Biomedical subjects

Y Sugisaki

Publications and source records attributed to Y Sugisaki.

At least 37 records · Page 2Linked to original sources

PubMed1998

Somatic mutations of the PTEN/MMAC1 gene in fifteen Japanese endometrial cancers: evidence for inactivation of both alleles.

Loss of heterozygosity (LOH) of chromosome 10q is observed in approximately 40% of endometrial cancers. Mutations in PTEN/MMAC1, a gene recently isolated from the 10q23 region, are responsible for two dominantly inherited neoplastic syndromes, Cowden disease and Bannayan-Zonana syndrome. Somatic mutations of this gene have also been detected in sporadic cancers of the brain, prostate and breast. To investigate the potential role of this putative tumor suppressor gene in endometrial carcinogenesis as well, we examined 46 primary endometrial cancers for LOH at the 10q23 region, and for mutations in the entire coding region and exon-intron boundaries of the PTEN/MMAC1 gene. LOH was identified in half of the 38 informative cases, and subtle somatic mutations were detected in 15 tumors (33%). Our results suggest that of the genes studied so far in endometrial carcinomas, PTEN/MMAC1 is the most commonly mutated one, and that inactivation of both copies by allelic loss and/or mutation, a pattern that defines genes as "tumor suppressors," contributes to tumorigenesis in endometrial cancers.

Alleles↗

PubMed1998

Recovery of damaged glomerular capillary network with endothelial cell apoptosis in experimental proliferative glomerulonephritis.

Capillary repair can occur in damaged glomeruli in recovery models of glomerulonephritis (GN). In order to clarify whether capillary repair is an essential component in glomerular recovery from GN, we have examined the development of the capillary repair after inflammatory injury in both the repairing glomeruli and the segmental sclerotic scar lesions in Thy-1 GN. Mesangiolytic glomerular damage was induced in rats with anti-Thy-1.1 antibody administration. Diffuse mesangiolysis and segmental microaneurysmal ballooning developed in damaged glomeruli by day 3, with reduction of endothelial cellularity. Thereafter, histological proliferative GN developed between day 5 and week 3. Endothelial cell proliferation began on day 1 and peaked on day 5, and the number of glomerular endothelial cells increased and exceeded the level of control values on day 7. Angiogenic glomerular capillary repair occurred through the process of not only capillary regeneration from remaining endothelial cells in capillary aneurysmal lesions but also new capillary growth derived from the glomerular vascular poles by day 7. The number of glomerular capillary lumina also increased to the level of controls by week 3. Subsequently, mesangial proliferative GN resolved, and most of the glomeruli recovered to their normal structure with the reconstruction of the capillary network by weeks 4-6. In the glomerular capillary repair, significant apoptosis of glomerular endothelial cells was present during the period of mild endothelial cell hypercellularity between day 7 and day 10 (0.06 +/- 0.02 apoptotic endothelial cells/glomerular cross section vs. 0.00 +/- 0.00 in controls, mean +/- SEM; p < 0.05. In Thy-1 GN, most of the damaged glomeruli recovered with angiogenic capillary repair. However, segmental sclerotic scar lesions remained in 10-30% of the glomeruli with an incomplete repair of glomerular capillaries. Therefore, it is concluded that following the destruction of the glomerular capillary network in GN, angiogenic capillary repair plays an essential role in the recovery of damaged glomeruli, and incomplete capillary repair leads to sclerotic scar lesions in damaged glomeruli. Glomerular capillary repair occurs through the process of capillary regeneration from remaining endothelial cells as well as new glomerular capillary growth from the glomerular vascular poles. In glomerular capillary repair, apoptosis is necessary in regulating the number of intrinsic endothelial cells.

Animals↗

PubMed1998

Lymphoblastic lymphoma of natural killer cell origin, presenting as pancreatic tumour.

AIMS: We describe the first case of lymphoblastic lymphoma (LBL) of natural killer (NK) cell origin initially presenting as a pancreatic tumour, and review this type of lymphoma. METHODS AND RESULTS: A 38-year-old woman with abdominal pain was found to have a pancreatic mass. Twenty days later, she developed diffuse lung infiltrates and leucoerythroblastosis of the peripheral blood, and her bone marrow was diffusely infiltrated with blasts. The blasts were positive for CD56, CD16 and P-glycoprotein, but lacked cytoplasmic azurophilic granules, T. B and myeloid cell markers on the cell surface, rearrangement of the genes for T-cell receptor and immunoglobulin, and the Epstein-Barr virus (EBV) genome. The diagnosis was LBL of NK cell origin. She received aggressive therapy, but died of the lymphoma. In contrast to ordinary NK-cell lymphoma, this case and reported cases of LBL of NK-cell origin showed the following common characteristics. The tumour cells often lack cell surface CD2, cytoplasmic CD3, cytoplasmic azurophilic granules, and EBV genome. The prognosis was extremely poor. CONCLUSIONS: LBL of NK-cell origin should be included in the differential diagnosis of pancreatic tumours. To fully characterize this type of lymphoma, further cases must be evaluated.

Adult↗

PubMed1998

[Evaluation of peritoneal lavage smears and intraperitoneal administration of anti-neoplastic agents in stage III and IV gastric cancer].

Examinations of peritoneal lavage smears (cy) in gastric cancer surgical stages III and IV are very important for determining the disease stage. We have been carrying out these examinations for 8 years. One hundred sixty patients with gastric cancer were examined. The incidence of cy positivity was higher in T4 than in T3, and higher in P1,2,3 than in P0. We performed intraperitoneal administration of CDDP in 10 patients with gastric cancer using a reservoir (Infuse-A-Port) implanted in the abdominal wall once a week. No difference in survival was observed between patients who received chemotherapy via i.p. and those who received it i.v.

Adenocarcinoma↗

PubMed1997

Rare glomerular capillary regeneration and subsequent capillary regression with endothelial cell apoptosis in progressive glomerulonephritis.

Glomerulonephritis (GN) leading to glomerular sclerosis remains an important cause of renal failure. The glomerulus is a capillary network, but endothelial and vascular reactions during progressive GN are not well understood. We have, therefore, examined the morphological alterations of glomerular capillary network and endothelial cells during the progression of damaged glomeruli to glomerular sclerosis. A progressive model of anti-glomerular basement membrane (GBM) GN was induced in Wistar-Kyoto (WKY) rats with a single injection of anti-rat GBM antibody. Severe necrotizing glomerular injuries were observed between day 5 and week 3 with a reduction in the number of total glomerular endothelial cells and total glomerular capillary lumina per glomerular cross sections. In necrotizing lesions, the glomerular endothelial cells were lost with the destruction of the glomerular capillary network. Moreover, angiogenic capillary repair with proliferation of endothelial cells was rare in severely damaged regions of glomeruli. Subsequently, mesangial hypercellularity and marked mesangial matrix accumulation occurred with absence of the development of a capillary network, and the necrotizing lesions progressed to sclerotic scars until 8 weeks. Although active necrotizing lesions could not be seen in damaged glomeruli between week 4 and week 8, the number of apoptotic endothelial cells gradually increased in the glomerular capillaries (0.10 +/- 0.01 apoptotic endothelial cells/glomerular cross section at week 8 versus 0.00 +/- 0.00 control cells (mean +/- SEM; P < 0.05) with the progression of glomerular sclerosis. Whereas the number of apoptotic endothelial cells increased in the damaged glomeruli, the number of total glomerular endothelial cells decreased (9.3 +/- 3.0 cells/glomerular cross section at week 8 versus 24.8 +/- 3.0 cells in control (mean +/- SD); P < 0.001) with regression of glomerular capillaries (3.6 +/- 2.5 capillary lumina/glomerular cross section at week 8 versus 35.0 +/- 5.0 capillary lumina in control (mean +/- SD); P < 0.001). Finally, glomerular endothelial cells could not be detected in the sclerotic lesions in progressive anti-GBM GN in WKY rats. These data indicate that the destruction of the capillary network of glomeruli and subsequent incomplete angiogenic capillary repair leads to glomerular sclerosis in progressive GN. Endothelial cell apoptosis with glomerular capillary regression may also contribute to the development of glomerular sclerosis. Injury of the glomerular capillary network with endothelial cell damage, including apoptosis and subsequent incomplete capillary repair, plays an important role in the progression of glomerular sclerosis during anti-GBM GN in WKY rats.

Animals↗

PubMed1996

ACTH independent Cushing's syndrome occurring in siblings.

Familial Cushing's syndrome due to ACTH independent bilateral macronodular adrenocortical hyperplasia occurring in siblings is reported. The proband was a 69-year-old woman who presented with a typical Cushingoid appearance. The serum cortisol level was elevated, with a loss of diurnal rhythm, and the plasma ACTH level was undetectable. Dynamic testing showed no suppression of urinary 17-OHCS by high dose dexamethasone and no stimulation by metyrapone. An abdominal CT scan showed bilateral adrenal enlargement. The patient died of a subarachnoid haemorrhage, and autopsy revealed a massively thickened adrenal cortex composed of nodules up to 3.5 cm in diameter. A pituitary adenoma was not found. We learned that the patient's elder brother was also diagnosed at 59 years of age with Cushing's syndrome due to bilateral macronodular adrenocortical hyperplasia. His plasma cortisol levels were not suppressed by high dose dexamethasone and the plasma ACTH level was undetectable. Screening of the available family members by administering 1 mg dexamethasone at midnight and performing abdominal CT scan revealed impaired suppressibility of serum cortisol associated with enlarged bilateral adrenal glands in a 64-year-old sister and a 54-year-old brother. The 64-year-old sister was considered as a possible 'affected' case in the early stages of development, because the basal level of ACTH was not suppressed and hyperplasia of the bilateral adrenal glands as revealed by CT scan was less evident.

Adrenal Cortex↗

PubMed1996

Glomerular capillary regeneration and endothelial cell apoptosis in both reversible and progressive models of glomerulonephritis.

In summary, angiogenetic capillary regeneration with endothelial proliferation occurred among mesangiolytic lesions in Thy-1 GN, and the damaged glomerulus recovered its normal structure with the reconstruction of the capillary network. In anti-GBM GN on WKY rats, the damaged glomerulus showed rare capillary regeneration and progressed to global sclerosis. In Thy-1 GN, endothelial cell apoptosis was found in the regenerated capillaries with endothelial cell hypercellularity. On the other hand, in anti-GBM GN on WKY rats, the number of endothelial cell apoptosis increased during the evolution of glomerular sclerosis. We have concluded that glomerular capillary regeneration plays an essential role in the recovery of damaged glomeruli. Moreover, apoptosis is indispensable in regulating the number of intrinsic endothelial cells. We also found that endothelial apoptosis is important in progression of glomerular sclerosis.

Animals↗

PubMed1996

Infantile acute monocytic leukemia with tumor formation in the skin expressing adhesion molecules as seen by electronmicroscopy.

We report a case of infantile acute monocytic leukemia associated with solid tumors in the skin. Light microscopy showed that the tumor cells were mainly spindle-shaped and arranged in tandem. Immunohistochemical staining showed that fibronectin was detected in the extracellular matrix (and partially on the surface of tumor cells), integrin alpha 5 beta 1 on the cell surface, and vinculin and actin were detected in the cytoplasm of the tumor cells. Electron microscopy showed that the tumor cells had perpendicular transmembranous fibrils and closely situated collections of cytoplasmic microfilaments beneath the cell membrane suggesting fibronexus-like structures. We conclude that the expression of fibronectin, integrin alpha 5 beta 1, vinculin, cytoplasmic actin and fibronexus-like structure in leukemic cells indicate these cells possess an adhesive function. The mechanism of formation of the extramedullary solid tumors in this patients involved these adhesion molecules of the tumor cells.

Bone Marrow↗

PubMed1996

Apoptosis in progressive crescentic glomerulonephritis.

Recent studies in the experimental proliferative glomerulonephritis (GN) indicate that apoptosis is the major mechanism that mediates the resolution of glomerular hypercellularity during the repair process of experimental GN. The role of apoptosis during progressive GN, however, has not yet been well understood. We have, therefore, examined the role of apoptosis during the progression of experimental crescentic GN to end-stage renal failure. A progressive model of antiglomerular basement membrane GN was induced in Wistar-Kyoto rats with a single injection of anti-rat glomerular basement membrane antibody. Renal function and histologic studies were performed chronologically from Day 0 to Week 8 after disease induction. The incidence of apoptosis in glomeruli as well as glomerular crescents was examined during the progression of crescentic GN to end-stage kidney disease. Many leukocytes infiltrated glomeruli from the early phase of GN, and severe necrotizing and mesangiolytic glomerular damage was observed from Day 5 to Week 3. After glomerular damage, mesangial hypercellularity with mesangial cell proliferation and extracellular matrix accumulation began with crescent formation. Thereafter, glomerular inflammation continued with marked extracellular matrix accumulation until Week 4, and the renal function deteriorated. The proliferative glomerular lesions subsequently progressed to sclerotic lesions and eventually to chronic renal failure in Week 8. Although the number of proliferating cells and infiltrating leukocytes slowly decreased, glomerular inflammation resolved with scar formation as mesangial sclerosis. Significant apoptosis was present from Day 7 (mean +/- SEM, 0.53 +/- 0.12 cells/glomerular cross-section) and gradually increased in number with the proliferating lesions as glomerular inflammation continued. Moreover, apoptosis increased during the resolution of the glomerular inflammation, and many apoptotic cells were present in the sclerotic lesions in Week 8 (1.97 +/- 0.27 cells/glomerular cross-section). As glomerular inflammation subsided, cellular crescents progressed to fibrous crescents with a reduction of cellularity by Week 8, and apoptosis increased significantly within these lesions. These findings indicate that apoptosis plays an essential role in the resolution of intra- and extraglomerular inflammation and in the elimination of glomerular cells within the scarring regions for progressive crescentic GN. The regulation of the apoptotic phenomenon during crescentic GN may be important in the progression of glomerular inflammation and the development of pathologic glomerular sclerosis.

Animals↗

PubMed1995

Endothelial regeneration during the repair process following Habu-snake venom induced glomerular injury.

In this study, the kinetics of glomerular endothelial cells during the repair process following glomerular injury was investigated in a model of mesangial proliferative glomerulonephritis induced by Habu-snake venom (HSV) in rats. Intravenous injection of HSV led to a cystic ballooning type lesion at day 1. Subsequently a marked segmental proliferative lesion was observed in the cystic areas at day 5. Thereafter cellularity decreased and reconstruction of the glomerular tuft was gradually observed with time. The histological structure of the glomeruli had almost returned to normal 21 days following HSV injection. After prominent depletion at day 1, the number of endothelial cells increased rapidly and reached a plateau at day 7, not significantly different from that of the control group. Morphologically endothelial cell elongation from the vascular pole into the cystic lesion was seen together with premature capillary formation in the proliferative lesion. Accompanying the reduction of mesangial expansion, the endothelial cells gradually formed definite capillary lumens. We conclude that the mesangial proliferative glomerulonephritis induced by HSV recovers to its original structural state and that the migration and proliferation of endothelial cells with accompanying capillary formation are essential for the repair process, in addition to mesangial cell proliferation.

Animals↗

PubMed1995

Apoptosis in the repair process of experimental proliferative glomerulonephritis.

The recovery from the proliferative glomerulonephritis (GN) with reduction of hypercellularity is known in various experimental and human GN. To elucidate the participation of apoptosis in GN, we studied the experimental Thy-1.1 GN for six weeks. Apoptosis was recognized by both light and electron microscopy, and the biochemical expression of apoptosis was morphologically confirmed by in situ end-labeling method of fragmented DNA, using terminal deoxy-transferase. Mesangioproliferative GN was induced by a single administration of anti-Thy-1.1 monoclonal antibody in a rat. Mesangial cell proliferation started early in the process and the number of glomerular cells peaked from day 7 to day 10. Subsequently, the degree of proliferative lesion diminished with obvious reconstruction of the capillary structure, as well as decrease in the number of glomerular cells. During this period, proliferated mesangial cells returned to their original level of cellularity and apoptosis apparently increased in number among the glomeruli. Apoptosis was significantly noted from day 7 to week 4 and was in its maximum at day 10 to week 2. Following this period, by week 6 most of the glomeruli reverted to their original structure. The number of infiltrated neutrophils and macrophages in the glomeruli slowly decreased during the course of the disease, and a few apoptosis were also observed. It is concluded that proliferated glomerular cells regress by apoptosis in the repairing process of GN. Apoptosis plays an essential role in the recovery to the original glomerular structure in GN.

Animals↗

PubMed1995

Sebaceous carcinoma of the vulva.

Extraocular sebaceous carcinoma (SC) is a rare tumor usually found on the head and neck. A 78 year old Japanese female who had an asymptomatic vulvar tumor is reported here. The excised specimen showed SC with metastasis to the inguinal lymph nodes. This is the fourth reported case of SC arising from female genitalia, and the second case that apparently arose from the labia minora. Contrary to the previously reported cases, tumor cells in the present case had abundant glycogen. Thus, differential diagnosis of SC from metastatic renal cell carcinoma is difficult morphologically because both of them have glycogen and lipid. Intraepidermal invasion of tumor cells has been reported in SC, but a suspected lesion of this phenomenon in the present case was proved to be histiocytic infiltration by immunohistochemistry using anti-CD 68 antibody.

Adenocarcinoma, Sebaceous↗

PubMed1994

Tubular dilatation in the repair process of ischaemic tubular necrosis.

To elucidate the mechanisms of renal tubular dilatation in acute tubular necrosis (ATN), morphological findings after 60 min ischaemia were studied in rats. The characteristics of the tubular basement membrane (BM) were also examined. A morphometric analysis of cell proliferation, epithelial cellularity and the circumference of damaged tubules was performed. The ischaemic injury resulted in widespread necrosis of renal tubules at day 1, and the BM of damaged tubules appeared thin. The intensity of the immunohistochemical staining for BM components decreased. The epithelial cell proliferation was particularly active in the early phase. Dilatation of the damaged tubules began at day 2, and the degree of dilatation increased up to day 6. Regenerative epithelial hyperplasia occurred and abnormalities of tubular BM were seen. Epithelial hyperplasia and dilatation of damaged tubules was most prominent at day 6 and the tubular BM was thickened by newly produced BM components. Tubular obstruction was not seen and tubules returned to normal size by day 28. Epithelial hyperplasia and abnormalities of tubular BM disappeared progressively. Regenerative tubular epithelial hyperplasia and abnormalities of tubular BM may play an important role in pathogenesis of tubular dilatation in ATN, and tubular dilatation is not due to tubular obstruction.

Animals↗

PubMed1994

Stimulatory effect of EGF and inhibitory effect of sialoadenectomy on growth of an EGF receptor-hyperproducing human gastric cancer xenograft in nude mice.

We recently established epidermal growth factor (EGF) receptor-hyperproducing human gastric cancer xenografts in nude mice. The present study was designed to examine whether the growth of a xenograft having 1,098 +/- 276 fmol/mg protein of EGF receptor would either be stimulated by the administration of EGF or inhibited by the removal of the submandibular glands (sialoadenectomy) which contain a large amount of EGF. A miniosmotic pump containing 2 micrograms or 20 micrograms of EGF was implanted on the back of the animals in the EGF stimulation experiments. The tumor growth was stimulated by the administration of EGF (P < 0.01), and the doubling time of the tumor was reduced relative to the controls (P < 0.01). Both the mitotic indices and the bromodeoxyuridine (BrdU)-labeling indices of the tumor were higher than those of the controls (P < 0.01). Tumor growth inhibited by the sialoadenectomy (P < 0.05) while the tumor doubling time was prolonged compared with the sham-operated mice (P < 0.05). These results suggest that the growth of a human gastric cancer xenograft may be modulated by EGF.

Adenocarcinoma↗

PubMed1994

A role for histones and ubiquitin in lupus nephritis?

Glomerulonephritis frequently develops in Systemic lupus erythematosus (SLE) but the pathogenesis is still poorly understood. Experimental evidence now suggests that histones can participate in immune complex formation in lupus nephritis. In a retrospective study, using samples from Northern and Southern Europe, Japan and South America, we searched for glomerular deposits of histones, both in native and ubiquitinated forms, in renal biopsy specimens from 48 patients with SLE and 70 cases of glomerulonephritis from patients without SLE. Positive glomerular immunofluorescent staining was revealed with rabbit antibodies to synthetic peptide 1-21 of histone H3, 22-45 of ubiquitin and to the branched region of ubiquitinated histone H2A (U-H2A) in 65% (31/48), 29% (14/48) and 54% (26/48) of the cases of SLE respectively. In total positive staining with at least one of the antibodies was seen in 36/48 (75%) cases. The staining was granular in nature and was present in capillary and mesangial areas. Only 3% (2/70) of non-SLE renal biopsies revealed positive staining with the above antibodies. None of the biopsy specimens from SLE patients were positive for ss- or ds-DNA, when tested with intercalating dyes. Serum samples were available from 15/48 SLE cases and were analysed with peptides and parent proteins by ELISA; epitopes in the N-terminal regions of core histones and in the C-terminus of histone H1 were often recognised by IgG antibodies in SLE sera, as was ubiquitin and the branched octapeptide of U-H2A. These results support the notion that the nuclear autoantigens histone and ubiquitin may be involved in the induction of glomerulonephritis in human SLE.

Animals↗

PubMed1993

Relationship of C-erbB-2 protein expression and gene amplification to invasion and metastasis in human gastric cancer.

BACKGROUND: Amplification and/or overexpression of the C-erbB-2 gene has been demonstrated in breast and gastric cancer and is thought to be involved in the process of gastric cancer metastasis. METHODS: The expression of C-erbB-2 protein in human gastric cancer was examined by immunohistochemistry and amplification of the C-erbB-2 gene by Southern blot hybridization. RESULTS: C-erbB-2 protein was located on the cell membrane of cancer cells in formalin-fixed, paraffin-embedded sections. Fourteen percent of specimens were positive for C-erbB-2, and no positive reaction was evident in noncancerous tissue. The presence of C-erbB-2 in gastric cancer was correlated with the depth of invasion, histologic type, growth pattern, and presence of liver metastasis. C-erbB-2 was found more often in advanced cancers (P < 0.05), papillary adenocarcinoma (P < 0.01), nonscirrhous cancer (P < 0.05), and cancers with liver metastasis (P < 0.01). The incidence of C-erbB-2 positivity in lymph nodes with metastasis was higher than in primary sites (P < 0.01) and was significantly higher in differentiated adenocarcinoma (P < 0.01). Patients with C-erbB-2-positive tumors had poorer survival rates those with C-erbB-2-negative tumors in the early stages (P < 0.001), but not in the advanced stages. Amplification of the C-erbB-2 gene was detected at the primary site and in metastatic nodes in the same case, and expression of the protein was also evident. CONCLUSIONS: The expression and/or gene amplification of C-erbB-2 is related to invasion and nodal involvement in differentiated adenocarcinoma of the human stomach.

Adenocarcinoma↗

PubMed1992

New morphological changes induced by FK506 in a short period in the rat kidney and the effect of superoxide dismutase and OKY-046 on THEM: the relationship of FK506 nephrotoxicity to lipid peroxidation and change in production of thromboxane A2 in the kidney.

Juxtaglomerular (JG) hyperplasia and tubular damage along with a decrease in the urine creatinine level induced by FK506 in rat kidney have already been reported in previous paper by us. In this paper, we document the relationship of FK506 nephrotoxicity to the change in the production of thromboxane (Tx) A2 and the lipid peroxidation of the cellular membrane in the rat kidney in order to clarify its morphogenesis. The urinary excretion of TxB2 increased with FK506 administration even on day 1 (P < 0.02). Histologically, OKY-046 (thromboxane synthetase inhibitor) decreased tubular damage, although JG hyperplasia was not eradicated, while biochemically the excretion of TxB2 decreased significantly (P < 0.02), and both the decrease in the urine creatinine level and the increase in the N-acetyl-beta,D-glucosaminidase (NAG) index were relatively smaller. Although the FK506-induced morphological and biochemical changes could not be prevented by the continuous administration of superoxide dismutase (SOD) 30,000 U/kg daily, the malondialdehyde content in renal tissue removed 1 h after FK506 administration had increased. These data suggest that FK506 nephrotoxicity is related to the change in the production of TxA2 and lipid peroxidation of the cellular membrane. However, other mechanisms such as the involvement of sympathomimetic effects of FK506 and other vasoconstrictive factors cannot be ruled out.

Acetylglucosaminidase↗

PubMed1992

Glomerular immune deposits in murine lupus models may contain histones.

Two types of lupus mice, NZB/NZW F1 female hybrids and mice with graft-versus-host disease (GVHD), were studied. Histones H3 and H2A were detected by immunofluorescence in glomeruli of 22/22 proteinuric GVHD and 8/12 proteinuric NZB/W F1 female mice; in non-proteinuric animals, 3/5 GVHD and 2/27 NZB/W F1 female were positive. Using antibodies to histone peptides it was shown that mainly the N-terminal regions of histones H3 and H2A were exposed in glomerular deposits. Western blot analysis revealed antibodies to histone subfractions in sera of 33/34 lupus mice that developed proteinuria. This study provides evidence that histones are involved in the pathogenesis of lupus nephritis.

Animals↗