Metalloproteinase activity is present in rat urine and derived from the renal cortex

Summary: Matrix metalloproteinases (MP) are important candidates for the degradation of extracellular matrix, but the role of MP in the diseased kidney remains poorly understood. to examine the significance of urinary MP, we first investigated the characteristics of MP in normal rat urine and renal cortex, and then evaluated the urinary MP activity in anti-thymocyte induced glomerulonephritis (Thy.1 GN). Metalloproteinase activity was measured as the EDTA-inhibitable degradation of [³H] gelatin. the enzyme was purified from urine and the renal cortex homogenate in normal Wistar rats by using several chromatographic and gel filtration methods. Both materials contained the identical molecular weight (Mr 126 kDa by gel permeation method) of gelatin-degrading enzymes, the activity of which was inhibited by metal chelating agents and reactivated by ZnC1₂ but not by other proteinase inhibitors. Thy.1 GN was induced by intravenous injection of rabbit anti-thymocyte serum into rats, and daily urine was collected at sequential time points. Urinary MP activity was markedly reduced soon after the serum injection, and returned to the control level in 9 weeks. Conversely, urinary MP-inhibitor activity (Mr 30 kDa), determined as inhibiting activity against MP derived from renal cortex, showed serial changes strikingly reflected as urinary MP activity. These findings suggested that rat urine contained the MP which seemed to be derived from the renal cortex, and the urinary MP activity was decreased in Thy.1 GN model, probably due to the presence of MP-inhibitor. As urinary MP is likely to reflect intra-renal MP, the evaluation of urinary MP may be useful to search metabolic alteration of extracellular matrix in the diseased kidney.     

The bronchodilating effect of pirenzepine]

The purpose of this study was to clarify the bronchodilating effect of pirenzepine (PZ) and to verify its mechanism. Ten asthmatic patients (6 men, 4 women: aged 20 to 65, 5 atopic 5 non-atopic) and ten non-asthmatic volunteers (8 men, 2 women: aged 25 to 60) were studied. Forced vital capacity (FVC), forced expiratory volume in one second (FEV1.0) and peak expiratory flow rate (PEFR) were measured after intravenous administration of 20 mg PZ. PZ increased FVC, FEV1.0 and PEFR significantly by 15%, 29% and 37% respectively in asthmatic patients (p less than 0.01). We also studied the effects of PZ on the contractile responses of tracheal smooth muscle to intra-arterially administered acetylcholine (ACh) and the electrical stimulation of the vagus nerves (VNS) using isometric technique in situ in 5 mongrel dogs. PZ significantly inhibited the contractile responses elicited with ACh at doses larger than 1000 micrograms/kg (p less than 0.01). PZ also significantly inhibited the contractile responses elicited by VNS at doses larger than 100 micrograms/kg (p less than 0.01). These data demonstrate that intravenously administered PZ dilates the airway in asthmatic patients and also suggest that the bronchodilating effect of PZ related to inhibition of the M1 and M3 muscarinic receptors.     

Hematopoietic recovery in a patient with acute lymphoblastic leukemia after an autologous marrow graft purged by combined hyperthermia and interferon in vitro.

We describe a patient with acute lymphoblastic leukemia (ALL) in whom hemopoiesis recovered after an autologous marrow graft purged by in vitro hyperthermia. A 17-year-old woman was diagnosed as having ALL in April 1985. After clinical remission was induced, marrow cells were harvested. The marrow cells were treated with hyperthermia at 42.0 degrees C for 1 h in the presence of alpha-interferon to eliminate residual leukemic cells, and then cryopreserved. In January 1990, during her fourth remission she was treated with busulfan and cyclophosphamide, and then received the thawed autologous marrow. Her hematopoietic recovery was prompt with normal trilineage regeneration without any life-threatening complications. She is in good health without evidence of a leukemic relapse at 6 months after autologous bone marrow transplantation. This case suggests that human multilineage progenitor cells retain self-renewal capacity in vivo even after treatment with heat and alpha-interferon in vitro followed by the freezing and thawing procedures.     

Techniques of nasotracheal intubation with the fiberoptic bronchoscope

When nasotracheal intubation with a fiberoptic bronchoscope is performed, the tube may be blocked in the nasal cavity or larynx, resulting in several complications including epistaxis and hoarseness. We review the causes and complications of tube blockage and discuss optimal techniques for minimizing it.     

Glomerular deposition of complex-forming glycoprotein heterogenous in charge (protein HC) in IgA nephropathy.

IgA immune complexes and polymeric IgA are presumed to play important roles in the development and progression of IgA nephropathy. Complex-forming glycoprotein heterogenous in charge (protein HC), being inhibitors of neutrophilic chemotaxis, has been reported as binding to IgA. As a working hypothesis it was assumed that complexes of protein HC and IgA are present in glomeruli from IgA nephropathy patient in stable state. In this study, we examined the glomerular deposition of protein HC in 40 patients with IgA nephropathy and in 10 patients with non-IgA nephropathy. We used highly specific antibody against protein HC, that does not cross-react with alpha-1-microglobulin. An immunofluorescent study revealed that 10 out of the 40 patients (25%) showed an intensity of 1+, 16 (40%) showed weak positive (+/-), and the other 14 (35%) were negative. There was no deposition of protein HC in non-IgA nephropathy patients. Histopathological analysis demonstrated a significant correlation between the intensity of glomerular-deposited protein HC and pathological activity (p less than 0.005); the latter was defined as having either crescents in more than 15% of the remaining glomeruli (excluding global sclerotic glomeruli), or segmental necrosis or sclerosis in more than 30% of the remaining glomeruli. A significant correlation was observed between pathological activity and the intensity of deposited IgG, IgA and IgM (p = 0.01), and lambda chain (p less than 0.005). Considering anti-inflammatory activity of protein HC, these results suggest that protein HC cannot protect sufficiently acute inflammation or tissue damages due to co-deposited IgG and IgM and/or other factors.(ABSTRACT TRUNCATED AT 250 WORDS)     

Suprasellar pituitary adenoma arising from the pars tuberalis: case report

A rare case of suprasellar pituitary adenoma arising from the pars tuberalis in a 53-year-old woman is presented. The tumor was located exclusively above the diaphragma sellae, and no invasion into the sella turcica was noted.     

Mechanism of methylmercury cytotoxicity

Although a large number of epidemiological, clinical, and pathological studies on methylmercury intoxication have been published, these investigations have not been able to elucidate the detailed mechanisms by which the metal alkyl causes a wide variety of biological dysfunctions. Thus, the cultured cells which are free from the influence of whole body complexities, such as absorption, distribution, metabolism, etc., which complicate the interpretation of in vivo experimental results, attract the attention of many scientists who are interested in clarifying the mode of toxic action of methylmercury. The aim of this article is to review the recent studies on the toxicity of methylmercury at the cellular level and to outline the mechanisms which have been proposed to be responsible for cell injuries.     

Effects of nitrogen dioxide and ozone in combination on xenobiotic metabolizing activities of rat lungs

Male Jcl:Wistar rats were exposed continuously to 0.2 ppm ozone (O3) and 4 ppm nitrogen dioxide (NO2), alone and in combination, for 1 and 2 months to examine the effects of combined gas on the xenobiotic metabolizing systems of lung microsomes. The cytochrome P-450 content increased to 200% and 253% of the control values during 2-month exposures to O3, while it was not increased by NO2 exposures. Addition of NO2 to O3 reduced the increased level of cytochrome P-450 to 179% and 178% of the control values. The activities of cytochrome P-450-dependent monooxygenase, benzo[a]pyrene hydroxylase and 7-ethoxycoumarin O-deethylase were changed in the same fashion by exposures to NO2 and O3. The 7-ethoxycoumarin O-deethylase activity was increased to 147% and 142% of the control values by O3 exposure, whereas it was decreased to 71% and 75% of the control values by NO2 exposures. This activity was decreased to 124% and 97% of the control values by combination of O3 with NO2 after 1 and 2 months, respectively. Similarly, the benzo[a]pyrene hydroxylase activity was increased to 157% and 153% of the control values during O3 exposures, while it was not changed by NO2 exposures. Addition of NO2 to O3 reduced the activity to 140% and 115% of the control values after 1 and 2 months, respectively. The alteration of coumarin hydroxylase activity was different from those of others. This activity decreased to 44% and 29% of the control values after 1- and 2-month exposures to NO2, respectively, and was also decreased by O3 exposures. However, the magnitude of decrease was not reinforced by combination of NO2 with O3. These results indicate that an increased level of xenobiotic metabolizing activity produced by O3 exposures is lowered by combination with NO2. These phenomena may be antagonistic effects of these gases on the xenobiotic metabolizing systems of lung microsomes.