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Biomedical subjects

R Demir

Publications and source records attributed to R Demir.

At least 37 records · Page 2Linked to original sources

High resolution computed tomography of the lungs in patients with rheumatoid arthritis.

Pulmonary involvement is one of the most common extra-articular manifestations of rheumatoid arthritis (RA). The aim of this prospective study was to assess pulmonary involvement with high resolution computerized tomography (HRCT) in lifelong non-smoking patients with RA. Twenty-six female and eight male patients with a mean age of 45.26 +/- 11.6 years and without any evidence or symptoms of a respiratory disease were included in the study. Data were obtained regarding duration of disease, clinical symptoms and disease activity parameters. Standard chest roentgenographs, pulmonary function tests (PFT) and HRCT were performed. PFT was abnormal in eight (23.5%) and HRCT was abnormal in 23 patients (68%). The most frequent abnormalities obtained on HRCT were interstitial involvement including septal and peribronchial thickening and fibronodular infiltration, which were found in 23 patients, and bronchiectasis was found in nine patients. Using a highly sensitive technique such as HRCT the incidence of pulmonary abnormalities in asymptomatic rheumatoid patients may be much higher than previously reported.

Arthritis, Rheumatoid↗

Posterior mediastinal goiter.

A patient with chronic cough and recent dysphagia was found to have a retrotracheal mass extending into the mediastinum on chest radiography. A computed tomographic scan confirmed a retrotracheal posterosuperior mediastinal lesion which was believed to have a neurogenic origin. A thyroid 131I scan revealed no uptake of tracer in the chest and results of thyroid function tests were normal. A large retrotracheal colloidal nodular goiter was excised through a right thoracotomy. The diagnostic approach and the safety of surgical access by thoracotomy for thyroid lesions in this unusual site are discussed.

Goiter, Substernal↗

Voltage imaging of epileptiform activity in slices from rat piriform cortex: onset and propagation.

The piriform cortex is a temporal lobe structure with a very high seizure susceptibility. To investigate the spatiotemporal characteristics of epileptiform activity, slices of piriform cortex were examined by imaging electrical activity with a voltage-sensitive fluorescent dye. Discharge activity was studied for different sites of stimulation and different planes of slicing along the anterior-posterior axis. Epileptiform behavior was elicited either by disinhibition with a gamma-aminobutyric acid-A receptor antagonist or by induction with a transient period of spontaneous bursting in low-chloride medium. Control activity recorded with fluorescent dye had the same pharmacological and temporal characteristics as control activity reported previously with microelectrodes. Simultaneous optical and extracellular microelectrode recordings of epileptiform discharges showed the same duration, latency, and all-or-none character as described previously with microelectrodes. Under all conditions examined, threshold electrical stimulation applied throughout the piriform cortex evoked all-or-none epileptiform discharges originating in a site that included the endopiriform nucleus, a previously identified site of discharge onset. In induced slices, but not disinhibited slices, the site of onset also included layer VI of the adjoining agranular insular cortex and perirhinal cortex, in slices from anterior and posterior piriform cortex, respectively. These locations had not been identified previously as sites of discharge onset. Thus like the endopiriform nucleus, the deep agranular insular cortex and perirhinal cortex have a very low seizure threshold. Additional subtle differences were noted between the induced and disinhibited models of epileptogenesis. Velocity was determined for discharges after onset, as they propagated outward to the overlying piriform cortex. Propagation in other directions was examined as well. In most cases, velocities were below that for action potential conduction, suggesting that recurrent excitation and/or ephaptic interactions play a role in discharge propagation. Future investigations of the cellular and organizational properties of regions identified in this study should help clarify the neurobiological basis of high seizure susceptibility.

Animals↗

A histochemical, morphometric and ultrastructural study of gastrocnemius and soleus muscle fiber type composition in male and female rats.

The fiber type composition of gastrocnemius and soleus muscles of adult male and female rats was examined by histochemical, morphometric and ultrastructural methods. Six male and 6 female, 3.5-month-old rats were used in the study. The fiber types were determined using the adenosine triphosphatase (ATPase) and succinate dehydrogenase (SDHase) staining techniques. The number of fibers of different types and the diameters of these two muscles were examined by morphometric methods. Gastrocnemius muscles were also examined by transmission electron microscopy. Z-line thickness, actin length, sarcomere length and M-line thickness of the fiber types were compared at the ultrastructural level. No significant differences were observed between the diameters of the gastrocnemius muscle (p > 0.05) of male and female rats although the male animals were significantly larger than the females (p > 0.05). In males, type I fibers of the gastrocnemius were larger than in females (p < 0.05). Region II of the gastrocnemius muscles of females contained more type IIA and type IIB fibers than in males. Sarcomere lengths were also longer in females (p < 0.05). The composition of fiber types of gastrocnemius and soleus muscles may be sex dependent.

Animals↗

Placental villous stroma as a model system for myofibroblast differentiation.

Different subtypes of myofibroblasts have been described according to their cytoskeletal protein patterns. It is quite likely that these different subtypes represent distinct steps of differentiation. We propose the human placental stem villi as a particularly suitable model to study this differentiation process. During the course of pregnancy, different types of placental villi develop by differentiation of the mesenchymal stroma surrounding the fetal blood vessels. In order to characterise the differentiation of placental stromal cells in the human placenta, the expression patterns of the cytoskeletal proteins vimentin, desmin, alpha- and gamma-smooth muscle actin, pan-actin, smooth muscle myosin, and the monoclonal antibody GB 42, a marker of myofibroblasts, were investigated on placental tissue of different gestational age (7th-40th week of gestation). Proliferation patterns were assessed with the proliferation markers MIB 1 and PCNA. Additionally, dipeptidyl peptidase IV distribution was studied in term placenta and the ultrastructure of placental stromal cells was assessed by electron microscopy. Different subpopulations of extravascular stromal cells were distinguished according to typical co-expression patterns of cytoskeletal proteins. Around the fetal stem vessels in term placental villi they were arranged as concentric layers with increasing stage of differentiation. A variable layer of extravascular stromal cells lying beneath the trophoblast expressed vimentin (V) or vimentin and desmin (VD). They were mitotically active. The next layer co-expressed vimentin, desmin, and alpha-smooth muscle actin (VDA). More centrally towards the fetal vessels, extravascular stromal cells co-expressed vimentin, desmin, alpha- and gamma-smooth muscle actin, and GB 42 (VDAG). Cells close to the fetal vessels additionally co-expressed smooth muscle myosin (VDAGM). Ultrastructurally, V cells resembled typical mesenchymal cells. VD cells corresponded to fibroblasts, while VDA and VDAG cells developed features of myofibroblasts. Cells of the VDAGM-type revealed a smooth muscle cell-related ultrastructure. In earlier stages of pregnancy, stromal cell types with less complex expression patterns prevailed. The media smooth muscle cells of the fetal vessels showed a mixture of different co-expression patterns. These cells were separated from extravascular stromal cells by a layer of collagen fibres. The results obtained indicate a clearly defined spatial differentiation gradient with increasing cytoskeletal complexity in human placental stromal cells from the superficial trophoblast towards the blood vessels in the centre of the stem villi. The spatial distribution of the various stages of differentiation suggests that human placental villi could be a useful model for the study of the differentiation of myofibroblasts.

Biomarkers↗

A histochemical study on the enzymatic activity in the proximal epiphysis of the humerus during the prenatal and postnatal periods in rats.

In order to investigate the activity of certain enzymes [Alkaline phosphatase (ALP), Acid phosphatase (ACP), Adenosine triphosphatase (ATPase), 5'-Nucleotidase (5'-N)] in the proximal epiphysis of the humerus, tissue specimens were obtained from pregnant rats on the 15th, 17th, 19th and 20th days of gestation and on the 1st, 10th, 20th, 30th, 40th and 60th days of postnatal development. Enzymatic activity in the chondral ossification, in the perichondral areas of the epiphysis, was first seen on the 15th day of gestation. ALP and ATPase could also be observed for the first time in fetuses aged 15 days, whereas ACP and 5'-N could not be detected. These latter enzymes were observed for the first time in the proximal humeral epiphysis of fetuses aged 17 days. ALP, a marker for hypertrophic and calcifying cartilage, was observed extensively in the central hypertrophic part of the cartilaginous perichondral zones, which showed calcification during the development of the epiphysis. ALP, ATP and 5'-N activity was very marked in the cytoplasm of osteoblasts and in the periosteal matrix, but strong ACP activity was found in the cells of the chondrolysis zone. In conclusion; according to our observations, heterogeneity of the proximal epiphysis of the humerus exhibits intrinsic differences between the cells of different zones. The activity of all enzymes showed an increase according to the developmental age. This suggests that all of these enzymes play a role during developmental ossification.

5'-Nucleotidase↗

The fine structure of normal and ectopic (tubal) human placental villi as revealed by scanning and transmission electron microscopy.

The aim of this study was to examine the development of chorionic villous trees during early periods of normal intrauterinal and ectopic (tubal) pregnancies, and to study the structural specializations on the free surface of mature placental villi by scanning and transmission electron microscope (SEM and TEM). In order to study the structures of placental villi between 28 and 34 days old (pc), early, 6-8 week normal and ectopic, and full term human placenta samples were obtained from legal curettage and hysterectomized cases, and spontaneous deliveries, and tissues samples were prepared for SEM and TEM. Three-dimensional configurations of the developing chorionic villous trees were observed as large main villus groups, covered with abundant microvilli of different size and diameters. It appeared that the chorionic villous trees which emerged from the chorionic plate divided gradually into branches of which ramifications originated as buds. These buds gradually grew and were transformed into shoots. The number of developing new villi appeared to increase gradually from 28 days to 9 weeks (pm) of gestation. From the 4th week onwards the massive trophoblastic sprouts were observed on the surface of main chorionic villi which transformed into primary, secondary and tertiary villous trees. When the placental villi formation in ectopic pregnancy was compared with the intra-uterinal pregnancy, an arrested development was remarkable. The configurations of ectopic placental villi seemed to be disparate, such as curved lines or compressed and wrinkled positions so that the three dimensional aspect had been wizened. The ramification and new villi formation seen as in the normal placenta were not only decreased but also infrequent. Some placental villi samples displayed a gradually thinning terminal region. Trophoblastic degenerations were frequently found on the surface of ectopic villi ultrastructurally. According to these results, we comment that in ectopic pregnancy the placental villi formation and development could have been delayed. At term, some specialized structural modifications were observed on the free surface of the mature placental villi. The presence of some dome-like balloonings and many crateriform hollows were the most striking features of the mature intermediate and terminal villi. According to the increasing physiological needs of the growing fetus, these special structures that are related to lung-like and kidney-like functions and named "nephropneumonic-like units", formed in the mature placental barrier. We have observed that these special units were showing a smooth surface similar to an inflated balloon.(ABSTRACT TRUNCATED AT 400 WORDS)

Chorionic Villi↗

Structural changes in placental barrier of smoking mother. A quantitative and ultrastructural study.

Human placental villi from all three trimesters of pregnancy, in 90 non-smoking pregnants and 244 cigarette smoking pregnants, were investigated. In smokers, the numbers of syncytial knots and cytotrophoblastic cells increased, depending on the cigarettes per day, syncytial buds and vasculo-syncytial membranes decreased as the pregnancy proceeded. The mean birth weight and placental weight in smokers were decreased, depending on the cigarettes per day at the third trimester. The ultrastructure of placental villi from smokers were compared with that on non-smokers. The villi from smokers had abnormalities of the microvilli, focal syncytial necrosis, decreased syncytial pinocytotic activity, degenerated cytoplasmic organelles. Using a morphometric method, the basement membranes were measured throughout pregnancy. The mean thickness of the basement membranes of trophoblastic layer and fetal capillary were found to not only increase with the maternal smoking during pregnancy but also attain the maximum in the heavy smokers by the third trimester of pregnancy. There was increased collagen in the villous stroma and shrinkage endothelial changes in fetal capillaries, in smokers the deleterious effect of the cigarette smoking on the placental barrier was heavy damage. As a result of impairment of placental barrier, the transports between mother and fetus were hampered.

Female↗

Fetal vasculogenesis and angiogenesis in human placental villi.

Placental villi of 5 exactly defined early human specimens ranging from day 21 post conception (p.c.) until day 42 p.c. and from an additional 43 specimens from about 5 to 40 weeks menstrual age have been analyzed ultrastructurally with regard to fetal vasculogenesis and angiogenesis. The following results were obtained: The first cells differentiating at day 21 p.c., probably originating from mesenchymal precursors, are macrophage-like cells. At almost the same time, mesenchymal cells transform into haemangioblastic cell cords which are the forerunners of the capillary endothelium and haematopoietic stem cells. A third cell population related to the fetal circulatory system and derived from the mesenchymal cells are presumptive pericytes. Capillary formation takes place by the aggregation of haemangioblastic cells which are attached to each other by intercellular junctions. The lumen is formed by the dehiscence of the intercellular clefts. A capillary basal lamina cannot be detected earlier than in the last trimester. In this last period of gestation, fetal villous angiogenesis takes place by the proliferation of the existing endothelium and pericytes rather than via haemangioblastic cells.

Blood Vessels↗

Some new findings about Hofbauer cells in the chorionic villi of the human placenta.

The cytological structure of the Hofbauer cells was investigated in human placentas of the first and second trimesters of gestation. These cells are found in the stromal channel system of the chorionic villi core. Their walls, which are supported by collagen fiber bundles, are produced by reticulum cells and fibroblasts. The cytoplasmic processes of the Hofbauer cells are in contact with the walls of the channels without being associated with them by desmosomal complexes. Some of these cells have features in common with macrophages, such as cytoplasmic processes, larger vacuoles, many pinocytotic vesicles and intracytoplasmic granules. This system of vacuoles and vesicles enables micropinocytotic activity and phagocytosis. This type of Hofbauer cell resembles the typical macrophages. These cells may play a role in the regulation of stromal water content, transportation of ions and the flow of interstitial fluid. The most original finding of this study are long tubes observed in some Hofbauer cells and extending between the nucleus and the extracellular ground substance through the cytoplasm. One of these tubular formations resembles a cilium in structure with three limiting membranes and is filled with a slightly electron-dense substance. This type of Hofbauer cell may transport information between the nucleus and the extracellular ground substance by means of these tubular structures.

Chorionic Villi↗

Ultrastructure of the epithelium of the chorionic villi of the human placenta.

Human placenta samples obtained at 4, 6, 8 and 10 weeks of gestation and at full term were studied by transmission electron microscopy (TEM). The chorionic villi at early stages of gestation exhibited abundant microvilli on the free surface of the syncytium. The chorionic villi at full term were covered by syncytium which bore short microvilli on its free surface. The syncytial cells were remarkably higher in density than Langhans' cells. In the earlier period of gestation, a dividing membrane was noticed in the inside of the syncytial cells. The cytoplasm of the syncytial cell contained comparatively small mitochondria, well-developed endoplasmic reticulum cells, ill-developed Golgi systems, electron-dense lipoid droplets and plenty of ribosomes. A great number of Langhans' cells were noticed in early gestation; only very few were noticed the later part. Mitochondria of Langhans' cells were comparatively large and the Golgi system was well-developed in the first trimester. Endoplasmic reticulum was less well developed and there were few ribosomes. The basement tended to become thicker a pregnancy proceeded and lamellar structures appeared on its inner face.

Chorionic Villi↗

Scanning electron-microscopic observations on the surfaces of chorionic villi of young and mature placentas.

Mature placental material of full-term spontaneous births and 4-, 6-, 8- and 10-week-old placentas obtained from curettage cases were fixed in glutaraldehyde and osmium tetroxide for SEM examination. In young placentas, the ramifications of the chorionic villi start in the form of buds. The buds are transformed into tendrils with swollen extremities. These swellings resemble buds ready to bloom. The villi intertwine in different positions; both the villi and their tendrils are covered with dense layers of microvilli. In mature placentas, the surfaces of the chorionic villi and their ramifications are covered with microvilli. However, in comparison with the microvilli of young placentas, the microvilli here are less numerous and shorter. Invaginations were clearly visible on the surfaces of the villi; younger and newly budding microvilli, similar to those observed in young placentas, were seen in the invaginated regions. We had the impression that the mature placentas must regenerate in order to meet the increasing physiological requirements of the fetus.

Chorionic Villi↗

Classification of human placental stem villi: review of structural and functional aspects.

The stem villi of the human placenta represent the central branches of the villous trees. They are characterized by a condensed fibrous stroma in which the fetal arteries and veins as well as the arterioles and venules are embedded. Functionally they are accepted as the mechanically supporting structures of the villous trees, and they are supposed to control fetal blood flow to the maternofetal exchange area, which is located in the peripheral villi. To obtain further insights into the functions of the stem villi, the recent literature has been reviewed, and some immunohistochemical, ultrastructural, and reconstruction studies have been added. These new studies were aimed at identifying immunohistochemically different subtypes of stem villi, their branching patterns, the distribution of macrophages, the stromal proliferation patterns, and the differentiation of extravascular stromal cells. Our findings demonstrate that the stem villi and their precursors, the immature intermediate villi, can selectively be identified by anti-gamma-smooth muscle (sm) actin staining. Furthermore, the existence of three different subtypes of stem villi is shown; these differ regarding the presence and distribution of gamma-sm actin-positive cells. These cells were immunohistochemically and ultrastructurally identified as smooth muscle cells and myofibroblasts. Increasingly complex coexpression patterns of cytoskeletal proteins reflect a clearly defined differentiation gradient of extravascular stromal cells, which covers the whole range of an undifferentiated germinative layer beneath the trophoblast to highly differentiated myofibroblasts surrounding the medias of the stem vessels. Possible functions of the extravascular contractile system include the regulation of villous turgor and the control of intervillous blood flow impedance.

Actins↗

Sustained hypoglycemia affects glucose transporter expression of human blood leukocytes.

The scarce data available on leukocyte glucose transporter expression are contradictory and nothing is known about its regulation by glycemic state. Therefore, cytospin preparations of blood leukocytes were searched immunocytochemically for the high-affinity glucose transporters GLUT1, 3, and 4. Hypoglycemia-associated quantitative changes in transporter expression were assessed by flow cytometry. Granulocytes and monocytes stained for GLUT1, 3, and 4. Granulocyte GLUT4 levels were increased by 73% (P < 0.05) under hypoglycemic conditions, which was paralleled by a reduction in GLUT1 and a rise in GLUT3. In monocytes, GLUT3 was elevated by 134% (P < 0.05), whereas GLUT1 and GLUT4 remained unaffected upon hypoglycemia. Apart from a minor subpopulation, lymphocytes were negative for these carriers. In conclusion, GLUT1, 3, and 4 are abundantly expressed in granulocytes and monocytes. The differential response of individual isoforms to hypoglycemia may represent a mechanism to protect the cells from the stress of glucose deprivation.

Adaptation, Biological↗