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Biomedical subjects

M Bennett

Publications and source records attributed to M Bennett.

At least 379 records · Page 21Linked to original sources
PubMed1982

Analysis of low natural killer cell activity in 89Sr-treated mice.

Treatment of mice with the long-lived bone-seeking radioisotope 89Sr results in the selective irradiation and destruction of the bone marrow. This is accompanied by a marked reduction in natural killer cell activity against YAC-1 lymphoma [NK(YAC-1)]. To test for the presence of cellular suppressors of NK(YAC-1) in 89Sr-treated mice, in vitro and in vivo cell mixture protocols were used. In vitro, we did not observe any specific inhibitory effect of spleen cells from 89Sr-treated mice on NK(YAC-1) activity of normal spleen cells. The NK(YAC-1) activity of 89Sr-treated mice, measured in vivo by their ability to clear radiolabeled YAC-1 cells from the lungs, was impaired. However, spleen cells from 89Sr-treated mice, when adoptively transferred with normal spleen cells, failed to inhibit the NK(YAC-1) activity of the latter in the lung clearance assay. Further, when normal spleen cells were injected into 89Sr-treated mice, the ability of the transferred cells to mediate in vivo activity was not suppressed in the 89Sr-treated host. These experiments support the suggestion that the low NK(YAC-1) activity in 89Sr-treated mice is not mediated by suppressor cells, but may be due to the destruction of the marrow microenvironment which is essential for the generation of functional NK(YAC-1) cells.

Animals↗
PubMed1982

Extended self-renewal capacity of pluripotent hemopoietic stem cells: association with persistent Friend spleen focus-forming virus.

The pluripotential hemopoietic stem cells (CFU-S) of genetically resistant Fv2rr adult C57BL/6 (B6) mice can be persistently infected by Friend virus (FV) when exposed to defective spleen focus-forming virus (SFFV) and helper virus (LLV) at the time of transplantation into heavily irradiated syngeneic recipients (that is, B6 leads to B6 isologous chimeras). Whereas normal and LLV+ marrow were depleted of CFU-S after three serial transplantations at 14-day intervals, SFFV+ donor marrow exhibited prolonged self-renewal capacity. SFFV+ CFU-S from B6. Fv2rr chimeric mice gave rise to normal erythroid and myeloid progenitor cells and were easily detected and quantified over 17 serial marrow transfers equivalent to 260 cumulative days. Marrow cellularity on day 14 of each transfer remained constant during the entire transplantation time. When SFFV fell below detectable levels at passage 15, CFU-S self-renewal exhibited rapid and total decline. Since the frequency of LLV-infected cells in late marrow transfers rose during the period of CFU-S decline, we conclude that SFFV is directly associated with the triggering of CFU-S self-renewal. It is also suggested that this proliferative event may be a prerequisite for the development of FV-induced leukemia.

Animals↗
PubMed1982

Health policy, student selection and curriculum reform.

Student selection is a major component of the training process. This paper argues that the traditional approach taken to selection--using the criterion-prediction model--has limited utility in the training of health care professionals. Not only are there additional educational purposes which selection can fulfil (such as increasing the heterogeneity of students, encouraging realistic self-selection and providing the first exposure to the "ethos" of a profession), but selection can also be used as a direct strategy to assist in the implementation of health service policies--for example, by contributing to social equalization, community participation in health services and community responsibility for health.

Analysis of Variance↗
PubMed1982

Undergraduate medical education for primary care: a case study in New Mexico.

To address the dual problems of maldistribution of physicians and an increasing need for physicians who are lifelong learners, an experimental curricular track was developed at the University of New Mexico School of Medicine. Increased student responsibility for learning is encouraged by student-centered, small-group, problem-based tutorial learning, and early, primary care role modeling is offered during an early, lengthy, rural preceptorship. Preliminary outcomes reveal there is reinforcement of career interest in rural primary care with important linkages forged between the university and communities as a program by-product. Further, the experimental students, as compared to students in the conventional track, showed a greater appreciation of their learning environment, showed less stress, and failed to become cynical. The reorientation of undergraduate medical education toward the future health care needs of communities and the learning needs of physicians may require major modifications of curriculum design and role modeling experiences.

Curriculum↗
PubMed1982

Cytologic cell collection, suspension and preservation for automated screening procedures.

Since disaggregation for monodispersion is optimal when the specimens are suspended in solutions of low alcohol content, we evaluated a modified Davis' solution as a collection and suspension medium. The preservation of specimens maintained at room temperature (21 C) in this solution, which contained only 10% ethanol instead of the usual 20%, was evaluated both qualitatively and quantitatively. Control slides were made on day 1, and experimental slides were made on days 3, 7, 14, 21 and 28. The slides were evaluated by a cytotechnologist and confirmed by a pathologist for the onset of degenerative changes and loss of diagnostic value. The slides were also quantitatively analyzed by a semiautomatic instrument, the Cyto-Tally, adding substantial numerical value to the inquiry. The fragility of leukocytes was evident by the 14th day. Squamous cell degeneration was seen in the interval between two and four weeks depending on the initial state of the specimen. However, the specimens were of diagnostic value for up to four weeks.

Cell Aggregation↗
PubMed1982

Suppression of the cytotoxic response of mouse lymphocytes to syngeneic tumor cells by tumor-promoting phorbol ester.

We have investigated the effects of tumor-promoting phorbol esters on the generation of T-killer cells against syngeneic tumor cells in tissue culture. C57BL/6 or BALB/c spleen cells were cultured with irradiated EL-4 or MPC-11 tumor cells, respectively, for 3 to 7 days at responder:stimulator ratios of 25:1 to 200:1. Lysis was measured in a 4-hr 51Cr release assay. During the sensitization phase, 12-O-tetradecanoylphorbol-13-acetate (TPA) at concentrations as low as 10 ng/ml inhibited the response by 90 to 100% at all responder: stimulator ratios and when added on Day 0, 1, 2, or 4 of a 5-day assay. Thus, TPA was able to suppress the response following successful activation of lymphocytes, since cytotoxicity could be detected as early as Day 3. Addition of TPA on Day 0 caused complete suppression of lysis when measured on Day 3, 5, or 7, indicating that the suppression was not due to a change in the kinetics of the cytotoxic response. The degree of suppression caused by five different phorbol compounds was positively correlated with their tumor-promoting activity. TPA was much less suppressive when added at the effector phase. Indomethacin, an inhibitor of prostaglandin synthesis, did not reverse the TPA effect even when added daily, beginning 3 days before the addition of TPA. The data suggest that one mechanism of phorbol ester tumor promotion may be the inhibition of T-cell immunity against tumor cells initiated by carcinogens.

Animals↗
PubMed1981

Heterogeneity of natural killer cells in the mouse.

Mice were treated with the bone-seeking isotope, 89Sr, cyclophosphamide, and short-term lethal irradiation in vivo, and murine spleen cells are treated with anti-Nk-1.2 plus complement (C) in vitro. Fresh spleen cell suspensions from the above groups and from beige and neonatal mice were subsequently tested for natural killer (NK) cell activity against a panel of lymphoid and nonlymphoid tumor cell target. NK cell reactivities against YAC-1, MPC-11, and Cl.18 tumors were markedly and consistently reduced in (a) mice treated with 89Sr, (b) spleen cells treated with anti-Nk-1.2 plus C, and (c) C57BL/6 bg/bg mice. In contrast, NK activities against FLD-3 and WEHI-164.1 tumors were usually normal in mice treated with 89Sr, in beige mutant mice, and in spleen cells after treatment with anti-Nk-1.2 antibody and C. It appears, therefore, that two major groups of NK cells exist in fresh mouse spleen cells suspensions. NK-A cells are marrow dependent, Nk antigen positive, and deficient in beige mice; these lyse YAC-1, MPC-11, and Cl.18 tumors. NK-B cells, which are responsible for the lysis of WEHI-164.1 and FLD-3, are Nk antigen negative, marrow independent, and unaffected by the bg/bg mutation. Other features of NK-B cells, suggest that these NK cells, although they share the characteristics mentioned above, differ among themselves especially with respect to age of maturation and susceptibility to cyclophosphamide and total body irradiation. The NK-B group may therefore induce subsets that remain to be defined.

Aging↗
PubMed1981

Concanavalin A-induced resistance to Listeria monocytogenes and activation of macrophages: defect in mice treated with 89Sr.

89Sr-treated mice injected with concanavalin A (Con A) 24 h prior to infection with Listeria monocytogenes (LM) could not enhance the clearance of LM from the spleen. Adoptive transfer of normal syngeneic spleen cells together with Con A rendered these animals more resistant. Spleen cells of 89Sr-treated or age-matched control mice were stimulated with con A for 24 h, and supernatant fluids were assessed for macrophage-activating factor (MAF), i.e. the ability to activate resident peritoneal macrophages to kill LM intracellularly in vitro. A defective MAF production by spleen cells was observed in 89Sr-treated, 2 week-old, and athymic nude mice. Also, treatment of spleen cells with anti-Thy-1.2 antiserum plus complement inhibited MAF production. Synergism between spleen cells from 89Sr-treated and nude mice did not occur. The cells required for MAF production were relatively resistant to gamma irradiation. Nylon wool filtration did not modify the ability of spleen cells to make MAF. 89Sr-treated mice possess macrophages responsive to MAF derived from normal spleen cells. The data suggest that the failure of 89Sr-treated mice to develop an anti-LM response observed in thi system could be due to a defective capacity to produce protective humoral factors and/or cells in response to Con A.

Animals↗
PubMed1981

Real time computerization of two-dimensional echocardiography.

A computerized system was developed for real time acquisition, enhanced processing, analysis, and display of cross-sectional images of the left ventricle derived by two-dimensional echocardiography (2DE). The new methodology couples a standard medical imaging computer system to the video output of any current 2DE unit, uses a 128 x 128 or 64 x 64 matrix window and stores the real time 30 frames/sec digitized images on a magnetic disk. Computerized beat-to-beat and frame-by-frame processing employs space-time smoothing the automatic detection of endocardial interfaces by standard threshold and second derivative techniques. Multiple views are displayed in real time with 256 levels of gray and color. The methodology was used to analyze and graphically display frame-by-frame changes throughout the cardiac cycle. In addition, regional wall motion and thickness were analyzed in 12 sectors of individual cross-sections using a standardized angular subdivision originating at the center of area and indexed by an external reference point. An algorithm was developed to correct cross-sectional interference definition from the commonly used trailing-to-leading edge to the more valid leading-to-leading outline technique. Computerized analysis of spatial and temporal variations of cardiac contraction were demonstrated in several clinical and experimental applications, including bicycle exercise testing, investigation of acute myocardial infarction, and assessment of interventions. Initial evaluation indicates that the new real time computerized digital acquisition and data analysis represents a major advances toward quantitation of left ventricular function using 2DE.

Animals↗
PubMed1981

Intracranially recorded responses from the human auditory nerve: new insights into the origin of brain stem evoked potentials (BSEPs).

Auditory evoked potentials were recorded intracranially from the 8th nerve during neurosurgical procedures. The potentials had a large negative peak that occurred 3.0--3.7 msec after the onset of the stimulus (2 000 Hz tone bursts). When these potentials were compared with the scalp recorded brain stem evoked potentials (BSEPs) the intracranial response was found to match the latencies of the P2N3 complex of the BSEP. The results are interpreted as showing that the neural generator of the second peak of the BSEP is the intracranial portion of the auditory nerve and not, as was earlier assumed, the cochlear nucleus.

Acoustic Stimulation↗
PubMed1981

Terminal deoxynucleotidyl transferase expression in acute non-lymphoid leukaemia: an analysis by immunofluorescence.

Indirect immunofluorescence for terminal transferase enzyme (TdT) was used to study the blasts of 64 patients with acute non-lymphoid leukaemia (ANLL). In 32 patients no TdT positive cells were seen. In 19 cases a small subpopulation of cells expressing TdT was detected; these constituted up to 5% of total nucleated cells, and it was not clear whether these TdT positive cells were part of the leukaemic process or represented residual normal bone marrow lymphoid cells. The remaining 13 patients had TdT positive cells accounting for 7-90% of the total. In two of these cases TdT was expressed on blasts with myeloid features, representing an aberrant expression of TdT by myeloid cells; in contrast, in three cases mixed populations of TdT positive lymphoid blasts and TdT negative myeloid blasts were observed. In the remaining cases it was not possible to determine whether the TdT positive cells had definite lymphoid or myeloid features. Cytogenetic analysis showed no evidence of the Philadelphia chromosome. Response to treatment was assessed in 11 of the 13 patients. Only one patient remitted with the initial choice of therapy (DAT); four failed to respond to initial regimes of vincristine and prednisone (V & P) while the other five patients did not respond to myelotoxic combinations (DAT). Only one patient subsequently entered complete remission on second line therapy (V & P). This group of patients with TdT+ ANLL had a particularly bad prognosis, and appeared to differ from cases of TdT positive acute undifferentiated leukaemia, which often respond to V & P therapy.

Acute Disease↗
PubMed1981

Hybrid resistance to EL-4 lymphoma cells. II. Association between loss of hybrid resistance and detection of suppressor cells after treatment of mice with 89Sr.

(C57BL/6 X DBA/2)F1 hybrid (B6D2F1) mice resist the growth of parental-strain (B6) EL-4 lymphoma cells inoculated intraperitoneally; that is, B6D2F1 mice survive longer than B6 mice and do not develop ascites. As compared with B6 mice, B6D2F1 mice have higher levels of natural killer (NK) activity against 51Cr-labelled EL-4 cells in their lymphoid organs. B6D2F1 mice treated with 89Sr lose NK activity for certain lymphoma cell targets, e.g. YAC-1, but NK(EL-4) function is usually intact. However, 89Sr-treated mice had lost hybrid resistance to EL-4 cells in vivo, as determined by survival by irradiated or unirradiated EL-4 cells, Corynebacterium parvum, or polyinosinic:polycytidylic acid (pI:pC) in spleens of normal B6D2F1 mice, but NK(EL-4) activity was depressed within 3 days by such treatment in B6D2F1 mice previously injected with 89Sr. Suppressor cells for NK(EL-4) but not for NK(YAC-1) effectors were easily detected in spleens of 89Sr-treated mice "challenged' with C. parvum. Thus, agents capable of stimulating NK cell function in normal mice may lead to suppression of that activity in mice depleted of marrow-dependent cell function by 89Sr. Spleen cells of 89Sr-treated B6D2F1 mice were also unable to generate anti-EL-4 cytotoxic T lymphocytes in a cell-mediated lympholysis system; this defect appeared also to be mediated by suppressor cells. Lymphoid cells depleted by 89Sr-induced marrow aplasia may have two functions in host defences against tumours (especially lymphomas): they may lyse tumour cells directly and they may "down-regulate' suppressor cells capable of inhibiting other "natural' or "induced' immune functions.

Animals↗