Showing papers by "Kettering University published in 1970"
TL;DR: During therapeutic trials with E. coli L‐asparaginase in 131 children and 143 adults with neoplastic disease the following signs of toxicity have been observed: fever, nausea and vomiting, weight loss, somnolence, lethargy, confusion, hypolipidemia, hyperlipidemia and hypoproteinemia.
Abstract: During therapeutic trials with E. coli L-asparaginase in 131 children and 143 adults with neoplastic disease the following signs of toxicity have been observed: fever, nausea and vomiting, weight loss, somnolence, lethargy, confusion, hypolipidemia, hyperlipidemia, hypoproteinemia, abnormal liver function tests, fatty metamorphosis of the liver, pancreatitis (in rare instances), azotemia, granulocytopenia, lymphopenia, thrombocytopenia, and hypersensitivity reactions. While these effects have been moderately severe and reversible in most instances, some patients have shown dangerous degrees of toxicity. This has been the case most frequently in adult patients receiving a dose of 5000 IU/kg/day.
284 citations
TL;DR: A serological study of immunoglobulin-forming cells of the mouse, normal and malignant, shows that they lack all known surface differentiation antigens of the thymocyte-lymphocyte axis, implying that either immunoglOBulin-producing cells are not derived from thymic lymphocytes, or if they are, the program responsible for the transition must include extensive revision of cell surface structure.
Abstract: A serological study of immunoglobulin-forming cells of the mouse, normal and malignant, shows that they lack all known surface differentiation antigens of the thymocyte-lymphocyte axis: TL, theta, Ly-A, Ly-B, and MSLA. Two systems of normal alloantigens are expressed on these cells, H-2 and a new system named PC. The gene Pca (Plasma cell antigen) which specifies PC.1 alloantigen segregates as a mendelian dominant not closely linked with H-2. This cell surface antigen is absent from thymocytes, leukemias, and very probably from thymus-derived lymphocytes also; it is present on cells of the liver, kidney, brain, and lymph nodes as well as on hemolytic plaque-forming cells of the spleen, and on myelomas. So PC.1 is properly classified as a differentiation alloantigen. The strain distribution of PC.1 does not conform to that of any known immunoglobulin allotype or cell surface alloantigen previously described. Thus the cell surface antigens of immunoglobulin-producing cells are clearly different from those of cells belonging to the thymocyte-lymphocyte axis. Each family of cells has distinctive alloantigens, and the two families share alloantigens of only one known system, H-2. This implies that either immunoglobulin-producing cells are not derived from thymic lymphocytes, or if they are, the program responsible for the transition must include extensive revision of cell surface structure.
259 citations
TL;DR: It is found that many patients coming to the Emergency Room of the Henry Ford Hospital with a hypertensive crisis have stopped previous antihypertensive treatment, and why do patients drop out of treatment?
190 citations
TL;DR: Of the 73 adequately treated ALL patients, the overall remission rate was 62%; the median duration of remission was 60 days with a range of 15 to 248 days; the duration of relapse appeared to be independent of dose.
Abstract: One hundred thirty-one children between 1 and 15 years of age have been treated. Ninety-five children had acute lymphoblastic leukemia (ALL); 13 had other types of leukemia; 8 had lymphoma; and 15 had other solid tumors. The dosage ranged from 10 to 5,000 IU/kg daily. Treatment schedules included maintenance after remission and no maintenance. Nine patients in bone marrow remission with other chemotherapy prior to treatment with A-ase received a 28-day course. Six patients received the enzyme intrathecally for meningeal leukemia. Of the 73 adequately treated (over 14 days) ALL patients, the overall remission rate was 62%; the median duration of remission was 60 days with a range of 15 to 248 days. The duration of remission appeared to be independent of dose. Six nonlymphoblastic leukemias demonstrated transient fall in WBC and decreased organ size but no bone marrow remission. One of 4 with Hodgkin's disease demonstrated decrease in size of nodes, liver, and spleen. None of the solid tumors responded. The usual side effects of conventional chemotherapeutic agents, mucous membrane ulcerations, alopecia, and diarrhea were not seen. Side effects included reversible abnormal biochemical liver function tests, fever, and anaphylaxis.
175 citations
TL;DR: Rats which have both a massive local tumour and metastasis to local lymph nodes, and which have survived for a comparatively long time after they received the leukaemic transplants, are most likely to yield antisera.
Abstract: IN 1966, Geering, Old and Boyse1 identified group-specific (gs) antigens of murine leukaemia viruses (MuLV) in immunoprecipitation tests with antigen in the form of disrupted virions or extracts of infected tissue. Antisera containing a wide range of precipitating MuLV antibodies are obtained from inbred rats bearing large subcutaneous transplants of syngeneic leukaemias induced by wild-type Gross virus1. Usually a large number of rats have to be screened in order to find one with antibody to the complete set of MuLV antigens known to be demonstrable by immunoprecipitation. Rats which have both a massive local tumour and metastasis to local lymph nodes, and which have survived for a comparatively long time after they received the leukaemic transplants, are most likely to yield such antisera.
139 citations
TL;DR: E. coli L‐asparaginase (A‐ase) was administered to 163 adults with different forms of leukemia, lymphoma, and solid tumors; some toxic manifestations of A‐ase occurred in almost all patients; these were generally more severe and sometimes were intolerable at higher dosage levels.
Abstract: E. coli L-asparaginase (A-ase) was administered to 163 adults with different forms of leukemia, lymphoma, and solid tumors. Six of 11 patients with acute lymphoblastic leukemia and 4 of 32 patients with acute myeloblastic, myelomonoblastic, or undifferentiated leukemia had complete or good partial remissions. Doses of 10 to 5000 IU/kg/day were used, but there was no clear correlation between dose and therapeutic response, nor with any particular preparation of A-ase. Some of the others had transient physical and/or hematologic improvement, but remission was not achieved. Nineteen patients with myeloblastic leukemia, 4 with lymphoblastic and 3 with undifferentiated, had no response. Eight patients with acute leukemia (7 lymphoblastic and one myeloblastic), who were already in complete remission induced with other agents, were treated with 1000 IU/kg/day or higher doses of A-ase for one month or longer. Seven were given no further therapy. The disease relapsed within 2-5 months in 6 patients, but one is still in remission after 8 months. The eighth patient is still in remission after 3 months but is receiving other chemotherapy. Partial hematologic responses occurred in one patient with untreated chronic granulocytic leukemia, in 4 of 5 patients in a blastic phase of chronic granulocytic leukemia, and in 2 of 3 patients with chronic lymphocytic leukemia, but in none of these patients was the response of substantial clinical benefit. Two patients with disseminated lymphosarcoma or reticulum cell sarcoma had excellent therapeutic responses to A-ase, and 4 others showed some improvement while 14 had no detectable response. Eight patients with advanced Hodgkin's disease showed no response. One patient with malignant melanoma with multiple cutaneous metastases had temporary regression of his metastatic nodules with A-ase on several occasions, but evaluation of this case was complicated by other chemotherapy. Twenty-nine other patients with melanoma had no response nor did 45 patients with other types of solid tumors. Some toxic manifestations of A-ase occurred in almost all patients; these were generally more severe and sometimes were intolerable at higher dosage levels. The toxicity will be discussed in detail in an accompanying report.
124 citations
TL;DR: These findings stimulated a study of the possible universal appearance of embryonic antigens in cancer tissues, which has been detected in colonic, hepatic and lung cancers.
Abstract: VARIOUS reports of embryonal antigens in extracts of tumour tissues have appeared since 1932 (refs. 1–9). Such antigens, absent from homologous normal tissues, have been detected in colonic6, hepatic7 and lung cancers8. These findings stimulated a study of the possible universal appearance of embryonic antigens in cancer tissues.
124 citations
TL;DR: In this paper, low-temperature absorption spectra of selected carotenoids have been examined in order to investigate the scope and limitations of lowtemperature spectroscopy in the carotensoid field.
103 citations
TL;DR: A comparison of lesions arising in the axial skeletal system with lesions originating in theHead and neck indicated that lesions of the head and neck occur in much younger persons and that these tumors are not as aggressive.
Abstract: Summary Eighteen primary chondrosarcomas of the head and neck were reviewed at the Memorial and James Ewing Hospitals. Twelve patients presented with a painless mass arising within the oral cavity. Headache, blurred vision, proptosis, swelling, and numbness of the face were the other prominent complaints. The maxilla was involved in ten of the eighteen patients; the lower jaw was involved in four of the other cases studied. Surgery was the prime method of treatment in all cases; additional surgery and radiation therapy were employed for recurrent tumor. Eight of the eighteen patients were alive and free of disease more than five years. Tumor recurrence at or near the region of primary resection was the major factor leading to the patient's death. A comparison of lesions arising in the axial skeletal system with lesions originating in the head and neck indicated that lesions of the head and neck occur in much younger persons and that these tumors are not as aggressive.
100 citations
89 citations
TL;DR: Use of the technique of acquired tolerance suggests that epidermal cells contain distinctive transplantation allo-antigens, antigens not also possessed by marrow and lymphoid cells.
Abstract: Use of the technique of acquired tolerance suggests that epidermal cells contain distinctive transplantation allo-antigens—antigens not also possessed by marrow and lymphoid cells.
TL;DR: In this article, a numerical simulation of polymer flow is applied to the injection molding fill process to predict fill lengths and fill times of thin constant crossection cavities, and the simulation sensitivity is explored by performing experimental molding trials with two different cavity thicknesses.
Abstract: This paper illustrates a numerical simulation of polymer flow as applied to the injection molding fill process. The simulation model considers heat conduction and viscous heat generation along with the temperature dependence of the flow parameters to predict fill lengths and fill times of thin constant crossection cavities. This simulation is designed for molding situations where fill is difficult, such as thin cavity sections, long flow length requirements, or difficult-to-process materials. The simulation sensitivity is explored by performing experimental molding trials with two different cavity thicknesses. The thinner cavity illustrated a short shot in all cases with the thick cavity completely filling. The simulation accurately distinguishes between the short shot and fill conditions, although significant error is noted for the length prediction of the short shot and the time-to-fill of the full shot condition.
TL;DR: An algorithm based on convex programming is developed for optimum time compression in network scheduling systems that allows for the activity time-cost trade-off functions to be any differentiable convex function.
Abstract: An algorithm based on convex programming is developed for optimum time compression in network scheduling systems. The development allows for the activity time-cost trade-off functions to be any differentiable convex function. Decomposition theory is then applied to reduce the amount of computation necessary. This along with a limited number of rules to structure any incoming vector makes the algorithm amenable to time compression in large project networks.
TL;DR: Positive identification of α-Tocopherol was identified in lipid extracts of bovine retinal outer segment (ROS) preparations by the thin layer chromatographic characteristics of the tocopherol form and its oxidation product α-tocopherylquinone, and by the ultraviolet spectrum of the oxidized and KBH4-reduced form of thetocopherol.
Abstract: α-Tocopherol was identified in lipid extracts of bovine retinal outer segment (ROS) preparations. Positive identification was obtained by the thin layer chromatographic characteristics of the tocopherol form and its oxidation product α-tocopherylquinone, and by the ultraviolet spectrum of the oxidized and KBH4-reduced form of the tocopherylquinone. In the ROS preparations used, α-tocopherol chromanol was the predominant species, the quinone form accounting for 25% or less of the total. The concentration of α-tocopherol in the ROS preparations was about 0.1 mole α-tocopherol per mole rhodopsin, or about 1 nmole/mg, protein. Mitochondria from bovine retina contained about 0.4 nmole α-tocopherol per mg protein.
TL;DR: Vojtiskova et al. concluded that H-2 antigens were probably detectable on spermatozoa by all three procedures, and it is difficult to exclude entirely the possibility that contaminating cells were responsible for the positive findings with the first two techniques.
Abstract: HISTOCOMPATIBILITY antigens of the type H-2 are found on most cells of the mouse, but there are conflicting reports concerning their expression on spermatozoa. Using the indirect immunofluorescence technique, Barth and Russell1 found no H-2 antigen on spermatozoa. Using the techniques of immunogenicity, antibody absorption, and indirect immunofluorescence, Vojtiskova et al.2 concluded that H-2 antigens were probably detectable on spermatozoa by all three procedures. As these authors point out, however, it is difficult to exclude entirely the possibility that contaminating cells were responsible for the positive findings with the first two techniques.
TL;DR: The chlorophyll-depleted LG and LY types had less total acyl lipids per leaf weight when compared to the DG type and the monogalactosyl and digalactOSyl diglycerides were reduced in the LG paralleling the chlorophyLL depletion.
Abstract: A nuclear mutation of Glycine max (soybean) segregates 1:2:1 in regard to chlorophyll content. The heterozygous (LG) leaf blade contains about one-half the pigment content of the wild type (DG) per gram fresh weight. A lethal yellow (LY) type contains about 1 to 2% of the DG leaf pigment values. The chlorophyll a/b ratio in the LG is about 5 compared to about 2 in the DG. Protein/leaf values are lower in the LG and LY types when compared to DG. The LG plastid lamellae contain more protein/chlorophyll, cytochromes/chlorophyll, and quinones/chlorophyll than the DG. P(700)/chlorophyll values are similar in the DG and LG types.The chlorophyll-depleted LG and LY types had less total acyl lipids per leaf weight when compared to the DG type. Similar amounts of sulfolipid and phosphatidyl glycerol per protein residue weight were found in the LG and DG plastids; however, the monogalactosyl and digalactosyl diglycerides were reduced in the LG paralleling the chlorophyll depletion.Thin sections of leaf tissue show similar-sized LG and DG plastids but reduced grana formation in the LG. The LY has very few grana and very small grana compared to either DG or LG. The two characteristic particles revealed in higher plant chloroplasts by freeze-etching are about 15% smaller in the LG compared to the DG plants.
TL;DR: An electrostatic interaction of the bacteriochlorophyll reaction-center complex and mammalian cytochrome c resulted, and a collision-independent electron-transfer with a halftime of 25 μsec can be attained by laser-flash excitation, indicating a good stoichiometry of the reaction.
TL;DR: An automated method has been developed for the assay of L‐asparaginase activity in plasma and other biological fluids, and the activity in the spinal fluid was reduced to negligible amounts within 24 hours when enzyme was injected directly into the cerebrospinal fluid.
Abstract: An automated method has been developed for the assay of L-asparaginase activity in plasma and other biological fluids. By means of this method, L-asparaginase activity has been determined in plasma, cerebrospinal fluid, and urine in patients receiving E. coli L-asparaginase (EC-2) therapy. The height of the plasma activity was related to the dosage. In some patients, the plasma enzyme activity fell despite continued administration of L-asparaginase. The disappearance of the E. coli L-asparaginase from the plasma was related to the commercial source of the enzyme. From one source the half-life in adults was 11.2 ± 2.7 hours and from another, 22.6 ± 4.7 hours. Intramuscular administration of enzyme resulted in plasma levels that were about half those observed following intravenous administration of enzyme. Following intravenous administration of L-asparaginase at doses up to 5000 IU/kg/day, no activity was found in urine. At the highest dosage levels, small amounts of activity were observed in cerebrospinal fluid. When enzyme was injected directly into the cerebrospinal fluid, there was a rapid transfer of enzyme to the plasma, and the activity in the spinal fluid was reduced to negligible amounts within 24 hours.
TL;DR: Studies of six patients using autologous 131I-fibrinogen showed that at a dose of 1000 I.U./kg./day L-asparaginase, the fall in patients' plasma fibrInogen levels must have been a result of decreased synthesis since it could not be ascribed to increased utilization or destruction of fibrinogens.
TL;DR: Sera from nasopharyngeal carcinoma and African Burkitt lymphoma patients showed the opposite behavior, with a majority of highly reactive sera according to all three tests, and high membrane reactive antibody levels were seen in the course of tumor regression, but fell to low levels before and immediately after recurrence.
Abstract: Comparisons were made between 151 sera from 131 donors with Burkitt's lymphoma, nasopharyngeal carcinoma and other tumors of the head and neck area, from patients having had infectious mononucleosis and from healthy controls, in three EBV-associated serological tests: intracellular immunofluorescence on fixed smears of EBV-carrying lymphoblastoid cell lines (“anti-EBV-reaction”), blocking of membrane fluorescence on similar lines and immunoprecipitation against the soluble antigen extracted from the EBV-carrying P3J culture line. Anti-EBV and membrane blocking antibody levels showed concordant patterns in 122 sera (81%) and discordant in 29 (19%), in agreement with previous results. If the anti-EBV and the precipitin tests are compared, 81.5% of the sera gave concordant and 18.5 discordant results. Blocking of membrane reactivity gave concordant results with the precipitin test in 71.5% of the sera whereas 28.5% were discordant. All three tests gave concordant results in 67% of the serum material; this figure fits expectations if it is assumed that the probability of an association between the anti-EBV titer and the membrane blocking antibody level is independent of the probability of an association between the anti-EBV titer and the antibody detected by the precipitin test. Analysis of the serological patterns in relation to disease categories shows that the sera of patients with head and neck tumors other than carcinoma of the post-nasal space or Burkitt's lymphoma fell mainly within the low reactive categories. Sera from nasopharyngeal carcinoma and African Burkitt lymphoma patients showed the opposite behavior, with a majority of highly reactive sera according to all three tests. Most control sera were negative or low in all three tests. In one Burkitt patient, the serological findings could be related to the clinical course of the disease; high membrane reactive antibody levels were seen in the course of tumor regression, but fell to low levels before and immediately after recurrence. Precipitating antibodies showed the opposite pattern, being absent during regression and highly positive after recurrence.
TL;DR: It seems likely that these results are indicative of a more active Photosystem I or a different size photosynthetic unit in C(4) cycle plants than in the reductve pentose phosphate cycle plants.
Abstract: Representative plants containing either the reductive pentose phosphate cycle or the C(4) dicarboxylic acid cycle of photosynthetic carbon dioxide fixation have distinctly different contents of P(700) and chlorophylls a and b. With leaf extracts and isolated chloroplasts from C(4) cycle plants, the mean value of the relative ratio of P(700) to total chlorophyll was 1.83 and the mean value of the ratio of chlorophyll a to b was 3.89. The respective values in similar extracts and chloroplasts from pentose cycle plants are 1.2 and 2.78.It seems likely that these results are indicative of a more active Photosystem I or a different size photosynthetic unit in C(4) cycle plants than in the reductve pentose phosphate cycle plants.
TL;DR: The clinical, hemodynamic and pathologic features of 5 cases of anatomically proved myxomatous degeneration of the mitral valve resulting in mitral regurgitation are presented and should be considered among the causes of acquired mitral Regurgitation.
Abstract: The clinical, hemodynamic and pathologic features of 5 cases of anatomically proved myxomatous degeneration of the mitral valve resulting in mitral regurgitation are presented. Four patients manifested refractory congestive failure. Examination revealed cardiomegaly, third and fourth heart sounds and a grade 3– 4 6 apical holosystolic murmur transmitted to the axilla. One patient had a late systolic murmur. None exhibited signs suggestive of Marfan's syndrome. On fluoroscopy, the left atrium and ventricle were enlarged without valvular calcification. Sinus rhythm and nonspecific ST-T wave changes were recorded on the electrocardiogram. The apex cardiogram showed prominent A waves. Intracardiac pressures (range in mm Hg) were: mean left atrial 16–46; left ventricular end-diastolic 9–25; mean pulmonary arterial 15–61; right ventricular end-diastolic, 5–29, mean right atrial 3–16. Cardiac output ranged from 2.5 to 6.9 liters/min (Fick method). Cineangiography demonstrated massive mitral regurgitation. Coronary cineangiograms were normal. At surgery, the mitral valve leaflets were observed to be quite flaccid and “floppy”. Papillary muscle and chordae tendineae were normal. There was no valvular calcification. Anatomy of the mitral leaflets demonstrated typical features of myxomatous degeneration including layers and foci of dense, hyalinized, relatively acellular collagen. Among the denser layers of collagen were loose, lightly stained zones with small fibrocytes. Myxomatous degeneration of the mitral valve should be considered among the causes of acquired mitral regurgitation.
TL;DR: While DBcAMP may be activated in vivo by a 2′-O-deacylation to MBcAMP, a similar activation process occurs in mildly alkaline buffers, most rapidly in Krebs-Ringer bicarbonate buffer.
TL;DR: Glyoxysomes, a form of microbody, are present in castor bean endosperm during the first 8 days of seed germination and have a "typical" microbody form and are shown histochemically to contain catalase.
Abstract: Glyoxysomes, a form of microbody, are present in castor bean endosperm during the first 8 days of seed germination. They have a "typical" microbody form and are shown histochemically to contain catalase. The catalase label is distributed throughout the microbody and is not an exclusive feature of the crystalline or amorphous core.Castor bean endosperm contain a second cytosome, only slightly larger than the glyoxysomes, which is bound by a rough-surfaced membrane and which does not label for catalase. We have not observed these cytosomes in other tissues, suggesting that they may have a specific cellular function characteristic of castor bean endosperm.
TL;DR: Nucleoplasm isolated from non-growing rat livers contains a complex mixture of ribonucleoprotein particles, none of them mature ribosomes, polysomes or poly-somal-like structures.
TL;DR: Temporary riboflavin deficiency in young mice tends to enhance chemically‐induced skin carcinogenesis, but when mice are kept on a normal diet, the injection of rib oflavin before initiation or promotion does not affect the tumor induction by the two‐step mechanism of chemical carcinogenesis.
Abstract: Temporary riboflavin deficiency in young mice tends to enhance chemically-induced skin carcinogenesis. When mice are kept on a normal diet, the injection of riboflavin before initiation or promotion does not affect the tumor induction by the two-step mechanism of chemical carcinogenesis.