Does H2-receptor antagonist alter the renal function of cyclosporine-treated kidney grafts?

Histamine-type 2 antagonists (H₂-blockers) as represented by cimentidine have been shown to adversely affect renal allograft function, particularly when coadministered with cyclosporine, currently a major immunosuppressant. To determine whether or not a newer and more powerful H₂-blocker, famotidine, would produce similar adverse effects, we assessed seven cyclosporine-treated renal allograft recipients with regard to changes in their renal function on or off the H₂-blocker over a one-week period. Neither the administration nor withdrawal of famotidine (20–40 mg/day) resulted in any significant changes in serum creatine, BUN, urine output or cyclosporine trough levels, suggesting that famotidine can be safely administered as an H₂-blocker to cyclosporine-treated renal allograft recipients.     

Impact of lymph node metastasis on survival in patients with pathological T1 carcinoma of the ampulla of vater

To determine the prognostic factors for patients with pathological T1 (pT1) carcinoma of the ampulla of Vater, 36 consecutive patients with carcinoma of the ampulla of Vater who underwent surgery were retrospectively analyzed in terms of clinicopathological features. The overall 5-year Kaplan-Meier survival in all patients was 50.2%, and the median survival of all patients was 64.0 months. Factors favorably influencing a long-term outcome were the absence of lymph node metastasis (P<0.0001), the absence of ulcer formation of the tumor (P=0.0062), and the absence of tumor invasion into the duodenum (P = 0.0025) and the pancreas (P=0.0098). In a multivariate analysis, lymph node metastasis was the only predictor of survival (P=0.0023). In the pT1 stage patients, 20% of the patients had lymph node metastasis, and their survival was statistically poor compared to the pT1 patients without lymph node metastasis (P=0.017). As for survival after the operation, there was no significant difference between pancreatoduodenectomy and pylorus-preserving pancreatoduodenectomy.     

The effects of high dose of parathyroid hormone on fetal osteoclasts and their precursors in vivo: An ultrastructural-cytochemical study

Background: It is not well known how the immediate precursors of osteoclast develop into osteoclasts in the fetus. This ultrastructural-cytochemical study was designed to clarify the formation process of the osteoclasts and their increased activities in the fetal mouse limb buds after administration of high dose parathyroid hormone (PTH). Methods: Twenty-four or forty-eight hours after the high doses of PTH were injected into amniotic fluid of the pregnant C₃H mice, the femoral limb buds of embryos were dissected out. Tartrate-resistant acid phosphatase (TRAP) reactions were performed while preparing specimens for electron microscopy. Results: Both control and PTH-given preosteoclasts and osteoclasts exhibited TRAP-positivities in dense bodies and vesicles. As effects of PTH, a binucleated preosteoclast of tandem fashion was observed. More osteoclastic hyperactivities were observed in the diaphyseal bone marrow. An osteoclast with a large cytoplasm exhibited two sets of clear zones and ruffled borders. Some osteoclasts demonstrated prominent amoeboid figures, while other osteoclasts developed large cytoplasmic vacuoles, which contained pieces of calcified chondroid bars. Conclusions: Our results revealed the progression of maturation from young preosteoclasts to osteoclasts. An existence of a peculiar binucleated preosteoclasts suggested one of the processes for multinucleation of the osteoclast. Quite remarkable osteoclastic hyperactivities were obviously the effects of high dose PTH. Our results also indicated the endophagocytic ability of the osteoclast. How PTH affected the osteoclasts and their precursors in the diaphyseal bone marrow can be speculated. © 1995 Wiley-Liss, Inc.     

A role for the P1 anchor residue in the thermal stability of MHC class II molecule I-Ab

The thermal stability of the murine MHC class II molecule, I-A(b), in complex with invariant chain-derived peptide (CLIP) and an antigenic peptide derived from the alpha subunit of the I-E molecule (Ealpha) at mildly acidic and neutral pH were analyzed using circular dichroism (CD). The stability of I-A(b)-CLIP was increased by a single amino acid substitution in the P1 anchor residue, from Met of CLIP to Phe of Ealpha, similar, in this respect, to I-A(b)-Ealpha. This indicates that hydrophobic interaction in the P1 pocket is critical and plays a primary role in the stability of the complex. The structural models of I-A(b)-peptides based on the crystal structure of I-A(d) might explain the increased stability and the preference for hydrophobic residues in this site. Taken together with what is known of the resident stability at a mildly acidic pH, the difference in stability would closely correlate with the ability of MHC class II to exchange peptides from CLIP to antigenic peptides in the endosome.     

Evidence of allosteric conformational changes in the antibody constant region upon antigen binding

We have addressed the question of whether antigen binding induces a conformational change in the heavy chain constant (C(H)) domain of antibodies using staphylococcal protein A or streptococcal protein G as probes, since these proteins are known to bind to IgG domains such as C(H)1 and C(H)2-C(H)3 domains. Biosensor assays on interactions between these proteins and mouse IgG specific to (4-hydroxy-3-nitrophenyl)acetyl (NP) or their enzymatic fragments conducted in the presence or absence of the hapten, NP-epsilon-aminocaproic acid (NP-Cap), showed that the binding of IgG to these proteins was inhibited by the binding of NP-Cap. The results of isothermal titration calorimetry also revealed that the association constant for the interaction of protein A with IgG2b decreased by the addition of NP-Cap. These results suggested that antigen binding induced conformational changes in binding sites for protein G or protein A located at C(H)1 and C(H)2-C(H)3 domains, respectively.     

Responsiveness of the ANP providing system to volume load in conscious dogs

We examined in detail changes in arterial plasma ANP concentration in response to volume load in conscious dogs. In a 5-min volume load experiment, 18 ml/kg of isosmotic and isooncotic 3% Dextran 40 in saline was infused over a period of 5 min. Mean left atrial pressure (MLAP) increased transiently by 7.6±0.9 mm Hg. Plasma ANP level (P-ANP) did not significantly increase. Assayed P-ANP levels were corrected for hemodilution. Corrected P-ANP (C-ANP) significantly increased from 206±17 to 348±34 pg/ml. However, the level of C-ANP did not reach a steady state. No significant linear correlation was found between increases in MLAP and normalized C-ANP. In a 45-min volume load experiment, the elevated level of MLAP caused by the 5-min volume load was maintained for 40 min by supplemental infusion. C-ANP significantly increased from 196±18 pg/ml to 435±73 ng/ml. The level of C-ANP reached a steady state. A close linear correlation was observed between increases in MLAP and normalized C-ANP. However, the peak time of C-ANP lagged 10 min behind MLAP. These results indicate that it takes 10 min for P-ANP to reach a steady state in fully responding to a volume load, and that the long-term volume load is a prerequisite to the response of the ANP providing system.     

Infantile hemangioendothelioma of the thymus with massive pleural effusion and Kasabach-Merritt syndrome: Histopathological, flow cytometrical analysis of the tumor

Infantile hemangioendothelioma of the thymus is a rare disease. We describe a patient who developed a large anterior mediastinal mass, severe thrombocytopenia and massive pleural effusion at 1 month of age. Glucocorticosteroid and irradiation therapy had no effect on either the tumor size or clinical symptoms and the tumor was resected subtotally. Three months after the subtotal resection, the remaining tumor had almost disappeared and the symptoms had resolved. The patient has now been well for 1 year after surgery without evidence of recurrence. The tumor tissue was characterized by prominent vascular endothelial proliferation intermixed with a normal thymic structure, producing a picture consistent with that of an infantile hemangioendothelioma in the thymus, lmmunohistochemically, the tumor cells showed positive staining for vimentin, factor VIII and CD34. The DNA stemline and proliferative activity were examined by flow cytometry, which revealed a diploid stemline with a low growth fraction. DNA content and cell cycle analyses of the tumor tissue may be useful for predicting the biological behavior of the tumor.