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Biomedical subjects

H Rubin

Publications and source records attributed to H Rubin.

At least 217 records · Page 12Linked to original sources
PubMed1976

The effect of Corynebacterium parvum in combination with 5-fluorouracil, L-phenylalanine mustard, or methotrexate on the inhibition of tumor growth.

Previous reports from this laboratory have demonstrated conclusively that cyclophosphamide administered asynchronously with Corynebacterium parvum (CP) results in greater C3H mammary tumor inhibition than that observed with either agent alone. An analysis of this combination has revelaed that the chemotherapeutic component contributes more significantly to tumor inhibition than does the immunotherapeutic one. This study was conducted to investigate the inhibition of C3H mammary tumors by other chemotherapeutic agents when used with CP. The results have demonstrated that 60 mg of cyclophosphamide per kg, 90 mg of 5-fluorouracil per kg, and 10 mg of L-phenylalanine mustard per kg administrated weekly have similar tumor-inhibiting properties. The addition of CP enhanced the tumor-inhibiting properties of each agent but to differing degrees. The effect of the immunopotentiator when used in combination with alkylating agents was greater than that seen when it was used with the antimetabolite 5-fluorouracil. The tumor inhibition observed when cyclophosphamide was administered asynchronously with CP was significantly greater than that observed when L-phenylalanine mustard was similarly used. Of particular interest was the finding that the addition of CP to a combination of chemotherapeutic agents resulted in no greater tumor growth inhibition than that which occurred when CP was used along with the most effective single agent in the combination. The data have indicated that, contrary to clinical impression, there is no evidence that CP through its toxicity-sparing effect permits the utilization of larger doses of chemotherapy. Consideration has been given to the mechanisms that might account for the differences in tumor growth inhibition encountered when CP was used with different chemotherapeutic agents.

Animals↗
PubMed1976

Evidence that the platelet retention factor is separate from the factor VIII-related antigen and factor VIII.

Plasmas from a pregnant patient with von Willebrand's disease and from a patient with von Willebrand's disease who is taking Premarin had elevated levels of Factor VIII-related antigen and Factor VIII activity without any improvement in their platelet retention abnormality. When these were added to the blood from nonpregnant patients with von Willebrand's disease no significant improvement in platelet retention followed. This suggests that the "retention factor" is independent of the antigenic Factor VIII-like material.

Blood Coagulation↗
PubMed1975

Reversible alterations in the mitotic cycle of chick embryo cells in various states of growth regulation.

Chick embryo cells which have been kept overnight at pH 6.8 in the absence of serum multiply very slowly. Only a small fraction of cells is in the S period at any given time, and the rate of uptake of 2-deoxy-D-glucose is very low. Upon raising the pH to 7.4 and adding serum ("turn-on") the uptake of 2-deoxy-D-glucose increases immediately; the rate of DNA synthesis increases after a lag of about 4 hours, and represents an increase in the fraction of cells synthesizing DNA. the uptake of 2-deoxy-D-glucose is rapidly returned to its original low rate at any time by again lowering the pH and removing serum ("turn-off"). The synthesis of DNA in the culture remains constant or continues to rise at a markedly reduced rate following the same treatment. Lowering pH or removing serum independently of each other is less efficient at inhibiting the increase in DNA synthesis than the combined treatment but each accomplishes a similar result. Cultures which have been "turned-off" during the early stages of the rapid increase in DNA synthesis, resume their prior rate of increase immediately if "turned-on" again within 2.5 hours. If the cultures have been "turned-off" for 5.5 hours before restoring the "turn-on", there is a 2 hour delay before they resume an increased rate of DNA synthesis. The results until shortly before, or at the time of the onset of the S period. Up to 96% of the cells in post-confluent cultures growing in conventional medium become labeled upon continuous, prolonged exposure to 3H-thymidine. Seventy-eight percent of the cells in serum-deprived cultures growing at a very low rate become labeled. These and other considerations suggest that the inhibition of cell multiplication by high population density or serum deprivation is caused by a lengthening of the time cells remain in the prereplicative G1 period rather than by shifting cells into a qualitatively distinct G0 period. There may, however, be a period common to all cells regardless of growth rate, in which cells are not progressing toward the S period. The length of this variable period would then determine the growth rate of a population of cells.

Animals↗
PubMed1975

Glucose utilization, pH reduction and density dependent inhibition in cultures of chick embryo fibroblasts.

The multiplication rate of sparse cultures of chick embryo cells is only slightly lower at pH 6.9 than at pH 7.4. There is, however, a marked reduction in the multiplication rate of the pH 6.9 cultures before they reach confluency. Cultures at pH 7.4 continue to multiply beyond confluency with only a slight decrease in the multiplication rate. Eighty to ninety percent of the glucose taken up by the cells growing at each pH is converted to lactic acid which is released into the medium. Metabolic reduction in pH of the medium is almost entirely accounted for by the amount of lactic acid produced by the cells. Neither the intracellular nor extracellular accumulation of lactic acid nor the accompanying reduction in pH is sufficient to explain density dependent inhibition of the rate of multiplication of chick cells. The rate of lactic acid production and the multiplication rate of chick cells are independent of glucose concentration in the range of 2--16 mM. In view of the kinetic parameters for the uptake of glucose, this shows that glycolysis is not limited by the rate of glucose uptake and that depletion of glucose from the medium cannot account for the onset of density dependent inhibition of multiplication. However, when cells reach very high population densities, conventional glucose concentrations of 5 mM can be depleted overnight by chick cells. Since the multiplication rate of cells is dependent on glucose concentration when it falls below 2 mM, depletion of glucose may cause some growth inhibition in crowded cultures supplied with conventional medium.

Animals↗
PubMed1975

Early cellular responses to diverse growth stimuli independent of protein and RNA synthesis.

Serum, elevated pH, excess Zn++, 9,10 dimethyl-1,2 dibenzanthracene (DMBA) and insulin accelerate the progress of growth-inhibited chick embryo cells into the S-period of DNA synthesis. A comparative study was made of their capacity to elicit other cellular responses within two hours after their application. All the agents studied stimulated the uptake of the glucose analogue 2-deoxy-D-glucose (2-dGlc). Elevated pH elicited a more striking increase than the other agents in the uptake of the amino acid analogue alpha-amino isobutyric acid (AIB). The application of subtoxic concentrations of Zn++ or DMBA did not stimulate the uptake of uridine by cells nor its incorporation into RNA when tested at 2 hours. However, it was found that the stimulation of uridine utilization did occur but was delayed several hours. Similarly, the accelerated onset of DNA synthesis was also delayed for several hours by these agents. Insulin acted like serum in stimulating the utilization of 2-dGlc, AIB and uridine. Serum and DMBA were particularly effective in stimulating the utilization of choline. It was concluded that the utilization of 2-dGlc, uridine and thymidine are affected similarly by all the agents, but that there may be differential effects in the utilization of AIB and choline. The inhibition of RNA synthesis by actinomycin D did not prevent the relative stimulation of 2-dGlc, AIB and choline utilization by serum and pH treatment. The inhibition of protein synthesis by cycloheximide did not prevent the relative stimulation of 2-dGlc and choline utilization by serum and pH treatment. It partially blocked the increased uptake of AIB and had erratic effects on the utilization of uridine. It was concluded that neither RNA nor protein synthesis is required for some, if not all, the early responses to growth stimuli measured here. The inhibited cell appears to be a poised system which carries out a programmed array of reactions characteristic of the cell type following perturbation by a variety of unrelated agents. In vivo specificity is provided by the physiological reagents available (i.e., hormones) and their capacity to interact with different cell types.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1975

Stimulation of lactic acid production in chick embryo fibroblasts by serum and high pH in the absence of external glucose.

Lactic acid production by chick embryo fibroblasts occurs in the absence of exogenous glucose. Fifteen to 50-fold less lactic acid is formed in the absence of glucose than in its presence. Nevertheless, serum and pH stimulation enhances this residual lactic acid production to the same relative extent as when glucose is present. The amount of lactic acid formed cannot be accounted for by the catabolism of residual glucose in the medium since its concentration is less than one-tenth that of the lactic acid eventually produced. Moreover, the residual glucose concentration remains constant or increases during the course of the experiment. To a large extent lactic acid accumulation in the absence of external glucose is dependent on the presence of amino acids in the medium, but amino acid transport is not affected by the stimulatory agents used in this study. The results suggest that treatments which stimulate cell multiplication also activate those enzymatic pathways which convert amino acids to pyruvic and thence to lactic acid.

Amino Acids↗
PubMed1975

Nonspecific nature of the stimulus to DNA synthesis in cultures of chick embryo cells.

The rate of DNA synthesis in chick embryo cultures deprived of serum is stimulated 5- to 20-fold by a large variety of substances, including subtoxic concentrations of certain metal ions such as Zn++, Cd++, and Hg++. The stimulatory concentrations of Zn++ and Cd++ have sharp optima, which are just below the concentrations that produce frank morphological damage in each case. A much wider gap exists between stimulatory and morphologically damaging concentrations of Hg++. These metal ions also stimulate RNA synthesis, and the uptake of 2-deoxy-D-glucose. The stimulatory effects of Zn++, but not those of Hg++, are prevented by treatment with EDTA. Although medium from cultures stimulated by Zn++ or Hg++ retains its stimulatory capacity for a new set of cultures, the capacity in the case of Zn++-treated cultures is almost entirely lost upon addition of EDTA. It is also lost upon dialysis of conditioned medium from cultures treated with either Zn++ or Hg++. It is concluded that the stimulatory effect is the direct result of interaction between metal ions and cells, and not to the release of growth-stimulatory materials from the cells. The stimulation is thus seen as a non-specific event resulting in an integrated, metabolic response by the cells.

Animals↗
PubMed1975

Interaction of hemoglobin with three ligans: organic phosphates and the Bohr effect.

The assumption that the Bohy coefficient (less than log p 50)/(less than pH) is equal to the haldane coefficient (less than h minus plus) of hemoglobin is shown to be incorrect in the presence of allosteric effectors such as 2,3-diphosphoglycerate. The theoretical relation between the two coefficients in the presence of 2.3-diphosphoglycerate as derived. Experimental data on the variation of both coefficients with diphosphoglycerate concentration are presented and shown to be in agreement with prediction.

Diphosphoglyceric Acids↗
PubMed1975

Central role for magnesium in coordinate control of metabolism and growth in animal cells.

The rate of DNA synthesis in cultures of chicken embryo fibroblasts is reduced by deprivation of serum, high population density, and other "physiological" effectors, through a reduction in the number of cells in the S-period of the cell cycle. The same effect can be produced by drastically reducing the concentration of Mg++ added to the medium. This effect is erratic, however, and better control of [Mg++] can be achieved with phosphorylated compounds which preferentially bind Mg++. Both ATP and ADP, at concentrations in the medium less than or equal to [Mg++], stimulate DNA synthesis in cultures, and at greater concentrations inhibit DNA synthesis by affe-ting the proportion of cells in the S-period. Sodium pyrophosphate, which strongly complexes Mg++, causes little stimulation of DNA synthesis at low concentrations, but causes a striking decrease at concentrations exceeding [Mg++] of the medium. The inhibition can be fully reversed by adding an excess of Mg++, and the kinetics of increase in DNA synthesis resemble those which follow the restoration of serum to serum-deprived cultures. Limitation of [Mg++] by pyrophosphate also reduces the rates of RNA and protein synthesis, 2-deoxy-D-glucose uptake, and lactic acid production to an extent comparable to the reduction caused by the removal of serum from the medium. A model for the coordinate control of metabolism, differentiated function, and growth through the activity of divalent cations is described. The compartmentalization of Mg++ within the cell serves as the key element in this coordinate control by regulating those metabolic pathways in which the rate-limiting steps are transphosphorylation reactions.

Adenine Nucleotides↗
PubMed1975

Further observations on the inhibition of tumor growth by Corynebacterium parvum with cyclophosphamide. I. Variation in administration of both agents.

Studies from this laboratory have indicated that the administration of cyclophosphamide (CY) and Corynebacterium parvum (CP) over a prolonged time to C3H mice with established measurable tumors resulted in complete arrest of tumor growth as well as partial and complete regressions in many instances. The present investigations on optimal dosage, route, frequency, and sequence of administration of CY and CP in the model system were performed to obtain information that could be useful in the design of chemotherapeutic and immunotherapeutic regimens for the treatment of human tumors. Findings have suggested the need for administration of CP in more than one instance. Although a single dose of CP in combination with weekly injections of CY had a significantly prolonged inhibitory effect, weekly doses of CP and CY were more effective. We also concluded that the time between doses of an immunostimulating agent (I-I interval) as well as between administration of chemotherapy (C-C interval) may be critical for an optimal result. In this model system, C-C and I-I intervals of 7 days inhibited tumor growth most effectively. The time between administration of chemotherapy and immunotherapy (C-I interval) has been considered critical. Whereas slightly better results were achieved in these studies when the immunotherapy was administered 4 days after the CY or when the C-I interval was +4 days, almost equally good results were obtained when both agents were given on the same day, which signified that the C-I interval may not be as critical as other investigators have reported. The present findings confirmed and extended our prior observations and indicated that the iv and ip routes of administration were superior to the im and sc routes in our model. The observed tumor growth inhibition was a result of both chemotherapeutic and immunotherapeutic modalities; also, the inhibitory properties of the regimen were more related to the chemotherapeutic component. Finally, almost identical tumor growth inhibition was observed when CP obtained from two different laboratories was used in conjunction with CY.

Animals↗
PubMed1975

Correlation of psychophysiologic variables with vocational rehabilitation outcome in patients with chronic obstructive pulmonary disease.

Despite the magnitude of the public health problem presented by respiratory diseases, there have been few studies concerned with vocational rehabilitation (VR) potential of patients with chronic obstructive pulmonary disease (COPD). Certain physiologic variables which show a high degree of relationship to VR success are identified. The three independent variables which most highly correlate with the VR potential of patients with COPD are the percentages predicted for the first-second forced expiratory volume (FEV(1.0)), forced expiratory flow between 25 and 75 percent of the forced vital capacity (FEF(25-75 percent)), and maximum voluntary ventilation (MVV). The mean "cutting" percentages for inclusion in VR programs were 50, 27, and 40, respectively. The emotional variables studied do not differentiate potential VR success or failure as clearly as the physiologic factors. The criteria set forth not only can be used by rehabilitation workers but could serve as a basis for future demonstration studies.

Adult↗
PubMed1975

Implementation of the medication technician concept.

The implementation of a pharmacy-controlled medication technician program is discussed. Qualified candidates are selected and trained to administer medications to patients under the supervision of a pharmacist. A centralized unit dose drug distribution system is employed. The responsibilities of the technicians and the pharmacists are presented.

Allied Health Personnel↗