Kinetics and characterization of initially regenerating proximal tubules in S3 segment in response to various degrees of acute tubular injury.

BACKGROUND: We examined kinetics and characterization of regenerating proximal tubule (PT) cells after various degrees of tubular injury in S3 segments of PT and assessed label-retaining slow cycling cells in S3. METHODS: PT injury was induced by different doses of uranyl acetate (UA) injection into rats, and initially regenerating PTs were identified by in vivo bromodeoxyuridine (BrdU)-labelling before sacrifice or were examined on vimentin positivity. Next, the 3H-thymidine pulse/chase approach was applied to the early regenerating PTs identified by BrdU-labelling after UA injection. RESULTS: Low-dose UA induced focal PT depletion and initial BrdU positivity in the proximal three-quarters of the S3 segment of PT. Autoradiography showed the increased number of label-retaining and label-diluted cells in the proximal three-quarters of S3 in rats treated with low-dose UA compared to normal rats. High-dose UA induced almost complete PT depletion in the proximal three-quarters of S3 and less PT depletion in the distal quarter of S3 and initial BrdU+ cells were restrictedly found in the distal quarter of S3. Label-retaining and label-diluted cells were increasingly found in the entire S3 at day 7, but only label-retaining cells remained in similar numbers in the distal quarter of S3 until day 42. Initially regenerating PT cells with any doses of UA expressed vimentin, suggesting dedifferentiated PT cells. CONCLUSIONS: Initially regenerating cells after PT injury in S3 are dedifferentiated pre-existing PT cells, which may scatter throughout S3 and be responsible for focal repair of S3. Some initially regenerating PT cells in the distal S3 showed persistent label-retaining cells at day 42 after high-dose UA insult and contributed to renewal of the entire S3, thus they might be slow cycling cells with responsibility for S3 repair.     

Diagnostic value of MRCP and indications for ERCP

BACKGROUND/AIMS: To assess the diagnostic value of magnetic resonance cholangiopancreatography (MRCP) and examine the indications for endoscopic retrograde cholangiopancreatography (ERCP). METHODOLOGY: MRCP was performed in 185 patients with hepatobiliary disease in whom abdominal ultrasonography (US) had not been of diagnostic value. These patients were selected for MRCP in view of their abdominal symptoms, high levels of hepatobiliary enzymes, and pancreatic/bile duct dilatation found by abdominal US. Based on MRCP findings, 75 patients were selected for ERCP. RESULTS: ERCP provided new findings in 14 (18.%) patients. In 110 patients subjected to only MRCP and follow-up as well as in 75 patients with MRCP followed by ERCP, MRCP-based diagnosis corresponded with the final diagnosis. In our study, patients who would have conventionally required ERCP, such as those with natural passed choledocholithiasis and postoperative bile duct dilatation, could be followed up without ERCP. These results the importance of considering indications for ERCP. CONCLUSIONS: MRCP can be an alternative to ERCP at least for diagnosis.     

Acquired resistance to rechallenge injury in rats recovered from subclinical renal damage with uranyl acetate—Importance of proliferative activity of tubular cells

Animals recovered from acute renal failure are resistant to subsequent insult. We investigated whether rats recovered from mild proximal tubule (PT) injury without renal dysfunction (subclinical renal damage) acquire the same resistance. Rats 14 days after recovering from subclinical renal damage, which was induced by 0.2 mg/kg of uranyl acetate (UA) (sub-toxic dose), were rechallenged with 4 mg/kg of UA (nephrotoxic dose). Fate of PT cells and renal function were examined in response to nephrotoxic dose of UA. All divided cells after sub-toxic dose of UA insult were labeled with bromodeoxyuridine (BrdU) for 14 days then the number of PT cells with or without BrdU-labeling was counted following nephrotoxic dose of UA insult. Rats recovered from subclinical renal damage gained resistance to nephrotoxic dose of UA with reduced renal dysfunction, less severity of peak damage (necrotic and TUNEL+ apoptotic cells) and accelerated PT cell proliferation, but with earlier peak of PT damage. The decrease in number of PT cells in the early phase of rechallenge injury with nephrotoxic UA was more in rats pretreated with sub-toxic dose of UA than vehicle pretreated rats. The exaggerated loss of PT cells was mainly caused by the exaggerated loss of BrdU+ divided cells. In contrast, accelerated cell proliferation in rats recovered from sub-toxic dose of UA was observed mainly in BrdU- non-divided cells. The findings suggest that rats recovered from subclinical renal damage showed partial acquired resistance to nephrotoxic insult. Accelerated recovery with increased proliferative activity of non-divided PT cells after subclinical renal damage may mainly contribute to acquired resistance.     

A clinicopathological study of a patient with familial amyotrophic lateral sclerosis associated with a two base pair deletion in the copper/zinc superoxide dismutase (SOD1) gene

The recognition of mutations in the copper/ zinc superoxide dismutase (SOD1) gene in familial amyotrophic lateral sclerosis (FALS) has been a landmark in ALS research. We report a clinicopathological study of a female patient with FALS showing a two base pair deletion in exon 5 of the SOD1 gene. Her clinical course was rapid and she died 2 years after the onset. The SOD1 activity was down to 30% of the normal level. Western blot analysis did not reveal the mutant protein which was expected to be ∼2.4 kDa smaller than normal SOD1 protein in molecular mass. In contrast to the neuropathological findings of the previously reported cases showing the same mutation, our case was characterized by sparing of the dorsal column and the presence of only a modest number of intracytoplasmic eosinophilic inclusions showing weak or partial immunoreaction for neurofilament and negative reaction for SOD1. Thus, the same mutation in the SOD1 gene does not necessarily induce consistent pathological changes in the central nervous system. Received: 7 March 1997 / Revised, accepted: 9 June 1997     

Accumulation of peripheral myelin protein 22 in onion bulbs and Schwann cells of biopsied nerves from patients with Charcot-Marie-Tooth disease type 1A

Peripheral myelin protein 22 (PMP-22) is a glycoprotein expressed in the myelin sheath of myelinated Schwann cells. Duplication of the PMP-22 gene and its gene dosage effect have been postulated to be involved in the pathogenesis in the majority of individuals with Charcot-Marie-Tooth disease type 1A (CMT1A). Northern blot analysis has demonstrated that the mean relative ratio of PMP-22 mRNA/β-actin mRNA in biopsied nerves of patients with CMT1A is significantly higher than that in disease controls. To investigate whether the elevated expression of PMP-22 mRNA is reflected in the amount and the localization of PMP-22, we analyzed PMP-22, myelin basic protein (MBP), protein zero (P0), and S-100 immunoreactivities in biopsied nerves from six patients with CMT1A, five patients with other types of CMT, five patients with acquired demyelinating neuropathies, and two normal subjects. In all patients with CMT other than CMT1A and acquired demyelinating neuropathy, as well as in normal subjects, the myelin sheath was immunoreactive for PMP-22, MBP, and P0, while the Schwann cell cytoplasm was immunoreactive only for S-100. In five out of six patients with CMT1A, however, the PMP-22 immunoreactivity was present not only on the myelin sheath but also in the Schwann cell cytoplasm and onion bulbs (OBs). Although OBs are nonspecific and also seen in other inherited or acquired demyelinating neuropathies, the PMP-22-positive OBs were seen exclusively in CMT1A.The finding suggested that the expression of PMP-22 was abnormal for its localization and probably for the amount in patients with CMT1A carrying duplication of the PMP-22 gene. Received: 5 February 1996 / Revised, accepted: 20 May 1996     

Evaluation of driver stress in a motor-vehicle driving simulator using a biochemical marker

The purpose of this study was to evaluate salivary amylase activity (sAMY) as an indicator of the acute psychological effects of driving. The influence of the operation of a device not directly associated with driving was also estimated using a car navigation system. The psychological effects of driving were examined using sAMY analysis, oculomotor angle and subjective evaluation with a questionnaire, and the methods were compared. The change in sAMY over time was analysed before and during driving. The results indicate that the psychological effect of driving-induced stress, a condition that cannot be easily detected or recognized by a subjective evaluation, is quickly quantified using sAMY. Moreover, the results suggest that the operation of a non-driving-related device may also reduce the driver's capacity to concentrate on driving.