Kunihiko Wakaki

Synovitis in rheumatoid arthritis: Scoring of characteristic histopathological features

Synovial tissue specimens obtained from the knee joints of 40 patients with rheumatoid arthritis (RA) and from 22 patients with osteoarthritis (OA) were examined histologically. The histopathological features of RA synovitis and OA synovitis were then compared. Seven criteria items of histopathological features characteristic to RA synovitis were given a score of 1–3 points each in order to evaluate the histological severity of the seven items. Their total scores were then calculated. A comparison of the total RA synovitis score and the total OA synovitis score revealed that RA synovitis showed more than 11 points (maximum 20 points), while OA synovitis showed less than 10 points in all but two cases. Furthermore, the total scores of RA synovitis were then determined in the same manner for other joints, where it was confirmed that five other joints had scores of more than 11 points as well; that is, the intercarpal, wrist, elbow, ankle and hip joints in 52 patients with RA. From these results, it was concluded that in the histological examination of biopsied synovial tissue of RA, if the total score for synovitis is more than 11 points (maximum 20 points), an histological diagnosis of RA synovitis can be confirmed.

Animal model of diabetic nephropathy

Injection of subtotally nephrectomized rats with streptozotocin produced metabolic abnormalities resembling diabetic nephropathy in humans. These abnormalities were hyperglycemia, hypoinsulinemia, azotemia, hypertriglyceridemia and hypercholesterolemia, accompanied with an increase in glycosylated protein. Extraordinary changes in the urinary excretion of glucose and protein were also observed in rats that received streptozotocin treatment after subtotal nephrectomy. In addition, the level of creatinine clearance was significantly decreased. The pathological findings in the kidney of these rats revealed lesions of the glomerular capillary loops, mesangial area and Bowmans capsule. Coagulation was also found in the glomerular capillaries. Our results suggest that this rat model would be useful for studies of diabetic nephropathy.

Vascular Lesions In Systemic Lupus Erythematosus (Sle) With Pulmonary Hypertension

An autopsy case with SLE suffering from Raynauds phenomenon and pulmonary hypertension was reported. Histological examinations revealed systemically marked fibrous intimal thickening of arteries and arterioles with or without thrombus throughout the whole body, especially of the pulmonary arteries and arterioles. Pulmonary arterial changes in the present case were compared with those in 52 autopsied cases with SLE without pulmonary hypertension, but there were no cases with such marked arterial changes as the present case. In addition, the incidence of pulmonary thrombosis was significantly higher in the cases with Raynauds phenomenon than the cases without this phenomenon. However, the relation between pulmonary hypertension and Raynauds phenomenon, pulmonary thrombosis, fibrous pericarditis, or type of lupus nephritis in SLE could not be clarified with a significant difference. ACTA PATHOL. JPN. 34: 593–604, 1984.

HISTOPATHOLOGICAL ANALYSIS OF SIXTEEN SUBCUTANEOUS RHEUMATOID NODULES

An immunopathological study was carried out on subcutaneous nodules (rheumatoid nodules) biopsied from 16 patients with rheumatoid arthritis. Sixteen rheumatoid nodules were histologically classifled into three stages; the 1st stage (acute inflammatory stage, 3 cases), the 2nd stage (granulomatous stage, 10 cases), and the 3rd stage (scar‐formed stage, 3 cases). In necrotic or granulation tissue of the nodules in the 3 stages, immunofluorescent analysis using FITC‐labeled rabbit anti‐human immunoglobulins, β1C, and flbrinogen serum γ‐globulins and FITC‐labeled aggregated human IgG gave results that were strongly positive in the 1st stage, moderately positive in the 2nd stage, and only slightly positive or almost negative in the 3rd stage. Acute or chronic thrombotic endoarteritis was observed around rheumatoid nodules in 6 out of the 16 cases. Among them, 2 cases of the 1st stage showed acute thrombotic endoarteritis with marked infiltration of neutrophils in the wall, and 2 cases of the 2nd and the 3rd stages respectively showed chronic endoarteritis with organized thrombi.

CYSTINOSIS WITH MARKED ATROPHY OF THE KIDNEYS AND THYROID

The eldest autopsied case (a 23‐year‐old man) of infantile form of cystinosis with uremia and myxoedema was reported. The cystine content per gram wet tissue of various organs was arranged as follows: the thyroid (4.61 mg), kidney (1.71 mg), eye (0.75 mg), spleen (0.65 mg), liver (0.49 mg), and brain (0.016 mg). In polariased light microscopy, cystine crystals were detected in the epithelial cells and epithelial lumina of both kidneys by Wollaston test, and foam cells with cystine crystals were histologically found in the reticuloendothelial and other organs, especially in the bone marrows. Moreover, electron microscopic findings revealed square, rectangular or lozenge‐shaped small cystine crystal profiles in osmophilic dense bodies of the histiocytic cells and in the cytoplasm of the foam cells. In some of them, positive reaction for acid phosphatase activity was specifically localized at the periphery of the cystine crystal profiles.

Site of Methylguanidine Production and Factors That Influence Production Levels

The site of methylguanidine (MG) production in the kidney was investigated using animal models of renal disease and cultured renal epithelial cells. In rats with proximal tubular injury induced by adenine, the blood and urinary levels of MG increased as the severity of injury increased. In contrast, in cases of glomerular injury, there were no such changes in MG levels. Thus, it was apparent that proximal tubular injury served to promote MG production. In addition, a marked increase was observed in the intensities of bands attributable to 5,5-dimethyl-1-pyrroline-N-oxide (DMPO)-OH in the electron spin resonance spectrum of the kidney in the rats given adenine. In these rats, the activity of the radical-scavenging enzymes superoxide dismutase, catalase, and glutathione peroxidase was decreased. This suggests that the formation of excessive radicals and deterioration of defense mechanisms that contribute to the development of oxidative stress underlie the enhanced MG production. The experiments using cultured cells revealed that an oxide of adenine, 2,8-dihydroxyadenine (DHOA), directly induced renal tubular injury. These findings indicate that the accumulation of creatinine due to DHOA, combined with oxidative stress, resulted in increased MG production.

Experimental granulomatous vasculitis induced by sensitization with Ascaris suum antigen in mice

Experimental sensitization by repeated intramuscular injection of Ascaris suum antigen (Ag‐As) supplemented with Freunds incomplete and complete adjuvants was carried out in 50 BALB/c CrSl c male mice (sensitized group) for 24 weeks, and the results were compared with those in a control group of 25 mice. At the injection sites of the sensitized group, granulomatous angiitis with eosinophil infiltration was observed in all mice, and fibrinoid angiitis in only four. By light and electron microscopic examinations pulmonary granulomatous vasculitis with a few eosinophils was observed at a high frequency (80%) after 12 experimental weeks. lmmunohistochemical examination revealed pulmonary vascular and perivascular infiltration of L3/T4 (CR4) positive cells, B cells, IgG and C3 positive cells in addition to activated macrophages, Thy‐1 T cells, IgE positive cells, and IgM positive cells after 12 experimental weeks. There were significant increases in the eosinophil cell count of the peripheral blood, the hemagglutination titers of the sheep erythrocytes, IgE and IgM antibodies to Ag‐As by ELISA and Western blotting after 8 experimental weeks. After 12 experimental weeks the lgG antibody to the Ag‐As was low, but it increased significantly, and the sera showed multiple precipitation lines to the Ag‐As by the Ouchterlony method. In conclusion, the pulmonary granulomatous vasculitis in this study is considered to consist of allergic reactions of type IV and probably type III based on type 1.

Co-expression of fibroblastic, histiocytic and smooth muscle cell phenotypes on cultured adherent cells derived from human palatine tonsils: a morphological and immunocytochemical study

Adherent cells derived from human palatine tonsils were isolated and cultivated. Exponentially growing adherent cells (TAC) were observed by phase‐contrast microscopy and transmission electron microscopy. Immunocytochemical studies were also performed. TAC were composed of relatively monotonous cells with polygonal or spindle shapes and high proliferative activity. In addition to the development of rough endoplasmic reticulum and lysosomes, the TAC possessed a moderate amount of pinocytotic vesicles and a few microfilaments. All of the TAC strongly expressed fibroblastic markers and partial mono‐cyte/macrophage markers, such as beta‐subunit of prolyl 4‐hydroxylase (DAKO‐fibroblast), lysozyme, anti‐alpha‐1‐antichymotrypsin (OlACT), and CD68 (KP‐1, EBM/11). It was noted that, as the TAC were cultured for a longer period, they gradually increased the reactivity with the monoclonal antibody PG‐M1. Furthermore, the TAC expressed myocytic phenotype, such as alpha‐smooth muscle actin (αSMA) with various intensity. Moreover, as to extracellular matrix, TAC stained for collagen type I, collagen type III, Iaminin, and fibronectin. Collagen type IV was weakly positive. The results presented here showed that the TAC expressed three different phenotypes of fibroblasts, histiocytes and smooth muscle cells at the same time. The monoclonal antibody raised against the TAC reacted strongly with the sub‐endothelial pericytes andlor smooth muscle cells in the extrafollicular area in human tonsils. The present resutts also suggested that the origin of the TAC was probably sub‐endothelial pericytes andlor smooth muscle cells of the microvasculatures in the tonsil.

Lung carcinoma mimicking malignant lymphoma: Report of three cases

Three cases of lung carcinomas with unusual histologic appearances that have received little or no comment in the literature are presented. They were initially confused with malignant lymphoma because of a diffuse proliferation of relatively monotonous cells simulating large‐cell immunoblastic lymphoma. In each case, the possibility of malignant lymphoma was excluded with confidence after the immuno‐histochemical study (leucocyte common antigen negative and cytokeratins positive), although with conventional microscopy several foci of cohesive groups of tumor cells were observed. The tumors were ranked at the clinical stage II or III when they were initially discovered, but all patients died of disease within 1 year. The present three tumors show an aggressive behavior and could be classified into a peculiar variant of ‘large cell’ carcinoma. It is necessary for surgical pathologists to have an idea of these variants of lung carcinoma in order to avoid erroneous diagnosis.

Effect of a Chinese Medical Preparation, Hokoei-to, on Lipids in Blood and Involvement of Cells of Vascular Origin

A significant increase in high‐density lipoprotein‐cholesterol and a tendency for total cholesterol and low‐density lipoprotein‐cholesterol to decrease were found in parous rats given Hokoei‐to orally for 25 days, resulting in improvement of the atherogenic index. In experiments using cells of vascular origin, significantly increased proliferation of endothelial cells and suppressed proliferation of smooth muscle cells were obtained in the presence of Hokoei‐to. When the action of each component galenical of Hokoei‐to was examined, all five components, i.e. Taraxaci Radix, Angelicae Radix, Cyperi Rhizoma, Moutan Cortex and Dioscoreae Rhizoma, promoted the proliferation of endothelial cells. However, Taraxaci Radix and Angelicae Radix also promoted the growth of smooth muscle cells, showing inconsistency with the effect of Hokoei‐to as a whole.