. Thus, fAP expression appears to be linked to the growth factor-dependent proliferative capacity of normal cells and is not merely a secondary event in proliferating cells; furthermore, FAP expression is inversely correlated with growth factor independence and tumorigenicity in transformed cell lines. This distribution pattern is consistent with a role for p95/p105 in mediating extrinsic, growth regulatory signals in normal cells, possibly as a heteromeric cell surface receptor. Such a physiological function may be obviated when oncogenes with cytoplasmic or nuclear sites of action are activated, reducing extrinsic growth factor dependence and permitting down-regulation of FAP in certain transformed cells.

Antigens, Neoplasm↗

Identification of endosialin, a cell surface glycoprotein of vascular endothelial cells in human cancer.

Cell surface antigens of transformed cells are the traditional targets for antibody-guided detection and therapy of solid neoplasms. Alternative targets may be found in the tumor stroma, which contains newly formed blood vessels, reactive fibroblasts, and extracellular matrix proteins. The F19 cell surface glycoprotein of reactive fibroblasts is a prototypic stromal antigen since it is found in the stroma of > 90% of common epithelial cancers but is absent or expressed at low levels in normal tissues and benign epithelial tumors. In the present study, we define an additional tumor stromal antigen, FB5, that is selectively expressed in vascular endothelial cells of malignant tumors. Immunohistochemical analysis of 128 tumors identified FB5 in endothelial cells in 67% of the samples (including 41 of 61 sarcomas, 26 of 37 carcinomas, and 18 of 25 neuroectodermal tumors) whereas normal blood vessels and other adult tissues tested lacked FB5 expression. In vitro studies showed that FB5 is a M(r) 165,000 cell surface glycoprotein, comprised of a M(r) 95,000 core polypeptide and highly sialyated O-linked oligosaccharides but few if any N-linked sugars, and that the FB5 gene is located on chromosome 11q13-qter. The restricted tissue distribution of the FB5 protein, which we refer to as endosialin, suggests strategies for tumor imaging and therapy that are aimed primarily at the tumor vasculature.

Adult↗

Species diversity of neuronectin and cytotactin expression patterns in the vertebrate central nervous system.

Two extracellular matrix proteins of brain tissue, neuronectin (NEC1) and cytotactin (CT), are disulfide-bonded multimers of M(r) 180,000-250,000 subunits. The previously known distribution of these molecules is, however, very different. Human NEC1 is found throughout the white matter of rostral segments of the adult central nervous system (CNS) but not in rostral gray matter or in caudal CNS segments, including the cerebellum. In contrast, CT is absent or expressed at a low level in the adult chicken cerebrum but highly expressed in the cerebellum. Despite these differences in distribution, results obtained with antibodies that recognize NEC1 and CT in several vertebrate species indicate that these molecules are identical or at least closely related: (1) alpha NEC1 antibodies recognize proteins affinity-purified with CT-binding proteoglycan; (2) proteins recognized by alpha NEC1 and alpha CT antibodies in cells constitutively expressing the molecules, cells in which expression is induced by growth factors and phorbol ester and cells treated with tunicamycin (to block glycosylation) are identical in subunit composition and mobility on SDS gels; (3) the removal of NEC1 from culture supernatants by immunoprecipitation removes all molecules reactive with alpha CT antibodies and vice versa; (4) immunoblots of brain extracts with alpha NEC1 and alpha CT antibodies yield identical results. Having demonstrated the structural similarity between NEC1 and CT, we reexamined their distribution in the CNS. Surprisingly, the temporal and spatial distribution pattern of NEC1/CT varied greatly among species. Immunohistochemical and immunoblot experiments with adult human CNS tissues revealed significant levels of NEC1/CT in rostral but not caudal segments. In contrast, in cows and pigs the molecule is found throughout the CNS. Adult rat and mouse brains show regionally restricted expression of NEC1/CT in several areas of the cerebrum--distinct from those showing NEC1/CT in the human--and in the molecular layer of the cerebellum. Tests with fetal and newborn tissues revealed that CNS development in humans, cows and pigs is not accompanied by the marked decline in NEC1/CT levels or the changes in subunit composition found in the chicken CNS. The marked species diversity in temporospatial expression patterns suggests that intrinsic and/or extrinsic elements controlling the expression of NEC1/CT have diverged during vertebrate evolution.

Animals↗

Baclofen intoxication: report of four cases and review of the literature.

Four cases of baclofen intoxication are reported, with a review of 33 cases from the literature. Analysis of these 37 cases suggests that there are two types of baclofen intoxication syndrome. Patients with acute intoxication present with four major clinical manifestations: encephalopathy (disturbance of consciousness and/or seizure), respiratory depression, muscular hypotonia, and generalized hyporeflexia. Patients with chronic intoxication present with hallucinosis, impaired memory, catatonia, or acute mania. The acute intoxication syndrome has a faster onset, shorter duration, more severe clinical manifestations, and higher incidence of seizures than the chronic intoxication syndrome. Baclofen intoxication, although it may cause grave encephalopathic manifestations and electroencephalographic findings, has a benign outcome if actively managed.

Adult↗

Biochemical and genetic characterization of the HBA71 Ewing's sarcoma cell surface antigen.

Monoclonal antibody HBA71 detects a cell surface antigen of human Ewing's sarcomas and peripheral neuroepitheliomas that distinguishes these tumors from other small round cell tumors of childhood and adolescence. In the present study, we show that monoclonal antibody HBA71 reacts with polypeptides of Mr 32,000 and 30,000 and that the HBA71-coding gene segregates with human chromosomes X and Y in rodent-human hybrids. Therefore, we compared HBA71 to the T-cell leukemia antigen 12E7, which is encoded by the pseudoautosomal region of chromosomes X and Y. We show that monoclonal antibodies HBA71 and 12E7 (a) detect polypeptides of identical size, (b) react with mouse cells transfected with complementary DNA corresponding to the 12E7-coding gene, MIC2, and (c) give similar patterns of reactivity with human tumor cell lines and small round cell tumor tissues. Thus, HBA71 and 12E7 are identical or closely related antigens and the available MIC2 probes will facilitate analysis of the molecular mechanisms that determine differential HBA71 expression in small round cell tumors of childhood and adolescence.

12E7 Antigen↗

Binding of Bacillus subtilis ermC' methyltransferase to 23S rRNA.

ermC 23S rRNA methyltransferase dimethylates adenine 2085 in Bacillus subtilis 23S rRNA and also regulates its own synthesis by autogenous translational repression. We have characterized the binding of ermC' methyltransferase to 23S rRNA. This protein differs in only five amino acid residues from the ermC product and was chosen for study because of its greater stability and ease of isolation. A filter binding assay was used to study the physical aspects of binding in the absence of methylation. The dissociation equilibrium constant of the binding was found to be 4 x 10(-9) M at 37 degrees C. Kinetic studies of complex formation and dissociation revealed that the kon and koff were 4 x 10(6) M-1 s-1 and 6.8 x 10(-2) s-1 respectively at 16 degrees C. Equilibrium competition experiments showed that the enzyme has varying affinities for a variety of nucleic acids in the order 23S rRNA greater than 16S rRNA greater than M13 DNA, f2 RNA greater than tRNA. One of the end products of methylation, methylated 23S rRNA, had an affinity for the ermC' methyltransferase similar to that of unmethylated 23S rRNA. The binding affinity to 23S rRNA and the kinetics of the interaction were not detectably affected by the presence of AdoMet. The binding of ermC' methyltransferase to 23S rRNA had an unfavorable van't Hoff enthalpy (delta H = +6.2 kcal mol-1) and was driven by entropy (delta S = +56.2 cal mol-1 deg-1). The interaction between the two ligands involved at most two to three ionic pairings, and nonelectrostatic interactions contributed approximately 85% of the binding energy. The structural aspect of the interaction was investigated by probing with dimethyl sulfate, for ermC' methyltransferase dependent protection of 23S rRNA. A region of protection was detected, in the vicinity of the central loop of rRNA domain V and surrounding the site of methylation.

Autoradiography↗

Neuro-Behçet's disease: report of three cases with a review of the literature.

We report three cases of neuro-Behçet's disease, including one woman and two men (age range 52-56 years), who displayed symptoms of high fever, headache and confusion. The EEG showed generalized slowing in two cases, and periodic lateralized epileptiform discharges in one. Brain CT scans from two patients revealed cortical atrophy with multiple low density areas in one case, and focal contrast enhancement in the other. The CSF study revealed pleocytosis in all cases, but only one showed lymphophagocytosis. All of the patients responded dramatically to steroid therapy, although administration of the drug was somewhat delayed in two cases, during which initial management was aimed at the CNS infection of bacterial origin. Recurrent attacks of confusion or mental dullness were found in two patients, and high cortical dysfunction persisted on follow-up for some time. The clinical manifestations, laboratory findings, and neuroradiological features of neuro-Behçet's disease in the reported cases are reviewed.

Behcet Syndrome↗