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Biomedical subjects

M Clark

Publications and source records attributed to M Clark.

14 recordsLinked to original sources

Killing of human leukaemia/lymphoma B cells by activated cytotoxic T lymphocytes in the presence of a bispecific monoclonal antibody (alpha CD3/alpha CD19).

Bispecific antibodies (BsAb) can be used to retarget T cells irrespective of their specificity to certain target cells inducing target cell lysis. We have tested the efficacy of the BsAb SHR-1, directed against the T cell antigen CD3 and the B cell antigen CD19 to induce (malignant) B cell kill by T cells as measured in a 51Cr-release assay. Two cytotoxic T cell clones (CTL), expressing TCR alpha beta or TCR gamma delta, were effective in killing CD19 expressing B cell lines at different stages of differentiation in the presence, but not in the absence, of the BsAb. CD19- target cells were not killed. Fresh CD19+ leukaemia/lymphoma cells were also efficiently killed by SHR-1 preincubated CTL clones. In addition, phytohaemagglutinin (PHA) or CD3-activated IL-2 expanded peripheral blood mononuclear cells (PBMC) of normal donors did so after 2 weeks of stimulation. A concentration of 100 ng/ml of the BsAb was sufficient to obtain optimal lysis of all target cells tested. These results show that fresh human leukaemia/lymphoma cells, freshly derived from active lymphoblastic leukaemia (ALL) as well as non-Hodgkin's lymphoma (NHL) patients, can be effectively killed in the presence of this BsAb by activated T cells.

Animals

Expression of receptors for atrial natriuretic peptide on the murine bone marrow-derived stromal cells.

Atrial natriuretic peptide (ANP) receptors were identified on both murine bone marrow-derived stromal cell lines A-3 and ALC and primary cultured cells using [125I]ANP binding assays and Northern blot analyses. The binding of [125I] ANP to the stromal cells was rapid, saturable, and of high affinity. The dissociation constants between ANP and its receptors on these cells showed no difference among cell types, while maximal binding capacity values were different among cell types. Competitive inhibition of [125I]ANP binding with C-atrial natriuretic factor, specific for ANP clearance receptor (ANPR-C), revealed that most of [125I]ANP-binding sites corresponded to ANPR-C. Northern blotting data corroborated that bone marrow-derived stromal cells expressed ANPR-C. However, in ALC cells, ANP biological receptors (either ANPR-A or ANPR-B), the mol wt of which is approximately 130K, were detected, and cGMP was accumulated after stimulation with ANP. On the other hand, in another stromal cell clone, A-3 cells, the expression of biological receptor was not detected in the affinity cross-linking and competitive inhibition experiments using [125I]ANP. However, A-3 cells accumulated cGMP by responding to ANPR-B-specific ligand, C-type natriuretic peptide. These results suggest that ALC cells equally express ANPR-A and ANPR-B, while A-3 cells express ANPR-B dominantly. Although the physiological roles of these receptors in the bone marrow is still not resolved, ANP is expected to play a role in the regulation of stromal cell functions in bone marrow.

Animals

Detection of deep venous thrombosis by impedance plethysmography.

Ninety-eight limbs in sixty-seven patients supected of having lower extremity deep venous thrombosis were evaluated by physical examination, venous impedance plethysmography (IPG), and venography. Diagnosis based on physical signs commonly associated with deep venous thrombosis was false-positive in 43 to 66 per cent and false-negative in 26 to 73 per cent when compared with evidence obtained by venography. The overall accuracy of IPG was 94 per cent, with false-positive results occurring in 10 per cent and false-negative results in 4 per cent. IPG is sufficiently accurate to be considered a reliable screening test for lower extremity deep venous thrombosis.

Adolescent

Macrophages in experimental and human brain tumors. Part 1: Studies of the macrophage content of experimental rat brain tumors of varying immunogenicity.

Although the presence of lymphoreticular cells within tumors has been recognized for over 100 years, it is only within the last decade that the concept has arisen that standard histological examination techniques may lead to an underestimation of the true extent of tumor infiltration by lymphoreticular cells, and particularly by macrophages. The macrophage content of certain systemic tumors has been correlated with their immunogenicity and growth characteristics. Since the central nervous system is to some extent an "immunologically privileged site" and contains within it specialized reticuloendothelial cells called microglia, the authors determined the macrophage content of three rodent brain-tumor cell lines, and attempted to correlate this macrophage content with their immunogenicity and growth characteristics. Their findings indicate a direct correlation between the immunogenicity and macrophage content of these three neural tumor cell lines.

Animals

Macrophages in experimental and human brain tumors. Part 2: studies of the macrophage content of human brain tumors.

The authors have analyzed 47 tumors of the central nervous system (11 glioblastomas, nine meningiomas, three medulloblastomas, 12 assorted primary neural tumors, and 12 brain metastases) for their content of macrophages. Cell suspensions were prepared by enzymatic digestion and macrophages were quantitated by IgGEAC rosette formation. Adsorption of sensitized indicator cells (EA) to sections of tumor was used as a measure to determine the distribution of IgGFc receptor-positive cells within the tumors and to serve as a control for selective release of IgGFc receptor-positive cells by enzyme digestion. The 11 glioblastomas had a mean macrophage content of 45% (range: 8% to 78%), the nine meningiomas had a mean of 44% (range: 5% to 81%), the three medulloblastomas a mean of 6% (range 2% to 15%), and the metastatic tumors a mean of 24% (range: 4% to 70%). Adsorption of EA demonstrated that IgGFc receptor-positive cells were distributed throughout the tumor mass, although different types of patterns were observed. There was an excellent correlation between the percent of IgGEAC positive cells in suspensions and the extent of EA adsorption to the tumor sections. Compared to systemic neoplasms, most nervous system tumors have a high macrophage content. It is possible that the high macrophage content of brain tumors is related to their immunogenicity, and may be a partial explanation for tha rarity of brain-tumor metastases.

Brain Neoplasms

An assessment of carotid phonoangiography and oculoplethysmography in the detection of carotid artery stenosis.

Carotid phonoangiography (CPA) and oculophlethysmography (OPG) examinations for the detection of extracranial carotid occlusive disease were performed in 308 patients, 103 of whom underwent arch angiography. When correlated with angiographic findings, the overall accuracy of CPA/OPG was 86 per cent. There were 4 per cent false-positive 9.6 per cent false-negative results, and these were further analyzed. Significant carotid bruits demonstrated by CPA strongly suggested the presence of appreciable carotid stenosis. Noninvasive CPA/OPG is an excellent diagnostic tool in patients with non-hemispheric symptoms, in those with asymptomatic bruits, as a screening procedure in potential stroke victims, and for follow-up after cartotid endarterectomy. Caution is advised in relying on this and other noninvasive technics as the sole method for recommending angiography and operative treatment in symptomatic patients.

Adult

Affect, accessibility of material in memory, and behavior: a cognitive loop?

Two studies investigated the effect of good mood on cognitive processes. In the first study, conducted in a shopping mall, a positive feeling state was induced by giving subjects a free gift, and good mood, thus induced, was found to improve subjects' evaluations of the performance and service records of products they owned. In the second study, in which affect was induced by having subjects win or lose a computer game in a laboratory setting, subjects who had won the game were found to be better able to recall positive material in memory. The results of the two studies are discussed in terms of the effect that feelings have on accessibility of cognitions. In addition, the nature of affect and the relationship between good mood and behavior (such as helping) are discussed in terms of this proposed cognitive process.

Affect

Diagnosis of coronary artery disease by estimation of coronary sinus lactate.

In an attempt to assess the value of coronary sinus lactate estimation before and during atrial pacing for the diagnosis of obstructive coronary artery disease, 70 patients with angina were investigated in this way and by selective coronary arteriography. Thirty-five had radiologically normal coronary arteries and 35 had coronary artery disease. When the change in coronary arteriovenous lactate difference was less than 0.09 mmol/l (0.8 mg/100 ml) between the control and the peak atrial pacing sample, the coronary arteries were normal except in one patient who had distal disease of a single vessel. When the change was greater than 0.22 mmol/l (2.0 mg/100 ml) coronary artery disease was always found, and when the change was greater than 0.39 mmol/l (3.5 mg/100 ml) there was always disease of two or three vessels. Unfortunately, the presence or absence of coronary artery disease could not be predicted when the change fell between 0.09 and 0.22 mmol/l (0.8 and 2.0 mg/100 ml). Estimation of coronary sinus lactate before and during atrial pacing can thus frequently distinguish patients with normal coronary arteries from those with coronary artery disease.

Adult

Generation and ethnic identity: a typological analysis.

Data bearing on cognitive acculturation, ethnic behavior, and values were gathered from three generations of Mexican and Japanese Americans. Two dimensions of ethnic behavior were identified and named: Anglo Face and Traditional Orientation. Although subcultures and generations differed in value orientation, the values data did not contribute to the identification of ethnic identity types. Typological analysis using Anglo Face, Traditional Orientation, and Acculturative Balance Scale scores identified six types of ethnic identity, two for each generation. Immigrants differ mainly on whether or not they retain Traditional Orientation; later generations differ mainly on Anglo Face. Although there are large differences between generations in Acculturative Balance, the two types within each generation do not differ.

Acculturation

Development of an instrument to study the sexual relationship of partners during pregnancy.

The development of an objective self-report instrument designed to identify the domain of sexual behaviours during pregnancy is described. The Pregnancy and Sexuality Questionnaire (PSQ) is concerned with sexual interest and arousal and with specific sexual behaviours of partners in a stable heterosexual relationship. Data were obtained two weeks apart from 15 couples presenting to an antenatal class and from two additional females whose partners did not participate. The validity and reliability of the PSQ are considered with particular emphasis on test-retest reliability. The results in general support the reliability of the instrument. The questionable reliability of some items is attributed to the natural sequence of change in sexual behaviours during pregnancy and to the relatively small sample size used. The PSQ appears to be sufficiently robust to be confidently applied both in sexual behaviour research and as an adjunct to clinical practice.

Adult

Glucose-6-phosphate dehydrogenase deficiency and infection: a study of hospitalized patients in Iran.

The Mediterranean variant of glucose-6-phosphate dehydrogenase (G6PD) is functionally deficient and found in a variety of cell types of affected individuals, including both erythocytes and neutrophils. To determine if the presence of this sex-linked gene is associated to any degree with the occurrence of severe bacterial infection, a study of hospitalized male patients in Iran was undertaken. As determined by erythrocyte assay, allele prevalence in male patients with infection was 22% vs. 12% in a patient group matched for the absence of other risk factors for infection and 6% in a second group who had additional risk factors for infection. When the control and patient groups were considered together the difference between the frequency of G6PD deficiency (10.2%) was significantly different from that found in the infected patients (p less than .05). Furthermore, the mean age of infected patients with G6PD deficiency was significantly less than that of infected patients without G6PD deficiency or non-infected control groups. These data suggest that host defenses may be altered in G6PD deficiency so that bacterial infections are more severe. Alternatively, G6PD deficiency and infection might represent concomittant risk factors which lead to hospitalization during bacterial infection. Potential mechanisms by which host defenses might be altered in G6PD deficiency are discussed.

Adult