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PubMed1995

Polymorphism of palmar main line terminations as an indicator of relationships among Sardinian linguistic groups of males.

Palmar main line modal types were used to calculate distance coefficients between Sardinian linguistic groups of males. By using correlation matrix analyses of the coefficients, we then determined whether or not the dermatoglyphic traits could reliably identify the biological relationships on the basis of the linguistic backgrounds of these groups. With Sanghvi's (X2)1/2 and by using palmar main lines both singly and together, we calculated dermatoglyphic distance matrices. Mantel tests of matrix correspondence showed that, by using C and D lines singly or all palmar main lines together, statistical significance between dermatoglyphic and linguistic distances can be obtained, even when the effect of geography is removed; there is no statistically significant correspondence between geographic and dermatoglyphic distance matrices, even when the effect of language is removed. Considering the historical and linguistic background, the results obtained by means of the Mantel test procedure, and the present dermatoglyphic differences in Sardinian linguistic groups of males, we can hypothesize that these groups were already genetically differentiated before the Romance languages and their respective dialects developed.

Dermatoglyphics↗

PubMed1995

A modeling method to improve quantitation of fluorodeoxyglucose uptake in heterogeneous tumor tissue.

UNLABELLED: The standard approach for evaluating FDG-PET kinetic studies is based upon an assumption that tissue within a representative region of interest (ROI) is relatively homogeneous in terms of FDG kinetics. In neoplasms and other disease states, tissue within an ROI may be grossly heterogeneous, due to adjacent infarcted tissue and other causes. We have developed a method employing two ROIs (one over the tumor and another over a "reference region") to deal with this level of heterogeneity. METHODS: The method is based on the regular FDG model but consists of six variable parameters (6P model) which uses the kinetics in the reference region to account for the normal tissue within the tumor ROI, so that the kinetic data only associated with the tumor can be estimated. Monte Carlo simulations and human PET FDG studies were used to analyze the performance of the 6P model. RESULTS: The narrower 95% confidence intervals of parameter estimates, which centered at the true tumor rate constants, and the smaller correlation matrix of the 6P model showed the better performance of the 6P model compared to the standard "homogeneous" four-parameter FDG model. Computer simulations further showed that the 6P model can accurately estimate the microparameters (rate constants: K1* (ml/min/g), k2* (min-1), k3* (min-1), k4* (min-1)) and the macroparameter (K (ml/min/g)) of tumor cells regardless of the percent weight of tumor cells in the lesions. CONCLUSIONS: The new method can produce more reliable and accurate estimates of tumor glucose metabolic rates with dynamic PET FDG studies.

Confidence Intervals↗

PubMed1993

[An application of multiple logistic regression analysis to an outcome study on surgery for patients with femoral neck fracture].

Sixty five patients with femoral neck fracture were examined to find any risk factor for their postoperative complications. Here, postoperative complications included cardiac catastrophe, pulmonary embolism, central nervous system accident, and respiratory failure requiring mechanical ventilation during the period of one week after operation. Multiple logistic regression analysis was used to predict these factors. Explanatory variables were selected based on the clinical judgement. Those variable are age, sex, preoperative underlying cardiac disease, preoperative underlying respiratory complications, the use of cement for the procedure, and anesthetic technique. The analysis revealed that the sex was the only variable that was considered significant based on the P value less than 0.05. However, multi-colinearity between variables was suspected to exist based on the correlation matrix analysis which may indicate that the factor is not, in fact, significant. In short, further study will be required to find any significant variables or risk factors to predict the outcome of untoward events.

Aged↗

PubMed1995

Effect of kanji and kana reading on cerebral blood flow patterns measured by PET.

To investigate the respective functions of pathways in processing visual information from different types of symbols, by positron emission tomography (PET) we examined the effect on cerebral blood flow (CBF) of reading the Japanese morphogram (kanji) versus the syllabogram (kana). Nine Japanese men were presented with three visual conditions in random order 2 minutes before the scan: eyes open controls, kanji morphogram reading, and kana syllabogram reading. Three words written in kanji or kana were shown, and subjects were instructed to read them silently and to identify the word unrelated logically to the other two. The reading and analyzing tasks activated wide areas of vision-related cortices. The comparison of the kanji and kana readings showed higher metabolism, with the former only in the posterior part of the primary visual cortex. Most of the CBF increases were common for both stimuli, although the patterns of these increases differed slightly. The correlation matrix of CBF change in the left hemisphere showed a ventral connection in kanji reading and a dorsal connection in kana reading. Our results suggest there is a functional differentiation in the brain between patterned and sequential perception when reading Japanese morphograms and syllabograms.

Adult↗

PubMedDate not supplied

[Physical anhedonia and depression: distinct concepts? Study of the construct validity of these dimensions in a group of 224 normal subjects].

The aim of the study was to precise the relationship between physical anhedonia and depression in healthy subjects. The construct validity of these two dimensions were determined using a principal components analysis. 224 normal subjects were recruited for the study. They filled out the abrigded version of the Beck Depression Inventory (BDI) and a physical pleasure scale (Fawcett Clark Pleasure Capacity Scale--FCPCS-PP). A principal components analyses following by a varimax rotation was done. The correlation matrix comprising items from both the BDI and the FCPCS-PP yielded a three-factor solution (two "pleasure" factors and one "depression factor") with no overlap of the significant factor loading for the items from each scale. The findings support the view that physical anhedonia is a construct that is distinct and separate from depression.

Adult↗

PubMed1996

Myocardial acoustics in pediatric allograft rejection.

BACKGROUND: Ultrasonographic tissue characterization is the assessment of physical properties of biologic tissue on the basis of quantitative analysis of its acoustic characteristics. Abnormalities in microscopic structure that occur with cardiac allograft rejection may result in characteristic alterations in myocardial acoustics. Ultrasonographic tissue characterization may allow noninvasive detection of rejection. METHODS: Findings in 22 pediatric heart transplant patients undergoing routine surveillance for rejection by endomyocardial biopsy were prospectively evaluated. Off-line ultrasonographic tissue characterization analysis was done on transthoracic echocardiograms obtained at each biopsy. Within patients, tissue characterization texture measures derived from the ultrasonographic image data were compared with histologic findings. Univariate multiple regression analysis was used to identify texture measures associated with acute allograft rejection in a subgroup (n = 8) with at least one biopsy-proven episode of moderate rejection. RESULTS: Measures of homogeneity (co-occurrence matrix correlation and heterogeneity (run-length nonuniformity) decreased with moderate rejection (p < 0.03). Homogeneity measures decreased if the patient had a previous episode of rejection. Several measures of heterogeneity (gray level difference and run-length statistics) were affected by the presence of edema. Run-length nonuniformity was the only measure that differentiated moderate rejection from edema. Discriminant analysis on all 22 patients correctly identified 96% of first rejection episodes (sensitivity 80%, specificity 64%), 93% of moderate and severe rejection episodes (sensitivity 71%; specificity 62%), and 69% of all rejection episodes (sensitivity 51%, specificity 91%). CONCLUSIONS: Histologic changes associated with moderate and severe pediatric allograft rejection as reflected by characteristic alterations in myocardial acoustics can be assessed with ultrasonographic tissue characterization. Histologic changes associated with transplantation itself (resolution of rejection and edema) also affect myocardial acoustics and must be taken into account in rejection surveillance.

Acute Disease↗

PubMedDate not supplied

[A four-dimensional model of chronic schizophrenia based on the factorial structure of the Positive and Negative Syndrome Scale (PANSS). A study of a group of 153 chronic schizophrenic patients and comparison with the factorial structure of the BPRS].

The aim of the study is to explore the latent dimensions in chronic schizophrenia using factorial analysis methods. 153 subjects (89 males, 64 females) with a mean age of 38.83 years (sd = 10.15) meet the RDC criteria for chronic schizophrenia and were included in the study. They were 127 inpatients and 26 outpatients and the mean duration of the illness since the first psychotic episode was 14.69 years (sd = 9.64). The majority of the schizophrenics received antipsychotic treatment with a mean dose (in chlorpromazine-equivalent) of 401.86 mg (sd = 368.13). The schizophrenics were rated using the French versions of the Positive and Negative Syndrome Scale (PANSS) and the Brief Psychiatric Rating Scale (BPRS). Two successive principal components analyses (PCA) were carried out on the correlation matrix of the 30 PANSS and 18 BPRS items. The numbers of factors were limited using several guidelines : eigenvalues higher than 1, screen test and the parallel analysis of Horn. Then an orthogonal equamax rotation was made and the saturation value was chosen using and ad-hoc paradigm. The results have shown a four-factors solution for the PANSS with the following factors : negative, positive-hostility, disorganization-impulsivity, depressive-anxious. The composition of the four preceding factors was respectively : negative [N1, N2, N3, N4, N6, N7, G7, P4 (-)]; positive-hostility (P1, P2, P3, P5, P6, P7, G8, G9, G12, G15, G16); disorganization-impulsivity (G5, G10, G11, G13, G14, N5); depressive-anxious (G1, G2, G3, G4, G6). The ACP of the BPRS have shown a three factors solution (positive-disorganization, negative, depressive-anxious). The factorial structure of the PANSS was discussed with the different studies. Our results confirm the division of the productive symptomatology into two components, delusions-hallucinations and cognitive (disorganization). Moreover depressive and negative symptomatology constitute two separate dimensions. Contrary to the others studies we did not find an excited component, the corresponding items were found in the positive and disorganization factors. The inclusion of solely chronic schizophrenics could explain the lack of the excited component. Our data in chronic schizophrenia allow us to propose a four-dimensional model explaining the symptomatology of this disease.

Adult↗

PubMedDate not supplied

[Construct validity and reliability of the Newcastle Endogeniety Index I].

The authors study the construct validity of the Newcastle's Endogeneity Index (NEI). They use the correlation matrix published originally by Carney et al (1965). The results show a high reliability of the NEI (alpha = 0.77). The Factorial Analysis shows two factors, not independent, that explain a 45% of the total obtained variance; it seem to indicate a drop construct validity of the NEI. The authors discuss the validity of the endogenous/neurotic classification of the depression because of the high agreement the NEI and the clinical criterion.

Depressive Disorder↗

PubMed1997

[Univariate analysis of potential risk factors for early mortality (within 28 days) after aortocoronary bypass in Italy. OP-RISK Study Group].

The multicenter OP-RISK study, developed during 1994-96, was aimed at: 1) investigating early (28 days) death rates following aortocoronary bypass surgery among patients recruited from four Centers representing geographical distribution in Italy; 2) defining possible risk factors for early mortality, also comparing these factors with those reported in previous studies. Average values are reported and compared of 65 variables (36 preoperative, 10 operative and 19 postoperative) out of 984 patients subdivided into alive (n = 940) or dead (n = 44, 4.47%) at 28 days (155 +/- 174 hours, interval between 12 and 576 hours) postoperatively. Causes of death were cardiac in 37 (77%), pulmonary in 3 (0.7%), vascular in 2 (0.5%) and infective in 2(0.5%) patients, respectively. During the study a total of 1126 patients were operated upon in the collaborative Centers with the diagnosis of coronary artery disease and 51 deaths were reported officially in-hospital (4.53%). Therefore, OP-RISK data represent 87% of overall patients and a superposable death rate. The potential role as risk factors of early mortality was assessed univariately for 17 preoperative, 5 operative (in 3 cases for the first time) and 5 postoperative factors. In general, it was confirmed that factors defining left ventricular function are sensitive predictors of mortality. In OP-RISK we were able to show, in addition, that tachycardia (> 130 b/min) at induction of anesthesia, and total time of anesthesia, cardiopulmonary bypass and aortic cross clamping may be significant factors among operative variables as might be among postoperative ones several arrhythmia types or a lower rate in antithrombotic therapy with aspirin at 6-12 hours postoperatively. The protective role of bypass surgery performed with at least 1 arterial segment was also ascertained. Most of these potential factors were significantly related to outcome (either directly or inversely) as were among them, as seen in a subsample (65%) of 639 patients in whom a correlation matrix was performed among 16 factors selected on the basis of the common denominator principle. Our results suggest that it is possible to collect in a multicenter experience univariate predictors of early mortality following aortocoronary bypass surgery in Italy, which are not different from those reported from previous studies performed abroad. Operative indicators may also have predictive capabilities. The effort may be worthwhile and demands further cooperative studies to be undertaken, aimed at obtaining nationwide coefficients of risk along with representative average values of factors that soon might emerge once multivariate statistics will be performed on this material.

Analysis of Variance↗

PubMed2004

[The expression of platelet-derived growth factor (PDGF) receptor-beta and its correlation with extracellular matrix in hepatic tissue in hepatic fibrosis rats].

OBJECTIVE: To investigate the expression of PDGF receptor-beta and its correlation with extracellular matrix in hepatic tissue during hepatic fibrosis. METHODS: The model of hepatic fibrosis in rats was induced by carbon tetrachloride. PDGF receptor-beta subunit, collagen I, collagen III and a-SMA in hepatic tissues of these rats were examined using immunohistochemistry. The correlation between PDGF receptor-beta subunit and collagen I, III was analyzed using SAS software after the results of immunohistochemistry were semi-quantified. RESULTS: PDGF receptor-beta subunit and a-SMA were not detected in normal controls. Collagen I and III were distributed in the portal tracts and beneath the endothelia of the central veins and of the Disse spaces. Two weeks after CCl4 injection, the PDGF receptor-beta and a-SMA were detected, and the expression of collagen I and III increased. At the end of 4 and 6 weeks, the above four proteins were further increased. Two weeks after CCl4 injection, PDGF receptor-beta had no apparent correlation with collagen I and III. However, PDGF receptor-beta had a significant correlation with collagen I and III 2 weeks later, and the correlation coefficient was 0.74 and 0.60 respectively at 4 weeks, and 0.83 and 0.67 respectively at 6 weeks. PDGF receptor-beta had a significant correlation with a-SMA during the whole process of hepatic fibrosis and the correlation coefficient was 0.62, 0.69 and 0.81, respectively at the time of 2, 4 and 6 weeks after CCl4 injection. CONCLUSION: The PDGF receptor-beta was overexpressed during the process of hepatic fibrosis development, and it significantly correlated with collagen I and collagen III.

Animals↗

PubMed2002

Random matrix approach to cross correlations in financial data.

We analyze cross correlations between price fluctuations of different stocks using methods of random matrix theory (RMT). Using two large databases, we calculate cross-correlation matrices C of returns constructed from (i) 30-min returns of 1000 US stocks for the 2-yr period 1994-1995, (ii) 30-min returns of 881 US stocks for the 2-yr period 1996-1997, and (iii) 1-day returns of 422 US stocks for the 35-yr period 1962-1996. We test the statistics of the eigenvalues lambda(i) of C against a "null hypothesis"--a random correlation matrix constructed from mutually uncorrelated time series. We find that a majority of the eigenvalues of C fall within the RMT bounds [lambda(-),lambda(+)] for the eigenvalues of random correlation matrices. We test the eigenvalues of C within the RMT bound for universal properties of random matrices and find good agreement with the results for the Gaussian orthogonal ensemble of random matrices-implying a large degree of randomness in the measured cross-correlation coefficients. Further, we find that the distribution of eigenvector components for the eigenvectors corresponding to the eigenvalues outside the RMT bound display systematic deviations from the RMT prediction. In addition, we find that these "deviating eigenvectors" are stable in time. We analyze the components of the deviating eigenvectors and find that the largest eigenvalue corresponds to an influence common to all stocks. Our analysis of the remaining deviating eigenvectors shows distinct groups, whose identities correspond to conventionally identified business sectors. Finally, we discuss applications to the construction of portfolios of stocks that have a stable ratio of risk to return.

Journal Article↗

PubMed2004

Influence of dissolution media composition on drug release and in-vitro/in-vivo correlation for paracetamol matrix tablets prepared with novel carbomer polymers.

The influence of dissolution media composition on drug release kinetics and in-vitro/in-vivo correlation (IVIVC) for hydrophilic matrix tablets based on Carbopol 971P and Carbopol 71G was investigated. A number of buffered and unbuffered media differing with respect to their pH value, ionic strength and ionic species was evaluated. The observed in-vitro drug release profiles were compared with the hypothetical drug release profiles in-vivo calculated by numerical deconvolution from the results of an in-vivo study. The obtained IVIVC plots were examined using linear and non-linear (proportional odds, proportional hazards and proportional reversed hazards) mathematical models. Although the studied sustained release agents were chemically identical, they exhibited pronounced differences in drug product behaviour both in-vitro and in-vivo. The use of non-linear modelling resulted in an improved level of correlation, especially in the case of Carbopol 71G matrices. The obtained results indicated the susceptibility of drug release kinetics and hence IVIVC in the case of anionic polymer matrices to media composition, and emphasized the need for thorough evaluation of applied media during the development of biorelevant dissolution methodology. Although the use of non-linear modelling could be advantageous, the need for a simple and meaningful non-linear relationship is pointed out.

Acetaminophen↗

PubMed2005

Matrix metalloproteinases expression correlates with survival in patients with esophageal squamous cell carcinoma.

OBJECTIVES: The matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases capable of degrading the extracellular matrix and play important roles in malignancies. We evaluated the expression of four MMPs in esophageal squamous cell carcinoma (ESCC), and assessed the association between MMP expression and clinicopathologic characteristics and disease-free survival time. METHODS: We evaluated MMP1, MMP7, MMP9, and MMP13 expression in tissues from 208 patients with ESCC using immunohistochemistry (IHC), and correlated MMP expression to clinicopathologic characteristics and disease-free survival time. To confirm MMP9 expression at different levels, we simultaneously performed RT-PCR, Western blotting, and IHC on tissues from a separate cohort of 23 patients with ESCC. RESULTS: IHC analysis showed that 63.0%, 41.8%, 49.0%, and 32.2% of 208 ESCC samples were positive for MMP1, MMP7, MMP9, and MMP13, respectively. MMPs were strongly expressed in the cytoplasm of cancer cells, especially in the invasive margin, and weakly expressed in stromal cells. No immunostaining was detected in non-cancerous esophageal mucosa. MMP9 expression was positively associated with poor tumor cell differentiation (p= 0.001), vessel permeation (p= 0.027), and lymph node metastasis (p= 0.027). MMP9 expression was a negative, independent predictor of disease-free survival time (Hazard ratio, 1.470; 95% CI, 1.105 approximately 1.955; p= 0.008). The expression of MMP7 (median survival time: 23 months for MMP7 positive patients, >77 months for MMP7 negative patients; p= 0.001) and MMP13 (median survival time: 18 months for MMP13 positive patients, 39 months for MMP13 negative patients; p= 0.014) correlated negatively with disease-free survival in relatively early stage ESCC patients. Co-expression of MMP7, MMP9, and MMP13 in relatively early stage ESCC samples identified patients with a poor prognosis (13 months median survival time) compared to those lacking MMP7, MMP9, and MMP13 expression (58 months median survival time, p < 0.001). CONCLUSIONS: MMP9 expression is a negative, independent prognostic factor in ESCC and correlates with tumor cell differentiation, vessel permeation, and lymph node metastasis. MMP7, MMP9, and MMP13 may function in early stage ESCC, and their co-expression predicts poor outcome for relatively early stage ESCC patients.

Adult↗

PubMed2005

Induced sputum matrix metalloproteinase-9 correlates with lung function and airway inflammation in children with cystic fibrosis.

Matrix metalloproteinases (MMPs) degrade extracellular matrix and are implicated in causing airway damage in chronic inflammatory lung diseases, including cystic fibrosis (CF). Our primary objective was to examine the relationship between matrix metalloproteinase-9 (MMP-9) and pulmonary function, as measured by forced expiratory volume in 1 sec (FEV1), in children with CF. We measured MMP-9 and its natural tissue inhibitor of metalloproteinase-1 (TIMP-1) in induced sputum from 18 clinically stable CF children with normal to mildly abnormal lung function and 7 healthy control children. Measures of airway inflammation from induced sputum included cell counts and differentials, interleukin-8 (IL-8), neutrophil elastase, MMP-9, and TIMP-1. Infection was assessed through quantitative bacterial counts. Induced sputum levels of MMP-9 and TIMP-1 were significantly increased in children with CF compared with healthy controls. Also, the MMP-9/TIMP-1 molar ratio was higher in the CF group. Among CF children, there was a significant inverse relationship between MMP-9 and FEV1. In addition, sputum MMP-9 and TIMP-1 concentrations significantly correlated with total white cells and neutrophils, IL-8, and neutrophil elastase. Neither MMP-9 nor TIMP-1 correlated with airway infection. We conclude that clinically stable CF children with normal to mildly abnormal lung function have an increased burden of MMP-9 in their airways. The observed relationships of MMP-9 with lung function and other measures of airway inflammation suggest that this enzyme may be a useful marker of airway injury and airflow obstruction in persons with CF.

Adolescent↗

PubMed2000

Changes in the expression of cytokeratins and nuclear matrix proteins are correlated with the level of differentiation in human prostate cancer.

The nuclear matrix-intermediate filament complex (NM-IF) is a protein scaffold which spans the whole cell, and several lines of evidence suggest that this structural frame represents also a functional unit, which could be involved in the epigenetic control of cancer development. Here we report the characterization by high resolution two-dimensional gel electrophoresis and Western blot analysis of the NM-IF complex isolated from prostate cancer (PCa); tumor-associated proteins were identified by comparing the electrophoretic patterns with those of normal human prostate (NHP). Extensive changes in the expression of both the NM and IF proteins occur; they are, however, related in a different way to tumor progression. Poorly differentiated PCa (Gleason score 8-9) shows a strong down regulation of several constitutive cytokeratins (CKs 8, 18, and 19); their expression significantly (P < 0.05) decreases with respect to both NHP and benign prostatic hyperplasia (BPH) and, more interestingly, also with respect to moderately (Gleason score 6-7) and well (Gleason score 4-5) differentiated tumors. Moreover, we have identified a tumor-associated species which is present in all of the tumors examined, systematically absent in NHP and occurs only in a few samples of BPH; this polypeptide, of M(r) 48,000 and pI 6.0, represent a proteolytic fragment of CK8. At variance with these continuing alterations in the expression, the NM proteins undergo stepwise changes correlating with the level of differentiation. The development of less differentiated tumors is characterized by the appearance of several new proteins and by the decrease in the expression of others. Six proteins were found to be expressed with a frequency equal to one in poorly differentiated tumor, namely in all the samples of tumor examined, while in moderately and well differentiated tumors the frequency is less than one, and decreases with increasing the level of differentiation. When tumors of increasing Gleason score are compared with NHP a dramatic increase in the complexity of the protein patterns is observed, indicating that tumor dedifferentiation results in a considerable increase in the phenotypic diversity. These results suggest that tumor progression can be characterized using an appropriate subset of tumor-associated NM proteins.

Adenocarcinoma↗

PubMed2003

Matrix metalloproteinase-8 correlates with the cervical ripening process in humans.

BACKGROUND: To determine levels of matrix metalloproteinases MMP-1, -3 and -8 and localize them and the tissue inhibitors of metalloproteinases TIMP-1 and -2 in human cervical tissue during the cervical ripening process. METHODS: Cervical biopsies were obtained from 10 term-pregnant (TP) women and from nine women immediately after vaginal delivery. Ten nonpregnant (NP) women served as controls. Levels of MMP-1, -3 and -8 were analyzed in supernatants of homogenized cervical tissue by specific enzyme-linked immunosorbent assay (EIA). Localization with immunohistochemistry of these MMPs and TIMP-1 and -2 was performed using monoclonal antibodies. RESULTS: MMP-8 reached its peak median level, 7300 ng/mg wet weight, in biopsies obtained from postpartum (PP) women, as compared to 86 ng/mg wet weight in NP (p<0.001) and 266 ng/mg wet weight in TP (p=0.016) women. The immunohistochemical results confirmed these findings, with a clear increase in MMP-8 staining in ripened cervix localized primarily in the stromal tissue. Levels of MMP-1 and -3 as measured with EIA were low in all three groups, but immunohistochemically a more frequent positive staining for MMP-1 and -3 was registered in pregnant cervical tissue compared to nonpregnant. For TIMP-1 and also for TIMP-2 immunohistochemical analysis showed that staining in all groups was more prominent in pregnant cervical tissue compared to nonpregnant. CONCLUSION: The results indicate that MMP-8 is involved in the process of cervical ripening, and that MMP-1 and -3 and their inhibitors TIMP-1 and -2 may also play a role in this complicated process.

Adult↗

PubMed2002

Increase in gelatinase-specificity of matrix metalloproteinase inhibitors correlates with antimetastatic efficacy in a T-cell lymphoma model.

The recognition that matrix metalloproteinases (MMPs) facilitate tumor cell invasion and metastasis has led to the development of synthetic MMP inhibitors (MMPIs) as cancer therapeutic agents. Because several Phase III trials failed recently to show efficacy of broad-spectrum MMPIs in advanced cancer, the feasibility of MMPs as therapeutic targets has been challenged. However, it has not yet been determined whether MMPIs that have increased specificity may have greater benefit. We show that MMP-9 expression closely correlates with the progression of liver metastasis in a T-cell lymphoma model. MMPIs with greater selectivity/specificity for MMP-9 in vitro showed greater efficacy against liver metastasis in vivo. These data demonstrate a link between increased specificity of MMPIs and enhanced anticancer activity.

Animals↗

PubMed2002

Matrix metalloproteinase expression correlates with virulence following neurotropic mouse hepatitis virus infection.

The relationship(s) between viral virulence and matrix metalloproteinase (MMP) expression in the central nervous system (CNS) of mice undergoing lethal and sublethal infections with neurotropic mouse hepatitis virus was investigated. Lethal infection induced increased levels of MMP-3 and MMP-12 mRNAs as well as that of tissue inhibitor of matrix metalloproteinases 1 (TIMP-1) compared to sublethal infection. Increased induction of MMP, TIMP, and chemokine expression correlated with increased virus replication but not with inflammatory cell infiltration. Infection of immunosuppressed mice suggested that expression of most MMP, TIMP, and chemokine mRNA was induced primarily in CNS-resident cells. By contrast, MMP-9 protein activity was associated with the infiltration of neutrophils into the CNS. These data indicate an association between the magnitude of inflammatory gene expression within the CNS and viral virulence.

Animals↗