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An 82-year-old male patient was admitted for liver dysfunction. Laboratory test showed the following data; aspartate aminotransferase (AST) 79 IU/l, alanine aminotransferase (ALT) 28 IU/l, total bilirubin (T. Bil) 0.9 U, zinc sulfate turbidity test (ZTT) 48.9 U, gamma-globulin 4.9 g/dl, immunoglobulin G (IgG) 5,046 mg/dl, anti-nuclear antibodies x 320, anti-mitochondrial antibodies (-), hepatitis B virus surface antigen (HBsAg) (-), HBcAb (-), anti-hepatitis C virus (anti-HCV) (-), hepatitis C virus (HCV-RNA) (-), anti-hepatitis G virus (anti-HGV) (-), alpha-fetoprotein 306.8 ng/ml, carcinoembryonic antigen (CEA) 2.3 ng/ml, carbohydrate antigen (CA) 19-9 77.2 U/ml. Abdominal ultrasonography and computed tomography showed a large mass occupying most of the right lobe and portal thrombosis in the liver. Liver biopsy revealed cirrhosis with inactive hepatitis in the nontumorous lesion and well-differentiated hepatocellular carcinoma in the tumorous lesion. We report a rare case of an aged male patient with autoimmune hepatitis complicated by hepatocellular carcinoma.

We isolated and characterized cDNAs and a genomic clone encoding an Arabidopsis thaliana MutM homolog (AtMMH). AtMMH is a single-copy gene spanning about 3 kb in the nuclear genome, and comprises ten exons. The AtMMH gene encodes two types of mRNA (AtMMH-1 and AtMMH-2) formed by alternative splicing of exon 8. Western analysis of a crude extract from leaves of A. thaliana, using polyclonal antibodies against the recombinant proteins, demonstrated the presence in vivo of a single 44-kDa polypeptide that comigrates with the product of in vitro translation of the AtMMH-1 mRNA. AtMMH-1 protein prepared in vitro is able to nick double-stranded oligonucleotides containing 8-oxo-7,8-dihydroguanine (8-oxoG) and to bind such oligonucleotides, as does the Escherichia coli MutM protein, which possesses 8-oxoG DNA glycosylase and apurinic/apyrimidinic (AP) lyase activities. Deletion of six amino acids (PELPEV), which are conserved among all known MutM homologs, from the N-terminal end of the AtMMH-1 protein abolishes its nicking but not its DNA-binding activity, indicating that these residues are essential for catalytic activity. Although the AtMMH-1 protein has a unique structure at its C-terminal end, which consists of alternating repeats of basic and acidic amino acids, this structure is dispensable for activity. However, the adjacent amino acid sequence (residues 268 to 281) is essential for repair activity.

To examine early intellectual deficits in elderly patients with dementia of the Alzheimer type (DAT), 25 mildly impaired patients with DAT and 25 normal controls were compared using the Japanese version of the Wechsler Adult Intelligence Scale-Revised (WAIS-R). The two groups did not differ significantly in age, years of education, or sex ratio. Based on Horn's modified fluid and crystallized model, the WAIS-R subtests were classified into two categories (i.e., fluid intelligence and crystallized intelligence). The DAT group showed a significantly lower crystallized intelligence score, whereas the fluid intelligence scores did not differ significantly between the two groups. When the subtests were examined individually, the subtests for crystallized intelligence (i.e., information, comprehension, and similarities) were found to show the most significant deficits. These results suggest that elderly subjects with mild DAT have more impaired crystallized intelligence than those without dementia.

This study was designed to examine the profiles of cognitive deficits in 11 mildly demented patients with dementia of Alzheimer's type (DAT), five with vascular dementia with multiple subcortical lacunar infarcts (VDS), and seven with vascular dementia with extensive white matter lesions (VDW) in comparison with 23 aged individuals without dementia. Memory, attention, abstract thinking, and visuospatial function were assessed using the Japanese translation of the Wechsler Memory Scale-Revised (WMS-R) and the Japanese version of the Wechsler Adult Intelligence Scale-Revised (WAIS-R). Compared with normal aged individuals, three dementia groups were significantly impaired in the memory and abstract thinking. However, the performances on several tests on attention (i.e. Mental Control and Visual Memory Span Backward from WMS-R) and visuospatial function (i.e. Object Assembly from WAIS-R) differed significantly between the DAT and VDS groups, with VDS being the worst in terms of performance than was DAT. This study suggests that, in the mildly demented stage, the patients with DAT have few problems in the attention and visuospatial function, but those with VDS have impairments in these cognitive abilities.

One hundred and three family caregivers of relatives with dementia were longitudinally surveyed to examine the course of caregivers' mental health after the relatives had been placed in full-time care facilities. Mental health was assessed twice, with a 6-month interval, using the Japanese version of the 60-item General Health Questionnaire. The degree of social dysfunction was significantly reduced within 6 months after placement, while the other indicators of mental health (e.g. anxiety-insomnia, depression, somatic symptom and psychiatric morbidity) were not reduced within this term. However, anxiety-insomnia and psychiatric morbidity were significantly reduced more than 6 months after placement. Analyses by caregivers' lineal relations to the relatives indicated that only daughters-in-law showed a significant decrease in anxiety-insomnia and a marginal reduction in psychiatric morbidity. This study suggests that caregivers' social dysfunction was more greatly reduced than anxiety-insomnia and psychiatric morbidity within a relatively short term after placement, and that its effects on mental health might vary with the lineal relations.

The change in immunological parameters was studied during the clinical course of a myasthenia gravis (MG) patient with chronic graft-versus-host disease (GVHD), which developed after bone marrow transplantation from an HLA-identical donor. Anti-acetylcholine receptor antibody gradually decreased in the patient treated with immunosuppressive agents, but was not detected in the donor. Lymphocyte numbers were low just before the onset of MG, increased abruptly within several days and then gradually decreased with treatment. The percentage of CD3+ and CD19+ lymphocytes was higher at onset than before, the percentage of CD4+ cells was higher at onset and gradually decreased with treatment, while CD8+ cells showed the lowest level just before onset and gradually increased during the clinical course. CD4+/CD45RA- cells also showed the highest levels at onset and a gradual decrease with treatment. Cellular, as well as humoral immune responses, might be associated with the pathogenesis of MG with chronic GVHD.

Ninety-eight caregivers of elderly patients with cognitive impairment were surveyed by questionnaires in order to examine the relationship between their coping strategies and subjective burden. Confrontative coping and avoidance coping were significantly associated with their burden. The severity of cognitive impairment and the behavioral problems of the patients were also significantly associated with the caregivers' burden. However, a multiple regression analysis suggested that the caregivers' coping strategies may be more important than the patients' condition in terms of the effects on the burden.

Twenty-eight sediment samples collected from Osaka Bay, Japan, were analyzed for phospholipid ester-linked fatty acids (PLFA) to determine regional differences in microbial community structure of the bay. The abundance of three major groups of C(10) to C(19) PLFA (saturated, branched, and monounsaturated PLFA), which accounted for 84 to 97% of the total PLFA, indicated the predominance of prokaryotes in the sediment. The distribution of six clusters obtained by similarity analysis in the bay revealed a marked regional distribution in the PLFA profiles. Total PLFA concentrations (0.56 to 2.97 mug/g [dry weight] of the sediment) in sediments also showed marked variation among the stations, with higher concentrations of total PLFA in the central part of the bay. The biomass, calculated on the basis of total PLFA concentration, ranged from 0.25 x 10 to 1.35 x 10 cells per g (dry weight) of the sediment. The relative dominance of microbial groups in sediments was described by using the reported bacterial biomarker fatty acids. Very small amounts of the characteristic PLFA of microeukaryotes in sediments indicated the restricted distribution of microeukaryotes. By examining the distribution of clusters and groups of microorganisms in the bay, there were two characteristics of the distribution pattern: (i) the predominance of anaerobic bacteria and gram-positive prokaryotes, characterized by the high proportions of branched PLFA in the eastern and northeastern sides of the bay, where the reported concentrations of pollutants were also high, and (ii) the predominance of aerobic prokaryotes and eukaryotes, except for a few stations, in the western and southwestern sides of the bay, as evidenced by the large amounts of monounsaturated PLFA. Such significant regional differences in microbial community structure of the bay indicate shifts in microbial community structure.

Although thrombomodulin (TM) in circulating blood is regarded as an indicator of vascular endothelial disorders, blood TM levels are also known to be affected by renal dysfunction. We measured plasma TM levels in primary glomerular disease (PGD) and lupus glomerulonephritis (GN) with the EIA method, and assessed the extent to which renal dysfunction and endothelial disorders contribute to plasma TM levels in these diseases. The plasma TM/serum creatinine (TM/Cr) ratio was significantly higher in lupus GN patients than in PGD patients or normal controls. A significant positive correlation was found between plasma TM and serum Cr levels in both PGD and lupus GN patients, but the slope (A) of the regression line (TM = A.Cr+B) in lupus GN patients was significantly steeper than in PGD patients. We conclude that plasma TM levels are greatly influenced by renal dysfunction, but that not only renal dysfunction but endothelial disorders may be an important determinant of increased plasma TM levels in diseases such as lupus GN.

Therapeutic effect of hemodialysis on gouty arthritis and tophi in 2 patients with chronic renal failure (CRF) is described. One patient was 74-year-old man with CRF due to benign nephrosclerosis, and had severe secondary gout. There were many tophi in metatarsophalangeal joints of the fingers and toes. Another patient was 44-year-old man with CRF probably due to familial gout. He had many tophi in elbows, knees, wrists, fingers and toes. In both cases initiation of hemodialysis treatment, at first temporally exacerbated gouty arthritis, but thereafter gradually eliminated the tophi. From these results, dialysis treatment is considered to be quite efficient method of treatment for gouty arthritis and tophi in patient with CRF. Gouty arthritis in CRF patient, which does not respond to the conservative therapy, should be considered to be one of the indices for commencement of hemodialysis.

A 68-year-old Japanese male (Case 1) and a 59-year-old Japanese male immigrant to Brazil (Case 2) who suffered from subcutaneous eosinophilic lymphoid granuloma (Kimura's disease) of several years duration, developed nephrotic syndrome. Renal biopsy demonstrated membranous nephropathy in Case 1 and minimal-change lesion in Case 2. Both patients were treated with prednisolone for several months. There was complete remission of nephrotic syndrome in eight years in Case 1 and in three months in Case 2. Proteinuria did not reappear after remission of nephrotic syndrome in either case. In contrast subcutaneous tumors subsided in both cases during steroid treatment but again became active immediately following discontinuation of the drug. These clinical observations suggest that, though some common factor(s) might mediate the development of both skin and renal lesions, the mechanism of action on these two target organs may differ, perhaps serving only as a "trigger" for the initiating mechanism of renal disease.

The distribution of phospholipid ester-linked fatty acids (PLFA) in sediments of eutrophic bays (Hiroshima Bay and Aki Nada) was studied to quantify the microbial biomass, community structure, and nutritional status. A total of 63 fatty acids in the range of C(10) to C(24) were determined. They consist of saturated fatty acids, branched fatty acids, monounsaturated fatty acids, and polyunsaturated fatty acids, and variation was revealed in the relative proportions of these fatty acids in sediments. On the basis of the PLFA concentration in sediments, the calculated microbial biomass showed variation (mean +/- standard deviation = 0.70 x 10 +/- 0.53 x 10 cells per g [dry weight] of sediment) in the eutrophic bays. In sediments, a higher amount of biomass was observed in the coastal area of Hiroshima Bay than that observed in the rest of the bay and adjacent Aki Nada. The microbial community structure of the present study area, as characterized by the PLFA profiles, showed very low percentages of polyunsaturated fatty acids and long-chain fatty acids characteristic of microeukary-otes and terrestrial input, respectively, and high percentages of fatty acids characteristic of bacteria. The distribution of PLFA profiles also showed the relative contribution of both aerobic and anaerobic bacteria, especially sulfate-reducing bacteria, in the study area. The relative proportions of PLFA revealed distinctive differences among the stations of the study area, as is evidenced from six clusters obtained for the PLFA profiles. The results of Tukey's honestly significant difference test further confirmed that the sediments in the coastal area of Hiroshima Bay were significantly enriched by a number of fatty acids when compared with other areas investigated where relatively few fatty acids were present in significant quantities. No marked variation in environmental parameters in the surface- and bottom-water samples was observed, indicating the absence of any water movement in the study area. Furthermore, low redox potential and the levels of sulfide in the sediment revealed the reduced condition of the sediment. The existing environmental conditions and pollution of the study area were attributed to the observed microbial community structure in the sediments.

A case of SLE with moderately deteriorated renal function due to lupus nephritis developed cryptococcal meningitis. Long term administration of amphotericin B (cumulative dose 5 g) combined with 5-flucytosine eradicated this fungal infection. Throughout amphotericin B administration urinary excretions of Na and K, as well as plasma HCO3 concentration were monitored, and, Na, K and HCO3 were supplemented orally and intravenously so much as to replace their urinary losses. Neither prominent water-electrolyte disturbance nor severe azotemia, which are the most serious side effects of amphotericin B, did not ensue. This case study indicates that sufficient water.electrolytes supplementation is important to prevent the nephrotoxicity of amphotericin B.

We report a case of massive pulmonary hemorrhage which emerged in the course of polyarteritis nodosa (PN). Pulmonary hemorrhage was the major manifestation which determined the mortality of this patient, though severe renal failure concurrently developed. The diagnosis of PN should be considered in all cases of pulmonary hemorrhage coexisting with renal failure. As pulmonary hemorrhage can be life-threatening, early diagnosis is essential for the prompt start of adequate therapy.

A 66-year-old man with kappa-light chain multiple myeloma had adult Fanconi syndrome. Renal tubular transport abnormalities consisted of renal tubular acidosis, renal glycosuria, aminoaciduria, phosphaturia and renal hypouricemia. After therapy for multiple myeloma, urinary Bence Jones protein became undetectable, and all these renal tubular abnormalities except urate wasting were corrected. Histological examination revealed electron-dense tubular and rod-like deposits in proximal tubular epithelium. This clinical observation suggests that the renal tubular transport defects were secondary to the myeloma process, possibly due to Bence Jones proteinuria.

Isolated ultrafiltration, hemodialysis & peritoneal dialysis (Tx) were recently used in the treatment of intractable heart failure (HF). We examined the relation between the response of HF to Tx and the residual kidney functions. Tx was carried out in 17 patients (Pts) with HF who did not respond to aggressive medical treatment. Ten Pts (R) responded to Tx and 7 Pts (N) did not. Serum urea nitrogen (UN), creatinine (Cr), uric acid (UA), sodium (Na), potassium (K), and chloride (Cl) concentrations on admission and before Tx were not different between R and N. Urine UN, Cr, Na, K, and Cl on admission and before Tx were also not significantly different. Fractional sodium excretions (FENa), renal failure indices (RFI), and urine/plasma Cr ratios (U/P Cr) on admission were 2.0 +/- 1.6, 2.7 +/- 2.2, and 30.5 +/- 20.0 in R and 5.9 +/- 4.2, 8.2 +/- 6.0 and 11.5 +/- 3.8 in N. They were significantly different (p less than 0.05). However, these did not differ before and after Tx. These data show that FENa, RFI and U/P Cr might be useful indices in predicting the responsiveness of intractable HF to Tx.

The mechanism of kaliuresis induced by massive antibiotic administration was studied using alpha-sulfobenzyl penicillin (SBPC). In experimental group (n = 8), urinary electrolytes excretion were compared between following the infusion of 10 g SBPC in 200 ml water at a constant rate and following the infusion of 48 mmol of NaCl (equal to that contained in 10 g SBPC) in 200 ml water. For the control group, 96 mmol NaCl in 400 ml water was infused (n = 5). In the experimental group, urinary Na (UNaV) and urinary K excretion (UKV) increased relative to the control period. In the control group, UKV was not increased although UNaV was increased (p less than 0.05). UKV following SBPC infusion was correlated with UNaV (p less than 0.05) and urinary SBPC excretion (p less than 0.05). The ratio of urinary anion gap to urinary cation [1-(urinary Cl concentration/(urinary Na concentration + urinary K concentration))] was significantly increased following SBPC infusion (p less than 0.005) but not in the control group. This increase in anion gap is possibly due to urinary SBPC, which will be ionized over 90% as nonreabsorbable anion in maximally acidic urine. We conclude that the kaliuresis induced by massive SBPC administration in man is probably caused by the nonreabsorbable anion effect of SBPC itself.

A 42-year-old housewife had hypouricemia (serum uric acid ranging from 0.5 to 1.5 mg/dl; 30-89 mumol/l), increased uric acid clearance (47.6-83.0 ml/min), increased maximum tubular secretory capacity for para-aminohippurate, and idiopathic edema. Urate excretion was only minimally suppressed by pyrazinamide, and paradoxically decreased by probenecid. Uric acid clearance did not show any appreciable change after long-term administration of ticrynafen. In response to an increment of extracellular volume by hypertonic saline infusion or long-term 9 alpha-fluorohydrocortisone administration, urate clearance did not show any substantial increase. These data may suggest that not only presecretory but possibly also postsecretory reabsorption of urate is impaired in this patient. No other renal tubular abnormalities were detected. Family study revealed that her renal hypouricemia is hereditary. She was unable to increase urinary excretion of sodium during hypertonic saline infusion and failed to change the response to the sodium-retaining action of 9 alpha-fluorohydrocortisone, presumably accounting for her edema.

Two patients had hypouricemia due to increased uric acid clearance. Their daily urinary uric acid excretions were normal. In both patients, pyrazinamide decreased urinary uric acid clearance to almost while probenecid increased it markedly. No other renal tubular or metabolic abnormalities were found. The serum electrolytes and the urinary electrolytes excretions showed no abnormalities. It appears that increased secretion of uric acid in the renal tubule is most probably responsible for hypouricemia in these patients. This report adds to the list of hypouricemic conditions due to a new isolated renal tubular abnormality.

We measured plasma levels of immunoreactive human atrial natriuretic factor (ANF) in chronic renal failure patients treated by hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD). Predialysis plasma ANF was significantly higher in HD patients (271.8 +/- 173.4 pg/ml) as compared to CAPD patients (81.8 +/- 80.5 pg/ml) and healthy subjects (31.5 +/- 19.8 pg/ml). Plasma volume was higher in HD patients than in CAPD patients. Plasma ANF and plasma volume showed a significant positive correlation. In HD patients, high plasma ANF value decreased significantly to a value comparable with that of CAPD patients after each dialysis. The removal rates of ANF by HD and CAPD were comparable. Ultrafiltration corresponding to 2% of body weight without dialysis also reduced plasma ANF. Thus, the difference in plasma ANF values between HD and CAPD patients seems to be mostly due to the difference in plasma volume, indicating that plasma ANF is sensitive to volume status even in chronic dialysis patients.

The mechanism of lowered renin-aldosterone system was investigated in 17 patients with diabetic nephropathy (serum Cr less than 3 mg/100 ml) with concomitant control of the blood sugar level. The response of plasma renin activity (PRA) to upright stimulation was lower in the low renin group (group I) than in the normal to high renin group (group II) and in the control group. The PRA response to theophylline was delayed in group I. The percentage of the luminal area of the arteriole in the biopsy specimens was larger in group I and the control group than in group II. Plasma aldosterone concentration (PAC) was not increased by angiotensin II in group I. Low PRA in diabetic nephropathy with slightly to moderately impaired renal function may not be due to hyaline destruction of the arteriolar walls, but to other factors such as sympathetic nervous dysfunction. The adrenal responses of PAC to angiotensin II may also be impaired.

The effect of long-term gentamicin administration on sodium, potassium, chloride and phosphorus concentrations was studied in individual rat renal tubular cells using electron microprobe analysis. Histological damage was apparent only in proximal tubular cells. The extent of damage was only mild after 7 days of gentamicin administration (60 mg/kg body wt/day) but much more pronounced after 10 days. GFR showed a progressive decline during gentamicin treatment. In non-necrotic proximal tubular cells, sodium was increased from 14.6 +/- 0.3 (mean +/- SEM) in controls to 20.6 +/- 0.4 after 7 and 22.0 +/- 0.8 mmol/kg wet wt after 10 days of gentamicin administration. Chloride concentration was higher only after 10 days (20.6 +/- 0.6 vs. 17.3 +/- 0.2 mmol/kg wet wt). Both cell potassium and phosphorus concentrations were diminished by 6 and 15, and by 8 and 25 mmol/kg wet wt after 7 and 10 days of treatment, respectively. In contrast, no major alterations in distal tubular cell electrolyte concentrations could be observed after either 7 or 10 days of gentamicin administration. As in proximal tubular cells, distal tubular cell phosphorus concentrations were, however, lowered by gentamicin treatment. These results clearly indicate that gentamicin exerts its main effect on proximal tubular cells. Decreased potassium and increased sodium and chloride concentrations were observed in proximal tubular cells exhibiting only mild histological damage prior to the onset of advanced tissue injury. Necrotic cells, on the other hand, showed widely variable intracellular electrolyte concentration patterns.

A 65-year-old woman with mild renal insufficiency had persistent hyperkalemia and hyperchloremic acidosis. Her plasma aldosterone level was relatively low for her hyperkalemia, and her urine pH was low. Fludrocortisone acetate administration corrected both hyperkalemia and acidosis by increasing urinary excretion of potassium and net acid, implicating deficient mineralocorticoid activity in the distal renal tubule in this patient. During this medication urinary ammonium excretion increased, but urine pH remained low, so that urinary titratable acid excretion did not decrease. On the other hand, correction of hyperkalemia by administration of a potassium-calcium exchange resin alone also resolved the acidosis by increasing urinary ammonium excretion. This increment exceeded the decrement of urinary titratable acid excretion, which was caused by raised urine pH secondary to increased urinary ammonium excretion, and resulted in increase of net acid excretion. Thus, in this patient, hyperkalemia appears to be a decisive causative factor in the acidosis, with deficient mineralocorticoid effect only contributing in part to the reduction of net acid excretion and the acidosis.