Activation of mRNA expression of collagen,collagenase and its inhibitor on renal biopsy specimens in patients with IgA nephropathy

Summary: In situ hybridization of mRNA for collagen IV, collagen VI, stromelysin (MMP-3) and TIMP1 was examined in renal biopsy specimens from patients with IgA nephropathy (IgAN) or diabetic nephropathy with various degrees of tissue damage. The majority of cells in the glomeruli expressed these mRNA almost simultaneously, but a few cells demonstrated positive expression for only one of these probes. There was a parallel relationship between the degree of tissue damage and that of mRNA expressions of these probes in patients with IgAN, while patients with diabetic nephropathy showed a reverse relationship between these two parameters. It is concluded that patients with mesangial proliferative glomerulonephritis expressed mRNA for collagen collagenase and its inhibitor in the glomeruli in parallel with the progress of tissue damage. In contrast, glomerular samples from patients with diabetic nephropathy showed that there was an inverse relationship between tissue damage and expression of mRNA. It is concluded that expression of collagen, collagenase and its inhibitor parallels the progression of glomerular changes in IgAN, but such parallel expression was not observed in patients with diabetic nephropathy.     

Destination after discharge from a senile dementia therapy ward before and after the implementation of long-term care insurance in Japan

Background: In Japan a new long‐term care insurance (LTCI) system, the so‐called ‘Kaigo‐Hoken’, was started in April 2000. The present study analyzes the change in the type of destination after discharge from a senile dementia therapy ward before and after the implementation of LTCI at Fukuoka Prefectural Onga Hospital, Japan. Methods: The present study examines data from 199 inpatients discharged from the Fukuoka Prefectural Onga Hospital that had been diagnosed with dementia and met the DSM IV criteria for Alzheimer's type, vascular dementia or other type of dementia. For the purposes of comparison two periods were defined, ‘the first period’ was defined as the period from 1 April 1999 to 31 March 2000, before LTCI was implemented, while ‘the second period’ was defined as the period from 1 April 2000 to 31 March 2001, after LTCI had started. Subject data was analyzed on the basis of where the subject had resided pre‐admission and their destination after discharge using the following classifications: nursing home or geriatric care facility, hospitalization, home and death. Results: While the certification rate of inpatients regarding long‐term care increased slightly in the second period, no significant change was observed based on where the subject had resided pre‐admission and their destination after discharge between the first and second periods. Conclusions: While LTCI is essential for Japan, it is necessary that people with dementia in senile dementia therapy wards are encouraged to return to their homes under the care and support of LTCI.     

Rapid decrease of urinary pyridinoline excretion in growth hormone deficient children following discontinuation of growth hormone therapy

In order to examine the effect of growth hormone on urinary pyridinoline excretion, 32 patients with complete or partial growth hormone deficiency had their urinary pyridinoline excretion measured while receiving growth hormone and for 14 days after it was discontinued. There was a significant positive correlation between increases in growth velocities during the first year of growth hormone administration compared to before it, and the ratio of the urinary pyridinoline excretion levels while receiving growth hormone to those after discontinuation. Therefore, urinary pyridinoline excretion rapidly decreased in patients with growth hormone deficiency when the administration of growth hormone was stopped. Exogenous growth hormone appears to stimulate bone resorption in these patients.     

Microvascular disturbances in the colonic mucosa in antibiotic-associated haemorrhagic colitis: Involvement of platelet aggregation

An ultrastructural study of the colonic mucosa was performed in four patients with antibiotic-associated haemorrhagic colitis and new findings are reported. Colonoscopy was performed and biopsy specimens were obtained within 24 h of the onset of bloody diarrhoea. Colonoscopy demonstrated diffuse oedematous and haemorrhagic mucosa with erosions and white coat. Light microscopy revealed mucosal haemorrhage and inflammatory cell infiltration. Ultrastructurally, platelet aggregation was frequently present in the lumina of colonic mucosal capillaries, causing engorgement of red blood cells in adjacent microvessels. Mild to severe damage was observed in capillary endothelial cells, including discontinuity of basement membranes, gaps between endothelial cells and the destruction of capillaries. There was no evidence of microvascular spasm. In conclusion, our findings suggest that antibiotics directly or indirectly cause microcirculatory disturbances, which result in tissue damage and haemorrhage, in the colonic mucosa.     

Liver transplantation in a case of hypoproteinemia and coagulopathy

A female infant with hypoproteinemia and coagulopathy associated with hypertyrosinemia was successfully treated with living-related liver transplantation (LRLT). On the 12th day of life plasma amino acid analysis revealed a marked elevation of tyrosine, so the patient was fed on a low-tyrosine and low-phenylalanine diet. However, hepatosplenomegaly. hypotonia, alopecia, eczema and psychomotor delay did not improve and recurrent episodes of disseminated intravascular coagulation (DIC) caused her condition to deteriorate. Liver biopsy on the 230th day revealed marked fatty change accompanied by mild to moderate cholestasis. Therefore. LRLT from her father was performed on the 286th day resulting in improvement of all the aforementioned signs and symptoms. Despite a thorough examination, no diagnosis of a known disorder could be established. However, her elder brother had also been born with severe hypoproteinemia and coagulopathy, and died of DIC on the second day of life. Thus, the disorder is designated as a new entity, namely ‘congenital hypoproteinemia and coagulopathy associated with hypertyrosinemia’.     

A sensitive sandwich ELISA for measuring thrombopoietin in human serum: serum thrombopoietin levels in healthy volunteers and in patients with haemopoietic disorders

A sensitive sandwich enzyme-linked immunosorbent assay (ELISA) has been established to estimate serum thrombopoietin (TPO) concentrations in healthy volunteers and patients with haemopoietic disorders. The ELISA uses a mouse monoclonal antibody (Ab) as the capture Ab and a biotinylated rabbit polyclonal Ab as the detector. The ELISA was reproducible, highly sensitive and specific for human TPO. The coefficients of intra- and inter-assay variation were from 3.0% to 4.9% and from 5.9% to 6.1%, respectively. The quantitative limit of the ELISA was 0.09 fmol/ml in serum. The quantitative limit was lower than the normal level. The dose–response curves of serum samples from healthy volunteers and patients with haemopoietic disorders were parallel to the standard curves. The ELISA did not cross-react with a variety of blood components and cytokines to produce false-positive results.
The serum TPO concentrations from 29 normal males and 21 females were 0.79 ± 0.35 and 0.70 ± 0.26 fmol/ml, respectively. Serum TPO levels in patients with aplastic anaemia (AA), acute lymphocytic leukaemia (ALL) and essential thrombocythaemia (ET) were measured using the ELISA. The serum TPO levels in the patients with ET ( n  = 6, 2.80 ± 1.55 fmol/ml) were higher than the normal level. The patients with AA ( n  = 7, 18.53 ± 12.37 fmol/ml) and ALL ( n  = 5, 10.36 ± 5.57 fmol/ml) had significantly higher serum TPO levels than normal individuals. These results indicate that the ELISA specific to TPO should prove useful in measuring the TPO concentration in serum samples.