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P Stock

Publications and source records attributed to P Stock.

At least 37 records · Page 2Linked to original sources
PubMed1995

Clinical islet transplantation experience of the University of California Islet Transplant Consortium.

BACKGROUND: The University of California Islet Transplant Consortium was formed to evaluate the feasibility of performing clinical islet transplantation at different transplant centers by using a single centralized islet isolation laboratory. METHODS: From July 1992 through February 1995 seven adult islet transplantations were performed, six allografts and one autograft. Once procured, human pancreata were brought to the UCLA-VA Islet Core Laboratory for islet isolation and purification, which were then transported to different centers for transplantation. Patients 1 through 3 received their transplants in Los Angeles, patient 4 received her islet transplant in Torrance, and patients 5 through 7 received their transplants in San Francisco. RESULTS: Although none of these patients achieved insulin independence, four of seven had functioning grafts longer than 6 months as indicated by circulating C-peptide level greater than 0.7 ng/ml. Furthermore, improved glucose control as shown by a decreased insulin requirement was seen in 57% (four of seven patients) of these patients. The ability to isolate islets at a single laboratory and transport them long distances to different centers was shown in patients 4 through 7. CONCLUSIONS: Islet transplantation can be performed with improvements in blood glucose control, and islets can be isolated at a centralized location and successfully transported to different centers for transplantation.

Adult↗
PubMed1995

Local renin-angiotensin systems in cardiovascular tissues: localization and functional role.

In its classical definition, the renin-angiotensin system (RAS) acts predominantly by endocrine mechanisms. This view has been modified since several components of the RAS and their mRNAs were found in peripheral tissues. These findings gave rise to the concept of local tissue renin-angiotensin systems. Although no cells of cardiovascular organs containing a complete RAS have been identified as of this writing, angiotensinogen and angiotensin-converting enzyme (ACE) are most likely synthesized within the vasculature for example. Local synthesis of renin may be limited to very small amounts, but uptake of renin from the circulation is very likely. The function of local RASs is shown by reduction of blood pressure by ACE inhibitors, which correlates better with the inhibition of ACE activity in certain tissues than with its activity in the plasma. Further studies have put forward the notion that the circulating RAS could mainly be important for acute hemodynamic stability, whereas the tissue RAS could be involved in more long term maintenance of hemodynamics. This review will try to summarize the findings leading to the concept of a local tissue renin-angiotensin system, and discuss interactions between the circulating and the local RAS in the light of recent experimental findings.

Angiotensin II↗
PubMed1991

Beneficial and detrimental effects of RBC-adsorbed antilymphocyte globulin and prednisone on purified canine islet autograft and allograft function.

We have examined the effects of prednisone, cyclosporine, azathioprine, and RBC-adsorbed goat antidog antilymphocyte globulin on islet graft function in totally pancreatectomized canines with purified, quantitatively defined, autologous, or allogeneic islets transplanted to the liver. The objectives were twofold: (1) to determine the potential detrimental effects to islet autograft function of the aforementioned agents, and (2) to determine the relative efficacy of the "nontoxic" agents in prolonging purified islet allograft function administered in doses that would be considered tolerable in human. The islet autograft studies demonstrated that prednisone given in doses of 1-2 mg/kg/day had a detrimental effect on islet autograft function, and that the combinations of immunosuppression involving CsA, azathioprine, and ALG were not detrimental to islet autograft function to the extent that hyperglycemia would ensue. In the subsequent allograft studies, three groups of canines received islet transplants: (1) controls (n = 5; 7860 +/- 750 islets/kg/weight), (2) canines given CsA and azathioprine (n = 6; 6810 +/- 890 islets/kg/body weight), and (3) canines given CsA, azathioprine, and RBC-adsorbed goat antidog ALG (n = 8; 6540 +/- 710 islets/kg/body weight). The mean (+/- SE) day of rejection (serum glucose greater than or equal to 200 mg/dl) in the group of canine islet allograft recipients receiving CsA, azathioprine, and ALG was 11.8 +/- 1.4 days--significantly prolonged versus islet allograft recipients receiving no immunosuppression (mean survival 4.8 +/- 1.1 days, P less than 0.03), and versus allograft recipients receiving CsA/azathioprine without ALG (mean survival 4.4 +/- 1.4 days, P less than 0.05). Prednisone appears to be detrimental to islet graft function, even at low doses. ALG was not toxic, and significantly extended the survival of canine islet allografts. The inclusion of steroids as part of maintenance immunosuppression, or as treatment for acute rejection of islets, in human islet transplants should be reconsidered, whereas ALG or other antilymphocyte agents should continue to be used.

Adsorption↗
PubMed1990

Seroconversion to human immunodeficiency virus in prison inmates.

We evaluated the prevalence and incidence of human immunodeficiency virus (HIV) infection in 3,837 inmates of a state prison system. Ninety-two (2.4 percent) were HIV-seropositive. The highest proportion of HIV-seropositive inmates was found among Blacks (5.4 percent), females, and those 30 years of age or older. HIV-seropositivity of entering inmates was also 2.4 percent and was unchanged over the three years of the study. Seroconversion occurred in two inmates while in prison, a rate of one conversion per 604 person-years, but HIV infection could have occurred before entry. Seroconversion to HIV was rare in inmates in this correctional facility.

Adult↗
PubMed1989

Pharmacokinetics of 6-thiouric acid and 6-mercaptopurine in renal allograft recipients after oral administration of azathioprine.

The immunosuppressive activity of azathioprine (AZA) is unpredictable and depends on the formation of intracellular thiopurine ribonucleotides. However, the quantification of these active thiopurines presents difficult analytical problems. It has recently been postulated that plasma concentrations of 6-thiouric acid (6-TU) and 6-mercapto-purine (6-MP), metabolites of AZA, may provide more readily measurable indices of the pharmacologic activity of AZA. In order to evaluate the utility of 6-TU and 6-MP plasma concentrations in monitoring AZA therapy, we studied their pharmacokinetics in 6 renal transplant patients, and their in vitro immunosuppressive potency in a mixed lymphocyte proliferation assay. A peak plasma 6-TU concentration of 710.7 ng/ml was observed at 3.8 h after oral dosing. Good correlation was observed between the elimination t1/2 of 6-TU and serum creatinine, and between AUC over 24 h and serum creatinine. However, we did not observe a second peak in plasma 6-TU concentration that could be attributed to the degradation of active AZA metabolites. 6-MP plasma concentrations in the patients were low (mean peak concentration 36.0 ng/ml) and rapidly disappeared within 8 h. In vitro immunosuppressive activity could not be demonstrated for 6-TU over a concentration range of 1.25 ng/ml to 0.25 mg/ml. We conclude that 6-TU is pharmacologically inert and is primarily eliminated by the kidneys. Our findings currently do not support the use of plasma concentrations of 6-TU or 6-MP to monitor AZA therapy. In order to optimize AZA therapy, analytical techniques that are technically feasible and that can directly quantify the active intracellular thiopurines are being explored.

Adult↗
PubMed1987

Functional and phenotypical characterization of activated T cells from intra-articular sites in inflammatory joint diseases. Possible modulation of the CD3 antigen.

The presence of activated T lymphocytes bearing interleukin 2 (IL-2) receptors and HLA class II (Ia) antigens accompanied by impaired T cell functions such as a decreased mitogenic responsiveness are characteristic findings, especially in intra-articular sites in chronic inflammatory joint diseases. The objective of the present study was to further characterize these in vivo activated T cells by the investigation of IL-2 production and a possible T cell receptor modulation. IL-2 receptors were found to be expressed primarily in the CD4+ subset. The Ia+ subset expressing both DR and DQ antigens showed a weaker mitogen-induced response as compared to the Ia- fraction. A decreased mitogen-induced IL-2 production and a lower response to anti-CD3 monoclonal antibodies was observed with synovial T lymphocytes as compared to peripheral blood T cells. The density of the CD3 molecule, known to be closely associated with the T cell receptor, was significantly lower in intra-articular sites, while other T cell-specific surface molecules were expressed to a similar extent in both compartments. The decreased synovial T cell mitogenesis was not restored by the addition of lymphokines (IL-1 and IL-2) or blood monocytes, nor by removing CD8+ T cells. These data present further evidence for a significant T cell activation in intra-articular sites in chronic inflammatory joint diseases. The decreased expression of the CD3 glycoprotein suggests a modulation by so far unidentified antigen(s), which could also be responsible for the weak T cell response elicited by polyclonal mitogens.

Antibodies, Monoclonal↗
PubMed1986

Intraarticular T lymphocytes in monoarticular and oligoarticular inflammatory joint diseases. Normal subset distribution and less numbers of activated T cells indicate major differences as compared to rheumatoid arthritis.

T lymphocyte subpopulations and the expression of T cell activation antigens were determined in peripheral blood, synovial fluid and/or synovial tissues of patients with recurring monoarticular arthritis and patients with HLA-B27 associated oligoarthritis in comparison to patients with rheumatoid arthritis (RA). In individuals with monoarthritis or oligoarthritis, there was a normal T cell subset distribution, both in peripheral blood and in intraarticular sites, with only a small number of T cells bearing Ia antigens. This was in marked contrast to the patient group with RA that demonstrated a significantly decreased ratio of T helper/inducer to T suppressor/cytotoxic cells in addition to large numbers of Ia+ T cells in intraarticular sites. The expression of the Tac antigen was similar in all disease groups.

Adolescent↗
PubMed1979

Calcium secretion in the isolated perfused canine pancreas.

The quantitative relation of calcium and protein secretion was studied on the isolated perfused canine pancreas at different secretory states of hydrokinetic and ecbolic stimulation and various extracellular Ca++-concentrations. 1. Calcium and protein secretion are correlated at both ecbolic and hydrokinetic stimulation as well as by biological or synthetic secretion. 2. Enzyme-associated calcium was estimated at 35 nmol/mg protein and did not vary under differing stimulatory and secretory conditions. 3. During variable concentrations of synthetic secretin basal protein and calcium concentrations in the pancreatic juice show a hyperbolic relationship to the respective rates of fluid secretion. At flow rates beyond 3 ml/5 min the calcium concentrations asymptotically tend to 0.46 mEq/l while protein concentrations nearly decrease to zero. Moreover, the y-intercept of the regressionline correlating the calcium and protein concentrations gives with 0.48 mEq/l Ca++ additional evidence of the existence and magnitude of an enzyme-independent calcium fraction, which seems to remain constant over the whole range of secretory rates. 4. The omission of perfusate calcium does not abolish the calcium-protein correlation either at hydrokinetic or at ecbolic stimulation, but diminishes the enzyme-independent calcium fraction. 5. Enhancing perfusate Ca++-concentrations augments calcium output byt fails in stimulating enzyme secretion. It is concluded that at exclusively hydrokinetic stimulation basal secreted protein with a definite amount of chelated calcium is diluted by variable rates of pancreatic juice containing enzyme independent Ca++ at a constant concentration. During different secretory states of hydrokinetic or ecbolic stimulation the respective proportions of enzyme associated and independent calcium vary, and thus determine changes in the calcium-protein ratios. Extracellular calcium can only influence the non-protein-bound calcium fraction of the pancreatic juice presumably by diffusion from the extracellular fluid through the ductal epithelium rather than by an active secretory mechanism.

Animals↗
PubMed1977

[The influence of extracellular calcium on volume, enzyme and calcium secretion in the isolated perfused canine pancreas (author's transl)].

1. The kinetics of Ca++ and enzyme secretion are of corresponding pattern as well at hydrokinetic as at ecbolic stimulation. 2. Physiological respectively pathophysiologically relevant changes of perfusate Ca++ concentrations do not influence pancreatic Ca++ secretion. Extracellular Ca++ concentrations beyond 12 mEq/1 initiate an enzyme independent Ca++ secretion. 3. Hydrokinetic or ecbolic stimulated pancreatic secretion do not distinguish in calcium/protein ratio. 4. Basal and stimulated enzyme secretion of isolated perfused canine pancreas remain unaffected by increments of extracellular Ca++ concentrations even at pharmacological values. 5. The stimulated enzyme- and Ca++ secretion remain constant during hypocalcemic perfusate conditions but decrease to basal values in Ca++ free media, rapidly and completely reversible by recalcification of the perfusate. 6. The secretin stimulated volume secretion remains unchanged either by extremely hypercalcemic or Ca++ depleted perfusate conditions.

Animals↗