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PubMed1996

The need for standardized pathologic staging of pancreaticoduodenectomy specimens.

A standardized method for pathologic evaluation and staging of pancreaticoduodenectomy (PD) specimens is critical for accurate reporting of the number and location of lymph nodes and margins of resection. We examined the impact of standardized pathologic evaluation (SPE) of PD specimens on the identification of regional lymph nodes and describe our detailed system for the pathologic analysis of the PD specimen. Forty consecutive patients underwent PD for histologically confirmed adenocarcinoma of the pancreatic head between April 1990 and August 1993. Fifteen consecutive specimens were examined before the introduction of the SPE, and 25 consecutive specimens underwent SPE. Resection margins were evaluated by frozen-section analysis, and then the specimen was divided into six regions on an anatomic dissection board for lymph node identification. The 25 specimens examined according to the SPE had a significantly increased number of lymph nodes identified (P = 0.0001) compared with the 15 specimens examined without the SPE. Twelve of the 25 specimens contained positive lymph nodes, 6 of which were confined to the pancreaticoduodenal region. No positive nodes were found in the periaortic region. There were no differences in pathologic variables between patients found to have negative and those with positive regional lymph nodes. SPE of PD specimens provides a method for improved lymph node identification, ensures accurate prospective evaluation of margins of resection, and provides a complete analysis of potentially important pathologic variables. We offer this system as a standardized model for groups engaged in protocol-based clinical research examining innovative multimodality treatment strategies for patients with resectable pancreatic cancer.

Adenocarcinoma↗

PubMedDate not supplied

Pathological grief: diagnosis and explanation.

Pathological grief deserves a place in the diagnostic nomenclature. Because posttraumatic stress disorder requires an event beyond the range of usual experience and bereavement is virtually a universal experience, a new diagnosis of signs and symptoms precipitated by a loss event is needed. Many varieties of pathological grief have been noted in clinical research studies, and multiple diagnoses of pathological grief would make research difficult. The authors advance a solution in a personality-based explanation of abnormal responses to loss events; this allows for a single diagnosis of pathological grief. The authors also present a predictive model to partially explain pathological grief by antecedent trait combinations. The hypothesis is that persons with a preloss combination of both contradictions in relational schemas about the deceased and tendencies toward excessive control to stifle unwanted affect will tend to have unsuccessful processes of mourning. Types of contradictions and overcontrol may vary, yielding personality-based varieties of response within a single diagnostic category.

Adaptation, Psychological↗

PubMed1997

Modern analysis of pathologic uterine rings.

A computerized medical record search of 61,406 live births from January 1, 1990, through December 31, 1994, identified 14 cases of pathologic uterine rings. This yielded an incidence of pathologic uterine rings of 0.02% of all live births. In a retrospective, matched study design, three control subjects having vaginal delivery and three having cesarean delivery were matched with each case of pathologic uterine ring for age, race, parity, estimated gestational age, single or multiple gestation, primary or repeat cesarean section, and indication for the cesarean delivery. Comparison with controls who had cesarean section showed no significant differences in duration of labor, rupture of membranes, use of oxytocin, or fetal head position. Pathologic uterine rings continue to occur in modern obstetrics, but their reported incidence has decreased. These data suggest that the characteristics of parturition have no clear association with the formation of a pathologic uterine ring.

Case-Control Studies↗

PubMed2001

Magnetic resonance imaging of multiple sclerosis: new insights linking pathology to clinical evolution.

Magnetic resonance imaging methods allow observation of pathological changes in vivo. Magnetic resonance-based studies have provided a number of important insights into the spatio-temporal evolution of the pathology of multiple sclerosis in vivo, particularly with respect to the relation between pathology and progression of disability. Magnetic resonance techniques have shown that this pathology is not restricted to the plaques that are evident at autopsy, but also involve the so-called normal-appearing white matter. Nonconventional magnetic resonance imaging strategies such as magnetization transfer imaging and spectroscopic imaging provide measures with higher pathological specificity for myelin and axonal injury. These and other advanced magnetic resonance techniques (such as the measurement of atrophy, lesion relaxation spectra, and lesion dynamics) are affording opportunities to use observations of patients to test biologically specific hypotheses. This should help us to better define new targets for drug therapy and to assess responses to new therapeutic agents.

Aspartic Acid↗

PubMed2004

The pathology of ligamentum flavum in degenerative lumbar disease.

STUDY DESIGN: A pathologic study of the ligamentum flavum in degenerative lumbar disease. OBJECTIVES: To elucidate the clinical significance of each pathologic finding of the ligamentum flavum. SUMMARY OF BACKGROUND DATA: In many reports, researchers observed the ligamentum flavum removed partially during surgery and did not evaluate the whole image of the ligamentum flavum. In addition, there are only a few reports that examined the possible association between various histologic findings and clinical findings. And, thus, there are many unclear points in the clinical significance indicated by each pathologic finding. METHODS: The study participants were 50 patients with degenerative lumbar diseases who underwent surgical decompression with removal of the ligamentum flavum of the affected spinal level. Tissue specimens of the removed ligamentum flavum in cross section were prepared, and changes in the elastic fibers and collagen fibers were evaluated in three grades to evaluate the whole image. In addition, we observed the presence or absence of any focal lesions and statistically analyzed the possible association between these histologic findings and clinical symptoms or image findings. RESULTS: In regard to the association between histologic findings and clinical symptoms or image findings, calcification was observed in significantly older patients, who tended to have low scores in preoperative JOA score, and was frequently observed in patients with cauda equina symptoms. Patients with ossification had a significantly greater % slip, and chondroid cells were frequently observed in patients with spondylolisthesis. CONCLUSION: Various pathologic findings provided important foundations for discussing the pathogenesis of lesions in ligamentum flavum. Calcification was frequently observed in elderly patients and those with cauda equina symptoms, and these patients tended to have severer preoperative symptoms. Chondroid cells were frequently observed in patients with spondylolisthesis, and patients with ossification had a greater % slip, suggesting involvement of mechanical load in ossification of ligaments. The pathologic findings were significantly related to the clinical features, and these findings will be profitable for understanding the pathogenesis of degenerative lumbar disease.

Aged↗

PubMed2005

Benign lichenoid keratosis: a clinical and pathologic reappraisal of 1040 cases.

Benign lichenoid keratosis, otherwise known as lichen planus-like keratosis, is a common, cutaneous entity that is often confused with cutaneous malignancy. Few studies have examined the multiple clinical and pathologic guises of this entity, particularly within the context of clinical pathologic correlation or magnitude of this study. We examined the epidemiologic, clinical, and pathologic attributes of 1040 consecutive cases of benign lichenoid keratosis referred for pathologic examination at a busy laboratory over an entire year. Clinical parameters assessed included the age, anatomic location, gender, and multiplicity of the lesions. Pathologic attributes were assessed yielding discernment of five different subtypes that included a classic type, bullous type, atypical type with cytologically atypical lymphocytes, an early or interface type, and a late regressed or atrophic type. The results yielded an average age at presentation of 59.5 years with an age range of 36 to 87 years. The gender frequency was 76% female, 24% male. The trunk was the most common location (76%), followed by the extremities (33%) and head and neck (7%); 8% of patients presented with two lesions and less than 1% with three lesions prompting consideration of lichen planus. The classic, atypical, and bullous forms of the disease clinically presented with erythematous papule/plaque(s). The early or interface type showed erythematous to hyperpigmented brown macules and the regressed or atrophic type presented as violaceous papules or irregularly distributed macular pigmentation; 81% of the lesions showed the classic histology consisting of epidermal acanthosis with a band-like lichenoid lymphocytic infiltrate. Variable numbers of plasma cells, eosinophils, and neutrophils were identified as well as epidermal parakeratosis distinguishing these lesions from typical lichen planus. The bullous variant showed intraepidermal or subepidermal bullous cavities with a dense associated lymphocytic infiltrate and increased numbers of necrotic basilar layer keratinocytes. The atypical variant showed features of the classic type with scattered enlarged CD-3, CD-30 (+) lymphocytes possessing hyperchromatic, irregular nuclei. The early interface type showed single lymphocytes aligned along the dermoepidermal junction without epidermal acanthosis and adjacent lentigo. The regressed or atrophic variant showed epidermal atrophy with papillary dermal scarring, patchy lymphocytic infiltrates and melanin incontinence. The clinicopathologic spectrum of benign lichenoid keratosis is broad and encompasses several unrelated entities. An awareness of its expanded presentation is essential to avoid misdiagnosis and may serve as an important forerunner of pathogenic discernment.

Adult↗

PubMed2005

Genotypically defined lissencephalies show distinct pathologies.

Lissencephaly is traditionally divided into 2 distinct pathologic forms: classic (type I) and cobblestone (type II). To date, mutations in 4 genes, LIS1, DCX, RELN, and ARX, have been associated with distinct type I lissencephaly syndromes. Each of these genes has been shown to play a role in normal cell migration, consistent with the presumed pathogenesis of type I lissencephaly. Based on these data, we hypothesized that all forms of radiographically defined type I lissencephaly independent of genotype would be pathologically similar. To test this hypothesis, we examined brains from 16 patients, including 15 lissencephalic patients and one patient with subcortical band heterotopia. Of these 16 patients, 6 had LIS1 deletions, 2 had DCX mutations, and 2 had ARX mutations. In addition, 6 patients had no defined genetic defect, although the patient with subcortical band heterotopia exhibited the same pattern of malformation expected with an XLIS mutation. In all cases, the cortex was thickened; however, the topographic distribution of the cortical pathology varied, ranging from frontal- to occipital-biased pathology to diffuse involvement of the neocortex. Although brains with LIS1 deletions exhibited the classic 4-layer lissencephalic architecture, patients with DCX and ARX mutations each had unique cytoarchitectural findings distinct from LIS1. Furthermore, 2 of the 5 patients with no known genetic defect showed a fourth type of histopathology characterized by a 2-layered cortex. Interestingly, the 2 brains with the fourth type of lissencephaly showed profound brainstem and cerebellar abnormalities. In summary, we identified at least 4 distinct histopathologic subtypes of lissencephaly that stratify with the underlying genetic defect. Based on these data, a new classification for lissencephaly is proposed that incorporates both pathologic and genetic findings.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

PubMed2003

Is Hispanic race an independent risk factor for pathological stage in patients undergoing radical prostatectomy?

PURPOSE: Hispanic-Americans are the most rapidly growing population in the United States. Although many studies have assessed differences in pathological stage at radical prostatectomy between white and black American men, to our knowledge none has assessed it in Hispanic men. We compared pathological stage at radical prostatectomy in contemporaneous groups of Hispanic and white American men. MATERIALS AND METHODS: A total of 141 consecutive Hispanic and 314 consecutive white American men underwent radical retropubic prostatectomy for clinically localized prostate cancer from 1995 to 2002 at a single institution, as performed by one of us (ETG or MCB). Preoperative prostate specific antigen (PSA), age at diagnosis, race, clinical stage, biopsy and specimen Gleason score, pathological stage, specimen volume and calculated specimen PSA density were collected for each patient. Data were compared using standard statistical methods. RESULTS: Biopsy Gleason score, biopsy Gleason score distribution, specimen Gleason score, specimen Gleason distribution, pathological stage, calculated specimen PSA density, Gleason score change from biopsy to specimen and specimen prostate volume did not differ statistically between Hispanic and white men. Mean age and median preoperative PSA were statistically significantly higher in Hispanic vs white men (62.1 vs 59.5 years and 6.6 vs 5.4 ng/ml, respectively). In addition, no differences in the incidence of positive surgical margins, nonorgan confined disease, seminal vesicle invasion or positive lymph nodes were found between Hispanic and white men undergoing radical prostatectomy. CONCLUSIONS: This study shows that in contemporaneously treated groups of Hispanic and white men at the same institution pathological stage was similar between the groups. To our knowledge this is the largest comparison of surgically treated prostate cancer between these 2 groups. Further followup in terms of PSA outcome in these groups is planned.

Hispanic or Latino↗

PubMed2004

Six additional systematic lateral cores enhance sextant biopsy prediction of pathological features at radical prostatectomy.

PURPOSE: We evaluated the contribution of 6 additional systematically obtained, laterally directed biopsy cores to traditional sextant biopsy for the prediction of final pathological findings in the radical prostatectomy specimen. MATERIALS AND METHODS: We studied 178 consecutive patients with no history of prostate biopsy in whom prostate cancer was diagnosed during an initial systematic 12 core biopsy and who subsequently underwent radical prostatectomy. Of the systematic 12 cores we compared the subset of the 6 traditional sextant cores (S6C), the set of 6 laterally directed cores (L6C) and the complete 12 core set, which included the 6 traditional sextant and the 6 laterally directed cores. Biopsy Gleason score, number of positive cores, total cancer length and percent of tumor in the biopsy sets were examined for their ability to predict extracapsular extension, total tumor volume and pathological Gleason score. RESULTS: On univariable analyses the biopsy parameters of the complete 12 core set correlated more strongly with extracapsular extension and total tumor volume than the biopsy parameters of S6C or L6C. On multivariable analyses S6C and L6C were independent predictors of pathological features at prostatectomy. CONCLUSIONS: The addition of 6 systematically obtained, laterally directed cores to traditional sextant biopsy improved the ability to predict pathological features at prostatectomy by a statistically and prognostically significant margin. Preoperative nomograms that use data from a full complement of 12 systematic cores, specifying sextant and laterally directed biopsy cores, should demonstrate improved performance in predicting prostatectomy pathology.

Aged↗

PubMed2004

Calponin h1 expression in renal tumor vessels: correlations with multiple pathological factors of renal cell carcinoma.

PURPOSE: We determined whether the architecture of renal tumor vessels is immunohistochemically different from that of normal renal vessels and related to the various pathological factors that affect prognosis of renal cell carcinoma (RCC). MATERIALS AND METHODS: A total of 52 cases of primary RCC were selected. Tissues from radical nephrectomy specimens were stained with antibody to alpha-smooth muscle actin (alpha-SMA) and calponin h1. Immunostaining was evaluated semiqualitatively as 0-no staining to 3+-strong staining. Tumor cell proliferation was observed using proliferating marker Ki-67. Data were statistically compared with pathological factors, such as tumor size, histological pattern, growth pattern, cell type, nuclear grade, pathological stage and presence or absence of venous invasion. RESULTS: In normal renal tissues smooth muscle cells of the blood vessels showed strong immunoreactions with antibody to calponin h1 and alpha-SMA. Although alpha-SMA antibody showed similar strong immunoreactions in all types of renal tumor vessels, we observed qualitative alterations in the expression of calponin h1 in different types of RCCs. Strong to moderate immunoreactions with calponin h1 were observed in tumors with expansive growth and an alveolar pattern. Small tumors without venous invasion and chromophobe cell carcinomas also showed strong to moderate expression of calponin h1. Weak or absent expression of calponin h1 was observed significantly in infiltrating tumors, sarcomatous type, large, high grade and high stage tumors associated with significantly higher proliferating indexes. CONCLUSIONS: Our results strongly suggest that the renal tumor vessels are immunohistochemically different from normal renal vessels in respect to calponin h1 expression. We speculate that due to the decrease in or absence of calponin h1 tumor vessels do not develop adequate maturity to maintain vascular integrity. In addition, the distribution of calponin h1 significantly correlated with multiple pathological factors of RCC. Therefore, calponin h1 expression in renal tumor vessels could be a new, important pathological factor in RCC.

Adult↗

PubMed2004

The impact of polymorphism on prostate specific antigen gene on the risk, tumor volume and pathological stage of prostate cancer.

PURPOSE: A single nucleotide polymorphism with adenine (A) to guanine (G) substitution is identified at position -158 in the androgen response elements region of the prostate specific antigen (PSA) gene. We evaluated the relationship between the PSA -158A/G polymorphism and the risk, tumor volume and pathological stage of prostate cancer. MATERIALS AND METHODS: Peripheral venous blood samples were obtained from 122 patients with prostate cancer and 84 controls with benign prostatic hyperplasia. The diagnosis, tumor volume and pathological stage of prostate cancer were all determined according to the pathological reports of transrectal ultrasound guided prostate biopsy, transurethral prostate resection and radical prostatectomy. The PSA -158A/G polymorphism was determined by polymerase chain reaction based restriction fragment length polymorphism methods. RESULTS: Patients with prostate cancer had significantly greater frequencies of the G allele (87.3% vs 77.4%) and GG genotype (78.7% vs 61.9%) than the control group (p = 0.008 and 0.028, respectively). The OR of GG to AG and AA was 2.27 (p = 0.008). In the prostate cancer group the GG genotype was also associated with larger tumor volume (2.34 vs 0.82 ml) and higher pathological stage (organ confined cancer 68.2% vs 31.8% and extracapsular extension 100% vs 0%) than the GA and AA genotypes (p = 0.013 and 0.036, respectively). CONCLUSIONS: The PSA -158A/G polymorphism is associated with prostate cancer. The G allele increases the risk of prostate cancer and the GG genotype is associated with larger tumor volume and higher pathological stage.

Aged↗

PubMed2004

Outcomes in patients with pathological carcinoma in situ only disease at radical cystectomy.

PURPOSE: Pathological stage influences patient outcome after radical cystectomy. We present our experience with patients who have only transitional cell carcinoma in situ of the bladder (pCIS-only) on final pathological examination after radical cystectomy. MATERIALS AND METHODS: Between August 1995 and June 2003, 576 patients underwent radical cystectomy at our institution. Of these patients 54 were pathological stage CIS-only on final cystectomy specimen. Four patients simultaneously had invasive transitional cell carcinoma of the ureter or renal pelvis and were excluded from evaluation. Variables examined included demographic characteristics, preoperative pathological stage, high risk features and followup parameters. RESULTS: Of the 50 patients with pCIS-only 44 (88%) were disease-free at last followup. Mean followup was 37.2 months (range 3.6 to 93.5). Of the 50 patients 21 had focal CIS while 29 had multifocal disease. There was no difference in disease recurrence between these 2 groups (9.5% vs 13.7%, p = 0.8). There were 9 patients with proximal urethral CIS involvement, of whom metastatic disease developed in 3. Only 1 of the 8 patients (12.5%) with ureteral orifice involvement had recurrence. Of the 50 patients 22 had muscle invasive disease on initial transurethral resection without residual invasive disease at cystectomy. This subset fared significantly worse after radical cystectomy than the 28 patients with less than stage T2 disease on transurethral bladder tumor resection (22.7% vs 3.6% metastasis, p < or = 0.05). CONCLUSIONS: The outcome of patients who have pCIS-only after radical cystectomy is not uniform. Patients may be at higher risk for recurrence if disease extends to the proximal urethra. In addition, patients demonstrating invasion on clinical staging (stage T2 or greater) but subsequent pCIS-only disease have a worse prognosis compared to those with superficial clinical staging. Patients with CIS-only on clinical and pathological staging have an excellent disease-free survival with radical cystectomy even with the presence of multifocal disease.

Adult↗

PubMed2006

Can [18F]-fluorodeoxyglucose standardized uptake values of PET imaging predict pathologic extrathyroid invasion of thyroid papillary microcarcinomas?

OBJECTIVE: To evaluate the hypothesis that the [F]-fluorodeoxyglucose (FDG) standardized uptake values (SUVs) of positron emission tomographic (PET) imaging can predict pathologic extrathyroid invasion of thyroid papillary microcarcinomas (TPMC) DESIGN: Prospective clinical study. METHOD: From 2004 to 2005, 44 consecutive patients with TPMC (< or =1 cm), confirmed by ultrasonography and aspiration cytology, had FDG PET scans performed. Among them, 66 tumor foci in 41 patients were confirmed to be of less than 1 cm in diameter by the final surgical pathology report. According to the microcarcinoma tumor focus, prediction of pathologic extrathyroid invasion, by clinical variables including sonographic findings and SUVs from PET imaging, was evaluated by the univariate and multivariate logistic regression analysis. RESULTS: : Univariate analysis showed that the tumor site attached to the thyroid capsule and the SUVs of PET imaging could predict pathologic extrathyroid invasion. However, the tumor site attached to thyroid capsule and an age older than 45 were significant predictors by multivariate analysis (P = .001 and P = .036). SUVs from PET imaging were only correlated with the size of tumor (P < 0.001). CONCLUSION: The SUVs from FDG PET imaging alone cannot predict the pathologic extrathyroid invasion in patients with TPMC. However, the ultrasonographic findings, such as tumor site, provide better information about the extrathyroid invasion of TPMC tumor foci.

Adult↗

PubMed2006

Accuracy of physical examination, ultrasonography, and mammography in predicting residual pathologic tumor size in patients treated with neoadjuvant chemotherapy.

OBJECTIVE: To assess the accuracy of physical examination, ultrasonography, and mammography in predicting residual size of breast tumors following neoadjuvant chemotherapy. BACKGROUND: Neoadjuvant chemotherapy is an accepted part of the management of stage II and III breast cancer. Accurate prediction of residual pathologic tumor size after neoadjuvant chemotherapy is critical in guiding surgical therapy. Although physical examination, ultrasonography, and mammography have all been used to predict residual tumor size, there have been conflicting reports about the accuracy of these methods in the neoadjuvant setting. METHODS: We reviewed the records of 189 patients who participated in 1 of 2 protocols using doxorubicin-containing neoadjuvant chemotherapy, and who had assessment by physical examination, ultrasonography, and/or mammography no more than 60 days before their surgical resection. Size correlations were performed using Spearman rho analysis. Clinical and pathologic measurements were also compared categorically using the weighted kappa statistic. RESULTS: Size estimates by physical examination, ultrasonography, and mammography were only moderately correlated with residual pathologic tumor size after neoadjuvant chemotherapy (correlation coefficients: 0.42, 0.42, and 0.41, respectively), with an accuracy of +/-1 cm in 66% of patients by physical examination, 75% by ultrasonography, and 70% by mammography. Kappa values (0.24-0.35) indicated poor agreement between clinical and pathologic measurements. CONCLUSION: Physical examination, ultrasonography, and mammography were only moderately useful for predicting residual pathologic tumor size after neoadjuvant chemotherapy.

Adult↗

PubMed2003

Hepatitis C virus dynamics and pathology: the role of CTL and antibody responses.

This paper investigates the role of CTL and antibody responses in hepatitis C virus (HCV) dynamics and pathology. Mathematical models suggest that a strong CTL response is required for resolution of HCV infection and that a weak CTL response can result in persistent infection. According to the model, establishment of persistent infection is accompanied mainly by an ongoing antibody response, while CTLs are not maintained at high levels. In the model, this outcome correlates with absence of pathology. Persistent infection in the face of an ongoing antibody response can result in evolution of antigenic escape. According to the model, evolution towards escape from antibodies can shift the balance of immune responses so that the weak CTL levels become increasingly more dominant relative to antibodies. This shift results in onset of liver pathology as the virus evolves towards increased levels of antigenic escape. Therefore, the relative balance of the immune response can be a decisive factor that determines whether patients are asymptomatic or whether pathology is observed. Virus evolution can shift this balance towards pathology over time. Theoretical results are discussed in the context of published data.

Acute Disease↗

PubMed2024

Desmoplakin mutations in cardiac fibroblasts cause TGFβ1-mediated pathological fibrogenesis in desmoplakin cardiomyopathy via beclin-1 regulation.

BACKGROUND: Pathological fibrosis is a major finding in cardiovascular diseases and can result in arrhythmia and heart failure. Desmosome gene mutations can lead to arrhythmogenic cardiomyopathy (ACM). Among ACM, pathogenic desmoplakin ( DSP ) variants cause a distinctive cardiomyopathy with excessive cardiac fibrosis that could precede ventricular dysfunction. DSP variants are also linked to other fibrotic diseases. Whether DSP plays any role in pathological fibrosis remain unknown. METHODS: Mesenchymal stromal cells (MSCs) are resident fibroblast-like cells that are responsible for fibrogenesis in most organs, including hearts. We first used unbiased genome-wide analyses to generate cardiac fibroblasts-like, induced pluripotent stem cell-derived MSCs from normal donors and ACM patients with DSP mutations. We then studied the fibrogenic responses of cardiac MSCs to transforming growth factor beta-1 (TGF-β1) using Western/Co-IP, autophagy assay, gene knockdowns/over-expressions, genomic analyses, mouse DSP knockdown models, immunostaining, and qPCR. RESULTS: TGFβ1 induced excessive accumulations of vimentin (VIM)/fibrillar collagens, and over-activated fibrotic genes in DSP- mutant MSCs when compared to normal MSCs. In normal MSCs, VIMs bind to wild-type DSP during normal fibrogenesis after TGFβ1. DSP- mutant MSCs exhibited a haplo-insufficient phenotype with increased DSP-unbound VIMs that sequestered beclin-1 (BECN1) from activating autophagy and caveolin-1 (CAV1)-mediated endocytosis. Decreased autophagy caused collagen accumulations and diminished CAV1 endocytosis resulted in abnormal CAV1 plaque formation that over-activated fibrotic genes [ COL1A1, COL3A1, and fibronectin ( FN )] via heightened p38 activities after TGFβ1. Genome-wide analysis and DSP knockdown in mouse fibroblasts confirmed this novel role of DSP mutations in pathological fibrosis. Overexpression of VIM-binding domains of DSP could suppress pathological fibrosis by increasing collagen autophagic degradation and decreasing fibrotic gene expressions. CONCLUSIONS: Our data reveal that DSP deficiency in MSCs/fibroblasts leads to exaggerated fibrogenesis in DSP-cardiomyopathy by decreasing BECN1 availability for autophagy and CAV1-endocytosis. Overexpression of VIM binding domains of DSP could be a new strategy to treat pathological fibrosis.

Journal Article↗

PubMed2000

Laryngeal pathology detection by means of class-specific neural maps.

Most of the existing systems and methods for laryngeal pathology detection are characterized by a classification error. One of the basic problems is the approximation and estimation of the probability density functions of the given classes. In order to increase the accuracy of laryngeal pathology detection and to eliminate the most dangerous error--classification of a patient with laryngeal disease as a normal speaker--here an approach based on modeling of the probability density functions (pdf's) of the input vectors of the normal and pathological speakers by means of two prototype distribution maps (PDM), respectively, is proposed. The pdf of the input vectors of an unknown normal or pathological speaker is also modeled by such a prototype distribution neural map--PDM(X)--and the pathology detection is done by means of a ratio of specific similarities rather than by a direct comparison of some type of distance/similarity with a threshold. The experiments show an increased classification accuracy and that the proposed method can be used for screening the laryngeal diseases. The method is applied in a consulting system for clinical practice.

Algorithms↗

PubMed2004

The pathology of Rasmussen syndrome: stages of cortical involvement and neuropathological studies in 45 hemispherectomies.

PURPOSE: Rasmussen syndrome (RS) is a rare form of epilepsy characterized by progressive destruction of a single hemisphere. To characterize the profile of cortical involvement in RS, we studied the pathological changes in the cerebral cortex of 45 hemispherectomies performed at Johns Hopkins Hospital between 1985 and 2002. METHODS: The patterns of pathologic changes and stages of cortical abnormalities were studied by histology and immunocytochemistry methods. The burden of pathology (BP) was quantified in all brain regions of each of the 45 hemispheres. RESULTS: Our study demonstrated significant heterogeneity in the stages of cortical pathology and the multifocal nature of the disease. These stages varied from early inflammation defined by infiltration of T lymphocytes and neuroglial reactions, to more severe stages with extensive neuronal cell death and cavitation of the cerebral cortex. A greater BP was significantly associated with an early age at onset (p = 0.01) and longer duration of disease (p < or = 0.001). The BP was similar in all brain regions except the occipital lobe, where the BP was significantly lower (p = 0.032). CONCLUSIONS: The multifocal distribution of pathologic changes, as well as the heterogeneity in the stages of cortical damage in each patient, is consistent with an ongoing and progressive immune-mediated process of neuronal damage that involves neuroglial and lymphocytic responses, resembling other autoimmune CNS disorders such as multiple sclerosis.

Age of Onset↗