Two cases of congenital nephrotic syndrome

The clinical course and renal histological changes in two patients with congenital nephrotic syndrome are presented. Both patients developed edema and proteinuria at 2 days of age. Steroids and immunosuppressive drugs were not used in either patient. One patient showed gradual disappearance of nephrotic syndrome and proteinuria during the 16-month follow-up. In the other patient, the nephrotic state persisted and nephrotic complications necessitated bilateral nephrectomy when she was 12 months old. Renal biopsy showed minimal change lesions in one patient, while the nephrectomized kidneys showed mild mesangial proliferation and matrix increase in the glomeruli. No tubular dilatation or microcysts were observed in either patient.     

Prenatal developmental toxicity studies of 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (p, p'-DDT) in rats and rabbits

ABSTRACT  The studies were conducted in rats and rabbits to elucidate the potential developmental toxicity of p, p '-DDT in general accordance with the improved Japanese MAFF guidelines (12-Nousan-No. 8147,2–1–18, 2000). p, p '-DDT suspended in 1% aqueous solution of CMC was administered orally to pregnant Jcl:SD rats on gestational days (GD) 6–19 at a dose of 0,5, 25, or 100 mg/kg/day and to pregnant KbI: JW rabbits on GD 6–27 at a dose of 0,5,20, or 80 mg/kg/day. Maternal animals were killed on the day after the last day of administration for morphological examination of their fetuses with special attention to the reproductive organs.
Adverse effects on maternal animals were found only at the highest dose in both species; i.e. , clonic convulsion (2/24 in rats, 5/22 in rabbits), mortality (1/24 in rats), abortion or premature delivery (4/22 in rabbits), and reduced body weight gains and food consumption. However, the control and treated groups showed comparable values for the numbers of corpora lutea and implants, percent preimplantation losses, number of live fetuses, percent resorptions and fetal deaths, sex ratio, fetal body weights, and placental weights in both species, and anogenital distance and testicular histology in rats. Although fetal examination revealed slightly increased incidence of 27 presacral vertebrae in the highest dose group in rats, there was no treatment-related increase in the incidence of malformations in any of the species.
Based on these results, it is concluded that p, p '-DDT causes no malformations, including male reproductive organ abnormalities, in either rats or rabbits, although it results in an increased incidence of skeletal variations in rats at a maternally toxic dose.     

Elevation of Anti-cytokeratin 19 Antibody in Sera of the Patients With Idiopathic Pulmonary Fibrosis and Pulmonary Fibrosis Associated With Collagen Vascular Disorders

It has been suggested that cytokeratin 19 is expressed in regenerated bronchoepithelial cells in patients with pulmonary fibrosis, and serum cytokeratin 19 fragment is elevated in patients with pulmonary fibrosis. We hypothesized that serum antibodies to cytokeratin 19 may be formed in patients with pulmonary fibrosis. To prove the existence of anti-cytokeratin 19 antibodies in patients' sera, human recombinant cytokeratin 19 was stained with patients' sera by a Western immunoblot. Then, we tried to establish an enzyme-linked immunosorbent assay to quantitate anti-cytokeratin 19 antibody in the sera of patients with idiopathic pulmonary fibrosis (IPF) and pulmonary fibrosis associated with collagen vascular disorders (PF-CVD). We demonstrated the anti-cytokeratin 19 antibody in patient' sera by a Western immunoblot. In patients with IPF and PF-CVD, significantly high anti-cytokeratin 19 antibody was demonstrated compared with normal volunteers, patients with chronic bronchitis, and patients with pneumonia. These results suggest that anti-cytokeratin 19 antibody may have played a role in the process of lung injury in pulmonary fibrosis. Accepted for publication: 27 May 1999     

Comparison of growth during continuous ambulatory peritoneal dialysis and renal transplantation using conventional immunosuppressive drugs in children.

OBJECTIVE: Growth during continuous ambulatory peritoneal dialysis (CAPD) and after renal transplantation (Tx) was assessed in children under the age of 12 years. DESIGN: Growth was assessed by calculating the standard deviation score for height of normal children of the same age and gender. PATIENTS: Twenty-one patients undergoing CAPD and 13 patients who had received renal Tx at Kitasato University Hospital. RESULTS: Overall growth in those children undergoing CAPD and after renal Tx was not good, but growth during CAPD seemed to be slightly better than after renal Tx using conventional immunosuppressive drugs. Only young children who had started CAPD or received renal Tx before the age of 5 years with functioning graft showed catch-up growth, but the final height of these children may still be smaller than normal. CONCLUSION: Growth in children with end-stage renal disease is poor but growth during CAPD seems to be slightly better than after renal Tx using conventional immunosuppressive drugs.     

A correlative electrophysiologic study of nerve fiber involvement in carpal tunnel syndrome using current perception thresholds.

OBJECTIVE: To relate clinical severity of idiopathic carpal tunnel syndrome (CTS) to current perception threshold (CPT). METHODS: Subjects were 51 patients with CTS (involving 51 hands), and 50 healthy control subjects (50 hands). Involved hands were grouped into three clinical grades (mild, moderate, severe). Using a neurometer (Neurotron, Baltimore, MD), we investigated the relationship between clinical grade and CPT abnormalities. RESULTS: In the mild CTS group, most hands showed CPT abnormalities only at 2000 Hz stimulation. The moderate group included a higher percentage of hands showing abnormalities at both 2000 and 250 Hz stimulation increased. The severe group included the highest percentage of hands with abnormal values at all frequencies tested. CONCLUSIONS: CPT showed abnormalities appear progressively from 'higher to lower' frequency stimulations relative to the increasing severity of CTS. SIGNIFICANCE: Sensory nerve fiber dysfunction apparently begins in larger fibers, extending stepwise to smaller fibers as the clinical grade of CTS progresses.     

Comparison of surgical therapy and combined irradiation in rectal cancer--second report. Effect of irradiation and ACNU on the tumor]

As part of a joint study on preoperative radiotherapy for developing an optimal mode of rectal cancer therapy, ACNU sensitization was studied in a total of 120 cases, with the cooperation of 48 facilities participating nationwide. The following results were obtained. Improvement in depth of invasion was more distinct in the combination preoperative therapy-ACNU group than in the preoperative radiotherapy group, with no other significant differences between the two. This finding suggests that dose and administration method could be improved. White blood cells and platelets were reduced in some cases of the ACNU combination group, but these reductions were not serious enough to impede surgical procedures. In addition, no significant difference in complications was noted between the two.     

Interference by adrenaline with chondrogenic differentiation through suppression of gene transactivation mediated by Sox9 family members

In contrast to osteoblasts, little attention has been paid to the functional expression of adrenergic signaling machineries in chondrocytes. Expression of mRNA was for the first time demonstrated for different adrenergic receptor (AdR) subtypes in chondrogenic ATDC5 cells and mouse metatarsals isolated before vascularization in culture, but not for other molecules related to adrenergic signaling. In neonatal mouse tibial sections, β₂AdR and α_2aAdR mRNA expression was found in chondrocytes at different developmental stages by in situ hybridization. Exposure to adrenaline significantly suppressed expression of several maturation markers through the cAMP/protein kinase A pathway activated by β₂AdR without affecting cellular proliferation in both cultured ATDC5 cells and metatarsals. Adrenaline also significantly inhibited gene transactivation by sry-type HMG box 9 (Sox9) family members essential for chondrogenic differentiation in a manner prevented by the general βAdR antagonist propranolol, with a concomitant significant decrease in the levels of Sox6 mRNA and corresponding protein, in ATDC5 cells and primary cultured mouse costal chondrocytes. Systemic administration of propranolol significantly promoted the increased expression of mRNA for collagen I and collagen X, but not for collagen II, in callus of fractured femur in mice. These results suggest that adrenaline may interfere with chondrogenic differentiation through downregulation of Sox6 expression for subsequent suppression of gene transactivation mediated by Sox9 family members after activation of β₂AdR expressed by chondrocytes.     

Adhesion Molecules on Murine Lymphokine-activated Killer Cells Responsible for Target Cell Killing: A Role of CD2

Lymphokine-activated killer (LAK) cells were induced from C57BL/6 mouse spleen cells and the effects of culture time on the expression of cell surface phenotypes and cytotoxic activity of LAK cells were determined. The expression of CD2 remarkably decreased after culture of LAK cells for 30 days, while LFA-1, a principal adhesion molecule in LAK cells, and CD3 were not changed by the culture. LAK cells cultured for 90 days completely lost CD2. In accordance with the decrease of CD2, the cytotoxic activity of LAK cells declined but a certain leven was retained even after the complete loss of CD2. The established LAK cell clones were also strongly positive for the expression of LFA-1 but negative for CD2. When the LAK cell clones were transfected with the CD2 cDNA, they started to express CD2 on their cell surface and to show greater binding ability and stronger cytotoxicity to target tumor cells. These results indicated that CD2 plays a role as an adhesion molecule responsible for target cell killing in murine LAK cells.     

Fenestration of the extracranial internal carotid artery: report of two cases]

Fenestration of the internal carotid artery (ICA) is extremely rare on clinical settings. Six cases of fenestration in intracranial and 8 in extracracranial ICA have ever been reported in literature. Authors describe two cases of fenestration at the extracranial ICA that were initially suspected of the dissection of ICA on MRA/I. Both angiography and CT angiography (CTA) disclosed the fenestration, which located at C2 vertebral levels. To confirm the fenestration at extracranial ICA is important in such an occasion that mimic the dissection of ICA, especially in patients who complain of cervical pain, mass and other related symptoms. Differences in the fenestration, the dissection and atherosclerosis on imaging, were reviewed and discussed.     

Phase 1 study of tazemetostat in Japanese patients with relapsed or refractory B-cell lymphoma

BackgroundTazemetostat is a selective and orally available inhibitor of enhancer of zeste homolog 2 (EZH2), a histone methyltransferase and epigenetic regulator of cellular differentiation programs. We carried out a phase I study of tazemetostat in Japanese patients with relapsed or refractory B‐cell non‐Hodgkin‐type lymphoma (B‐NHL) to evaluate its tolerability, safety, pharmacokinetics, and preliminary antitumor activity.MethodsTazemetostat was given orally at a single dose of 800 mg on the first day and 800 mg twice daily (BID: total 1600 mg/d) on following days in a 28‐day/cycle manner. Tazemetostat dose‐limiting toxicity (DLT) was evaluated up to the end of the first treatment cycle. Archival tumor tissues were analyzed for hotspot EZH2 mutations.ResultsAs of 15 January 2018, seven patients (four follicular lymphoma [FL] and three diffuse large B‐cell lymphoma [DLBCL]) were enrolled. The median age was 73 (range, 59‐85) years, and the median number of prior chemotherapy regimens was three (range, one to five). No DLT was observed (one patient was not evaluable due to early disease progression). The common treatment‐related adverse events (AEs) were thrombocytopenia and dysgeusia (three patients each; 42.9%). No treatment‐related serious AEs were observed. The objective response rate was 57% (4/7 patients), including responses in three of four patients with FL and one of three patients with DLBCL. An EZH2 mutation was detected in one patient with FL responding to treatment.ConclusionsTazemetostat at 800 mg BID showed an acceptable safety profile and promising antitumor activity in Japanese patients with relapsed or refractory B‐NHL.