Biomedical subjects

H C Hsu

Publications and source records attributed to H C Hsu.

At least 163 records · Page 9Linked to original sources

PubMed1996

Identification of naturally occurring dominant negative mutants of thyroid hormone alpha 1 and beta 1 receptors in a human hepatocellular carcinoma cell line.

To understand the function of thyroid hormone nuclear receptors (TRs) in human hepatocellular carcinoma cells (HCC), we characterized the hormone binding and transactivational activity of TRs in a HCC cell line, J7. TR alpha 1 (J7-TR alpha 1) and TR beta 1 (J7-TR beta 1) complementary DNAs were cloned from this cell line, and the binding activity to the hormone response elements (TREs) and to the thyroid hormone, 3,3',5-triiodo-L-thyronine (T3) of the expressed TR proteins were evaluated. J7-TR alpha 1 and J7-TR beta 1 bound to TREs similarly as the TRs isolated from other tissues. However, J7-TR alpha 1 did not bind to T3, and J7-TR beta 1 bound to T3 with only about 10% the affinity of the wild-type TR beta 1. Sequencing of the complementary DNAs shows a single Met259Ile mutation in J7-TR alpha 1 and Met334Val in J7-TR beta 1. Using reporters containing TREs, we found that J7-TR alpha 1 and J7-TR beta 1 had virtually lost their transactivational activity. Moreover, these two mutants inhibited the transactivational activity of the wild-type TRs by a dominant negative effect not only on the transfected TRs, but also on endogenous TRs in other two HCC cell lines, SK-Hep-1 and HepG2. The potency of the dominant negative effect of these two mutants inversely correlated with the expression level of endogenous TRs. The present studies identified two novel naturally occurring TR mutants that have potent dominant negative action. The identification of both the alpha and beta dominant negative mutants in J7 made this cell line a useful model system to further understand the molecular mechanism of the dominant negative action of TR mutants.

Carcinoma, Hepatocellular↗

PubMed1996

Production of hematopoietic regulatory cytokines by peripheral blood mononuclear cells in patients with aplastic anemia.

The aim of this study was to measure the level of cytokines produced by peripheral blood mononuclear cells (PBMNC) in patients with aplastic anemia (AA) and determine their effect on normal bone marrow (BM) colony growth. Thirty-five patients with AA and 21 normal controls were enrolled in the study. Medium conditioned by PBMNC of AA patients in the presence of phytohemagglutinin (PHA) was found to be suppressive to the clonal growth of normal BM cells. Thus, we further determined the presence in the PBMNC conditioned medium (CM) of inhibitory cytokines (macrophage inflammatory protein-1 alpha [MIP-1 alpha], transforming growth factor-beta 2 [TGF-beta 2], interferon-gamma [IFN-gamma], and tumor necrosis factor-alpha [TNF-alpha]) and stimulatory cytokines (granulocyte-macrophage colony-stimulatory factor [GM-CSF], interleukin-3 [IL-3], and stem cell factor [SCF]). The results show no significant difference between AA patients and normal controls in the spontaneous production of all cytokines by PBMNC. After PHA stimulation, the production of MIP-1 alpha, IFN-gamma, TNF-alpha, and GM-CSF significantly increased in the cultures of AA patients (p = 0.0009, 0.0002, 0.0022, and 0.0156, respectively). However, both TGF-beta 2 and SCF were undetectable in most of the tested samples. IL-3 was measured in the conditioned medium only after PHA stimulation, but without significant difference between the two groups (p = 0.67). Furthermore, the myelopoietic suppressing effect of AA-PBMNC CM could be significantly blocked by pretreatment with specific antibodies to the corresponding inhibitory cytokines (MIP-1 alpha, IFN-gamma, and TNF-alpha). After antibody neutralization, an apparent change occurred in the clonal growth of normal BM cells incubated with AA-PBMNC CM, resulting in colony enhancement of 205, 131, and 237% by anti-MIP-1 alpha, anti-IFN-gamma, and anti-TNF-alpha, respectively. These results suggest that overproduction of inhibitory cytokines, rather than underproduction of stimulating cytokines, may play a role in the progression of at least some patients with AA.

Anemia, Aplastic↗

PubMed1996

Effects of colony-stimulating factors on the all-trans retinoic acid-induced differentiation of acute promyelocytic leukemic cells.

BACKGROUND: NB4, a cell line derived from a patient with t(15;17) acute promyelocytic leukemia (APL) that undergoes granulocytic differentiation when treated with pharmacological doses of all-trans retinoic acid (ATRA), was used as a model for induction of differentiation. In this study, we examined the interaction of colony-stimulating factors (CSF) and ATRA in affecting the proliferation and differentiation of NB4 cells. METHODS: Nitroblue tetrazolium (NBT) reduction was used as a functional marker of leukemia cell differentiation. The number of viable cells was counted by trypan blue exclusion test. RESULTS: Proliferation of NB4 cells increased when exposed to 10(-9)M of ATRA, but reduced progressively when exposed to ATRA at the concentrations of 10(-8)M to 10(-6)M. After culture for 5 days, NBT-positive cell was not detectable in the control cultures with medium alone, but its percentage apparently increased to 84% at 10(-7)M ATRA. Granulocyte (G)-CSF per se had no effect on the granulocytic differentiation of NB4 cells, but it could enhance the NBT reduction when used in combination with various concentrations (10(-9)M -10(-6)M) of ATRA. Interleukin (IL)-3 or granulocyte-macrophage-CSF (GM-CSF) alone also had no effect on the NBT reduction in NB4 cells. However, when combined with ATRA, both caused a slight suppression of NBT reduction. No synergistic effect was noted between IL-3 and G-CSF on the ATRA-induced granulocytic differentiation. CONCLUSIONS: G-CSF, but not IL-3 or GM-CSF, can enhance the differentiating activity of ATRA. Further investigations are necessary to evaluate its clinical use.

Cell Differentiation↗

PubMed1996

Patellar dislocation after total knee arthroplasty.

BACKGROUND: Patellar problem is an important cause of nonseptic failure of the current condylar design of total knee arthroplasties. Patellar dislocation after total knee arthroplasty is infrequent but can cause disabling symptoms. METHODS: From March, '84 to July, '92, 1652 total knee arthroplasties were performed at this Hospital. Of these 1100 knees in 978 patients were available to be followed up regularly at the Outpatient Department. Eleven cases of patellar dislocation after total knee arthroplasty were encountered during follow-up. Among these patients, nine patients had received operation at this Hospital; the other two patients had been referred here by the other hospitals. All 11 patients had been treated with surgical methods: proximal realignment of the quadriceps alone in 6 knees, lateral retinacular release combined with revision of the malaligned components in 2 knees, combined proximal and distal realignment in 2 knees and patellar tendon transfer in 1 knee. RESULTS: After an average follow-up of 21.8 months, from April, '84 to April, '93, there was one redislocation, unfortunately caused by trauma. Using the average knee rating scale of the Hospital for Special Surgery, New York, USA, the results of 90.5 were satisfactory and encouraging. CONCLUSIONS: Patellar dislocation after total knee arthroplasty can cause disabling symptoms, including pain, weakness, limited range of motion, extension lag and difficulty when climbing up or down stairs. The cause of patellar dislocation after total knee arthroplasty was error in surgical technique in this series. Revision of the component should be performed in those with malaligned component. Proximal realignment is recommended in those with quadriceps imbalance. Distal realignment is recommended only when proximal realignment alone has failed to restore proper patellar tracking, this should be carried out with great caution due to the potential for serious complications.

Aged↗

PubMed1995

Cloning and expression of CD24 gene in human hepatocellular carcinoma: a potential early tumor marker gene correlates with p53 mutation and tumor differentiation.

To search for genes related to hepatocarcinogenesis, the differential display technique for eukaryotic mRNA was conducted. We have cloned a gene that encodes the CD24 protein from the cDNA library of human hepatocellular carcinoma (HCC). A single 2.1-kb mRNA was identified in HCC specimens and the HuH-7 HCC cell line but only rarely in small amounts in nontumor livers. In 79 unicentric HCC, CD24 mRNA was overexpressed in 52 cases (66%), found in trace amounts in 11, and not detectable in 16 (20%). In 12 cases of multicentric HCC, CD24 mRNA was overexpressed in 21 (68%) of 31 tumor nodules and was helpful for the determination of tumor clonal origin. There was an increased frequency of CD24 mRNA overexpression in patients younger than 50 years with HCC (86% versus 59%, P < 0.025), in serum hepatitis B surface antigen-positive individuals (74% versus 48%, P < 0.023), in those with an elevated serum alpha-fetoprotein level (82%, versus 56%, P < 0.04), and in HCC with alpha-fetoprotein mRNA expression (82% versus 56%, P < 0.04). There was a strong correlation of CD24 mRNA overexpression with p53 gene mutation in HCC (91% versus 46%, P < 0.0005) and poorly differentiated HCC (82% versus 53%, P < 0.0008). Despite its correlation with p53 mutation and the unfavorable outcome of HCC with p53 mutation, the CD24 mRNA expression did not correlate with tumor size, tumor invasiveness, or patient's prognosis. Thus, the CD24 gene expression appears to be a common event in HCC and may serve as an early but not prognostic biomarker for malignant transformation of hepatocytes.

Amino Acid Sequence↗

PubMed1995

A novel multivariate approach for estimating the degree of similarity in bioavailability between two pharmaceutical products.

Statistical assessment of bioavailability and bioequivalence of drug products is generally carried out with a univariate analysis by independently comparing each relevant parameter [such as, area under the drug concentration curve (AUC) and peak drug concentration (Cmax)] of the test and reference products. The assumption is made that AUC and Cmax are independent of each other. In reality, AUC, Cmax, and other pharmacokinetic parameters are dependent on each other. Therefore, a multivariate approach is theoretically superior. In this report, a novel multivariate approach to determine the bioavailability and bioequivalence of pharmaceutical products is described. The method determines the bivariate confidence ellipse (CE) between Cmax and AUC and the trivariate confidence ellipsoid (CED) among Cmax, AUC, and either Tmax or MRT for test and reference products. The similarity between the test and reference products can be assessed by the fraction of overlapping areas of CE and volumes of CED. The method and its comparison with conventional univariate analysis are demonstrated with data obtained from a bioequivalence study of ketoconazole tablets.

Analysis of Variance↗

PubMed1995

Overproduction of inhibitory hematopoietic cytokines by lipopolysaccharide-activated peripheral blood mononuclear cells in patients with aplastic anemia.

The aim of this study was to measure the level of cytokines produced by peripheral blood mononuclear cells (PBMNC) in patients with aplastic anemia (AA) and to determine their effect on the clonal growth of normal bone marrow (BM) cells. Twenty-one patients with AA and 11 normal controls were enrolled in this study. Medium conditioned by PBMNC of AA patients in the presence of lipopolysaccharide (LPS) was found to be suppressive to the colony growth of normal BM cells. Thus, we further determined the presence in the PBMNC-conditioned medium (CM) of both inhibitory cytokines: macrophage inflammatory protein-1 alpha (MIP-1 alpha), tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta 2 (TGF-beta 2), and interferon-gamma (IFN-gamma), and stimulatory cytokines: interleukin-3 (IL-3) and stem cell factor (SCF). Spontaneous production of MIP-1 alpha was higher in the AA patients than the normal controls (1887 +/- 174 pg/ml vs 1643 +/- 93 pg/ml), but the difference was not significant. After LPS stimulation, the production of MIP-1 alpha was markedly increased in the AA patients, and its level was significantly higher than that of the normal controls (2360 +/- 149 pg/ml vs 1517 +/- 92 pg/ml, p = 0.0022). The level of TNF alpha was also higher in the AA patients. However, IFN-gamma, TGF-beta 2, SCF, and IL-3 were not detectable in the PBMNC-CM of either AA patients or normals. The myelopoietic suppressing effect of AA-PBMNC-CM from each AA patient was significantly blocked by pretreatment with anti-TNF-alpha, resulting in a colony-forming enhancement of 174% +/- 12%. A similar effect was noted in six of 11 AA patients by pretreatment with anti-MIP-1 alpha. We conclude that TNF alpha and MIP-1 alpha can be overproduced by the PBMNC of some AA patients, which may play a role in the progression of AA.

Anemia, Aplastic↗

PubMed1995

Constituents and cytotoxic principles of Nothapodytes foetida.

A new naturally occurring alkaloid, acetylcamptothecin, together with 17 known compounds, (+)-1-hydroxypinoresinol, omega-hydroxypropioguaiacone, p-hydroxybenzaldehyde, scopoletin, uracil, thymine, sitosterol, sitosteryl-beta-D-glucoside, 3 beta-hydroxy-stigmast-5-en-7-one, stigmast-5-en-3 beta,7 alpha-diol, 6 beta-hydroxystigmast-4-en-3-one, sitost-4-en-3-one, linoleic acid, trigonelline, camptothecin, 9-O-methoxycamptothecin and pumiloside were isolated and characterized from the stem of Nothapodytes foetida. Among them, scopoletin, camptothecin, 9-O-methoxycamptothecin and O-acetylcamptothecin showed significant cytotoxic activity.

Antineoplastic Agents, Phytogenic↗

PubMed1995

Fish oil supplementation attenuates myointimal proliferation of the abdominal aorta after balloon injury in diet-induced hypercholesterolemic rabbits.

The effects of supplementing with fish oil on the myointimal proliferation of the abdominal aorta after balloon injury were studied in control and in rabbits fed a 1% cholesterol-enriched diet, with and without 10% fish oil supplementation. Twenty-one animals in each group underwent a balloon injury of the abdominal aorta and left common iliac artery after 2 weeks of feeding. The animals remained on their respective diets thereafter. In 7 balloon-injured and 7 sham-operated animals of each group, the abdominal aorta was harvested 3 days later for the analysis of prostanoids, malondialdehyde, superoxide dismutase activity, [3H]thymidine uptake, and cholesterol levels. In the other 7 balloon-injured rabbits of each group, the tissue was harvested 3 weeks later for morphometric study. The fish oil-treated rabbits had the lowest aortic production of thromboxane B2 levels and the highest 6-keto-PGF1 alpha/thromboxane B2 ratios among the three groups after balloon injury. The aortic malondialdehyde levels of the cholesterol-fed rabbits were significantly higher than the other two groups (each P < 0.001) independent of balloon injury. The myointimal proliferation of the abdominal aorta and left common iliac artery in the fish oil-treated rabbits was less severe than in the cholesterol-fed animals (both P < 0.001) and was comparable with the controls. These results suggest that a fish oil supplement changes prostanoid metabolism to a favorable pattern and reduces lipid peroxidation on the abdominal aortic wall, thus attenuating myointimal proliferation after balloon injury in diet-induced hypercholesterolemic rabbits.

6-Ketoprostaglandin F1 alpha↗

PubMed1995

Increased expressions of CD69 and HLA-DR but not of CD25 or CD71 on endometrial T lymphocytes of nonpregnant women.

To investigate lymphocyte subpopulations and the status of T-cell activation at different phases of the menstrual cycle, lymphocytes in endometrial tissue were analyzed by dual-color flow cytometry in 39 patients. Compared with peripheral blood, the lymphocytes in the endometrium had a higher CD3-/(CD56+ or CD16+) ratio (25.2% +/- 6.8% vs 11.1% +/- 7.0%), but an inverted CD3+ CD8-/CD3+ CD8+ ratio (0.5 vs 1.8) and a minimal amount of B cells (3.3% +/- 3.1%). TcR gamma delta + T cells accounted for a minor proportion (7.8% +/- 5.1%) in endometrium. The proportions of TcR alpha beta + (85.0% +/- 6.6%) and CD3+ CD56+ (7.4% +/- 4.4%) endometrial T lymphocytes were found significantly different from those in peripheral blood (89.1% +/- 5.6% and 3.8% +/- 3.4%, respectively). As the endometrium proceeded from proliferative phase to luteal phase, the proportion of CD3+ CD8+ T cells in peripheral blood increased from 35.6% +/- 6.9% to 41.3% +/- 8.4% and CD3+ CD8- T cells decreased from 64.4% +/- 6.9% to 58.7% +/- 8.4%. The endometrial T cells expressed high levels of CD69 (84.1% +/- 18.9%) and DR (75.9% +/- 9.7%), but rarely expressed CD25 (7.0% +/- 5.4%) and CD71 (2.8% +/- 1.8%). The patterns of expression of these activation markers were similar in both proliferative and luteal phases. Our observations suggest that endometrial T lymphocytes are in a state of recent and persistent activation. Lymphocytes expressing the NK cell markers (CD56 or CD16) and CD8+ accounted for a significant proportion, suggesting that they may play important roles in local defense.

Adult↗

PubMed1995

The effect of hypercholesterolemia on the sodium inward currents in cardiac myocyte.

To determine whether chronic hypercholesterolemia affects sodium inward currents in cardiac myocytes, whole-cell clamp recordings were made in single cardiac myocytes isolated from normo- and hypercholesterolemic rabbits. Modification of the serum cholesterol was accomplished by feeding ten 3-month-old male New Zealand white rabbits with control diet (group I) and ten with 0.5% cholesterol-enriched diet (group II), for 3 months. The serum cholesterol levels of group II were much higher than those of group I (2042 +/- 231 v 82 +/- 9 mg/dl, P < 0.001). The cholesterol-ester and free cholesterol component of cardiac sarcolemma of group II were also significantly higher than those of group I (26.6 +/- 12.4 v 10.8 +/- 4.5 nmole/dl, P < 0.001, and 50.9 +/- 14.8 v 27.5 +/- 6.2 nmole/dl, P < 0.001, respectively). The cell capacitance of hyperlipidemic myocytes seemed larger than that of normolipidemic ones (157.4 +/- 6.4 pF v 103.6 +/- 3.0 pF, P < 0.05). However, the sodium current density on hypercholesterolemic ventricular sarcolemma was significantly lower than that of normolipidemic sarcolemma. This effect was associated with a leftward shift in the inactivation potential and a slowing of the time course of recovery. In conclusion, hypercholesterolemia has important effects on the sodium inward currents in ventricular myocytes, which may be due to a decrease in current density and an alteration in channel functional state.

Animals↗

PubMed1995

Effects of fish oil supplementation on atherosclerosis in different regions of the aorta of rabbits with diet-induced hypercholesterolaemia.

1. The effects of fish oil supplementation on atherosclerosis in different regions of the aorta in rabbits with diet-induced hypercholesterolaemia were studied. Control and experimental rabbits were fed a 1% cholesterol-enriched diet with or without 10% fish oil supplementation (seven in each group), and were killed after 2 weeks of feeding. The ascending, descending and abdominal aortas as well as the pulmonary artery were harvested for analyses of prostanoid production, malondialdehyde, superoxide dismutase activity and cholesterol levels. The tissues from the other seven rabbits of each group were obtained after 6 weeks of feeding for the identification of atherosclerotic lesions by a Sudan IV stain. 2. The cholesterol-fed rabbits had a significantly higher thromboxane B2 production, a lower 6-keto-prostaglandin1 alpha/thromboxane B2 ratio and a higher malondialdehyde level than the other two groups in the ascending and abdominal aortas as well as the pulmonary artery; this finding paralleled the severity of atherosclerotic lesions. These manifestations were most prominent in the ascending aorta. The fish oil-supplemented rabbits had the most beneficial aortic prostanoid production, attenuated lipid peroxidation and significantly suppressed atherosclerosis. 3. These results suggest that a high-cholesterol diet induces more atherosclerotic lesions, especially on the ascending aorta, in rabbits. A fish oil supplement favours prostanoid production and attenuates lipid peroxidation on all four regions of the great arteries, thus suppressing atherosclerosis in diet-induced hypercholesterolaemic rabbits.

Animals↗

PubMed1995

Clinical management of recurrent hepatocellular carcinoma.

OBJECTIVE: The aim of this study was to evaluate the long-term benefits of the aggressive treatments with resection or transarterial chemoembolization (TACE) for recurrent hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: Primary HCC is one of the most fatal malignancies in Taiwan. The result of resection for HCC remains unsatisfactory, primarily due to the high recurrence rate. To improve surgical results, recurrent HCC must be treated with aggressive resection or TACE. METHODS: The authors evaluated the results of repeated hepatic resection among 25 patients with recurrent HCC and of TACE among 12 patients with resectable recurrent HCC. The outcomes of an additional 64 patients with unresectable recurrent HCC were also evaluated. RESULTS: During the follow-up period from 2-112 months, 52% (13/25) of patients receiving repeat resection (group 1) were alive, whereas 42% (5/12) of patients receiving TACE (group 2) were alive. No perioperative deaths within 30 days after surgery occurred in the repeated resection group. The cumulative survival rates at 1, 2, 3, and 5 years after the first operation were 92%, 84%, 71.6%, and 65.1% in group 1 and 83.3%, 75%, 75%, and 22.5% in group 2. The survival rates at 6 months and at 1, 2, and 3 years after recurrence were 92%, 72%, 64%, and 44.8% in group 1 and 83.3%, 75%, 66.7%, and 48% in group 2. The survival of patients with unresectable recurrent HCC was much worse: 1-, 2-, 3-, and 5-year survival after surgery was 57.8%, 29.8%, 15.5%, and 0%; and 6-month and 1-, 2-, and 3-year survival after recurrence was 46.5%, 29.2%, 12.5% and 7.8%. CONCLUSIONS: More aggressive treatment with repeated hepatic resection can prolong survival time after recurrence of HCC in selected patients. However, TACE can also achieve good results although it is not thought of as curative.

Aged↗

PubMed1995

Immunoelectrophoretic differentiation of alpha-fetoprotein in disorders with elevated serum alpha-fetoprotein levels or during pregnancy.

Our study aims to make differential diagnosis by immunoelectrophoresis for some common conditions with elevated levels of serum alpha-fetoprotein (AFP). One hundred and nine cases with elevated AFP levels were included in this study: yolk sac tumor (n = 8), hepatocellular carcinoma (n = 26), gastric cancer (n = 12), chronic hepatitis (n = 27) and normal pregnancy (n = 36). Lectin agarose gel electrophoresis, antibody-affinity blotting, and immunoreaction were used to identify the specific patterns of AFP in the respective conditions. The results showed that there were three possible bands: L1, L2 and L3. Yolk sac tumor produced a prominent L2 band and a light L3 band. Hepatocellular carcinoma produced a prominent L1 band and a light L3 band. Gastric cancer produced only an L1 band. Chronic hepatitis had a light L1 band and a pronounced L3 band. In pregnancy, the AFP pattern is similar to that of hepatocellular carcinoma. Immunoelectrophoresis is a useful method facilitating the differentiation of AFP origins.

Biomarkers, Tumor↗

PubMed1995

Cyclins and autoimmunity: cyclin B1 gene expression and restriction fragment length polymorphism in lupus-prone mice.

Cyclin B1 is the major component of M-phase promoting factor that plays a major role in the G2/M transition of cell cycle. We examined the expression of cyclin B1 at the protein and mRNA levels in the thymus of 12-week-old autoimmune and normal mice. We found an abundance of cyclin B1 protein (58 kDa) in the thymus of lupus-prone MRL-lpr/lpr mice, whereas the level of this protein was negligible in other strains. The level of the predominant cyclin B1 mRNA (1.7 kb) species was not markedly different in these strains, suggesting post transcriptional modification of cyclin B1 in the thymus of MRL-lpr/lpr mice. Southern blot analysis of cyclin B1 gene showed multiple forms of cyclin B1-related sequences in various murine genomes. Flow cytometry showed a significantly higher level of cells in the G2/M phase and a significantly lower level in the S phase in thymocytes of MRL-lpr/lpr compared to that in normal BALB/c mice, indicating an alteration of cell cycle machinery in thymocytes of MRL-lpr/lpr mice. Taken together, these data show that an upregulation of cyclin B1 protein and accumulation of thymocytes at the G2/M phase in MRL-lpr/lpr mice might play an important role in the aberrant development of T cells in these mice.

Animals↗

PubMed1995

Correlation between tumor angiogenesis and metastasis in breast cancer.

New vessel formation (angiogenesis) plays an important role in the metastasis of cancer cells. To investigate the correlation between tumor angiogenesis and metastatic potential in breast cancer, the microvessel counts of tumor specimens from 81 women with primary infiltrating ductal carcinomas were examined. Histologic parameters (nodal status, tumor size and tumor grade) and hormone receptor status were also analyzed. We found that axillary node metastasis correlated significantly with the microvessel counts per 200x field and with tumor size, but not with age, tumor grade or hormone receptor status. Tumors without axillary node involvement had a lower microvessel count, irrespective of age, tumor size, tumor grade or hormone receptor status. Logistic regression demonstrated that the microvessel count provided the most important estimate of the relative risk of metastasis. These results suggest that, in invasive breast carcinoma, angiogenesis is closely related to metastatic potential.

Adult↗

PubMed1995

A clinicopathological study of idiopathic nephrotic syndrome in children.

This paper retrospectively examines the association of outcome with histological and clinical manifestations in 107 pediatric patients with idiopathic nephrotic syndrome (INS). At the time of renal biopsy, the patients were between 2 and 15 years of age. The interval from the onset of the disease to renal biopsy ranged from 1 to 156 months with a mean of 21 months. Continuous clinical follow-up was successfully conducted in 96 patients. The average duration of INS in these patients was 86.6 months (31 to 208 months). IgM deposition in the mesangium may play an important role in the pathogenesis of INS and our data showed that even in a minor glomerular abnormality (MCNS) subgroup, nearly half of the cases (42.9%) showed mesangial IgM deposition. However, the severity of hematuria, response to drug therapy with either steroids or cyclophosphamide, and the outcome, were not related to the presence or absence of IgM deposition, but were more closely associated with the type of histological category. The subgroup of patients with focal segmental glomerulosclerosis (FSGS) and diffuse mesangial proliferation (FSGS + DP) showed the most significant ultrastructural changes with positive mesangial IgM deposition (73.6%). The presence of IgM deposition in most of the patients in the subgroups with diffuse mesangial proliferative glomerulonephritis (DPGN) and FSGS + DP closely corresponded to the presence of electron-dense mesangial deposition. The FSGS + DP subgroup had a high incidence of denudation, vacuolization and detachment of podocytes, partial collapse of the glomerular basement membrane, and a very high incidence of resistance to steroid therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1995

Histomorphometric study in children with idiopathic nephrotic syndrome.

From 1981 to 1987, renal specimens obtained from 91 children with idiopathic nephrotic syndrome were categorized into 5 histologic subgroups, according to the WHO classification. We analyzed differences in the ratios of the size of the mesangial stalks and attached capillary, including the Bowman's space between the capillary tufts (E), mesangial matrix (Mx), and approximate capillary lumens (E-Mx) to the whole glomerular area of these subgroups using the histomorphometer-IBAS. Focal segmental glomerulosclerosis with diffuse mesangial proliferation (FSGS + DP) had the largest matrix area (Mx/G > 0.5), and smallest capillary lumen size (E/G-Mx/G) (0.3474 +/- 0.0702). On the contrary, FSGS with minimal change (FSGS + MC) had the smallest mesangial matrix (Mx/G), 0.2834 +/- 0.07726, but preserved a larger capillary lumen (0.427 +/- 0.1215). The approximate size of capillary lumens, from the smallest to the largest, was in the following order: FSGS + DP, diffuse mesangial proliferative glomerulonephritis (DPGN), focal segmental proliferative glomerulonephritis (FSPGN), FSGS + MC and minimal change nephrotic syndrome (MCNS). The ratio of the total number of mesangial cells to the area of the whole glomerulus (MCN/G) derived from the light microscopic examination was parallel to the value of Mx/G obtained by the histomorphometric technique. In summary, we introduced the histomorphometric technique using the histomorphometer-IBAS for quantitative measurement of various areas in the glomeruli. The data derived from the system is compatible with those obtained by experienced nephrologists, suggesting that the histomorphometric technique is helpful in histopathology. It is hoped that this new methodology will be used more extensively in the near future.

Adolescent↗