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Biomedical subjects

A Papadimitriou

Publications and source records attributed to A Papadimitriou.

At least 55 records · Page 3Linked to original sources

"Checkerboard" assessments of periodontal microbiota and serum antibody responses: a case-control study.

BACKGROUND: We explored the association between subgingival microbial profiles and serum IgG responses to periodontal microbiota in relation to clinical periodontal status. METHODS: One hundred thirty-one (131) periodontitis patients aged 29 to 74 years (mean 51.8) were age- and gender-matched with 74 periodontally intact controls (range 26 to 77, mean 49.3). Smoking habits and health history were recorded and assessments of plaque, bleeding on probing, probing depth, and attachment level were performed at 6 sites per tooth on all present teeth, excluding third molars. Subgingival plaque samples were obtained from each tooth in one upper and one lower quadrant (maximum 14 samples/subject; 2,440 samples total) and analyzed with respect to 19 species by means of whole genomic DNA probes. Serum IgG antibodies against the same 19 species were assessed by an immunoassay. RESULTS: Cases displayed an average of 22.7 teeth, 20.3 sites with probing depth > or =6 mm, and 18.9 sites with attachment loss > or =6 mm. Corresponding figures for controls were 27.1, 0.1, and 1.0, respectively. Heavy smoking was 3 times more frequent among cases than controls (32.1% versus 9.6%). Higher levels of Porphyromonas gingivalis, Porphyromonas endodontalis, Prevotella intermedia, Prevotella nigrescens, Prevotella melaninogenica, Bacteroides forsythus, Fusobacterium nucleatum, Treponema denticola, Eubacterium nodatum, Peptostreptococcus micros, and Campylobacter rectus were found in cases and higher levels of Eikenella corrodens, Veillonella parvula, and Actinomyces naeslundii in controls. Cases displayed higher IgG levels against P. gingivalis and Actinobacillus actinomycetemcomitans, while controls displayed higher levels against F. nucleatum, T. denticola, E. nodatum, and Capnocytophaga ochracea. Positive correlations between bacterial colonization and antibody responses were identified for 9 species in controls. In cases, however, statistically significant correlations were observed for only 3 species out of which only one was positive (V. parvula). Both bacterial levels and antibody responses declined in ages over 55 years. A logistic regression employing selected elements of bacterial colonization and antibody responses as independent variables resulted in 81.1% correct diagnosis, with sensitivity of 83.1%, specificity of 77.8%, positive predictability of 86%, and negative predictability of 73.7%. Smoking did not reach statistical significance in this model. CONCLUSION: A combined microbial colonization/antibody response profile can effectively discriminate between periodontitis patients and periodontally intact controls.

Actinomyces↗

Mitochondrial neurogastrointestinal encephalomyopathy: an autosomal recessive disorder due to thymidine phosphorylase mutations.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive disorder defined clinically by severe gastrointestinal dysmotility; cachexia; ptosis, ophthalmoparesis, or both; peripheral neuropathy; leukoencephalopathy; and mitochondrial abnormalities. The disease is caused by mutations in the thymidine phosphorylase (TP) gene. TP protein catalyzes phosphorolysis of thymidine to thymine and deoxyribose 1-phosphate. We identified 21 probands (35 patients) who fulfilled our clinical criteria for MNGIE. MNGIE has clinically homogeneous features but varies in age at onset and rate of progression. Gastrointestinal dysmotility is the most prominent manifestation, with recurrent diarrhea, borborygmi, and intestinal pseudo-obstruction. Patients usually die in early adulthood (mean, 37.6 years; range, 26-58 years). Cerebral leukodystrophy is characteristic. Mitochondrial DNA (mtDNA) has depletion, multiple deletions, or both. We have identified 16 TP mutations. Homozygous or compound heterozygous mutations were present in all patients tested. Leukocyte TP activity was reduced drastically in all patients tested, 0.009 +/- 0.021 micromol/hr/mg (mean +/- SD; n = 16), compared with controls, 0.67 +/- 0.21 micromol/hr/mg (n = 19). MNGIE is a recognizable clinical syndrome caused by mutations in thymidine phosphorylase. Severe reduction of TP activity in leukocytes is diagnostic. Altered mitochondrial nucleoside and nucleotide pools may impair mtDNA replication, repair, or both.

Adult↗

Mutated alpha-synuclein gene in two Greek kindreds with familial PD: incomplete penetrance?

The G209A mutation in the alpha-synuclein gene has been associated with autosomal dominant PD (ADPD) in a family from Contursi, Italy, and three apparently unrelated Greek families. Several groups around the world failed to identify the G209A mutation in a sizable series of familial and sporadic cases of PD. The authors present two additional Greek families with ADPD associated with the G209A mutation. In both families, asymptomatic carriers older than the expected age at onset were found.

Adult↗

Preserved negative patterning and impaired spatial learning in pigeons (Columba livia) with lesions of the hippocampus.

Pigeons (Columba livia) with bilateral electrolytic lesions of the hippocampus and area parahippocampalis were compared with control pigeons on 2 tasks: negative patterning and delayed spatial alternation. Negative patterning demands configural stimulus representations for its successful solution. The only effect of hippocampal lesions on this task was an increased response rate to the rewarded stimuli. On the delayed spatial alternation task, hippocampal birds showed deficits relative to controls. Differences in the results of prior studies on negative patterning appear to be due to different response requirements to the nonreinforced stimuli. These results are consistent with prior work with rats and suggest that the avian hippocampus is essential for spatial memory and response inhibition but is not involved in configural learning.

Animals↗

Purging of mammary carcinoma cells during ex vivo culture of CD34+ hematopoietic progenitor cells with recombinant immunotoxins.

Tumor cells have been found in autologous hematopoietic cell transplants used after high-dose chemotherapy. To specifically eliminate contaminating mammary tumor cells during ex vivo expansion of CD34+ hematopoietic progenitor cells, we used recombinant immunotoxins (ITs) directed against cell-surface antigens expressed on mammary carcinoma cells. ITs were expressed from fusion cDNAs combining a single-chain antibody fragment (scFv) directed against the Erb-B2 or epidermal growth factor (EGF) receptors with a truncated Pseudomonas exotoxin A fragment devoid of its cell-binding domain. CD34+ hematopoietic progenitor cells did not express Erb-B2 and EGF receptors as detected by Western blotting. Ex vivo expansion of total hematopoietic cells or of colony-forming cells from CD34+ progenitors in the presence of stem-cell factor (SCF), interleukin-1 (IL-1), IL-3, IL-6, and erythropoietin (Epo) was not affected when ITs were added to the cultures. In contrast, MDA-MB 453 and MCF-7 mammary carcinoma cells were depleted in a dose- and time-dependent manner by more than 3 log in coculture with CD34+ cells over a period of 7 days in the presence of 100 to 1,000 ng/mL of anti-Erb-B2 IT. This included elimination of the subpopulations with regrowth potential. Similarly, addition of either anti-Erb-B2 or anti-EGF receptor ITs to primary breast cancer cells isolated from patients with metastatic disease resulted in elimination of cytokeratin-positive cells in seven of seven samples. ITs are highly efficient and convenient to use for the depletion of mammary tumor cells during ex vivo expansion of hematopoietic progenitor-cell autografts.

ADP Ribose Transferases↗

The variants of reading epilepsy. A clinical and video-EEG study of 17 patients with reading-induced seizures.

We present the clinical and electrographic data of 17 patients with reading-induced seizures documented with ictal video-EEG studies during provocation with language related tasks. The median age at onset was 15 years (range 11-22 years) and the male:female ratio was 2.4. Fourteen patients had no spontaneous seizures of any type while the remaining three had infrequent generalized tonic-clonic seizures during nocturnal sleep. Two distinct electroclinical ictal patterns were confirmed on video-EEG analysis. (i) Fifteen patients had reading-induced jerks which invariably involved the region of the jaw but also included the upper limbs in five of them. Ictal EEG discharges were noted in 12 patients; these were brief but varied in terms of morphology and spatial distribution, with a clear tendency for left-sided predominance. All but one of these patients had similar myoclonic seizures induced by linguistic activities other than reading, the phenomenon probably justifying the term 'language-induced epilepsy'. Some patients had evidence of transient cognitive impairment associated with the reading-induced jaw or limb jerks. Three patients had a sibling with reading epilepsy but there was no other family history of epileptic seizures. (ii) Two patients had reading-provoked paroxysmal alexia without motor symptoms, associated with prolonged focal ictal EEG abnormalities. Reading provoked a subclinical, continuous and reproducible EEG activation over the left posterior temporal area. We propose that ictogenesis in reading or language-induced epilepsy is based on the reflex activation of a hyperexcitable network that subserves the function of speech and extends over multiple cerebral areas on both hemispheres. The parts of this network responding to the stimulus may, secondarily, drive the relative motor areas producing the typical regional myoclonus. This network hyperexcitability can be genetically determined and its clinical expression is age-related.

Adolescent↗

Cat scratch disease in Greece.

An indirect fluorescent antibody test for Bartonella henselae, B quintana, and B elizabethae was performed in all 18 children who presented to our paediatric outpatient clinic with cat scratch disease over a six year period. Serum samples were taken on admission, after 15 days, and after six months. Diagnosis was confirmed in 15 patients (83%) and was based on seroconversion or a fourfold change of the antibody titre to B henselae in 12 patients and on a single high titre (> 128) in three patients. Lymphadenopathy was present in all patients, erythema nodosum in one, osteomyelitis in one, hepatitis in one, transverse myelitis in one, and liver or spleen granulomata, or both, in three patients. Cat scratch disease developed in autumn or winter in 12 patients. All had a history of physical contact with a cat. Our study shows that our clinical suspicion was accurate in the diagnosis of cat scratch disease in a high percentage of patients presenting to a hospital and that indirect fluorescent antibody testing for B henselae is a useful diagnostic tool.

Adolescent↗

Partial depletion and multiple deletions of muscle mtDNA in familial MNGIE syndrome.

OBJECTIVE: To describe the unique combination of partial depletion and multiple deletions of mitochondrial DNA (mtDNA) on muscle DNA analysis of three siblings with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). BACKGROUND: MNGIE is a relatively homogeneous autosomal recessive disorder characterized by gastrointestinal dysmobility, ophthalmoparesis, peripheral neuropathy, mitochondrial myopathy, and altered white matter signal at brain imaging. Muscle multiple mtDNA deletions have been found in about half of the described cases. METHODS: We studied three affected siblings (two were monozygotic twins) born to nonconsanguineous parents. Muscle mtDNA was investigated by quantitative Southern and Slot blot techniques and by PCR analysis. Morphologic confirmation in the muscle tissue was achieved by using in situ hybridization with a mtDNA probe complementary to an undeleted region and by DNA immunohistochemistry. RESULTS: All three patients showed ragged red (RRF) and cytochrome c oxidase-negative fibers, as well as partial deficiency of complexes I and IV. Southern and Slot blot analyses showed mtDNA depletion in all patients. Multiple mtDNA deletions were also detected by PCR analysis. In situ hybridization demonstrated an overall signal weaker than controls, with a relatively higher signal in RRF. Antibodies against DNA showed a decreased cytoplasmic network. CONCLUSIONS: The muscle histopathology and respiratory chain enzyme defects may be accounted for by the decreased mtDNA amount and by the presence of mtDNA deleted molecules; however, relative levels of mtDNA seem to correlate with life span in these patients. The combination of partial depletion and multiple deletions of mtDNA might indicate the derangement of a common genetic mechanism controlling mtDNA copy number and integrity.

Biopsy↗

A rapidly progressive adolescent-onset oculopharyngeal somatic syndrome with rimmed vacuoles in two siblings.

We describe 2 Greek siblings who developed a rapidly progressive oculopharyngeal somatic syndrome, at the ages of 11 and 14 years, with muscle biopsies showing rimmed vacuoles and, in 1 case, cytoplasmic and intranuclear tubulofilamentous inclusions 25 nm in diameter. Although a similar pattern of muscle involvement with rimmed vacuoles is described in autosomal dominant oculopharyngeal muscular dystrophy, the age of onset, the rapid progression of the symptoms, and the nature of the tubulofilaments distinguish this as a separate entity.

Adolescent↗

Vaginal intraepithelial neoplasia (VAIN) following hysterectomy in patients treated for carcinoma in situ of the cervix.

OBJECTIVE: To determine the number of patients with carcinoma in situ of the cervix treated by hysterectomy who proceeded to develop vaginal intraepithelial neoplasia (VAIN) and define whether the subsequent development of VAIN justifies intensive cytology and colposcopy follow-up. MATERIALS AND METHODS: Nine hundred and ninety-three women who were subjected to hysterectomy with CIN, (793 patients had completed 10 years of cytology and colposcopy follow-up) were identified. RESULTS: Forty-one patients with VAIN presented with CIN 3 after hysterectomy. The upper one half of the vagina was the area more affected. The middle age group developed VAIN in the shortest time. Atypical Cells (ASCUS) were found in 42% of these patients. Colposcopy revealed VAIN involving the vault angles of the suture line in 54% of the cases. In 51% of the cases the grade of vaginal abnormality was the same as that of the original lesion in the cervix. CONCLUSION: With such data we would propose screening over a 5-year period. Follow-up should also include colposcopic review during every examination.

Adult↗

Pre-tRNA 3'-processing in Saccharomyces cerevisiae. Purification and characterization of exo- and endoribonucleases.

We investigated ribonucleases from Saccharomyces cerevisiae which are active in pre-tRNA 3'-processing in vitro. Two pre-tRNA 3'-exonucleases with molecular masses of 33 and 60 kDa, two pre-tRNA 3'-endonucleases with molecular masses of 45 kDa/60 kDa and 55 kDa and 70-kDa 3'-pre-tRNase were purified from yeast whole cell extracts by several successive chromatographic purification steps. The purified exonucleases are non-processive 3'-exonucleases that catalyze the exonucleolytic processing of 3'-trailer sequences of pre-tRNAs to produce mature tRNAs. The 45-kDa/60-kDa 3'-endonuclease is tRNA-specific and catalyzes the processing of pre-tRNAs in a single endonucleolytic step. Two isoenzymes of this activity (p45 and p60) were identified by chromatography. The second endonuclease, p55, is dependent on monovalent ions and cleaves about three nucleotides downstream the mature 3'-end. All of the purified 3'-pre-tRNases accept homologous as well as heterologous pre-tRNA substrates. Pre-tRNAs carrying a 5'-leader are processed with almost the same efficiency as those lacking this 5'-leader. Mature tRNAs carrying the CCA 3'-sequence and tRNA pseudogene products carrying mutations in the mature domain are processed by the 3'-exonucleases, not by the 3'-endonucleases. The specific endonuclease p45/p60 discriminates between UUUOH as a 3'-flank, which is cleaved, and the CCA 3'-end of mature tRNAs, which is not cleaved. This study suggests that several 3'-pre-tRNases are active on tRNA precursors in vitro and might therefore in pre-tRNA 3'-processing in yeast, partly in a cooperative manner.

Base Sequence↗

Reduced brain stem excitability in mitochondrial myopathy: evidence for early detection with blink reflex habituation studies.

Blink reflex (BR) was studied in 17 patients with histochemically and genetically confirmed mitochondrial myopathy (MM). Fourteen patients had chronic progressive external ophthalmoplegia (CPEO) associated with a mild to moderate craniosomatic myopathy without any symptoms or signs of central nervous system (CNS) involvement, 2 myoclonic epilepsy with ragged red fibers syndrome, and 1 Kearns-Sayre syndrome. The mean latencies of the early (R1) and late (R2) responses were prolonged (P < 0.01 and P < 0.001, respectively), and the corresponding amplitudes decreased (P < 0.001). Increased habituation of the reflex was clearly observed in 10 out of 14 patients tested (71.4%), 9 of whom presented CPEO. These findings suggest that the brain stem reticular network is in a state of basal inhibition which is presumably due to a subclinical impairment of the cerebral cellular metabolism. Multimodal evoked potentials revealed abnormalities suggestive of CNS involvement in 7 out of 17 patients (41.2%), 4 of whom had CPEO. These observations document the validity of BR in detecting clinically silent brain stem impairment in patients with apparently pure MM and provide important clues for a further understanding of the underlying pathophysiology.

Adolescent↗

The influence of Coenzyme Q10 on total serum calcium concentration in two patients with Kearns-Sayre Syndrome and hypoparathyroidism.

Two patients with Kearns-Sayre Syndrome and hypoparathyroidism were treated with alfacalcidol (1a-OH D3) and total serum calcium concentration remained within normal range for a long period. After two months of combined therapy with Coenzyme Q10 (CoQ10), hypercalcemia was noticed and as a result, 1a-OHD3 was gradually discontinued. Normal total serum calcium concentration was obtained with CoQ10 monotherapy while the replacement of CoQ10 with placebo led to hypocalcemia. The mechanism of action of CoQ10 is difficult to explain. Since the parathormone level remained unchanged during CoQ10 or placebo therapy, we speculate that the capacity of producing an active form of vitamin D in mitochondria of proximal tubules was restored by CoQ10 therapy.

Calcium↗

Myoglobinuria due to quail poisoning.

Quail poisoning is known to produce an acute myoglobinuric syndrome. The cause of this syndrome is still unknown. It has been suggested that a toxic effect or a genetic sensitivity plays a major role. Ten patients with a history of quail poisoning were examined to determine their present state and the course of the disease. A muscle biopsy was performed in 2 of these patients who complained of muscle cramps after exercise. The activities of several glycolytic mitochondrial and lipolytic enzymes were estimated. In all 10 patients the physical examination, electromyogram findings and conduction velocities were normal. Serum levels of CK, aldolase and lactic acid were also within normal range. In the 2 patients with cramps, all enzyme activities were normal in muscle tissue. Our findings possibly exclude a preexisting enzyme defect as a cause of myoglobinuria in quail poisoning. Considering that 4 of our patients continued the consumption of quails without further problems, we suggest that the major factor contributing to quail poisoning must be toxic.

Adolescent↗

Power Doppler ultrasound: a potentially useful alternative in diagnosing pelvic pathologic conditions.

INTRODUCTION: To evaluate the efficacy of power Doppler sonography in depicting soft-tissue hyperemia in endometriosis and other pelvic inflammatory conditions thirty-one patients with predominantly pelvic inflammatory symptoms were evaluated. MATERIALS AND METHODS: Power Doppler sonography at 5 MHz and a pulse repetition frequency of 800 Hz was used. All the women underwent laparoscopy after 10 days. RESULTS: Soft-tissue hyperemia was seen on power Doppler sonograms in 22 of the symptomatic patients. In these women Doppler demonstrated a diffused "blush" of almost or the entire symptomatic sites. Specificity was 52.4%, sensitivity 47.1% and the positive predictive value was 53.2%. CONCLUSION: Power Doppler sonography showed hyperperfusion in many cases associated with pelvic inflammatory pathology. It is a potentially useful adjunct to standard color Doppler imaging in depiction of vascular flow.

Adult↗