Heat shock protein hsp72 induction in cortical and striatal astrocytes and neurons following infarction

Transient global and transient focal ischemia induced the 72 kDa heat shock protein (hsp72) in neurons in cortex, striatum, and other regions known to be injured during transient ischemia. A novel finding was the induction of hsp72 in islands (cylinders in three dimensions) of cells composed of astrocytes around the perimeter and neurons in the interior. Since histology showed pale staining in these regions, it is proposed that these islands represent areas of focal infarction in the distribution of small cortical and lenticulostriate arteries. Although the factors responsible for hsp72 induction during ischemia and infarction are unknown, these results suggest differences in mechanisms of hsp72 induction in astrocytes compared to neurons.     

Delineating the sites and progression of in vivo atrophy in multiple system atrophy using fluid-registered MRI.

We describe the pattern and progression of atrophy delineated using fluid registration of serial magnetic resonance imaging scans in a case of multiple system atrophy (MSA). The in vivo findings were consistent with those found at postmortem, including significant supratentorial atrophy concurrent with an unusual degree of cognitive impairment for MSA.     

Transforming growth factor-beta(1) in the kidney and urine of patients with glomerular disease and proteinuria.

BACKGROUND: Transforming growth factor-beta(1) (TGF-beta(1)) is the major fibrogenic growth factor implicated in the pathogenesis of renal scarring. Proteinuria is a poor prognostic feature for various types of glomerular disease and its toxic action may be related to the activation of tubular epithelial cells towards increased production of cytokines and chemoattractant peptides. In this work we studied the site of synthesis and expression profile of TGF-beta(1) in the renal tissue of patients with heavy proteinuria and examined the relation of this expression with the urinary excretion of TGF-beta(1). METHODS: Twenty-five patients with heavy proteinuria (8.4+/-3.0 g/24 h) were included in the study. All patients underwent a diagnostic kidney biopsy and were commenced on immunosuppressive therapy with corticosteroids and cyclosporin. The sites of synthesis and expression profile of TGF-beta(1) mRNA and protein in the kidney were examined by in situ hybridization and immunohistochemistry. Urinary and plasma TGF-beta(1) levels were determined by ELISA before the initiation of treatment and 6 months later and compared with those of normal subjects and of patients with IgA nephropathy and normal urinary protein excretion. RESULTS: The site of synthesis and expression of TGF-beta(1) in the renal tissue of patients with heavy proteinuria was mainly localized within the cytoplasm of tubular epithelial cells. Interstitial expression was also present but glomerular TGF-beta(1) expression was found only in patients with mesangial proliferation. Urinary TGF-beta(1) excretion was significantly higher in nephrotic patients compared with normal subjects and with patients with IgA nephropathy and normal urinary protein excretion (783+/-280 vs 310+/-140 and 375+/-90 ng/24 h, respectively; P<0.01). In patients with remission of proteinuria after immunosuppressive therapy, urinary TGF-beta(1) excretion was significantly reduced (from 749+/-290 to 495+/-130 ng/24 h; P<0.01), while in patients with persistent nephrotic syndrome, it remained elevated. CONCLUSIONS: The localization of TGF-beta(1) mRNA and protein within tubular epithelial cells, along with its increased urinary excretion in patients with nephrotic syndrome, suggest the activation of these cells by filtered protein towards increased TGF-beta(1) production.     

Neonatal gallbladder enlargement and alpha 1-antitrypsin deficiency

Patients with clinical signs of alpha 1-antitrypsin deficiency in the neonatal period usually present with prolonged obstructive jaundice. We report a patient with alpha 1-antitrypsin deficiency who presented with gallbladder enlargement in the neonatal period. This gallbladder enlargement may be due to cystic duct hypoplasia or atresia, which has been reported in association with alpha 1-antitrypsin deficiency. The diagnosis of alpha 1-antitrypsin deficiency should be considered in neonates with gallbladder enlargement and prolonged obstructive jaundice.     

The pros and cons of fecal occult blood testing for colorectal neoplasms

Testing feces for occult blood is widely recommended as a means of detecting subclinical colorectal tumors. Guaiac tests such as Hemoccult^® are the most widely used, but chemical sensitivity is relatively low and the tests are affected by dietary peroxidases, the state of fecal hydration, and certain drugs. The newly devised HemoQuant^® and immunologic techniques appear more sensitive and specific, but they require further evaluation before widespread clinical usage can be recommended.Occult blood screening has both merits and weaknesses. Testing does uncover subclinical colorectal cancer, often at a relatively early stage, but whether this actually improves the prognosis remains to be proven. Benign neoplastic polyps are also detected, although it is debatable whether this is a valid rationale for screening. Test sensitivity for malignancy varies from good to moderate, but is poor for benign polyps. Specificity is usually around 97%–98%, yet the predictive value of a positive test for cancer is only about 10%: hence most test-positive individuals are needlessly subjected to invasive colonic investigations. Reported figures on public compliance with occult blood testing vary widely from excellent to poor. Published costs of screening are usually quite low, but these overlook important indirect and hidden expenses and are therefore misleading.On balance, the problems of occult blood testing currently appear to outweight the merits. This could change, however, with the newer testing techniques and with awaited mortality data from controlled clinical trials now underway.