Showing papers by "University of Texas System published in 1982"
TL;DR: These findings imply that the shape of the dose-survival curve for the target cells whose depletion results in late effects is different from that for target cells for acute effects: as the dose increases the contribution to cell killing from accumulated sublethal injury, relative to killing from single hit events, increases more rapidly in thetarget cells for late effects.
Abstract: Clinical and experimental evidence for divergent changes in early and late radiation responses in normal tissues after changes in dose fractionation indicate a greater sensitivity of late responses to changes in dose per fraction. In experimental studies of the effect of dose per fraction on early and late isoeffects, a larger number-of-fractions exponent for the late responses is the rule. These findings imply that the shape of the dose-survival curve for the target cells whose depletion results in late effects is different from that for target cells for acute effects: as the dose increases the contribution to cell killing from accumulated sublethal injury, relative to killing from single hit events, increases more rapidly in the target cells for late effects. In other words, the survival curve for the target cells for late injury must be "curvier" than that for acute effects. Although such survival curve characteristics are independent of the survival curve model chosen to describe them, they would represent, in terms of the parameters of the linear quadratic model, S = e − αD − βD 2 , a higher βα ratio for late effects. If the dose survival characteristics of tumor clonogens resemble those of the target cells in acutely responding normal tissues, and if late injury in normal tissues is dose-limiting, then a therapeutic gain would result from reducing the size of dose per fraction by hyperfractionation. Conversely, increasing the size of dose per fraction should reduce the therapeutic differential.
817 citations
Patent•
18 Jun 1982TL;DR: In this article, a trioma cell is the fusion product of a hybridoma cell which produces an antibody having specific binding affinity to one desired antigen and a lymphocyte which produces a corresponding antibody with specific affinity to another desired antigen.
Abstract: Antibodies having binding affinity for two desired antigens, hereinafter "recombinant monoclonal antibodies"; recombinant monoclonal antibodies produced by a quadroma cell or a trioma cell; and methods for producing recombinant monoclonal antibodies by means of a quadroma cell or a trioma cell, wherein a quadroma cell is the fusion product of a hybridoma cell which produces an antibody having specific binding affinity to one desired antigen and a hybridoma cell which produces an antibody having specific binding affinity for another desired antigen, and wherein a trioma cell is the fusion product of a hybridoma cell which produces an antibody having specific binding affinity to one desired antigen and a lymphocyte which produces an antibody having specific binding affinity to another desired antigen.
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TL;DR: Six patients with metastatic mixed germ‐cell tumors who had been treated successfully with chemotherapy had recurring solitary enlarging masses and each had the presumed chemotherapy refractory mass surgically resected and was found to have mature teratoma with absence of malignant histologies.
Abstract: Six patients with metastatic mixed germ-cell tumors who had been treated successfully with chemotherapy had recurring solitary enlarging masses. Four had enlarging pulmonary masses and two patients had enlarging abdominal masses. Each had the presumed chemotherapy refractory mass surgically resected and was found to have mature teratoma with absence of malignant histologies. The growth in two patients can be attributed to tense and expansile cysts; the remaining four had firm masses. All patients remain free of disease without further therapy at 5, 13, 14, 25, 66, and 108 months. Early recognition of this previously unreported and unusual clinical circumstance of a benign teratoma to grow after chemotherapy will allow for surgical salvage.
453 citations
Washington University in St. Louis1, Harvard University2, Radiation Therapy Oncology Group3, University of Texas System4, University of Rochester Medical Center5, Thomas Jefferson University6, Drexel University7, Loyola University Chicago8, Allegheny General Hospital9, SUNY Downstate Medical Center10
TL;DR: Strict quality assurance criteria in radiotherapy are necessary to achieve optimal treatment results and a careful program to evaluate techniques of irradiation and protocol compliance should be maintained in cooperative group studies in order to enhance the validity of clinical trials.
Abstract: An analysis of intrathoracic tumor control was carried out in 378 patients with histologically proven unresectable non-oat cell carcinoma of the lung treated with definitive radiotherapy, randomized to one of four treatment regimens: 4000 rad split course (2000 rad in five fractions in one week, two weeks rest and additional 2000 rad in five fractions in one week) or 4000, 5000 or 6000 rad continuous courses, five fractions per week. Between 85 and 101 patients are analyzed in each treatment group. The complete plus partial response was 46-51% in the 4000 rad groups in contrast to 61-66% in the 5000 to 6000 rad groups (P = 0.008). The overall two year survival rate was 10-11% for the patients treated with 4000 rad split or continuous course, and 19% in the patients treated with 5000 to 6000 rad. The complete response in patients with tumors 3 cm or less in diameter was 16% when treated with 4000 rad in contrast to 20-31% in those treated with 5000-6000 rad. In the patients with lesions from 4 to 6 cm in diameter, complete and partial tumor regression was 48% in the 4000 rad group, 67% with 5000 rad, and 71% with 6000 rad.more » Strict quality assurance criteria in radiotherapy are necessary to achieve optimal treatment results and a careful program to evaluate techniques of irradiation and protocol compliance should be maintained in cooperative group studies in order to enhance the validity of clinical trials. (JMT)« less
392 citations
TL;DR: Patients with recurrent lymphoma can be successfully salvaged by the use of this combination regimen, especially if introduced early after relapse or preferably before progressive disease develops.
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222 citations
TL;DR: Immunocytochemistry was used to examine the morphology and distribution of cholecystokinin-like immunoreactive neurons in the visual cortex of the developing and mature albino rat.
Abstract: Using conventional immunocytochemical techniques, we have examined the morphology and distribution of somatostatin-like immunoreactive neurons in the visual cortex of albino rats between the first postnatal day and maturity. In the adult, somatostatin-immunoreactive neurons were observed in layers II to VI but were concentrated in layers II and III. These cells displayed morphological features characteristic of the multipolar and bitufted varieties of cortical non-pyramidal neurons as described in Golgi preparations of rat visual cortex. On the first postnatal day and in the subsequent few days, immunoreactivity was confined to immature bipolar and multipolar neurons concentrated in layers V and VI. Labelled cells first appeared in the more superficial layers at the beginning of the second postnatal week and attained a distribution similar to that observed in adult animals at the end of this week. At this time they closely resembled their adult counterparts from which they appeared indistinguishable by the end of the third postnatal week. The late appearance of labelled cells in the superficial layers, where they are predominantly located in adult animals, suggests that the somatostatin immunoreactivity exhibited by most of these neurons develops several days after they have completed their migration and assumed their positions in the visual cortex.
217 citations
TL;DR: Endometrial stromal sarcoma is a distinct tumor entity whose diagnosis should not depend on mitotic rate, and it is suggested that poorly differentiated endometrial sarcomas is closely related to malignant mixed Müllerian tumor, in view of clinical and pathologic similarities.
Abstract: U.T.M.D. Anderson Hospital cases filed as endometrial sarcoma were reviewed. Malignant mixed Mullerian tumors, Mullerian adenosarcomas, and poorly differentiated sarcomas of uncertain origin were excluded, and a minimum of 36 months follow-up was required. On pathologic examination, the remaining cases fell into two distinct groups: endometrial stromal sarcoma (11 cases) and poorly differentiated endometrial sarcoma (seven cases). The former were characterized histologically by small to medium-sized uniform cells and distinctive arterial vasculature resembling the spiral arteries of the normal endometrium; they were thus considered to exhibit endometrial stromal differentiation. The latter showed topographic configurations indicative of endometrial origin but did not demonstrate endometrial stromal differentiation; they were composed of generally larger cells with nuclear hyperchromatism and pleomorphism and had no distinctive vascular pattern. The mitotic rate was usually low in endometrial stromal sarcoma and high in poorly differentiated endometrial sarcoma, although two examples of the former had more than 20 mitoses per 10 high-power fields. All but one of the patients with endometrial stromal sarcoma were less than 50 years of age, whereas all of those with poorly differentiated endometrial sarcoma were older than 50 years. One patient with endometrial stromal sarcoma died of tumor, two were living with tumor at latest follow-up, and eight were clinically tumor-free. By contrast, six of those with poorly differentiated endometrial sarcoma died of tumor, all within 34 months. The extent of tumor was the major prognostic factor in both groups; the three patients with endometrial stromal sarcoma who were dead or living with tumor all had extrauterine extension at the time of hysterectomy (only one of the other eight did so) and all six who died with poorly differentiated endometrial sarcoma had myometrial invasion (the one survivor had a tumor limited to the endometrium). Other pathologic factors, including mitotic rate, had no prognostic significance in either category; of particular interest was that both patients who had endometrial stromal sarcomas with high mitotic rates were tumor-free. It is concluded that endometrial stromal sarcoma is a distinct tumor entity whose diagnosis should not depend on mitotic rate, and it is suggested that poorly differentiated endometrial sarcoma is closely related to malignant mixed Mullerian tumor, in view of clinical and pathologic similarities.
217 citations
TL;DR: It is concluded that in normal subjects, Na-induced renal hypercalciuria is accompanied by increased 1,25-(OH)2D synthesis and enhanced intestinal Ca absorption and mediation by PTH is suggested.
Abstract: Earlier studies have shown that an oral sodium (Na) load may induce hypercalciuria in previously normocalciuric subjects and may also increase intestinal calcium (Ca) absorption. To probe the cause of the increased intestinal Ca absorption, we simultaneously measured parathyroid function, serum 1,25-dihydroxyvitamin D [1,25-(OH)2D], and fractional intestinal 47Ca absorption before and after a salt load. Eleven normal subjects and two patients with postsurgical hypoparathyroidism were placed on a 10 meq Na, 400 mg Ca per day diet for 10 days, followed by another 10-day period in which the same diet was supplemented by 240 meq Na daily. Measurements were performed on the final 3 days of each phase. In the normal subjects, urinary Na excretion increased from 7 +/- 2 to 226 +/- 8 meq/day (mean +/- SEM), urinary Ca rose from 110 +/- 14 to 167 +/- 16 mg/day, serum parathyroid hormone (PTH) increased from 20 +/- 1 to 22 +/- 1 muleq/ml, serum 1,25-(OH)2D rose from 38 +/- 4 to 51 +/- 7 pg/ml, and fractional intestinal 47Ca absorption increased from 0.39 +/- 0.03 to 0.49 +/- 0.03 (P less than 0.05 for all changes). Serum Ca corrected for total protein did not change (9.9 +/- 0.1 to 9.8 +/- 0.1 mg/dl). The patients with hypoparathyroidism who were maintained on vitamin D therapy also showed increases in urinary Na (20 +/- 12 to 245 +/- 11 meq/day) and urinary Ca (271 +/- 48 to 305 +/- 43; P less than 0.05). However, there were no increases in serum PTH (13 +/- 1 to 11 +/- 1 muleq/ml), serum 1,25-(OH)2D (44 +/- 1 to 40 +/- 6 pg/ml), or intestinal Ca absorption (0.41 +/- 0.03 to 0.42 +/- 0.05). Corrected serum Ca decreased from 9.4 +/- 0.2 to 8.6 +/- 0.2 mg/dl. We conclude that in normal subjects, Na-induced renal hypercalciuria is accompanied by increased 1,25-(OH)2D synthesis and enhanced intestinal Ca absorption. Since this adaptive mechanism did not occur in two patients with hypoparathyroidism, mediation by PTH is suggested.
TL;DR: DNA rearrangements involving restriction fragment length polymorphism and variation in copy number were detected in the human genome by blot hybridization with a cloned segment of human DNA initially present in a cluster of Alu repeat sequences, indicating the presence of transposable elements in human cells.
Abstract: DNA rearrangements involving restriction fragment length polymorphism and variation in copy number were detected in the human genome by blot hybridization with a cloned segment of human DNA initially present in a cluster of Alu repeat sequences. These rearrangements involve both extrachromosomal circular duplex DNAs and integrated sequences, indicating the presence of transposable elements in human cells.
TL;DR: Patients with an initial white blood cell count of greater than or equal to 25000/microliter were more likely to die of hemorrhage at all times during treatment, and the presence of an antecedent hematologic disorder increased the risk of both fatal fungal infection and resistance to chemotherapy.
TL;DR: The diacylglycerol content of human amnion tissue obtained during early labor was greater than that of amnions tissue obtained before the onset of labor, supportive of the proposition that arachidonic acid is released from the phosphatidylinositol of ammion tissue during human parturition.
TL;DR: Recommendations for purifying the nomenclature of pigmented lesions of the mucosae are presented, and the poorer prognosis for melanomas of the upper aerodigestive tracts is noted, as a group, when compared with cutaneous melanomas.
Abstract: Pigmented lesions, including melanomas, of the mucous membranes of the head and neck are far outnumbered by their counterparts in the skin. This relative dearth is partially responsible for the fact that scientific inquiry into mucosal melanomas has not kept pace with the advances in knowledge of the pathogenesis of cutaneous melanomas and their diagnosis and treatment. Integral to these latter advances have been the refinements in clinical and histologic classification and clinicopathologic correlations with quantitative evaluation of melanomas of skin—enhancements that up to now have been singularly lacking for mucosal melanomas. This report acknowledges this slowness in progress, presents recommendations for purifying the nomenclature of pigmented lesions of the mucosae, and at the same time, also notes the poorer prognosis for melanomas of the upper aerodigestive tracts, as a group, when compared with cutaneous melanomas. Only prospective studies will answer the question of whether the poor prognosis is intrinsic to these mucosal melanomas or whether delay in detection and removal are responsible.
TL;DR: The MDAH System is an improvement over other grading systems in that it is a simple, low‐power microscopic method that depends only on the percentage of gland formation in the tumor and further reflects the biologic behavior of the tumor as measured by the patient's survival.
Abstract: A new grading system for adenocarcinoma of the prostate (MDAH System) and its simplified version, both based on the percentage of tumor that is differentiated (gland-forming) or undifferentiated (non-gland-forming), were compared with the grading systems of Mostofi and Gleason. In a study group of 182 patients with Stage C adenocarcinoma of the prostate, the MDAH system identified 84 patients (46%) as Grade 1, 75 (41%) as Grade 2--3, and 23 (13%) as Grade 4. Kaplan-Meier survival curves predicted a 91% five-year survival for Grade 1 patients, a 60% 5-year survival for Grade 2--3 patients, and a 15% five-year survival for Grade 4 patients. Wilcoxon (Gehan modification) tests showed that the survival was significantly different among Grades 1, 2--3, and 4. The MDAH System is an improvement over other grading systems in that it is a simple, low-power microscopic method that depends only on the percentage of gland formation in the tumor and further reflects the biologic behavior of the tumor as measured by the patient's survival.
TL;DR: Besides tumor burden, tumor proliferative activity and ploidy both appear to have additional prognostic importance for patients with multiple myeloma.
TL;DR: The identification of the major organic-soluble metabolites of arachidonic acid is reported, which are the 5,6,8,9,11,12, and 14,15-epoxy-eicosatrienoic acid derivatives of archidonic Acid.
TL;DR: Like mammalian mitochondria but unlike those from Neurospora, yeast mitochondria use AUA as a methionine codon, which strongly suggests that some size polymorphism of var1 protein results from in-frame insertions of a variable number of AAT (Asn).
TL;DR: The results indicate that endocrine deficiencies after radiotherapy for tumors of the head and neck are common and should be detected early and treated.
Abstract: One hundred-ten patients who had nasopharyngeal cancer and paranasal sinus tumors and were free of the primary disease were studied one to 26 years following radiotherapy. There were 70 males and 40 females ranging in age from 4 to 75 years, with a mean age of 36.5 years. During therapy both the hypothalamus and the anterior pituitary gland were in the field of irradiation. The radiation dose to the hypothalamus and the anterior pituitary gland was estimated to be 400 to 7500 rad with a median dose of 5618 rad to the anterior pituitary gland and a median dose of 5000 rad to the hypothalamus. We found evidence of endocrine deficiencies in 91 of the 110 patients studied. Seventy-six patients showed evidence of one or more hypothalamic lesions and 43 patients showed evidence of primary pituitary deficiency. Forty of the 66 patients who received radiotherapy to the neck for treatment or prevention of lymph node metastasis showed evidence of primary hypothyroidism. The range of the dose to the thyroid area was 3000 to 8800 rad with a median of 5000 rad. One young adult woman who developed galactorrhea and amenorrhea 2 years following radiotherapy showed a high serum prolactin level, but had normal anterior pituitary function and sella turcica. She regained her menses and had a normal pregnancy and delivery following bromocriptine therapy. These results indicate that endocrine deficiencies after radiotherapy for tumors of the head and neck are common and should be detected early and treated. Long-term follow-up of these patients is indicated since complications may appear after the completion of radiotherapy.
TL;DR: It is concluded that the vasoactive compounds, histamine and bradykinin, stimulate formation of prostaglandins in endothelial cells by the release of arachidonic acid from phospholipids of the cell membrane.
TL;DR: S-T segment elevation of 0.1 mV or greater in one or more of leads V4R to V6R is both highly sensitive and specific in identifying acute right ventricular infarction.
Abstract: The value of 0.1 mV or greater of S-T segment elevation in at least one right precordial lead (V4R to V6R) in defining right ventricular myocardial infarction was assessed prospectively in 43 subjects (33 consecutive patients with enzymatically confirmed infarction of varying type and location, 4 patients with unstable angina and 6 healthy volunteers). Patients with acute myocardial infarction were studied with radionuclide ventriculography and technetium-99m stannous pyrophosphate myocardial scintigraphy 18.2 ± 14.3 (mean ± standard deviation) and 85.1 ± 18.0 hours after the onset of symptoms, respectively. Eleven patients (Group A: 9 patients with transmural inferior infarction, 1 with transmural inferolateral infarction and 1 with transmural anteroseptal infarction) demonstrated right precordial S-T segment elevation and 22 patients (Group B: 6 patients with transmural inferior infarction, 2 with transmural posterior infarction, 3 with transmural inferolateral infarction, 3 with transmural anteroseptal infarction, 3 with transmural extensive anterior infarction, 4 with subendocardial anterior infarction and 1 with unclassified infarction) did not. Right ventricular ejection fraction was significantly lower in Group A (0.47 ± 0.11) than in Group B (0.60 ± 0.12) (p < 0.01). Right ventricular total wall motion score was 63.8 ± 15.6 percent of normal in Group A versus 94.3 ± 8.5 percent in Group B (p < 0.001). Technetium-99m pyrophosphate uptake (2+ or greater) over the right ventricle occurred in nine patients (81.8 percent) in Group A and in one patient (4.5 percent) in Group B (p < 0.001). No patient with unstable angina and no healthy volunteer had S-T segment elevation in a right precordial lead. S-T segment elevation of 0.1 mV or greater in one or more of leads V4R to V6R is both highly sensitive (90 percent) and specific (91 percent) in identifying acute right ventricular infarction.
TL;DR: It is suggested that short-term assays that measure survival of stem cells can be used to predict the duration and extent of sterility, regardless of the cytotoxic agent used.
Abstract: Treatment of mice with high doses of radiation or certain cytotoxic drugs results in killing of spermatogonial stem cells, a prolonged period of reduced sperm production, and infertility. In this study, quantitative relationships between these parameters are shown to exist after radiation, Adriamycin (Adria Laboratories, Wilmington, Delaware) or thiotepa treatment. The same relationships are valid for the different cytotoxic agents tested.
The survival of spermatogonial stem cells was assessed by counts of repopulating tubule cross sections at five or eight weeks after treatment. Testicular sperm head counts, eight weeks after treatment, were also used as an assay of stem cell survival. These two assays are highly correlated, demonstrating that the sperm head count at eight weeks is directly related to stem cell survival.
Sperm production declines after cytotoxictreatment and partially recovers to a plateau level. The level of this recovery is correlated with stem cell survival. The restoration of fertility is related to the recovery of sperm production. Under the conditions employed, fertility returns when sperm production by the testis reaches about 10% of control levels. The duration of the sterile period is also highly correlated with stem cell survival.
These results strongly suggest that short-term assays that measure survival of stem cells can be used to predict the duration and extent of sterility, regardless of the cytotoxic agent used.
TL;DR: It is demonstrated that purified mitochondria obtained from CAPr and EFr cells are taken up by endocytosis and transfer antibiotic resistance to chloramphenicol-(CAPs) and efrapeptin-(EFs) sensitive cells.
Abstract: Resistance to the antibiotics chloramphenicol (CAPr) and efrapeptin (EFr) in mammalian cells is cytoplasmically inherited1,2. We demonstrate here that purified mitochondria obtained from CAPr and EFr cells are taken up by endocytosis and transfer antibiotic resistance to chloramphenicol-(CAPs) and efrapeptin-(EFs) sensitive cells. The resultant cells, termed mitochondrial transformants, are stably resistant to the antibiotics and are produced with high efficiency. The ability to transfer antibiotic resistance using mitochondria supports the notion that CAPr is due to a mutation of the mitochondrial DNA3. This technique of mitochondrial-mediated transfer of antibiotic resistance may provide a novel means for studying mitochondrial genetics in mammalian cells.
TL;DR: The morphology and distribution of vasoactive intestinal polypeptide-like immunoreactive neurons in the visual cortex of albino rats whose ages were closely spaced in time between the first postnatal day and adulthood were examined using immunocytochemistry.
Abstract: Using immunocytochemistry, we have examined the morphology and distribution of vasoactive intestinal polypeptide-like immunoreactive neurons in the visual cortex of albino rats whose ages were closely spaced in time between the first postnatal day and adulthood. In the adult, immunoreactive neurons were located in layers II to VI but were concentrated in layers II and III. All labelled neurons had the morphological characteristics of cortical non-pyramidal cells with the majority being of the bipolar variety as described in Golgi preparations. Some multipolar forms were also present.
TL;DR: In this paper, the authors developed that unless the predominant cure-limiting factor can be predicted, little benefit may be seen in trails of new treatment strategies using heterogeneous tumor populations.
Abstract: Tumor radioresistance in clinical radiotherapy implies failure to achieve loco-regional disease control with radiation doses producing an acceptable degree of morbidity. Such radioresistance may be a result of many different causes (biological and technical) which are reviewed in terms of possible remedial actions. Dose response relationships for human cancers suggest that in many sites, tumors are heterogenous with respect to their cure-limiting characteristics. The case is developed that unless the predominant cure-limiting factor can be predicted, little benefit may be seen in trails of new treatment strategies using heterogeneous tumor populations. The fundamental problem of clinical radioresistance is therefore perceived as the inability to predictively identify its cause in the individual patient.
TL;DR: This study demonstrates that DNA content-derived information on instrinsic tumor cell features pertaining to cytogenetics and cytokinetics may provide an objective means of biologically relevant cancer classification.
TL;DR: Oral administration or pretreatment with probenecid maintains drug close to this maximally efficient amount more persistently than does intravenous administration, and total response to an oral dose approaches that of intravenous dosing despite delivering half the amount of drug to the active site.
TL;DR: In 202 patients with rhabdomyosarcoma of the head and neck who registered in the first Intergroup Rhabdomo-Head and neck Study, the primary lesions arose about the eye and orbit in 26%, in parameningeal sites in 46%, and in other head and head areas in 28%.
Abstract: In 202 patients with rhabdomyosarcoma of the head and neck who registered in the first Intergroup Rhabdomyosarcoma Study, the primary lesions arose about the eye and orbit in 26%, in parameningeal sites in 46%, and in other head and neck areas in 28%. Histopathologically, 78% were embryonal-botryoid, 9% alveolar, 10% undifferentiated, and 3% extraosseous Ewing's types. Actual three-year relapse-free survival rates were calculated from data on 103 of these patients who were free of distant metastases at diagnosis and in whom follow-up had been completed for a three-year period. The actual relapse-free survival rates were 91% (21/23) for those with eye/orbit primaries, 46% (20/44) for those with parameningeal primaries, and 75% (27/36) for those with other head and neck sites affected. Among those with no clinical evidence of tumor activity at two years, 8% (6/75) had subsequent relapses.
TL;DR: The occurrence of congestive heart failure in three patients and the observation of significant pathologic changes in endomyocardial biopsies in approximately half of the patients treated with a median cumulative adriamycin dose level of 550 mg/m2 indicate that alpha-tocopherol does not offer substantial protection against adriamicin-induced cardiac toxicity.
Abstract: Our data indicate that alpha-tocopherol used in an oral dose of 2 g/m2 daily results in a six- to eightfold increase of the vitamin E levels in serum. The occurrence of congestive heart failure in three patients and the observation of significant pathologic changes in endomyocardial biopsies in approximately half of the patients treated with a median cumulative adriamycin dose level of 550 mg/m2 indicate that alpha-tocopherol does not offer substantial protection against adriamycin-induced cardiac toxicity. The antitumor activity of the drug, however, is not compromised by the concomitant administration of the vitamin.