Biomedical subjects
Publications and source records attributed to L Bennett.
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Forty-two patients with chronic lymphocytic leukemia (CLL) were studied for immunoglobulin gene and T-cell receptor gene rearrangements. Immunoglobulin heavy chain gene rearrangements were demonstrable in 41 cases. One rearrangement of the T-cell receptor beta chain gene was detected. Quantification of the relative intensities of germline and rearranged DNA bands suggests that a significant component of the lymphocytosis may be due to cell populations other than the malignant clonal population, particularly in earlier stages of the disease. A direct relationship was found between severity of disease and the relative amount of clonal immunoglobulin heavy chain gene rearrangement. Preliminary data for 12 patients followed sequentially indicated that clinical deteriorations or improvements are reflected in an increase or decrease, respectively, in the proportion of cells with rearranged immunoglobulin genes. Change in the relative proportion of cells with germline versus rearranged genes may provide an additional useful criterion for staging CLL, for more precisely defining the abnormal lymphocyte population, and for monitoring progression of the disease and efficacy of treatment.
Genomic DNA digests of peripheral blood lymphocytes from 13 patients with the leukemic phase of the T cell neoplasm cutaneous T cell lymphoma were studied by hydridization using probes for the constant region of the beta chain of the T cell receptor, the joining region of the immunoglobulin heavy chain gene, and the kappa and lambda light chain genes. Lymphocytes from all 13 cutaneous T cell lymphoma patients contained DNA with clonal rearrangements of the beta chain gene of the T cell receptor. In addition, DNA from 4 patients contained an immunoglobulin gene rearrangement. T cell enrichment studies of peripheral blood lymphocytes from 2 patients confirmed that the immunoglobulin gene joining region rearrangement was confined to the T cell population. These results demonstrate that cutaneous T cell lymphoma is a clonal T cell malignancy that frequently expresses a dual genotype. A multiparameter approach, including DNA probes for the beta chain of the T cell receptor, as well as the immunoglobulin genes, immunophenotyping, and cytogenetics, is valuable in the diagnosis of cutaneous T cell lymphoma.
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In the present study the influence of oestradiol, catechol oestrogens, and O-methylated oestrogens was determined on the contractile responses of the isolated rabbit aorta to (-)-adrenaline. Oestradiol (40 mumol/l), 2-hydroxyoestradiol (2OHE2) (20 mumol/l), and 2-methoxyoestradiol (2MeOE2) (20 mumol/l) all sensitized the rabbit aorta to contractile responses to (-)-adrenaline. Similarly, the 2-hydroxy and 2-methoxy derivatives of oestrone and oestriol also sensitized the aorta to (-)-adrenaline-induced contractions. The largest degree of sensitization was seen in the presence of the 2-methoxysteroids. Oestradiol and 2OHE2 did not increase responses of the aorta to (-)-noradrenaline, while slight potentiation of contraction was seen in the presence of 2MeOE3. The potentiating effect of 2OHE2 on contractile responses to (-)-adrenaline was abolished by prior treatment of the tissue with a COMT inhibitor (U-0521, 55 mumol/l). Conversely, pretreatment of the tissue with 2OHE2 prevented the augmented aortic contraction to (-)-adrenaline usually seen after inhibition of COMT. The non-additive nature of the sensitization seen after combined treatment with 2OHE2 and U-0521 was qualitatively similar to that seen following combined exposure to maximally effective concentrations of U-0521 and an inhibitor of extraneuronal uptake (hydrocortisone 100 mumol/l). Oestradiol and 2MeOE2 reduced the formation of both the 3H-O-methylated, 3H-deaminated and the 3H-O-methylated deaminated metabolites of 3H-(-)-adrenaline (0.15 mumol/l) during exposure of the aorta to the tritiated catecholamine.(ABSTRACT TRUNCATED AT 250 WORDS)
Two DNA probes for the breakpoint cluster region (bcr) of chromosome # 22 have been used to determine the proportion of Philadelphia chromosome (Ph)-positive chronic myeloid leukemia (CML) cases that can be diagnosed by Southern blot analysis. Studies on 17 normal individuals and 17 patients with lymphomas and leukemias (other than CML) indicated that for the restriction enzymes chosen, only expected germ line DNA bands were obtained. In contrast, novel DNA bands interpreted as being the product of translocation within the bcr region could be demonstrated in 31 of 31 cases of Ph-positive CML. One commercially available 1.2 kb bcr probe detected most cases of CML. Because of the frequent presence of deletion of part of the bcr region, however, a probe from the 5' end of bcr is essential to detect some cases. An analysis of the bcr breakpoints occurring in CML patients suggested a difference in the location of the breakpoints for the blast crisis patients versus chronic phase patients although the difference between these two groups was not statistically significant. It is concluded that bcr analysis provides a powerful aid in the diagnosis of CML. This technique is of particular merit in cases when cytogenetic analysis is inconclusive and has considerable potential for improved speed and sensitivity of diagnosis.
Using a dummy test driver with a simulated flaccid forearm capable of representing either a large or zero friction condition, six powered wheelchairs were examined for bucking tendencies. In the zero friction condition, bucking was easily induced in 5 of 6 tested wheelchairs. Adding friction to the simulated forearm prevented bucking in all tested wheelchairs but one. Bucking is not simply related to wheelchair performance measures such as speed or acceleration. Sustained bucking corresponds to neutral stability in a speed regulated machine. Changes in natural frequency and damping characteristics are predicted as useful in reducing powered wheelchair bucking.
To assess plethysmographic waveform diagnostic utility in peripheral vascular disease, a spectrum analyzer was attached to the output of a conventional mercury strain gauge sensor. The resulting quantified waveforms were compared with geometrically determined waveform characteristics and resting ankle pressure ratios for a group of 16 men who ranged from healthy to severely occluded (lower extremities). Of the various harmonics contained within the waveform, second harmonic magnitude best correlated with those geometric waveform characteristics believed to possess diagnostic value. Second harmonic magnitude was positively related (0.9 correlation coefficient) to the 1.33 power of resting ankle pressure ratio. Because it does not require exercise or pressure cuffs, spectrum analyzer waveform based diagnosis may be suited for mass screening purposes.
Sitting paraplegic subjects, tested on a hard seat at a location 2 to 3cm lateral to the ischial tuberosities, develop roughly the same median pressure values (range 52 to 60mmHg) as groups of normal subjects and hospitalized geriatric patients. However, median paraplegic and hospitalized geriatric shear values are roughly three times median normal values. Median rates of pulsatile skin blood flow volumes for sitting paraplegic subjects, while roughly equal to those of hospitalized geriatric subjects, are only one third those of comparable normal subjects.
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A hard seat was equipped with devices sensing arteriolar pulsatile blood flow volume rate, externally developed pressure, and shear, all taken in lateral proximity to the ischial tuberosities of sitting subjects. Tests of 14 geriatric hospitalized patients and 9 healthy young men indicated the following: (1) No young healthy man demonstrated blood flow occlusion at pressure values less than 120mmHg. Of the geriatric hospitalized subjects, 2 occluded at less than 20mmHg. (2) Average shear values developed by the geriatric hospitalized group were 3 times that of the young healthy group. (3) Average pressure values demonstrated by the geriatric hospitalized subjects were roughly equal to those of the younger subjects (roughly 70mmHg). (4) Tipping the seat backwards through 20 degrees produced major benefits to the hospitalized geriatric group in terms of increased blood flow, lessened pressure, and lower shear. The young, healthy group experienced some increase in blood flow with no significant change in sitting reactions when tested in a tipped attitude.
Two-dimensional gel electrophoresis was employed for the protein analysis of several different mouse tissues and Drosophila. The number of protein spots detected with conventional protein dye staining techniques ranged from 110 in erythrocyte lysate to 320 in liver homogenate. Strain variation of protein spots on the gels was examined in five different tissues from two strains of inbred mice (DBA/2J and C57BL/6J) and their F1 hybrids. The protein spots which exhibited strain variation were shown to be autosomally inherited and to follow Mendelian genetics. From these analyses, it was shown that the frequencies of protein variations between these two strains of mice vary from 1 to 5% with the tissue examined. During the course of this study, the protein spots corresponding to nine muscle proteins and three testis enzymes from the mouse as well as two Drosophila enzymes were assigned on two-dimensional gels of their respective homogenates. Radioisotope labelling of Drosophila and autoradiography of the two-dimensional gels were also performed to improve the sensitivity and resolution of the technique. The potential application of two-dimensional gel electrophoresis for mutant screening as well as biochemical genetic studies is discussed.
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An instrument was developed to measure the external pressure, shear, and pulsatile arteriolar blood flow existent at a given portion of the anatomy. Application of this device to the thenar eminence of 4 healthy subjects showed that externally applied pressure was approximately twice as effective as shear in reducing pulsatile arteriolar blood flow. The combination of pressure plus shear was found particularly effective in promoting blood flow occlusion. At a sufficiently high level of shear (roughly 100 g/cm2) the pressure necessary to produce occlusion was half that required when little shear was present.