PubMed Health⌕ Search

Biomedical subjects

J H Galla

Publications and source records attributed to J H Galla.

At least 19 recordsLinked to original sources
PubMed2001

Molecular genetics in IgA nephropathy.

Evidence from both genotypic and phenotypic perspectives is considered that patients may be genetically predisposed to IgA nephropathy (IgAN) or Henoch-Schönlein purpura (HSP) or that a factor(s) might exclusively contribute to their progression to chronic renal failure. In contrast to most other renal diseases, both IgAN and HSP are uncommon in blacks; this is unexplained but is not due to their low frequency of the A2m(1) allotype. The association of these diseases or their progression with a variety of abnormalities of IgA immunobiology in patients and their families has not been linked to any genotype; similarly, no HLA antigen has been positively or negatively associated in any consistent way. Although complement factor 3 universally accompanies IgA glomerular deposition, complement pathway abnormalities are only sporadically reported with either IgA deposition or disease progression. Whether angiotensin-related polymorphism including the converting enzyme alleles have a specific predictable role, particularly in the progression of renal failure in IgAN, remains problematic. The promising possibility that a structural defect in IgA1 due to an as yet unidentified genetic defect accounts for the deposition of IgA is considered in some detail. Nevertheless, the genetic mechanism(s) of progressive renal failure, whether exclusive to IgAN or to glomerular diseases generally, is of paramount importance.

Animals↗
PubMed2000

Pathways for HCO3-reabsorption in mouse medullary collecting duct segments.

To determine pathways of HCO3- reabsorption in the collecting duct of the mouse kidney, the outer medullary collecting duct (OMCD) and the terminal inner medullary collecting duct (IMCDt) were dissected and perfused at 1 to 2 nL/min, and total CO2 was measured by microfluorometry. In the OMCD, net HCO3- flux (JtCO2) was 12.2 +/- 0.7 pmol/min/mm tubule length and decreased to 6.9 +/- 0.6 pmol/min/mm tubule length (n = 5) with 10 mol/L Schering 28080 (SCH) in perfusate (P < .001) and to 7.7 +/- 0.6 pmol/min/mm tubule length (P < .004; n = 4) with 50 micromol/L diethylstilbestrol (DES), an inhibitor of H+-adenosine triphosphatase; together they reduced JtCO2 to 3.7 +/- 0.2 pmol/min/mm tubule length (P = .0002; n = 4). In IMCDt, JtCO2 was 10.9 +/- 1.1 pmol/min/mm tubule length, and it decreased to 4.3 +/- 0.9 pmol/min/mm tubule length (n = 4) with 10 micromol/L SCH in perfusate (P < .05) and to 7.0 +/- 1.1 pmol/min/mm tubule length (P < .05; n = 4) with 50 micromol/L DES; together they decreased JtCO2 to 2.3 +/- 0.3 pmol/min/mm tubule length (P < .002; n = 4). Ouabain (1 mmol/L), an inhibitor of colonic H-K-adenosine triphosphatase (cHKA), in perfusate had no effect on JtCO2 in either segment. Northern hybridization studies showed a high level of expression of gastric HKA (gHKA) in outer medulla and a low level in inner medulla; cHKA expression was undetectable. Thus, in normal mouse OMCD and IMCDt, HCO3- reabsorption is predominantly mediated by gHKA and H+-adenosine triphosphatase and not cHKA. A third isoform of HKA could be present in mouse IMCDt.

Absorption↗
PubMed2000

Economics of an academic renal division: an approach.

Nephrology divisions work within the systems and constraints of a department of medicine in a college of medicine, and in an increasing number of cases, also within a larger health care delivery system. Key to the division's stability are a consistently applied practice pan, how the tenure and clinical track systems function, how teaching funds are distributed, mechanisms of incentive for the division, and its faculty and the ability to establish and maintain reasonable financial reserves, especially for investment in research. Dialysis, transplantation, hypertension, research, and the teaching of medical students, residents, and fellows are the key elements the divisional organization must address. Incentives for faculty performance should be included in all of these areas. The division director must recognize his or her control of earning capacity in the distribution of responsibilities; financial returns as compared with effort involved vary considerably. Three main problems confront the future of our divisions: manpower shortages in nephrology; the effects of managed care systems on nephrology practice; and the future existence and success of departments of internal medicine and academic health centers.

Hospitals, University↗
PubMed1999

NH4+ secretion in inner medullary collecting duct in potassium deprivation: role of colonic H+-K+-ATPase.

UNLABELLED: NH4+ secretion in inner medullary collecting duct in potassium deprivation: Role of colonic H+-K+-ATPase. BACKGROUND: In K+ deprivation (KD), gastric (g) H+-K+-ATPase (HKA) is suppressed, whereas colonic (c) HKA is induced in the terminal inner medullary collecting duct (IMCD). We hypothesized that in KD, cHKA is induced and can mediate the secretion of NH4+. METHODS: Rats were sacrificed after 2, 3, 6, or 14 days on regular (NML) or K+-free (KD) diet. mRNA expression of HKA isoforms in terminal inner medulla was examined and correlated with NH4+ secretion in perfused IMCD in vitro. RESULTS: Urinary NH4+ excretion increased after K+-free diet for six days. In terminal inner medulla, cHKA expression was strongly induced, whereas gHKA expression was decreased. NH4+ secretion increased by 62% in KD (JtNH4+ 0.57 vs. 0.92 pmol/min/mm tubule length, P < 0.001). Ouabain (1 mM) in perfusate inhibited NH4+ secretion in KD by 45% (P < 0.002) but not in NML. At luminal pH 7.7, which inhibits NH3 diffusion, NH4+ secretion in IMCD was 140% higher in KD (0.36 vs. 0.15, P < 0.03) and was sensitive to ouabain. ROMK-1 mRNA expression was induced in parallel with cHKA in inner medulla. CONCLUSIONS: These data suggest that in KD, cHKA replaces gHKA and mediates enhanced secretion of NH4+ (and H+) into the lumen facilitated by K+ recycling through ROMK-1.

Acid-Base Equilibrium↗
PubMed1999

Rewarding teaching faculty with a reimbursement plan.

OBJECTIVE: To develop a system for measuring the teaching effort of medical school faculty and to implement a payment system that is based on it. DESIGN: An interventional study with outcomes measured before and after the intervention. SETTING: A department of internal medicine with a university hospital and an affiliated Veterans Administration hospital. INTERVENTION: We assigned a value in teaching units to each teaching activity in proportion to the time expended by the faculty and the intensity of their effort. We then calculated total teaching units for each faculty member in the Division of General Internal Medicine and for combined faculty effort in each subspecialty division in the Department of Medicine. After determining the dollar value for a teaching unit, we distributed discretionary teaching dollars to each faculty member in the Division of General Internal Medicine and to each subspecialty division according to total teaching units. MEASUREMENTS AND MAIN RESULTS: The distribution of discretionary teaching dollars was determined. In the year after the intervention, there was a substantial redistribution of discretionary teaching dollars among divisions. Compared with an increase in total discretionary dollars of 11.4%, the change in allocation for individual divisions ranged from an increase of 78.2% to a decrease of -28.5%. Further changes in the second year after the intervention were modest. The distribution of teaching units among divisions was similar to the distribution of questions across subspecialties on the American College of Physicians In-Training Examination (r =.67) and the American Board of Internal Medicine Certifying Examination (r =.88). CONCLUSIONS: It is possible to measure the value of teaching effort by medical school faculty and to distribute discretionary teaching funds among divisions according to the value of teaching effort. When this intervention was used at our institution, there were substantial changes in the amounts received by some divisions. We believe that the new distribution more closely approximates the desired distribution because it reflects the desired emphasis on knowledge as measured by two of the most experienced professional groups in internal medicine. We also believe that our method is flexible and adaptable to the needs of most clinical teaching

Academic Medical Centers↗
PubMed1999

HCO-3 reabsorption in renal collecting duct of NHE-3-deficient mouse: a compensatory response.

Mice with a targeted disruption of Na+/H+ exchanger NHE-3 gene show significant reduction in HCO-3 reabsorption in proximal tubule, consistent with the absence of NHE-3. Serum HCO-3, however, is only mildly decreased (P. Schulties, L. L. Clarke, P. Meneton, M. L. Miller, M. Soleimani, L. R. Gawenis, T. M. Riddle, J. J. Duffy, T. Doetschman, T. Wang, G. Giebisch, P. S. Aronson, J. N. Lorenz, and G. E. Shull. Nature Genet. 19: 282-285, 1998), indicating possible adaptive upregulation of HCO-3-absorbing transporters in collecting duct of NHE-3-deficient (NHE-3 -/-) mice. Cortical collecting duct (CCD) and outer medullary collecting duct (OMCD) were perfused, and total CO2 (net HCO-3 flux, JtCO2) was measured in the presence of 10 microM Schering 28080 (SCH, inhibitor of gastric H+-K+-ATPase) or 50 microM diethylestilbestrol (DES, inhibitor of H+-ATPase) in both mutant and wild-type (WT) animals. In CCD, JtCO2 increased in NHE-3 mutant mice (3.42 +/- 0.28 in WT to 5.71 +/- 0.39 pmol. min-1. mm tubule-1 in mutants, P < 0.001). The SCH-sensitive net HCO-3 flux remained unchanged, whereas the DES-sensitive HCO-3 flux increased in the CCD of NHE-3 mutant animals. In OMCD, JtCO2 increased in NHE-3 mutant mice (8.8 +/- 0.7 in WT to 14.2 +/- 0.6 pmol. min-1. mm tubule-1 in mutants, P < 0.001). Both the SCH-sensitive and the DES-sensitive HCO-3 fluxes increased in the OMCD of NHE-3 mutant animals. Northern hybridizations demonstrated enhanced expression of the basolateral Cl-/HCO-3 exchanger (AE-1) mRNA in the cortex. The gastric H+-K+-ATPase mRNA showed upregulation in the medulla but not the cortex of NHE-3 mutant mice. Our results indicate that HCO-3 reabsorption is enhanced in CCD and OMCD of NHE-3-deficient mice. In CCD, H+-ATPase, and in the OMCD, both H+-ATPase and gastric H+-K+-ATPase contribute to the enhanced compensatory HCO-3 reabsorption in NHE-3-deficient animals.

Absorption↗
PubMed1998

Colonic H+-K+-ATPase is induced and mediates increased HCO3- reabsorption in inner medullary collecting duct in potassium depletion.

BACKGROUND: Potassium depletion increases HCO3- reabsorption in outer medullary collecting duct (OMCD) by activation of colonic (c) H-K-ATPase (HKA). The purpose of the current experiments was to examine the role of the isoforms of HKA in HCO3- reabsorption by terminal inner medullary collecting duct (IMCD) cells in potassium depletion. METHODS: Sprague-Dawley rats were fed a potassium-free diet and studied after 8 to 10 days. mRNA expression of HKA isoforms in terminal portion of inner medulla was examined and correlated with HCO3- reabsorption in the terminal IMCD. RESULTS: Gastric (g) HKA mRNA decreased whereas colonic (c) HKA mRNA expression was heavily induced in terminal portion of inner medulla in potassium depleted rats. Net HCO3- flux (JtCO2) in terminal IMCD increased in potassium depletion (4.56 to 7.06 pmol/min/mm tubule length, P < 0.001). In normal rats, 1 mM ouabain in perfusate had no effect on JtCO2, whereas 10 microM Schering 28080 (SCH) decreased JtCO2 to 2.4 (P < 0.002). In KD rats, 1 mM ouabain decreased JtCO2 to 4.9 (P < 0.005) and 10 microM SCH decreased JtCO2 to 3.3 (P < 0.001). However, the inhibitory effects of SCH and ouabain on JtCO2 in potassium depleted animals were not additive. CONCLUSIONS: The data indicate that gHKA is suppressed whereas cHKA is induced in potassium depletion and mediates increased HCO3- reabsorption in terminal IMCD. The results further indicate that cHKA in vivo is sensitive to both SCH and ouabain.

Animals↗
PubMed1998

Tubulointerstitial nephritis due to a mutant polyomavirus BK virus strain, BKV(Cin), causing end-stage renal disease.

A renal biopsy from a 36-year-old man with AIDS showed a severe tubulointerstitial nephritis with intranuclear inclusions in epithelial cells. Electron microscopy revealed the characteristic findings of a polyomavirus (PyV) infection, and immunofluorescence indicated the presence of BK virus (BKV) antigen. Inoculation of rhesus monkey kidney cell cultures both with urine and with buffy coat blood cells resulted in a cytopathic response which was subsequently confirmed to be due to BKV. Further characterization of the viral DNA from the kidney by PCR amplification and Southern blot analysis with PyV and strain-specific primers and probes indicated that the virus was closely related to the BK(Dun) strain but different in its apparent sequence arrangement. Subsequent cycle sequencing showed a dinucleotide mutation of TG-->AA which substitutes hydrophilic Gln for hydrophobic Leu in a sequence homologous to an origin DNA-binding domain of simian virus 40 T antigen. It is suggested that the mutation and a coding region rearrangement of this strain of BKV designated BKV(Cin) has the potential to alter viral DNA replication and enhance pathogenicity.

Acquired Immunodeficiency Syndrome↗
PubMed1998

K+ depletion increases HCO3- reabsorption in OMCD by activation of colonic H(+)-K(+)-ATPase.

To probe the role of the isoforms of H(+)-K(+)-ATPase (HKA) in potassium depletion (KD), rats were placed on a KD diet for 2 wk. Colonic HKA (cHKA) mRNA levels increased approximately 30-fold in outer medulla, and net HCO3-flux (JtCO2) in outer medullary collecting duct (OMCD) increased (13.1 pmol.min-1.mm tubule length-1 in control to 17.7 pmol.min-1.mm tubule length-1 in KD; P < 0.01). In normal rats, 1 mM ouabain in perfusate had no effect on JtCO2, whereas 10 microM Sch-28080 decreased JtCO2 to 5.1 pmol.min-1.mm tubule length-1 (P < 0.001). In KD rats, ouabain 1 mM decreased JtCO2 to 6.3 pmol.min-1.mm tubule length-1 (P < 0.001). Although 10 microM Sch-28080 also decreased JtCO2 to 4.6 pmol.min-1.mm tubule length-1 (P < 0.001), the inhibitory effects of Sch-28080 and ouabain were not additive. Removal of K+ from perfusate blocked Sch-28080-sensitive JtCO2 in both normal and KD tubules. The data suggest that, in KD, cHKA is induced and mediates increased HCO3-reabsorption in OMCD, cHKA in vivo is sensitive to both Sch-28080 and ouabain, and cHKA activity is dominant.

Absorption↗
PubMed1995

Bicarbonate transport in collecting duct segments during chloride-depletion alkalosis.

Renal correction of chloride-depletion alkalosis (CDA) by chloride replacement results in bicarbonate secretion in the cortical collecting duct (CD) and urinary bicarbonate excretion. To assess the participation of the more distal segments of the CD, we determined net total CO2 transport in the outer medullary (OMCD), initial (IMCDi) and terminal (IMCDt) inner medullary CD segments obtained from Sprague-Dawley rats with normal acid-base balance (NML) or with CDA produced by peritoneal dialysis. Tubules were bathed and perfused with isotonic solutions containing Cl 110 mM and HCO, 25 mM. Net total CO2 transport was decreased in all segments: OMCD 22.1 +/- 4.2 to 9.2 +/- 2.0; IMCDi 38.1 +/- 4.6 to 9.3 +/- 1.7; IMCDt 6.7 +/- 1.2 to -0.5 +/- 0.4 pmol/min/mm tubule length. Perfusion rates, tubule lengths, and transepithelial voltages did not differ between groups in any segment. These data show that all CD segments beyond the cortical segment decrease bicarbonate reabsorption during CDA. This permits the bicarbonate secreted by the cortical CD to be excreted, and is likely an important mechanism for the correction of CDA.

Acid-Base Equilibrium↗
PubMed1995

IgA nephropathy.

IgAN is the most common type of glomerulonephritis worldwide, and is found more in men and distinctly less in blacks. It presents with macroscopic hematuria in about 40 to 45% of patients, with microscopic hematuria and proteinuria in about 35 to 40%, and with nephrotic syndrome or acute renal failure in the remainder. The diagnosis continues to rely on the finding of the dominant or codominant mesangial deposition of IgA on immunohistologic examination of the kidney. No blood or urine test is sufficiently reliable for diagnosis. While the pathogenesis remains unknown, accumulating evidence suggests that polyclonal stimulation of immunoglobulins perhaps coupled with structural abnormalities of IgA play pivotal roles. These defects may account for the variety of autoantibodies detected in patients with both IgAN and HSP. While IgAN has an indolent course, about 30% of patients will reach ESRD after 20 years, particularly in those who present with hypertension, heavy proteinuria or renal insufficiency. At present, therapy is disappointing, but immunoglobulin supplementation and newer agents that interrupt the pathways of mesangial proliferation and sclerosis hold promise for the future. Kidney transplantation has shown excellent allograft survival.

Glomerulonephritis, IGA↗
PubMed1993

HCO3- transport in rat CCD: rapid adaptation by in vivo but not in vitro alkalosis.

Acute chloride-depletion alkalosis (CDA) in vivo results in sustained net total carbon dioxide (tCO2) secretion in vitro in the rat cortical collecting duct (CCD) for several hours. To determine whether altering in vitro pH and electrolytes similarly result in tCO2 secretion, CCD were incubated for 1 h at 37 degrees C in an alkalotic environment similar to in vivo arterial pH, PCO2, and electrolytes (pH 7.6, 40 mM HCO3). The in vitro alkalosis incubation had no effect on tCO2 transport. Second, alteration of the magnitude of vivo alkalosis was correlated with in vitro tCO2 transport. After generation of CDA by intraperitoneal dialysis against 154 mM HCO3-, rats received an infusion for 2.5 h of either 5% dextrose to maintain alkalosis or 154 mM NaCl at differing rates to partially correct or fully correct the systemic alkalosis. After in vitro isolation and perfusion, in vitro tCO2 flux correlated with in vivo Cl- balance (r2 = 0.82), serum HCO3- (r2 = 0.84), and arterial H+ concentration (r2 = 0.78), but not with K+ balance (r2 = 0.33). These findings suggest that: 1) the regulation of tCO2 transport in vitro correlates with the degree of systemic alkalosis and Cl- balance in vivo, and 2) simulating alkalotic pH and electrolytes in vitro does not rapidly alter transport as does in vivo CDA within a similar time. Taken together, pH and electrolyte changes alone cannot account for the rapid adaptation of tCO2 transport in the CCD, but an in vivo factor(s) contributes importantly to alter tCO2 transport in magnitude and direction that would tend to restore normal acid-base balance.

Animals↗
PubMed1992

IgA-containing immune complexes after challenge with food antigens in patients with IgA nephropathy.

The possibility that patients with IgA nephropathy (IgAN) might have abnormal IgA immune responses to immunogens commonly encountered at mucosal surfaces, resulting in the formation of circulating immune complexes (CIC), was examined. Since it is generally held that such increased IgA responses are characterized by detectable aberrancies in handling of IgA-containing CIC, IgAN patients and controls were given a large volume of bovine milk (after dietary deprivation of bovine antigens) and immune complex levels were measured over a period of 12 h. An assay based on binding of CIC containing C3 to solid-phase anti-C3 and subsequent development with isotype-specific antibody revealed no differences in responses of patients and controls with respect to IgG- and IgM-containing CIC. Although IgAN patients tended to have higher levels of IgA-containing CIC, there were no differences in response patterns when IgA CIC levels after ingestion of the milk stimulus were related to baseline levels. Polymorphonuclear leucocytes (PMNC), which bear surface receptors for IgA, were isolated from some subjects at the same times as the samples for CIC levels and examined by two-colour immunofluorescence for the coincident presence of IgA and milk antigens. In contrast to the data obtained in the CIC assays, these experiments revealed the simultaneous presence of IgA and two of three milk proteins in PMNC of IgAN patients but not controls. Follow-up experiments designed to assess more quantitatively the coincidental presence of IgA and milk antigens indicated no significant differences between patients and controls. However, milk proteins seemed to be more commonly associated with IgA in PMNC of IgAN patients, suggesting the presence of non-complement-fixing IgA/antigen CIC after mucosal challenge of some IgAN patients.

Adolescent↗
PubMed1992

Response of intercalated cells to chloride depletion metabolic alkalosis.

We examined the effect of Cl- depletion metabolic alkalosis (CDA) on H(+)-ATPase and band 3 protein localization in intercalated cells (IC) of the rat cortical collecting duct (CCD) and the outer medullary collecting duct (OMCD). After 30 min of peritoneal dialysis against 0.15 M NaHCO3 to produce CDA, or Ringer bicarbonate to serve as controls (CON), both groups were infused intravenously with an 80 mM Cl- solution for 90 min. For CDA vs. CON, physiological parameters were as follows: plasma total CO2, 38.0 +/- 1.1 vs. 27.8 +/- 0.6 meq/l (P less than 0.001); urinary total CO2 excretion, 141 +/- 89 vs. 20 +/- 3 neq.min-1.100 g body wt-1; and urinary Cl- excretion, 20 +/- 10 vs. 486 +/- 144 neq.min-1.100 g body wt-1 (P less than 0.001). H(+)-ATPase was localized in thin sections using a rabbit polyclonal antibody against the 70-kDa subunit of bovine brain H(+)-ATPase. Band 3 protein was localized using a polyclonal antibody against the 43-kDa subunit of the cytoplasmic domain of human erythrocyte band 3 protein. In CON rats, H(+)-ATPase localized along the apical plasma membrane and over the apical cytoplasmic vesicles of type A ICs in the CCD and ICs of the OMCD. H(+)-ATPase was observed along the basolateral plasma membrane and over cytoplasmic vesicles throughout type B ICs. In CDA rats, H(+)-ATPase was only observed over apical cytoplasmic vesicles in type A ICs and in the majority of OMCD ICs. In type B ICs, H(+)-ATPase staining was intensified along the basal plasma membrane in CDA. Band 3 protein was consistently localized in the basolateral plasma membrane of all type A cells in the CCD and ICs of the OMCD in both CON and CDA. In summary, stimulation of HCO3- secretion in rats caused withdrawal of H(+)-ATPase from the apical plasma membrane and storage in apical cytoplasmic vesicles of ICs of the OMCD and type A ICs of the CCD. H(+)-ATPase appeared to be inserted into the basal plasma membrane of type B ICs. These findings suggest that, during correction of CDA, proton secretion by type A and OMCD ICs is suppressed and proton transport across the basolateral plasma membrane of type B ICs is stimulated.

Adenosine Triphosphatases↗
PubMed1992

H(+)-K(+)-ATPase activity in rat collecting duct segments.

Previous studies have suggested the presence of an H(+)-K(+)-ATPase in rat cortical and medullary intercalated cells with similar properties to the gastric proton pump. The purpose of this study was to determine the functional contribution of an H(+)-K(+)-adenosinetriphosphatase(ATPase) to total CO2 (tCO2) transport along the rat collecting duct. After baseline determination of tCO2 transport in isolated perfused collecting duct segments, Sch 28080 (10 microM) was added to either the perfusate or bath. When Sch 28080 was added to the perfusate, there was no effect in the cortical collecting duct (CCD, 20.8 +/- 6.7 vs. 25.3 + 3.0 pmol.mm-1.min-1), but a marked decrease in tCO2 absorption was effected in both the outer medullary (OMCD, 37.6 + 6.2 vs. 10.7 +/- 4.1 pmol.mm-1.min-1) and initial inner medullary collecting duct (IMCD1, 34.4 +/- 8.1 vs. 16.2 +/- 5.6 pmol.mm-1.min-1). In the CCD from rats with acute alkalosis in vivo, Sch 28080 added to the bath inhibited tCO2 secretion in the CCD (-17.1 +/- 4.4 vs 3.5 + 3.3 pmol.mm-1.min-1). These findings suggest that 1) H(+)-K(+)-ATPase is important in tCO2 absorption in the OMCD and IMCD1 and in tCO2 secretion in the CCD, 2) HCO3(-)-absorbing intercalated cells differ functionally in the cortex and medulla, 3) HCO3- secretion is not the reverse process of HCO3- absorption in the CCD, and 4) H(+)-K(+)-ATPase is important in distal acidification under normal and altered acid-base conditions.

Adenosine Triphosphatases↗
PubMed1991

Epstein-Barr virus transformation of B lymphocytes from IgA nephropathy patients and first-degree relatives results in increased immunoglobulin synthesis not restricted to IgA.

In order to study B-cell activation patterns independent of T-cell regulation in patients with IgA nephropathy (IgAN), peripheral blood mononuclear cells from 67 patients with IgAN, 15 first-degree relatives of patients with familial disease, and 13 normal controls were transformed with Epstein-Barr virus (EBV). Culture supernatants of these transformed cells were assayed for levels of IgG, IgA, and IgM, and results obtained on the three populations were compared. EBV-transformed cells of IgAN patients, as well as the population of first-degree relatives, secreted significantly elevated levels of all three isotypes as compared with the normal controls. However, in comparing ratios of secreted isotypes, it was determined that more IgA relative to IgG and IgM was synthesized by cells of these two populations as compared with the normal controls. Our results imply that (1) the population of B cells susceptible to EBV activation is increased in IgAN patients; (2) this population of "activatable" B lymphocytes is polyclonal and not restricted to the IgA class; and (3) even though there may be a primary B-cell abnormality in IgAN, an additional defect(s) is probably operative in the pathogenesis, since cells of clinically unaffected relatives behaved in a pattern similar to that of patients.

B-Lymphocytes↗