Search PubMed⌕ Search

Biomedical subjects

J Freeman

Publications and source records attributed to J Freeman.

At least 109 records · Page 6Linked to original sources
PubMed1995

In vivo radiation sensitivity of glioblastoma multiforme.

PURPOSE: Human glioblastoma (GBM) is one of the most resistant tumors to radiation. In previous reports, we have demonstrated a wide range of radiation sensitivity of GBM in vitro; that is, SF2 values of 0.2 to 0.8. The great sensitivity of some of the cell lines is not in accord with the almost invariably fatal clinical outcome of patients with GBM. The sensitivity of cells in vitro pertains to cells cultured in optimal nutritional conditions. The TCD50 (the radiation dose necessary to control 50% of the tumors locally) determined in lab animals is analogous to the use of radiation with curative intent in clinical radiation oncology. The aim of the present study was (a) to evaluate the sensitivity of GBM in vivo relative to that of other tumor types and (b) assess the relationship between the single dose TCD50 of the xenografts and the sensitivity of the corresponding cell lines in vitro. METHODS AND MATERIALS: The TCD50 assay was used to study twelve human tumor lines. Four previously published values were added. A total of 10 GBM, 4 squamous cell carcinoma (SCC), 1 soft tissue sarcoma (STS), and 1 cancer colon (CC) are included in the analysis. For further suppression of the residual immune system, all the animals received 6 Gy whole-body irradiation 1 day before transplantation. Local tumor irradiations were given as a single dose, under conditions of clamp hypoxia using a Cs irradiator. RESULTS: The TCD50 values for the 10 GBM xenografts varied between 32.5 and 75.2 Gy, with an average of 47.2 +/- 13.1 Gy. The TCD50 values for the SCC were similar to those of the GBM and ranged from 40.7 and 54.4 Gy, with a mean of 46.8 +/- 6.4. The difference between the average TCD50 of GBM and SCC was not significant. The STS and CC xenografts had TCD50 values of 46.0 and 49.2 Gy, respectively. No correlation was found between the TCD50 in vivo and the SF2 or D0 in vitro. CONCLUSIONS: Our data on GBM xenografts showed a wide range of sensitivities to single dose irradiation in vivo, which does not correlate with the almost invariably fatal clinical outcome of these patients. No correlation was observed between the TCD50 in vivo and the in vitro SF2/D0 of the corresponding cell lines. Our in vivo and in vitro data on GBM suggest that radiation sensitivity alone does not explain the cause of the poor clinical response of GBM to radiation, and other factors could contribute to this response.

Animals↗
PubMed1995

The effect of the overall treatment time of fractionated irradiation on the tumor control probability of a human soft tissue sarcoma xenograft in nude mice.

PURPOSE: To study the impact of the overall treatment time of fractionated irradiation on the tumor control probability (TCP) of a human soft tissue sarcoma xenograft growing in nude mice, as well as to compare the pretreatment potential doubling time (Tpot) of this tumor to the effective doubling time (Teff) derived from three different schedules of irradiation using the same total number of fractions with different overall treatment times. METHODS AND MATERIALS: The TCP was assessed using the TCD50 value (the 50% tumor control dose) as an end point. A total of 240 male nude mice, 7-8 weeks old were used in three experimental groups that received the same total number of fractions (30 fractions) with different overall treatment times. In group 1, the animals received three equal fractions/day for 10 consecutive days, in group 2 they received two equal fractions/day for 15 consecutive days, and in group 3 one fraction/day for 30 consecutive days. All irradiations were given under normal blood flow conditions to air breathing animals. The mean tumor diameter at the start of irradiation was 7-8 mm. The mean interfraction intervals were from 8-24 h. The Tpot was measured using Iododeoxyuridine (IudR) labeling and flow cytometry and was compared to Teff. RESULTS: The TCD50 values of the three different treatment schedules were 58.8 Gy, 63.2 Gy, and 75.6 Gy for groups 1, 2, and 3, respectively. This difference in TCD50 values was significant (p < 0.05) between groups 1 and 2 (30 fractions/10 days and 30 fractions/15 days) vs. group 3 (30 fractions/30 days). The loss in TCP due to the prolongation of the overall treatment time from 10 days to 30 days was found to be 1.35-1.4 Gy/day. The pretreatment Tpot (2.4 days) was longer than the calculated Teff in groups 2 and 3 (1.35 days). CONCLUSION: Our data show a significant loss in TCP with prolongation of the overall treatment time. This is most probably due to an accelerated repopulation of tumor clonogens. The pretreatment Tpot of this tumor model does not reflect the actual doubling of the clonogens in a protracted regimen.

Animals↗
PubMed1995

Quantitative comparison of xenotransplantation of a human soft tissue sarcoma into the subcutaneous tissue of normal, postincision, and postincision plus indomethacin-treated nude mice.

The purpose of this study was to test the hypotheses that (1) surgical wounding can enhance the xenotransplantability of a human soft tissue sarcoma (HSTS26T) into subcutaneous (s.c.) tissue of nude mice, and (2) Indomethacin may reduce the xenotransplantability of this human tumor in the surgical wounding animal model by suppressing angiogenesis. The experimental method was to employ the quantitative transplantation assays (TD50, the number of tumor cells that, on average, would be expected to induce a tumor in 50% of the recipients). After an incisional wound (1.0-1.2 cm long) was made on the right leg of each experimental mouse, tumor cells were inoculated into the surgical wound, or into the contralateral leg at 24 and 72 hr postincision, and in another group tumor cells were inoculated into the wound at 72 hr postincision, plus daily s.c. injection of indomethacin, 2 mg/kg body weight for 8 consecutive days in a separate experiment. Nonincisional mice received the same inoculation as the control groups. The TD50s of surgically wounded groups were 3.5-10.7 times lower than that of the control groups. Significantly lower TD50 values were found in groups of cells inoculated into the surgical wound at 72 hr postincision (P < 0.05 or P < 0.01) and into the contralateral leg at 24 hr postincision (P = 0.05). No significant difference was found between the TD50 values in mice that received cells inoculated at 72 hr postincision plus indomethacin treatment, and those with no wound controls. Our conclusion is that the surgical wound can enhance the xenotransplantability of HSTS26T in nude mice. Indomethacin can decrease this enhancing effect level similar to that in no-wound controls and may prevent tumor recurrence in a surgical wound.

Animals↗
PubMed1995

Speech-language outcomes of hemispherectomy in children and young adults.

Children and young adults who had undergone right or left hemispherectomy for intractable seizures after a period of normal language acquisition were compared with respect to scores on speech and language tests. The majority of the subjects had full scale IQs in the borderline to mentally retarded range. Language scores were computed in relation to estimated mental age, not chronological age. On this basis, the left hemispherectomized children were more likely to show syntactic comprehension and rapid-rate auditory processing deficits than the right hemispherectomized. The two groups were similar to one another and to normal children in speech production. The findings are discussed in relation to developmental language disorders.

Adolescent↗
PubMed1995

In vitro cytolytic activity of lymphocytes from tumor-draining lymph nodes is associated with increased numbers of CD8+ cells and increased cytokine production.

A murine footpad tumor model was used to determine the cytotoxic activity, tumor specificity, phenotypic profile, and cytokine production of stimulated cells from draining lymph nodes (DLN). Popliteal DLN from 5-day-old P-815 footpad tumors were stimulated with 10(-7) M phorbol 12, 13-dibutyrate +5 x 10(-7) M ionomycin for 16 hr and cultured in IL-2 (20 units/ml) for 7 or 14 days without autologous tumor. Most cells in both groups were CD3+ (93% at Day 7, 99% at Day 14); however, the percentage of CD8+ cells increased as the cell population matured in the presence of low-dose IL-2. On Day 7, the phenotypic profile was 62% CD4+ and 29% CD8+, whereas on Day 14 it was 16% CD4+ and 81% CD8+. Similarly, in vitro cytokine production increased with time in culture. After 7 days, the level of tumor necrosis factor-alpha (TNF-alpha) was 220 pg/mL and the interferon-gamma (IF-gamma) production was 150 pg/ml. At Day 14 the TNF level had increased to 500 pg/ml, and IF production had increased to 350 pg/ml. These increases in the CD8+ population and in cytokine production correlated with the increase in the percentage of target cells killed by the DLN cells. Cytolytic activity against P-815 was only 13% on Day 7 but 39% on Day 14. Neither group of effector cells (Day 7 or Day 14) had any cytolytic activity against the syngeneic tumor cell line L-1210, demonstrating the tumor specificity of the DLN cells. We describe a model for generating tumor-specific cytotoxic T-cells that have significant cytokine production, which may account for previously described in vivo activity.

Animals↗
PubMed1995

Role of gastroesophageal reflux disease in patients with cervical symptoms.

Otolaryngologists commonly see patients with various nonspecific upper aerodigestive or "cervical" symptoms. The relationship between gastroesophageal reflux disease and these symptoms has been studied but remains unclear. We reviewed the records of 216 patients with various cervical symptoms. Each patient underwent a uniform investigation that included barium swallow, esophageal manometry, acid stimulation testing, and esophagoscopy with distal biopsy. Patients were treated with a combination of a histamine H2 blocker or omeprazole and a prokinetic agent. Follow-up was obtained in 194 patients. Overall, evidence of gastroesophageal reflux disease was detected in 73% of patients. Complete resolution or improvement of symptoms was seen in 84% of patients with treatment. We believe gastroesophageal reflux disease is an important factor in the cause of cervical problems.

Adolescent↗
PubMed1995

Trisomy 22: prenatal diagnosis--a case report.

Multiple abnormalities of a fetus were detected on a routine antenatal anomaly scan at 19 weeks' gestation. Amniocentesis and karyotype analysis showed trisomy 22. The ultrasound and postmortem features are presented.

Abnormalities, Multiple↗
PubMed1995

A longitudinal primary care program in an urban public medical school: three years of experience.

The experience of the University of Illinois at Chicago's College of Medicine with implementing a pilot generalist program focuses on institutionalization and management. Various features of the program make it an interesting case study: It is inter-disciplinary, comprising pediatricians, general internists, and family practitioners; students join the program in the autumn of their first year; and it is changing from a voluntary to a required, institutionally ingrained course of study. The difficulties and procedures encountered in making room for an interdisciplinary primary care program in a traditional medical school curriculum are discussed.

Chicago↗
PubMed1995

Growth and metastatic behavior of five human glioblastomas compared with nine other histological types of human tumor xenografts in SCID mice.

The growth and metastatic behavior of five human glioblastoma multiforme xenografts and nine human xenografts of various histological types were compared in severe combined immunodeficient (SCID) mice. The results demonstrate that the metastatic behavior of the human glioblastoma multiforme xenografts did not differ significantly from a variety of other histological xenografts when evaluated at the same transplantation site in the SCID model. These results are consistent with the hypothesis that the site of glioblastoma multiforme growth influences the extraneural metastatic spread of this disease and lead the authors to suggest that the clinical rarity of distant metastasis is not a fundamental property of these cells. A total of 340 male 7- to 8-week-old SCID mice received subcutaneous transplantation of tumor fragments (21-25 mice per tumor type). The tumor-bearing leg was amputated when the tumor reached a volume of 500 mm3; mice were observed for up to 5 months. There was a trend for a lower take rate, longer latent period, longer volume doubling time (VDT) and growth time (GT) in glioblastoma multiforme as opposed to carcinoma and soft tissue sarcoma xenografts. The highest local recurrence rates (78% and 68%) were observed in two glioblastomas multiforme. Both the glioblastoma multiforme and the other histological xenografts exhibited a widely varying metastatic rate: no correlation was demonstrated between VDT, GT, local control/recurrence, and distant metastasis. These findings show SCID mice to be an attractive model for further biological and preclinical studies of human glioblastoma multiforme.

Adenocarcinoma↗
PubMed1994

Mutation of conserved domain II alters the sequence specificity of DNA binding by the p53 protein.

We have mutagenized human p53 expressed in yeast and selected two mutants, 121F and 123A, which activate transcription from one, rather than the normal two, copies of the consensus p53 DNA binding sequence. Both mutants have a 6-fold increase in affinity for a single copy of the sequence GGG CATG CCC. The 121F mutant has a decrease, and the 123A mutant an increase, in the affinity for the sequence GAA CATG TTC. This genetic and biochemical evidence supports the crystallographic finding that amino acid 120 contacts guanine in the major groove at the second position in the consensus. The major p53 binding site in the p21WAF1/CIP1 promoter resembles the GAA CATG TTC form of the consensus. Compared with wild type p53, the 121F mutant has a 7-fold lower affinity for the p21WAF1/CIP1 site in vitro, and the 121F mutant is defective in p21 induction in vivo. Mutants with subtly altered sequence specificity may facilitate dissection of downstream pathways activated by p53.

Animals↗
PubMed1994

p53 gene mutations are associated with decreased sensitivity of human lymphoma cells to DNA damaging agents.

The present study assessed the role of the p53 tumor suppressor gene in cell cycle arrest and apoptosis following treatment of Burkitt's lymphoma and lymphoblastoid cell lines with gamma-rays, etoposide, nitrogen mustard, and cisplatin. Cell cycle arrest was measured by flow cytometry; p53 and p21Waf1/Cip1 protein levels were measured by Western blotting; cell survival was measured in 72-96-h growth inhibition assays and by trypan blue staining, and apoptotic DNA fragmentation was assessed by either agarose gel electrophoresis or a modified filter elution method. We found that gamma-rays and etoposide induced a strong G1 arrest in the wild-type p53 lines while nitrogen mustard and cisplatin induced relatively little G1 arrest. All agents failed to induce G1 arrest in cells containing mutant p53 genes. The degree of G1 arrest observed with these agents correlated with the rate of p53 and p21Waf1/Cip1 protein accumulation: gamma-rays and etoposide induced rapid accumulation of both p53 and p21Waf1/Cip1; nitrogen mustard and cisplatin induced slow accumulation of p53 and no major accumulation of the p21Waf1/Cip1 protein. Despite differences in G1 arrest and kinetics of p53 or p21Waf1/Cip1 protein accumulation, all agents tended to decrease survival to a greater extent in the wild-type p53 lines compared to the mutant p53 lines. Cell death in the wild-type p53 lines was associated with intracellular DNA degradation into oligonucleosomal sized DNA fragments, indicative of apoptosis. We also observed an inverse sensitivity relationship between nitrogen mustard/cisplatin and etoposide in the mutant p53 lines and this was found to correlate with topoisomerase II mRNA levels in the cells. Our results suggest that p53 gene status is an important determinant of both radio- and chemosensitivity in lymphoid cell lines and that p53 mutations are often associated with decreased sensitivity to DNA damaging agents.

Apoptosis↗
PubMed1994

The highly expressed tapetum-specific A9 gene is not required for male fertility in Brassica napus.

An antisense approach was used to attempt to determine the function of the highly abundant, tapetum-specific A9 transcript in microsporogenesis. A Brassica napus A9 cDNA clone was linked in sense and antisense orientations to the Arabidopsis thaliana A9 promoter and the resulting chimaeric genes introduced into B. napus. A high proportion of the offspring of B. napus antisense A9 plants had very low or undetectable levels of A9 mRNA. However, these plants set seed and had pollen of normal or near normal viability. Therefore, under the conditions studied, the A9 protein appears not to be essential for male fertility in B. napus.

Arabidopsis Proteins↗
PubMed1994

Poisoned landscapes: the epidemiology of environmental lead exposure in Massachusetts children 1990-1991.

This research models the geographic variation in lead poisoning among children living in Massachusetts between 1990 and 1991. Elevated levels of blood lead, which reduce educational performance, arise because children are exposed to unnaturally concentrated sources of lead in the built environment. A Poisson regression model indicates that a large number of children with lead poisoning may be detected in towns with a high proportion of older housing, female headed households, African-Americans, and an industrial heritage. Our results suggest links between the processes of urbanization and industrialization in Massachusetts and today's lead poisoned landscapes.

Child, Preschool↗
PubMed1994

Lightness perception can be affected by surface curvature from stereopsis.

It is demonstrated that lightness perception can be affected by shape from stereopsis. The starting point was a report by Knill and Kersten that the perceived lightness of a monocularly viewed surface can be affected by outline-contour cues indicating that the surface is three-dimensional (3-D). In that study stimuli consisted of two equally sized abutting regions each having the same vertical linear-intensity ramp, so that the horizontal abutting boundary of the two patches created a sharp change in intensity. When this version of the Craik-O'Brien-Cornsweet stimulus has a rectangular outline, it exhibits the standard simultaneous contrast illusion: equivalent patches in the top and bottom regions appear to have different brightness despite having the same luminance. Knill and Kersten replicated this phenomenon with stimuli whose outline-contour cues were consistent with a flat (planar) surface. They found, however, that the illusion was greatly reduced in stimuli with outlines consistent with two abutting 3-D quarter cylinders, for which equivalent regions in the two halves appeared of similar lightness. Knill and Kersten interpreted this effect in terms of surface-lightness computations that took into account 3-D surface shape to achieve an integrated interpretation of the luminance and shape data. In the present report three experiments are described for which these earlier findings were taken as the starting point. In the first experiment the results were replicated by the use of a different methodology. In the second experiment it was shown that shape-from-stereo can produce similar effects on lightness perception to that caused by shape-from-contour. Real 3-D objects with curved surfaces, luminance profiles of the Knill and Kersten type, and carefully controlled outline-contour cues were used so that the objects appeared flat when viewed monocularly but curved in 3-D when seen binocularly. The third experiment was a control confirming that the stereo effect was not simply due to differences caused by monocular versus binocular viewing. It is concluded that the human visual system uses stereo cues, as well as outline-contour cues, in the interpretation of luminance data to recover surface lightness.

Adult↗