Etidronate (EHDP) Inhibits Osteoclastic-Bone Resorption, Promotes Apoptosis and Disrupts Actin Rings in Isolate-Mature Osteoclasts

Bisphosphonates, therapeutic reagents against tumoral bone diseases (Paget's disease or osteoporosis), are potent inhibitors of bone resorption. The mechanisms by which they directly act on mature osteoclasts remain unclear. Using a recently developed technique for isolation of highly purified mammalian mature osteoclasts, we demonstrated that etidronate [ethane-1-hydroxy-1,1-diphosphonate (EHDP), 1-hydroxy-1,1-ethylidenebisphosphonate], inhibited directly osteoclastic bone-resorbing activity by pit assay. In addition, EHDP also directly induced apoptosis and disrupted actin rings in osteoclasts. The data support previous data on non-purified osteoclasts and results in vivo. Received: 26 June 1997 / Accepted: 27 July 1998     

Renal cell carcinoma recurrence in the mediastinum lymph node 19 years after nephrectomy: a case report]

A 62-year-old male, who had undergone right nephrectomy to treat renal cancer 19 years earlier, was recently referred to our hospital to receive a detailed examination and treatment of mediastinal lymph node swelling. Biopsy of the swollen lymph nodes allowed a diagnosis of renal cell carcinoma (alveolar type, clear cell subtype, GI) to be made. The pathological features of his tumor were consistent with those of the renal tumor resected 19 years previously. Because there was a high probability of further growth of the swollen mediastinal lymph nodes and consequent high probability of compression of the superior vena cava, we performed mediastinal lymph node excision. Immediately after surgery, prophylactic interferon therapy was started. To date, five cases (including the present case) in which renal tumors recurred more than 15 years after surgical treatment have been reported in Japan.     

Antegrade internal ureteral stenting: a technical refinement

A pliable, easy to place, double pigtail, internal ureteral stent made of elastomeric polyurethane is described. The tapered distal pigtail end minimizes bladder irritation and the combination of a pusher and absorbable suture enables optimal placement of the proximal pigtail end in the renal pelvis. Ten stents used in eight patients remained functional without bladder irritation for a mean period of 8 months (range, 2-14 months).     

Recognition of carbohydrate antigen epitopes by sperm-immobilizing antibodies in sera of infertile women.

STUDY OBJECTIVE: To study carbohydrate natures in the antigen epitopes corresponding to sperm-immobilizing antibodies in infertile women. DESIGN: Antibody absorption with human sperm and seminal plasma before and after treatments with trifluoromethanesulfonic acid or sodium metaperiodate. PATIENTS: Thirty-three patients who showed a positive sperm immobilization test provided their sera for the experiment. RESULTS: In 25 patients' sera whose sperm-immobilizing antibodies were absorbed with human seminal plasma, the antibody absorbing capabilities were completely abolished by deglycosylation treatment with trifluoromethanesulfonic acid. The sperm-immobilizing antibodies in 4 patients' sera were absorbed out with sperm membrane fraction before the treatment but not after the treatment with trifluoromethanesulfonic acid. In some patients' sera, the antibody-absorbing capabilities of ejaculated sperm were markedly reduced by sodium metaperiodate treatment. CONCLUSION: The majority of sperm-immobilizing antibodies in infertile patients might be generated to carbohydrate structures of the sperm-coating antigens or sperm membrane antigens.     

Establishment and characterization of a human hybridoma secreting monoclonal antibody with high titers of sperm immobilizing and agglutinating activities against human seminal plasma

Peripheral blood lymphocytes isolated from an infertile woman possessing strong sperm immobilizing and agglutinating antibodies were stimulated by culturing with poke-weed mitogen (PWM) and spermatozoa from a healthy donor for 5 days. The stimulated lymphocytes were fused with mouse myeloma NS-1 by PEG-1000. Fused growing hybrid cells were observed in 58 of 96 wells, and 22 of these showed the production of human immunoglobulin. Among the 22, one hybridoma clone (H6-3C4) was found to produce human IgM (lambda) with strong sperm immobilizing and agglutinating activities. The supernatant from the culture medium contained approximately 1.5 microgram IgM/ml and the antibody titers were 5000 SI50 units on sperm immobilization and 1:1600 dilutions on sperm agglutination. The hybridoma H6-3C4 has continuously produced high titers of antibody exhibiting sperm immobilizing and agglutinating activities over 8 months and contains chromosomes of acrocentric type from mouse and metacentric type from human. The monoclonal antibody (Mab) H6-3C4 reacted specifically to human seminal plasma, ejaculated spermatozoa and male accessory gland but not to testis, any other somatic tissues, or secreted fluids tested. Immunofluorescence staining indicated that the antigen corresponding to Mab H6-3C4 was present over the surface of ejaculated spermatozoa. The binding of Mab H6-3C4 to human spermatozoa was blocked by the serum of the patient from whom the lymphocytes were obtained for cell fusion.     

Alagille's syndrome associated with cystic renal disease

Although renal abnormalities have been described in children with Alagille's syndrome, cystic kidney disease has not often been documented, and then usually only at necropsy. Three children with Alagille's syndrome are described, in two of whom a unilateral multicystic dysplastic kidney was detected by prenatal ultrasound; in the other, a solitary cortical cyst was found later in childhood. All have normal renal function, growth, and liver synthetic function but continue to have clinical and biochemical signs of cholestasis. These cases show that unilateral cystic kidney disease with or without renal dysplasia may be associated with Alagille's syndrome, that the clinical course is not necessarily unfavourable, and that Alagille's syndrome should be included in the differential diagnosis of cystic kidney disorders associated with cholestatic liver disease. Patients with Alagille's syndrome should be evaluated by renal ultrasound.