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Biomedical subjects

A L Rubin

Publications and source records attributed to A L Rubin.

At least 19 recordsLinked to original sources
PubMed1992

High rate of diversification and reversal among subclones of neoplastically transformed NIH 3T3 clones.

NIH 3T3 cells undergo neoplastic transformation when exposed to conditions of moderate physiological growth constraint. One of several characteristics of this transformation that indicates its adaptational nature is its gradual reversibility under conditions of unconstrained growth. We explored the origins of reversibility by isolating cells from each of three highly transformed foci and comparing their focus-forming capacity with that of derivative clones and subclones. A high proportion of the parental cells made dense foci. Six of the nine clones obtained from the three foci produced foci, though the percentage varied widely. The other three clones produced no foci at all. The transformed clones were subcloned and analyzed to evaluate the possibility that the negative clones were genuine revertants, rather than being derived from a small minority of nontransformed cells surrounding or underlying the original foci. In each case the subclones varied widely in the percentage of focus-forming cells and the average was much lower than the parental clone from which they were derived. Indeed, 15 of the 53 subclonal populations produced no foci. The high degree of heterogeneity, including complete reversal of focus-forming capacity, provides additional support for the hypothesis that "spontaneous" transformation is driven by an adaptive response to moderate growth constraint rather than by one or more effectively irreversible mutations.

3T3 Cells↗
PubMed1992

Hypertension is not adequately controlled in hemodialysis patients.

To examine the adequacy of hypertension control, we monitored the blood pressure (BP) of 53 hemodialysis patients who received treatment for hypertension. BP measurement using an ambulatory BP monitor began 1 hour before dialysis and continued every 30 to 60 minutes for 48 hours until the next dialysis. Diet, medications including antihypertensive drugs, and hemodialysis prescription were not changed during this study. Each patient had a mean of 68 BP measurements during the monitoring period. Mean (+/- SD) systolic and diastolic BP levels of all patients over 48 hours were 158.6 +/- 22.7 mm Hg and 88.7 +/- 16.6 mm Hg, respectively, without diurnal variations. In these, BP loads (the percentage of systolic BP exceeding 150 mm Hg and diastolic BP exceeding 90 mm Hg) were 58.4% and 39.4%, respectively, suggesting that hypertension was inadequately controlled for more than half of the study period. Eight patients (15%) maintained BP within normal ranges at all times. All patients lost weight (2.9 +/- 0.9 kg) at the end of dialysis by ultrafiltration. However, only 27 patients (51%) had a greater than 5% decrease in mean arterial BP post-dialysis, which returned to predialysis levels within 12 to 24 hours. Reduction of BP postdialysis was significantly more common among black patients (72%) than white patients (30%) (P less than 0.01). However, there was no difference in age, cause of kidney disease, amount of ultrafiltration, and BP loads between those whose BP decreased and those whose did not. BP monitoring was repeated in eight patients, 2 to 3 months after adjustment of their antihypertensive regimens.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Keratinocyte differentiation markers: involucrin, transglutaminase, and toxicity.

Studies of three keratinocyte differentiation markers are described. First, the involucrins of several mammals are identified, facilitating use of this marker in animal models of human disease. The rapid evolution of involucrin has prevented its routine immunochemical identification beyond the primates, but its unusual solubility and its labeling by transglutaminase have permitted detection in rats, cats, and sheep. Second, the re-expression of keratinocyte transglutaminase in carcinoma cells lacking the enzyme is demonstrated. Lack of this enzyme expression has been observed previously in squamous cell carcinomas. The present finding suggests genomic hypermethylation could contribute to this phenomenon and offers an approach to analyzing transcriptional features of the enzyme regulation. Third, the sensitivity of keratinocytes to growth suppression by aflatoxin B1 is reported. The observed toxicity appears to be mediated by aryl hydrocarbon hydroxylase, a metabolic enzyme inducible in keratinocytes by environmental agents. Such expression may be relevant to carcinogenesis in tissues subject to squamous metaplasia as well as in other exposed cell types stimulated to express this biotransformation enzyme.

Aflatoxins↗
PubMed1992

Keratinocyte transglutaminase: differentiation marker and member of an extended family.

Transglutaminases stabilize a variety of biological structures by cross-linking constituent proteins. This action appears physiologically important in stabilizing (1) keratinocyte cornified envelopes, (2) fibrin clots, (3) the copulation plug in rodents, and (4) the fertilized egg surface in aquatic species. Several transglutaminases that participate in such processes have been well characterized and found, though highly divergent, to differ in sequence primarily at the amino terminus. Comparison of their gene structures suggests a likely mechanism by which new members may arise that assume a diversity of functions. The functions of some members of this family are presently unknown, including the tissue transglutaminase found in many mammalian cell types, and those found in plants. Most of the transglutaminases identified are soluble enzymes, but several that are membrane-bound have gained recognition recently. The best characterized of the latter is keratinocyte transglutaminase, which is anchored in the membrane by acylated fatty acid. Important for proper epidermal cell maturation, expression of this enzyme is greatly altered by physiological effectors and toxic agents. In addition, it is induced by cultivation of cells from non-squamous epithelia. Thus, it is a promising marker for helping to elucidate the molecular basis by which keratinocyte differentiation is elicited or altered.

Amino Acid Sequence↗
PubMed1979

Delayed hyperacute rejection in recipients of kidney transplants from HLA identical sibling donors.

Delayed hyperacute rejection, with its characteristic clinical course and histopathologic findings, occurred within one month after transplantation in five recipients of kidney transplants from HLA-A, B and D identical sibling donors. In all cases, unidirectional mixed lymphocyte cultures and immunologic studies to detect cytotoxic antibodies in the recipients against their respective donors, before kidney transplantation and after transplant nephrectomy, were unresponsive or negative. Onset of delayed hyperacute rejection was preceded by bacteremia in two of these patients. Two of these received second kidney transplants, three to six months later, from HLA-A, B and D identical sibling donors again. Although both have had an episode of acute rejection in the early postoperative period, the grafts have maintained excellent function for 21 and 25 months, respectively. Irreversible forms of transplant rejection, such as delayed hyperacute rejection, do occur even in recipients of kidney transplants from HLA-A, B and D identical sibling pairs, indicating that genetic determinants other than HLA-A, B and D loci, and perhaps other nongenetic immune mechanisms, play an important role in the ultimate results of kidney transplantation.

Adult↗
PubMed1979

Possible involvement of the central nervous system in graft rejection.

Electrolytic lesions were produced in the tuberal hypothalamus and amygdala of male Fischer and female BNLF1 rats, and in male Fischer and female BNLF1 rats that had received antecedent hypophysectomies. Skin grafts from Lewis rats survived less well on tuberal-lesioned male Fischer rats than similar grafts on sham-operated and amygdala-lesioned male Fischer rats. Lewis skin graft survival was also curtailed in male Fischer rats that had received hypophysectomies followed by tuberal lesions. These differences were not apparent across the male to female (H-Y) BNLF1 histocompatibility barrier. We conclude: (1) that tuberal hypothalamic lesions stimulate allograft reactivity in rats, (2)that this response is greater when the immunogenetic disparity between donor and host is greater, and (3) that the mechanism governing this response involves a direct neural pathway which bypasses the hypothalamic-hypophyseal axis.

Amygdala↗
PubMed1979

Detection of memory cells by chemical modification of the lymphocyte cell surface.

Stringent alloantigen requirements, necessary for the differentiation of human memory cells into specific secondary cytolytic T cells (2 degrees CTL), can be bypassed by chemical modification of memory cells with the mitogenic oxidising agent, galactose oxidase. Treatment of memory cells generated in a long-term primary mixed lymphocyte culture with neuraminidase and galactose oxidase (NAGO) results in the differentiation of memory cells into 2 degrees CTL. In contrast, treatment of unprimed cells with NAGO does not result in CTL production despite the proliferation resulting from such treatment.

Cell Membrane↗
PubMed1979

Adverse presensitization to renal transplants. Detection by utilization of a D locus antigen-defined lymphoblastoid cell panel as targets in antibody-dependent cell-mediated cytotoxicity assays.

Sera obtained before transplantation from 52 consecutive renal allograft recipients were tested for antibody-dependent cell-mediated cytotoxicity (ADCC) and for complement-dependent cytotoxic antibodies (CDC). A D locus antigen-defined lymphoblastoid cell panel (B lymphoblastoid cell panel) was used as targets for the ADCC, and a peripheral blood lymphocyte (PBL) panel from 40 donors was used as targets for the CDC. Of the 343 ADCC assays, 118 of 168 performed with pretransplant sera from 24 recipients with early graft loss were positive, whereas only 81 of 175 performed with pretransplant sera from 25 recipients with a successful graft outcome were positive (P less than 0.001). A significantly greater degree of presensitization to the B lymphoblastoid cell panel was found in the group that lost their grafts as compared to the group with successful grafts (69% versus 49%, P less than 0.001). Sera from all six recipients with hyperacute rejection were positive in the ADCC before and after absorption with pooled platelets. In contrast, pretransplant CDC results were not predictive of ultimate graft outcome. Utilizing any level of cytotoxicity against the PBL panel as an index of adverse presensitization, no significant correlation between pretransplant CDC results and graft outcome was observed. These results suggest a prognostic role for ADCC using a B lymphoblastoid cell panel as targets to screen and identify high-risk potential graft recipients.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1979

Human gamma globulin enhances the survival of renal allografts.

Ninety seven transplant recipients participated in a controlled, clinical trial measuring the graft-enhancing property of a human gamma globulin preparation. The latter was prepared from the blood of pregnant women (RPGG) and contained antibodies with specificities for HLA locus products. Data analysis indicated that RPGG treated recipients had enhanced survival rates of their grafts if they had received one or more blood transfusions prior to transplantation.

Antilymphocyte Serum↗
PubMed1978

Collagen-induced platelet aggregation and release. I Effects of side-chain modifications and role of arginyl residues.

To investigate the mechanisms governing collagen interaction with blood platelets, the effects of side-chain modifications on collagen-induced platelet aggregation and release of serotonin were studied. Since many chemical modifications alter the ability of collagen to form fibers that, according to current theory, may complicate interpretation of data, we eliminated this possibility by using collagen stabilized in a native-type fibrillar structure by treatment with either glutaraldehyde or ultraviolet irradiation. Acetylation, methylation, succinylation, treatment with 2,4-dinitrofluorobenzene, 2,4,6-trinitrobenzene sulfonic acid or 1,2-cyclohexanedione, and deguanidination with hypobromite were used to modify collagen side-chain reactive groups: amino, carboxyl, hydroxyl and guanidino. Both unmodified monomeric dispersed and fibrillar collagen preparations initiated platelet aggregation and release, although the kinetics and magnitude of the response were different. Monomeric collagen which had been modified by deguanidination, methylation or succinylation, failed to polymerize in physiological conditions and did not induce platelet aggregation and release. However, none of the chemical modifications of stabilized native-type collagen fibers, except treatment with hypobromite or cyclohexanedione, had an effect on collagen-induced platelet aggregation and release. Both hypobromite and cyclohexanedione modified guanidino groups of arginyl residues. Results showed that the ability of a collagen sample to induce platelet aggregation and release of serotonin is dependent on the arginine content of fibrillar collagen. These data demonstrate that manipulation of amino, carboxyl and hydroxyl groups is unimportant as long as the native-type fibrillar structure is maintained, and that arginyl residues are directly involved in collagen-platelet interaction. Moreover, the data suggest that only the arginyl residues in the Y position of the tripeptide unit Gly-X-Y of collagen are responsible.

Amino Acid Sequence↗
PubMed1978

Association between Streptococcus faecalis urinary infections and graft rejection in kidney transplantation.

In the first month after transplantation 50% of 193 consecutive renal transplant recipients had bacteriuria. The most common organisms isolated were Streptococcus faecalis (34), Escherichia coli (28), Pseudomonas spp. (11), and staphylococcus (9). There was a significant correlation between infection with Str. faecalis and graft failure at one, three, and twelve months. This observation suggests that urinary infection with Str. faecalis may be associated with graft failure which is probably the result of immunological factors.

Adult↗
PubMed1978

Eye findings in the diagnosis of Fabry's disease. Patients with renal failure.

Two patients underwent renal transplantation for what was thought to be glomerulonephritis and chronic pyelonephritis. The diagnosis of Fabry's disease was made as an incidental finding during an ophthalmologic consultation for evaluation of blurred vision. These two cases illustrate the usefulness of an eye examination in the correct diagnosis in patients with the multisystem complaints of Fabry's disease. The correct diagnosis was extremely important in understanding the other manifestations of this disease in the affected patient and in the genetic counseling of the family.

Adult↗