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Biomedical subjects

A Demetriou

Publications and source records attributed to A Demetriou.

13 recordsLinked to original sources
PubMed2025

HLA-E and NKG2A Mediate Resistance to BCG Immunotherapy in Non-Muscle-Invasive Bladder Cancer.

Bacillus Calmette-Guérin (BCG) is the first-line therapy for high-grade non-muscle-invasive bladder cancer (NMIBC), yet many patients experience recurrence due to immune evasion. We identify HLA-E and NKG2A as mediators of adaptive resistance involving chronic activation of NK and T cells in BCG-unresponsive tumors. Prolonged IFN-γ exposure enhances HLA-E and PD-L1 expression on recurrent tumors, accompanied by the accumulation of NKG2A+ NK and CD8 T cells. HLA-Ehigh tumor cells preferentially cluster near CXCL12-rich stromal regions with dense effector cell presence, underscoring a spatially segregated tumor architecture. Although cytotoxic lymphocytes retain effector potential, their activity is restrained by HLA-E/NKG2A and PD-L1/PD-1 pathways located in their immediate neighborhood within the bladder tumor microenvironment. These data reveal a spatially organized immune escape program that limits anti-tumor immunity. Our findings support dually targeting NKG2A and PD-L1 checkpoint blockade as a rational, bladder-sparing strategy for patients with BCG-unresponsive NMIBC.

BCG-unresponsive↗
PubMed1996

Neurological and psychological sequelae in transplant recipients after bridging with the bioartificial liver.

Prior to the advent of the bioartificial liver there was little hope to offer the families of comatose patients unless an organ could be found immediately, or xenografting was attempted. The elevated intracranial pressure that develops is more life-threatening than prolonged bleeding times. Over a 2-year period, nine patients were bridged to transplantation using the BAL to keep them neurologically intact prior to surgery. The goal is to maintain the ICP less than 20 mmHg in adults and between 10 and 15 mmHg in children, so that the cerebral perfusion pressure remains above 50 mmHg. The first patients, a 35-year-old woman, arrived in stage II coma. The second patient, a 10-year-old boy in stage IV coma, had decerebrate posturing and anisocoria. The third patient, an 18-year-old girl, had an ICP of 28 mmHg with decerebrate posturing and disconjugate gaze. The fourth patient, a 34-year-old male, had an ICP of > 38 mmHg. The fifth patient, a 24-year-old male, had fixed dilated pupils. The sixth patient, a 50-year-old woman, had readings to 52 mmHg. The seventh patient, a 48-year-old male, had postoperative numbness in his fingertips that remitted. The eighth patient, a 31-year-old female, had decerebrate posturing and an ICP of 64 mmHg transiently. The ninth patient, a 52-year-old woman, had decerebrate posturing with a peak ICP of 50 mmHg. All nine patients survived.

Adolescent↗
PubMed1993

The architecture and dynamics of developing mind: experiential structuralism as a frame for unifying cognitive developmental theories.

This Monograph presents a theory of cognitive development. The theory argues that the mind develops across three fronts. The first refers to a general processing system that defines the general potentials of mind to develop cognitive strategies and skills. The second refers to a hypercognitive system that governs self-understanding and self-regulation. The third involves a set of specialized structural systems (SSSs) that are responsible for the representation and processing of different reality domains. There are specific forces that are responsible for this organization of mind. These are expressed in the Monograph in terms of a set of five organizational principles. The developmental course of the major systems is outlined. Developmental change is ascribed by the theory to the interaction between the various systems. Different types of development require different change mechanisms. Five studies are presented that provide empirical support for these postulates. Study 1 demonstrated the organizational power of principles and SSSs. Study 2 showed that the SSSs constrain the effect of learning. Study 3 established that the hypercognitive system does function as the interface between tasks and SSS-specific processes or between SSSs and general cognitive functions such as attention and memory. Study 4 investigated the relations between one of the components of the processing system, storage, and two different SSSs expressed via two different symbolic systems, namely, the numeric and the imaginal. Finally, Study 5 examined the interaction between the components of the processing system and the relations between each of these components and one SSS, namely, the quantitative-relational SSS. The theoretical implications of these studies with regard to general issues, such as the nature of representation, the causation of cognitive change, and individual differences in cognitive development, are discussed in the concluding chapter.

Adolescent↗
PubMed1992

Loss of keratin expression in anaplastic carcinoma cells due to posttranscriptional down-regulation acting in trans.

Rat keratin K5 and vimentin complementary DNAs have been isolated, identified, and used to study keratin and vimentin expression as markers for cell differentiation. Isologous rat neoplastic epithelial cell lines used were based on a clonal benign epithelial line (A5P/B10) and a clonal anaplastic malignant derivative line (T952/F7). Stable cytoplasmic mRNA was detected for keratin but not vimentin in the benign cells. The anaplastic derivative cells expressed vimentin but showed a 1000-fold reduction in the keratin message, which nuclear run-on assays identified as being due to posttranscriptional down-regulation. An identical pattern of posttranscriptional down-regulation was found in independent malignant somatic cell hybrids of the benign and anaplastic cells. trans-acting regulatory mechanisms implicated in posttranscriptional (pretranslational) keratin down-regulation in these anaplastic malignant cells may play a role in the apparent loss of differentiation evident in tumor progression.

Animals↗
PubMed1990

Pathological effects of pellagra on the esophagus.

This study determined the pathological effects of niacin/tryptophan deficiency on the esophagus. Nine patients with severe clinical pellagra and 31 age- and sex-matched controls were assessed. All pellagrins had an esophagitis varying from severe to mild. The esophagitis improved in five patients following six to seven days of vitamin therapy. The relationship between vitamin deficiencies and esophageal cancer is discussed.

Adult↗
PubMed1989

The person's conception of the structures of developing intellect: early adolescence to middle age.

According to experiential structuralism, thought abilities have six capacity spheres: experimental, propositional, quantitative, imaginal, qualitative, and metacognitive. The first five are applied to the environment. The metacognitive capacity is applied to the others, serving as the interface between reality and the cognitive system or between any of the other capacities. To test this postulate, 648 subjects aged 12 to 40 years, solved eight tasks that were addressed, in pairs, to the first four capacity spheres. One of the tasks in each pair tapped the first and the other the third formal level of the sphere. Having solved the tasks, the subjects were required to rate each pair of tasks in terms of similarity of operations, difficulty, and success of solution. Factor analysis of difficulty and success evaluation scores revealed the same capacity-specific factors as the analysis of performance scores. Factor analysis of similarity scores differentiated between same- and different-sphere pairs. Analysis of variance showed that difficulty and success evaluation scores preserved performance differences between the first and the third formal tasks. Cognitive level, age, socioeconomic status, and sex were related to the metacognitive measures in ways similar to their relations to performance measures. These findings were integrated into a model aimed at capturing real-time metacognitive functioning.

Adolescent↗
PubMed1986

Rectal manifestations of pellagra.

Twenty (44%) of 45 patients with cutaneous pellagra had diarrhoea. Inflammation was seen on sigmoidoscopy in 42 and was severe in 5 (11%), moderate in 4 (9%) and mild in 33 (73%). Six patients (13%) had perianal excoriation. Rectal biopsies taken in all cases showed extensive ulceration in 1 case, moderate to severe inflammation in 16 (36%) and mild inflammation in 18 (40%). Minimal oedema of the lamina propria was seen in 11 (24%) patients. At 5 to 7 days after starting vitamin treatment in nine cases histological changes had returned to normal in 4, improved in 3 and had not changed in 2. Diarrhoea stopped within a week in all cases.

Adult↗
PubMed1978

A case of paragonimiasis.

A 2 1/2-year-old girl recently arrived from eastern Nigeria presented with a soft tissue swelling of the infraclavicular region. Subsequent investigation revealed a cavity in the left lung associated with a small pleural effusion and leucocytosis with pronounced eosinophilia. Clinical and serological findings were compatible with the diagnosis of paragonimiasis. After a course of Bitin-S the chest x-ray returned to normal, the soft tissue changes disappeared, and the eosinophil count fell.

Child, Preschool↗
PubMed1975

Antitumor action of vitamin A in mice inoculated with adenocarcinoma cells.

Vitamin A palmitate was incorporated into a laboratory chow (150,000 IU/kg diet) and fed ad libitum to C3H/HeJ female mice inoculated with 1 times 10-6 C3HBA tumor cells, beginning the day of inoculation. Control female mice of the same strain similarly inoculated were fed the laboratory chow alone. Vitamin A did not affect rate for the first 19 days, after which growth rates were independent of treatment. Vitamin A-treated mice survived for significantly longer times than did control mice.

Adenocarcinoma↗
PubMedDate not supplied

Survey results of transplant patients' attitudes on xenografting.

For centuries, many cultures have described mythical creatures with bodies that combined human and animal features, often the result of violating taboos. This study attempted to investigate the beliefs of transplant patients about xenografting. A survey was given to 100 patients ranging in age from 17 to 74 years old, with 65 men and 35 women, including 72 whites, 18 Hispanics, 5 African Americans, and 4 Asian Americans. The subjects included liver, heart, kidney, lung, and multi-organ transplant patients. The patients were not aware of plans for xenografting at the center under study. Eighty patients agreed with xenografting in an emergency situation. Ten subjects replied, "under no circumstances." Ninety percent believed animal research has advanced medical science. In descending order, the patients preferred human (96%), monkey (44%), mechanical (43%), pig (42%), or dog (34%) organs. Twenty-four patients thought a xenograft would change their appearance, personality, or eating or sexual habits. Twenty patients believed animals have souls. The patients also documented any ethical concerns about xenografting.

Adolescent↗