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Biomedical subjects

Y Yao

Publications and source records attributed to Y Yao.

At least 127 records · Page 7Linked to original sources

[The relationship between angiogenesis and p53 overexpression in endometrioid adenocarcinoma].

OBJECTIVE: To determine the relationship between angiogenesis and p53 overexpression and explore the relationship between angiogenesis and clinicopathologic features in endometrioid adenocarcinoma. METHODS: Angiogenesis was evaluated by intratumoral microvessel density (IMD). Eighty-five endometrioid adenocarcinomas' IMD were identified by immunohistochemical staining of endothelial cells for factor VIII-related antigen, and the expression of p53 protein was stained with the same method by it's monoclone antibody. RESULTS: (1) The positive rate of p53 expression in endometrioid adenocarcinoma was 50.6%. The positive rate in stage III-IV (69.2%) was higher than that in stage I-II(42.4%) (P < 0.05). (2) IMD was higher in stage III-IV (13.27 +/- 6.14) than that in stage I-II (8.31 +/- 4.78) (P < 0.01). IMD in G1, G2 and G3 was 8.95 +/- 5.51, 9.28 +/- 4.87 and 14.73 +/- 7.66, respectively (P < 0.05). In groups of non-myoinvasion, < 1/2 myoinvasion and > or = 1/2 myoinvasion, IMD was 8.45 +/- 5.53, 8.95 +/- 4.99 and 11.96 +/- 6.39, respectively (P < 0.05). (3) In negative, weakly positive and strong positive groups of p53 overexpression, IMD was 5.52 +/- 2.11, 11.75 +/- 4.18 and 16.00 +/- 4.63, respectively (P < 0.01). CONCLUSIONS: Angiogenesis tightly correlated with clinicopathologic factors, such as stage, grade and myoinvasion, is promoted by p53 overexpression in endometrioid adenocarcinoma. It can be concluded that angiogenesis may act as a predictor of prognosis of endometrioid adenocarcinoma.

Adult↗

[The relationship between tissue tumor necrosis factor-alpha(TNF-alpha) mRNA expression and gut-derived endotoxemia in rats after thermal injury].

OBJECTIVE: To investigate the dynamic changes in tumor necrosis factor-alpha(TNF-alpha) mRNA expression and the relationship between TNF-alpha mRNA and gut-derived endotoxemia in rats after thermal injury. METHODS: 56 male Wistar rats were subjected to a 35% total body surface area full-thickness thermal injury and randomly divided into 3 groups: normal controls, 35% III* injury group, and polymyxin B treatment group. Plasma endotoxin was measured by limulus amebocyte lysate test, and tissue TNF-alpha mRNA expression was determined by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: It was found that a significant elevation of endotoxin concentration in both portal and systemic circulation was observed at 2 hours after thermal injury, peaking at 8 hours (P < 0.05-0.01) and lowering at 24 hours. Meanwhile, TNF-alpha mRNA expression significantly increased in liver, lung, intestine, and kidney at 2 hours, peaking at 8 hours, and a high level was maintained till 24 hours. However, treatment with a low-dose polymyxin B could lower both portal and systemic endotoxin levels, and markedly inhibit TNF-alpha mRNA expression in various organs. In addition, a positive correlation between portal endotoxin concentration and pulmonary, intestinal and renal TNF-alpha mRNA expression was noted (r = 0.365-0.484, all P < 0.05). CONCLUSION: This study suggests that major burns can lead to a marked elevation of tissue TNF-alpha mRNA expression in vital organs, which may be associated with gut-derived endotoxemia caused by acute thermal injury.

Animals↗

[The time course and tissue distribution of endotoxin in rats after thermal injury].

OBJECTIVE: To observe the time course and tissue distribution of endotoxin, and to evaluate the potential role of local endotoxin in mediating multiple organ damage following burns. METHODS: Wistar rats were subjected to a 35 percent full-thickness scald injury. They were grouped according to time of sacrifice: no burn, and 12, 24, 48, 72 hours postburn. Tissue specimens from liver, kidneys, lungs and intestine were aseptically harvested to determine tissue endotoxin levels. In addition, blood samples were obtained for measurement of organ function parameters. RESULTS: It was found that endotoxin levels in liver, spleen and lungs increased markedly after thermal injury, with the highest level in liver. Meanwhile, serum GPT, GOT, CK-MB levels, and pulmonary myeloperoxidase(MPO) activities markedly elevated after scald injury, reaching a maximum between 12 and 24 hours. Intestinal diamine oxidase(DAO) activities tended to decrease at various time points postburn. In addition, there were highly positive correlations between pulmonary endotoxin levels and MPO activities, and also between renal endotoxin levels and serum Cr values. CONCLUSION: Burn injury per se can result in gut-derived endotoxin translocation which is mainly distributed to the liver, spleen and lungs. Endotoxin accumulated in local sites may play an important role in mediating multiple organ damage secondary to major burns.

Animals↗

[The effect of intestinal ischemia/reperfusion on increased sensitivity to endotoxin and its potential mechanism].

OBJECTIVE: To investigate the effect of intestinal ischemia/reperfusion injury (I/R) on increased sensitivity to endotoxin and its potential mechanism(s). METHODS: Sprague-Dawley rats underwent 45 minutes of superior mesenteric artery occlusion followed by reperfusion. Twelve hours after reperfusion, endotoxin (Escherichia coli LPS, 1.5 mg/kg) was injected intravenously and rats were killed 12 hours later for measurement of organ function parameters. Also, in vitro study was performed to determine LPS-induced tumor necrosis factor (TNF)release in whole blood. RESULTS: LPS injection after I/R resulted in marked hemodynamic dysfunction and multiple organ damage(P < 0.01), while no significant or only minor changes in organ function parameters were observed in both I/R and LPS groups. In whole blood, monoclonal antibody to CD14 significantly blocked the release of TNF at low LPS concentration (< or = 10 ng/ml), and this response was dose dependent. Moreover, TNF release in LPS-stimulated whole blood obtained after I/R was inhibited to a significantly greater degree than that in baseline blood samples or sham-operation group(P < 0.05-0.01). CONCLUSION: Splanchnic artery occlusion followed by reperfusion could lead to increased sensitivity to the subsequent LPS challenge, which may be associated with a shift toward CD14-dependent mechanism(s).

Animals↗

[The effect of bactericidal/permeability-increasing protein on lipopolysaccharide-binding protein and lipopolysaccharide receptor CD14 mRNA expression in rats after thermal injury].

OBJECTIVE: To elucidate the possible mechanisms underlying beneficial effect of recombinant bactericidal/permeability-increasing protein (rBPI) on multiple organ damage secondary to major burns. METHODS: Wistar rats were subjected to a 35% full-thickness scald injury, and randomly divided into 3 groups: normal controls (n = 8), thermal injury (n = 21), and rBPI21 treatment (n = 12). In thermal injury and rBPI21 treatment groups, animals were sacrificed at 12 and 24 hours after burn, respectively. Tissue samples from liver, kidneys, lungs and intestine were collected to measure lipopolysaccharide-binding protein (LBP)/lipopolysaccharide receptor CD14 and tumor necrosis factor-alpha (TNF-alpha) mRNA expression. In addition, blood samples were obtained for measurement of organ function parameters. RESULTS: Treatment with rBPI21 could significantly decrease tissue LBP and CD14 mRNA expression in various organs (P < 0.05-0.01). Also, TNF-alpha mRNA expression in liver, kidneys and lungs were markedly inhibited by rBPI21 secondary to acute insults (P < 0.05-0.01). Moreover, in the rBPI21 treatment group, significant reduction in serum GPT levels and elevation in intestinal DAO activities were found compared to those in the thermal injury group (P < 0.05-0.01). CONCLUSIONS: Treatment with rBPI21 is effective in attenuating multiple organ damage resulted from gut origin endotoxin translocation after thermal injury, which might be associated with down-regulation effect of tissue LBP and CD14 gene expression by use of rBPI21.

Acute-Phase Proteins↗

[A study on the endotoxin and bacterial contamination in reverse osmosis water and dialysis fluids].

OBJECTIVE: To evaluate the endotoxin (ET) and the bacterial contamination in reverse osmosis (RO) water and dialysis fluids for hemodialysis treatment. METHODS: Specimens of RO water and dialysis fluids were obtained at random from 18 hospitals in Beijing. ET was measured with chromogenic limulus amoeboeyte lysate (LAL) assay. Bacteriologic samples were processed on heterotrophic plate count agar with pour plate technique. The plasma IL-1, IL-6 and TNFalpha were tested with enzyme-linked immunosorbent assay (ELISA). RESULTS: The level of ET in RO water was 0.116 +/- 0.063 EU/ml, and the culture of bacteria had 2 positive results, both counting 100 CFU/ml. The level of ET was much higher in acid concentrate (Protocol B) than in basic concentrate (Protocol A). The culture of bacteria had 11 positive results in Protocol B concentration with 8 samples equal or higher than 2,000 CFU/ml. The culture of bacteria had only 3 positive results in Protocol A concentration, all being lower than 2,000 CFU/ml. Another investigation showed that the level of ET in dialysis inlet was higher than 0.5 EU/ml in 5 cases of a total of 16. Their plasma IL-1 and TNFalpha levels were significantly increased. CONCLUSION: Both ET and bacterial contamination exist in RO water and dialysate. It is essential to examine the level of ET and perform bacterial culture, as well as to disinfect RO and dialysate tank at regular intervals in order to reduce pyrogenic reactions.

Endotoxins↗

[Biopterin synthesis and GTP cyclohydrolase I mRNA expression in rats following endotoxic shock].

OBJECTIVE: To investigate the potential role of changes in biopterin (tetrahydrobiopterin and more oxidized species) synthesis and GTP cyclohydrolase I (GTP-CHI) mRNA expression in endotoxic shock. METHODS: SD rats were subjected to endotoxic shock by a bolus injection of lipopolysaccharide (15 mg/kg, i.p.), biopterin and GTP-CHI mRNA levels in liver, kidney, and intestine were determined at 4, 8 hours following endotoxin challenge. RESULTS: Tissue biopterin levels significantly elevated in liver, kidney, and intestine, with high levels sustaining for 8 hours after endotoxin challenge (P < 0.05, P < 0.01). Similarly, GTP-CHI mRNA induction in various tissues substantially increased within 4 hours compared to normal controls (P < 0.05, P < 0.01). It was also shown that hepatic and renal biopterin levels were positively correlated with glutamic pyruvic transaminase (GPT) and also blood urea nitrogen (BUN) values (both P < 0.01). In addition, treatment with recombinant bactericidal/permeability increasing protein (rBPI(21)) markedly reduced tissue biopterin and GTP-CHI mRNA levels, concomitant with significant decreases in GPT, BUN as well as D-lactate values. CONCLUSIONS: Biopterin synthesis and release may be involved in the development of endotoxin-induced multiple organ dysfunction, and early use of rBPI(21) is effective to inhibit marked GTP-CHI mRNA expression and biopterin formation following septic shock.

Animals↗

[Gene expression of lipopolysaccharide receptor CD14 and tumor necrosis factor-alpha in rats after thermal injury].

OBJECTIVE: To investigate changes in lipopolysaccharide receptor CD14 and tumor necrosis factor-alpha (TNF-alpha) gene expression in vital organs, and their significance in the pathogenesis of systemic inflammation after burns. METHODS: Wistar rats were subjected to a 35 percent full-thickness scald injury, then sacrificed pre-burn, and postburn 12, 24, 48, 72 hours, respectively. Tissue samples from liver, kidney, lung and intestine were collected to measure CD14 and TNF-alpha mRNA expression. Peritoneal macrophages were harvested by peritoneal lavage to determine CD14 mRNA expression. RESULTS: CD14 mRNA expression increased markedly after thermal injury, peaking at both 12 and 48 hours. Likewise, CD14 mRNA levels were significantly up-regulated in peritoneal macrophages. Gene expression of TNF-alpha elevated markedly in liver, lungs, and kidneys after acute insults. Positive correlation was found between CD14 mRNA and TNF-alpha mRNA in liver, lung, and kidney tissues. CONCLUSIONS: Thermal injury per se can markedly up-regulate both CD14 and TNF-alpha gene expression in various organs. Excessive CD14 mRNA expression may enhance synthesis and release of TNF-alpha stimulated by endotoxin translocation, and the interaction between CD14 and TNF-alpha may play an important role in mediating multiple organ damage secondary to major burns.

Animals↗

[Long term effect of thymectomy for patients with myasthenia gravis].

OBJECTIVE: To evaluate the long term effect of thymectomy for patients with myasthenia gravis. METHODS: Patients with myasthenia gravis 4 - 54 months after thymectomy were followed up. RESULTS: 124 patients with myasthenia gravis were treated by thymectomy from April 1990 to August 1994. The mean age at the time of surgery was 29.2. According to the modified Osserman classification. 29 patients were type I, 23 type II a, 41 type II b and 11 type III. After thymectomy 82.7% patients had good response to the operation. 13.5% had no response and 1.9% were even worse. Of 104 patients followed up, no early death was found and late death occurred in 2. Type II patients and those with shorter preoperative course responded better. CONCLUSIONS: The surgical outcome is related to clinical classification of myasthenia gravis and the duration of preoperative period. Sex and pathologic type of thymus lesion seem to be irrelevant factors to the surgical outcome. To perform thymectomy or not should be very carefully weighed for patients younger than 10 years of age.

Adolescent↗

[Microvessel count in normal cervical tissue and in cervical carcinomas].

This study was conducted to determine microvessel count(MVC) status in normal cervical tissue (NCT) and in cervical carcinomas (CCs). 15 cases of NCT and 80 cases of CCs were stained by immunohistochemical method for Factor VIII related antigen (F8RA). The results showed that the MVC in CCs was much higher than that in NCT and it was correlated with clinical stage, size of tumor and lymph node status (P < 0.05). Every time when MVC increased by 5 in number (LM x 200, field 0.739 mm2), the chance of lymph node metastasis increased by 1.61 times. There was no relationship between MVC and tumor grade. These suggested that MVC might be a useful early parameter in the diagnosis and prognosis of CCs.

Carcinoma, Squamous Cell↗

[Study on the mechanism of glutamate mediated neurotoxicity by cortical neuron culture technique in vitro].

This study was intended to further explain the mechanism of glutamate (Glu) mediated neurotoxicity. The concentrations of TCa and Ca2+ i were measured in 32 cortical neuron cultures, which were divided into four groups: normal control group (n = 8); 0.5 mmol/L Glu group (Glu group n = 8); 0.5 mmol/L Glu + 100 mmol/L Nimodipine group (antagonist I, n = 8); 0.5 mmol/L Glu + 12 mumol/L MK-801 group (antagonist II, n = 8). The results showed that TCa and Ca2+ i concentrations in Glu group were significantly higher than those in normal control group (P < 0.05); TCa and Ca2+i in both antagonist I and II groups were evidently lower than those in Glu group (P < 0.05); No difference was found between antagonist I and II groups. The results suggest that Glu neurotoxicity is due to the intracellular calcium overload, which may be from the pathway of voltage-dependent calcium channels (VDCCs) and NMDA receptor-operated channels (NROCs).

Animals↗

Characterization of PKCI and comparative studies with FHIT, related members of the HIT protein family.

We previously described the isolation of a human cDNA that encodes a protein termed protein kinase C inhibitor (hPKCI). We elucidated the three-dimensional structure of this protein and demonstrated that in vitro, it enzymatically hydrolyzes adenosine polyphosphates. To identify other proteins that interact with hPKCI, in the present study, we used the hPKCI as a bait in the yeast two-hybrid system, together with a mouse embryo cDNA library. This led to the isolation of a murine PKCI homologue (mPKCI). This finding is consistent with our previous structural studies indicating that hPKCI exists as a homodimer and indicates the strong conservation of the PKCI sequence during evolution. Northern blot analysis indicated that a 0.7-kb PKCI mRNA was expressed in several tissues obtained from adult mice and also in a variety of rodent and human cell lines. Western blot analyses, using a polyclonal antibody prepared against hPKCI, indicated that this protein is expressed at relatively high levels in several murine tissues and in a variety of human cell lines prepared from normal tissues or tumors. In contrast to these findings, parallel studies with a polyclonal antibody to FHIT, a related histidine triad (HIT) protein and putative tumor suppressor, indicated that FHIT was expressed at low or undetectable levels in some of the same cell lines. Microscopy of immunostained cells indicated that the PKCI protein was present mainly in the nucleus of both normal and tumor-derived epithelial cell lines. Evidence presented in this and previous studies suggest that in vivo the ubiquitously expressed PKCI protein does not function as an inhibitor of PKC but rather acts as an enzyme in a yet to be identified pathway.

Acid Anhydride Hydrolases↗

Progressive decline in the ability of calmodulin isolated from aged brain to activate the plasma membrane Ca-ATPase.

To identify possible relationships between the loss of calcium homeostasis in brain associated with aging and alterations in the function of key calcium regulatory proteins, we have purified calmodulin (CaM) from the brains of Fischer 344 rats of different ages and have assessed age-related alterations in (i) the secondary and tertiary structure of CaM and (ii) the ability of CaM to activate one of its target proteins, the plasma membrane (PM) Ca-ATPase. There is a progressive, age-dependent reduction in the ability of CaM to activate the PM-Ca-ATPase, which correlates with the oxidative modification of multiple methionines to their corresponding methionine sulfoxides. No other detectable age-related posttranslational modifications occur in the primary sequence of CaM, suggesting that the reduced ability of CaM to activate the PM-Ca-ATPase is the result of methionine oxidation. Corresponding age-related changes in the secondary and tertiary structure of CaM occur, resulting in alterations in the relative mobility of CaM on polyacrylamide gels, differences in the intrinsic fluorescence intensity and solvent accessibility of Tyr99 and Tyr138, and a reduction in the average alpha-helical content of CaM at 20 degreesC. Shifts in the calcium- and CaM-dependent activation of the PM-Ca-ATPase are observed for CaM isolated from senescent brain, which respectively requires larger concentrations of either calcium or CaM to activate the PM-Ca-ATPase. The observation that the oxidative modification of CaM during normal biological aging results in a reduced calcium sensitivity of the PM-Ca-ATPase, a lower affinity between CaM and the PM-Ca-ATPase, and the reduction in the maximal velocity of the PM-Ca-ATPase is consistent with earlier results that indicate the calcium handling capacity of a range of tissues including brain, heart, and erythrocytes isolated from aged animals declines, resulting in both longer calcium transients and elevated basal levels of intracellular calcium. Thus, the oxidative modification of selected methionines in CaM may explain aspects of the loss of calcium homeostasis associated with the aging process.

Aging↗

Assay for enzyme activity by following the absorbance change of pH-indicators.

Based on the absorbance change of indicators with the concentration of hydrogen ion released from an enzyme-catalyzed reaction, a convenient colorimetric method was established for the assay of acidic phospholipase A2 and glycogen phosphorylase b. Brilliant yellow and bromothymol blue were chosen as indicators for assays of acidic phospholipase A2 and glycogen phosphorylase b by following the absorbance changes at 495 and 615 nm, respectively. The method is simple, sample-saving, sensitive and valid for a wide range of enzyme concentrations. It can be extended for assaying other enzymes catalyzing reactions with hydrogen ion concentration changes.

Animals↗

Localization and expression of p27KIP1 in multistage colorectal carcinogenesis.

The cyclin-dependent kinase inhibitor p27Kip1 can inhibit the G1 to S transition of the cell cycle and is a putative tumor suppressor. However, our laboratory found that a variety of human cancer cell lines express relatively high levels of this protein and that this is often associated with increased expression of cyclin D1 or cyclin E. Therefore, in the present study we analyzed by immunohistochemistry the expression of p27Kip1 in a series of human tissue samples representing various stages of colon carcinogenesis, using 20 samples of normal colon mucosa, 20 hyperplastic polyps, 19 samples of adenomatous polyps, and 40 samples of various types of colorectal carcinomas. Parallel immunostaining was done for cyclin D1 and also for Ki67 to evaluate cell proliferation. An additional 17 human colon carcinoma samples, together with paired adjacent normal mucosa samples, were analyzed for levels of expression of the p27Kip1 protein by Western blot analysis, and 7 of these pairs of samples were examined by Northern blot analysis for levels of p27Kip1 mRNA. We did not find a positive or negative correlation between p27Kip1 expression and cell proliferation in the normal mucosa and tumor samples. There was, however, an inverse correlation between p27Kip1 and Ki67 expression in the lymphoid follicles present in the colonic mucosa. There was no evidence for a consistent increase or decrease in p27Kip1 expression in the mucosal cells during colon carcinogenesis, because the mean values for percentage p27Kip1-positive cells were similar in the normal mucosa, adenomatous polyps, and carcinoma samples. This is in contrast to Ki67 and cyclin D1 expression, which did show significant increases in mean values with tumor development. A subset (35%) of the carcinomas displayed diffuse cytoplasmic staining, in addition to nuclear staining, for p27Kip1, and in these cases the percentage of cells that were positive for p27Kip1 was higher than in cases that had only nuclear staining. There was a significant correlation between p27Kip1 expression and tumor grade; ie., well and moderately differentiated carcinomas had high p27Kip1 expression, whereas poorly differentiated carcinomas had lower expression. The Western blot analysis data on p27Kip1 expression confirmed this correlation. Comparisons of Northern and Western blots did not show a correlation between the level of p27Kip1 mRNA and the corresponding protein, a finding consistent with evidence that the p27Kip1 protein is regulated mainly via a posttranscriptional mechanism. The immunostaining studies revealed a significant correlation between high p27Kip1 protein expression and high cyclin D1 expression in the adenomatous polyps and in the subset of carcinomas that had only nuclear p27Kip1 expression. This may reflect the existence of a homeostatic feedback mechanism that is lost in the high-grade carcinomas that express low levels of p27Kip1.

Adult↗

Loss of conformational stability in calmodulin upon methionine oxidation.

We have used electrospray ionization mass spectrometry (ESI-MS), circular dichroism (CD), and fluorescence spectroscopy to investigate the secondary and tertiary structural consequences that result from oxidative modification of methionine residues in wheat germ calmodulin (CaM), and prevent activation of the plasma membrane Ca-ATPase. Using ESI-MS, we have measured rates of modification and molecular mass distributions of oxidatively modified CaM species (CaMox) resulting from exposure to H2O2. From these rates, we find that oxidative modification of methionine to the corresponding methionine sulfoxide does not predispose CaM to further oxidative modification. These results indicate that methionine oxidation results in no large-scale alterations in the tertiary structure of CaMox, because the rates of oxidative modification of individual methionines are directly related to their solvent exposure. Likewise, CD measurements indicate that methionine oxidation results in little change in the apparent alpha-helical content at 28 degrees C, and only a small (0.3 +/- 0.1 kcal mol(-1)) decrease in thermal stability, suggesting the disruption of a limited number of specific noncovalent interactions. Fluorescence lifetime, anisotropy, and quenching measurements of N-(1-pyrenyl)-maleimide (PMal) covalently bound to Cys26 indicate local structural changes around PMal in the amino-terminal domain in response to oxidative modification of methionine residues in the carboxyl-terminal domain. Because the opposing globular domains remain spatially distant in both native and oxidatively modified CaM, the oxidative modification of methionines in the carboxyl-terminal domain are suggested to modify the conformation of the amino-terminal domain through alterations in the structural features involving the interdomain central helix. The structural basis for the linkage between oxidative modification and these global conformational changes is discussed in terms of possible alterations in specific noncovalent interactions that have previously been suggested to stabilize the central helix in CaM.

Amino Acid Sequence↗

Skeletal muscle regeneration induced by chorio-allantoic grafting.

To examine whether the expression pattern of fast-muscle type troponin-T (TnT) isoforms was fixed in cell lineage, breast muscle pieces (pectoralis major) from chick embryos and young and adult chickens were grafted on to chorio-allantoic membrane of 9-day-old chick embryos and cultured until the host embryos hatched out. Muscle fibre formation of the grafts was investigated by histological and immunohistochemical methods with anti-fast-muscle type and anti-slow-muscle type TnT sera, and the expression of fast-muscle type TnT in the grafts from chick embryos and young chickens was studied by SDS-polyacrylamide gel electrophoresis (SDS-PAGE), two-dimensional SDS-PAGE, and immunoblotting. In the chorio-allantoic grafting, the breast muscle initially degenerated forming pyknotic nuclei and hyaline cytoplasm. The surviving cells, which were supposed to be satellite cells, regenerated new muscle fibres of the same type as those of the grafted muscle in respect of TnT isoform expression. Therefore, we considered that the ability to express specific isoforms of TnT was fixed in the satellite cells, and that chorio-allantoic grafting was a useful technique for studying muscle differentiation.

Allantois↗

A model of coccidioidal meningoencephalitis and cerebrospinal vasculitis in the rabbit.

Coccidiodal meningitis is a devastating complication of disseminated coccidioidomycosis. An animal model of this infection could enhance understanding of the pathogenesis of the disease and lead to improvements in therapy. A rabbit model of central nervous system infection simulating human disease was established using a blind cisternal tap technique to inoculate 4 x 10(3)-1 x 10(6) arthroconidia of Coccidioides immitis into the cisterna magna. Systemic, neurologic, and histopathologic findings of meningitis were observed in all rabbits, but an inoculum of 2 x 10(4) arthroconidia produced a chronic illness in which meningeal endarteritis obliterans was consistently observed. Serial sampling of cerebrospinal fluid demonstrated an inflammatory response. Growth of C. immitis was demonstrated by quantitative fungal culture from brains and proximal spinal cords.

Animals↗