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Biomedical subjects

N Yoshikawa

Publications and source records attributed to N Yoshikawa.

At least 181 records · Page 10Linked to original sources

[Effects of H2-receptor antagonist on gastrin and somatostatin secretion of rat stomach].

To investigate the effects of 14 days administration of H2-receptor antagonist (famotidine) on gastric gastrin and somatostatin secretion, bombesin and glucagon were perfused in the isolated pancreas-duodenum deprived rat stomach. Then serum gastrin concentration, gastric mucosal gastrin and somatostatin content, and gastric mucosal G-cell and D-cell numbers were examined. The 14 days administration of famotidine caused the significant increase of basal gastrin secretion, antral G-cell hyperplasia, high gastrin sensitivity to the stimulation by bombesin, and the low somatostatin sensitivity to the stimulation by glucagon. These facts would suggest that 14 days famotidine administration disturbed not only gastrin secretion but also somatostatin secretion. These results may contribute, at least in part, to the high recurrence of ulcers after withdrawal of H2-receptor antagonists.

Animals↗

[Hereditary nephropathies].

Hereditary nephritis is usually accompanied by hematuria in childhood and, when associated with neurosensory deafness, is known as Alport's syndrome. In recent years, we have begun to understand that there are primary defects in glomerular basement membrane structure in hereditary nephritis. Increased knowledge concerning clinical and pathologic features has led to the identification of 4 types of hereditary nephritis. Herein, we review and update basic and clinical aspects of hereditary nephritis.

Basement Membrane↗

Repeat renal biopsy in children with IgA nephropathy.

Serial renal biopsy findings in 61 children with IgA nephropathy were correlated with their clinical course. At the time of the second biopsy, 23 patients showed clinical remission defined as complete disappearance of proteinuria and hematuria with normal renal function while 38 had persistent urinary abnormalities with normal renal function at the second biopsy. There were no differences between the two groups with regard to initial clinical findings and pathologic findings of the initial renal biopsy. The second biopsy of patients with clinical remission showed improvement of the glomerular changes on light microscopy, disappearance or diminution of IgA deposits in the mesangium and decrease of electron-dense deposits, whereas the second biopsy of patients with persistent urinary abnormalities showed progression of glomerular changes on light microscopy, persistence of mesangial IgA deposits and persistence of electron-dense deposits. Our study results show the importance of repeat renal biopsy in children with IgA nephropathy with persistent urinary abnormalities, as a progression of glomerular changes is common in these patients. These observations suggest that the deposition of IgA in the mesangium may be responsible for the glomerular damage in children with IgA nephropathy.

Adolescent↗

Acute interstitial nephritis associated with Yersinia pseudotuberculosis infection.

We report two cases of acute interstitial nephritis associated with Yersinia pseudotuberculosis infection. The patients had fever, abdominal pain, vomiting and acute renal failure coinciding with elevated agglutination antibody titer for Y. pseudotuberculosis. Renal biopsy revealed interstitial nephritis in both patients. Although it is well known that yersiniosis sometimes affects glomeruli, this is the first report to demonstrate acute interstitial nephritis in patients with Y. pseudotuberculosis infection.

Acute Disease↗

Thyroid-stimulating activity in sera of normal pregnant women.

To evaluate the effect of a thyroid stimulator on thyroid function in the sera of normal pregnant women, we measured thyroid-stimulating activity (TSA) using a highly sensitive bioassay based on cAMP accumulation in cultured rat FRTL-5 thyroid cells. Serum was pretreated with 10% polyethylene glycol (PEG), and the supernatant (PEG-pretreated serum) was then used in the following studies. FRTL-5 cells were preincubated in 5H medium and incubated for 2 h with PEG pretreated serum, and cAMP was measured. All 11 patients with untreated hyperthyroid Graves' disease with strongly positive thyroid-stimulating antibody activity had normal TSA, because only 5.6% of their immunoglobulin G was recovered in the PEG-pretreated serum. In 32 normal pregnant women, 29 (91%) had positive TSA. Their TSA showed statistically significant positive correlations with serum hCG and free T4 levels, and a negative correlation with serum TSH levels. Moreover, when hCG was absorbed from sera by incubation with the solid phase anti-HCG monoclonal antibody, a significant positive correlation was observed between the rate of decrease in hCG and that in TSA. In conclusion, 1) TSA exists in the sera of normal pregnant women, which reflects hCG itself; and 2) thyroid glands of normal pregnant women may be stimulated by TSA to induce a slight suppression of TSH but not sufficient to induce overt hyperthyroidism.

Adult↗

Activity of thyroid stimulating antibody and thyroid stimulation blocking antibody determined by radioiodine uptake into FRTL-5 cells.

To investigate the pathophysiology of patients with autoimmune thyroid diseases, we measured serum thyroid stimulating antibody (TSAb) activity and thyroid stimulation blocking antibody (TSBAb) activity by determining the radioiodine (125I) uptake into FRTL-5 cells. FRTL-5 cells were pre-incubated for seven days with 5H medium and then incubated for 48 hours with patients' crude IgG prepared by polyethylene glycol precipitation. In order to measure TSBAb, 10 microU/ml TSH was also added. 125I was added one hour before the end of the 48 hour incubation period. After the incubation, the medium was aspirated, and the radioactivity in the cells was counted. In patients with untreated hyperthyroid Graves' disease, TSAb was detectable in 18 of 20 patients, the detectability being 90%, and activity showed a statistically significant positive correlation with TSAb activity determined by c-AMP accumulation. Out of 41 patients with hypothyroidism, TSBAb determined by 125I uptake was positive in six cases, the detectability being 14.6%. The inhibition of 125I uptake by one of these six IgGs was suggested to be at the TSH receptor level because it inhibited TSH induced c-AMP accumulation and showed positive thyrotropin binding inhibitor immunoglobulin (TBI I) activity, but did not inhibit the forskolin- and (Bu)2cAMP-induced 125I uptake. Inhibition of another IgG was suggested at the post-receptor level because it did not inhibit TSH induced cAMP accumulation and showed negative TBI I activity, but inhibited forskolin- and (Bu)2cAMP-induced 125I uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

A sensitive and practical bioassay for thyrotropin using cultured FRTL-5 cells: assessment of bioactivity for serum TSH in patients with chronic renal failure.

A sensitive bioassay for TSH employing a practical extraction method was developed, and the bioactivities in patients with chronic renal failure receiving hemodialysis were compared with those in normal subjects. Serum samples were obtained from 12 normal subjects and 12 patients with chronic renal failure receiving hemodialysis. TSH was extracted from the serum using anti-human TSH monoclonal antibody coated tubes, followed by elution with 2.0 mol/l guanidine-HC1 solution (pH 3.2). After the eluate had been dialyzed against phosphate buffered saline (pH 7.4) and again against TRIS-HC1 solution (pH 7.4) and then lyophilized, it was reconstituted with hypotonic Hanks' solution. Bioassay for TSH was performed by measuring the levels of cAMP released into the medium from cultured FRTL-5 cells incubated with the extract. The mean immunoreactive recovery rates of TSH from the serum in normal subjects and patients with chronic renal failure were about 42% (+/- 6) and 40% (+/- 2), respectively. The present bioassay was sufficiently sensitive to detect a serum TSH level of 1.0 mU/l when 3.0 ml of serum was used. Extracts from standard sera at concentrations ranging from 1.0 to 10 mU/l added to the culture medium caused significant linear increases in cAMP production. Based on analysis of covariance the regression line between the immunoreactivities and bioactivities of serum TSH in patients with chronic renal failure (y = 0.90x + 0.3, r = 0.92) was not significantly different from that in normal subjects (y = 1.04x + 0.1, r = 0.93).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Focal and diffuse membranoproliferative glomerulonephritis in children.

Characteristic deposition of C3 has been reported in type I membranoproliferative glomerulonephritis (MPGN). Immunofluorescence microscopy shows diffuse granular deposition of C3 along the majority of capillary loops with lobular pattern. To determine the specificity of this immunofluorescence finding which might aid in distinction between type 1 MPGN, particularly focal MPGN, and the other glomerulopathies, 530 renal biopsies from 437 children were studied retrospectively. Nineteen patients showed diffuse granular deposits of C3 along the capillary walls with lobular distribution. Three patients had lupus nephritis. Nine patients showed the light microscopic changes of diffuse type I MPGN with the characteristic double-walled capillaries. Six patients showed the changes of focal MPGN, and 1 had diffuse mesangial proliferation but without double contours, and they were regarded as examples of a mild or early form of MPGN. A similar deposition of C3 was not seen in the 418 patients with other conditions. We concluded that diffuse granular deposits of C3 along the capillary walls with a lobular distribution appear to be confined to type I MPGN and lupus nephritis and are seen in all patients with diffuse and focal type I MPGN.

Biopsy↗

Relationship among thyrotropin (TSH), thyroid stimulating immunoglobulins, and results of triiodothyronine (T3) suppression test in patients with Graves' disease.

To investigate the relationship between TSH and abnormal thyroid stimulator(s) in patients with hyperthyroid Graves' disease in whom normal thyroid hormone levels in the serum were maintained by antithyroid drug therapy and in patients with euthyroid Graves' disease, determinations were made of the TSH concentration, action of thyroid stimulating immunoglobulins (TSAb and TBII), and T3 suppression. Out of thirty-three patients with hyperthyroid Graves' disease, twelve patients with subnormal TSH levels were all non-suppressible according to the T3 suppression test results and the detectability of TSAb and/or TBII was as high as 75%. In three out of five patients with euthyroid Graves' disease, the serum TSH level was subnormal. All three showed non-suppressibility in the T3 suppression test and positive action of either TSAb or TBII. One of them became clinically thyrotoxic when the TSAb activity was further increased and TBII became positive, and was therefore diagnosed as having hyperthyroid Graves' disease. The present findings suggest that there are still abnormal thyroid stimulator(s) in patients with hyperthyroid Graves' disease who have low TSH, even if their thyroid hormone concentrations remain normal. Moreover, it is likely that some of the patients with euthyroid Graves' disease are actually in a state of subclinical hyperthyroidism because of the presence of abnormal thyroid stimulator(s).

Adolescent↗

Hereditary nephritis in children with and without characteristic glomerular basement membrane alterations.

Characteristic ultrastructural alterations of the glomerular basement membrane (GBM) have been reported in hereditary nephritis. However, these GBM changes are not present in all patients with hereditary nephritis. In a retrospective study of 42 children with hereditary nephritis characteristic GBM changes were found in 28. The clinical features, renal biopsy findings and subsequent course were compared with those in the 14 without such changes. All 42 patients had hematuria. Eighty-two percent of the patients with the GBM changes showed progression of nephritis and 39% showed neurosensory deafness when last seen. In contrast, all patients without the GBM changes had a normal audiogram, ran a nonprogressive course and had hematuria only when last seen. Light microscopy of renal biopsy specimens revealed segmental glomerular sclerosis and interstitial foam cells only in patients with the GBM changes. Our study shows that the presence or absence of these GBM changes is the most reliable indicator of the prognosis in children with hereditary nephritis.

Adolescent↗

A sensitive radioimmunoassay for circulating alpha-interferon in the plasma of healthy children and patients with measles virus infection.

The mean circulating alpha-interferon of healthy children aged 2 to 13.5 yrs as measured by a radioimmunoassay was 0.119 +/- 0.031 ng/ml, which was significantly lower than that of young adults. Circulating alpha-interferon of children with measles virus infection aged 1 to 11 yrs, on their first visit to the hospital when they were fully symptomatic, was 0.095 +/- 0.035 ng/ml (n = 39). It was 0.105 +/- 0.070 ng/ml (n = 21) on their second visit, 7 to 10 days after their first visit when the patients were convalescent. The difference was statistically insignificant. It is concluded that immunoreactive circulating alpha-interferon is low in children and reaches maximum level in young adults, subsequently declining gradually with age. Immunoreactive circulating alpha-interferon, a possible reflection of endogenous alpha-interferon, does not change significantly by the infection of measles virus.

Acute Disease↗

Benign familial hematuria.

Fifty children had benign familial hematuria. They were from 43 families showing neither deafness, heavy proteinuria, nor chronic renal failure and had a nonprogressive course. Light microscopy of renal biopsy specimens showed little or no glomerular changes. Immunofluorescence showed no significant glomerular deposits of immunoglobulins or complement components, but deposition of C3 in the arteriolar walls was observed in 21 of the 39 patients examined. Electron microscopy demonstrated widespread attenuation of the glomerular basement membrane (GBM) in 19 patients, focal attenuation in 22, and normal GBM in nine. These observations suggest that patients with benign familial hematuria are heterogeneous and that the thin GBM may be related to hematuria.

Basement Membrane↗

Immunoelectron microscopic study of childhood IgA nephropathy and Henoch-Schönlein nephritis.

Renal biopsy specimens from 11 children with Henoch-Schönlein nephritis and 14 with IgA nephropathy were examined by immunoelectron microscopy. The distribution of IgA reaction product (RP) was found to be similar to that of the electron-dense deposits seen with conventional electron microscopy. Deposits of IgA-RP were present in the mesangium and in the subendothelial region of the peripheral glomerular capillary wall in all patients. Subepithelial deposits of IgA-RP were seen in 12 patients. Deposits of IgG-RP were rare and no deposits of IgM-RP were observed. Deposits of C3-RP were found frequently, although they were smaller and less extensive than deposits of IgA-RP. There was no significant difference between Henoch-Schönlein nephritis and IgA nephropathy with regard to immunoelectron microscopy findings. These observations suggest that Henoch-Schönlein nephritis and IgA nephropathy are both forms of mesangiopathic glomerulo-nephritis caused by immune complexes, mainly composed of IgA.

Adolescent↗

Nonfamilial hematuria associated with glomerular basement membrane alterations characteristic of hereditary nephritis: comparison with hereditary nephritis.

Characteristic ultrastructural alterations of the glomerular basement membrane (GBM) have been reported in hereditary nephritis and in children without a family history of renal disease. The clinical features, renal biopsy findings, and subsequent course were studied retrospectively in 48 children with such GBM changes to compare findings in those with and without a family history of nephritis and to determine the significance of the GBM changes in patients with nonfamilial disease. All 48 patients had hematuria. For 30, there was hematuria in at least one other member of the family (familial hematuria group); for 18, there was no familial incidence. There were no differences between the two groups with regard to clinical and pathologic findings. At the latest follow-up six boys with familial hematuria and three boys with nonfamilial hematuria had reduced renal function, and nine boys with familial hematuria and four boys and one girl with nonfamilial hematuria had neurosensory deafness. Our study results show that children with these GBM changes, with or without a family history of hematuria, tend to have a progressive course, with frequent occurrence of neurosensory deafness, and that the prognosis is more severe in boys. These observations suggest that such GBM changes in patients with nonfamilial hematuria may represent new mutations for hereditary nephritis.

Basement Membrane↗

Clinical course of immunoglobulin A nephropathy in children.

The clinical presentation, initial laboratory and renal biopsy findings, and subsequent clinical course of IgA nephropathy were studied retrospectively in 200 children, and findings in those with younger onset and older onset were compared. Eighty-three patients were 8 years of age or younger (group 1) and 117 were 9 years of age or older (group 2) at onset. There were no differences between the two groups with regard to sex, initial renal function, incidence of hypertension and macroscopic hematuria, degree of proteinuria, and pathologic findings. At the latest follow-up, two patients in group 1 and eight in group 2 had chronic renal failure, and five patients in group 1 and 21 in group 2 had heavy proteinuria with or without hypertension (P less than 0.01), whereas 36 (43%) patients in group 1 and 29 (25%) in group 2 had normal urine, blood pressure, and glomerular filtration rate (P less than 0.01); the disease followed a significantly more benign course in children with younger onset than in those with older onset. These observations suggest some age-related differences in the natural history of childhood IgA nephropathy.

Age Factors↗

Mesangial changes in IgA nephropathy in children.

The mesangial changes in 92 renal biopsy specimens from 81 children with IgA nephropathy were correlated with the clinical and the other renal biopsy findings. Three types of mesangial changes were identified: mesangial hypercellularity was predominant compared with the increase in matrix in 34 biopsy specimens (type A), the degrees of mesangial hypercellularity and matrix increase were similar in 36 (type B) and matrix increase was predominant in 22 (type C). The interval between the onset of disease and biopsy was significantly shorter in biopsies with type A mesangial changes (P less than 0.01) and significantly longer in those with type C (P less than 0.01). Serial pathologic observations revealed that predominant mesangial hypercellularity was almost exclusively seen in the initial biopsy but predominant matrix increase was usually seen in the follow-up biopsy. The percentage of glomeruli showing sclerosis was significantly higher in biopsies with type C mesangial changes (P less than 0.05). At the latest follow-up, 58% of the patients showing type A and 57% showing type B lost their proteinuria, whereas only 9% showing type C lost their proteinuria (P less than 0.01). These findings suggest that predominant mesangial hypercellularity is characteristic of the early lesion of childhood IgA nephropathy, and progression of disease leads to gradual decrease of mesangial cellularity and increase of matrix with sclerosis.

Biopsy↗

In vitro characterization of various factor VIII concentrates.

The in vitro properties of 5 heat-treated Factor VIII (F VIII) concentrates were studied and compared with those of conventional non heat-treated concentrates with special reference to F VIII/von Willebrand Factor (vWF) activities. The heat-treated F VIII concentrates were found to contain about 25 U/ml of F VIII: C as indicated on the label, 59.5-103.3 U/ml of F VIII: Ag, 20.0-74.0 U/ml of ristocetin cofactor activity (RCof), and 67.3-96.0 U/ml of vWF: Ag. The F VIII/vWF activities in the heat-treated concentrates were almost the same as those in the 6 non heat-treated concentrates. The antihemophilic factor (AHF)-cryoprecipitate contained 2.3 U/ml of F VIII: C which was roughly equivalent to the amount of F VIII: Ag. In addition, it contained 7.3 U/ml of RCof which was equivalent to the amount of vWF: Ag. The ratio of F VIII: Ag to F VIII: C in the F VIII concentrates ranged from 2.5 to 4.4. The ratio of vWF: Ag to RCof in the concentrates ranged from 1.1 to 4.8. There were, however, no significant differences in F VIII/vWF activities between the heat-treated and the non heat-treated F VIII concentrates with two exceptions. These findings suggest that the inactivation of the biological activities of F VIII and RCof, and/or the denaturation of both the F VIII: C protein and the vWF protein antigen occurred during the production procedure, while the heat-treatment did not lead to further changes of F VIII/vWF.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoradiography↗