Search PubMed⌕ Search

Biomedical subjects

D M Green

Publications and source records attributed to D M Green.

At least 163 records · Page 9Linked to original sources

Enhanced removal of detergent and recovery of enzymatic activity following sodium dodecyl sulfate-polyacrylamide gel electrophoresis: use of casein in gel wash buffer.

The inclusion of 1% casein or bovine serum albumin in buffer used to reactivate enzymes subjected to sodium dodecyl sulfate (SDS)-polyacrylamide electrophoresis resulted in accelerated removal of SDS and restoration of nuclease and beta-galactosidase enzyme activities. Nuclease and beta-galactosidase activities which are absent from gels after longer wash procedures are detectable with this technique. Enzyme activity in gels prepared with SDS which contained inhibitory contaminants was partially restored by the casein wash procedure. The threshold of detection of two-dimensionally separated deoxyribonuclease I using the casein wash procedure was 1 picogram.

Autoradiography↗

Surgery only for the treatment of patients with stage I (Cassady) Wilms' tumor.

A prospective pilot study was undertaken to examine the outcome of patients with Stage I (Cassady) Wilms' tumor treated with nephrectomy only. Eight consecutive patients fulfilling the criteria for Stage I (Cassady) Wilms' tumor (age less than 2 years with unilateral, nonmetastatic, favorable histopathologic type, and tumor weight less than 550 g) underwent nephrectomy with no further therapy. All eight patients were alive and free of disease with a mean follow-up period of 5 years. There was one tumor recurrence that involved a metachronously occurring bilateral tumor. Overall survival (100%) and event-free survival (88%) were comparable with clinical trials in which patients received adjuvant therapy. Patients with Stage I (Cassady) Wilms' tumor can be successfully treated with nephrectomy alone, thereby eliminating the toxicity of adjuvant therapy.

Female↗

Effects of hyperthermia and irradiation on the growth of mouse melanoma tumors following immunotherapy.

Recent investigations suggest that adjuvant hyperthermia enhances the response of human malignant melanoma to ionizing radiation. A study was undertaken to explore the effect of radiation and hyperthermia on the responsiveness of melanoma following active immunization with lethally irradiated B16 melanoma cells in C57 BL 6 mice. Two groups of mice were treated: group 1 received immunotherapy on days 2-5 following tumor inoculation, and group 2 received immunotherapy on days 15-18 following tumor inoculation. The mice in each group were subsequently randomized into one of three subgroups: 1) no further treatment; 2) radiation therapy alone (6 Gy in a single fraction); 3) radiation therapy and regional hyperthermia (43 degrees C x 1 hour). Tumor sizes were measured regularly, and between day 52 and 63 the animals were sacrificed and the lungs sectioned for counting of metastatic tumors. Results from this study show that the immunomodulated B16 murine melanoma is responsive to radiation therapy alone and that this responsiveness is enhanced by the addition of adjuvant regional hyperthermia. There did not appear to be any significant effect of radiation therapy or radiation therapy plus hyperthermia on the development of lung metastases in this tumor model system.

Animals↗

Phase I study of a 120-hour continuous intravenous infusion of 5-fluorouracil in pediatric patients with recurrent solid tumors: a Pediatric Oncology Group study.

To determine the maximum tolerated dose of 5-fluorouracil administered as a 120-hour continuous intravenous infusion to pediatric patients, we performed a phase I study using a starting dosage of 900 mg/m2/day. The maximum tolerated dosage (MTD) was 1,100 mg/m2/day. At this dosage level 40% of courses were complicated by grade 3 mucositis. Three additional patients were treated at the dosage level of 1,000 mg/m2/day after the MTD was determined. We recommend the dosage level of 1,000 mg/m2/day for phase II studies of 5-fluorouracil administered as a 120-hour continuous intravenous infusion to pediatric patients.

Adolescent↗

Adjustment and vocational satisfaction of patients treated during childhood or adolescence for acute lymphoblastic leukemia.

This investigation evaluated the psychosocial consequences of the diagnosis and treatment of acute lymphoblastic leukemia (ALL) on the long-term adjustment of a sample of 46 patients less than 20 years of age at diagnosis (mean age: 7.46 years). Subjects were followed up for an average of 15.4 years after diagnosis and were a mean of 22.87 years old at assessment. A sample of Hodgkin's disease and non-Hodgkin's lymphoma survivors served as a comparison group. Patients completed standardized measures of well-being, stress reaction, vocational satisfaction, and a questionnaire assessing defensiveness regarding their history of cancer treatment, experienced job discrimination, and social involvement. Overall, the subjects appeared to be well-adjusted; female subjects, however, exhibited an increased tendency to experience anxiety in stressful situations. Vocational discrimination did not appear to be a significant problem for this group of survivors, and subjects exhibited levels of vocational satisfaction that did not differ from population norms. Greater defensiveness regarding a history of cancer treatment was associated with lower levels of well-being and heightened stress reaction. Survivors who received CNS prophylaxis that included cranial irradiation had lower well-being scores than did those survivors receiving only intrathecal methotrexate.

Adaptation, Psychological↗

Stimulus selection in adaptive psychophysical procedures.

In adaptive psychophysical procedures, the stimulus should be presented at a relatively high level rather than near the middle of the psychometric function, which is often defined as the "threshold" value. For some psychometric functions, the optimal stimulus placement level produces 84% to 94% correct responses in a two-alternative forced-choice task. This result is disquieting because the popular two-down one-up rule tracks a relatively low percentage of correct responses, 70.7%. Computer simulations and a variety of psychometric functions were used to confirm the validity of this analysis. These simulations also demonstrate that the precise form of the psychometric function is not critical in achieving the high efficiencies. Finally, data from human listeners indicate that the standard deviation of threshold estimates is indeed larger when the stimulus presented on each trial is at a stimulus level corresponding to 70.7% rather than 94% correct responses.

Acoustic Stimulation↗

Directional dependence of interaural envelope delays.

Interaural envelope delays were measured in six human subjects as a function of the location of a movable sound source, bandpassed between 3 and 16 kHz. A total of 324 source locations were tested in horizontal and vertical increments of 10 degrees. A method is described for estimating the complex directional transfer function of the external ear, independent of the position of the recording microphone in the ear canal. To compute interaural envelope delays, directional transfer functions from the left and right ears were convolved with a critical-band filter, the envelopes were computed, and the envelopes were cross correlated. Interaural envelope delays, as well as interaural group delays, varied somewhat with the center frequency of the critical-band filter and with the vertical location of the sound source. Nevertheless, to a first approximation, envelope delays measured in the ear canals increased monotonically with increasing angle of incidence relative to the median plane, as they would for two microphones on the surface of a rigid sphere. The results are discussed in relation to the possible contribution of interaural envelope delays to sound localization behavior.

Attention↗

Sensitivity to envelope coherence.

Measurements are reported on the ability of observers to discriminate whether the envelope of two amplitude-modulated sinusoids are in phase or out of phase. Spacing between the two carriers was either 2/3 or 4/3 octave, and the depth of modulation was varied to determine threshold. Discrimination performance improved as the level of the carriers increases up to about 60 dB SPL. The frequency locus of the two carriers (geometric mean of the two frequencies), which varied from 500 to 8000 Hz in different experiments, had little effect on discrimination accuracy. Discrimination performance was relatively constant for modulation rates below 100 Hz and deteriorates for higher modulation rates. These results are compared with data obtained from comodulation masking release experiments.

Acoustic Stimulation↗

Spectral weights in profile listening.

The COSS analysis suggested by Berg [B. G. Berg, J. Acoust. Soc. Am. 86, 1743-1746 (1989)] is applied to a profile listening task. The listener's task is to detect an increment in the level of the middle component of an n-component spectrum. The overall level of the components is randomly selected from a 20-dB range on each presentation; thus the detection task is essentially one of detecting a change in spectral shape. To implement the COSS analysis, a small perturbation in level is added to each component of the complex. COSS functions are generated from these perturbations, and the spectral weight that the listener assigns to each component is estimated. Data are reported for n = 3, 5, and 11 components and for perturbations with standard deviations of 0.5, 1, and 2 dB. The estimated weights are similar to those derived for an optimum detector; namely, the level at the signal component is compared with the average level of the nonsignal components. This result supports the view that profile analysis involves an across-channel comparison process. The pattern of weights also provides insight into differences among listeners. In a separate experiment, the spectral weights of a very poor profile listener are estimated, and the pattern of the weights suggests reasons for the inferior detection performance.

Adult↗

Pyelonephritogenic Escherichia coli and killing of cultured human renal proximal tubular epithelial cells: role of hemolysin in some strains.

Acute pyelonephritis, a complication of Escherichia coli bacteriuria, must represent a bacterial invasion through the kidney epithelium. To study this process, we overlaid bacterial suspensions onto monolayers of cultured human kidney proximal tubular epithelial cells and measured cytotoxicity by release of lactate dehydrogenase (LDH). Thirty-four isolates cultured from patients with acute pyelonephritis were screened for the ability to cause pyelonephritis in CBA mice by transurethral challenge. The eight most virulent strains (greater than or equal to 70% of mice challenged developed greater than or equal to 10(3) CFU/g of kidney after 48 h) were selected for study. Each strain displayed mannose-resistant hemagglutination of human O erythrocytes; three strains were phenotypically and genotypically hemolytic. Pyelonephritogenic strains were significantly more cytotoxic (30.1 +/- 9.5% LDH release after 18 h) than eight fecal control strains (13.5 +/- 11.5% LDH release; P = 0.0068). We selected the most cytotoxic strain, CFT073, for further study. Sterile filtrate from this hemolytic strain was significantly more cytotoxic than was the filtrate of the fecal control strain, FN414. Transposon mutagenesis of CFT073 with TnphoA abolished hemolytic activity and cytotoxicity by both whole cells and sterile filtrate. Southern blot analysis revealed that the Tnphoa insertion mapped to the E. coli chromosomal hly determinant within a 12-kilobase SalI restriction fragment. Transformation of a nonhemolytic strain, CPZ005 with plasmid pSF4000, which carries a cloned hemolysin determinant, resulted in highly elevated cytotoxicity. Light micrographs of proximal tubular epithelial cell cultures demonstrated cell damage by pyelonephritogenic strains that was not induced by a fecal strain or the hemolysin-deficient mutant. Results indicate that pyelonephritogenic E. coli strains are more frequently cytotoxic for a putative target, that is, human renal tubular epithelium, than are fecal isolates. Hemolysin, in some strains, is apparently responsible for this cytotoxicity.

Bacterial Toxins↗

Severe hepatic toxicity after treatment with vincristine and dactinomycin using single-dose or divided-dose schedules: a report from the National Wilms' Tumor Study.

To evaluate the effect of dactinomycin (AMD) dose and schedule on the frequency of severe hepatic toxicity in unirradiated National Wilms' Tumor Study-4 (NWTS-4) patients, we reviewed the records of 154 children randomized to single-dose AMD and 176 children randomized to divided-dose AMD administration. All the children also received vincristine in identical dose schedules for the first 10 weeks. The frequency of severe hepatic toxicity encountered in the early weeks of therapy was 14.3% (five of 35) among patients treated with 60 micrograms/kg of AMD, 3.7% (four of 108) among patients given 45 micrograms/kg, and 2.8% (five of 176) among patients treated with 15 micrograms/kg per dose times five doses (P = .025). The data suggest an increased frequency of severe hepatic toxicity with the higher, single-dose schedule of administration. However, the frequency of severe hepatic toxicity among the patients in the two remaining groups is markedly higher than the 0.4% observed among similar unirradiated patients in NWTS-3. The relationship of this toxicity to factors such as anesthetic agents, blood transfusions, intercurrent viral infection, or other presently unrecognized causes can be further evaluated only with a detailed investigation such as a case-control study.

Antineoplastic Combined Chemotherapy Protocols↗

Pregnancy outcome after treatment for acute lymphoblastic leukemia during childhood or adolescence.

To evaluate gonadal function and pregnancy outcome after treatment for acute lymphoblastic leukemia during childhood or adolescence, 44 former patients who were less than 20 years of age at diagnosis, 5 or more years from diagnosis, and 18 or more years of age were contacted. Thirty-nine (88%) provided information regarding pregnancy outcome. Gonadal function as estimated by the ability to conceive or sire a pregnancy, was not impaired despite treatment with substantial cumulative doses of methotrexate, 6-mercaptopurine, vincristine, and 1-asparaginase. Twelve patients reported a total of 27 pregnancies. There were four spontaneous abortions, one stillborn, and 22 liveborn infants. The birthweights were 1928 to 4536 g (median, 3430 g). Two infants had congenital anomalies. The childrens' ages ranged from 1 month to 10 years, 2 months (median, 6 years, 1 month). None has been diagnosed with any type of childhood cancer. The results of this study suggest that pregnancy outcome is not affected adversely by treatment received during childhood or adolescence for acute lymphoblastic leukemia.

Abortion, Spontaneous↗

Diffuse interstitial pneumonitis after pulmonary irradiation for metastatic Wilms' tumor. A report from the National Wilms' Tumor Study.

To evaluate the frequency, etiology, and outcome of diffuse interstitial pneumonitis after treatment of children with Stage IV (favorable histologic type) Wilms' tumor using whole-lung and abdominal radiation therapy, and combination chemotherapy, all cases reported in such patients entered on National Wilms' Tumor Study 3 were reviewed. Diffuse interstitial pneumonitis was reported in 13.0% of patients. The etiology was varicella, one patient; Pneumocystis carinii, three patients; and unknown, 15 patients. The time elapsed after the completion of whole-lung irradiation did not distinguish those patients with pneumonitis due to P. carinii from those with pneumonitis of unknown etiology. All three children with pneumonitis due to P. carinii survived the episode, whereas only four of 15 (27%) patients with pneumonitis of unknown etiology survived the episode. Management of Wilms' tumor patients who develop diffuse interstitial pneumonitis after whole-lung irradiation should include a diagnostic procedure known to be sensitive for the diagnosis of P. carinii infection.

Adolescent↗

Enterochromaffin-like cell populations in human fundic mucosa: quantitative studies of their variations with age, sex, and plasma gastrin levels.

The human gastric fundal mucosa contains a variety of endocrine cells, the most numerous of which are the so-called enterochromaffin-like (ECL) cells. We have studied the variations with age and sex of the ECL cell populations, utilizing an assessment based on multiple endoscopic biopsies from four groups of subjects. Plasma gastrin levels were also determined in these subjects. In males, endocrine cell densities declined with age but the ECL cell numbers in females opposed this trend. ECL cell counts showed no appreciable differences between young and old females. In older females, there was a high rate of gastritis and increased levels of circulating gastrin. Concentrations in older females (29.6 +/- 8.7 pmol/l) were higher than in both younger (less than 45 years) males (5.3 +/- 1.1 pmol/l) and older (greater than 55 years) males (6.3 +/- 0.6 pmol/l) (P less than 0.05). The plasma gastrin level was also higher in older females than in young females (13.1 +/- 4.5 pmol/l), although this difference failed to reach statistical significance. In conclusion, clinically silent gastritis, raised gastrin levels, and maintenance or rise of ECL cells numbers, in opposition to a general decrease in endocrine cells with age, appear to be features of women of more than 55 years of age. The variations in ECL cell populations reported here should be taken into account when evaluating possible pathological alterations of the stomach.

Adult↗

Auditory profile analysis: potential pitch cues.

The ability to detect changes in spectral shape, or profile analysis, was measured for both complex and simple changes in the power spectrum of a complex equal-amplitude standard. In an effort to determine whether detectability was mediated by changes in pitch that are concomitant with changes in spectral shape, the pitch of the stimuli were altered on a trial by trial basis. For moderate-range pitch randomizations, thresholds were on average 3 dB poorer than when no pitch randomization was employed. For large-range pitch randomizations, threshold changes were larger, but performance levels remained above chance levels. The psychophysical data, coupled with computer simulations of Feth's envelope-weighted average instantaneous frequency pitch model, indicate that changes in pitch contribute little to the discriminability of complex spectra.

Acoustic Stimulation↗

Directional sensitivity of sound-pressure levels in the human ear canal.

Changes in sound pressures measured in the ear canal are reported for broadband sound sources positioned at various locations about the subject. These location-dependent pressures are one source of acoustical cues for sound localization by human listeners. Sound source locations were tested with horizontal and vertical resolution of 10 degrees. Sound levels were measured with miniature microphones placed inside the two ear canals. Although the measured amplitude spectra varied with the position of the microphone in the ear canal, it is shown that the directional sensitivity at any particular frequency of the broadband stimulus is independent of microphone position anywhere within the ear canal. At any given frequency, the distribution of sound pressures as a function of sound source location formed a characteristic spatial pattern comprising one or two discrete areas from which sound sources produced maximum levels in the ear canal. The locations of these discrete areas varied in horizontal and vertical location according to sound frequency. For example, around 8 kHz, two areas of maximum sensitivity typically were found that were located laterally and were separated from each other vertically, whereas, around 12 kHz, two such areas were found located on the horizontal plane and separated horizontally. The spatial patterns of sound levels were remarkably similar among different subjects, although some frequency scaling was required to accommodate for differences in the subjects' physical sizes. Interaural differences in sound-pressure level (ILDs) at frequencies below about 8 kHz tended to increase monotonically with increasing distance of the sound source from the frontal midline and tended to be relatively constant as a function of vertical source location. At higher frequencies, however, ILDs varied both with the horizontal and with the vertical location of the sound source. At some frequencies, asymmetries between the left and right ears in a given subject resulted in substantial ILDs even for midline sound sources. These results indicate the types of horizontal and vertical spatial information that are available from sound level cues over various ranges of frequency and, within a small subject population, indicate the nature of intersubject variability.

Acoustic Stimulation↗

Signal uncertainty and psychometric functions in profile analysis.

Experiment 1 was conducted to compare the effects of signal frequency uncertainty on the detection of a change in spectral shape and on the detection of a tone in wideband noise. Results indicate that for both tasks the uncertainty effect was small, being on average about 3 dB. In a second experiment, psychometric functions were measured for the detection of changes in the spectral shape of multicomponent complexes. Psychometric functions for profile tasks have a 25-dB range and are similar to those measured for the detection of an increment in the level of a single sinusoid. These psychometric functions are different from those found when detecting a signal in noise, which typically have a 10-dB range. Three equations for the shape of the psychometric functions were compared. The difference in the resulting fits was small, thus preventing an unambiguous choice of functional form.

Acoustic Stimulation↗