Biomedical subjects
Publications and source records attributed to F Yoshida.
A case of pulmonary arteriovenous fistula (PAVF) with pulmonary hypertension (PH) occurring in an adult woman is described. Resection of PAVF was not performed and she has been followed up for 5 years, receiving repeated right cardiac catheterization. We discuss the causal relationship of PH and the development of PAVF.
To assess the effects of high blood glucose concentration on glomerular changes after the acute mesangial cell injury in the rat, the monoclonal anti-Thy1.1 antibody OX-7 was injected into streptozoticin-induced diabetic rats or normal rats. The increase in proliferating cell nuclear antigen-positive cells in glomeruli at day 4 and glomerular hypercellularity at day 18 was less prominent in diabetic rats than in normal rats. The expansion of mesangial matrix area assessed by fibronectin immunostaining was more prominent, and segmental glomerulosclerosis was observed at day 60 in the diabetic rats. These data suggest that the insulin-deficient group may reflect impaired "wound-healing," leading to the prolonged ECM accumulation under the hyperglycemic condition in vivo.
CD59 is a molecule which is present on the host cell membranes and inhibits formation of membrane attack complex. A monoclonal antibody, 6D1, recognizes a rat analogue of human CD59. 6D1 inhibits function of rat CD59 and can enhance complement-mediated hemolysis in vitro. To assess the role of CD59 in complement-mediated glomerular injury, 6D1 was tested in a model of experimental glomerulonephritis induced by a lectin and its antibodies. The left kidney of a rat was perfused either with 200 micrograms of Lens culinaris hemagglutinin (LCH) plus 1 mg of 6D1 (IgG1 fraction) (Group I and III) or with LCH only (Group II) through a cannula placed in the left renal artery. All the perfusate was discarded from a cannula in the renal vein. The holes in the artery and vein were repaired by microsurgery and the blood circulation was re-established. Rats were injected either with 0.125 ml of rabbit anti-LCH serum (Group I and II), or with normal rabbit serum (Group III) via tail vein one minute after the recirculation. Fifteen minutes after injection, significant C9 deposition in the glomeruli was observed only in Group I, whereas C3 deposition in Group I and II were comparable. At Day 4, total glomerular cells, proliferating cells, glomerular expression of intercellular adhesion molecule-1 and fibrin deposition in Group I were all significantly increased when compared with Group II. At Day 7, number of total glomerular cells and leukocytes in the glomeruli of Group I were significantly higher than in Group II. The glomeruli in Group III appeared normal throughout experiments. These data indicate that the functional inhibition of a rat analogue of human CD59 worsens complement-mediated glomerular injury in vivo.
The strain of FGS/Nga mouse is reported to develop proteinuria and progressive glomerulosclerosis. We studied the renal pathology of that strain periodically for 1 year. Focal and segmental glomerulosclerosis was observed 3 months after birth and the lesion progressed to the glomerular obsolescence in a year. Electron microscopic study revealed electron dense deposits (DD) in the mesangium and the splitting of glomerular basement membrane. Studies using immunofluorescence and immunoelectron microscopy revealed that these DD were contained IgA, IgM, C3 and the retroviral envelope antigen (gp70). Clinically, proteinuria began at the age of 3 months and the renal function was decreased on time course. No other organs were involved. We studied the renal lesions of FGS mice by the histological and immunohistochemical methods and concluded that this mouse strain provides the tool for studying the mechanisms of the progression of glomerulosclerosis.
The present study was conducted to investigate the intergroup behaviour from the perspective of social identity theory. It was predicted that (a) when group membership was based on trivial categorization (e.g., by drawing lots), minority group members would be more conscious of their social identity, and favour their own group more in reward distribution than majority group members; (b) when based on value-loaded categorization (e.g., by social attitudes), both minority group and majority group members would favour their own group; (c) both minority group and majority group members would perceive converted members, who move away from their initial attitudes, as a threat to their social identity, and discriminate them. Results from three experiments under the minimal group paradigm, with undergraduate students, supported these predictions. Findings were discussed in terms of salience of social identity in categorization of minority versus majority, and the impact of anonymity in the minimal group paradigm. They were also discussed to compare the theory with belief congruence theory, which argues that attraction due to similarity of belief is the cause of ingroup favoritism.
A 54-year-old woman was admitted to our hospital because of purulent meningitis caused by Streptococcus pneumoniae during a long-term administration of prednisolone for the treatment of bronchial asthma. After admission, both antibiotics and steroids were given, which resulted in her good general and neurological condition, and the normal protein and glucose content in her cerebrospinal fluid three weeks later. However, post-contrast computerized tomography (CT) at this time showed various size of multiple irregular high-densities devoid of capsular component in the white matter of the bilateral cerebral hemisphere. MRI examination revealed that the lesions were of low intensity on the T1-weighted sequence whereas high on T2-weighted sequence. Gd-DTPA enhanced the T1-weighted images on these lesions. These findings may indicate that the lesions were at the pre-encapsulation stage of cerebritis, because the lesions were gradually reduced and disappeared after the subsequent antibiotic therapy. It is emphasized that patients with purulent meningitis under steroid therapy require careful observation for the risk of bacterial cerebritis.
There are many studies in the literature on the subject of anti-neoplastic drugs for acute and chronic cardiac toxic function. It is important to check previously the cardiac toxicity of the new anti-neoplastic drugs. Now we have had a chance to study the first stage examination of RA-700, isolated from Rubia akane or Rubia cordifolia. Then we tried to study several kinds of parameters, for instance ECG, ultrasonic cardiograms and arterio-grams on cardiac toxicities of RA-700. We injected the first group of neoplastic patients only once with RA-700, while in the second group, we injected them with RA-700 for 5 consecutive days (see our previous report.) In the present study, we made some conclusions about the administration of RA-700. 1) Changes in cardiac function were noted in both groups. 2) Changes in blood pressure, sigma QRS, ejection fraction, and fractional shortening of the second group tended to be more extreme than those of the first group. Care for continuity is a concern with long-term and high doses of RA-700. 3) Because of the small sample, we could find no relationship between the changes in cardiac function and the injection doses of RA-700. 4) Therefore, the cardiac function must be checked by giving anti-neoplastic drugs to neoplastic patients.
We describe the development of acute renal failure and degenerative tubular lesions associated with local immune deposits in a patient with allogeneic bone marrow transplantation. A 21-year-old man with an acute myelocytic leukemia received a bone marrow graft from a cousin mismatched for a single HLA-DR locus antigen. Hemorrhagic cystitis due to adenovirus type 11 infection occurred 26 days after transplantation, and 17 days later the patients developed acute renal failure. A study of renal tissue obtained by needle biopsy showed degenerative and necrotic lesions, especially in the distal part of the nephron. By electron microscopy adenovirus type 11 particles were found in the nuclei of tubular cells and in cellular debris in tubular lumina. By immunofluorescence technique, granular immune deposits containing adenovirus type 11 related antigen(s), immunoglobulins, C3, and membrane attack complex (MAC) C5b-9 of the complement system were detected along the tubular basement membranes but not in glomeruli. The patient's IgG did not bind to normal human kidneys. These findings suggest that adenovirus type 11 directly induced acute tubular damage, and that the tubular immune deposits were formed "in situ" by viral antigens and circulating viral antibody.
We investigated the mechanisms by which corticosteroids affect atherosclerosis. Male New Zealand White rabbits were injected with 0.125 mg dexamethasone (n = 10) or vehicle (control group, n = 10). Both groups were fed a 1% cholesterol diet for 8 weeks. Although the dexamethasone-treated animals exhibited a greater degree of hyperlipidemia, they exhibited significantly less atherosclerotic plaque of the aortic surface than control animals (7.8% versus 47.2%). Immunofluorescence study of the aortic plaque specimens showed that dexamethasone administration reduced both macrophages and T lymphocytes. In vitro, dexamethasone suppressed the proliferation and differentiation of U937 cells and inhibited uptake and degradation of beta-very low density lipoproteins by mouse peritoneal macrophages. These findings suggest that dexamethasone suppresses the development of atherosclerosis in the aorta of rabbits by inhibiting recruitment and proliferation of macrophages and the formation of foam cells in plaques.
A 54-year-old woman with nephrotic syndrome underwent renal biopsy. By light microscopy, the glomerular capillary lumen was remarkably narrowed because of diffuse accumulation of Periodic acid Shiff (PAS) positive material along the glomerular capillary wall. By electron microscopy, collagenous fibers were observed in the mesangium and subendothelial area. The fibrous material reacted with antibodies against type I and III collagen but not with those against laminin or type IV collagen by an indirect immunofluorescence technique. This case seemed to be a case of collagenofibrotic glomerulonephropathy.
Experimental glomerulonephritis was induced in rats to investigate the consequence of the antigen-antibody interaction on the surface of glomerular endothelial cells (GENs). A lectin, Lens culinaris hemoagglutinin (LCH), was first planted in the left kidney by isolated perfusion of a left kidney, and then the circulation was reestablished. Rabbit anti-LCH antibodies were injected from the tail vein 3 minutes after the recirculation of the left kidney, and acute glomerulonephritis ensued. Fifteen minutes after the injection, rabbit immunoglobulin G (IgG), rat C3, and LCH were observed exclusively on the surface of GENs. Accumulation of platelets was prominent. Three hours later, the immune deposits were seen in the subendothelial space, and the polymorphonuclear cells were the dominant infiltrate in the glomeruli. Up to the seventh day, immune deposits were seen in the subendothelial space, and the widening of this area was increasingly observed. Fourteen days later, immune deposits containing rat IgG were observed in the subepithelial area, but they were only occasionally seen in the subendothelial space and in the mesangial area. No crescent formation was seen at day 14, but the mesangial area was expanded, with an increased number of cells. The number of nuclei in the cross-section of a glomerulus increased after the induction of glomerulonephritis, but the number of leukocyte common antigen-positive cells (infiltrating cells) decreased gradually from day 4 to day 14. The staining of Thy-1.1, a marker of mesangial cell, was markedly enlarged in the glomerulus at day 14. These data suggest that mesangial proliferative glomerulonephritis can be induced by the antigen-antibody interaction on the surface of GENs.
A 46-year-old female presented with POEMS syndrome. Hemodialysis was initiated to control severe anasarca and declining renal function. Corticosteroids were effective in treating renal insufficiency and other symptoms. Serum interleukin 6 (IL-6) was elevated before the corticosteroid therapy but returned to the normal level under the therapy. Immunostaining for the kidney tissue obtained by a renal biopsy showed a diffuse distribution of IL-6 in the glomeruli; thus, in contrast to normal, IL-6 was detected not only in mesangial cells but also in endothelial cells. IL-6 was also distributed in capillaries in the interstitium. While these results suggest a pathogenic role of IL-6 in POEMS syndrome, other factors may be necessary for the full expression of symptoms. Furthermore, it is suggested that chronically stimulated glomerular endothelial cells are capable of producing IL-6.
FK506 is a recently-developed immunosuppressive drug. The aim of the present work was to investigate the effects of FK506 in experimental autoimmune glomerulonephritis (active Heymann nephritis) in rats. Active Heymann nephritis was induced in female Lewis rats by two immunizations with the homologous brush border vesicles (BBVs) at day 0 and day 28 (groups I, II, V, and VI). Rats of groups III and IV received the third immunization at day 56. In rats of groups I and III, FK506 was injected (1 mg/kg/day IM) from day 0 for 14 days. In rats of groups II and IV, significant proteinuria was observed (group II, 112.8 mg/16 hours; group IV, 55.4 mg/16 hours) at the time the rats were killed (day 84). Coarse subepithelial immune deposits (IDs) were found in these rats. In contrast, urinary protein excretion remained within normal range (less than 3.0 mg/16 hours) in groups I and III rats, and tiny subepithelial IDs were only occasionally seen. Circulating anti-BBV antibody levels were markedly lower in group I and III rats than in those of groups II and IV during the period between day 14 and day 56. To investigate the effects of FK506 on the proteinuric rats, FK506 (1 mg/kg/day, IM) was administered every day for 2 weeks beginning on day 56 (group V).(ABSTRACT TRUNCATED AT 250 WORDS)
We found a strain of nonobese, nondiabetic (NON) mice which has spontaneous lipid deposition in glomerular capillary lumina. This strain was developed together with a diabetic strain of nonobese diabetic (NOD) mice for the generation of mouse models of diabetes mellitus. In the NON strain, contrary to the name, impaired glucose tolerance (IGT) was observed in about half of the mice. Meanwhile, peculiar glomerular abnormalities which remotely resemble those of diabetic nephropathy were observed in the NON strain. The lesions were characterized by massive lipid accumulation with proteinaceous material within the glomerular capillary lumina. In addition, positive staining for immunoglobulins, especially IgM, was observed by immunofluorescence microscopy. The overall frequency of this lesion was 91%. Mesangiolysis, capillary ballooning with many small lipid vesicles were the striking features by electron microscopy. Histochemical analysis revealed the presence of various lipids in these lesions. However, as far as we examined, these lesions did not correlate with hyperlipidemia or IGT. Lymphoid follicle-like structures were seen around the renal arterioles. The cellular components of these lymphoid follicles reacted with monoclonal antibodies to L3T4. High levels of serum immunoglobulins were observed in this strain. We suppose that the immunological disorders may have some bearing in the evolution of this lesion in NON mice. We believe that this model may be of use in studying the role of lipid derangements in renal diseases.
A 52-year-old female had a nephrotic syndrome without neurological or dermatological manifestations. Renal biopsy revealed that glomeruli were filled with tumor cells which bore leukocyte common antigen and pan B cell marker. These cells occupied the capillary lumen and invaded into the mesangial area. Morphological alteration of endothelial cells and glomerular basement membrane were also noticed. The interstitium was well preserved. After five cycles of a combination chemotherapy, CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone), the second biopsy revealed that tumor cells disappeared from glomeruli showing mild sclerosis. Proteinuria became absent. This is the first report of an angiotropic large cell lymphoma manifesting a nephrotic syndrome and treated successfully by CHOP therapy.
We reported earlier in the 1st report the use of treadmill walk apparatus and transcutaneous blood gas measurement apparatus as a newly designed exercise test. In this report, test was carried out in 90 persons (4 healthy, 66 recovered from pulmonary tuberculosis, 3 recovered from silico-pulmonary tuberculosis, 12 of COPD, and 5 of pulmonary fibrosis et bronchiectasis). The changing curves of transcutaneously measured O2 partial pressure (tPo2) were, as previously reported, classified into 4 types: 1. unchange-6, 2. slightly decreased-38, 3. moderately decreased-24, 4. markedly decreased-21. And unexpected odd curves were seen in 4 patients, 3 of whom were retested the other day, and their changing curves of tPo2 in the second test were corrected and classified into slightly or moderately decreased type. The decreasing slopes of 4 types of tPo2 curves were subclassified, in each type, into 3 to 4 forms. In recovered pulmonary tuberculosis patients, in general, when the spread of pathologic changes in the lungs was wider, the more decreased types of tPo2 curves were seen. But in COPD patients, such was not the case. In the exercise test, total tolerance time (minutes) against the definite load was significantly shorter in the more decreased type; unchanged-13.5-14.5, slightly decreased -7-10, moderately decreased-6-9, and markedly decreased-3-5. The recovering time of tPo2, pulse rate, blood pressure etc. from the records in the end of the exercise to the pre-exercise records, was longer in the more decreased type. On the other hand, usually the lower Pao2 of the patients were, the more their changing curves of tPo2 decreased. Pao2 was previously measured in blood taken from brachial artery in supine position before the test. But exceptionally in some patients with high Pao2 value, the curves belonged to markedly decreased type. The changes of oxygen values of some patients during exercise test were individually different, showing that this exercise test reflected their comprehensive respiratory function. Prognosis was especially bad in patients with markedly decreased type, 8 of whom had died from respiratory failure within 2 years after the test. In conclusion, it can be said that this exercise test was effective in judging the pulmonary reserve function and the prognosis in recovered pulmonary tuberculosis patients, but more detailed investigations are necessary, especially in more COPD patients, for the understanding of the respiratory distress.(ABSTRACT TRUNCATED AT 400 WORDS)
We studied four cases of Crow-Fukase syndrome with renal dysfunction. Kidney specimens obtained by needle biopsy showed glomerular lesions resembling those seen in conditions characterized by microangiopathy. Common glomerular findings by light microscopy were mesangial expansion and narrowing of the capillary lumina. An enlarged subendothelial space and mesangial area with deposition of amorphous material as well as swelling and vacuolization of endothelial cells were observed by electron microscopy. In an active phase, severe mesangial edema and segmental mesangiolysis, and in a late stage, mesangial cell interposition and sclerosis were seen. Tests by immunofluorescence microscopy for the presence of immunoglobulins A, M, G, lambda and kappa light chains, C3, and C4 were negative. Decay accelerating factor was found in glomeruli and in the vascular pole. Other findings included lymph node angiosclerosis, peripheral nerve microangiopathy and hemangioma formation with endothelial cell proliferation. These observations suggest that chronic endothelial injury constitutes the basic pathology of Crow-Fukase syndrome. Hemodialysis was required to manage anasarca in three of the patients although serum creatinine levels were below 5.0 mg/dl. Urinalysis revealed mild abnormalities and did not reflect the severity of the glomerular lesion. Corticosteroids given to three of the patients were effective in controlling fever and the lymphadenopathy; in two cases the corticosteroids induced a recovery of renal function. Thus Crow-Fukase syndrome may be due to chronic endothelial injury; the clinical symptoms and renal involvement respond to corticosteroid therapy.
In order to study the localization of Lentil lectin (LCH)-binding glycoresidues in glomeruli from patients with a variety of glomerulopathies, and to elucidate the relationship between LCH-binding sugars and the components of the extracellular matrix, laminin and type IV collagen, investigations of formalin-fixed, paraffin-embedded kidney tissues digested with trypsin were carried out by the direct and indirect immunofluorescence microscopy techniques. The glomerular basement membrane (GBM) and the mesangium reacted well with LCH, whereas areas with sclerotic lesions exhibited a decreased reactivity. The pattern of LCH binding to the GBM in various glomerulopathies was similar to that of laminin but different from that of type IV collagen. The pattern of localization of LCH-reacting sites and of laminin in the GBM included the double linear lines in diabetic nephropathy, inner linear line with outer projections (spikes) in membranous nephropathy, and reduplicated basement membrane in membranoproliferative glomerulonephritis. The results obtained by enzyme-linked immunoadsorbent assay showed that LCH had a stronger reactivity for laminin than for type IV collagen or fibronectin. These findings suggest that LCH is more reactive with laminin than with other components of the glomerular extracellular matrix.