Biomedical subjects

M Tsokos

Publications and source records attributed to M Tsokos.

At least 37 records · Page 2Linked to original sources

PubMed2002

Lectin binding patterns of alveolar epithelium and subepithelial seromucous glands of the bronchi in sepsis and controls--an approach to characterize the non-specific immunological response of the human lung to sepsis.

A delayed or deficient immunological protection as well as an overstimulation of the mucosal immune system may act as possible additional promoters of sepsis-induced lung injury in patients suffering from a severe septic condition. Lectin-binding patterns in pulmonary tissue samples obtained at autopsy from septic patients and control individuals were studied using 11 carbohydrate-specific lectins (Con A, UEA, GSA I, GSA II, MPA, PNA, Jac, WGA, MAA, LPA, and SNA). There were no differences in the secretory product of serous parts of bronchial glands detectable in the two study groups, whereas lectin binding patterns of alveolar epithelium and mucous parts of subepithelial seromucous glands were different in sepsis cases when compared to controls. Apart from differences in binding sites for alpha-mannose, N-acetyl-neuraminic acid and alpha-(2-6)-galactose (as detected by different expression for Con A, MAA and SNA) in the two study groups, the main finding was that no binding sites for alpha-N-acetyl-galactosamine (as investigated by MPA immunoreactivity) could be detected on alveolar epithelial cells and mucous parts of subepithelial seromucous glands in sepsis cases in contrast to the presence of such binding sites in the control cases. We hypothesize that the finding of an altered secretory product of alveolar epithelial cells and bronchial glands in sepsis may be a result of specific carbohydrate deprivation or consumption, respectively, possibly due to direct bacterial effects or pathogenetic events in response to bacterial toxins during the complex cascade of the host's systemic inflammatory response in sepsis. The altered type of mucus glycoprotein physiologically secreted by alveolar epithelium and mucous parts of subepithelial seromucous glands of the bronchi with subsequent loss of a considerable proportion of protection of the mucosal barrier in sepsis may play an important additional role in the development of sepsis-induced lung injury.

Adult↗

PubMed2002

Functional anatomy of the papilla Vateri: biomechanical aspects and impact of difficult endoscopic intubation.

BACKGROUND: Problems with intubation of the ampulla Vateri during diagnostic and therapeutic endoscopic maneuvers are a well-known feature. The ampulla Vateri was analyzed three-dimensionally to determine whether these difficulties have a structural background. METHODS: Thirty-five human greater duodenal papillae were examined by light and scanning electron microscopy as well as immunohistochemically. RESULTS: Histologically, highly vascularized finger-like mucosal folds project far into the lumen of the ampulla Vateri. The excretory ducts of seromucous glands containing many lysozyme-secreting Paneth cells open close to the base of the mucosal folds. Scanning electron microscopy revealed large mucosal folds inside the ampulla that continued into the pancreatic and bile duct, comparable to valves arranged in a row. CONCLUSIONS: Mucosal folds form pocket-like valves in the lumen of the ampulla Vateri. They allow a unidirectional flow of secretions into the duodenum and prevent reflux from the duodenum into the ampulla Vateri. Subepithelial mucous gland secretions functionally clean the valvular crypts and protect the epithelium. The arrangement of pocket-like mucosal folds may explain endoscopic difficulties experienced when attempting to penetrate the papilla of Vater during endoscopic retrograde cholangiopancreaticographic procedures.

Aged↗

PubMed2002

Esophageal variceal hemorrhage presenting as sudden death in outpatients.

CONTEXT: Some autopsy studies have dealt with histologic features of esophageal varices after different therapeutic procedures. However, to the best of our knowledge, no reports have been published describing outpatient characteristics that are associated with fatal esophageal variceal hemorrhage in a medicolegal autopsy population. OBJECTIVES: To (1) assess the incidence of sudden deaths from esophageal variceal hemorrhage in an unselected medicolegal autopsy population and (2) determine demographics of outpatients dying from esophageal variceal hemorrhage with special reference to blood alcohol concentrations at the time of death. DESIGN: We performed a retrospective study of all autopsy cases of sudden death from esophageal variceal hemorrhage from a total of 6038 medicolegal autopsies performed over a 5-year period (1997-2001). We analyzed individual cases to determine gender, age, location and histology of bleeding esophageal varices, pathogenic mechanism for esophageal varices, concomitant underlying diseases contributing to fatal outcome, body mass index, circumstances at the death scene, and blood alcohol levels at the time of death. We reviewed the results of toxicologic analyses of alcohol concentrations in samples of femoral venous blood and urine obtained at autopsy; concentrations had been determined by gas chromatography with mass spectroscopy and enzymatic assays. RESULTS: We identified 45 cases of fatal esophageal variceal hemorrhage that occurred out of hospital and presented as sudden death; the corresponding 5-year incidence in this autopsy population was 0.75%. All of the deceased were white; the male-female ratio was 1.6:1, and the mean age was 50.6 years. Ruptured esophageal varices were located in the lower third of the esophagus in 44 cases. Cirrhosis of the liver was present in all cases (alcoholic cirrhosis of the liver in 42 cases), and a hepatocellular carcinoma was present in 3 cases. Alcohol-induced pancreatic tissue alterations were frequently found. The results of toxicologic analysis were positive for alcohol in femoral venous blood and urine in 30 cases. Blood alcohol levels at the time of death were less than 100 mg/dL (21.7 mmol/L) in 15 cases, between 100 and 200 mg/dL (21.7 and 43.4 mmol/L) in 8 cases, and greater than 200 mg/dL (43.4 mmol/L) in the remaining 7 cases. CONCLUSIONS: Apart from abnormalities in coagulation due to poor liver function in long-term alcohol users, acute alcohol intake may represent an important factor influencing mortality in individuals with esophageal variceal hemorrhage. Acute alcohol intake has transient effects on blood clotting time caused by ethanol and its main metabolites. In the present study, bloodstains at the death scene and unusual body positions of the deceased that aroused suspicion of a violent death were leading reasons for conducting a medicolegal autopsy. Apart from aspects of forensic pathology, the demographics of our study population are also noteworthy from the viewpoint of social medicine. The data we present stress the importance of fatal esophageal variceal hemorrhage as a relevant cause of sudden death occurring outside the hospital in socially isolated, alcohol-addicted individuals.

Adult↗

PubMed2001

Recombinant human macrophage colony-stimulating factor augments pulmonary host defences against Aspergillus fumigatus.

The in vivo and ex vivo effects of macrophage colony-stimulating factor (M-CSF) were studied in a profoundly neutropenic rabbit model in order to determine its potential to augment pulmonary host defence against Aspergillus. M-CSF (100-600 microg/kg/d) was administered prophylactically to neutropenic rabbits with pulmonary aspergillosis starting three days pre-inoculation and then throughout neutropenia. Rabbits receiving M-CSF had significantly increased survival (P=0.01) and decreased pulmonary injury, as measured by decreased pulmonary infarction (P=0.004), when compared with untreated controls. Microscopic studies demonstrated greater numbers of activated pulmonary alveolar macrophages (PAMs) in lung tissue of rabbits receiving M-CSF, in comparison to controls (P<0.001). PAMs harvested from rabbits treated with M-CSF had a significantly greater percent phagocytosis of Aspergillus fumigatus conidia than did PAMs from controls (P=0.04). These data indicate that prophylactic administration of M-CSF augments pulmonary host defence against A. fumigatus and suggest a potential role for this cytokine as adjunctive therapy in the treatment of pulmonary aspergillosis in the setting of profound neutropenia.

Animals↗

PubMed2001

Fas-mediated apoptosis in neuroblastoma requires mitochondrial activation and is inhibited by FLICE inhibitor protein and Bcl-2.

Fas-mediated apoptosis proceeds though mitochondria-dependent or -independent pathways and is deficient in drug-resistant cells. Neuroblastoma, a common pediatric malignancy, often develops drug-resistance and has a silenced caspase 8 (FLICE) gene, which has been associated with Fas- and drug-resistance. We report that besides caspase 8, which was absent in approximately one-third of 26 neuroblastoma cases in this study, other proteins such as bcl-2 and FLICE-inhibitory protein (FLIP), are equally important in conferring Fas-resistance to neuroblastoma cells. Both bcl-2 and FLIP were frequently expressed in neuroblastoma tissues. Our in vitro studies showed that FLIP was recruited to the death-inducing signaling complex and interfered with the recruitment of caspase 8 in neuroblastoma cells. bcl-2 inhibited the activation of the mitochondria; but it also lowered the free cytoplasmic levels of caspase 8 by binding and sequestering it, thus acting through a novel antiapoptotic mechanism upstream of the mitochondria. In vitro down-regulation of bcl-2 with antisense oligonucleotides allowed the release of cytochrome c from mitochondria and the activation of caspases 8 and 3 upon Fas activation as well as sensitized neuroblastoma cells to Fas-mediated apoptosis. Down-regulation of FLIP had only a modest apoptotic effect because of the coexistent mitochondrial block. However, combined treatment with bcl-2 and FLIP antisense oligonucleotides had a statistically significant synergistic effect reversing Fas-resistance in neuroblastoma cells in vitro. These data indicate that Fas-mediated apoptosis in neuroblastoma cells is mitochondria-dependent and inhibited both at the mitochondrial level and at the level of caspase 8 activation. Thus, gene-targeting therapies for bcl-2 and FLIP may reverse Fas-resistance and prove useful in the treatment of drug-resistant neuroblastomas.

Adolescent↗

PubMed2001

Interleukin-6 and C-reactive protein serum levels in sepsis-related fatalities during the early postmortem period.

Postmortem interleukin-6 (IL-6) and C-reactive protein (CRP) serum levels were investigated prospectively in sepsis-related fatalities and non-septic fatalities by using a linear regression model. At least three blood samples were collected between 0.3 and 139 h postmortem from sepsis-related fatalities (n=8) and non-septic fatalities (n=16). In addition, one antemortem blood sample was collected shortly before death from the septic patients. Antemortem and postmortem IL-6 and CRP levels were highly elevated in all individuals included in the sepsis group. An excessive postmortem increase of IL-6 serum levels associated with progressive time after death was observed in five out of the eight septic patients. Both, IL-6 and CRP serum concentrations seem to be suitable biochemical postmortem markers of sepsis. The determination of IL-6 serum levels above 1500 pg/ml in peripheral venous blood obtained in the early postmortem interval can be considered as a diagnostic hint towards an underlying septic condition. A more precise postmortem discrimination between sepsis and non-septic underlying causes of death is provided by the postmortem measurement of serum CRP in peripheral venous blood: on condition that at least two postmortem CRP values have been determined at different time points postmortem, the CRP level of a deceased at the time of death can be calculated by using linear regression analysis. When assessing postmortem IL-6 and CRP concentrations as biochemical postmortem markers of sepsis, various clinical conditions, such as a preceding trauma or burn injury going along with elevated IL-6 and/or CRP levels prior to death as a result of the systemic inflammatory response syndrome (SIRS) should be taken into consideration, thus adding relevant information for the practical interpretation of the results.

Adolescent↗

PubMed2001

The Gem GTP-binding protein promotes morphological differentiation in neuroblastoma.

Gem is a small GTP-binding protein within the Ras superfamily whose function has not been determined. We report here that ectopic Gem expression is sufficient to stimulate cell flattening and neurite extension in N1E-115 and SH-SY5Y neuroblastoma cells, suggesting a role for Gem in cytoskeletal rearrangement and/or morphological differentiation of neurons. Consistent with this potential function, in clinical samples of neuroblastoma, Gem protein was most highly expressed within cells which had differentiated to express ganglionic morphology. Gem was also observed in developing trigeminal nerve ganglia in 12.5 day mouse embryos, demonstrating that Gem expression is a property of normal ganglionic development. Although Gem expression is rare in epithelial and hematopoietic cancer cell lines, constitutive Gem levels were detected in several neuroblastoma cell lines and could be further induced as much as 10-fold following treatment with PMA or the acetylcholine muscarinic agonist, carbachol.

Animals↗

PubMed2001

Ewing's sarcoma family tumors are sensitive to tumor necrosis factor-related apoptosis-inducing ligand and express death receptor 4 and death receptor 5.

In this study, we investigated the sensitivity of Ewing's sarcoma family tumors (ESFTs) of children and adolescents to the tumor necrosis factor-related apoptosis-inducing Ligand (TRAIL). TRAIL binds to death receptors (DRs) DR4, DR5, DcR1, and DcR2. Either DR4 or DR5 can induce apoptosis, whereas DcR1 and DcR2 are considered inhibitory receptors. Nine of 10 ESFT cell lines, including several that were Fas resistant, underwent apoptosis with TRAIL through activation of caspase-10, capase-8 (FLICE), caspase-3, and caspase-9. In contrast to the Fas signaling pathway, caspase-10, but not caspase-8 or the Fas-associated death domain-containing molecule, was recruited to the TRAIL receptor-associated signaling complex. We found that 9 of 10 ESFT cell lines expressed both DR4 and DR5 by Western blotting, whereas the TRAIL-resistant line expressed only DR4. However, DR4 was absent from the cell surface in the resistant and two additional lines (three of five tested lines), suggesting that it may have been nonfunctional. On the contrary, DR5 was located on the cell surface in all four sensitive lines tested, being absent only from the cell surface of the resistant line that was also DR5-negative by Western blotting. In agreement with these findings, the resistance of the line was overcome by restoration of DR5 levels by transfection. Levels of DcR1 and DcR2 or levels of the FLICE-inhibitory protein (FLIP) did not correlate with TRAIL resistance, and protein synthesis inhibition did not sensitize the TRAIL-resistant line to TRAIL. Because these data suggested that sensitivity of ESFTs to TRAIL was mainly based on the presence of DR4/DR5, we investigated the presence of these receptors in 32 ESFT tissue sections by immunohistochemistry. We found that 23 of 32 tumor tissues (72%) expressed both receptors, 8 of 32 (25%) expressed one receptor only, and 1 was negative for both. Our finding of wide expression of DR4/DR5 in ESFT in vivo, in combination with their high sensitivity to TRAIL in vitro and the reported lack of toxicity of TRAIL in mice and monkeys, suggests that TRAIL may be a novel effective agent in the treatment of ESFTs.

Apoptosis↗

PubMed2001

Post-traumatic meningitis: histomorphological findings, postmortem microbiology and forensic implications.

Infections of the leptomeninges with the infectious agent gaining access to the intracranial compartment by traumatic means are termed post-traumatic. In cases with fatal outcome, the manner of death has to be classified as non-natural. Six cases of post-traumatic meningitis as the cause of death from the archives of the Institute of Legal Medicine in Hamburg, Germany with histological and microbiological investigations are presented. There were all males, age varying between 24 and 90 years (mean 58 years); range of the interval between original trauma and beginning of symptoms was 2 days up to 8 years; in 50% of the cases meningeal swabs yielded Streptococcus pneumoniae. Findings concerning origin and mechanism of post-traumatic meningitis as well as microbiological studies are compared with selected cases from the literature.

Adult↗

PubMed2001

Matrix metalloproteinase-7-mediated cleavage of Fas ligand protects tumor cells from chemotherapeutic drug cytotoxicity.

Recent evidence suggests that one mechanism whereby cytotoxic drugs, such as doxorubicin, kill tumors is the induction or up-regulation of Fas ligand (FasL) expression on the tumor cell surface. The ensuing engagement of Fas by FasL on adjacent cells leads to apoptosis. However, despite cytotoxic drug-induced FasL expression, Fas-sensitive tumors frequently resist chemotherapy, suggesting that they may possess a mechanism that prevents or inactivates Fas-FasL interactions. In the present work, we addressed the involvement of the FasL/Fas signaling pathway in doxorubicin-induced apoptosis and the ability of matrix metalloproteinases (MMPs) to proteolytically cleave FasL in tumor cells. Doxorubicin-induced apoptosis was inhibited by expression of soluble Fas or incubation of the tumor cells with MMP-7 but not with MMP-2 or MMP-9. Resistance to doxorubicin was also induced by expression in the tumor cells of constitutively active MMP-7 but not of a catalytically inactive mutant. Conversely, inhibition of MMP-7 expression in tumor cells by transfection of MMP-7 cDNA in antisense orientation resulted in sensitization to doxorubicin. MMP-7 efficiently cleaved recombinant FasL in vitro and reduced cell surface FasL expression. Our observations provide evidence that one mechanism whereby MMP-7 may promote tumor survival and resistance to doxorubicin is by cleaving FasL and reducing its effectiveness in triggering Fas-mediated apoptosis.

Antineoplastic Agents↗

PubMed2001

Ewing sarcoma and sinonasal neuroectodermal tumors as second malignant tumors after retinoblastoma and other neoplasms.

BACKGROUND: Excesses of various childhood cancers have been reported after retinoblastoma, including a trickle of Ewing sarcoma (ES) and perhaps histologically similar olfactory neuroblastoma, both of which are neural tumors. To update and advance this information, case reports were sought by an extensive review of the literature. PROCEDURE: The search was made through the use of PubMed, and the Web of Science (Citation Index Expanded), keying on primary references. Three sinonasal cancers diagnosed as ES were immunohistochemically stained for MIC-2 protein (positive in ES). RESULTS: Retinoblastoma occurred before ES in ten cases (seven bilateral). In four others, retinoblastoma (three bilateral) developed before sinonasal neural tumors (poorly differentiated). ES also occurred after 14 cancers other than retinoblastoma (five lymphomas, four leukemias, and one each of five miscellaneous cancers). The predominance of retinoblastoma prior to ES differs markedly from the low-frequency of retinoblastoma among childhood cancers in the general population. On the contrary, cancers other than retinoblastoma were proportionate to those in the general population. Previously, retinoblastoma followed by excesses of osteosarcoma and soft tissue sarcomas has been attributed to the action of the inherited RB-1 gene. The sinonasal tumors stained negative for MIC-2 protein. CONCLUSIONS: Heritable retinoblastoma may predispose to ES and perhaps to a subset of poorly differentiated neuroectodermal tumors in the sinonasal region that may be related to olfactory neuroblastoma.

Adolescent↗

PubMed2001

Post-mortem markers of sepsis: an immunohistochemical study using VLA-4 (CD49d/CD29) and ICAM-1 (CD54) for the detection of sepsis-induced lung injury.

The up-regulation of different adhesion molecules such as VLA-4 (CD49d/CD29) and ICAM-1 (CD54) on the pulmonary endothelium and leukocytes, is a key event in sepsis-induced lung injury leading to inflammatory tissue alterations. The value of VLA-4 and ICAM-1 as micromorphological post-mortem markers for the detection of sepsis-induced lung injury, was evaluated in a semiquantitative immunohistochemical study. VLA-4 was strongly expressed on intravascular, interstitial and intra-alveolar leukocytes in sepsis-associated fatalities, whereas in non-septic fatalities an irregular weak immunoreactivity was observed on interstitial leukocytes and no positive immunohistochemical expression was detected on intravascular or intra-alveolar leukocytes. ICAM-1 was strongly expressed on endothelial cells of the pulmonary microvasculature and on pulmonary macrophages and lymphocytes in sepsis-associated fatalities. In contrast, an infrequent weak immunohistochemical reaction for ICAM-1 was found on pulmonary endothelium and on perivascular leukocytes in non-septic fatalities. Based on the results of the present preliminary study, VLA-4 and ICAM-1 can be considered as useful immunohistochemical post-mortem markers of sepsis.

Adult↗

PubMed2001

Serum procalcitonin (PCT): a valuable biochemical parameter for the post-mortem diagnosis of sepsis.

The aim of this prospective study was to investigate whether serum procalcitonin (PCT) can be used as a post-mortem marker of sepsis and to determine whether this biochemical parameter can be employed in the forensic elucidation of death due to sepsis. At least three blood samples were collected between 0.3 and 139 h post-mortem from sepsis-related fatalities (n = 8) and control individuals (n = 53, where death was due to various natural and unnatural causes). Additionally one ante-mortem blood sample was collected shortly before death from the patients in the sepsis group. In the sepsis group, serum PCT concentrations, determined by using an immunoluminometric assay, were elevated in all patients for the whole observation period, whereas in the control group serum PCT was not detectable in 94% of the cases. Measurement of PCT levels seems reasonable until at least approximately 140 h postmortem, depending on the ante-mortem levels. A linear regression model is presented that allows the serum PCT concentration of an individual at the time of death to be estimated on condition that at least two positive post-mortem PCT values have been determined. Ante-mortem PCT values correlated well with the predicted PCT values at the time of death in the sepsis group using the standardized PCT logarithms. According to the results of the present study, PCT is a valuable biochemical parameter for the post-mortem discrimination between sepsis and underlying non-septic causes of death.

Adolescent↗

PubMed2001

Comparative evaluation of pulmonary lactoferrin and lysozyme immunoreactivity for the postmortem diagnosis of death due to sepsis.

To determine whether lactoferrin (LF) and lysozyme (LZ) can be used as immunohistochemical postmortem markers of sepsis, pulmonary tissue sections from autopsy cases of sepsis-related fatalities (n = 13) and control cases of non-septic fatalities (n = 14) were evaluated for differences in leucocytic immunoreactivity. LF and LZ were investigated in paraffin sections using the AEC technique. The immunohistochemical expression of both markers was scored, evaluating the quantity of immunopositive cells and the intensity of the intracellular immunoreactivity. There was a statistically significant association between an enhanced expression of LF on pulmonary leucocytes in sepsis-related fatalities in contrast to non-sepsis cases (P < 0.001), whereas no such difference could be observed for LZ immunoreactivity between the two study groups. Pneumonic tissue alterations had no significant influence on LF and LZ immunoreactivity, thus suggesting differences between the degranulation of these non-specific antibacterial agents in local and systemic inflammatory processes. While the variability of LZ immunoreactivity, possibly reflecting a non-specific release from lysosomes according to the length of the postmortem interval, limits its application to the postmortem diagnosis of sepsis, the immunohistochemical detection of an enhanced expression of LF can contribute to the postmortem discrimination between sepsis and non-septic fatalities.

Adolescent↗

PubMed2001

Postmortem bacteriology in forensic pathology: diagnostic value and interpretation.

The proof of a pathogenetic germ can be of evidential value for the medico-legal expertise concerning etiopathogenetic conclusions towards a causal relationship between infection and fatal outcome. In specific cases the forensic pathologist may be confronted with the decision whether cultures for postmortem bacteriological investigations should be obtained at autopsy. The present review surveys the value and practicability of postmortem bacteriological cultures in the light of the literature. The most promising media for postmortem bacteriological cultures are spleen and heart blood. In contrast, postmortem lung culture results are often unreliable due to frequently false positive results. The collection of specimens from at least two different sampling sites should be the standard procedure in cases where an underlying (potentially fatal) infection is presumed. Multiple postmortem cultures from different sampling sites raise the probability to identify the etiologic agent of antemortem infection. A careful correlation of culture results from different anatomical sampling sites with autopsy and histological findings is essential for the differentiation between vitally acquired infection and postmortem contamination. Various factors (e.g. the time interval between death and sampling of specimens, agonal spread of microorganisms or preceding antibiotic therapy prior to death) may limit the diagnostic utility of postmortem culture results. Contamination of specimens may, e.g. originate from inadequate sampling techniques, use of unsuitable transport media or postmortem growth of bacteria. The number of contaminated postmortem cultures increases when bowel manipulation or evisceration occurs prior to sampling and is depending on the anatomy of the sampling site. Polymicrobial growth can be considered contamination in the majority of cases. For the medico-legal expertise a thorough histological examination of inner organs and tissues is needed; the histological section has to represent the sampling site for culture. The presence of an underlying infection can be proven when postmortem bacteriological cultures yield a primary infectious pathogen and a cellular response in the affected tissue can be detected on the histopathological level. Postmortem bacteriology can be regarded as a reliable diagnostic tool for postmortem quality control of preceding diagnostic and therapeutic procedures and can serve as an additional indicator of nosocomial infections within a specific hospital environment. From the medico-legal point of view, a more widespread application of this valuable investigative procedure, that adds to diminish the number of otherwise unresolved deaths in forensic autopsy practice, is desirable.

Journal Article↗

PubMed2001

Targeted deletion of the gene encoding iron regulatory protein-2 causes misregulation of iron metabolism and neurodegenerative disease in mice.

In mammalian cells, regulation of the expression of proteins involved in iron metabolism is achieved through interactions of iron-sensing proteins known as iron regulatory proteins (IRPs), with transcripts that contain RNA stem-loop structures referred to as iron responsive elements (IREs). Two distinct but highly homologous proteins, IRP1 and IRP2, bind IREs with high affinity when cells are depleted of iron, inhibiting translation of some transcripts, such as ferritin, or turnover of others, such as the transferrin receptor (TFRC). IRPs sense cytosolic iron levels and modify expression of proteins involved in iron uptake, export and sequestration according to the needs of individual cells. Here we generate mice with a targeted disruption of the gene encoding Irp2 (Ireb2). These mutant mice misregulate iron metabolism in the intestinal mucosa and the central nervous system. In adulthood, Ireb2(-/-) mice develop a movement disorder characterized by ataxia, bradykinesia and tremor. Significant accumulations of iron in white matter tracts and nuclei throughout the brain precede the onset of neurodegeneration and movement disorder symptoms by many months. Ferric iron accumulates in the cytosol of neurons and oligodendrocytes in distinctive regions of the brain. Abnormal accumulations of ferritin colocalize with iron accumulations in populations of neurons that degenerate, and iron-laden oligodendrocytes accumulate ubiquitin-positive inclusions. Thus, misregulation of iron metabolism leads to neurodegenerative disease in Ireb2(-/-) mice and may contribute to the pathogenesis of comparable human neurodegenerative diseases.

Animals↗

PubMed2001

Internal current mark in a case of suicide by electrocution.

Fatalities caused by electrocution often lack specific morphologic evidence. Investigation of the death scene along with technical inspection of the electrical apparatus may help in clarifying the cause and manner of death. Cutaneous current marks may be the only sign of low voltage associated fatalities. The authors report a case of an electrician who committed suicide by electrocution using a time switch after oral ingestion of diazepam. Electrodes (coins) were fixed with adhesive tape at the height of the heart to the front and back of the left side of the chest. Autopsy revealed a blackish linear mark on the pleura parietalis of the inner side of the thoracic cavity, connecting the cutaneous current marks. Current-related and heat-related changes, such as hypercontraction bands of the intercostal muscles and coagulative changes of the perineurium of peripheral nerves, were found at histologic examination. Taking into consideration that the body had been under the influence of low-voltage current for 7 days, the morphologic alteration on the pleura parietalis was in accordance with an internal current mark, indicating the main route of current flow through the body. To the authors' knowledge, such a current-related phenomenon has not been reported to occur on an inner body surface before.

Adult↗

PubMed2001

Malakoplakia involving the abdominal wall, urinary bladder, vagina, and vulva: case report and discussion of malakoplakia-associated bacteria.

A 29-year-old woman presented with a 3-month history of multiple purulent discharging nodules involving her lower abdomen, vulva, and left thigh. Physical examination also disclosed vaginal nodules and a left pelvic mass. Cystoscopy revealed multiple mucosal nodules and a perforation of the left vesical wall that appeared to communicate with the pelvic mass. Biopsies of the vesical and vulvar nodules revealed malakoplakia. Surgery and antibiotic therapy resulted in regression of all the lesions.

Abdominal Muscles↗