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Biomedical subjects

T Furuyama

Publications and source records attributed to T Furuyama.

At least 19 recordsLinked to original sources

Co-expression of glycine receptor beta subunit and GABAA receptor gamma subunit mRNA in the rat dorsal root ganglion cells.

We examined the expression of the beta subunit mRNA of the glycine receptor and the gamma subunit mRNA of the GABAA receptor in the rat dorsal root ganglion (DRG) using in situ hybridization histochemistry with oligonucleotide probes. About 44% and 37% of the all DRG neurons were labeled by the probes for glycine receptor beta subunit and GABAA receptor gamma subunit mRNAs. Labeled neurons were mostly large cells that simultaneously expressed both glycine receptor beta subunit and GABAA receptor gamma subunit mRNA as demonstrated using consecutive sections. Thus, we suggest the possibility that both GABA and glycine presynaptically regulate the activity of neurons involved in low-threshold mechanoreception at axo-axonic synapses in the spinal cord.

Animals

Impaired water diuresis in a patient with pseudo-Bartter syndrome.

A 32-year-old man was diagnosed as having pseudo-Bartter syndrome due to surreptitious habitual vomiting and to maldigestion related to decayed teeth. His chief complaints were muscle pain and weakness. In this case, metabolic alkalosis, hypokalemia, hypochloremia, increased plasma renin activity and aldosterone levels were noticed with marked decreases in urinary chloride excretion. Creatinine clearance (GFR) and renal plasma flow (RPF) were also decreased. Blood pressure was normal, but the pressor response to angiotensin II was attenuated. Before treatment with 0.9% saline infusion, plasma vasopressin (AVP) was not suppressed sufficiently by lowering the plasma osmolality (Posm) with an oral water load (WL), but it normally responded to a rise in Posm due to hypertonic saline infusion. Moreover, plasma AVP was normally suppressed by WL after the replenishment of saline. Plasma atrial natriuretic peptide (ANP) was low before WL, but increased normally in response to WL. However, inconsistent with the normal response in this case, decreases in plasma AVP failed to dilute urinary osmolality and to increase urine flow, irrespective of the levels of plasma ANP. These results indicate that chronic inanition due to surreptitious vomiting causes impaired renal diluting ability through decreases in GFR and RPF, irrespective of the levels of plasma AVP and ANP.

Adult

[Clinico-pathological features in four patients with Fabry's disease. The possible role of degenerative lesions in the interstitial vessels in renal dysfunction].

Clinical courses and histopathological changes of four patients with Fabry's disease were discussed in this report. All of them were male and revealed to have angiokeratomas of the skin and markedly decreased activity of alpha-galactosidase--A in leukocytes. They were from different families. No consanguinity was noted. Two of them, around 40 years of age, showed rapid impairment of renal function with simultaneously development of hypertension, progressing to uremia within several months. Their light and electron microscopic findings in renal biopsies were similar: severe degenerative changes in muscle cells of small arteries and arterioles with remarkable swelling of intima, and multiple sclerosing and collaptic lesions in glomeruli. The other 2 patients were about 20 years old and their renal functions were almost normal. No significant changes but fine vacuolization of epithelial cells of glomeruli were observed in renal biopsy specimens. It is concluded that marked degenerative changes in the vessels due to Fabry's disease might be the principal etiology of hypertension and rapid deterioration of renal function.

Adolescent

[Prognosis of chronic glomerulonephritis--study on renal survival ratio of mesangial proliferative glomerulonephritis and membranoproliferative glomerulonephritis].

Renal survival curves for the adult patients at the ages between 15 and 60 with mesangial proliferative glomerulonephritis (MesPGN, N = 366) and membranoproliferative glomerulonephritis (MPGN, N = 76) were calculated using the method designed by Kaplan and Meier. In MesPGN, 80% and 68% of the patients survived 10 and 20 years after biopsy respectively; 88% and 72% survived 10 and 20 years after apparent onset. These results were similar to those analyzed by the research team "progressive renal lesions" in Ministry of Health and Welfare, Japan. When patients were histologically divided into 4 groups according to the index of glomerular lesions, % survival in each group was reduced in relation with the severity of the glomerular lesions, and there was significant difference between renal survival curves of each 2 groups. The influence of urinary protein and hypertension at the time of biopsy on survival curves was also significant. Patients with IgA nephropathy (N = 74) showed the renal survival curve similar to those of MesPGN. The influence of hypertension on % survival was also significant in IgA nephropathy. In MPGN, 53% and 73% of patients survived 10 years after biopsy and apparent onset respectively. Therefore MPGN was poorer in prognosis than MesPGN. These results seem to be important as the controls when we try to study the long-term effects of various therapies against chronic glomerulonephritis.

Adolescent

Progression of experimental focal glomerulosclerosis in the spontaneously hypertensive rat.

To study the influence of hypertension on the progression of focal glomerulosclerosis (FGS), we produced an experimental model of FGS in spontaneously hypertensive rats (SHRs) by the combined administration of puromycinaminonucleoside (AMNS) and protamine sulfate (PS). SHRs and normotensive Wistar Kyoto rats as a control strain were given daily injections of subcutaneous AMNS (1 mg/100 gm body weight) and intravenous PS (two separated doses of 2.5 mg/100 mg body weight) for 4 days; they were killed on day 80 after three series of injections at 10-day intervals. The levels of urinary protein, serum creatinine, and urea nitrogen in SHRs given AMNS and PS were elevated throughout the experiment and were significantly higher than these levels in other control groups on day 80. Histology in SHRs given AMNS and PS showed advanced FGS associated with glomerular hypertrophy and widespread interstitial fibrosis. Most small arteries and arterioles showed "onion peel" thickening and fibrinoid necrosis of the intima, which is characteristic of malignant arteriosclerosis. We observed that the gradient of glomerulosclerosis increased from superficial to deep cortical zones; this phenomenon had often been reported in human FGS. However, these distinguished lesions were not found in control groups. Therefore, it is suggested that systemic hypertension is one of the deleterious factors enhancing histologic and functional deterioration in FGS.

Animals

Renal lesions in Cockayne's syndrome.

A nine-year-old boy who exhibited mild proteinuria and severe renal dysfunction with short stature, mental retardation, retinitis pigmentosa, deafness, and intracranial calcification was presented. Clinical features of the patient were in the most part consistent with those of Cockayne's syndrome. On the renal biopsy, two-thirds of the glomeruli had fallen into global sclerosis. The remaining one-third showed thickening of the capillary walls and expansion of the mesangial matrix. Immunofluorescence study proved no significant deposition of immunoglobulins or complements. Electron microscopy revealed diffuse homogeneous thickening of the glomerular basement membrane. These histological findings were thought to be characteristic of the Cockayne's syndrome. Although the pathogenesis of Cockayne's syndrome is yet unknown, its renal lesions resembled those of an aged kidney, and a prematurely aged metabolic state was supposed as a principal cause of the disease.

Aging

Quantitation of C3 nephritic factor of alternative complement pathway by an enzyme-linked immunosorbent assay.

We have developed an enzyme-linked immunosorbent assay (ELISA) for the quantitation of C3 nephritic factor of the alternative pathway of complement (NeFA). Incubation of the NeFA-positive serum (patient KS serum) with normal human serum (NHS) in Mg-EGTA resulted in the formation of C3-B-IgG complex. No complex was formed in EDTA. At first this was detected as three types of complexes: C3-IgG, B-IgG and B-C3, by the combination of antibodies. The reaction mixture in Mg-EGTA was filtered through an ACA 22 column, from which the complexes were eluted in the same part as the first protein peak. When IgG purified from KS serum was incubated with NHS in Mg-EGTA, B-C3 complex increased in proportion to the dose of IgG. These results indicated that only one kind of complex consisting of IgG, C3 and B (IgG-C3-B) was generated by the addition of NeFA to NHS. Serum NeFA could be quantified as the titer of B-C3 complex formed after its incubation with NHS in Mg-EGTA. Using the ELISA method, NeFA was positive in five out of six patients with membranoproliferative glomerulonephritis (MPGN) type II and in only one of 17 with MPGN type I. Titers obtained by the new method were in good accordance with those by C3 conversion and C3bBb stabilization assays for NeFA, and the new method was more exact and simple than the conventional methods.

Antigen-Antibody Complex

Histologic studies on the nephrotic syndrome in the elderly.

Renal histopathology in 87 patients, aged over 60, with nephrotic syndrome were studied. In 57 patients diagnosed as primary glomerular disease, membranous glomerulonephritis (MGN) was of the most common histologic type (52.6% of the cases), and mesangial proliferative glomerulonephritis (21.1%), membranoproliferative glomerulonephritis (12.3%) and minimal change (12.3%) were the other types of primary glomerular disease. In the remaining 30 patients, nephrotic syndrome resulted from secondary glomerular diseases including diabetic nephropathy and renal amyloidosis. In comparison with the nephrotic syndrome of younger age group (669 cases, younger than 60 years of age), the incidence of MGN, diabetes and amyloidosis were significantly higher in the elderly. In contrast with unfavorable prognosis of diabetic nephropathy and amyloidosis, most cases of MGN and minimal change recovered from the nephrotic state with steroid treatment even in the elderly. Thus, a statistical finding that the prognosis of senile nephrotic syndrome is unfavorable as a whole, appears to be ascribable to the increased incidence of secondary glomerular diseases rather than to "aging" itself. The present results that the incidence of diabetic nephropathy was high and the outcome of MGN was favorable in the elderly, taken together with the results from other studies in Japan, are fairly different from the results of similar studies in the Western world.

Adrenal Cortex Hormones

Dense deposit disease: its possible pathogenesis suggested by an observation of a patient.

A girl, aged 8, was admitted to a hospital in a state of nephrotic syndrome of one year's duration. The renal biopsy showed mesangial and endocapillary proliferations with lobulation. Dense deposit was not demonstrated by electron microscopy, but lamellation of the lamina densa was found in most of the capillary loops. Her condition was improved by steroid treatment in a few months, but moderate proteinuria persisted. Five and half years later, follow-up biopsy showed typical pathological features of dense deposit disease. It is suggested that the lamellation of the lamina densa in the first biopsy could be related to the dense alteration of glomerular basement membrane in the second biopsy.

Basement Membrane

Distribution of fibronectin and other connective tissue components in human placenta.

Human placenta specimens obtained at term were investigated for distribution of fibronectin, collagens and glycosaminoglycans. When examined by the immunofluorescence staining technique with anti-plasma fibronectin antiserum, fibronectin was shown to be present around the fetal blood vessels and in the stroma of placental villi. The distribution of type IV collagen also was examined with specific antiserum. It was found that its distribution was similar to that of fibronectin. Conventional alcian blue staining indicated that the placental villi contained only small amounts of glycosaminoglycans. These data suggest that fibronectin and type IV collagen play important roles in tissue organization of the placental villi.

Chorionic Villi

Modified anti-C3 immune complex assay which avoids interference by anti-F(ab')2 antibodies.

The present authors and Olds et al. reported that the anti-F(ab')2 antibodies (Abs) in serum interfere with the solid phase (SP) anti-C3 immune complex assay. The anti-F(ab')2 Abs in human sera bind solid phase F(ab')2 anti-C3 of rabbit or goat, and were measured erroneously as C3 bearing circulating immune complexes (CIC). Gel filtration analysis of SP anti-C3 assay revealed that C3 bearing CIC is detected only in heavy fractions and 7S CIC-like activity is not CIC but anti-F(ab')2 activity. As the molecular weight of such CIC is heavy enough to be precipitated by 5% polyethylene glycol (PEG) and IgG anti-F(ab')2 Abs and free C3 are not included in 5% PEG precipitates, 5% PEG precipitates of the test sera were used for SP anti-C3 (Modified SP anti-C3). CIC measured by modified SP anti-C3 were positive in 14/16 at active stage of SLE and positive only in 2/16 at inactive stage. CIC by this test were also correlated well to serum complement activity, and were thought to be clinically reliable and useful.

Antibodies

Circulating immune complex-like materials which bind to heat inactivated C1q interfere with the C1q solid phase assay for immune complexes.

C1q solid phase assay (C1q SP) was devised based on the fact that immune complexes (IC) and aggregated human globulin (AHG) bind to C1q. Neither IC nor AHG was found to bind to heat inactivated C1q. On the other hand, circulating immune complex (CIC)-like materials in patients' sera were able to bind to heat inactivated C1q, indicating that these CIC-like materials are not true CIC. Gel filtration analysis showed that molecular size of such CIC-like materials was almost the same as monomeric IgG, while true CIC were in heavy fractions. True CIC did not bind to heat inactivated C1q but bind only to native C1q. The CIC-like activity is not due to rheumatoid factors. About 2/3 of CIC positive sera by C1q-SP are not really CIC positive but are due to interference by the CIC-like materials.

Animals

A new and specific enzyme-linked immunosorbent assay for the detection of C3 nephritic factor.

C3 nephritic factor (C3 NeF) was measured by assessing its capacity to form complex with C3 and B using an enzyme-linked immunosorbent assay (ELISA). Incubation of C3 NeF with normal human serum in the presence of MgEGTA resulted in a dose-dependent increase of C3-B-IgG complex. No complex was formed in EDTA. The C3 NeF titer estimated in this way was in good accordance with those reported previously by other indirect methods.

Complement C3

Changes in distribution of connective tissue components of human placentae with maturation.

The distributional changes of type IV collagen and laminin with normal maturation of human placentae were examined in relation to those of fibronectin by the histochemical methods including immunofluorescence staining. In the early chorionic villi, these components were detected along the trophoblastic basement membrane, around the fetal blood vessels, and in the villous stroma. Laminin was detected also in the pericellular matrices of nonvillous cytotrophoblasts where type IV collagen was rarely detected. In the late and term placentae, laminin and type IV collagen were detected along the trophoblastic basement membrane, while this structure was virtually not stained for fibronectin. These observations suggest that type IV collagen and laminin are the constituents of the trophoblastic basement membrane throughout the maturation period of the placentae, while fibronectin is a transient constituent.

Chorionic Villi