Spinal cord lesions of multiple sclerosis

The neuropathological findings of the spinal cord lesions of six human multiple sclerosis cases are described. The spinal cord was extensively necrotic and occasionally cystic in five remitting and relapsing cases. The lesions became more severe as the disease course prolonged and relapses increased. The spinal cords of two cases in particular, with a duration of illness of more than 5 years, were severely atrophic. In these cases, peripheral type remyelination was prominent, although central type remyelination was minimal. In contrast, in mouse spinal cords, in which experimental demyelination and remyelination were induced by ethidium bromide, the degree of central type remyelination and peripheral type remyelination was almost the same. Longitudinal sections of the transitional zone between the areas of central type remyelination and peripheral type remyelination contrained Ranvier nodes, in which central type myelin and peripheral type myelin were situated side by side around a central type axon. These transitional zones were similar to those of the normal transitional zone between the central nervous system and peripheral nervous system of the nerve roots. One chronic progressive case, despite the very long duration of illness, showed classical sharply demarcated demyelinated lesions with marked fibrillary gliosis. The spinal cord of this case was not atrophic and axons were well preserved.     

DNA lability induced by nimustine and ramustine in rat glioma cells.

The DNA labile sites induced by two nitrosoureas, nimustine (ACNU) and ramustine (MCNU) synthesised in Japan, have been examined in highly reiterated DNA sequences of rat glioma cells. Reiterated fragments of 167 and 203 base pairs (bp), obtained after Hind III and Hae III restriction endonuclease digestion of rat glioma cells DNA, were used as target DNA sequences to determine the labile sites. In vitro reaction with ACNU and MCNU resulted in scission products corresponding to the locations of guanine. Subsequent piperidine hydrolysis produced more frequent breaks of the phosphodiester bonds at guanine positions, thus forming alkali-labile sites.     

INDUCTION OF A RETINAL DISORDER WITH CYCASIN IN NEWBORN MICE AND RATS

The newborns, less than 24 hours old, of C57BL/kg/day) was studied in rats which were kept either on a standard laboratory diet, or on a diet containing a large amount of fat (40%) and cholesterol (5%). PDC significantly increased the lactate dehydrogenase activity in the aortae of rats kept on a standard diet, and the malate dehydrogenase activity in the aortae of rats kept on high-fat diet.6 strain mice and Morlyamaso strain rats received a single subcutaneous Injection of cycasin (0.5 mg/kg/day) was studied in rats which were kept either on a standard laboratory diet, or on a diet containing a large amount of fat (40%) and cholesterol (5%). PDC significantly increased the lactate dehydrogenase activity in the aortae of rats kept on a standard diet, and the malate dehydrogenase activity in the aortae of rats kept on high-fat diet.g body weight In mice, 0.2 mg and 0.5 mg/g body weight In rats), and effects of cycasin on the retina were studied. Rosette formations were seen after the necrosis of cells in the neuroblasts layer. Especially, In rats treated with a large dose of cycasin, retinal hemorrhage from the choroid completely arrested the differentiation to each layer in the retina and resulted In its severe disorder. These changes were considered to belong to the same category as necrotic damage in the external granular layer of the cerebellum induced by cycasin.     

Decreased fractional excretion of urate as an indicator of prerenal azotemia

Although the fractional excretion of uric acid (FEUA) is known to reflect extracellular fluid volume changes, the diagnostic significance of decreased FEUA in dehydration has not been previously reported. We studied the possible association between low FEUA and acute prerenal azotemia, and its diagnostic value, compared with other traditional indices, in discriminating prerenal azotemia from renal parenchymal causes of acute renal failure. In 65 chronic renal disease patients, 174 FEUA measurements were obtained from 24-hour urine collections. FEUA levels increased as reciprocal serum creatinine levels decreased. All 8 patients with prerenal azotemia showed significantly decreased FEUA values compared with chronic renal disease patients with a comparable degree of serum creatinine elevation, whereas all 7 patients with acute renal failure had FEUA values higher than those of chronic renal disease patients with comparable creatinine levels. FEUA values in prerenal azotemia were distinctly lower than those in acute renal failure (p less than 0.001). Patients with prerenal azotemia showed a lower fractional excretion of sodium, a lower fractional excretion of chloride and renal failure index, and a higher urine-to-plasma creatinine ratio than those with acute renal failure (p less than 0.05). However, these traditional indices were not useful in discriminating between the two conditions. The urine-to-plasma urea nitrogen ratio and the ratio of plasma urea nitrogen to creatinine showed no statistical difference between prerenal azotemia and acute renal failure. We conclude that, in acute azotemia, a decreased FEUA value may represent a reliable indicator of prerenal azotemia in the differential diagnosis of acute renal failure.     

Studies on a new herbicidal antibiotic, homoalanosine

Homoalanosine having a herbicidal activity was isolated from the culture filtrate of a soil isolate SC-1688 which was classified as Streptomyces galilaeus. The chemical structure of homoalanosine was determined to be L-2-amino-4-nitrosohydroxyaminobutyric acid by analyses of spectral and biological data. The antibiotic has high herbicidal activity at low concentrations against especially common cocklebur and ladysthumb among the tested weeds and crops. Foliar application of this antibiotic inhibited the growth of roots and buds. This result indicated that homoalanosine had a systemic herbicidal activity.     

Retina, tear and serum beta-N-acetylglucosaminidase activities in diabetic patients.

In previous studies, beta-N-acetyglucosaminidase activities were found to be markedly decreased in streptozotocin diabetic rat kidney, while that of the liver, spleen and intestine remained unchanged. The decrease in total kidney enzyme activity was in parallel with a decrease in the enzyme activity of the main isozyme of beta-N-acetylglucosaminidase, of which little or none was contained in the other three tissues. The present paper reports that the retina, also sensitive to diabetic microangiopathy, showed a similar isozyme pattern to that of kidney, composed of mainly type II isoenzyme of beta-N-acetylglucosaminidase. Type II isoenzyme was not detectable in any of the other materials tested including human and rat erythrocytes, lymphocytes and platelets, and human buccal epithelia and saliva, except human tear. The physiologic significance of the human tear beta-N-acetylglucosaminidase is unknown, but this enzyme was found to contain a considerable amount of Type II isoenzyme, and the enzyme activities were decreased in poorly controlled diabetic patients. Patients with retinopathy also showed markedly lowered tear enzyme activity. The diabetic patients were followed up for several months with occasional ophthalmoscopic examination and determination of serum beta-N-acetylglucosaminidase activity. As a result, changes in the latter were found to be useful as an indicator of the development of microangiopathy.     

Ultrasound grade of hydronephrosis and severity of renal cortical damage on 99m technetium dimercaptosuccinic acid renal scan in infants with unilateral hydronephrosis during followup and after pyeloplasty

PURPOSE: We performed ultrasonography and (99m)technetium dimercaptosuccinic acid (DMSA) renal scan in infants with unilateral hydronephrosis during followup and after pyeloplasty to examine the correlation of ultrasound hydronephrosis grade with the severity of renal cortical damage and assess the recovery of renal function in the obstructed kidneys after surgery. MATERIALS AND METHODS: We studied 80 boys and 19 girls with unilateral hydronephrosis detected in the first year of life, including 75 (76%) in whom it was detected prenatally. Ultrasound images were graded according to the Society for Fetal Urology grading system. The severity of renal cortical damage was assessed by DMSA renal scan. Absolute function of the right and left kidneys was estimated by DMSA uptake and relative DMSA uptake was calculated by the formula, relative uptake = uptake in obstructed kidney/total uptake in right and left kidneys x 100%. RESULTS: On ultrasonography grades 1 to 4 hydronephrosis were diagnosed in 9, 21, 19 and 50 kidneys, respectively. On DMSA renal scan cortical damage was detected in 10 kidneys (53%) with grade 3 and 49 (98%) with grade 4 hydronephrosis but not in kidneys with grade 1 or 2 disease. Dysfunction in the obstructed kidney, defined as relative DMSA uptake less than 40%, was noted in 13 patients with grade 4 hydronephrosis. Relative DMSA uptake significantly increased after successful pyeloplasty compared with preoperative uptake (44% +/- 2% versus 40.1% +/- 2%, p <0.01). CONCLUSIONS: Ultrasound grading of hydronephrosis correlates with the severity of cortical damage or the decrease in renal function on DMSA renal scan. Differential renal function on DMSA renal scan may be a useful and less invasive tool for determining surgical indications and examining changes in renal function after surgery.     

Human leukocyte antigen DRB1 1302 protects against bile duct damage and portal lymphocyte infiltration in patients with chronic hepatitis C

BACKGROUND/AIMS: To confirm the immune reaction of hosts in chronic hepatitis C, we examined the association of human leukocyte antigen (HLA) DR with the histopathological outcome including bile duct damage and steatosis, which are characteristic of hepatitis C virus (HCV) infection. METHODS: One hundred and fifty-five patients with chronic HCV infection were examined. The pathological appearance of liver biopsy specimens was evaluated by both Knodell's histological activity index and examination of bile duct damage and steatosis. HLA DRB1 was determined by the polymerase chain reaction sequence-specific oligonucleotide probe method. RESULTS: HLA DRB1 1302 was found with significantly higher frequency in patients without than with bile duct damage (34.8% vs. 4.7%, p=0.0001, p corrected by Bonferroni's inequality method=0.002). It was also found more frequently in patients without marked portal lymphocyte infiltration (28.6% vs. 7.7%, p=0.0015, p corrected by Bonferroni's method=0.03). HLA DRB1 1101 was found more frequently in patients without than with piecemeal necrosis (p=0.004). In contrast, the frequency of HLA DRB1 1502 tended to be higher in patients with than without piecemeal necrosis and marked portal lymphocyte infiltration (p=0.015 and p=0.03, respectively). HLA DRB1 1201 and 0802 were seen more frequently in bile duct damage-negative (p=0.02) and piecemeal necrosis-negative patients (p=0.03), respectively. Interestingly, serum HCV levels of HLA DRB1 1302-positive patients were significantly higher than those of 1302-negative patients (mean: 7.7 Meq/ml vs. 3.1 Meq/ml, p=0.0007). CONCLUSION: These findings suggest that some histopathological changes in chronically HCV-infected livers could be caused by the host's immune reaction regulated by HLA DR.