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Biomedical subjects

A L Rubin

Publications and source records attributed to A L Rubin.

At least 55 records · Page 3Linked to original sources
PubMed1989

Kidney transplantation in insulin dependent diabetic patients: improved survival and rehabilitation.

Between 1977 and 1986, 50 insulin-dependent diabetic patients received a kidney transplant, 19 from living related donors and 31 from cadaveric donors. Cumulative patient survival was 81% and graft survival was 64% and 33% for living related and cadaveric donor kidneys, respectively, at five years. These results are comparable to that of nondiabetic patients. While physical performance and visual acuity significantly improved after a successful kidney transplantation, neuropathies and angiopathies might not improve. Physical performance improved even in those patients whose nerve conduction time had deteriorated. These findings suggest that kidney transplantation is an effective means of improving survival and rehabilitation of diabetic patients with end-stage renal disease.

Adult↗
PubMed1988

Altered nucleic acid contents of mononuclear cells in blood of renal allograft recipients.

The DNA and RNA contents of blood mononuclear cell populations of 29 cadaver renal allograft recipients and 49 blood donors (controls) were estimated by acridine orange flow cytometry (AO FCM) to assess their cell cycle status. All patients received azathioprine and prednisone for immunosuppression. The patients represented three clinical categories: clinically stable patients, those with acute rejections (clinically overt or impending), and those with infections. Three cell cycle compartments were analyzed for percentage (%) and RNA content (R) of cells: G0/1, consisting of all cells with diploid DNA content; 2 S.D., consisting of cells with diploid DNA content and RNA content 2 standard deviations above the mean RNA content of controls; and SG2M, consisting of cells with a DNA content higher than that of G0/1 cells. The relative coefficient of variation (rCV) of the DNA distribution of G0/1 cells was also determined. In such cell cycle evaluations, the means of rCV and SG2M% of stable recipients were significantly different from those of blood donors. Multivariate analysis of the variables of the three categories of patients resulted in the tentative formulation of two simple logistic equations: one that differentiates stable patients from those with impending or overt rejections based on 2SD% and another one that distinguishes infected patients from those with impending or overt rejections based on SG2M% and RG0/1.

Acridine Orange↗
PubMed1988

Characterization of the calcium sensitivity of differentiation in SCC-13 human squamous carcinoma cells.

The sensitivity to calcium of the human squamous carcinoma cell line, SCC-13, was demonstrated and characterized. Cultures grown to confluence in the presence of 0.2 to 2 mM calcium had approximately 10-fold higher levels of particulate transglutaminase activity and envelope competence than those grown in low calcium (0.025 to 0.05 mM) medium. Raising the calcium from 0.025 to 1.8 mM induced expression of this enzyme and of competence over the course of a week. Conversely, for cultures grown to confluence in 1.8 mM calcium, subsequent reduction of calcium to 0.025 mM resulted in a substantial decline in transglutaminase over a similar time period. Immunoprecipitable transglutaminase was clearly identifiable in cultures grown in 1.8 mM calcium-containing medium but not in those grown in low calcium medium or in the presence of retinoic acid, suggestive of regulation at the level of mRNA accumulation or translation rather than posttranslational modification.

Calcium↗
PubMed1988

2,3,7,8-Tetrachlorodibenzo-p-dioxin and polycyclic aromatic hydrocarbons suppress retinoid-induced tissue transglutaminase in SCC-4 cultured human squamous carcinoma cells.

Retinoic acid and retinyl acetate induce tissue transglutaminase to high levels in cultured SCC-4 keratinocytes, increasing the enzyme specific activity over 50-fold under optimal conditions. Pretreatment of the cells for a day with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3-methylcholanthrene (3-MC) or benzo[a]pyrene almost completely prevented the induction observed upon subsequent treatment with retinoic acid for 2 days. Similar aromatic compounds that do not induce aryl hydrocarbon hydroxylase (pyrene, dibenzofuran) did not exhibit this suppressive effect. The concentration dependence on TCDD for induction of aryl hydrocarbon hydroxylase was nearly identical to that for its suppression of transglutaminase induction, with half-maximal effects observed at approximately 20 pM in each instance. Similarly, the concentrations of 3-MC giving half-maximal stimulation of the hydroxylase and suppression of the transglutaminase were comparable (0.9 and 0.3 microM, respectively), although this agent was almost five orders of magnitude less potent than TCDD. These observations reveal a loss of cellular sensitivity to vitamin A mediated by the Ah receptor.

Carcinoma, Squamous Cell↗
PubMed1988

In vivo effects of high-dose steroids on nucleic acid content of immunocompetent cells of renal allograft recipients.

High-dose steroids administered to renal allograft recipients for treatment of acute graft rejection episodes may affect cell cycle progression of peripheral blood mononuclear (PBM) cells. DNA synthesis and cellular DNA and RNA contents of PBM cells were measured in 8 patients during clinically stable periods, and in another 10 patients both during acute rejection episodes and during 7 days of administration of high-dose steroids. Improved renal function documented successful reversal of the rejection episodes in the 10 patients. Compared with the stable patients, the rejecting patients had higher numbers of cells undergoing clonal expansion--namely, higher proportions of G1-cells and of proliferating, or S, G2, and M (SG2M) cells. Steroid treatment had no acute effects on proportions of G1 or SG2M cells in vivo or on incorporation of 3H thymidine by PBM cells in vitro. However, cells in the prereplicative compartment of the cell cycle (G0/1 cells) had significantly lower RNA content within 7 days of treatment with high doses of steroids. The results suggest that steroids do not acutely influence the posttranscriptional synthesis and the contents of nucleic acids of cells undergoing clonal expansion in vivo. The prereplicative phase of allogeneically stimulated PBM cells of renal allograft recipients may therefore be the cell cycle phase most sensitive to steroids in vivo.

Antibody-Producing Cells↗
PubMed1988

Periodate and recombinant interleukin-2-activated autologous leukocytes can induce regression of metastases of renal cancer.

We present the results of a pilot study that determined the effects of both intermittent injections of periodate and recombinant interleukin-2 (rIL-2)-activated leukocytes and continuous infusions of low doses of rIL-2 on metastases of nine patients with stage IV renal cancer. Four patients experienced regressions, two patients stabilized, and only three patients did not respond. The responses of individual lesions in six patients were heterogeneous with regard to both the degree (ranging from cessation of growth to regression to undetectability) and the duration (ranging from less than 3 to up to 8 months). Survival times from the time of diagnosis and from the time of start of the protocol treatment ranged from 12 to 20 months and 6 to 12 months, respectively, for three patients who expired and from 10+ to 28+ months and 6+ to 12+ months, respectively, for six patients who are alive. Only one patient experienced a grade 4 toxicity (transient renal failure requiring hemodialysis). All other toxicities (grades 1-3) were easily controlled and resolved completely after 7 days. This pilot study deserves clinical testing on a larger scale, since it combines regression inductions in a hitherto treatment-resistant cancer with little complicating toxicity.

Adult↗
PubMed1987

Adoptive immunotherapy for stage IV renal cell carcinoma: a novel protocol utilizing periodate and interleukin-2-activated autologous leukocytes and continuous infusions of low-dose interleukin-2.

In a pilot study involving 13 patients with advanced stage IV renal cell carcinoma, anti-tumor effects and toxicity of a novel form of adoptive immunotherapy were determined. The protocol utilizes infusions of autologous mononuclear leukocytes treated with the oxidizing mitogen sodium periodate (IO4-) and cultured in medium containing human recombinant interleukin-2 (IL-2), and continuous infusions of low-dose IL-2 (mean +/- SD dose = 39.5 +/- 8.6 X 10(3) U/kg/24 hours). Leukocytes (5 to 10 X 10(9] were removed by leukapheresis three times per week, mononuclear cells were separated, activated with IO4- and cultured in medium containing IL-2 (500 U/ml) for 48 to 72 hours. The cells were re-infused following the next leukapheresis procedure. IL-2 was administered five days per week. Treatment was continued for two three-week cycles. An increase in peripheral blood mononuclear cells bearing the natural killer cell (NK) surface marker, Leu 11, an increase in NK- and antibody-dependent cell-mediated cytotoxicity, and a slight increase in spontaneous cytotoxicity for non-NK targets were noted. Regressions (more than 50 percent decrease in tumor mass) of pulmonary, liver, bone, or soft tissue metastases were induced in six patients. Severe fluid retention did not develop in any patient and no patient required treatment in the intensive care unit. Five of the patients who showed a response have experienced a relapse at 5.2 +/- 1.0 (mean +/- SD) months. These observations indicate that IO4-/IL-2-activated killer cells plus continuous infusions of low-dose IL-2 can result in regression of metastatic renal cell carcinoma.

Adult↗
PubMed1987

Optimization of donor specific blood transfusion in kidney transplantation.

1. One hundred milliliters of stored whole blood DST, three times at weekly intervals is a practical, less immunizing and effective approach to enhance graft survival in recipients of a living-related donor kidney. 2. This protocol could also be used in sibling donor/recipient pairs who do not share a haplotype as well as in those who share two haplotypes to enhance graft survival. 3. The use of a short course of Cs (6 mg/kg/d for three weeks) along with DST appears to reduce the sensitization rate even lower. The dose of Cs used in this study produced no clinically significant adverse reactions, whereas Aza (1 mg/kg/d) often produces leukopenia. 4. DST produces significantly suppressed donor specific MLC responses in the early post-DST period; however, it increases the response at a later time. DST modulates immune responses in such a way that secondary responses upon grafting are more readily reversible by immunosuppressive agents.

Adult↗
PubMed1986

Alpha 2-adrenergic receptor function in depression. The cortisol response to yohimbine.

There is evidence that the abnormalities in hypothalamic-pituitary-adrenal (HPA) axis function observed in patients with depression may be related to changes in central neurotransmitter receptor function. To evaluate this possibility further, the alpha 2-adrenergic receptor antagonist yohimbine hydrochloride, which increases brain norepinephrine turnover, was administered to 40 patients with DSM-III major depression (18 melancholic, 22 nonmelancholic) and 16 healthy controls. Plasma free 3-methoxy-4-hydroxyphenylglycol (MHPG) level was measured as an index of noradrenergic function, and plasma cortisol level was used to assess the HPA response. Baseline cortisol levels were elevated in melancholic depressed patients, but not in nonmelancholic patients, when compared with healthy controls. The cortisol response to yohimbine was significantly greater in depressed patients than in controls, despite similar MHPG responses between groups. Since there is evidence that stimulation of postsynaptic alpha 2-adrenergic receptors inhibits HPA axis function, the abnormally increased cortisol response to the alpha 2-antagonist yohimbine suggests a relative subsensitivity of postsynaptic alpha 2-adrenergic receptors in depression.

Adult↗
PubMed1986

Removal of low-density lipoproteins in patients by extracorporeal immunoadsorption.

A new technique called LDL-pheresis was used in patients to lower low-density lipoprotein cholesterol levels. This procedure combines continuous extracorporeal plasma separation with immunoadsorption of low-density lipoprotein on columns containing monospecific antibody to human apolipoprotein B. Six patients underwent a total of 164 procedures without significant side effects or nonspecific protein depletion. Acutely, LDL-pheresis lowered plasma cholesterol levels by removing up to 82 percent of the circulating low-density lipoprotein. Weekly LDL-pheresis combined with a portacaval shunt in a patient with homozygous familial hypercholesterolemia resulted in normalization of plasma cholesterol levels and rapid regression of skin xanthomata. Three of four patients with atherosclerotic coronary artery disease have noted improvement in their angina. LDL-pheresis appears to be a promising new technique capable of safely and efficiently lowering plasma low-density lipoprotein cholesterol levels.

Adult↗
PubMed1986

Does the cholecystokinin antagonist proglumide possess antipsychotic activity?

Cholecystokinin (CCK), a neuropeptide which fulfills almost all criteria for neurotransmitter status, has been co-localized with dopamine in midbrain mesolimbic and mesocortical neurons that have been implicated in the pathogenesis of schizophrenia. Preclinical research suggests that CCK may in part act to enhance central dopaminergic activity. In an attempt to evaluate the role of CCK relative to the dopamine hyperactivity hypothesis of schizophrenia, in the present investigation the putative CCK receptor antagonist, proglumide, was administered to four schizophrenic patients in a double-blind, placebo-controlled study. All patients were receiving concurrent neuroleptic medication, but were still significantly symptomatic. Proglumide was without effect on the patients' psychosis ratings. Potential reasons for this negative finding are discussed.

Adult↗
PubMed1986

Plasma high density lipoprotein is increased in man when low density lipoprotein (LDL) is lowered by LDL-pheresis.

Plasma high density lipoprotein (HDL) concentrations were increased in five hypercholesterolemic normoglyceridemic patients after removal of plasma low density lipoprotein (LDL) by LDL-pheresis. In each patient up to 80% of circulating LDL was removed by passing plasma through immunoadsorption columns containing antibody to apolipoprotein B immobilized to Sepharose. Rebound of LDL was slow after the procedure: 5-7 days in four non-familial hypercholesterolemic patients and greater than 14 days in one patient with homozygous familial hypercholesterolemia. Plasma HDL rose above the pretreatment baseline during the interval between treatments in four of the five patients. When treatments were repeated weekly, time-averaged plasma LDL was lowered by 40-70%, while plasma HDL cholesterol and apolipoprotein AI were increased up to 2-fold, depending on the degree of LDL lowering. Plasma HDL concentrations fell back to their baseline values when LDL-pheresis was stopped and rose again when treatment was restarted. Thus, LDL-pheresis may augment the therapeutic effectiveness of LDL lowering by raising plasma HDL levels and the concentration of HDL relative to LDL.

Adult↗
PubMed1986

Differential regulation by retinoic acid and calcium of transglutaminases in cultured neoplastic and normal human keratinocytes.

In five lines of cultured human squamous carcinoma cells, transglutaminase activity and envelope competence were highly sensitive to retinoic acid and calcium levels in the growth medium. In cells grown in low calcium medium, these measures of keratinocyte differentiation were reduced. Retinoic acid suppressed envelope competence but total transglutaminase activity was markedly reduced, slightly affected, or greatly stimulated depending upon the cell line and whether the cells were grown in low calcium or 1.8 mM calcium-containing medium. Examination by anion exchange chromatography of the transglutaminase activity in SCC-12B2 cultures showed that expression of the particulate form (type I) of the enzyme was greatly stimulated by calcium. The increase in this activity to high levels that occurs at confluence could be almost completely suppressed by retinoic acid in the medium. The soluble form (type II) in the SCC-12B2 cells was induced in growing or confluent cultures by retinoic acid independent of the calcium concentration in the medium, but the 50% effective concentration (100 nM) for its stimulation was approximately 50-fold higher than the 50% effective concentration for suppression of the type I enzyme (2 nM). Thus, these enzymes appear to be distinct and independently regulated. This conclusion is supported by the finding that SCC-4 and SCC-9 almost exclusively expressed types II and I forms, respectively. In contrast to the results with neoplastic cells, in cultured normal epidermal cells type I enzyme comprised the overwhelming majority of activity and was only partially (75-90%) suppressible by retinoic acid, while type II enzyme seemed poorly if at all stimulable. Thus, the SCC lines appear appropriate for studying biochemical mechanisms of action of certain physiological agents, the molecular basis for altered regulation of differentiated function in neoplastic cells, and the origin of diversity within tumors.

Calcium↗
PubMed1985

Noradrenergic function and the cortisol response to dexamethasone in depression.

Abnormalities of the hypothalamic-pituitary-adrenal (HPA) axis and the noradrenergic system have been reported in depression. To study possible interrelations between these two systems, plasma free 3-methoxy-4-hydroxyphenylglycol (MHPG) was compared with the cortisol response to dexamethasone in 64 depressed patients. Postdexamethasone cortisol nonsuppressors had higher baseline plasma free MHPG values than did cortisol suppressors. Increased severity of some depressive symptoms was associated with increased post-dexamethasone cortisol levels. These results indicate that depressed patients with dexamethasone nonsuppression have increased noradrenergic turnover.

Adolescent↗
PubMed1985

Inhibition of pokeweed mitogen-induced B cell differentiation by compounds containing primary amine or hydrazine groups.

The present study examined the effect of two drugs, which contain either an aromatic amine or hydrazine moiety and are known to induce lupus like syndromes in man (procainamide and hydralazine) and an aliphatic amine (dansylcadaverine), on pokeweed mitogen (PWM)-induced B cell production of immunoglobulin G (IgG). These compounds all inhibited IgG production and generation of IgG plaque forming cells, whereas derivatives of them, without free amine groups, had little or no effect. The compounds inhibited differentiation of B cells to plasma cells, rather than production and secretion of IgG. Mitogen free culture supernatants of peripheral blood mononuclear cells (PBM) activated by the oxidizing mitogen, neuraminidase and galactose oxidase (NAGO), prevented the inhibition of B cell maturation. Moreover, incubation of NAGO treated PBM with hydralazine prevented the production of soluble factors capable of promoting B cell maturation in the presence of hydralazine. We conclude from these studies that procainamide, hydralazine and dansylcadaverine inhibit PWM-induced B cell maturation to plasma cells by an indirect mechanism, via inhibition of production of lymphokines by helper cells. The primary amine or hydrazine group appears to be required for the inhibitory effect, since analogues of the inhibitory compounds, without primary amine groups, are non-inhibitory.

Adult↗