82 results on '"J. Harold Helderman"'
Search Results
52. Identifying and addressing potentially preventable causes of renal allograft loss
- Author
-
J. Harold Helderman and Anthony Langone
- Subjects
kidney transplant ,medicine.medical_specialty ,business.industry ,Graft thrombosis ,acute rejection ,Kidney transplant ,graft thrombosis ,Quality of life (healthcare) ,quality of life ,Nephrology ,medicine ,Renal allograft ,Intensive care medicine ,business - Published
- 2002
- Full Text
- View/download PDF
53. Isolated pleural involvement by Cryptococcus in a kidney–pancreas transplant recipient
- Author
-
Venkataraman Ramanathan, R. Stephen Dummer, Simin Goral, J. Harold Helderman, and Rumeyza Kazancioglu
- Subjects
Transplantation ,Pathology ,medicine.medical_specialty ,Kidney ,biology ,business.industry ,Transplant recipient ,Cryptococcus ,biology.organism_classification ,medicine.anatomical_structure ,Nephrology ,medicine ,Pancreas ,business - Published
- 2002
54. New and emerging immunosuppressive agents for kidney transplantation
- Author
-
J. Harold Helderman
- Subjects
Transplantation ,medicine.medical_specialty ,Nephrology ,business.industry ,Medicine ,business ,Intensive care medicine ,medicine.disease ,Kidney transplantation - Published
- 2011
55. Principles and Practice of Renal Transplantation
- Author
-
J. Harold Helderman and Anthony Langone
- Subjects
Transplantation ,medicine.medical_specialty ,Nephrology ,business.industry ,Medicine ,business ,Intensive care medicine - Published
- 2001
56. Identification of a monocyte-derived factor which regulates synthesis of insulin receptors on activated T-lymphocytes (MIRRF)
- Author
-
Scott Womble, J. Harold Helderman, Debra Womble, and Elias Ghandour
- Subjects
medicine.medical_treatment ,T-Lymphocytes ,Immunology ,Cycloheximide ,In Vitro Techniques ,Protein Sorting Signals ,Lymphocyte Activation ,Biochemistry ,Monocytes ,chemistry.chemical_compound ,Insulin receptor substrate ,medicine ,Immunology and Allergy ,Animals ,Receptor ,Molecular Biology ,biology ,Monocyte ,Insulin ,Hematology ,IRS2 ,Receptor, Insulin ,Cell biology ,Rats ,Insulin receptor ,medicine.anatomical_structure ,Cytokine ,chemistry ,Solubility ,Culture Media, Conditioned ,biology.protein - Abstract
The regulation of the insulin receptor on the activated T-lymphocyte was studied. It has been previously shown that the monocyte with its constitutive insulin receptor can signal the quiescent T-lymphocyte with respect to ambient insulin concentration which regulates the copies of insulin receptors synthesized during the lymphocyte activation event. In this communication it is shown that the vehicle by which the monocyte signals the T-lymphocyte is a soluble, small molecular weight protein. Initially a bioassay was established to test the putative monocyte-derived factor in which freshly prepared purified populations of monocytes were incubated with insulin, extensively washed, and replated with lymphocytes in microwells or across a 3 microns filter from lymphocytes using the appearance of insulin receptors on T lymphocytes responding to lectin as measured by a radioligand binding assay as the outcome variable. Dose response and time course relationships were established to develop the ideal conditions for the bioassay. It was shown that the monocyte-derived insulin receptor regulatory factor (MIRRF) could be readily detected in conditioned medium of insulin-incubated and then washed monocytes as a starting point for attempts at later purification. Using rats fed an essential fatty acid deficient diet (EFAD), incapable of generating standard prostanoids, it was demonstrated that the MIRRF was readily detectable in our standard bioassay revealing that the factor was not a member of the arachidonic acid family. Lastly, it was shown that MIRRF is cycloheximide sensitive and either is a protein or requires protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1992
57. Immunobiological consequence of regulation of insulin receptor on alloactivated lymphocytes in normal and obese subjects
- Author
-
Michael Koffler, Debra Womble, Philip Raskin, and J. Harold Helderman
- Subjects
Adult ,Blood Glucose ,medicine.medical_specialty ,Cellular immunity ,Time Factors ,medicine.medical_treatment ,Endocrinology, Diabetes and Metabolism ,T-Lymphocytes ,In Vitro Techniques ,Lymphocyte Activation ,Insulin Infusion Systems ,Reference Values ,Internal medicine ,Hyperinsulinism ,medicine ,Hyperinsulinemia ,Internal Medicine ,Humans ,Obesity ,Cytotoxicity ,Receptor ,biology ,Insulin ,T lymphocyte ,medicine.disease ,Mixed lymphocyte reaction ,Receptor, Insulin ,Insulin receptor ,Kinetics ,Endocrinology ,biology.protein ,Glucose Clamp Technique ,Lymphocyte Culture Test, Mixed ,Algorithms - Abstract
Acute manipulations of insulin in vivo regulate the display of insulin receptors induced on activated T lymphocytes after presentation of alloantigen. This study explored the immunobiological consequences of regulation of insulin-receptor display by acute manipulations of insulin achieved during the hyperinsulinemic-euglycemic clamp in healthy normal individuals and obese subjects. T lymphocytes were isolated at 0, 1, and 4 h of hyperinsulinemia from seven normal volunteers and seven obese individuals and studied for their capacity to 1) synthesize a complement of insulin receptors on cell membrane, 2) respond to alloantigen in the mixed-lymphocyte culture (an immunologic activity unrelated to manipulations in insulin concentrations in complete medium), and 3) respond to the lymphocyte-mediated cytotoxicity reaction (an immunologic activity known to be modulated by insulin). In the face of a reduction in receptor numbers to 25% of baseline in normal individuals, alloreactivity in the mixed-lymphocyte culture was not affected (95 ± 9% of time 0 after 4 h of hyperinsulinemia), whereas lymphocyte-mediated cytotoxicity fell from 14 ± 4 at time 0 to 2 ± 2% sp Cr release (P < 0.02). Hyperinsulinemia achieved by the clamp in seven obese subjects did not alter the synthesis of insulin receptors on cell membrane after presentation of alloantigen. In the absence of further reduction of insulin-receptor membrane display, neither the mixed-lymphocyte culture nor lymphocyte-mediated cytotoxicity reaction was affected. It is concluded that those immunologic activities of lymphocytes that can be modulated by insulin are affected by regulation of insulin-receptor display on activated lymphocytes. Therefore, receptor regulation is not effete but carries significant immunologic consequence. This study supports the hypothesis that insulin-directed immunologic activity is regulated at the site of receptor display rather than at the locus of regulation of the ligand itself.
- Published
- 1991
58. A puzzle solved
- Author
-
J. Harold Helderman
- Subjects
medicine.medical_specialty ,Text mining ,medicine.diagnostic_test ,Nephrology ,business.industry ,General surgery ,Biopsy ,medicine ,Kidney pathology ,MEDLINE ,business - Published
- 1999
59. Xenotransplants: proceed with caution
- Author
-
Daniel R. Salomon, Ronald M. Ferguson, and J. Harold Helderman
- Subjects
Multidisciplinary - Published
- 1998
60. Introduction
- Author
-
J Harold Helderman
- Subjects
Transplantation - Published
- 2001
61. Progressive multifocal leukoencephalopathy in a renal transplant recipient
- Author
-
J. Harold Helderman, F. Kevin Murphy, Craig R. Saxton, Peter Gailiunas, Elliot D. Ross, Jan Diehl, Rosemary McCoy, Fred R. Silva, Arthur I. Sagalowsky, Duard L. Walker, and Robert A. Farkas
- Subjects
medicine.medical_specialty ,Kidney ,medicine.diagnostic_test ,Double dose ,business.industry ,Progressive multifocal leukoencephalopathy ,media_common.quotation_subject ,Brain biopsy ,General Medicine ,medicine.disease ,Computed tomographic ,Contrast medium ,medicine.anatomical_structure ,Renal transplant ,medicine ,Contrast (vision) ,Radiology ,business ,media_common - Abstract
A progressive, deteriorating neurologic disorder developed in a 28-year-old white man 10 years after he successfully received a living related donor kidney transplant. An extensive neurologic evaluation was unrevealing, including normal results of computed tomographic scanning of the brain with and without contrast medium. Repeated computed tomographic scanning after a double dose of radiocontrast medium in conjunction with delayed imaging revealed multiple areas of abnormal enhancement. This technique helped to direct brain biopsy, which led to the early diagnosis of progressive multifocal leukoencephalopathy and the institution of specific therapy.
- Published
- 1984
62. Relationship between lipoprotein levels and in vivo insulin action in normal young white men
- Author
-
Abhimanyu Garg, Michael Koffler, Philip Raskin, J. Harold Helderman, Romulo Ayuso, and Julio Rosenstock
- Subjects
Adult ,Blood Glucose ,Male ,medicine.medical_specialty ,Very low-density lipoprotein ,Adolescent ,Lipoproteins ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Lipoproteins, VLDL ,chemistry.chemical_compound ,Insulin Infusion Systems ,Endocrinology ,High-density lipoprotein ,Insulin resistance ,Internal medicine ,Hyperinsulinemia ,medicine ,Humans ,Insulin ,Triglycerides ,Cholesterol ,Cholesterol, HDL ,Glucose clamp technique ,medicine.disease ,Lipoproteins, LDL ,chemistry ,Low-density lipoprotein ,lipids (amino acids, peptides, and proteins) ,Insulin Resistance - Abstract
In epidemiologic studies, hyperinsulinemia has been found to be an independent risk factor for coronary heart disease (CHD). However, the mechanisms responsible for its role in atherogenesis remain unclear. We studied the relationship of in vivo insulin action and plasma lipids and lipoproteins in 44 normotriglyceridemic white men (aged 18 to 34 years). The euglycemic, hyperinsulinemic glucose clamp technique was used to quantitate insulin-mediated glucose disposal (MI value) at a plasma insulin concentration of approximately 100 μU/mL. The MI value correlated negatively with plasma triglycerides (r = −0.553, P < .0001), as well as with fasting plasma insulin levels (r = −0.483, P < .001), independent of age, body mass index, and fasting plasma glucose levels. A negative correlation of the MI value was also observed with very low density lipoprotein (VLDL)-cholesterol (r = −0.347, P < .05), VLDL-triglycerides (r = −0.474, P < 0.005), and total cholesterol/high density lipoprotein (HDL)-cholesterol ratio (r = −0.431, P < .01). The relationship between the MI value and the total cholesterol/HDL-cholesterol ratio was independent of VLDL-cholesterol and VLDL-triglycerides, however, not independent of plasma triglycerides. No relationship was observed between insulin-mediated glucose uptake and total cholesterol, low density lipoprotein (LDL)-cholesterol, and HDL-cholesterol values. Individual differences in plasma triglycerides, fasting insulin concentration, and the total cholesterol/HDL-cholesterol ratio accounted for about half the variance observed in the MI value. In conclusion, our findings in normal healthy men support the contention that hyperinsulinemia or insulin resistance may enhance the risk of CHD by adversely affecting lipoprotein levels such as VLDL-cholesterol, VLDL-triglyceride, and the ratio of total cholesterol/HDL-cholesterol.
- Published
- 1988
63. Disease due to cytomegalovirus and its long-term consequences in renal transplant recipients. Correlation of allograft survival with disease due to cytomegalovirus and rubella antibody level
- Author
-
Alan R. Hull, Sandra L. Butler, Athol J. Ware, C. Atkins, James P. Luby, J. Harold Helderman, and Peter Gailiunas
- Subjects
medicine.medical_specialty ,Leukopenia ,biology ,business.industry ,Congenital cytomegalovirus infection ,Rubella virus ,Disease ,medicine.disease ,medicine.disease_cause ,Rubella ,Gastroenterology ,Transplantation ,Pneumonia ,surgical procedures, operative ,Internal medicine ,Immunology ,Internal Medicine ,medicine ,biology.protein ,medicine.symptom ,Antibody ,business - Abstract
• We prospectively studied 52 consecutive renal allograft recipients who retained their grafts at least three months. The transplant recipients were observed for five years or longer. Disease due to cytomegalovirus (CMV) occurred in nine (17.3%). Manifestations of disease due to CMV that were significantly more common than in chronologically matched controls in comparable periods after transplantation included fever, leukopenia, hepatic function abnormalities, pneumonia, and renal dysfunction. Life-table analyses suggested a trend of decreased allograft survival with disease due to CMV, but the difference between controls was not statistically significant. A significant inverse correlation were noted between the level of hemagglutination inhibition antibody to rubella virus reached after transplantation and allograft survival. This correlation remained statistically significant even when patients with disease due to CMV were excluded from the analysis. ( Arch Intern Med 1983;143:1126-1129)
- Published
- 1983
64. A controlled study of cellular immune function in affective disorders before and during somatic therapy
- Author
-
Joachim Albrecht, A. John Rush, J. Harold Helderman, and Michael A. Schlesser
- Subjects
Adult ,Male ,medicine.medical_specialty ,Bipolar Disorder ,T-Lymphocytes ,medicine.medical_treatment ,chemical and pharmacologic phenomena ,Stimulation ,Endogeny ,Antidepressive Agents, Tricyclic ,Lithium ,Lymphocyte Activation ,Immune system ,Electroconvulsive therapy ,Internal medicine ,medicine ,Humans ,Electroconvulsive Therapy ,Biological Psychiatry ,Depression (differential diagnoses) ,Depressive Disorder ,Middle Aged ,Somatic psychology ,Lymphocyte blastogenesis ,Psychiatry and Mental health ,Endocrinology ,Immunology ,Female ,Psychology - Abstract
Lymphocyte blastogenesis induced by lectins (PHA, Con A, and PWM) was assessed in 27 drug-free patients with unipolar (n = 21) or bipolar (n = 5) depression and 13 normal controls. Fifteen patients were restudied after clinical remission. Symptomatic patients did not differ from controls nor did endogenous and nonendogenous depressions differ in their lymphocyte blastogenesis response to any of the three lectins. However, a significant reduction in lymphocyte blastogenesis with both PHA and Con A stimulation was found following somatic treatment. Cellular immune function appears to be normal in depressed patients, although the somatic therapies are associated with a reduction in this function.
- Published
- 1985
65. The pathogenesis of Alport syndrome involves type IV collagen molecules containing the α3(IV) chain: Evidence from anti-GBM nephritis after renal transplantation
- Author
-
Manfred Weber, Julie K. Hudson, Milton E. Noelken, William J. Stone, Dale R. Abrahamson, Billy G. Hudson, Michael A. Haralson, Raghuram Kalluri, Juan Saus, Fernando Ballester, J. Harold Helderman, Walter R. Richardson, Alan D. Glick, Michael P. Sarras, Harry R. Jacobson, and Sripad Gunwar
- Subjects
Adult ,Collagen Type IV ,Male ,Isoantigens ,Pathology ,medicine.medical_specialty ,Kidney Glomerulus ,Nephritis, Hereditary ,urologic and male genital diseases ,Autoantigens ,Basement Membrane ,Type IV collagen ,Isoantibodies ,medicine ,otorhinolaryngologic diseases ,Humans ,Goodpasture syndrome ,Alport syndrome ,Basement membrane ,Kidney ,Nephritis ,business.industry ,urogenital system ,Glomerular basement membrane ,Glomerulonephritis ,medicine.disease ,Kidney Transplantation ,female genital diseases and pregnancy complications ,Transplantation ,medicine.anatomical_structure ,Nephrology ,Immunology ,Collagen ,business - Abstract
The pathogenesis of Alport syndrome involves type IV collagen molecules containing the α3(IV) chain: Evidence from anti-GBM nephritis after renal transplantation. Mutations in the COL4A5 collagen gene have been implicated as the primary defect in Alport syndrome, a heritable disorder characterized by sensorineural deafness and glomerulonephritis that progresses to end-stage renal failure. In the present study, the molecular nature of the defect in Alport glomerular basement membrane (GBM) was explored using anti-GBM alloantibodies (tissue-bound and circulating) produced in three Alport patients subsequent to renal transplantation. The alloantibodies bound to the α3(IV)NC1 domain of type IV collagen and not to any other basement membrane component. In tissue sections, the alloantibodies bound specifically to peripheral GBM in normal kidney and the affected renal transplant but not to that of Alport kidney. These results establish that: the α3 chain in type IV collagen molecules, the Goodpasture autoantigen, is the target alloantigen in post-transplant anti-GBM nephritis in patients with Alport syndrome, and that a molecular commonality exists in the pathogenesis of anti-GBM nephritis causing loss of renal allografts in patients with Alport syndrome and renal failure in patients with Goodpasture syndrome. These findings implicate: (1) defective assembly of type IV collagen molecules containing the α3(IV) chain in Alport GBM; and (2) the existence of a mechanism linking the assembly of molecules containing the α3(IV) chain with those containing the α5(IV) chain.
- Full Text
- View/download PDF
66. The use of monoclonal antibodies in fine needle aspiration biopsy of the renal transplant
- Author
-
J. Harold Helderman
- Subjects
Graft Rejection ,Pathology ,medicine.medical_specialty ,medicine.drug_class ,Monoclonal antibody ,Kidney ,Lymphocyte Activation ,Giemsa stain ,Biopsy ,Medicine ,Humans ,Lymphocytes ,Kidney transplantation ,HLA-D Antigens ,medicine.diagnostic_test ,business.industry ,Biopsy, Needle ,Antibodies, Monoclonal ,medicine.disease ,Kidney Transplantation ,Transplantation ,medicine.anatomical_structure ,Fine-needle aspiration ,Nephrology ,Renal biopsy ,business - Abstract
This report deals with the clinical application of monoclonal antibody techniques to fine needle aspiration biopsy (FNAB) of the renal transplant. The technique was deemed to be quite helpful in corroborating cell type analysis made by classical cytochemistry (Giemsa staining), and determination of the nature of the lymphoid subset at play in rejection. The role of activation marker analysis and class 2 alloantigen analysis in particular for rejection was also discussed.
- Published
- 1988
67. The response of arginine vasopressin to intravenous ethanol and hypertonic saline in man: the impact of aging
- Author
-
John W. Rowe, Gary L. Robertson, Reubin Andres, Robert E. Vestal, Jordan D. Tobin, and J. Harold Helderman
- Subjects
Adult ,Male ,Vasopressin ,medicine.medical_specialty ,Aging ,Hypothalamo-Hypophyseal System ,Arginine ,Vasopressins ,Sodium Chloride ,Kidney ,Infusion Procedure ,Internal medicine ,medicine ,Humans ,Saline Solution, Hypertonic ,Osmoreceptor ,Ethanol ,business.industry ,Osmolar Concentration ,Middle Aged ,Stimulation, Chemical ,Hypertonic saline ,Arginine Vasopressin ,medicine.anatomical_structure ,Endocrinology ,Hypothalamus ,Renal physiology ,Depression, Chemical ,business ,Secretory Rate - Abstract
The effect of age on the hypothalamic-hypophyseal-renal axis in normal man was determined by assaying plasma arginine vasopressin (AVP) responses to inhibitory and to secretory stimuli. Nine young (21-49 years) and 13 old (54-92 years) subjects received IV ethanol (375 mg/m2 per min). AVP levels fell progressively during the infusion in the young group, but fell for only 30 min in the old group and then rose paradoxically despite the continuing increase in blood ethanol. Eight young (22-48 years) and 8 old (52-66 years) men were provided identical osmolal loads by a 2-hour IV infusion of 3% NaCl at 0.1 ml/kg per min. Serum AVP rose 2.5 times the baseline in the young and 4.5 times the baseline in the old men despite identical free water clearances. Osmoreceptor sensitivity (the slope of AVP on osmolality) was greater in the old subjects. The heightened sensitivity to hyperosomolality helps examine the paradoxical response to ethanol, since osmolality increased during that time. This increased AVP response may severe to compensate for the reduced renal ability to conserve salt and water in aging man.
- Published
- 1978
68. Dialysis and transplantation in end-stage lupus nephritis
- Author
-
J. Harold Helderman and Morris Ziff
- Subjects
medicine.medical_specialty ,Time Factors ,medicine.medical_treatment ,Lupus nephritis ,urologic and male genital diseases ,immune system diseases ,Renal Dialysis ,Internal medicine ,medicine ,Humans ,Lupus Erythematosus, Systemic ,Stage (cooking) ,skin and connective tissue diseases ,Dialysis ,Nephritis ,business.industry ,General Medicine ,medicine.disease ,Kidney Transplantation ,Transplantation ,Immunology ,Kidney Failure, Chronic ,Azotemia ,business ,Immunosuppressive Agents ,Anti-SSA/Ro autoantibodies - Abstract
Physicians who treat patients with systemic lupus erythematosus have long been aware that in those who reach a stage of advanced azotemia, remission of the nonrenal features of the illness and impr...
- Published
- 1983
69. Constancy of pharmacokinetic properties of the lymphocyte insulin receptor during aging
- Author
-
J. Harold Helderman
- Subjects
Adult ,Male ,medicine.medical_specialty ,Aging ,Lymphocyte ,medicine.medical_treatment ,T-Lymphocytes ,Carbohydrate metabolism ,Internal medicine ,Insulin receptor substrate ,medicine ,Humans ,Phytohemagglutinins ,Receptor ,Cells, Cultured ,Aged ,biology ,Insulin ,Infant, Newborn ,Receptor, Insulin ,Insulin receptor ,Kinetics ,medicine.anatomical_structure ,Endocrinology ,Hormone receptor ,biology.protein ,Beta cell ,Thymidine - Abstract
Carbohydrate metabolism is altered during aging. Alterations at the pancreatic beta cell and at the level of peripheral sensitivity to insulin have been invoked. The T lymphocyte insulin receptor from five younger and five older men were studied. Pharmacokinetic characteristics (affinity, kd, and receptor sites per cell) were the same for both. Peripheral insensitivity at the level of the hormone receptor does not explain the altered metabolism.
- Published
- 1980
70. Noninvasive monitoring of renal transplant function by analysis of beta2-microglobulin
- Author
-
L. Lee Hamm, Linda C. Edwards, J. Harold Helderman, David Ludwin, Peter Gailiunas, and Alan R. Hull
- Subjects
Graft Rejection ,medicine.medical_specialty ,Pathology ,medicine.medical_treatment ,Beta-Globulins ,Renal function ,Kidney ,chemistry.chemical_compound ,Internal medicine ,Sieving coefficient ,medicine ,Humans ,Creatinine ,business.industry ,Beta-2 microglobulin ,Glomerular basement membrane ,Acute Kidney Injury ,medicine.disease ,Kidney Transplantation ,Transplant rejection ,Endocrinology ,medicine.anatomical_structure ,chemistry ,Nephrology ,Hemodialysis ,business ,beta 2-Microglobulin - Abstract
Beta 2 -microglobulin (β 2 M) is a low molecular weight (11,800 daltons) globular protein detected on the cell membrane of all nucleated cells, including lymphocytes, where it is associated with the glycoproteins of the major histocompatibility complex. With a small sized Stokes radius, 16 Å, and a sieving coefficient of 0.7 to 1.0, β 2 M diffuses freely between intra- and extravascular space and is freely filtered through the glomerular basement membrane, then reabsorbed (99.9%) and degraded by the proximal tubular cells. The kidney, the major site of the catabolism of β 2 M [1, 2], can extract and metabolize β 2 M even in the absence of glomerular filtration [3, 4]. Under normal circumstances, cellular synthesis, release, and catabolism of this protein varies little in an individual. Although certain inflammatory, immunologic, and neoplastic disorders can produce elevated serum levels in patients with normal renal function, the usual cause of an elevation in serum beta 2 -microglobulin (sβ 2 M) is renal insufficiency. Because of these properties, β 2 M is an excellent indicator of GFR [1]. Moreover, in patients with recent kidney allografts who pass scanty amounts of urine, continued clearance of β 2 M from the plasma may be taken as evidence of graft viability [3, 4]. These properties permit an analysis of the utility of sβ 2 M measurements as a noninvasive laboratory assessment of renal transplant status. At present, serum creatinine (sCr) is the standard, noninvasive test available to evaluate renal function. However, creatinine values can lag behind the histologic changes observed in the rejection process and are of no use during hemodialysis or in the presence of postsurgical acute renal failure. The purpose, then, of this study was to explore the relationship between sCr and β 2 M serum concentrations and to evaluate the utility of monitoring transplant function with sβ 2 M. We found a strong correlation between β 2 M serum concentration and sCr, that a rise in sβ 2 M heralded the diagnosis of transplant rejection, and that continued clearance of sβ 2 M in the absence of excretory renal function supported a diagnosis of postsurgical acute renal failure.
- Published
- 1983
71. Quadruple Induction Immunosuppression in Cadaver Renal Transplantation
- Author
-
J. Harold Helderman, Paul C. Peters, Ingemar Dawidson, Arthur I. Sagalowsky, and Robert D. Toto
- Subjects
Transplantation ,medicine.medical_specialty ,Induction immunosuppression ,Cadaver ,business.industry ,Urology ,medicine ,business ,Surgery - Published
- 1987
72. Renal transplantation in diabetic patients: the end result does justify the means
- Author
-
J. Harold Helderman, Paul C. Peters, Peter Gailiunas, C. Atkins, Alan R. Hull, Arthur I. Sagalowsky, Richard M. Dickerman, and Charles W. Ransler
- Subjects
Adult ,Male ,medicine.medical_specialty ,Urology ,medicine.medical_treatment ,Postoperative Complications ,Allograft survival ,Medicine ,Humans ,Diabetic Nephropathies ,Kidney transplantation ,Dialysis ,business.industry ,Graft Survival ,Patient survival ,Middle Aged ,medicine.disease ,Kidney Transplantation ,Surgical morbidity ,Surgery ,Transplantation ,surgical procedures, operative ,Renal allograft ,Kidney Failure, Chronic ,Female ,business ,Cadaveric spasm - Abstract
There were 49 insulin-dependent diabetics who received 52 renal allografts: 13 from living related and 39 from cadaveric donors. The mean age and time on dialysis were similar for both recipient groups. Patient survival at 1 and 2 years was 100 per cent for living related donor recipients, and 76 and 56 per cent at 1 and 2 years for cadaveric recipients. Renal allograft survival was 92 and 85 per cent at 1 and 2 years for living related donor recipients. Cadaveric allograft survival was 49 and 41 per cent at 1 and 2 years. The cumulative mortality rate was 39 per cent and the over-all surgical morbidity was low. Renal transplantation in diabetic patients is worthwhile from the standpoint of patient and allograft survival.
- Published
- 1983
73. Urologic complications in 505 renal transplants with early catheter removal
- Author
-
Paul C. Peters, J. Harold Helderman, C. Atkins, Peter Gailiunas, Arthur I. Sagalowsky, Alan R. Hull, Charles W. Ransler, and Richard M. Dickerman
- Subjects
Postoperative Care ,Urologic Diseases ,medicine.medical_specialty ,business.industry ,Urology ,Graft Survival ,Urinary Bladder Diseases ,Patient survival ,Bladder catheter ,Kidney Transplantation ,Surgery ,Postoperative Complications ,Cadaver ,medicine ,Humans ,Ureteral Diseases ,Catheter removal ,business ,Urinary Catheterization - Abstract
Of 505 consecutive renal transplants urologic complications occurred in 4.1 per cent of cadaver, 2.6 per cent of living related, 1.9 per cent of diabetic and 3.8 per cent of nondiabetic allografts. Over-all, patient survival and graft salvage rates were 94 and 83 per cent, respectively. Principles of prevention, diagnosis and management of these complications are discussed. In contrast to prior standards the bladder catheter was removed within 36 hours postoperatively in nearly all cases without any increase in morbidity.
- Published
- 1983
74. THE INSULIN RECEPTOR ON THE T CELL: A MARKER OF ACTIVATION AFTER STIMULATION
- Author
-
J. Harold Helderman and Terry B. Strom
- Subjects
medicine.medical_specialty ,education.field_of_study ,Lymphocyte ,Insulin ,medicine.medical_treatment ,T cell ,Population ,Biology ,Insulin receptor ,Endocrinology ,medicine.anatomical_structure ,Internal medicine ,medicine ,biology.protein ,Macrophage ,Bovine serum albumin ,Cytotoxicity ,education - Abstract
Publisher Summary This chapter explores alloactivated T cells that express de novo an insulin receptor. The insulin receptor has been found on the membrane of a multitude of tissues—some insulin sensitive such as liver and fat and some seemingly insulin insensitive in a classical metabolic sense such as macrophage. In a study described in the chapter, allostimulation was accomplished by means of a skin graft from F1 to a male Lewis rat. The non-adherent cells were divided into one set that was placed in Hanks +0.1% bovine serum albumin for subsequent assay of insulin binding and another aliquot placed in the RPMI for the assay of lymphocyte mediated cytotoxicity. The cell-purification techniques employed yielded a population highly enriched for T cells (95%), poor for B cells (5%), and deplete for macrophages. Allostimulation induces the formation of clones of T cells capable of specific cell lysis and the appearance of insulin receptors.
- Published
- 1977
75. Prospective evaluation of renal allograft dysfunction with 99mtechnetium-diethylenetriaminepentaacetic acid renal scans
- Author
-
John D. McConnell, J. Harold Helderman, Ingemar Dawidson, Arthur I. Sagalowsky, Paul C. Peters, S. E. Lewis, and Peter Gailiunas
- Subjects
Graft Rejection ,medicine.medical_specialty ,Urology ,chemistry.chemical_element ,Technetium ,Scintigraphy ,Kidney ,Kidney Function Tests ,Isotopes of technetium ,Renal Circulation ,Medicine ,Humans ,Prospective Studies ,Radionuclide Imaging ,Clinical Trials as Topic ,medicine.diagnostic_test ,business.industry ,Blood flow ,Kidney Tubular Necrosis, Acute ,Pentetic Acid ,Kidney Transplantation ,medicine.anatomical_structure ,chemistry ,Renal blood flow ,Technetium Tc 99m Pentetate ,Differential diagnosis ,business ,Nuclear medicine ,Complication - Abstract
A prospective, single-blinded study was done to determine the ability of serial 99mtechnetium-diethylenetriaminepentaacetic acid scans to diagnose renal allograft rejection. Among 28 transplant recipients 111 renal scans were obtained 1 day postoperatively and every 3 to 4 days thereafter for 3 weeks in all patients retaining an allograft. Computer-generated time-activity blood flow curves were analyzed semiquantitatively for the 1) interval between curve peaks of the allograft and iliac artery, 2) renal transit time and 3) renal washout of radionuclide. Excretory function was assessed by degree and interval to appearance of radionuclide in the calices and bladder. Deterioration of renal blood flow and excretion compared to the initial scan was considered rejection. Of 52 scans performed during clinical rejection 47 (90.4 per cent) were interpreted as showing rejection (sensitivity). Of 53 scans interpreted as showing rejection 47 (88.7 per cent) were positive for clinical rejection. The remaining 6 patients (initial false positive results) suffered clinical rejection within 24 to 72 hours. We conclude that 99mtechnetium-diethylenetriaminepentaacetic acid renal scans are useful in the differential diagnosis of renal allograft dysfunction.
- Published
- 1984
76. Specific insulin binding site on T and B lymphocytes as a marker of cell activation
- Author
-
Terry B. Strom and J. Harold Helderman
- Subjects
medicine.medical_specialty ,Lymphocyte ,medicine.medical_treatment ,Biology ,Lymphocyte Activation ,Article ,Graft vs Host Reaction ,Lectins ,Internal medicine ,medicine ,Animals ,Transplantation, Homologous ,Cytotoxic T cell ,Lymphocytes ,Receptor ,Insulin-like growth factor 1 receptor ,Multidisciplinary ,Insulin ,Skin Transplantation ,Molecular biology ,Receptor, Insulin ,Rats ,Insulin receptor ,medicine.anatomical_structure ,Endocrinology ,Hormone receptor ,biology.protein ,Lymphocyte Culture Test, Mixed ,Cell activation ,Spleen - Abstract
Attempts to identify an easily measured cell surface marker that would detect activation of T or B lymphocytes in a variety of species have been unsuccessful. Although insulin receptors have been identified for fat, liver, skeletal and cardiac muscle, fibroblasts and monocytes1–8, quiescent rat splenic T lymphocytes do not bear such receptors. However, insulin receptors do emerge on T lymphocytes after concanavalin A treatment or allogeneic skin grafting9,10. Following our work on characterising a lymphocyte insulin receptor which participates in the modulation of immune response11, we have examined and report here the possibility that the emergence of a membrane-bound receptor for the peptide hormone insulin may be a universal marker for activated T and B lymphocytes. Rat splenic lymphocyte cell suspensions were established in RPMI-1640 media buffered with 5 mM HEPES and fortified with 5% sterile, heat-inactivated fetal calf serum (designated ‘enriched’ media). Leukocytes were collected from a Ficoll-Hypaque gradient. The cells were fractionated on nylon wool columns yielding T-enriched, nylon wool-nonadherent cells and B-enriched, nylon wool-adherent cells. Macrophages were removed from all final cell suspensions by removing the cells that phagocytose iron particles with magnetic attraction. Insulin binding assays were carried out in suspensions containing 107 cells per ml in Hank’s balanced salt solution enriched with 0.1% bovine serum albumin for analysis of receptor binding or the ‘enriched’ media for analysis of thymidine incorporation. Such purification techniques were evaluated using cell surface markers for the Fc receptor, the complement receptor, surface immunoglobulin, anti-θ determinants, and acridine orange and p-rosaniline staining characteristics. The insulin receptor was measured by the use of a modification of the insulin binding assay described by Gammeltoft and Gliemann12 which has been extensively described10. In brief, the assay involves a competitive binding reaction between radiolabelled insulin and unlabelled monocomponent porcine insulin. By such competition, both total and nonspecific isotopic binding may be measured, and specific (receptor) binding can be calculated. Specific binding is 50–60% of the total binding and is similar to that of the fibroblast. Final separation of cell-bound from free insulin was accomplished over oil with virtually no contamination of the cell fraction by free insulin and recovery of 93% of cells for analysis. Lymphocyte cultures were also evaluated for the intracellular accumulation of tritiated thymidine after a four-hour pulse of 106 cells in flat-bottom microtitre plates (1 μ Ci per well). Five separate experimental protocols which result in lymphocyte activation were tested (Table 1). In vivo activation was accomplished by: (1) skin transplantation with histoincompatible ((Lewis × Brown Norway) F1→ Lewis male rat) grafts; (2) graft-versus-host disease established by intraperitoneal injections of 2×l08 Lewis splenic lymphocytes weekly for four weeks into (Lewis × Brown Norway) F1 animals. In vitro activation was established in the following ways: (1) unidirectional mixed lymphocyte cultures were established using T-enriched Lewis splenic lymphocytes as responder cells and Brown Norway mitomycin-treated thymocytes as stimulating cells. Cells were collected after three days of culture. On termination of the cultures, stimulator cells were removed by specific antibody and complement treatment and the responder cells were assessed for the presence of insulin receptors; (2) varying lymphocyte populations were cultured with the plant lectin concanavalin A (con A), phytohaemagglutinin (PHA-P), or Escherichia coli lipopolysaccharide (LPS). Table 1 Appearance of specific insulin binding site on T or B lymphocytes after in vivo or in vitro stimulation Table 1 summarises our findings. After in vivo lymphocyte activation by either skin grafting or the graft-versus-host reaction, lymphocyte receptors with similar binding properties emerged. In vitro, T-enriched lymphocytes developed the insulin receptor after allogeneic stimulation in the unidirectional mixed lymphocyte culture or after mitogenic stimulation with con A or PHA but not LPS. B-enriched lymphocytes, but not T cells, developed the insulin receptor in vitro after specific T-dependent mitogen stimulation. When T lymphocytes and B lymphocytes were co-cultured with a T-cell mitogen (PHA-P), both cell populations developed the hormone receptor, probably secondary to T–B cellular interaction (data not shown). The specific binding site did not emerge after syngeneic skin grafting or co-culture with syngeneic cells. The insulin binding was saturable, specific, expressed high affinity for insulin, and was readily displaceable from the receptor. A representative binding isotherm and binding competition curve are shown in Fig. 1 for the experimental protocol using allogeneic skin engraftment. Fig. 1 A representative binding isotherm (a) and binding competition curve (b) for insulin on lymphocytes from Lewis rats 7 d after receiving (Lewis × Brown Norway) F1 skin allografts. The half maximal equilibrium constant, calculated from the concentration ... Most polypeptide hormones convey their signals to target cells through interaction with membrane recognition units, receptors13. The criteria which established binding sites on cell membranes as specific hormone receptors include a demonstration of ligand specificity, reversibility, saturation kinetics, an affinity for hormone consistent with ligand–receptor complex formation in vivo, and a biological function. The T lymphoctye insulin binding site satisfies the first four conditions after activation by in vivo or in vitro stimuli. The high affinity of binding potentially allows the lymphocyte to be functionally modulated by circulating concentrations of insulin. Furthermore, binding of insulin to its putative receptor augments cytotoxic effector lymphocyte function10,11. Thus, the specific binding site for insulin on the lymphocyte is a biological receptor. Previous attempts at identification of cell surface markers that identify the active state of lymphocytes have been either unsuccessful or restrictive. The Fc receptor on the T cell14, once thought to identify the active state, has been found in several resting lymphocytes15,16. Most recently, an antigen, Ala-1, has been described in mouse, occurring on lymphocytes exclusively as a result of cellular activation17, 18. This antigen, however, is species specific and genetically restricted with at least several alleles. In contrast, the insulin receptor on lymphocytes is a marker of cellular activation which can be widely and generally applied. It is not clone specific, may be applied to activated B as well as T lymphocytes, and is not genetically or species restricted but occurs in all strains in rat and mice so far tested after manoeuvres causing cellular activation. As T-cell and B-cell mitogens selectively stimulate the appearance of T-cell or B-cell insulin receptors, these data suggest that only the subpopulation of cells that has been activated develops a receptor for insulin. Preliminary evidence from our laboratory demonstrates that the receptor also marks the active state in man19. Thus, the lymphocyte insulin receptor may be a universal marker of lymphocyte activation.
- Published
- 1978
77. Long-Term Survival and Late Development of Bladder Cancer in Renal Transplant Patient with Progressive Multifocal Leukoencephalopathy
- Author
-
Paul C. Peters, Arthur I. Sagalowsky, J. Harold Helderman, Fred G. Silva, and Jeffrey R. Embrey
- Subjects
Male ,medicine.medical_specialty ,Time Factors ,Late development ,Adolescent ,Urology ,medicine.medical_treatment ,urologic and male genital diseases ,Long term survival ,medicine ,Recurrent disease ,Humans ,Cyclophosphamide ,Immunosuppression Therapy ,Carcinoma, Transitional Cell ,Bladder cancer ,business.industry ,Progressive multifocal leukoencephalopathy ,Leukoencephalopathy, Progressive Multifocal ,Immunosuppression ,medicine.disease ,Kidney Transplantation ,Surgery ,Transitional cell carcinoma ,Urinary Bladder Neoplasms ,Renal transplant ,business - Abstract
We describe a renal transplant recipient in whom progressive multifocal leukoencephalopathy and transitional cell carcinoma of the bladder developed. Despite these potentially fatal sequelae of chronic immunosuppression the patient remains free of recurrent disease.
- Published
- 1988
78. Hepititis C and renal transplantation: The controversy continues
- Author
-
J. Harold Helderman and Simin Goral
- Subjects
medicine.medical_specialty ,Cirrhosis ,medicine.medical_treatment ,graft survival ,Chronic liver disease ,Gastroenterology ,Organ transplantation ,Liver disease ,Internal medicine ,medicine ,Humans ,Renal replacement therapy ,Dialysis ,Hepatitis ,business.industry ,Contraindications ,virus transmission ,medicine.disease ,Hepatitis C ,Kidney Transplantation ,infection ,Transplantation ,Nephrology ,Immunology ,Kidney Failure, Chronic ,business ,liver disease ,transplantation - Abstract
Hepatitis C virus (HCV) infection, the leading cause of posttransplant liver disease, has recently been recognized as one of the major causes of morbidity and mortality in renal transplantation. Most HCV antibody-positive recipients acquire HCV infection before or at the time of transplantation. The prevalence of HCV among patients with end-stage renal disease (ESRD) undergoing dialysis is reported between 12% to 85%, depending on the techniques used such as antibody and RNA assays [1‐ 4]. It has been shown that HCV is transmissible by organ transplantation [5, 6]. In recipients of kidneys from HCV antibody positive donors, 57 to 96% were tested positive for HCV RNA by polymerase chain reaction (PCR) and 0 to 55% developed post-transplantation liver disease [7]. There have been controversial reports on the long-term effects of HCV infection on graft and patient survival in kidney transplant recipients. In this issue of Kidney International, Pereira and colleagues analyze the impact of HCV infection on survival of kidney transplant and ESRD patients [8]. They report that the presence of HCV infection was associated with an increased risk of death in patients referred for renal transplantation, and the effect of transplantation was similar in anti-HCV positive and negative patients. They conclude that anti-HCV positive status is not a contraindication for renal transplantation, which has a beneficial effect on long-term survival in anti-HCV positive patients. The report by Pereira and associates provides new fuel to the controversy as to how HCV infection alters outcomes in ESRD and transplant population [8]. Two important infection-related outcomes are described by the authors: the relationship of infection to chronic liver disease and to transplant outcome. There have been other reports of progressive liver disease in HCVinfected renal allograft recipients. A study by Morales et al demonstrated that more than 50% of HCV positive renal transplant recipients exhibited a severe pattern including cirrhosis, chronic active hepatitis and chronic persistent hepatitis in liver biopsies indicating the seriousness of HCV infection [9]. Older age at transplant, female sex, and morphologic diagnosis of advanced chronic hepatitis were found to be associated with histologic progression to cirrhosis [10]. On the other hand, several other groups have described the absence of dire consequences of HCV infection on patient and graft survival in renal allograft recipients [11, 12]. A group of HCV-infected ESRD patients (N 5 14) was prospectively followed for up to two years with pretransplant liver biopsies, and virologic and biochemical parameters post-transplant [11]. All patients did well with functioning grafts despite enhanced viral replication and mild increase in liver enzymes. Haem and colleagues followed 62 HCV positive renal transplant recipients with liver biopsies for a mean of 72 months (range 36 to 108 months) [12]. Although they found a 42% incidence of chronic active hepatitis, patient and graft survival were not significantly different from HCV negative recipients. At our institution, we found that, despite a predisposition to post-transplant liver disease in recipients with pre-existing HCV infection, overall patient and graft survival were similar in long-term follow up (median follow-up 9 years) in the HCV positive and HCV negative recipients [12]. Irrespective of the antibody status, the outcome was poor in patients with associated liver disease. Less controversial has been the variant impact of HCV infection on patient outcomes related to forms of renal replacement. Similar to the report by Pereira et al, in a study by Knoll and colleagues, HCV-positive renal transplant recipients had a better survival compared with HCV-positive patients who were acceptable candidates for transplantation but were on dialysis [14]. The importance of these studies lies in using a cohort of dialysis patients for outcome comparison very similar to the transplant group as they were on the transplant waiting list, reducing the possibility that differences discerned were merely a consequence of selection bias. The continuing controversy of the impact of HCV infection on the transplant recipient demands further study and analysis by examining such issues as variant viral strains or geographic differences, and improving our understanding of HCV related liver disease. Nevertheless, the report by Pereira and his colleagues supports the conclusion that transplantation is the preferred mode of renal replacement therapy for HCV positive patients with end-stage renal disease [8].
- Full Text
- View/download PDF
79. The effect of pancreas transplantation on cardiovascular mortality
- Author
-
Anthony Langone and J. Harold Helderman
- Subjects
medicine.medical_specialty ,Type 1 diabetes ,insulin ,business.industry ,type 1 diabetes ,Insulin ,medicine.medical_treatment ,Pancreas transplantation ,high-density lipoprotein ,medicine.disease ,chemistry.chemical_compound ,Endocrinology ,High-density lipoprotein ,chemistry ,Nephrology ,Internal medicine ,hyperinsulinemia ,medicine ,Hyperinsulinemia ,business ,vascular smooth muscle growth factors ,Cardiovascular mortality - Full Text
- View/download PDF
80. Summary: Diagnostic Uses
- Author
-
J. Harold Helderman
- Subjects
chemistry.chemical_classification ,Pathology ,medicine.medical_specialty ,biology ,medicine.diagnostic_test ,medicine.drug_class ,business.industry ,Lymphocyte ,Cell ,Monoclonal antibody ,Fine-needle aspiration ,medicine.anatomical_structure ,chemistry ,Nephrology ,Transferrin ,Immunology ,Biopsy ,biology.protein ,medicine ,Antibody ,Stage (cooking) ,business - Abstract
ONOCLONAL ANTIBODIES have ad vanced the clinical utility of various forms of renal transplant biopsies. With respect to core needle biopsies of the renal transplant, immuno peroxidase studies using monoclonal antibodies to specific cell markers have to date been adjunctive. Standard histochemical and pathologic analysis of the core biopsy permits an accurate clinical diagnosis to be made based on the architecture of the tissue and the presence, position, and nature of immunocompetent cell infiltrates. The role of monoclonal antibodies has been able to delineate the pedigree of the infiltrating lymphocyte respon sible for rejection that may be discerned. Because rejection is a heterogenous entity, cells from a wide range of different pedigrees participate in the phenomenon. Little additional diagnostic informa tion has so far been gained by analysis of these markers by monoclonal antibodies. In contrast, the presence of activation markers, such as the in terleukin 2 (IL-2) receptor, the transferrin recep tor, or the appearance of class II antigens on tubu lar cells has been instructive as it may confirm the presence of rejection diagnosed by standard technique. Dual markers will in the future improve the role that the surface structures playas diagnos tic elements. The most important role for the panel of described monoclonal antibodies at present may be prognosis. In terms of the fine needle aspiration biopsy, monoclonal antibodies may play a greater diagnostic role. The goal of this form of biopsy is to aspirate out of the allograft an array of cells including immunocompetent cells and isolated tubular structures. Morphologic analysis by stand ard histochemical techniques permits one to appre ciate the stage of maturation of the
- Published
- 1988
81. Chronic Phycomycosis in a Controlled Diabetic
- Author
-
Harry S. Cooper, J. Harold Helderman, and J. John Mann
- Subjects
Pediatrics ,medicine.medical_specialty ,business.industry ,Diabetes mellitus ,Internal Medicine ,medicine ,General Medicine ,medicine.disease ,business ,Rhinocerebral phycomycosis ,Ketoacidosis - Abstract
Excerpt Hyperglycemia or ketoacidosis is the classic setting for phycomycetic infection in man (1, 2). We report here a case of rhinocerebral phycomycosis in a patient with controlled diabetes mell...
- Published
- 1974
82. Advances in Nephrology. Edited by J.-F.Bach, J.Crosnier, J.-L.Funck-Brentano, J.P.Grünfeld and M.H.Maxwell. Chicago: Year Book Medical Publishers1984: 383
- Author
-
J. Harold Helderman
- Subjects
Nephrology ,Gerontology ,medicine.medical_specialty ,business.industry ,Urology ,Internal medicine ,Family medicine ,medicine ,business - Published
- 1985
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.