Genomic diversity of vibrios associated with the Brazilian coral Mussismilia hispida and its sympatric zoanthids (Palythoa caribaeorum, Palythoa variabilis and Zoanthus solanderi).

AIMS: A taxonomic survey of the vibrios associated with the Brazilian endemic coral Mussismilia hispida and the sympatric zoanthids (i.e. Palythoa caribaeorum, Palythoa variabilis and Zoanthus solanderi). METHODS AND RESULTS: Mucus of 54 cnidarian specimens collected in three different places at São Sebastião in two consecutive years (i.e. 2005 and 2006) was used for taxonomic characterization of the cnidarian microbiota. Ninety-eight of the 151 vibrio isolates fell within the vibrio core group according to partial 16S rDNA sequences. We performed the sequencing of recA and pyrH genes of all vibrio isolates. The most abundant taxa belonged to the vibrio core group (Vibrio harveyi, Vibrio rotiferianus, Vibrio campbellii and Vibrio alginolyticus), Vibrio mediterranei (=Vibrio shillonii) and Vibrio chagasii. With the exception of V. chagasii which was found only in the mucus of M. hispida, the other species appeared in different hosts with no evidence for the presence of host-specific clones or species. Using rep-PCR analysis, we observed a high genomic heterogeneity within the vibrios. Each vibrio isolate generated a different rep-PCR fingerprint pattern. There was a complete agreement between the grouping based on rep-PCR and concatenated sequences of pyrH, recA and 16S rDNA, but the pyrH gene has the highest discriminatory power for vibrio species identification. CONCLUSION: The vibrio core group is dominant in the mucus of these cnidarians. There is a tremendous diversity of vibrio lineages within the coral mucus. pyrH gene sequences permit a clear-cut identification of vibrios. SIGNIFICANCE AND IMPACT OF THE STUDY: The taxonomic resolution provided by pyrH (but not recA) appears to be enough for identifying species of vibrios and for disclosing putative new taxa. The vibrio core group appears to be dominant in the mucus of the Brazilian cnidarians. The overrepresentation of these vibrios may reflect as yet unknown ecological functions in the coral holobiont.

Somatic and psychological factors related to the body mass index of patients with anorexia nervosa.

OBJECTIVE: The aim of this study was to examine somatic and psychological factors related to the body mass index (BMI) of anorexia nervosa (AN) patients. METHOD: The analysis was of 24 hospitalized AN patients from the day after admission to the 4th day. The somatic factors analyzed were duration of AN, daily food intake, eating regulatory substances in blood (acylated ghrelin, desacyl ghrelin, leptin), serum cortisol, insulin and estimated creatinine clearance (CCr). The psychological factors analyzed were depression, anxiety, Eating Disorder Inventory (EDI), and hunger/fullness feeling. Measurement of BMI and collection of blood samples were done on the morning after hospitalization. Statistical analysis was by multiple linear regression analysis. RESULTS: BMI showed a reverse correlation with desacyl ghrelin (beta=-0.486, p=0.015) and maturity fears (beta=-0.375, p=0.046), but was not associated with any other factor by multiple regression analysis. CONCLUSION: The results suggest that desacyl ghrelin and maturity fears play important roles in the prolonged malnutrition state seen in AN patients.

Muscle-specific enhancement of gene expression by incorporation of SV40 enhancer in the expression plasmid.

Skeletal muscle is established as an ideal tissue for gene delivery to treat systemic diseases. However, the relatively low levels of gene expression obtained from using naturally occurring promoters, including the strong cytomegalovirus (CMV) enhancer/promoter (E/P), have limited the use of muscle as a target tissue. The relatively weak simian virus 40 (SV40) enhancer is known to have dual functions promoting localization of DNA to the nucleus and activating transcription. An SV40 enhancer incorporated either at the 5' end of CMV E/P or the 3' end of the polyadenylation site gave as much as a 20-fold increase in the level of exogenous gene expression in muscle in vivo, compared with expression observed with CMV E/P alone. The minimum requirement for this enhancement is a single copy of a 72-bp element of the SV40 enhancer, in combination with either the CMV E/P or skeletal actin (SkA) promoter. Enhancement of gene expression in muscle by this SV40 enhancer was also observed by using the powerful electroporation delivery. However, the SV40 enhancer does not increase the level of CMV E/P driven reporter gene expression in dividing tumor cells in vivo and in the dividing myoblast cell C2C12 in vitro. The data suggest that including this enhancer in the plasmid will enhance the level of gene production for muscle-based gene therapy.

Gene therapy for the treatment of hemophilia B using PINC-formulated plasmid delivered to muscle with electroporation.

Gene therapy, as a safe and efficacious treatment or prevention of diseases, is one of the next fundamental medical innovations. Direct injection of plasmid into skeletal muscle is still a relatively inefficient and highly variable method of gene transfer. However, published reports have shown that application of an electric field to the muscle immediately after plasmid injection increases gene expression at least 2 orders of magnitude. Using this methodology, we have achieved potentially therapeutic circulating levels of human factor IX (hF.IX) in mice and dogs. A plasmid encoding hF.IX formulated with a protective, interactive, noncondensing (PINC) polymer was injected into the skeletal muscle followed by administration of multiple electrical pulses (electroporation). In mice long-term expression was achieved and the ability to readminister formulated plasmid was demonstrated. In normal dogs, expression of hF.IX reached 0.5-1.0% of normal levels. The transient response in dogs was due to the development of antibodies against hF.IX. Elevated circulating creatine kinase levels and histological examination indicated transient minor trauma associated with the procedure. These data show that gene delivery using a plasmid formulated with a PINC polymer augmented with electroporation is scalable into large animal models and represents a promising approach for treating patients with hemophilia B.

Fatal Pneumocystis carinii pneumonia in HIV-seropositive infants in Harare, Zimbabwe.

Lung biopsies taken post mortem from 24 HIV-seropositive children who died of pneumonia in Harare Hospital (Zimbabwe) during 1995 were examined for pathogens using histology, culture, microscopy and polymerase chain reaction (PCR). Pneumocystis carinii was detected in 16 (67%) children, in 5 of whom bacterial pathogens were also detected. There were 2 cases of cytomegalovirus infection. On the basis of histology and PCR, none of the children had tuberculosis. These data add to the evidence that P. carinii pneumonia may be a significant cause of death in HIV-infected children in southern Africa. Policies on treatment for severe pneumonia, and on prophylaxis for children born to HIV-seropositive mothers need to be re-examined.

The expression of cyclins D1 and E in predicting short-term survival in squamous cell carcinoma of the lung.

Cyclins D1 (cD1) and E (cE) are G1 phase cyclins believed to participate in the pathogenesis of malignancy. Overexpression of cD1 has been reported to influence prognosis in squamous cell carcinomas (SCC) of the larynx, but was not significant in a limited study of non-small cell lung cancers (NSCLC). Altered expression of cE has been proposed as another potential prognostic marker in malignancy but its possible role in NSCLC has not been elucidated. In order to determine the prognostic value of cD1 and cE in NSCLC, paraffin-embedded sections of 467 NSCLC were immunostained with monoclonal antibody to cD1 (1:500, PharMingen, San Diego, CA) and 400 NSCLC with MA to cE (1:2500, PharMingen) using an enhanced sensitivity avidin-biotin complex technique. The number of tumor cells with nuclear and/or cytoplasmic immunopositivity was graded on a scale of: 0 = less than 1%, 1 = 1 to 10%, 2 = 10 to 25%, 3 = 25 to 50%, 4 = 50 to 75%, 5 = more than 75%. Results were correlated with survival by Kaplan-Meier survival plot using Stat-View software (Abacus Concepts, Berkeley, CA). Overall, 426 NSCLC with cD1 and 360 NSCLC with cE had adequate follow-up (median, 76 mo) for survival analysis. Both cyclins independently showed significance in prognosis of SCC but not other cell types. For cD1, absence of immunostaining was associated with worse prognosis than any immunopositivity for all stages of SCC (P = .025). For cE, Stage I and II SCC with less than 50% immunopositivity had a worse prognosis (P = .029). Of 70 Stage I and II SCC immunostained for both monoclonal antibodies, 55% of patients with tumors that demonstrated both absence of cD1 staining and cE immunopositivity in less than 50% of cells were dead at 5 years compared to 35% of patients with tumors that demonstrated positive staining with cD1 and cE immunopositivity in more than 50% of cells. These results strongly suggest cD1 and cE can independently predict prognosis in early stage SCC. Worse prognosis was associated with loss of expression, consistent with mechanisms other than overexpression of these cyclins in the progression of SCC.

Prognostic implications of calbindin-D28k expression in lung cancer: analysis of 452 cases.

Calbindin D28k (Ca-D28k) acts as a buffering system to maintain cellular calcium homeostasis and is thought to play a role in inhibiting apoptosis. The goals of this study were to assess CA-D28k expression in lung carcinomas and to correlate these results with patient survival. A total of 452 lung carcinomas were immunostained with a monoclonal antibody specific for Ca-D28K using an avidin-biotin peroxidase technique. The number of cells with nuclear staining was graded semiquantitatively into one of five groups: 0, fewer than 10%, 10 to 25%, more than 25 to 50%, more than 50 to 75%, and more than 75%. Results were correlated with patient survival using Kaplan-Meier survival curves. A total of 335 of 452 (74%) lung carcinomas were positive for Ca-D28k. There was no statistically significant difference in the prevalence of Ca-D28k expression in tumors of different histologic type. Kaplan-Meier survival analysis revealed that for patients with adenocarcinoma, those with Ca-D28k-positive tumors had a better overall survival than patients with Ca-D28k-negative tumors (P = .036). This difference was also significant for patients with Stages I and II adenocarcinomas (P = .033). No statistically significant difference in prognosis was observed for patients with Stages III and IV adenocarcinomas or for patients with other lung carcinoma types of varying stage. Ca-D28k is commonly expressed in lung carcinomas of all histologic types. For patients with localized adenocarcinoma of the lung, Ca-D28k expression correlated with improved survival. No correlation between Ca-D28k expression and patient survival was found for disseminated adenocarcinoma and for other histologic types of lung carcinoma.

Systemic inhibition of tumor growth and tumor metastases by intramuscular administration of the endostatin gene.

Tumors require ongoing angiogenesis to support their growth. Inhibition of angiogenesis by production of angiostatic factors should be a viable approach for cancer gene therapy. Endostatin, a potent angiostatic factor, was expressed in mouse muscle and secreted into the bloodstream for up to 2 weeks after a single intramuscular administration of the endostatin gene. The biological activity of the expressed endostatin was demonstrated by its ability to inhibit systemic angiogenesis. Moreover, the sustained production of endostatin by intramuscular gene therapy inhibited both the growth of primary tumors and the development of metastatic lesions. These results demonstrate the potential utility of intramuscular delivery of an antiangiogenic gene for treatment of disseminated cancers.

Artificial neural networks and logistic regression as tools for prediction of survival in patients with Stages I and II non-small cell lung cancer.

The prognosis of patients with Stage I and II non-small cell lung cancer (NSCLC) can be estimated but cannot be definitively ascertained by use of current clinicopathologic criteria and tumor marker studies. The potential value of probabilistic neural networks (NNs) with genetic algorithms and multivariate logistic regression to predict the survival of NSCLC patients has not been previously evaluated. Multiple prognostic factors (age, sex, cell type, stage, tumor grade, smoking history, and immunoreactivity to c-erbB-3, bcl-2, Glut1, Glut3, retinoblastoma gene and p53 were correlated with 5-year survival in 63 patients with Stage I or II NSCLC, treated solely by surgical excision at Baylor Medical College, Houston, Texas. Several probabilistic NNs with genetic algorithm models were developed using the prognostic features as input neurons and survival at 5 years (free of disease/dead of disease) as output neurons. The probabilistic NN yielded excellent classification rates for dependent variable survival. The best model was trained with 52 cases and classified all 11 "unknown" test cases correctly. Several statistically significant logistic regression models were fitted using 50 cases to build the models and 13 cases as "hold-out" test cases. These multivariate statistical models provide various cutoff values that predict/classify the probability of survival at 5 years. In conclusion, probabilistic NNs and logistic regression models can be useful in estimating the prognosis of patients with Stage I and II NSCLC using multiple clinicopathologic and molecular variables. These multivariate predictive models need to be validated with much larger groups of patients to assess their potential clinical value.

Hepatitis B virus DNA is frequently found in liver biopsy samples from hepatitis C virus-infected chronic hepatitis patients.

Human hepatitis B virus (HBV) and hepatitis C virus (HCV) are two major etiologic agents of chronic hepatitis, which is closely related to the development of hepatocellular carcinoma (HCC). A possible involvement of HBV co-infection was investigated in ongoing HCV-related liver diseases in HCV-infected patients. A prevalence of anti-HBc in anti-HCV-positive/HBsAg-negative chronic hepatitis patients and a low copy number of HBV DNA were found in most of the liver biopsy samples of anti-HCV-positive/HBsAg-negative patients. The present data suggest that HBV co-infects frequently with HCV and may play an important role in the development of HCC in the anti-HCV-positive/HBsAg-negative patients with chronic hepatitis.

Absence of prognostic significance of bcl-2 immunopositivity in non-small cell lung cancer: analysis of 427 cases.

The bcl-2 gene product inhibits apoptosis and is thought to participate in oncogenesis. Association of bcl-2 immunopositivity with improved prognosis of non-small cell lung cancers (NSCLC) is controversial. Although two studies have reported better survival in bcl-2-immunopositive NSCLCs, a third series has contradicted this finding. The authors studied a relatively larger case series involving 427 patients for whom detailed information on long-term follow-up was available to determine the prognostic significance of bcl-2 expression. The study included 252 adenocarcinomas (AC), 111 squamous cell carcinomas (SCC), and 64 large cell carcinomas (LC). After antigen retrieval, sections were immunostained using a monoclonal anti-bcl-2 antibody (1:60, Clone 124, Dako) and the avidin-biotin complex technique. Staining was scored as positive or negative and also on a semiquantitative scale as 0, low (<10%), moderate (10% to 75%), or extensive (>75%). Bcl-2 immunoreactivity was correlated with survival using the actuarial survival method, Kaplan-Meier method, and log-rank test and was not associated with statistically significant differences in survival for NSCLCs (P = .5537). Differences in survival remained insignificant even after NSCLCs were stratified for cell type, stage, or grade, singly or in combination. Therefore, using this method, bcl-2 immunopositivity does not appear to act as an independent prognostic indicator in NSCLCs.

Overexpression of Glut1 and Glut3 in stage I nonsmall cell lung carcinoma is associated with poor survival.

BACKGROUND: Increased expression of Glut1 and Glut3 has been reported in many human cancers, including nonsmall cell lung carcinoma (NSCLC). The aim of this study was to determine the biologic significance of Glut1 and Glut3 overexpression in Stage I NSCLC. METHODS: Using immunohistochemistry and polyclonal anti-Glut1 and anti-Glut3 antibodies, the authors immunostained sections of formalin fixed, paraffin embedded tissues from 289 Stage I NSCLCs. The Kaplan-Meier survival method, the log rank test, and Fisher's exact test were used for statistical analysis. RESULTS: Of the 289 cases, 49 (17%) were negative for both Glut1 and Glut3, 239 (83%) were Glut1 positive, 61 (21%) were Glut3 positive, 179 (62%) were positive for Glut1 but negative for Glut3, 1 (0.3%) was positive for Glut3 but negative for Glut1, and 60 (21%) were positive for both Glut1 and Glut3. Only 1 of 50 Glut1 negative tumors (2%) was positive for Glut3, whereas 60 of 239 Glut1 positive tumors (25%) were positive for Glut3 (P < 0.0001). Glut1 or Glut3 were detected more often in poorly differentiated and undifferentiated tumors (P < 0.0001 and P = 0.0008, respectively). Overexpression of Glut1 and/or Glut3 was associated with poorer survival (P = 0.0133), especially in patients with well-differentiated and moderately differentiated tumors (P = 0.0017). CONCLUSIONS: In Stage I NSCLC, Glut3 overexpression likely occurs after Glut1 overexpression. The appearance of Glut1 positive clones is associated with aggressive biologic behavior, which is worsened by the emergence of Glut3 positive clones. Glut1 and Glut3 are significant of poor prognosis indicators in cases of NSCLC.

Antitumor activity of TZT-1027, a novel dolastatin 10 derivative.

Dolastatin 10, a pentapeptide isolated from the marine mollusk Dolabella auricularia, has antitumor activity. TZT-1027, a dolastatin 10 derivative, is a newly synthesized antitumor compound. We evaluated its antitumor activity against a variety of transplantable tumors in mice. Intermittent injections of TZT-1027 were more effective than single or repeated injections in mice with P388 leukemia and B16 melanoma. Consequently, TZT-1027 shows schedule dependency. TZT-1027 was effective against P388 leukemia not only when administered i.p., but also when given i.v. However, although TZT-1027 given i.v. was active against murine solid tumors, TZT-1027 administered i.p. was ineffective against all the tumors tested with the exception of colon 26 adenocarcinoma. The i.v. injection of TZT-1027 at a dose of 2.0 mg/kg remarkably inhibited the growth of three murine solid tumors; colon 26 adenocarcinoma, B16 melanoma and M5076 sarcoma, with T/C values of less than 6%. The antitumor activities of TZT-1027 against these tumors were superior or comparable to those of the reference agents; dolastatin 10, cisplatin, vincristine, 5-fluorouracil (5-FU) and E7010. In experiments with drug-resistant P388 leukemia, TZT-1027 showed good activity against cisplatin-resistant P388 and moderate activity against vincristine- and 5-fluorouracil-resistant P388, but no activity against adriamycin-resistant P388. TZT-1027 was also effective against human xenografts, that is, tumor regression was observed in mice bearing MX-1 breast and LX-1 lung carcinomas. TZT-1027 at 10 microM almost completely inhibited the assembly of porcine brain microtubules. Therefore, its mechanism of antitumor action seems to be, at least in part, ascribable to the inhibition of microtubule assembly. Because of its good preclinical activity, TZT-1027 has been entered into phase I clinical trials.

High c-erbB-3 protein expression is associated with shorter survival in advanced non-small cell lung carcinomas.

c-erbB-3 is a new member of the Type I growth factor receptor family that includes epidermal growth-factor receptor (also called c-erbB-1) and HER-2/neu (also called c-erbB-2). Frequency and significance of c-erbB-3 overexpression in lung cancers have not been reported previously. A series of 549 cases of primary lung carcinomas were immunostained with a monoclonal anti-human c-erbB-3 antibody (Clone RTJ.1) using formalin-fixed, paraffin-embedded archival tissue. Sharp membranous staining or punctate cytoplasmic staining was interpreted as positive and scored 0 (< 5% of tumor cells), 1 (5-9%), 2 (10-49%), or 3 (> or = 50%). Medical records were reviewed for clinical data, including stage and survival. Actuarial cumulative survival analysis with the Mantel-Cox test was performed on 443 cases that had a single primary site in the lung of pure non-small cell carcinoma (adenocarcinoma, squamous cell carcinoma, large cell carcinoma) and that also had follow-up data for more than 3 months. In all stages, squamous cell carcinoma showed the greatest rate of high c-erbB-3 positivity (score, 3) (34/119; 28.6%), followed by adenocarcinoma (41/256; 15.9%) and large cell carcinoma (7/66; 10.6%). Patients with high c-erbB-3 expression (score, 3) survived for significantly shorter times than did patients with low c-erbB-3-expression (score, 0-2) in Stages III and IV (P = 0.002), but not in Stage I or II non-small cell lung carcinomas. In conclusion, high c-erbB-3 expression in advanced non-small cell lung carcinomas might be an adverse prognostic factor. This finding suggests that c-erbB-3 might be a potential target for molecular therapy in advanced non-small cell lung carcinomas.

Reduction in thermal hyperalgesia by intrathecal administration of glycine and related compounds.

We have previously shown in animal models that enhanced segmental glycine release is produced by neuroaugmentation techniques commonly used to control pain in humans. Our current hypothesis is that glycine administered intrathecally reduces the pain response evoked by the hotplate analgesia meter method. Neuropathic rats created by unilateral partial ligation of the sciatic nerve were treated with intrathecal infusion of glycine, strychnine, MK-801, or 5-7 DKA at 0.1 mumol for 2 hours at a rate of 10 microliters/min. Time required for limb withdrawal at 42 degrees C was significantly increased after glycine administration but not altered by strychnine, a specific glycine receptor antagonist. Administration of the NMDA receptor antagonist, MK-801, blocked the influence of glycine, with a less obvious antagonistic response from 5.7 DKA. Our results provide evidence that glycine and related compounds significantly modify thermal hyperalgesia, and may operate primarily through the NMDA receptor complex.

Reduction in the mechanonociceptive response by intrathecal administration of glycine and related compounds.

We have previously reported that enhanced glycine release is produced by epidural spinal cord stimulation, a clinical method for treating neuropathic pain. Our current hypothesis is that glycine administered intrathecally reduces neuropathic pain as measured by the Randall-Selitto method. Neuropathic rats created by unilateral partial ligation of the sciatic nerve were treated with intrathecal infusion of glycine, strychnine, MK-801, or 5,7-DKA at 0.1 mumol, or artificial CSF for 2 hours at a rate of 10 microliters/min. Force required to produce the pain response was significantly increased after glycine administration and reduced using strychnine, a specific glycine receptor (Gly l) antagonist. Strychnine blocked the response to glycine when infused together. Administration of the non-specific NMDA receptor MK-801 antagonist and 5,7-DKA, a specific glycine-NMDA receptor (Gly 2) antagonist, however, failed to block the response to glycine. Our results provide evidence for the use of glycine and related compounds to treat neuropathic pain.

p53 gene product in pleural effusions. Practical use in distinguishing benign from malignant cells.

OBJECTIVE: To determine the utility of positive p53 immunostaining as an adjunct in the diagnosis of malignancy in pleural effusions, we reviewed 103 effusions representing the typical range of diagnoses encountered in the evaluation of pleural fluid cytology. STUDY DESIGN: Immunohistochemistry was performed on paraffin-embedded cell blocks using a monoclonal antibody to the p53 suppressor gene product clone BP53-12 and a standard avidin-biotin complex technique with a citrate buffer antigen retrieval solution. RESULTS: Forty-one of 75 effusions with an unequivocal cytologic diagnosis of malignancy were immunopositive for p53 protein (55%). One of nine effusions cytologically interpreted as showing reactive mesothelial cells showed immunopositivity; that case was subsequently diagnosed as a mesothelioma on pleural biopsy. Nineteen cases were interpreted as suspicious for malignancy. Of these, 16 were negative, and 3 were positive for p53 protein. Of the three positive cases, two showed the presence of non-small cell and poorly differentiated large cell carcinoma. CONCLUSION: These findings suggest that p53 protein immunostaining is relatively sensitive and highly specific in differentiating benign mesothelial cells from malignant cells in pleural effusions. While negative p53 protein immunostaining does not exclude malignancy, positive staining in reactive or suspicious cells warrants further diagnostic evaluation of the patient.

p53 and MDM2 immunostaining in pulmonary blastomas and bronchogenic carcinomas.

Pulmonary blastomas (PBs) are rare primary malignancies that include adult types: biphasic pulmonary blastoma (BPB) and well-differentiated fetal adenocarcinoma (WDFA); and childhood type: pleuropulmonary blastoma (PPB). Their pathogenesis and relationship to bronchogenic carcinoma (BCA) are controversial. To determine whether or not PB share molecular pathological features with BCA, the authors immunostained three BPB, three WDFA, three PPB, and 80 standard BCA for p53 protein and MDM2 protein, gene products believed to be significant in the pathogenesis of BCA. Paraffin-embedded tissue sections were immunostained with monoclonal antibody to p53 and MDM2 proteins. Strong intranuclear staining in greater than 10% of cells was considered positive. Three (50%) BPB and WDFA stained for p53 and five (83%) for MDM2. None of the PPB stained for p53, and one PPB did not stain for either p53 or MDM2. Five of six adult type PB occurred in smokers, whereas none of the PPB was associated with smoking. Seventy-five (94%) of the BCA stained for MDM2 and 46 (61%) for p53. Immunostaining patterns for p53 and MDM2 in adult types of PB, and not PPB, appear similar to those for BCA. This may suggest that adult type PB, but not childhood PB, have a similar pathogenesis to BCA.

Synthesis and antitumor activity of novel dolastatin 10 analogs.

Dolastatin 10 (1) is a potent antineoplastic pentapeptide. Novel dolastatin 10 analogs each modified at one of the constituent amino acid derivatives, were synthesized and their antitumor activity was evaluated against P388 leukemia in mice. The structural requirements for antitumor activity are discussed. Some of the analogs, 31c, 35c, 38b, and 50c showed excellent activity in vivo. Highly active 50c, which lacks the thiazole group of 1, was selected for further development as an antitumor agent.

The influence of glycine and related compounds on spinal cord injury-induced spasticity.

Spasticity is a frequent and complex sequel to spinal cord injury. The neurochemical basis for the origin of spasticity is largely unknown. Glycine is among the most abundant neurotransmitters in the spinal cord. However, the role of glycine and related compounds in spasticity have received little attention. An ischemic spinal cord injury was created in rabbits, by an intraaortic balloon occlusion technique, which produced lower limb spasticity. A catheter was inserted into the cisterna magna and the spinal cord was bathed with 100 microM solutions of glycine, strychnine, D-serine, beta-alanine, MK-801, or artificial CSF for 4 hours at a rate of 10 microliters/min. H-reflexes were monitored before and during infusion by stimulating the posterior tibial nerve and recording from the plantar surface of the foot. Glycine, D-serine, and MK-801 depressed the H wave, strychnine produced a heightened H wave, and beta-alanine caused no significant changes. These results indicate that glycine and related compounds may influence spasticity.