Role of β2 integrins in glomerular leucocytes in Henoch-Schoenlein purpura nephritis: an age-matched comparative study with immunoglobulin A nephropathy

SUMMARY: A comparative immunohistological study was performed for the glomerular deposition of complements (C1q and C3c), fibrin/fibrinogen‐related antigen (FRA), the expression of intercellular adhesion molecule‐1 (ICAM‐1), and the infiltration of leucocytes bearing β₂ integrins (leucocyte function associated antigen‐1 (LFA‐1), complement receptor 3 (CR3) and complement receptor 4 (CR4)) on renal biopsy specimens from 49 cases with Henoch‐Schoenlein purpura nephritis (HSPN), and 49 age‐matched cases with immunoglobulin A nephropathy (IgAN). the glomerular expression of ICAM‐1 was signifcantly correlated with the glomerular infiltration of leucocyte function associated antigen (LFA)‐1⁺ leucocytes in both diseases, and with that of CR3⁺ leucocytes in HSPN. the expression of ICAM‐1 was closely localized with the infiltration of LFA‐1⁺ leucocytes in the study with double immunostaining. the incidence and intensity of glomerular deposition of FRA were significantly higher in HSPN than in IgAN (P< 0.001), and those of C3c were significantly lower in HSPN than in IgAN (P< 0.001). the glomerular deposition of FRA was significantly correlated with the glomerular infiltration of CR4⁺ leucocytes in HSPN (P<0.05) but not in IgAN. In contrast, the glomerular deposition of C3c was significantly correlated with the glomerular infiltration of CR4⁺ leucocytes in IgAN (P<0.05), but not in HSPN. Studies with double immunostaining revealed a close association of CR4⁺ leucocytes with FRA deposition in HSPN and with C3c deposition in IgAN, respectively. the number of glomerular leucocytes bearing β₂ integrins was significantly correlated with urinary protein at the time of renal biopsy in both diseases. These results suggested the differential roles of β₂ integrins in the induction of glomerular injury in HSPN and IgAN. the ICAM‐1/LFA‐1 interaction may commonly be involved in the glomerular infiltration of leucocytes in both diseases. the ICAM‐1/CR3 interaction may be involved only in HSPN. Complement receptor 4 may function as a fibrin/fibrinogen receptor in HSPN, while CR4 may function as a complement receptor in IgAN.     

DETECTION OF ANTIRIBOSOMAL P PROTEIN ANTIBODIES IN PATIENTS WITH SYSTEMIC SCLEROSIS

This study investigated the prevalence and clinical significanceof anti-ribosomal P protein (anti-P) antibodies in patientswith systemic sclerosis (SSc). Serum samples from 150 patientswith SSc were examined by indirect immunofluorescence, ELISAand immunoblotting. Anti-P antibodies were detected in four(3%) patients with SSc. Three of the four patients showed SSc/SLE(systemic lupus erythematosus) overlap syndrome, but psychiatricdisorders were not observed in these patients. By longitudinalimmunoblotting analysis one patient, who was initially diagnosedwith SSc, later developed anti-P antibodies along with clinicalmanifestations of SLE. Our data suggest that anti-P antibodiesare uncommon in SSc and that the presence of anti-P antibodiesin patients with SSc indicates an overlap with SLE. KEY WORDS: Anti-ribosomal P protein antibodies, Systemic sclerosis, Systemic lupus erythematosus     

Limitations of the Pressure Half-Time Method for Estimating Mitral Valve Area in the Presence of Atrial Flutter

A patient with congenital ventricular septal defect and acquired rheumatic mitral stenosis with atrial flutter was noninvasively studied. The influence of atrial flutter on Doppler flow patterns across the mitral valve and the limitations of the pressure half-time method for estimating mitral valve area in the presence of atrial flutter are discussed.     

Health-related quality of life after radical prostatectomy in Japanese men with localized prostate cancer

PURPOSE: We evaluated retrospectively health-related quality of life (HRQOL) after radical prostatectomy (RP) in Japanese men with localized prostate cancer. METHODS: The study was based on self-reported HRQOL of 280 patients. Patients were divided into seven groups: time 0 (T0), baseline before operation; T1, 1-3 months after RP; T2, 4-6 months after RP; T3, 7-12 months after RP; T4, 13-24 months after RP; T5, 25-36 months after RP; and T6, more than 36 months after RP. We measured the general and disease-specific HRQOL using the RAND 36-item Health Survey 1.0 (SF-36) and the University of California, Los Angeles Prostate Cancer Index (UCLA PCI). RESULTS: The general HRQOL of the postoperative groups was assessed by SF-36. The postoperative groups showed almost the same or higher scores than those of the baseline group. Urinary function scores decreased substantially after surgery. In contrast, there was no difference in urinary bother between the baseline and postoperative groups. Sexual function deteriorated substantially in all postoperative groups. Similarly, the sexual bother score significantly deteriorated after RP. The sexual bother score of men aged 65-years or younger was significantly worse than that of their counterparts in the T1-2 groups. CONCLUSION: Despite reports of problems with sexual activity and urinary continence, general HRQOL was mostly unaffected by RP. Although there was a substantial decrease in urinary function, recovery from urinary bother was rapid. Since the deterioration of sexual function was marked through the postoperative period, careful attention should be paid to this issue during preoperative counseling, especially for younger patients.     

ULTRASOUND MEASUREMENT OF SKIN THICKNESS IN SYSTEMIC SCLEROSIS

Sclerotic skin change in systemic sclerosis (SSc) usually accompaniesincreased skin thickness. In order to quantify the cutaneouschanges and to clarify the changes in the ‘uninvolved’skin in systemic sclerosis (SSc), we measured the skin thicknesson the chest, the forearms and the hands of 79 patients withSSc and 81 healthy controls with a B-mode ultrasound (30 MHz)apparatus. The thickness of the ‘uninvolved’, aswell as the ‘involved’ skin in patients with SScwas significantly greater than that of healthy controls. Increasedskin thickness on the forearms and/or the hands showed a 64.6%sensitivity and a 100% specificity for SSc. These results indicatedthat the skin which appears to be ‘uninvolved’ inpatients with SSc is already pathologic, as shown by increasedthickness. Moreover, measurement of skin thickness may be beneficialin the diagnosis of this disease at an early stage. KEY WORDS: Systemic sclerosis, Skin thickness, ‘Uninvolved’ skin, Ultrasound measurement     

Combination of vasopressin and angiotensin inhibition in experimental focal glomerulosclerosis

Summary: This study was designed to investigate the role of vasopressin and angiotensin II in the pathogenesis of focal glomerulosclerosis (FGS). A non-peptide vasopressin VI antagonist (OPC-21268) and an angiotensin converting enzyme inhibitor (ACE-I) were administered either alone or in combination for 15 weeks to FGS, spontaneously hypercholesterolaemic rats. Treatment with the V1 antagonist (1% OPC-21268) suppressed the rise in systolic blood pressure (SBP), serum triglyceride (TG), blood urea nitrogen (BUN) and serum creatinine (S-Cr) levels, but not the elevations of urinary protein excretion (UPE) or serum total cholesterol (TC) levels. Morphologically, V1 antagonist significantly prevented an increase in the index of glomerular sclerosis (IS) and relative interstitial volume (RIV). In the low dose/high dose of V1 antagonist supplementation, the administration of 0.2% OPC-21268 failed to suppress any increase in the SBP and TG levels, but significantly preserved renal function and attenuated renal lesions. In the combination study, rats were divided into four groups: (i) V1 antagonist (1% OPC-21268); (ii) ACEI (imidapril, 5 mg/kg/per day); (iii) both treated groups; and (iv) an untreated control group. Angiotensin-converting enzyme inhibitor significantly suppressed increases in SBP, UPE, TC, BUN, and S-Cr levels compared with V1 antagonist. the combination therapy significantly enhanced these effects. Both agents significantly reduced IS and RIV, and combination therapy further reduced these levels. the results indicated that vasopressin, as well as angiotensin II, via the V1 receptor cause hypertension and renal injury in FGS rats. Vi antagonist and ACE-I have antihypertensive and renoprotective effects in this FGS model, and enhanced their beneficial effects when used as combination therapy.     

Distribution of anti-p80-coilin autoantibody in collagen diseaseand various skin diseases

Anti-p80-coilin antibody produces a unique pattern of immunofluorescence staining called nuclear dots characterized by the presence of up to six discrete nuclear bodis in interphase cell nuclei. The distribution of this antibody and its clinical relevance have not been established. We studied the prevalence of anti-p80-coilin antibody in the sera from 810 patients with collagen diseases and various skin diseases. Five sera showed the nuclear dot pattern by indirect immunofluorescence on an HEp-2 cell substrate, and reacted by immunoblotting with 80-kDa protein in a nuclear extract from HeLa cells. Four of these sera were from patients with localized scleroderma, and the other was from a patient with primary Raynaud's phenomenon. The patients with localized scleroderma who were positive for anti-p80-colin antibody had all been classified as having linear scleroderma. They had only one or two lesions, and were negative for antihistone and anti-single-stranded DNA antibodies. Our data indicate that anti-p80-colin antibody is uncommon in skin diseases: however, this antibody is present in patients with a milder form of liner scleroderma, although the incidence of positivity may not be high.     

The aqueous conformation of cyclo(1,6)Ac-Cys-Arg-Gly-Asp-Phe-Pen-NH2

RGD peptides are known as important ligands for integrin receptors in the cell adhesion process. The selectivity of RGD peptides for a certain integrin receptor is partly dependent on the RGD conformation and the residues surrounding the RGD sequence. This paper investigates the effect of the addition of a phenyl-alanine residue on the RGD conformation in cyclo(1,6)Ac-Cys-Arg-Gly-Asp-Phe-Pen-NH₂ (1) as compared to the previously studied cyclo(1,5)Ac-Pen-Arg-Gly-Asp-Cys-NH₂ (2). The conformational study of peptide I was done in aqueous solution using nuclear magnetic resonance (NMR) spectroscopy and molecular dynamics simulations. This work will increase the understanding of the flanking residue's effect in RGD peptides.     

A case of generalized pustular psoriasis followed by bullous disease: and atypical case of bullous pemphigoid or a novel bullous disease?

Summary We describe a 31-year-old Japanese woman with generalized pustular psoriasis treated with PUVA who subsequently developed a bullous disease. Throughout the disease coures, there was no phase of psoriasis vulgaris. Although several reports describe coexistence of psoriasis vulgaris and bullous disease such as bullous periphigoid, coexistence of generalized pustular psoriasis without any phase of psoriasis vulgaris and bullous disease is rare. As for the bullous disease, direct immunofluorescence study showed lgG and C3 deposition along the basement membrane zone. Indirect immunofluorescence disclosed lgG antibasement membrane zone antibodies. Indirect immunofluorescence on 1 mol/1 sodium chloride-split skin demonstrated linear lgG staining almost exclusively on the dermal side of the split. Western immunoblot analysis revealed that the antibody was directed to neither epidermolysis bullosa acquisita antigen nor bullous pemphigoid antigens. Considering the unusual clinical course, we suspect the possibility of a novel autoimmune blistering disease.     

Measurement of anticardiolipin antibodies by ELISA using β2-glycoprotein I (β2-GPI) in systemic sclerosis

In order to determine the prevalence and clinical significance of β₂-GPI-dependent anticardiolipin antibodies (β₂-GPI/aCL) in patients with systemic sclerosis (SSc), serum samples from 80 patients with SSc, 20 patients with systemic lupus erythematosus (SLE), and 120 healthy control subjects were examined by ELISA using purified β₂-GPI. IgG isotype β₂-GPI/aCL was present in eight of 80 patients with SSc (10%), and the presence of β₂-GPI/aCL IgG was significantly correlated with the presence of isolated pulmonary hypertension (PH). Furthermore, levels of β₂-GPI/aCL IgG were significantly correlated with levels of mean pulmonary arterial pressure. These data suggest that IgG isotype β₂-GPI/aCL might be a serological indicator of the severity of PH in patients with SSc.