Tibor Glasz

Neurochemical mapping of the human hippocampus reveals perisynaptic matrix around functional synapses in Alzheimer’s disease

Perineuronal matrix is an extracellular protein scaffold to shape neuronal responsiveness and survival. Whilst perineuronal nets engulf the somatodendritic axis of neurons, axonal coats are focal extracellular protein aggregates surrounding individual synapses. Here, we addressed the chemical identity and subcellular localization of both perineuronal and perisynaptic matrices in the human hippocampus, whose neuronal circuitry is progressively compromised in Alzheimer’s disease. We hypothesized that (1) the cellular expression sites of chondroitin sulphate proteoglycan-containing extracellular matrix associate with specific neuronal identities, reflecting network dynamics, and (2) the regional distribution and molecular composition of axonal coats must withstand Alzheimer’s disease-related modifications to protect functional synapses. We show by epitope-specific antibodies that the perineuronal protomap of the human hippocampus is distinct from other mammals since pyramidal cells but not calretinin+ and calbindin+ interneurons, neurochemically classified as novel neuronal subtypes, lack perineuronal nets. We find that cartilage link protein-1 and brevican-containing matrices form isolated perisynaptic coats, engulfing both inhibitory and excitatory terminals in the dentate gyrus and entorhinal cortex. Ultrastructural analysis revealed that presynaptic neurons contribute components of perisynaptic coats via axonal transport. We demonstrate, by combining biochemical profiling and neuroanatomy in Alzheimer’s patients and transgenic (APdE9) mice, the preserved turnover and distribution of axonal coats around functional synapses along dendrite segments containing hyperphosphorylated tau and in amyloid-β-laden hippocampal microdomains. We conclude that the presynapse-driven formation of axonal coats is a candidate mechanism to maintain synapse integrity under neurodegenerative conditions.

The diagnosis, morphological particularities, and surgical technique in a case of intravascular leiomyoma extended to the right heart chambers

Intravenous leiomyoma is a benign smooth muscle cell tumor of uterine origin that may grow into the pelvic veins and the inferior vena cava. It usually affects premenopausal women and the majority (90%) are parous. Because cardiac involvement is present in up to 10% of cases, it may be misdiagnosed as a primary cardiac tumor or a venous thrombus-in-transit. We describe a case of intravascular leiomyomatosis with cardiac extension and the morphological particularities of the removed tumor.

Perisynaptic aggrecan-based extracellular matrix coats in the human lateral geniculate body devoid of perineuronal nets

The extracellular matrix surrounds different neuronal compartments in the mature nervous system. In a variety of vertebrates, most brain regions are loaded with a distinct type of extracellular matrix around the somatodendritic part of neurons, termed perineuronal nets. The present study reports that chondrotin sulfate proteoglycan‐based matrix is structured differently in the human lateral geniculate body. Using various chondrotin sulfate proteoglycan‐based extracellular matrix antibodies, we show that perisomatic matrix labeling is rather weak or absent, whereas dendrites are contacted by axonal coats appearing as small, oval structures. Confocal laser scanning microscopy and electron microscopy demonstrated that these typical structures are associated with synaptic loci on dendrites. Using multiple labelings, we show that different chondrotin sulfate proteoglycan components of the extracellular matrix do not associate exclusively with neuronal structures but possibly associate with glial structures as well. Finally, we confirm and extend previous findings in primates that intensity differences of various extracellular matrix markers between magno‐ and parvocellular layers reflect functional segregation between these layers in the human lateral geniculate body.

Chlamydia pneumoniae in different coronary artery segments in the young.

UNLABELLED Chlamydia pneumoniae has emerged as the most likely pathogen to have a causative role in the development and/or for progression of atherosclerosis. Evidence for this is based on epidemiological and pathological studies. In an effort to better understand the significance of finding C. pneumoniae in atheromata, we examined coronary artery segments of young adults (15-34 years) with and without atherosclerosis. Left anterior descending coronary arteries (LAD) of 74 young adults who died suddenly were examined histologically and for the presence of C. pneumoniae by immunohistochemistry. C. pneumoniae was identified in advanced lesions (Stary types III to VI) in 17 of 32 cases (53%), and in early lesions (Stary type I-II) in 8 of 37 cases (21%), mainly at the proximal segments of the LAD. C. pneumoniae was not found in the intimal and medial layer of normal-appearing coronary arteries. C. pneumoniae was detected in the adventitia in 51 (67%) coronary arteries: in 27 of normal arteries and early lesions (64%), and in 24 of atherosclerotic lesions (75%). C. pneumoniae was found most often in macrophages, less offen in smooth muscle cells. We also observed a correlation between C. pneumoniae positivity and cigarette smoking. IN CONCLUSION C. pneumoniae may relate to the severity of atherosclerosis in young people, and it may thus initiate atherosclerotic injury or facilitate its progression with other risk factors.

[Crohn's disease of the duodenum. Clinical signs, diagnosis, conservative and surgical treatment].

Duodenal localization of Crohns disease is rare, accounting for only 0.5-4% of all cases. Most common complaints are gastric outlet obstruction and weight loss. Histologic findings of endoscopic biopsy are frequently not definitive, making differentiation from other, benign structures complicated. There are also no standard guidelines regarding indications for surgical management. PATIENTS AND METHODS: We reviewed the cases of three surgically managed patients with duodenal Crohns disease at the 1st Department of Surgery, Semmelweis University of Medicine, Budapest, during a 5-year period (2002-2007). All three patients had persistent symptoms of stomach emptying disorder despite medical therapy and had severe weight loss (13-30 kg). In two cases resection of the stenotic duodenum was performed successfully using Billroth II method. Gastro-jejunal bypass was performed in one case, where the descendent duodenum was inflamed. RESULTS: All patients have been asymptomatic since surgery (9-45 months of follow-up) and recovered their earlier bodyweight. The postoperative period was uneventful. CONCLUSIONS: There is indication of surgery in cases of stenosing duodenal Crohns disease, when medical therapy is not successful, but long-standing malnutrition should be treated preoperatively. We found perioperative morbidity to be similar in patients with duodenal Crohns and in those with Crohns disease of other intestinal locations.UNLABELLED Duodenal localization of Crohns disease is rare, accounting for only 0.5-4% of all cases. Most common complaints are gastric outlet obstruction and weight loss. Histologic findings of endoscopic biopsy are frequently not definitive, making differentiation from other, benign structures complicated. There are also no standard guidelines regarding indications for surgical management. PATIENTS AND METHODS We reviewed the cases of three surgically managed patients with duodenal Crohns disease at the 1st Department of Surgery, Semmelweis University of Medicine, Budapest, during a 5-year period (2002-2007). All three patients had persistent symptoms of stomach emptying disorder despite medical therapy and had severe weight loss (13-30 kg). In two cases resection of the stenotic duodenum was performed successfully using Billroth II method. Gastro-jejunal bypass was performed in one case, where the descendent duodenum was inflamed. RESULTS All patients have been asymptomatic since surgery (9-45 months of follow-up) and recovered their earlier bodyweight. The postoperative period was uneventful. CONCLUSIONS There is indication of surgery in cases of stenosing duodenal Crohns disease, when medical therapy is not successful, but long-standing malnutrition should be treated preoperatively. We found perioperative morbidity to be similar in patients with duodenal Crohns and in those with Crohns disease of other intestinal locations.

Region Specific Differences of Claudin-5 Expression in Pediatric Intracranial Ependymomas: Potential Prognostic Role in Supratentorial Cases

Ependymomas are common pediatric brain tumors that originate from the ependyma and characterized by poor prognosis due to frequent recurrence. However, the current WHO grading system fails to accurately predict outcome. In a retrospective study, we analyzed 54 intracranial pediatric ependymomas and found a significantly higher overall survival in supratentorial cases when compared to infratentorial tumors. Next we performed region-specific immunohistochemical analysis of the ependyma in neonatal and adult ependyma from the central canal of spinal cord to the choroid plexus of lateral ventricles for components of cell-cell junctions including cadherins, claudins and occludin. We found robust claudin-5 expression in the choroid plexus epithelia but not in other compartments of the ependyma. Ultrastructural studies demonstrated distinct regional differences in cell-cell junction organization. Surprisingly, we found that 9 out of 20 supratentorial but not infratentorial ependymomas expressed high levels of the brain endothelial tight junction component claudin-5 in tumor cells. Importantly, we observed an increased overall survival in claudin-5 expressing supratentorial ependymoma. Our data indicates that claudin-5 expressing ependymomas may follow a distinct course of disease. The assessment of claudin-5 expression in ependymoma has the potential to become a useful prognostic marker in this pediatric malignancy.

Duodenal Ulceration in a Patient With Celiac Disease and Plasminogen I Deficiency: Coincidence or Cofactors?

Celiac disease (CD) is a gluten-dependent inflammatory disease of the small bowel that affects up to 1% of the worldwide population. Despite severe mucosal abnormalities including total villous atrophy and autoantibody deposition, duodenal ulcer is not a feature of CD. However, a recent study found an elevated rate of peptic ulcer disease in patients with CD. Plasminogen deficiency (PLD) is an autosomal recessive disease that causes pseudomembranous lesions in different organs, but gastrointestinal involvement is rare. Here we report the case of a 6-year-old girl who had a sudden onset of hematemesis caused by duodenal ulcer. On the basis of mucosal atrophy, elevated celiac antibody levels, decreased plasminogen serum activity, and homozygous missense mutation R216H in the plasminogen gene, CD and PLD were diagnosed. This report is, to our knowledge, the first description of the 2 entities, and results of our double-immunofluorescent studies also suggest that both diseases may have a role in the ulceration process. Excessive amounts of fibrin deposition due to PLD caused the distortion of the vessels and was responsible for the unusual celiac immunoglobulin A and tissue transglutaminase 2 in vivo binding pattern. On the basis of this result, patients with CD and unknown cause of gastrointestinal ulcer may require investigation for PLD.

Comparative Endoscopic Anatomic Description of the Mitral Valvular Complex: a Cadaveric Study

BACKGROUND We compared the aortic, left atrial, and apical approaches to visualize the mitral valve with the goal to investigate the endoscopic anatomy and give exact step-by-step descriptions of these views. MATERIALS AND METHODS The mitral valvular complex of human cadaveric fresh hearts was investigated from three approaches using 0, 30, and 70 degrees rigid endoscopic optics. In 30 cases after the removal of the hearts, the endoscopes were introduced directly into the aortic root through an aortotomy, left atrium through a standard atriotomy, and apex of the heart through a transmural incision. In 10 cases, the in situ visualization was performed using standard surgical approaches, such as partial upper ministernotomy, right and left minithoracotomy. The investigation was performed first with the mitral valve open, then the left ventricle was filled with saline, and the valve was closed by clamping the aorta. RESULTS For the visualization of ventricular surfaces of the mitral leaflets and the subvalvular apparatus, the apical approach was most optimal. The aortic approach had limitations at the posterior leaflet. Using the atrial approach, we did not obtain any direct visual information about the subvalvular apparatus with the valve closed. The atrial surfaces of the leaflets were best visible using both the atrial and apical approaches with the mitral valve open. In the case of a closed valve, the apical approach did not allow for an investigation of the atrial surfaces. The aortic approach was useful to visualize the atrial surface of the posterior leaflet with an opened valve. CONCLUSION In mitral valve repairs through the left atrium, an additional aortic or apical view could be useful to obtain functional information about the subvalvular apparatus by the sealing probe.

Removal of sessile recidiv rectal polyp with endoscopic submucosal dissection. Case report and review of the literature

UNLABELLED With the development of flexible endoscopy, removal of the large sessile polyps and superficial malignant tumors that do not exceed the layer muscular mucosa has become todays major challenge. Earlier in various types of mucosectomy performed with such indication it was difficult to control the depth and the lateral margin of the resection surface. Tumors larger than 20 mm could only be removed with the application of the piecemeal technique. PATIENT AND METHOD 64-year-old female patients large sessile polyp had been removed earlier with piecemeal technique followed by mucosectomy. On the area of these interventions a recidiv adenoma was found and for this reason endoscopic submucosal dissection was applied. RESULT The procedure took 55 minutes, and only small volume of bleeding was detected during the intervention. The postoperative period was uneventful, one day later the patient left the hospital. Vertical and lateral resection surface were free of tumor histologically. CONCLUSION The endoscopic submucosal dissection is suitable for the removal of the large sessile polyp, which could not be successfully removed with earlier techniques.Az intraluminalis invaziv endoszkopia fejlődesevel a nagy, sessilis polipok, a muscularis mucosa reteget nem meghalado malignus tumorok eltavolitasa jelent napjainkban kihivast. A korabban ilyen indikacioval vegzett mucosectomiak kulonboző formainal nehezseget okozott a melysegi es lateralis reszekcios szelek kontrollja, a 20 mm-nel nagyobb elvaltozasok pedig csak piecemealtechnikaval voltak eltavolithatok. Beteganyag: 64 eves nőbeteg nagy, korabban piecemealtechnikaval, majd mucosectomiaval eltavolitott sessilis rectumpolipjanak helyen eszlelt recidiv elvaltozas eltavolitasat vegeztuk endoszkopos submucosus dissectiot alkalmazva. Eredmenyek: Az 55 percig tarto beavatkozas soran csak minimalis verzes jelentkezett. A beavatkozas soran szovődmenyt nem eszleltunk, a beteg egynapos obszervacio utan panaszmentesen tavozott. A szovettani vizsgalat szerint az elvaltozas eltavolitasa vertikalisan es lateralisan is az epben tortent. Kovetkeztetes: Az endoszkopos submucosus dissectio olyan elvaltozasok radikalis eltavolitasara is alkalmas, melyek a korabban alkalmazott technikakkal nem voltak sikeresen reszekalhatok. | With the development of flexible endoscopy, removal of the large sessile polyps and superficial malignant tumors that do not exceed the layer muscular mucosa has become today’s major challenge. Earlier in various types of mucosectomy performed with such indication it was difficult to control the depth and the lateral margin of the resection surface. Tumors larger than 20 mm could only be removed with the application of the piecemeal technique. Patient and method: 64-year-old female patient’s large sessile polyp had been removed earlier with piecemeal technique followed by mucosectomy. On the area of these interventions a recidiv adenoma was found and for this reason endoscopic submucosal dissection was applied. Result: The procedure took 55 minutes, and only small volume of bleeding was detected during the intervention. The postoperative period was uneventful, one day later the patient left the hospital. Vertical and lateral resection surface were free of tumor histologically. Conclusion: The endoscopic submucosal dissection is suitable for the removal of the large sessile polyp, which could not be successfully removed with earlier techniques.

Sessilis recidív rectumpolip miatt végzett endoszkópos submucosus dissectio.Esetismertetés és irodalmi áttekintés@@@Removal of sessile recidiv rectal polyp with endoscopic submucosal dissection. Case report and review of the literature

UNLABELLED With the development of flexible endoscopy, removal of the large sessile polyps and superficial malignant tumors that do not exceed the layer muscular mucosa has become todays major challenge. Earlier in various types of mucosectomy performed with such indication it was difficult to control the depth and the lateral margin of the resection surface. Tumors larger than 20 mm could only be removed with the application of the piecemeal technique. PATIENT AND METHOD 64-year-old female patients large sessile polyp had been removed earlier with piecemeal technique followed by mucosectomy. On the area of these interventions a recidiv adenoma was found and for this reason endoscopic submucosal dissection was applied. RESULT The procedure took 55 minutes, and only small volume of bleeding was detected during the intervention. The postoperative period was uneventful, one day later the patient left the hospital. Vertical and lateral resection surface were free of tumor histologically. CONCLUSION The endoscopic submucosal dissection is suitable for the removal of the large sessile polyp, which could not be successfully removed with earlier techniques.Az intraluminalis invaziv endoszkopia fejlődesevel a nagy, sessilis polipok, a muscularis mucosa reteget nem meghalado malignus tumorok eltavolitasa jelent napjainkban kihivast. A korabban ilyen indikacioval vegzett mucosectomiak kulonboző formainal nehezseget okozott a melysegi es lateralis reszekcios szelek kontrollja, a 20 mm-nel nagyobb elvaltozasok pedig csak piecemealtechnikaval voltak eltavolithatok. Beteganyag: 64 eves nőbeteg nagy, korabban piecemealtechnikaval, majd mucosectomiaval eltavolitott sessilis rectumpolipjanak helyen eszlelt recidiv elvaltozas eltavolitasat vegeztuk endoszkopos submucosus dissectiot alkalmazva. Eredmenyek: Az 55 percig tarto beavatkozas soran csak minimalis verzes jelentkezett. A beavatkozas soran szovődmenyt nem eszleltunk, a beteg egynapos obszervacio utan panaszmentesen tavozott. A szovettani vizsgalat szerint az elvaltozas eltavolitasa vertikalisan es lateralisan is az epben tortent. Kovetkeztetes: Az endoszkopos submucosus dissectio olyan elvaltozasok radikalis eltavolitasara is alkalmas, melyek a korabban alkalmazott technikakkal nem voltak sikeresen reszekalhatok. | With the development of flexible endoscopy, removal of the large sessile polyps and superficial malignant tumors that do not exceed the layer muscular mucosa has become today’s major challenge. Earlier in various types of mucosectomy performed with such indication it was difficult to control the depth and the lateral margin of the resection surface. Tumors larger than 20 mm could only be removed with the application of the piecemeal technique. Patient and method: 64-year-old female patient’s large sessile polyp had been removed earlier with piecemeal technique followed by mucosectomy. On the area of these interventions a recidiv adenoma was found and for this reason endoscopic submucosal dissection was applied. Result: The procedure took 55 minutes, and only small volume of bleeding was detected during the intervention. The postoperative period was uneventful, one day later the patient left the hospital. Vertical and lateral resection surface were free of tumor histologically. Conclusion: The endoscopic submucosal dissection is suitable for the removal of the large sessile polyp, which could not be successfully removed with earlier techniques.