Therapeutic advantage of angiotensin converting enzyme inhibitors in chronic glomerulonephritis

Hypertension in chronic progressive renal disease is a major clinical problem leading to renal function loss. We studied the influence of ambulatory blood pressure (ABP) and the effect of hypertension therapy on renal function in 116 patients with chronic glomerulonephritis. Patients were subdivided as hypertensive, normotensive and hypotensive according to the level of ABP and age. Hypotensive subjects showed improvement of renal function and normotensive subjects showed slower rate of progression of renal function loss than hypertensives, suggesting the adequate level of ABP was 100-125/55-75 mm Hg in patients less than 40 years old, 100-135/60-80 mm Hg in patients 40-60 years old, and 105-140/60-85 mm Hg in patients over 60 years, respectively. The renal protection of calcium antagonists was associated with achieving lower blood pressure levels, whereas the blood pressure level did not affect progression of renal function in patient treated with angiotensin converting enzyme (ACE) inhibitor. ACE inhibitor, but not calcium antagonists, showed a reduction of urinary protein excretion. Thus, the mechanisms of renal protection were different between ACE inhibitors and calcium antagonists.     

Purification and characterization of an anti-inflammatory factor (AIF) from bovine serum.

An anti-inflammatory factor (AIF) was highly purified from normal bovine serum. The purified AIF was a polysaccharide which was formed from a low molecular substance Pro-AIF by macromolecularization. AIF showed potent inhibitory activities against carrageenin induced edema in rats and PMN-leucocyte chemotaxis. It showed no inhibition in cutaneous reaction with serotonin, bradykinin or a mediator releaser compound 48/80. No inhibition was also observed in thermally induced pain, reversed passive Arthus reaction and adjuvant polyarthritis in rats. With these results, the role of AIF in inflammation was discussed.     

The Studies of the Attacks of Abnormal Eye Movement in a Case of Infantile Spasms

We observed the attacks of nystagmus in a case of infantile spasms and carried out overnight sleep polygraphy. The following findings were obtained:

• 1 Awake time was prolonged to 56% of TIB, while sleep time was markedly shortened to 44% of TIB. Also REM sleep time was reduced to 20% of SPT and deep slow sleep (stage N3) was absent.
• 2 Attacks of nystagmus were observed only during wakefulness. At first, fast wave bursts appeared in the right occipital area, and were followed by left-upward deviations of eyeballs, and then the attacks of counterclockwise right-downward rotatory nystagmus. Also the fast wave bursts were succeeded by spreading of fast waves to adjacent areas. At the same time, EMG exhibited elevated muscle action potentials of mentalis and biceps fernoris. During the attacks of nystagmus, there was alteration of respiratory movements.

In NREM sleep, both fast wave bursts and the attacks of nystagmus were not observed. In REM sleep, the fast wave bursts and eye movements were observed but the attacks of nystagmus did not appear. During the fast wave bursts, alteration of respiratory movements were observed. From the results of this study, it was presumed that the brain lesions of this case were extended with severe degree of damage in the great parts of brain containing Cerebral cortex and brain stem.     

Molecular defect in siblings with prolidase deficiency and absence or presence of clinical symptoms. A 0.8-kb deletion with breakpoints at the short, direct repeat in the PEPD gene and synthesis of abnormal messenger RNA and inactive polypeptide.

Prolidase deficiency is an autosomal recessive disorder with highly variable symptoms, including mental retardation, skin lesions, and abnormalities of collagenous tissues. In Japanese female siblings with polypeptide negative prolidase deficiency, and with different degrees of severity of skin lesions, we noted an abnormal mRNA with skipping of 192 bp sequence corresponding to exon 14 in lymphoblastoid cells taken from these patients. Transfection and expression analyses using the mutant prolidase cDNA revealed that a mutant protein translated from the abnormal mRNA had an Mr of 49,000 and was enzymatically inactive. A 774-bp deletion, including exon 14 was noted in the prolidase gene. The deletion had termini within short, direct repeats ranging in size of 7 bp (CCACCCT). The "slipped mispairing" mechanism may predominate in the generation of the deletion at this locus. This mutation caused a 192-bp in-frame deletion of prolidase mRNA and was inherited from the consanguineous parents. The same mutation caused a different degree of clinical phenotype of prolidase deficiency in this family, therefore factor(s) not related to the PEPD gene product also contribute to development of the clinical symptoms. Identification of mutations in the PEPD gene from subjects with prolidase deficiency provides further insight into the physiological role and structure-function relationship of this biologically important enzyme.     

Brain lesion in congenital myotonic dystrophy

Congenital myotonic dystrophy (CMyD) affects the brain, causing mental changes and psychomotor retardation. However, the pathophysiology of the brain dysfunctions in CMyD remain to be clarified. We described two cases of CMyD with brain abnormalities. Case 1 was diagnosed as having ventricular dilation at 17 days after birth, and died at 3 years and 6 months. Case 2 was diagnosed as having ventricular dilation at birth, and died at 1 year and 3 months. Pathologically, both cases showed remote hypoxic ischemic brain damage and leptomeningeal glioneuronal heterotopia (LGH). In our patients, the white matter changes may have been caused by perinatal asphyxia, and LGH by embryological abnormalities. Taken our data and those of previous reports together, it is suggested that cerebral abnormalities in CMyD are ascribed to both hypoxic ischemic changes and histogenetic abnormalities.     

Influence of the radioactive strontium (89Sr) using for nuclear medical radiation therapy upon radioactive draining-water system

PURPOSE: Strontium-89 chloride (89Sr) is a new radiopharmaceutical that provides effective pain relief for metastatic bone lesions, and is expected to be available soon in the palliative management for metastatic bone pain in Japan. Because of relatively long physical half life (50.5 days), 89Sr may affect to the radioactive draining-water system by exceeding the limits of activity concentration for radioactive drain. In this article, the influence of 89Sr use on the radioactive drainage system was simulated. METHODS: The standard tank capacity of drainage and draining frequency was determined from the results of questionnaire carried out for the nationwide medical and research institutes where radioisotope treatment are performed. On the assumption that 89Sr of 148 MBq for one therapy was used twice a week and several common radionuclides were used as the same activity as used at Chiba Cancer Center, the influence of 89Sr was estimated. The calculation was performed using the activity contamination ration into the draining-water system of each radionuclide of 0.01, which was legally determined. RESULTS: The simulation revealed that the sum of the contamination ratios of individual radionuclides exceeded a legal value of 1.0 in standard drainage with the capacity of 5 m3 and 10 m3 and draining frequency of 7 times per year. The actual contamination ratios of common radiopharmaceuticals measured at Chiba Cancer Center ranged from 1/100 to 1/1000 of the legal values. CONCLUSION: It is necessary that the legal value of activity contamination ratios into the draining-water system should be reassessed before starting 89Sr therapy.     

Radiocesium in children residing in the western districts of the Bryansk Oblast from 1991-1996

Measurements of 137Cs body burden were carried out in 1991-1996 for children residing in the western part of Bryansk Oblast (Russia) where area contamination with 137Cs following the Chernobyl accident varied from 0.03-3.7 MBq m(-2). The mean and median values of 137Cs specific activity (SA) in the bodies of children 5-15 y old for the whole period of surveillance averaged for 26,029 measurements was 85 Bq kg(-1) and 49 Bq kg(-1), respectively. Mean values in different places of residence varied from 30-342 Bq kg(-1) for the settlements where the number of examinees was not less than 50. There is a moderately strong relationship between mean SA in the settlement and the level of area contamination with 137Cs. A strong seasonal effect on 137Cs body burden was found. The ratio of average SA values is 1:1.75 for spring to autumn 1992-1995 in the settlement where the largest number of children was examined. This effect might be attributed to a seasonal change in diet. Based on questionnaire information on individual consumption of locally produced foods, the descending rank of contribution of food items to 137Cs intake by children was found to be: meat-mushrooms-milk-vegetables. Assuming that the dose distribution would follow the distribution of SA values, internal doses to the whole body from ingested 137Cs were assessed. The mean value of annual internal dose averaged for the whole set of measurements is 0.21 mSv, and the median of the individual dose distribution is 0.12 mSv y(-1) For 2% of the total sample the annual dose exceeded 1 mSv, with the highest individual dose being 9 mSv in 1994 for a 7-y-old girl.     

Low plasma epinephrine in elderly female subjects of dementia of Alzheimer type

One of the robust features of brain pathologies of dementia of Alzheimer type (DAT) is the impairment of the hippocampus, especially the cholinergic system. Several animal studies have suggested that the cholinergic system in the hippocampus is involved in the control of the plasma level of catecholamines and glucose. The stimulation of the hippocampal cholinergic system has resulted in the elevation of plasma catecholamines and glucose in rats. In the present study, we measured the plasma level of epinephrine, norepinephrine, dopamine, glucose, and insulin during a fasting state in the morning in hospitalized DAT (n=66), vascular dementia (VD) (n=28), or non-demented (ND) (n=21) females (mean age DAT=82. 49+/-4.98, VD=82.86+/-5.86, ND=82.95+/-7.77, respectively). Statistical analysis showed that the plasma level of epinephrine during a fasting state in DAT subjects was significantly lower than that of ND subjects; however, in VD subjects the level of epinephrine was not different from that of ND subjects. Other values did not differ significantly among the groups.