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Biomedical subjects

A Dogan

Publications and source records attributed to A Dogan.

At least 73 records · Page 4Linked to original sources
PubMed1998

Base-specific sequences that bias somatic hypermutation deduced by analysis of out-of-frame human IgVH genes.

Somatic hypermutation introduces mutations into IgV genes during affinity maturation of the B cell response. Mutations are introduced nonrandomly, and are generally targeted to the complementarity determining regions (CDRs). Subsequent selection against mutations that result in lower affinity or nonfunctional Ig increases the relative number of mutations in the CDRs. Investigation of somatic hypermutation is hampered by the effects of selection. We have avoided this by studying out-of-frame human IgVH4.21 and 251 genes, which, being unused alleles, are unselected. By comparison of the frequency of A, C, G, and T nucleotides at positions -3 to +3 around mutated or unmutated A, C, and G nucleotides, we have identified flanking sequences that most commonly surround mutated bases. Distinct trends in flanking sequences that were unique for each base were observed. Statistically significant trends that were common to both IgVH4.21 and 251 were used to deduce motifs that bias somatic hypermutation. The motifs deduced from this data, with targeted bases in regular type, are AANB, WDCH, and DGHD (where W = A/T, B = C/G/T, D = A/G/T, H = A/C/T, and N = any base). Mutations from C and G in two further groups of out-of-frame human IgVH genes, not used in the deduction of the motifs, occurred significantly within the motifs for C and G. The proposed target sequence for G is within the reverse complement of the target sequence for C, suggesting that the hypermutation mechanism may target only G or C. The mutation in the complementary base would appear on the other strand following replication.

Adenine↗
PubMed1998

Increased ornithine decarboxylase activity and protein level in the cortex following traumatic brain injury in rats.

There is increasing evidence that the elevated levels of polyamines play an important role in the secondary injury following traumatic brain injury (TBI). Ornithine decarboxylase (ODC) is the rate-limiting enzyme of polyamine biosynthesis. Presently, we measured the ODC protein levels by Western blot analysis in the cerebral cortex of rats sacrificed at 2 h, 6 h, 24 h, 72 h and 168 h after controlled cortical impact injury. TBI resulted in a significant increase in ODC protein levels (2.5 to 5.5 fold, P<0.05) and enzyme activity (13 to 21 fold, p<0.01) between 2 and 6 h after the injury. ODC protein levels and enzyme activity returned to normal, control levels by 72 h after the injury. Increased ODC protein and enzyme activity could contribute to vasogenic edema and the pathogenesis of neuronal dysfunction after TBI by stimulating the formation of polyamines.

Animals↗
PubMed1998

Intraluminal suture occlusion of the middle cerebral artery in Spontaneously Hypertensive rats.

In models of middle cerebral artery occlusion using intraluminal suture, the size and the distribution of ischemic injury vary considerably among laboratories. In transcranial models of cerebral ischemia, a more consistent cerebral ischemic lesion is seen in Spontaneously Hypertensive rats (SHR). In the present study, we performed intraluminal suture occlusion of the MCA in SHR and compared its reproducibility with those in Sprague-Dawley (SD) rats. Male SHR and SD rats were anesthetized with halothane and subjected to 2 h of temporary middle cerebral artery occlusion by an intraluminal suture. Comparisons of regional cerebral blood flow figures taken throughout the experiment and lesion volume figures taken at 24 h after occlusion were made between the two groups. Total lesion volume in the SHR group was 263.6+/-30.5 mm3 (mean +/- SD), significantly larger and less variable than that in the SD group (145.4+/-123.7 mm3, p < 0.02). Throughout the ischemic period there was a tendency for rCBF to be lower in the SHR group than in the SD group. In some animals of both groups, recirculation could not be produced by withdrawal of the suture from the ICA. The mortality rate was 9% in the SD group and 17% in the SHR group. Intraluminal MCA occlusion in SHRs is associated with a more consistent, reliable and reproducible volume of ischemic injury. In the studies of temporary focal cerebral ischemia, this model must be accompanied by the monitoring of regional cerebral blood flow so as to obtain more reliable results.

Age Factors↗
PubMed1997

Preferential dissemination of B-cell gastric mucosa-associated lymphoid tissue (MALT) lymphoma to the splenic marginal zone.

The tendency for gastric mucosa-associated lymphoid tissue (MALT) lymphoma cells preferentially to localize around reactive B-cell follicles, both in the mucosa and regional lymph nodes, coupled with their immunophenotype, has led to the proposal that the normal cell counterpart of this lymphoma is the marginal zone B cell. In keeping with this proposition, lymphocytes expressing the lymphoma idiotype have been detected in the splenic marginal zone in a single case of gastric MALT lymphoma. To confirm that this truly represented preferential homing of MALT lymphoma to the splenic marginal zone, we have now re-examined this case, together with 17 other cases, using both immunohistochemical and molecular methods in an attempt to establish clonal identity between the gastric lymphoma and cells in the splenic marginal zone. In three cases, the spleen was characterized by marked expansion of marginal zones by cells showing the same pattern of Ig light chain restriction as the gastric lymphoma. None of the remaining 15 cases showed histologic evidence of lymphomatous infiltration. Analysis of the Ig genes by polymerase chain reaction (PCR), cloning, and sequencing confirmed clonal identity between the splenic marginal zone infiltrates and the gastric lymphoma in the histologically involved cases. Amplifiable DNA could be extracted from only 5 of the remaining 15 cases. In 3 of these cases, including the case previously studied using an anti-idiotype, involvement of the splenic marginal zone could be confirmed using microdissection and clone-specific PCR. No involvement could be detected in the remaining 2 cases. In addition, we have shown that mucosal addressin cell adhesion molecule-1 (MAdCAM-1), the primary homing receptor of gut-mucosa for lymphocytes, was strongly expressed by the sinus lining cells of the splenic marginal zone. These results provide strong evidence for preferential involvement of the marginal zone when gastric MALT lymphomas disseminate to the spleen, which is in keeping with the notion that the marginal zone B cells are the normal counterparts of MALT lymphoma cells.

Adult↗
PubMed1997

Regional brain polyamine levels in permanent focal cerebral ischemia.

Transient global cerebral ischemia has been shown to induce marked changes in the polyamine pathway with a significant increase in putrescine, the product of the ornithine decarboxylase reaction. This study examined the relationship between tissue and extracellular polyamines and regional cerebral blood flow and brain edema. Six hours of focal ischemia in cats (n = 10) was produced by permanent middle cerebral artery occlusion. Extracellular polyamines were measured in extracellular fluid obtained by microdialysis. Regional cerebral blood flow using laser Doppler flowmetry and specific gravity, an indicator of brain edema, were measured in contralateral (non-ischemic), penumbra and densely ischemic brain regions. A significant increase in the tissue putrescine level was found in the penumbra but there was no difference in the putrescine levels between contralateral and densely ischemic regions. There was no significant change in the spermidine and spermine levels in the three regions. Extracellular levels of putrescine and spermidine were found to be significantly lower than the tissue levels and no change in polyamines was observed in any region. Significant edema formation was observed in densely ischemic and penumbra regions. This is the first demonstration that tissue putrescine is increased in the penumbra region, an area of incomplete ischemia that is developing brain edema.

Animals↗
PubMed1997

Intravenous infusion of adrenomedullin and increase in regional cerebral blood flow and prevention of ischemic brain injury after middle cerebral artery occlusion in rats.

The intravenous infusion of rat adrenomedullin, at concentrations ranging from 0.1 to 1.0 microgram/kg/min, for 60 min increased the regional cerebral blood flow (rCBF) in a dose-dependent manner in rats. rCBF was measured using a laser Doppler flowmetry device placed on the surface of the parietal cortex. The increase in rCBF induced by 1.0 microgram/kg/min of adrenomedullin was up to 145 +/- 10.8% of controls at 60 min (n = 5, p < 0.001). These concentrations of adrenomedullin did not affect systemic blood pressure or other physiologic parameters, including pH, PaCO2, PaO2, hemoglobin, and blood glucose. Repeated infusion of 1.0 microgram/kg/min of adrenomedullin at 2-h intervals caused tachyphylaxis (n = 5, p < 0.01). Rat adrenomedullin (1.0 microgram/kg/min) demonstrated a more potent effect than the same dose of human adrenomedullin. The C-terminal fragment of human adrenomedullin (0.5 and 5.0 micrograms/kg/min), adrenomedullin22-52, which did not affect rCBF alone, inhibited the effect of rat adrenomedullin (0.5 microgram/kg/min) as a receptor antagonist in a dose-dependent manner. In a model of middle cerebral artery (MCA) occlusion in spontaneously hypertensive rats, pre- and postinfusion of 1.0 microgram/kg/min of adrenomedullin suppressed the reduction in rCBF following MCA occlusion (control, 29 +/- 15.1%; adrenomedullin group, 45 +/- 14.4%; not significant) and decreased the volume of ischemic brain injury (control, 288 +/- 35 mm3; adrenomedullin group, 232 +/- 35 mm3; p < 0.05). These results suggest that adrenomedullin increases rCBF and prevents ischemic brain injury, partly by increasing the collateral circulation.

Adrenomedullin↗
PubMed1997

Vasodilator effects on canine basilar artery induced by intracisternal interleukin-1 beta.

The effect of interleukin-1 beta (IL-1 beta) on a cerebral artery was investigated in anesthetized dogs. Intracisternal administration of IL-1 beta (0.03 and 0.3 micrograms) dilated the canine basilar artery in a dose-dependent manner, without affecting systemic blood pressure or heart rate. The increase in diameter induced by 0.3 micrograms of IL-1 beta was 28.4% +/- 13.4% of control at 2 hours and was inhibited by 30 micrograms of the IL-1 beta receptor antagonist, zinc protoporphyrin (4.5% +/- 13.5%, P < 0.05). Interleukin-1 beta did not affect the concentration of nitric oxide metabolites in CSF. However, there was an increase in the concentration of eicosanoids in CSF, and the elevation of 6-keto-PGF1 alpha paralleled the vasodilation. Pretreatment with 30 micrograms of the selective inducible cyclooxygenase (COX-2) inhibitor NS-398 also inhibited the IL-1 beta-induced vasodilation significantly (5.9% +/- 9.4% at 2 hours, P < 0.01). Western blot analysis revealed the expression of a 68-kD COX-2-like protein in basilar artery extracts. These findings suggest that the IL-1 beta-induced vasodilator effect is linked to the prostaglandin cascade, predominantly to prostaglandin I2, by induction of COX-2, but not to the stimulation of nitric oxide metabolism.

Animals↗
PubMed1997

Characterization of tumor-infiltrating T lymphocytes in B-cell lymphomas of mucosa-associated lymphoid tissue.

B-cell lymphomas of mucosa-associated lymphoid tissue invariably contain large numbers of reactive tumor-infiltrating T cells. In the stomach, these lymphomas develop secondary to Helicobacter pylori infection, and clinical and in vitro studies have shown that their growth depends on help provided by H. pylori-specific T cells. In this study we characterized tumor-infiltrating T cells in low- and high-grade B-cell lymphomas of mucosa-associated lymphoid tissue using immunohistochemistry. In most cases, CD4+ T cells dominated and almost all T cells were CD45RO+ memory cells. In 11 of 13 cases studied, the proliferating T cells were CD4+ and no proliferation was observed in the CD8+ subset. In low-grade lymphomas, between 7 and 24% of T cells expressed CD40L whereas no CD40L expression was observed in the majority of high-grade tumors. Examination of homing receptor profile showed that both alpha 4 beta 7 integrin+ and L-selectin+ T cells were present. Examination of T cell diversity by a panel of antibodies against different T-cell receptor V beta regions and by analysis of T-cell receptor genes using polymerase chain reaction suggested that the T cells in these tumors were polyclonal. These results show that low-grade B-cell lymphomas of mucosa-associated lymphoid tissue contain a significant population of activated helper T cells that may be important in supporting tumor growth.

Aged↗
PubMed1997

Expression of lymphocyte homing receptors and vascular addressins in low-grade gastric B-cell lymphomas of mucosa-associated lymphoid tissue.

In this study, we examined lymphocyte homing receptor and vascular addressin expression in a case of primary gastric B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) with a secondary intestinal spread. We compared the findings with that observed in B cells of normal MALT and MALT acquired as a consequence of Helicobacter pylori-associated gastritis and other low-grade gastric B-cell MALT lymphomas. The neoplastic B cells in the gastric tumor were alpha 4 beta 7-, CD62L+, whereas the intestinal secondary was alpha 4 beta 7+, CD62L-. Incubation of isolated tumor cells from the stomach by H. pylori generated T-cell-dependent proliferation of neoplastic B cells and induced expression of alpha 4 beta 7 integrin similar to the intestinal tumor. These observations indicate that reversal of homing receptor profile in the gastric tumor by antigen specific stimulation may be responsible for secondary intestinal dissemination. In normal stomach and normal MALT, alpha 4 beta 7 and CD62L expression reflected the differentiation of the B cell. Plasma cells were alpha 4 beta 7+, CD62L-, whereas a subset of memory B cells were alpha 4 beta 7-, CD62L+. Homing receptor expression in MALT lymphoma B cells was heterogeneous, however, in line with their memory B-cell phenotype in the majority of cases, the neoplastic B cells were alpha 4 beta 7-, CD62L+. Neoplastic plasma cells were always alpha 4 beta 7+, CD62L-. The venules in normal gastric mucosa expressed mucosal addressin cell adhesion molecule-1 but not peripheral lymph node addressin. In normal MALT, H. pylori-associated follicular gastritis and MALT lymphomas high endothelial venules coexpressed mucosal addressin cell adhesion molecule-1 and peripheral lymph node addressin. These findings suggest expression of lymphocyte homing receptors by B cells and vascular addressins by mucosal venules are similar in normal MALT and MALT lymphomas, and factors controlling normal mucosal B-cell traffic are also operational in MALT lymphomas.

Antigens, Surface↗
PubMed1996

Demonstration of local clonality of mucosal T cells in human colon using DNA obtained by microdissection of immunohistochemically stained tissue sections.

Intraepithelial lymphocytes have been shown to be oligoclonal and to be disseminated widely along the human intestine. However, studies using monoclonal antibodies have suggested that superimposed on the widespread clones, there is local variability in the mucosal T cell population. We have investigated the possibility that local dominant clones of T cells are present in the colonic mucosa by polymerase chain reaction (PCR) amplification of T cell receptor beta chain junctional regions using DNA extracted from microdissected fragments of tissue sections. Colon from two right hemicolectomy specimens was sampled at 7-cm intervals. Adjacent areas of mucosa were microdissected from sections from each colon sample. When the PCR products were separated according to size on polyacrylamide gels, bands of identical size were often observed when DNA extracted from adjacent fragments of mucosa had been used. Different bands were present when the different samples of colon had been studied. Sequencing of the PCR products confirmed that clonally related T cells were present in adjacent areas of mucosa, whereas different clones dominated at distant sites. DNA extracted from cells microdissected from the T cell zone of Peyer's patch was treated identically. The sequences obtained from the Peyer's patch, as expected, were diverse. However, one of the sequences identified was identical to that of one of the clones in the colon, implying that this clone was either trafficking through the Peyer's patch or possibly originated from the Peyer's patch. In this study, we also identified the Peyer's patches as a site of proliferation of CD4+ T cells. No T cell division was observed in the lamina propria. The molecular and immunohistochemical observations together support the hypothesis that the Peyer's patches are a source of mucosal T cells.

Adenocarcinoma↗
PubMed1996

Effect of the prostacyclin analogue, iloprost, on infarct size after permanent focal cerebral ischemia.

This investigation was undertaken to study the effect of iloprost, a stable analogue of prostacyclin, on infarct size after permanent focal cerebral ischemia in the rabbit. Forty-two adult rabbits were subjected to left middle cerebral artery occlusion via the transorbital route. Fourteen rabbits received an intravenous (i.v.) infusion of 30 micrograms/kg iloprost, 7 rabbits received an i.v. infusion of 10 micrograms/ kg, and 9 rabbits received an i.v. infusion of 20 micrograms/kg iloprost. Twelve rabbits received an intravenous infusion of saline. Treatment with iloprost started immediately after middle cerebral artery occlusion and continued for 1 h. After killing the animals, brains were removed and five coronal slices were incubated in a 2,3,5-triphenyltetrazolium chloride solution to determine the infarct size. Treatment with 30 micrograms/kg iloprost significantly reduced the infarct size compared with treatment with saline (3.49 +/- 2.79% vs. 9.03 +/- 4.26%, P < 0.001), but the lower doses of iloprost did not have a beneficial effect on the size of the infarct. These results suggest that intravenous iloprost treatment after occlusion has a highly protective effect without any side effects such as hypotension.

Animals↗
PubMed1995

The effects of nisoldipine on carotid artery stiffness and left ventricular functions.

Doppler echocardiographic determination, left ventricular (LV) fractional shortening (FS), cardiac output (CO), diastolic function parameter (E/A ratio) and carotid artery pulse wave velocity and stiffness were evaluated in 36 patients with essential hypertension before and after nisoldipine treatment. Blood pressure decreased significantly, and carotid artery width and fractional shortening increased significantly following nisoldipine administration (p < 0.0001). Carotid artery pulse wave peak velocity did not change following the treatment period (p > 0.05). In conclusion, short term nisoldipine administration improved blood pressure and LV systolic function, whereas LV diastolic function and carotid artery stiffness did not change. Nisoldipine did not alter serum biochemical parameters, including cholesterol, triglyceride, HDL-cholesterol, and LDL-cholesterol (p > 0.05). Only one patient manifested symptoms of hypotension as an adverse effect of the drug.

Adult↗
PubMed1993

An endodermal sinus tumor of the head and neck region.

A 2-year-old patient with a recurrent endodermal sinus tumor of the nasopharynx is presented. After the first attempt to surgically excise the tumor it recurred, causing upper airway obstruction within 2 months. Combined treatment with surgery, radiotherapy and chemotherapy resulted in a disease-free survival of four years.

Child, Preschool↗
PubMed1993

Immunoglobulin specificity of low grade B cell gastrointestinal lymphoma of mucosa-associated lymphoid tissue (MALT) type.

The specificity of the tumor cell immunoglobulin in three cases of low grade B cell gastrointestinal mucosa-associated lymphoid tissue (MALT) lymphoma has been studied. Using anti-idiotypic antibodies to detect the reactivity of tumor immunoglobulin in tissue sections from the patients and other individuals, we observed specificity for normal tissue components in all three cases studied. Reactivity in one case was with follicular dendritic cells, in the second case with a novel antigen on mucosal post capillary venules, and, in the third case, a broad pattern of reactivity was observed. This study suggests that autoimmunity may play a role in the pathogenesis of gastric lymphoma.

Antibodies, Anti-Idiotypic↗
PubMed1992

Effects of fibrin adhesive material (Tissucol) application on furcation defects in dogs.

A histological study was conducted to evaluate the effects of fibrin adhesive material (FAM) application on periodontal healing in seven experimental dogs. Bilateral class III furcation defects were surgically created at the second and third premolars, then orthodontic wires were placed around the teeth to induce periodontitis. Six weeks later, the wires were removed and the defects were treated by either surgery alone or surgery plus FAM application. A total of 21 specimens were obtained for histological and histometrical analysis on days 7, 21 and 42. The Mann-Whitney U test showed significantly more new attachment and bone regeneration in the FAM-treated group compared to the control (p less than 0.05). Surgery plus FAM application in the treatment of class III furcation defects seemed to be effective in promoting connective tissue attachment and bone regeneration.

Alveolar Process↗
PubMed1989

Immunoproliferative small-intestinal disease. An immunohistochemical study.

We performed a detailed histological and immunohistological study on both fresh-frozen and paraffin-embedded tissue from full-thickness jejunal biopsy specimens taken from three patients with immunoproliferative small-intestinal disease (IPSID). In all three patients, the mucosal infiltrate consisted of "centrocyte-like" (CCL) cells forming lymphoepithelial lesions and plasma cells. In one patient, the mucosal infiltrate was strikingly follicular. Immunohistochemistry showed alpha 1 heavy chain, but no light chain, in the perinuclear space and cytoplasm of the CCL cells and in the plasma cells. In two patients, the plasma cells (but not the CCL cells) also contained alpha 2 heavy chain. In the case showing a follicular pattern, the extrafollicular CCL cells and most of the cells within the mucosal follicles expressed alpha 1 heavy chain, but a minor and variable population of cells expressed polytypic IgM. The dendritic reticulum cells stained for alpha 1 (but not alpha 2) heavy chain, mu chain, and both light chains. In all cases, the CCL cells did not stain for common acute lymphoblastic leukaemia antigen (CALLA); in the follicles, CALLA negative cells displaced a residual CALLA-positive population to the periphery and merged with the CALLA negative cells outside the follicles. These findings confirm the homology between IPSID and low-grade B-cell "Western" lymphomas arising in mucosa-associated lymphoid tissue; they suggest that the follicular pattern sometimes seen in these lymphomas is caused by selective colonization of reactive follicles by CCL tumor cells.

Adolescent↗
PubMed1989

Histopathological changes in adult cryptorchid testes.

The histological specimens of 73 patients who presented with undescended testes after puberty were re-evaluated. None of the specimens revealed carcinoma in situ but in the specimens of 5 patients severe atypia was detected. None of the patients, including 5 with severe atypia, has shown any evidence of invasive testicular tumour during follow-up.

Adolescent↗