Biomedical subjects

C B Wilson

Publications and source records attributed to C B Wilson.

At least 307 records · Page 17Linked to original sources

PubMed1987

An evaluation of the development of experimental membranous nephropathy.

Heymann nephritis is a rat model of glomerulonephritis with morphologic manifestations of human membranous nephropathy. This model is generated by immunizing rats with Fx1A antigen. Passive Heymann's nephritis (PHN) can be produced by the administration of anti-Fx1A antibody (anti-Fx1A Ab) (with abnormal proteinuria appearing in 5 days). Studies were designed to examine the evolution of temporal changes in protein excretion, the glomerular ultrafiltration coefficient (LpA) and morphology of glomerular capillary three and five days after induction of PHN. Glomerular hemodynamic evaluation by micropuncture in euvolemic rats with PHN revealed normal values for nephron filtration rate (SNGFR), LpA and the glomerular hydrostatic pressure gradient (delta P) at day three, but by day five the whole kidney GFR and SNGFR were decreased, delta P increased and LpA significantly reduced. Glomerular binding of anti-Fx1A Ab increased from 38 micrograms/7.6 X 10(4) glomeruli on day three to 52 micrograms on day five. Immune complex deposits evaluated by immunofluorescence and electron microscopy appeared larger and were better defined on day five than on day three. Epithelial foot process fusion was more extensive on day five than day three. The onset of increased proteinuria correlated temporally with a reduction in LpA on day five, which in turn correlated with increased antibody binding, immune deposit accumulation and fusion of epithelial cell foot processes.

Animals↗

PubMed1987

Quantitative and qualitative studies of antibody-induced mesangial cell damage in the rat.

Intravenous administration of heterologous anti-rat thymocyte serum (ATS), which reacts with a Thy-1-like antigen present on rat glomerular mesangial cells, caused lytic (1 hr to 2 days), hypercellular (4 to 14 days), and sclerotic (2 to 3 months) mesangial lesions in Lewis rats. The normal control of 48.6 +/- 7.9 (mean +/- SD) glomerular nuclei on histologic section decreased significantly (P less than 0.001) to 39.8 +/- 6.1, 37.4 +/- 6.0, and 38.9 +/- 6.8 at one hour, four hours and two days after ATS administration, respectively. Thereafter glomerular nuclei increased to 54.7 +/- 11.5 (P less than 0.05) at four days, 62.5 +/- 9.6 (P less than 0.001) at one week and 64.1 +/- 14.2 (P less than 0.001) at two weeks, and normalized (P greater than 0.05) to 49.4 +/- 8.9 at one month and 50.6 +/- 9.0 at three months. By electron microscopy, glomerular damage in the lytic stage was restricted to mesangial cells and was manifested as hydropic degeneration or lysis. Rabbit IgG and rat C3 were found in the mesangium one hour after injection; they decreased at two days and were negligible at four days. By paired label isotope study, 11.6 micrograms of antibody bound per 7.6 X 10(4) glomeruli at one hour was needed to induce mesangial cell degeneration. No or only minimal changes in proteinuria and in serum creatinine were observed with the dosage used in this rat strain.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Induction, characterization, and cell transfer of autoimmune tubulointerstitial nephritis.

Autoimmune tubulointerstitial nephritis (TIN) was induced in Lewis (LEW) rats by immunization with homologous Brown-Norway (BN) rat renal basement membrane (RBM), complete Freund's adjuvant and Bordetella pertussis vaccine. The BN strain has a tubular basement membrane (TBM) antigen (Ag+) detectable by immunofluorescence which is lacking in unmodified LEW rat TBM. Development of TIN in LEW rats correlated with TBM Ag+ immunogens from homologous and heterologous RBM preparations. By day 14 after immunization TIN developed characterized by elevated serum creatinine levels and by tubular destruction with focal, circumscribed lesions containing epithelioid cells, giant cells and mononuclear cell infiltrates. Approximately 60% of the mononuclear cells bore T cell antigens with most cells expressing Ia markers. Immunofluorescence and elution studies revealed no selective IgG fixation to TBM at day 14 despite high titers of circulating alloantibody reactive with the immunizing TBM. Intravenous transfer of LNC and/or splenic cells (3.5 to 7 X 10(8)) to naive LEW rats resulted in less severe but histologically identical TIN in seven days with T cell subpopulations similar to those seen in the active model. This model strongly suggests an initiating role for cell-mediated immunity in TIN in the rat and may provide a parallel to human TIN.

Animals↗

PubMed1987

The influence of concomitant experimental hypertension and glomerulonephritis.

Utilizing the two kidney-one clip Goldblatt model (CH), we have examined the influence of hypertension upon the course of antiglomerular basement membrane antibody-induced glomerulonephritis (GN) over a period of 10 to 14 weeks after induction of CH and GN, utilizing evaluations in the awake rat by renal micropuncture of the unclipped kidney and morphologic analysis (control [C], GN, CH, and GN+CH). Metabolic studies revealed that GN and GN+CH rats developed proteinuria, elevations in serum creatinine and blood pressure (P less than 0.05). GN+CH resulted in significant reductions in two kidney glomerular filtration rate (GFR) below values in C, and GFR in the unclipped kidney was markedly reduced when compared to CH. The glomerular capillary hydrostatic pressure and the pressure gradient( (delta P) were elevated approximately 4 to 5 mm Hg in GN and CH rats and 6 mm Hg above GN and CH values in the GN+CH rats. The glomerular ultrafiltration coefficient (LpA) was reduced to approximately 40% of C in both GN and GN+CH in spite of further increases in delta P. Surface nephron filtration rate was similar in all groups, suggesting glomerular dysfunction was primarily in nephrons below the surface in GN+CH. Morphologic evaluation revealed that GN+CH exhibited a combination of diffuse and focally sclerotic lesions characteristic of GN and CH, respectively. Documented further increases in PG did not worsen glomerular morphology, but kidney GFR did decrease. Hypertension induced deterioration of glomerular function in nephrons below the surface was not associated with marked morphologic deterioration, but a combination of the characteristics of GN and CH.

Animals↗

PubMed1987

A small multigene family encodes Gi signal-transduction proteins.

The guanine nucleotide-binding regulatory proteins known as G proteins are receptor-associated signal-transduction molecules that are implicated in the control of a variety of metabolic processes. Recent evidence suggests that G proteins may mediate B-lymphocyte responses to bacterial lipopolysaccharide and may also transduce signals from the T-cell antigen receptor. Since these receptors are uniquely expressed on lymphoid cells, we used molecular cloning strategies to ask whether lymphocytes contain specialized G-protein alpha subunits to assist in signal transduction. Comparison of our two deduced human alpha i amino acid sequences with those previously determined for bovine and rodent G proteins permits the identification of three closely related but distinct types of alpha i molecules that comprise a small multigene family. Using gene-specific probes, we found that both of our alpha i genes are expressed in most cell types but in differing ratios. Our data support the view that a modest repertoire of extremely closely related G proteins mediates the transduction of signals derived from multiple different receptor molecules.

Animals↗

PubMed1987

Long-term immunization against the beta-subunit of ovine luteinizing hormone (oLH beta) has no adverse effects on pituitary function in rhesus monkeys.

One postulated safety hazard of contraceptive methods based on immunization against gonadotropic hormones is the possibility that circulating antibodies which crossreact with pituitary hormones may impair pituitary function through the deposition of immunoglobulin and/or complement suggesting immune complexes. In order to evaluate this possibility in rhesus monkeys actively immunized against the beta-subunit of ovine luteinizing hormone (oLH beta), we used three approaches to study the effects of long-term immunization on pituitary function: a) evaluation of pituitary responsiveness to challenge with a GnRH-agonist; b) examination of pituitary histology and immunostaining with gonadotropin antisera; and c) examination of pituitary cells for deposition of immune complexes. Our results indicate that circulating anti-oLH beta antibodies did not result in significant impairment of pituitary function in rhesus monkeys.

Animals↗

PubMed1987

Analysis of renal function in the two-kidney Goldblatt model.

We analyzed the renal functional responses in all rats 4-6 wk after application of a clip to one renal artery and maintained on either a normal NaCl-intake or a NaCl-depletion protocol utilizing both clearance methods and micropuncture evaluations of glomerular hemodynamics. Although mean arterial pressure (MAP) rose significantly, the response was quite variable and the frequency and degree of hypertension independent of NaCl dietary protocol (142 +/- 7 vs. 137 +/- 6 mmHg, NS). Glomerular filtration rate (GFR) of the unclipped kidney was well maintained regardless of absolute MAP, however, GFR in the clipped kidney was somewhat MAP dependent. The glomerular ultrafiltration coefficient (LpA) was reduced in all clipped rats independent of MAP and dietary NaCl (0.037 +/- 0.002 vs. 0.063 +/- 0.009 nl X s-1 X mmHg-1, P less than 0.05). Glomerular capillary hydrostatic (PG) and glomerular capillary hydrostatic gradient (delta P) were elevated in all clipped rats, regardless of MAP, and to a greater extent in clipped rats maintained on the NaCl-depletion protocol (PG, 59.6 vs. 53.2, P less than 0.05). Among clipped rats, multiple regression analysis revealed no correlation between PG or delta P and the degree of reduction in LpA. The unclipped kidney of the two-kidney, one-clip model is characterized by uniform reductions in LpA independent of the MAP and awake blood pressure produced. Although the increase in PG and delta P may contribute to the reduction in LpA observed, the degree of LpA reduction is independent of the magnitude of elevation in PG and delta P in clipped rats.

Animals↗

PubMed1987

Hypocomplementemic glomerulonephritis in an infant and mother. Evidence for an abnormal form of C3.

A mother developed hematuria during the fourth month of pregnancy, and her nursing infant son from this otherwise uncomplicated pregnancy developed hematuria at 3.5 months of age. Both had a mild glomerulonephritis characterized by mesangial prominence, focal thickening and mottling of the glomerular basement membrane and electron-dense deposits, predominantly in the intramembranous and subendothelial positions. Immunofluorescence studies revealed striking accumulations of C3 and other complement components associated with alternative complement pathway activation within glomeruli, and the presence of small or equivocal amounts of immunoglobulin. C1q, C4 and factor B were not detectable. The glomerular lesion was accompanied by hypocomplementemia. Sera of both mother and infant displayed half normal levels of C3 and factor B, increased levels of C4, and normal levels of 12 other complement proteins. High normal or slight elevation in nephritic factor-like activity was observed in serial serum samples. Studies suggested that this mother and son represent the second kindred having an abnormal form of C3 which produces an alternative complement pathway C3 convertase, C3b, Bb, resistant to control by factor H. No additional affected family members were identified. The course of the nephritis over 7 years without drug therapy has been mild with resolving hematuria and no abnormal proteinuria or decrease in creatinine clearance.

Adult↗

PubMed1987

Sequence of inflammatory cell migration into lung during recovery from hyaline membrane disease in premature newborn monkeys.

The appearance of polymorphonuclear leukocytes (PMN) and macrophages (MAC) in lung during the development of hyaline membrane disease (HMD) may be important in lung injury and repair. These inflammatory cells may cause additional lung injury during recovery from HMD and contribute to the development of bronchopulmonary dysplasia (BPD). By morphometric methods, we compared the proportion of PMN and MAC in lung tissue of premature M. nemestrina monkeys with HMD to the proportion of these cells in the lungs of healthy control animals of a similar postnatal age and to fetuses of the same gestational age. Expressed as a fraction of all lung cells, healthy premature control monkeys have the same %PMN and %MAC in lung tissue as fetal animals. However, during the development of acute HMD, there is an increase in %PMN (p less than 0.05), but not in %MAC, compared to fetal animals. During recovery, there is a greater than 10-fold increase in %MAC (p less than 0.02), but no significant additional increase in %PMN compared to animals with acute HMD. We conclude that the sequence of inflammatory cell migration into the premature lung injured during HMD is first a polymorphonuclear one, followed by entry of macrophages. Control of this inflammatory response during recovery from HMD may play a role in the pathogenesis of BPD.

Animals↗

PubMed1987

Hormonal regulation of expression of the endogenous and transfected human growth hormone gene.

Expression of the endogenous human GH (hGH) gene in response to glucocorticoids, thyroid hormone, and insulin was studied in cultures of dispersed GH-secreting human pituitary adenomas. Results were compared to those obtained when the hGH gene was transfected into rat pituitary tumor cells (GC). In the human pituitary cells the glucocorticoid dexamethasone [(Dex) 10(-6) M] increased the release of GH and the levels of GH mRNA by 2 to 4-fold (P less than 0.05). T3 (10(-8) M) had no effect on GH mRNA but increased hGH release by 2- to 6-fold (P less than 0.01). Insulin (5 x 10(-9) M) alone had no significant effect on either hGH mRNA or protein, but blunted the effect of Dex. Among 11 of 18 GC cell clones transfected with the hGH gene with detectable hGH mRNA expression, Dex increased hGH mRNA levels in seven and T3 treatment reduced hGH mRNA levels in eight. Conversely, rat GH mRNA levels from the endogenous rat gene were increased by either Dex or T3 in all 18 clones. Insulin alone or in combination with T3 or Dex was found to increase hGH mRNA levels in some cell lines and to decrease hGH mRNA levels in others; these effects were correlated strongly (r = 0.88; P less than 0.001) with the influence of insulin on the endogenous rat GH gene, implying that individual cellular differences can simultaneously affect the insulin responsiveness of both genes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗

PubMed1987

Radiation therapy in the treatment of partially resected meningiomas.

To address the question of whether radiation therapy is beneficial in the management of partially resected meningiomas, we reviewed the records of all patients admitted to the University of California, San Francisco, between 1968 and 1978 who had a diagnosis of intracranial meningioma. The patients were divided into three groups: 51 patients had gross total resection and did not receive radiation therapy, 30 patients had subtotal resection and no radiation therapy, and 54 patients had subtotal resection followed by radiation therapy. The subtotal resection groups were similar in average age, male:female ratio, and tumor location, which allowed a valid comparison of the effects of irradiation. The recurrence rate in the total resection group was 4% (2 of 51 patients). Among patients in the subtotal resection groups, 60% of nonirradiated patients had a recurrence, compared with only 32% of the irradiated patients. The median time to recurrence was significantly longer in the irradiated group than in the nonirradiated group (125 vs. 66 months, P less than 0.05). There was no complication related to irradiation. These results provide convincing evidence that radiation therapy is beneficial in the treatment of partially resected meningiomas.

Combined Modality Therapy↗

PubMed1987

Brachytherapy of recurrent tumors of the skull base and spine with iodine-125 sources.

Thirteen patients with recurrent, previously irradiated tumors of the skull base or spine were reirradiated with 125I sources implanted interstitially using microsurgical or stereotactic techniques. Patients harbored difficult, end-stage recurrences of chordoma, meningioma, malignant meningioma, fibrosarcoma, invasive pituitary adenoma, and malignant schwannoma. In two other patients with malignant meningioma, the dose of external radiation was augmented by implanting 125I sources during the initial operation for excision of the lesion or at a separate surgical procedure after conventional teletherapy. Microsurgical implantation of 125I sources into basal tumors was limited by the difficulties inherent in operating in this region; it is not possible to visualize the entire tumor that requires implantation. Three of five chordomas stabilized or regressed; these patients probably benefited from the procedure. Two patients with recurrent malignant meningiomas had long term remission after interstitial brachytherapy. Interstitial 125I brachytherapy for recurrent tumors at the base of skull or adjacent to the spine can be more successful only if more aggressive surgical exposures of these regions are attempted. Implantation of sources for a "boost" dose, either microsurgically during the initial surgical resection of the lesion before conventional teletherapy or stereotactically after conventional teletherapy, may be a valuable adjunct to external irradiation for the control of potentially devastating tumors (such as chordomas and malignant meningiomas) before they recur with the severe consequences seen in the patients reported here.

Adenoma↗

PubMed1987

Staged treatment of arteriovenous malformations of the brain.

Twenty-eight patients treated for arteriovenous malformations (AVMs) of the brain had staged therapy consisting of multiple surgical procedures or endovascular embolization followed by surgical treatment. There were 10 men and 18 women, aged 15 to 60 years (mean, 34 years). The clinical symptoms were those associated with intracranial hemorrhage in 13 patients, progressive neurological deficit not due to hemorrhage in 6, intractable headache in 5, and seizures in 4. Four groups were identified based upon the reason for staging therapy. Thirteen patients with large high flow AVMs (Group A) had staged treatment because of the risk of normal perfusion pressure breakthrough. The initial afferent artery occlusion was accomplished surgically in 9 patients and by endovascular embolization in 4. Postoperatively, no patient in this group had malignant cerebral edema or intracranial hemorrhage suggestive of normal perfusion pressure breakthrough, but 1 patient had an intraventricular hemorrhage after initial embolization. In 9 patients (Group B), the AVM had a complex multiple arterial supply that precluded resection from a single operative exposure. Seven had supratentorial AVMs, and 2 had AVMs of the posterior fossa. In 6 of these cases, the AVM was located in the midline and received bilateral arterial input. Six patients had staged surgical procedures, and 3 had an initial endovascular embolization followed by operation. Two patients had intracerebral hemorrhages, one after an initial surgical procedure and another after initial embolization. In 4 patients (Group C), the AVM had a major dural component that was treated separately from the parenchymal component. In 3 of these patients, embolization through the external carotid artery satisfactorily obliterated the dural component; in the remaining patient, a persistent internal carotid supply necessitated resection of the dural malformation. The parenchymal component was excised surgically in 2 patients. Two patients (Group D) had separate surgical procedures to treat an aneurysm associated with a parenchymal AVM. Overall, 19 of 28 patients had complete excision and 9 had partial obliteration of their AVMs. Late follow-up of 27 patients at a mean of 18.6 months showed that 16 patients were in excellent condition and 8 were in good condition. Three patients were in poor condition with debilitating neurological deficits. One patient had a delayed intracranial hemorrhage 22 months after incomplete obliteration of her AVM. Staged treatment of selected AVMs of the brain may avoid the occurrence of normal perfusion pressure breakthrough.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

PubMed1987

Reoperation for recurrent glioblastoma and anaplastic astrocytoma.

The advisability of a second operation for recurrent glioblastoma multiforme or anaplastic astrocytoma depends on the expected duration and quality of subsequent survival. We reviewed the results in 70 consecutive patients who underwent reoperation for supratentorial glioblastoma multiforme (n = 39) or anaplastic astrocytoma (n = 31) between 1975 and 1984. The operative morbidity rate was 5.7% (4 of 70 patients); the 6-week postoperative mortality rate was 4.3% (3 of 70 patients). The median duration of survival after reoperation was 36 weeks in patients with glioblastoma multiforme and 88 weeks in those with anaplastic astrocytoma. The median duration of high quality survival (defined as the period during which the patient had a Karnofsky performance score of at least 70) after reoperation was 10 weeks for patients with glioblastoma multiforme and 83 weeks for patients with anaplastic astrocytoma. Age and preoperative Karnofsky score in patients with glioblastoma multiforme and age in patients with anaplastic astrocytoma had statistically significant effects on the duration of high quality survival after reoperation, but not on postoperative survival independent of quality. Although age and functional status do not significantly affect the duration of survival after reoperation, they do have a significant effect on the quality of life after reoperation. Frequently, a patient can expect to spend a greater portion of his life at a higher level of function than he would have without reoperation. As adjunctive forms of therapy improve, reoperation will play an increasingly prominent role in the management of recurrent malignant astrocytic tumors.

Adult↗

PubMed1987

Cervical spine stenosis secondary to ossification of the posterior longitudinal ligament.

Ossification of the posterior longitudinal ligament (OPLL) is a well-documented cause of cervical spine stenosis and myelopathy among Japanese patients. Reports of OPLL in North Americans are rare. Choices of diagnostic method and treatment for this entity remain controversial. The authors report the results of management of 20 patients in the United States with symptomatic OPLL of the cervical spine. These represented 10% to 20% of patients operated on over the last 3 years for myelopathy secondary to structural spinal compression. Most of these OPLL patients were Caucasian (60%), male (male:female 4:1), and middle-aged (median age 47.5 years). Six had previously undergone laminectomy or discectomy. Cervical roentgenograms and standard myelography occasionally suggested the diagnosis. Axial computerized tomography (CT) metrizamide myelography with small interslice intervals proved invaluable for diagnosis and operative planning. Magnetic resonance imaging was not necessary for diagnosis. Retrovertebral calcification extended over one to five bodies (mean 2.75). The mass ranged in size from 5 to 16 mm in anteroposterior diameter and reduced the residual canal diameter to a mean (+/- standard deviation) caliber of 9.42 +/- 2.41 mm (mean narrowing ratio 0.44 +/- 0.12). Anterior cervical decompression by medial corpectomy and discectomy with fusion uniformly reduced preoperative myelopathy. Complications were limited to transient neurological deterioration in two patients, recurrent laryngeal nerve palsy in one, and halo device pin site infections in two. At a mean postoperative interval of 15 months, improvement was seen in each category of deficit: extremity weakness, hypesthesia, hypertonia, and urinary dysfunction. All fusions produced solid unions. It is concluded that OPLL of the cervical spine is an unexpectedly prevalent cause of myelopathy among patients treated in the United States. Thin-section axial CT metrizamide myelography with small interslice intervals is essential for the investigation of patients who may have OPLL. Anterior decompression and stabilization by medial corpectomy, discectomy, removal of the calcified mass, and fusion is a safe and effective method of treatment.

Adult↗

PubMed1987

Phase I-II study of eflornithine and mitoguazone combined in the treatment of recurrent primary brain tumors.

Eflornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, and mitoguazone (MGBG), a competitive inhibitor of S-adenosylmethionine decarboxylase, were evaluated in a phase I-II study for patients with primary recurrent malignant brain tumors. All patients had failed prior radiation therapy and most had also failed prior chemotherapy. Two dose schedules were used, with the second schedule (Group II) a modification of the first schedule (Group I). The Group II schedule, with different dose levels, was better tolerated than the Group I schedule. Gastrointestinal and myelotoxicity were dose-limiting in most patients, and tinnitus was dose-limiting in two patients. Nineteen of 33 evaluable patients had anaplastic gliomas, in whom response was observed in 21%, stable disease in 53%, and immediate progression after one course of therapy in 26%. Of six patients with glioblastoma multiforme, two had brief stabilization of disease. An additional patient with brainstem glioma and ependymoma also had disease stabilization. Four patients with medulloblastoma, a spinal cord mixed glioma, and one with oligodendroglioma failed DFMO-MGBG. Based on this study, we believe that a combination of DFMO and MGBG is well-tolerated and deserves further evaluation for patients with anaplastic gliomas, particularly those that appear to be biologically slow growing.

Adolescent↗

PubMed1987

Expression of HLA class II antigens and secretion of interleukin-1 by monocytes and macrophages from adults and neonates.

HLA class II antigen expression and IL-1 production by mononuclear phagocytes are important for antigen-stimulated T-cell activation. We examined these surface antigens and a monocyte marker antigen on fresh cord and adult blood monocytes, macrophages (M phi) derived from monocytes in vitro, human placental (fetal) M phi, from adult women. By FACS analysis, we found less DR on cord blood monocytes (80 +/- 7) than on adult monocytes (96 +/- 1) with greater heterogeneity in density of DR due to a weakly staining subpopulation of cord monocytes. There were markedly fewer DR and DQ positive placental M phi, 62 +/- 11% and 19 +/- 3%, compared to adult peritoneal M phi, 91 +/- 11% and 87 +/- 13%. DQ was more intense on peritoneal M phi than on any other cell type. Fresh cord monocytes secreted equal or greater amounts of interleukin-1 (IL-1) in response to lipopolysaccharide (LPS) or Group B streptococci than adult monocytes, although results with individual preparations varied. By Northern blot analysis, LPS-stimulated cord blood and adult monocytes contained similar amounts of IL-1 alpha, IL-1 beta and DR alpha mRNA. Each placental M phi preparation secreted IL-1 (200 +/- 85 U/ml to LPS). Peritoneal M phi preparations from women in the pre-luteal phase did not release detectable IL-1, whereas those from women in the post-luteal phase released as much as monocytes. Cultured monocytes failed to secrete IL-1 and expressed less DQ than fresh monocytes. Exposure to IFN gamma augmented IL-1 release by adult and cord cells and DQ expression on cord cells. These data indicate that class II antigen expression and IL-1 secretion by mononuclear phagocytes are only in part co-ordinately modulated. The differences between placental (fetal) M phi and adult peritoneal M phi may reflect both tissue-specific differences and generally diminished class II antigen expression on fetal and neonatal mononuclear phagocytes.

Adult↗

PubMed1987

Binding of anti-basement membrane antibody to alveolar basement membrane after intratracheal gasoline instillation in rabbits.

A possible causal relationship has been suggested between hydrocarbon (gasoline, solvents, etc.) exposure and development of anti-basement membrane antibody-associated Goodpasture's syndrome in man. The authors evaluated the effect of hydrocarbons on pulmonary capillary permeability and binding of heterologous anti-basement membrane antibodies in the lungs after intratracheal instillation of minute amounts of unleaded gasoline into rabbits. The anti-glomerular basement membrane (GBM) antibodies used reacted with the alveolar basement membrane (ABM) in vitro by indirect immunofluorescence. The gasoline treatment altered pulmonary capillary permeability, judging from the increased accumulation of systemically administered radioiodinated bovine serum albumin in the alveolar and extravascular spaces of lungs; it also induced focal macroscopic and microscopic pulmonary histologic lesions. The gasoline caused focal in vivo binding of the anti-GBM antibodies to the ABM detectable by immunofluorescence microscopy. No binding was observed in lungs from control rabbits given saline instillations when assayed by immunofluorescence. The paired label radioisotope technique confirmed the increased antibody binding to lungs injured with gasoline (1.08 +/- 0.03 micrograms) versus 0.37 +/- 0.07 microgram after saline (P less than 0.001). These results indicate that gasoline exposure damages a pulmonary barrier that normally prevents binding of anti-GBM/ABM antibody to ABM and suggest that hydrocarbon exposure may be one of perhaps several pneumotoxic events that contribute to the episodic pulmonary hemorrhage in Goodpasture's syndrome by temporarily allowing ABM binding of anti-basement membrane antibodies.

Animals↗