Jerry Winkelstein - Academia.edu (original) (raw)

Papers by Jerry Winkelstein

Research paper thumbnail of 1008 Theoretical and Biological Considerations in Successful Mismatched Bone Marrow Transplantation

Pediatric Research, Apr 1, 1985

Research paper thumbnail of Hereditary partial deficiency of the third component of complement associated with minimal change nephrotic syndrome

Pediatric Nephrology, 1987

We describe a 10 year old patient admitted to the Children's Hospital of Buffalo ... more We describe a 10 year old patient admitted to the Children's Hospital of Buffalo with hypocomplementemia associated with steroid responsive minimal change nephrotic syndrome. The sibling also had a low serum C3 concentration and all family members studied had C3 slow phenotypes. Factor I levels were at the lower limit of normal in the patient and his brother. Functional assays for CH50, total hemolytic C3 and serum concentration of C2, C4-C9 and factors B and H were all within normal limits. This case confirms that a depressed serum complement level can occur in minimal change nephrotic syndrome and indicates that this depression could represent a preexisting inherited rather than an acquired deficiency. The findings are consistent with the presence of a null or hypomorphic C3 slow allele in hypocomplementemic family members. Additional studies are needed to resolve the association between the inherited partial C3 deficiency and minimal change nephrotic syndrome.

Research paper thumbnail of Animal Model: Genetic Analysis of an Inherited Deficiency of the Third Component of Complement in Brittany Spaniel Dogs

American journal of medical genetics, Nov 1, 1986

Genetically determined C3 deficiency in Brittany spaniel dogs shares a number of biochemical and ... more Genetically determined C3 deficiency in Brittany spaniel dogs shares a number of biochemical and clinical characteristics with the human disorder. In humans, the gene for C3 deficiency is a null gene that is allelic to the structural gene tor C3 and is not linked to the major histocompatibility locus. The current study used allotype analysis of canine C3 in order to demonstrate that the gene for C3 deficiency in these dogs is also a null gene allelic to the structural gene for C3. In addition, preliminary pedigree analysis suggests that the gene for canine C3 deficiency is apparently not closely linked to the major histocompatibility complex of the dog. Thus, it appears that C3 deficiency in Brittany spaniel dogs not only shares biochemical and clinical features with C3 deficiency in humans, but also shares some genetic characteristics with the human disorder.

Research paper thumbnail of Hypomorphic variant of the slow allele of C3 associated with hypocomplementemia and hematuria

The American Journal of Medicine, May 1, 1985

Research paper thumbnail of Prevalence of Homozygous C4B Deficiency in Patients with Deficiencies of Terminal Complement Components and Meningococcemia

The Journal of Infectious Diseases, Nov 1, 1990

Research paper thumbnail of Prevalence of a mutation causing C2 deficiency in systemic lupus erythematosus

PubMed, Jun 1, 1994

Objective: In an effort to establish whether a 28 base pair (bp) deletion in the gene for the 2nd... more Objective: In an effort to establish whether a 28 base pair (bp) deletion in the gene for the 2nd component of complement (C2) constitutes a significant genetic risk factor for systemic lupus erythematosus (SLE), we determined the frequency of this mutation in SLE and control populations. The MHC associations of this mutation were also established. Methods: Polymerase chain reaction (PCR) was used to amplify DNA, and the wild type and mutant alleles were distinguished by gel electrophoresis. Results: Among 122 Caucasoid patients with SLE, 2 homozygous and 2 heterozygous carriers of the 28 bp deletion were found, giving a gene frequency of 0.0246. In contrast, 6 of 427 North American Caucasoid controls were heterozygous for the 28 bp deletion, giving a gene frequency of 0.0070 (p < 0.05). Carriers of the 28 bp deletion in C2 frequently carried the DRB1*1501 allele. The 28 bp deletion in C2 was not found in 194 African-American controls or in 127 African-American patients with SLE. Conclusions: A direct assay for the most common form of C2 deficiency established that the 28 bp deletion in the C2 gene is significantly more common in Caucasoid patients with SLE compared to controls (p < 0.05). When only heterozygous carriers of the 28 bp deletion were enumerated, they were not found more frequently in the Caucasoid population with SLE compared to controls.

Research paper thumbnail of The fixation of C3b to pneumococcal cell wall polymers as a result of activation of the alternative complement pathway

Journal of Immunology, Oct 1, 1981

Research paper thumbnail of Activation of C3 via the alternative complement pathway results in fixation of C3b to the pneumococcal cell wall

Journal of Immunology, May 1, 1980

Research paper thumbnail of Activation of the Alternative Pathway by Pneumococcal Cell Wall Teichoic Acid

Journal of Immunology, May 1, 1978

Research paper thumbnail of Purification of the third component of canine complement

Veterinary Immunology and Immunopathology, Apr 1, 1985

A rapid, simple procedure has been developed for the purification of the third component (C3) of ... more A rapid, simple procedure has been developed for the purification of the third component (C3) of canine complement. Dog plasma was initially fractionated by precipitation with 4% (w/v) polyethylene glycol (PEG) 4000. The supernatant was depleted of plasminogen using a Sepharose 4B-lysine column, and the effluent was again fractionated with PEG 4000 at 16% (w/v). The precipitate was resuspended and passed over a DEAE-Sephacel column. The fractions containing hemolytically active C3 were pooled, concentrated, and passed over a CM-Sepharose CL-6B column to yield the final purified product. Rabbit anti-whole dog serum identified only one protein in the purified material on immunoelectrophoresis. When injected into a rabbit, the purified product raised an antisera which reacted with only one protein in both whole dog serum and the purified product. Analysis by SDS-PAGE revealed a single band of MW 179,000 +/- 7,000 (+/- 1 S.D.) daltons which, upon reduction with 2-mercaptoethanol, resulted in 2 bands of 114,000 +/- 6,000 daltons and 65,000 +/- 3,500 daltons. Final recovery was 18% with respect to C3 antigen and 9% with respect to C3 hemolytic activity.

Research paper thumbnail of Infectious Complications of Complement Deficiencies

Principles and Practice of Pediatric Infectious Disease, 2008

Research paper thumbnail of Cytokine and Chemokine Dysregulation in Hyper-IgE Syndrome

Clinical Immunology, Jul 1, 2001

Research paper thumbnail of Dogs Deficient in C31

Chemical Immunology, Apr 20, 2015

Research paper thumbnail of Host modification of sindbis virus sialic acid alters alternative complement pathway activation in vitro and pathogenesis of infection in vivo

Molecular Immunology, Nov 1, 1982

Research paper thumbnail of Genetically determined deficiences of the complement system

Pediatric Allergy and Immunology, Aug 1, 1992

The complement system is composed of a series of interactive plasma proteins and cellular recepto... more The complement system is composed of a series of interactive plasma proteins and cellular receptors which mediate a wide variety of important defensive and inflammatory reactions (1,2). The first deficiency of an individual component of complement (C2) was identified in 1960 in an immunologist who was free of any significant clinical symptoms (3). Since that time, genetically determined deficiencies of nearly all of the components of complement have been identified (2,4,5). In addition, there has been a growing appreciation that, although some patients with complement deficiencies can be relatively asymptomatic, the majority manifest clinical illnesses (2,4,5). The identification of individuals with genetically determined deficiencies of complement has not only defined an important new group of patients with a primary immunodeficiency disease, but has also led to a better understanding of the physiologic role of the complement system in normal individuals.

Research paper thumbnail of Regulation of early complement components C3 and C4 in the synovium

Clinical and diagnostic laboratory immunology, 1996

To determine the cytokine inducibility of early complement component (C3 and C4) expression in th... more To determine the cytokine inducibility of early complement component (C3 and C4) expression in the synovium, explant tissue was maintained in culture for 7 days. C3 and C4 production was measured by specific enzyme-linked immunosorbent assay, and RNA was evaluated by semiquantitative PCR. The effects of leukemia inhibitory factor (LIF), gamma interferon (IFN-gamma), IFN-alpha, and estrogen on C3 and C4 expression were evaluated. C3 levels were unaffected by 7 days of LIF, IFN-gamma, or IFN-alpha treatment. In contrast, C4 levels were significantly induced in synovial samples treated for 7 days with either IFN-gamma or IFN-alpha. LIF had no effect on C4 levels in this system. Estrogen was found to down-modulate the induction of expression due to IFN-gamma. These data provide evidence for cytokine regulation of C4 expression in the synovium and for estrogen modulation of those effects.

Research paper thumbnail of Prenatal diagnosis of heterozygous deficiency of the second component of complement

Clinical and diagnostic laboratory immunology, Sep 1, 1994

Research paper thumbnail of Absence of Glomerulonephritis in Guinea Pigs Deficient in the Fourth Component of Complement

Veterinary Pathology, Mar 1, 1994

Research paper thumbnail of The Severe Chronic Neutropenia International Registry - 10 Years of Follow-Up

Research paper thumbnail of Serum complement determinations in patients with quiescent systemic lupus erythematosus

PubMed, Dec 1, 1996

Objective: To determine whether complement component analyses during a period of inactive disease... more Objective: To determine whether complement component analyses during a period of inactive disease can define clinically important subgroups and predict morbidity in patients with systemic lupus erythematosus (SLE). Methods: We identified 277 patients with SLE whose disease became clinically inactive at some point after diagnosis. Serum samples were obtained at that time and tested for total complement activity (CH100) and antigenic levels of C1q, C1r, C1s, C3 and C4. Results of complement determinations were correlated with demographic characteristics and clinical findings in the followup period (mean observation period 4.25 years). Results: We identified 25 (9%) patients with multiple complement determinations below the normal range. 24 other patients (8.5%) had a very low level of a single complement component. The group with multiple complement determinations below the normal range was much more likely than the normocomplementemic SLE controls to progress to renal insufficiency. In other respects, complement component determinations were neither reflective nor predictive of clinical course. Conclusion: In this group of patients with inactive SLE, complement component analyses did not generally correlate with longterm outcome; however, multiple low complement component determinations during disease quiescence was associated with increased risk of renal insufficiency.

Research paper thumbnail of 1008 Theoretical and Biological Considerations in Successful Mismatched Bone Marrow Transplantation

Pediatric Research, Apr 1, 1985

Research paper thumbnail of Hereditary partial deficiency of the third component of complement associated with minimal change nephrotic syndrome

Pediatric Nephrology, 1987

We describe a 10 year old patient admitted to the Children&amp;amp;#39;s Hospital of Buffalo ... more We describe a 10 year old patient admitted to the Children&amp;amp;#39;s Hospital of Buffalo with hypocomplementemia associated with steroid responsive minimal change nephrotic syndrome. The sibling also had a low serum C3 concentration and all family members studied had C3 slow phenotypes. Factor I levels were at the lower limit of normal in the patient and his brother. Functional assays for CH50, total hemolytic C3 and serum concentration of C2, C4-C9 and factors B and H were all within normal limits. This case confirms that a depressed serum complement level can occur in minimal change nephrotic syndrome and indicates that this depression could represent a preexisting inherited rather than an acquired deficiency. The findings are consistent with the presence of a null or hypomorphic C3 slow allele in hypocomplementemic family members. Additional studies are needed to resolve the association between the inherited partial C3 deficiency and minimal change nephrotic syndrome.

Research paper thumbnail of Animal Model: Genetic Analysis of an Inherited Deficiency of the Third Component of Complement in Brittany Spaniel Dogs

American journal of medical genetics, Nov 1, 1986

Genetically determined C3 deficiency in Brittany spaniel dogs shares a number of biochemical and ... more Genetically determined C3 deficiency in Brittany spaniel dogs shares a number of biochemical and clinical characteristics with the human disorder. In humans, the gene for C3 deficiency is a null gene that is allelic to the structural gene tor C3 and is not linked to the major histocompatibility locus. The current study used allotype analysis of canine C3 in order to demonstrate that the gene for C3 deficiency in these dogs is also a null gene allelic to the structural gene for C3. In addition, preliminary pedigree analysis suggests that the gene for canine C3 deficiency is apparently not closely linked to the major histocompatibility complex of the dog. Thus, it appears that C3 deficiency in Brittany spaniel dogs not only shares biochemical and clinical features with C3 deficiency in humans, but also shares some genetic characteristics with the human disorder.

Research paper thumbnail of Hypomorphic variant of the slow allele of C3 associated with hypocomplementemia and hematuria

The American Journal of Medicine, May 1, 1985

Research paper thumbnail of Prevalence of Homozygous C4B Deficiency in Patients with Deficiencies of Terminal Complement Components and Meningococcemia

The Journal of Infectious Diseases, Nov 1, 1990

Research paper thumbnail of Prevalence of a mutation causing C2 deficiency in systemic lupus erythematosus

PubMed, Jun 1, 1994

Objective: In an effort to establish whether a 28 base pair (bp) deletion in the gene for the 2nd... more Objective: In an effort to establish whether a 28 base pair (bp) deletion in the gene for the 2nd component of complement (C2) constitutes a significant genetic risk factor for systemic lupus erythematosus (SLE), we determined the frequency of this mutation in SLE and control populations. The MHC associations of this mutation were also established. Methods: Polymerase chain reaction (PCR) was used to amplify DNA, and the wild type and mutant alleles were distinguished by gel electrophoresis. Results: Among 122 Caucasoid patients with SLE, 2 homozygous and 2 heterozygous carriers of the 28 bp deletion were found, giving a gene frequency of 0.0246. In contrast, 6 of 427 North American Caucasoid controls were heterozygous for the 28 bp deletion, giving a gene frequency of 0.0070 (p < 0.05). Carriers of the 28 bp deletion in C2 frequently carried the DRB1*1501 allele. The 28 bp deletion in C2 was not found in 194 African-American controls or in 127 African-American patients with SLE. Conclusions: A direct assay for the most common form of C2 deficiency established that the 28 bp deletion in the C2 gene is significantly more common in Caucasoid patients with SLE compared to controls (p < 0.05). When only heterozygous carriers of the 28 bp deletion were enumerated, they were not found more frequently in the Caucasoid population with SLE compared to controls.

Research paper thumbnail of The fixation of C3b to pneumococcal cell wall polymers as a result of activation of the alternative complement pathway

Journal of Immunology, Oct 1, 1981

Research paper thumbnail of Activation of C3 via the alternative complement pathway results in fixation of C3b to the pneumococcal cell wall

Journal of Immunology, May 1, 1980

Research paper thumbnail of Activation of the Alternative Pathway by Pneumococcal Cell Wall Teichoic Acid

Journal of Immunology, May 1, 1978

Research paper thumbnail of Purification of the third component of canine complement

Veterinary Immunology and Immunopathology, Apr 1, 1985

A rapid, simple procedure has been developed for the purification of the third component (C3) of ... more A rapid, simple procedure has been developed for the purification of the third component (C3) of canine complement. Dog plasma was initially fractionated by precipitation with 4% (w/v) polyethylene glycol (PEG) 4000. The supernatant was depleted of plasminogen using a Sepharose 4B-lysine column, and the effluent was again fractionated with PEG 4000 at 16% (w/v). The precipitate was resuspended and passed over a DEAE-Sephacel column. The fractions containing hemolytically active C3 were pooled, concentrated, and passed over a CM-Sepharose CL-6B column to yield the final purified product. Rabbit anti-whole dog serum identified only one protein in the purified material on immunoelectrophoresis. When injected into a rabbit, the purified product raised an antisera which reacted with only one protein in both whole dog serum and the purified product. Analysis by SDS-PAGE revealed a single band of MW 179,000 +/- 7,000 (+/- 1 S.D.) daltons which, upon reduction with 2-mercaptoethanol, resulted in 2 bands of 114,000 +/- 6,000 daltons and 65,000 +/- 3,500 daltons. Final recovery was 18% with respect to C3 antigen and 9% with respect to C3 hemolytic activity.

Research paper thumbnail of Infectious Complications of Complement Deficiencies

Principles and Practice of Pediatric Infectious Disease, 2008

Research paper thumbnail of Cytokine and Chemokine Dysregulation in Hyper-IgE Syndrome

Clinical Immunology, Jul 1, 2001

Research paper thumbnail of Dogs Deficient in C31

Chemical Immunology, Apr 20, 2015

Research paper thumbnail of Host modification of sindbis virus sialic acid alters alternative complement pathway activation in vitro and pathogenesis of infection in vivo

Molecular Immunology, Nov 1, 1982

Research paper thumbnail of Genetically determined deficiences of the complement system

Pediatric Allergy and Immunology, Aug 1, 1992

The complement system is composed of a series of interactive plasma proteins and cellular recepto... more The complement system is composed of a series of interactive plasma proteins and cellular receptors which mediate a wide variety of important defensive and inflammatory reactions (1,2). The first deficiency of an individual component of complement (C2) was identified in 1960 in an immunologist who was free of any significant clinical symptoms (3). Since that time, genetically determined deficiencies of nearly all of the components of complement have been identified (2,4,5). In addition, there has been a growing appreciation that, although some patients with complement deficiencies can be relatively asymptomatic, the majority manifest clinical illnesses (2,4,5). The identification of individuals with genetically determined deficiencies of complement has not only defined an important new group of patients with a primary immunodeficiency disease, but has also led to a better understanding of the physiologic role of the complement system in normal individuals.

Research paper thumbnail of Regulation of early complement components C3 and C4 in the synovium

Clinical and diagnostic laboratory immunology, 1996

To determine the cytokine inducibility of early complement component (C3 and C4) expression in th... more To determine the cytokine inducibility of early complement component (C3 and C4) expression in the synovium, explant tissue was maintained in culture for 7 days. C3 and C4 production was measured by specific enzyme-linked immunosorbent assay, and RNA was evaluated by semiquantitative PCR. The effects of leukemia inhibitory factor (LIF), gamma interferon (IFN-gamma), IFN-alpha, and estrogen on C3 and C4 expression were evaluated. C3 levels were unaffected by 7 days of LIF, IFN-gamma, or IFN-alpha treatment. In contrast, C4 levels were significantly induced in synovial samples treated for 7 days with either IFN-gamma or IFN-alpha. LIF had no effect on C4 levels in this system. Estrogen was found to down-modulate the induction of expression due to IFN-gamma. These data provide evidence for cytokine regulation of C4 expression in the synovium and for estrogen modulation of those effects.

Research paper thumbnail of Prenatal diagnosis of heterozygous deficiency of the second component of complement

Clinical and diagnostic laboratory immunology, Sep 1, 1994

Research paper thumbnail of Absence of Glomerulonephritis in Guinea Pigs Deficient in the Fourth Component of Complement

Veterinary Pathology, Mar 1, 1994

Research paper thumbnail of The Severe Chronic Neutropenia International Registry - 10 Years of Follow-Up

Research paper thumbnail of Serum complement determinations in patients with quiescent systemic lupus erythematosus

PubMed, Dec 1, 1996

Objective: To determine whether complement component analyses during a period of inactive disease... more Objective: To determine whether complement component analyses during a period of inactive disease can define clinically important subgroups and predict morbidity in patients with systemic lupus erythematosus (SLE). Methods: We identified 277 patients with SLE whose disease became clinically inactive at some point after diagnosis. Serum samples were obtained at that time and tested for total complement activity (CH100) and antigenic levels of C1q, C1r, C1s, C3 and C4. Results of complement determinations were correlated with demographic characteristics and clinical findings in the followup period (mean observation period 4.25 years). Results: We identified 25 (9%) patients with multiple complement determinations below the normal range. 24 other patients (8.5%) had a very low level of a single complement component. The group with multiple complement determinations below the normal range was much more likely than the normocomplementemic SLE controls to progress to renal insufficiency. In other respects, complement component determinations were neither reflective nor predictive of clinical course. Conclusion: In this group of patients with inactive SLE, complement component analyses did not generally correlate with longterm outcome; however, multiple low complement component determinations during disease quiescence was associated with increased risk of renal insufficiency.