Hajime Nakahama

Prostate Cancer-Induced Oncogenic Hypophosphatemic Osteomalacia

A 65-year-old male with prostate carcinoma showed mild hypocalcemia of 7.9 mg/dl, marked hypophosphatemia of 1.7 mg/dl, hyperphosphaturia (tubular reabsorption of phosphorus 43% and tubular threshold for phosphorus of 0.6 mg/dl), low serum 1,25 (OH)2D level of less than 5 pg/ml and osteomalacia indicated by a marked increase of relative osteoid volume and fractional formation rate in the undecalcified section. Oncogenic osteomalacia due to prostatic carcinoma with suppression of 1,25 (OH)2D production and phosphaturia was suggested.

Ulinastatin ameliorates acute ischemic renal injury in rats

Effects of ulinastatin (a Kunitz-type proteinase inhibitor) administration was examined in a model of acute ischemic renal injury induced by bilateral renal artery occlusion in rats. Compared with rats administered vehicle, rats administered ulinastatin (150,000 U/kg body weight) intravenously 30 min preischemia had significantly lower serum creatinine and blood urea nitrogen, and much less injury evident by examination of kidney histologies over the course of 48 h postreperfusion. We conclude that ulinastatin exerts a protective effect against ischemic renal injury.

CYFRA 21-1 and ProGRP, tumor markers of lung cancer, are elevated in chronic renal failure patients.

Abstract Serum levels of CYFRA 21‐1(cytokeratin‐19 fragment) and ProGRP (pro‐gastrin‐releasing peptide), the new prognostic markers of lung cancer, were measured by ELISA (enzyme‐linked immunoadsorbent assay) in 27 (for CYFRA 21‐1; male 13, female 14; age 54 ± 17 years) or 22 (for ProGRP; male 9, female 13; age 59 ± 18 years) patients with various serum creatinine levels, 42 haemodialysis (HD) patients (male 24, female 18; age 59 ± 14 years) and 30 continuous ambulatory peritoneal dialysis (CAPD) patients (male 18, female 12; age 48 ± 9 years). All the patients were without clinical and radiological signs of lung cancer. Positive correlations were found between serum creatinine and serum CYFRA 21‐1 and ProGRP levels. Serum levels of CYFRA 21‐1 were above the cutoff limit (3.5 ng/mL) in 57% of HD patients (mean 4.07 ± 1.56 ng/mL) and in 73% of CAPD patients (mean 4.87 ± 1.56 ng/mL). Serum levels of ProGRP were above the cutoff limit (46.0 pg/mL) in 90% of HD patients (mean 107.0 ± 59.4 pg/mL) and in 93% of CAPD patients (mean 112.4 ± 4.5 pg/mL). Our data indicate that evaluation of renal function is essential when the measurement of these tumor markers is to be applied as one of the diagnostic tools of lung cancer.

Renin-Angiotensin System Component Gene Polymorphism in Japanese Bronchial Asthma Patients

The influence of renin-angiotensin system (RAS) component gene polymorphism in the pathogenesis of bronchial asthma was investigated in an association study involving 119 bronchial asthma patients and 208 control subjects. The selected RAS polymorphisms were angiotensinogen (Agt) T235/M235 and angiotensin I-converting enzyme (ACE) insertion/deletion (I/D). The control allelic frequencies of the Agt T235/M235 (0.84/0.16) and ACE I/D (0.63/0.37) in this study were similar to the previous reports in Japanese normal population. The allelic frequencies of the Agt T235/M235 (0.84/0.16) and ACE I/D (0.65/ 0.35) among the asthma patients were not significantly different from those among the control subjects. There was no association between severity of bronchial asthma and the selected RAS component gene polymorphism. From these data, we conclude that in the Japanese population, the RAS component gene polymorphism is not associated with increased risk for bronchial asthma.

Elevated Serum Pepsinogens in Chronic Renal Failure Patients

Human pepsinogens, the precursors of pepsin, originating from the stomach mucosa, are classified into two biochemically distinct groups, namely pepsinogen I (PG I) and pepsinogen II (PG II). We studied the serum levels of PG I and II in 51 normal volunteers, 23 chronic glomerulonephritis patients, 21 continuous ambulatory peritoneal dialysis (CAPD) patients and 40 hemodialysis patients. Serum pepsinogen levels were measured with a competitive binding double antibody radioimmunoassay. In the group of chronic glomerulonephritis patients, a positive correlation between the serum creatinine and the pepsinogen levels were found. The serum pepsinogen levels were remarkably elevated in CAPD and hemodialysis patients. The median levels of post-hemodialysis PG I (265.4 +/- 165.2 ng/ml) and PG II (41.7 +/- 38.0 ng/ml) were significantly higher than prehemodialysis values (PG I 207.4 +/- 127.5 ng/ml, PG II 29.0 +/- 16.6 ng/ml). Pepsinogen release by isolated gastric glands of guinea pigs was suppressed by guanidinosuccinic acid and was facilitated by calcium. The data suggest that both removal of guanidinosuccinic acid and infusion of calcium during hemodialysis contribute to the raised serum levels of these pepsinogens after hemodialysis.

Effect of a Novel Immunosuppressant, FK 506, on Autoimmune Glomerulonephritis in Brown Norway Rats

Mercuric-chloride (HgCl2) induces a lymphoproliferative disorder and autoimmune glomerulonephritis in Brown Norway rats. The effects of a new immunosuppressant FK 506 on this model of glomerulonephritis were studied. Brown Norway rats were treated with HgCl2 according to a standard protocol (HgCl2 1 mg/kg s.c. 3 times/ week). Rats developed proteinuria at day 7, which reached a plateau level at day 14. On day 14, renal histology showed prominent mesangial cellular proliferation and the expansion of mesangial matrix. Electron microscopic study showed the effacement of visceral epithelial foot processes and the microvillous transformation of the visceral epithelium. Immunofluorescence study showed a strong linear staining for IgG and the adhesion molecule ICAM-1 in all glomeruli. Coadministration of FK 506 (1 mg/kg s.c. daily) prevented the appearance of proteinuria at day 14 (621.4 ± 30.5 vs. 2.2 ± 2.7 mg/day) and the morphological lesions. These findings suggest that FK 506 could be useful for the therapy of certain types of human glomerulonephritis.

Effect of FK 506 in the treatment of autoimmune glomerulonephritis in brown Norway rats

Mercuric chloride (HgCl2) induces a lymphoproliferative disorder and autoimmune glomerulonephritis in Brown Norway (BN) rats. The effects of a new immunosuppressant, FK 506, on this model of glomerulonephritis were studied. BN rats were treated with HgCl2 according to a standard protocol (HgCl2 1 mg/kg s.c. 3 times/week). FK 506 was inoculated subcutaneously daily from day 15 to day 28. Animals were divided into 4 groups: group 1, rats were treated with normal saline alone and sacrificed on day 28; group 2, rats were treated with HgCl2 alone and sacrificed on day 14; group 3, rats were treated with HgCl2 alone and sacrificed on day 28, and group 4, rats were treated with HgCl2 and FK 506 (from day 15 to day 28) and sacrificed on day 28. Rats developed proteinuria by day 7, which reached a plateau level by day 14. On day 14, renal histology showed prominent mesangial cellular proliferation and the expansion of mesangial matrix. Electron microscopic study showed the effacement of visceral epithelial foot processes and the microvillous transformation of the visceral epithelium. Immunofluorescence study showed strong linear staining for IgG and the adhesion molecule ICAM-1 in all glomeruli. Treatment with FK 506 (1 mg/kg s.c. daily) resulted in a remarkable reduction in proteinuria on day 28 (493.5 ± 48.3 vs. 24.4 ± 13.5 mg/day) and an improvement in the morphological lesions. These findings suggest that FK 506 could be useful in the treatment of some human glomerulonephritides.

Two cases of eosinophilic gastroenteritis associated with analgesic‐induced bronchial asthma

Abstract Two patients (one male and one female) with bronchial asthma were diagnosed as having eosinophilic gastroenteritis (EG). The condition was revealed by biopsies through fibrescopic endoscopy. According to the Klein classification, they had mucosal disease. The symptoms were abdominal pain and nausea. The symptoms subsided with corticosteroid administration in one patient and with palliative treatment in the other patient. It was suggested that fibrescopic endoscopy biopsy is needed to identify coexisting EG if a bronchial asthma patient complains of severe gastrointestinal symptoms.

Hypercalcemia Reduces Renal Medullary Content of Organic Osmolytes

Hypercalcemia is often associated with a urinary concentration defect. During antidiuresis, organic osmolytes [sorbitol, myo-inositol, taurine, and glycerophosphorylcholine (GPC)] accumulate in the renal inner medulla and are essential for urinary concentration. To clarify the relationship between organic osmolytes and urinary concentration defect in hypercalcemia, examination was made of the effects of hypercalcemia on renal medullary osmolytes content. Rats were put in a state of hypercalcemia by a calcium-rich diet supplemented with CaCO3 (2.5%/wt) and daily s.c. injection of 1.25(OH)2VitD3 (1.6 micrograms/kg). They were killed on days 7 and 14. Hypercalcemia induced a urinary concentration defect. Myo-inositol, sorbitol, and GPC contents in the renal medulla were significantly reduced. Aldose reductase activity decreased significantly. Hypercalcemia would thus appear to directly affect renal medullary content of organic osmolytes, thereby modifying renal concentration ability.

Acute glomerulonephritis in an 85-year-old woman

Postinfectious acute glomerulonephritis revealed at biopsy is extremely rare in the elderly. We present an 85-year-old woman who developed symptoms typical of acute nephritis one week following an upper respiratory tract infection. The renal biopsy showed typical postinfectious endocapillary proliferative glomerulonephritis.