Encephalitis caused by human herpesvirus-6B in pancreas-after-kidney transplantation.

Human herpesvirus-6 (HHV-6) is a common pathogen among children, classically presenting with fever and rash that resolves without specific therapy. HHV-6 can be reactivated in the immunosuppressed patient. After bone marrow and solid organ transplantation, HHV-6 has been linked to various clinical syndromes, including undifferentiated febrile illness, encephalitis, myelitis, hepatitis, pneumonitis, and bone marrow suppression. However, HHV-6 encephalitis after pancreatic transplant has rarely been reported. Early diagnosis and treatment of HHV-6 encephalitis may be important for affected patients. We report the case of a 53-year-old pancreas-after-kidney transplant recipient who initially presented with high fever and confusion 3 weeks after operation. We managed to save the patient's life and preserve the pancreas graft function. We also review previously reported cases of HHV-6B encephalitis in solid organ transplant recipients.

Serum αKlotho as a Predictor of Graft Dysfunction After Kidney Transplantation.

OBJECTIVE: To improve the long-term survival rate after kidney transplantation (KTx), allograft injury should be identified as soon as possible. Regardless of aggressive immunosuppressive therapies, recipients of kidney transplants still have a significant risk of graft failure. No specific predictor for the progression of chronic kidney disease (CKD) after KTx has yet been found. Aberrant molecular mechanisms involving the αKlotho-fibroblast growth factor (FGF) 23 axis may be a useful determinant of renal impairment and graft failure over time. METHODS: Plasma and spot urine samples were collected from 47 patients 1 year after KTx. Evaluation of renal function after KTx was performed using levels of biomarkers including serum intact FGF23, soluble αKlotho, 25(OH) vitamin D (25(OH)D), and the difference in the estimated glomerular filtration rate (eGFR) between the first and third year after KTx (ΔeGFR). RESULTS: The median serum αKlotho, intact FGF23, and 25(OH)D were 516.3 pg/mL, 58.7 pg/mL, and 5.7 ng/mL, respectively. No marked changes in the standard biomarkers that regulate phosphate homeostasis were found. Serum αKlotho levels were associated with ΔeGFR. Multivariate regression analysis revealed that serum αKlotho levels significantly predicted a decrease in eGFR in the graft kidney 2 years after KTx, but serum 25(OH)D and FGF23 levels were not significant. Serum αKlotho levels showed an inverse correlation with fractional excretion of magnesium, which reflects tubular injury in the early stage of CKD. CONCLUSION: Measurement of serum αKlotho may serve as a useful predictor of KTx patients who require initiation of pre-emptive medication.

Efficacy of Eculizumab Therapy for Atypical Hemolytic Uremic Syndrome Recurrence and Antibody-Mediated Rejection Progress After Renal Transplantation With Preformed Donor-Specific Antibodies: Case Report.

Atypical hemolytic uremic syndrome (aHUS) develops as the result of unregulated complement progression and precipitates de novo thrombotic microangiopathy. Plasma therapy is used to control the progression of the complement cascade, but that therapy is not effective in all patients and is accompanied by risk of infection and/or allergy. Eculizumab has been reported as an efficient therapy for aHUS. We report the case of a 35-year old woman who underwent effective eculizumab therapy for aHUS recurrence and antibody-mediated rejection (AMR) progress after renal transplantation with preformed donor-specific antibodies (DSA). She developed end-stage renal disease due to suspicious IgA nephropathy at age 33 years. Kidney transplantation was performed at age 35 years, and aHUS recurred 2 weeks later, leading to the progressive hemolytic anemia and renal dysfunction. Therefore, she underwent plasma therapy several times. Because it was difficult to continue to plasma therapy for severe allergy, eculizumab was proposed as an alternate therapy. Treatment with eculizumab was initiated 36 days after renal transplantation. After 3 years of eculizumab treatment, and without plasma therapy, schistocytes decreased, haptoglobin increased to within normal limits, creatinine levels stabilized, and no further episodes of diarrhea were reported. At protocol biopsy 1 year after transplantation, she was diagnosed with C4d-negative subclinical AMR. However, her pathologic findings at follow-up biopsy 3 years after transplantation were recovered. We conclude that eculizumab alone, without plasma therapy, is sufficient to treat recurrence of aHUS and AMR due to DSA after renal transplantation and to maintain long-term graft function.

Substrate-binding region of cytochrome P-450SCC (P-450 XIA1). Identification and primary structure of the cholesterol binding region in cytochrome P-450SCC.

Cytochrome P-450SCC (P-450 XIA1) from bovine adrenocortical mitochondria was investigated using a suicide substrate: [14C]methoxychlor. [14C]Methoxychlor irreversibly abolished the activity of the side-chain cleavage enzyme for cholesterol (P-450SCC) and the inactivation was prevented in the presence of cholesterol. The binding of [14C]methoxychlor and cytochrome P-450SCC occurred in a molar ratio of 1:1 and the cholesterol-induced difference spectrum of cytochrome P-450SCC was similar with the methoxychlor-induced difference spectrum. [14C]Methoxychlor-binding peptides were purified from tryptic-digested cytochrome P-450SCC modified with [14C]methoxychlor. Determination of the sequence of the amino-acid residues of a [14C]methoxychlor-binding peptide allowed identification of the peptide comprising the amino-terminal amino-acid residues 8 to 28.

Characteristic properties of retinal oxidase (retinoic acid synthase) from rabbit hepatocytes.

Retinal oxidase (retinoic acid synthase) (EC 1.2.3.11) was purified electrophoretically, as a single protein band, from rabbit liver cytosol. The characteristic properties, enzymatic reaction mechanism, substrate specificity and kinetic parameters for retinals and molecular oxygen of the retinal oxidase were investigated. The Km values for all-trans-retinal of the retinal oxidase was the lowest than those for the other retinal derivatives. The retinal oxidase is a metalloflavoenzyme containing 2 FADs as the coenzyme, and 8 irons, 2 molybdenums, 2 disulfide bonds and 8 inorganic sulfurs. Its relative molecular mass was determined to be 270 kDa by gel filtration HPLC on a TSKgel G3000swXL column. Its minimum molecular mass was estimated to be 135 kDa by SDS-PAGE. The optical spectrum of the retinal oxidase showed absorption peaks at 275, 340 and 450 nm, and shoulders at 420 and 473 nm, in the oxidized form. The molecular extinction coefficients of the oxidase at selected wavelengths were determined. Circular dichroism spectra of the retinal oxidase were measured in the ultraviolet and visible regions. These spectra showed positive absorption in the visible region. The amino-acid composition was determined. The activity of the oxidase was not affected by any cofactors, such as NADP+, NAD+, NADPH and NADH, and it did not occur under anaerobic conditions. The oxidase was not inhibited by BOF-4272, a potent inhibitor of xanthine dehydrogenase, or rat anti-xanthine dehydrogenase IgG. Experiments on retinoic acid formation under 18O2 or H2(18)O demonstrated that the oxygen of water was incorporated into retinoic acid by the retinal oxidase, but not molecular oxygen.

Apolipoprotein-mediated cellular cholesterol/phospholipid efflux and plasma high density lipoprotein level in mice.

Helical apolipoprotein(apo)s generate pre-beta-high density lipoprotein (HDL) by removing cellular cholesterol and phospholipid upon the interaction with cells. To investigate its physiological relevance, we studied the effect of an in vitro inhibitor of this reaction, probucol, in mice on the cell-apo interaction and plasma HDL levels. Plasma HDL severely dropped in a few days with probucol-containing chow while low density protein decreased more mildly over a few weeks. The peritoneal macrophages were assayed for apoA-I binding, apoA-I-mediated release of cellular cholesterol and phospholipid and the reduction by apoA-I of the ACAT-available intracellular cholesterol pool. All of these parameters were strongly suppressed in the probucol-fed mice. In contrast, the mRNA levels of the potential regulatory proteins of the HDL level such as apoA-I, apoE, LCAT, PLTP, SRB1 and ABC1 did not change with probucol. The fractional clearance rate of plasma HDL-cholesteryl ester was uninfluenced by probucol, but that of the HDL-apoprotein was slightly increased. No measurable CETP activity was detected either in the control or probucol-fed mice plasma. The change in these functional parameters is consistent with that observed in the Tangier disease patients. We thus concluded that generation of HDL by apo-cell interaction is a major source of plasma HDL in mice.

Effect of probucol in lecithin-cholesterol acyltransferase-deficient mice: inhibition of 2 independent cellular cholesterol-releasing pathways in vivo.

Cellular cholesterol release takes place by at least 2 distinct mechanisms: the lecithin-cholesterol acyltransferase (LCAT)-driven net efflux by cholesterol diffusion and the generation of high density lipoprotein (HDL) with cellular cholesterol and phospholipid on the cell-apolipoprotein interaction. Therefore, LCAT deficiency impairs the former pathway, and the latter can be inhibited by probucol, which interferes with the apolipoprotein-cell interaction. Hence, probucol was given to the LCAT-deficient mice in the attempt to suppress both of these pathways. The mice were fed low (0.2%) and high (1.2%) cholesterol diets containing 0.5% probucol for 2 weeks. LCAT deficiency and probucol markedly decreased plasma HDL, and the effects were synergistic. Tissue cholesterol content was lower in the adrenal glands and ovaries in the LCAT-deficient mice and in the probucol-treated mice, suggesting that HDL is a main cholesterol provider for these organs. It was also moderately decreased in the spleen of the low cholesterol-fed female mice and in the thyroid gland of the low cholesterol-fed male mice. On the other hand, the esterified cholesterol content in the liver was substantially increased by the probucol treatment with a high cholesterol diet in the LCAT-deficient mice but not in the wild-type mice. Among the groups, there was no significant difference in the tissue cholesterol levels in other organs, such as the liver, spleen, thymus, brain, erythrocytes, thyroid gland, testis, and aorta, resulting from either LCAT deficiency or probucol. Thus, the apolipoprotein-mediated mechanism plays a significant role in the export of cellular cholesterol in the liver, indicating that the liver is a major site of the HDL assembly. Otherwise, tissue cholesterol homeostasis can largely be maintained in mice even when the assembly of new HDL is inhibited by probucol in the absence of LCAT. Nonspecific diffusion of cholesterol perhaps adequately maintains the homeostasis in the experimental condition.

Retinal oxidase is identical to aldehyde oxidase.

Retinal oxidase (EC 1.2.3.11) and aldehyde oxidase (EC 1.2.3.1) were compared with respect to their enzymatic and physiochemical properties. It was found that the molecular weights, subunits, optical spectra, chemical and immunological properties, cellular localization and substrate specificities of the two oxidases are identical on almost all points. The physiological function of aldehyde oxidase appears to be the synthesis of retinoic acid from retinal.

Expression cloning of a sheep adreno-ferredoxin using the polymerase chain reaction.

In addition to the selective amplification of cDNA from total RNA by the PCR method, the distinctive properties of ferredoxin-expressing colonies can be used for cloning a ferredoxin cDNA. This strategy for cloning and expressing cDNA in E. coli was applied to a sheep adreno-ferredoxin. The expressed sheep ferredoxin showed a spectral pattern typical of [2Fe-2S] proteins. The amino acid sequence deduced from the DNA sequence showed that the mature form of sheep ferredoxin consists of 128 amino acid residues. This rapid and simple method for cloning and expressing cDNA can be applied to other ferredoxins.

Discrimination between NK and LAK cytotoxic activities of murine spleen cells by MTT assay: differential inhibition by PGE(2) and EDTA.

In the present study we propose a mathematical approach to improve the analysis of NK and LAK activities measured by MTT assay adapted for murine cells. We found that to calculate NK activity, high E:T ratios should be used (up to 50:1) and the phenomenon fits to a linear least-squares analysis. However, 5-fold less effector cells (10:1, E:T) should be used to detect LAK activity and the phenomenon has a nonlinear exponential behavior. Using this approach, we showed that EDTA inhibits LAK but not NK activity whereas PGE(2) inhibits NK but not LAK activity. In conclusion, this analytical approach allowed the discrimination between NK and LAK activities and exposed differences between these two cytotoxic activities.

Clinical evaluation of long-term treatment using cernitin pollen extract in patients with benign prostatic hyperplasia.

Seventy-nine patients with benign prostatic hyperplasia (BPH) were treated with cernitin pollen extract. Patient ages ranged from 62 to 89 years (mean, 68 years). Mean baseline prostatic volume was 33.2 cm3. Cernitin pollen extract was administered in a dosage of 126 mg (2 tablets, 63 mg each), three times a day, for more than 12 weeks. Symptom scores, based on a modified Boyarsky scoring scale, uroflowmetry, prostatic volume, residual urine volume, and urinalysis results were examined before and after administration of cernitin pollen extract. Symptom scores significantly decreased from baseline, and the favorable results continued during the treatment period. Urine maximum flow rate and average flow rate increased significantly from 9.3 mL/s to 11 mL/s and from 5.1 mL/s to 6 mL/s, respectively. Residual urine volume decreased significantly from 54.2 mL to less than 30 mL. There was no change in prostatic volume. However, 28 patients treated for more than 1 year showed a mean decrease of prostatic volume to 26.5 cm3. No adverse reactions were observed. Clinical efficacy at 12 weeks was rated excellent, good, satisfactory, and poor in 11%, 39%, 35%, and 15% of patients, respectively. Overall clinical efficacy was 85%. In conclusion, cernitin pollen extract showed a mild beneficial effect on prostatic volume and urination variables in patients with symptomatic BPH.

Plant responses to short- and long-term exposures to high carbon dioxide levels in closed environments.

When higher plants are exposed to elevated levels of CO2 for both short- and long-term periods photosynthetic C-gain and photoassimilate export from leaves are generally increased. Water use efficiency is increased on a leaf area basis. During long-term exposures, photosynthesis rates on leaf and whole plants bases are altered in a species specific manner. The most common pattern in C3 plants is an enhanced rate of whole plant photosynthesis in a well irradiated canopy. Nevertheless, in some herbaceous species prolonged exposure to high CO2 results in remobilization of nitrogenous reserves (i.e., leaf protein degradation) and reduced rates of mature leaf photosynthesis when assayed at ambient CO2 and O2 levels. Both short- and long-term exposures to those CO2 levels (i.e., 100 to 2,000 microliter l-1) which modify photosynthesis and export, also modify both endogenous ethylene gas (C2H4) release, and substrate, 1-aminocyclopropane-1-carboxylic acid (ACC), saturated C2H4 release rates from irradiated leaves. Photosynthetically active canopy leaves contribute most of the C2H4 released from the canopy. Prolonged growth at high CO2 results in a persistent increase in the rate of endogenous C2H4 release from leaves which can, only in part, be attributed to the increase of the endogenous pools of C2H4 pathway intermediates (e.g., methionine, M-ACC, and ACC). The capacity for increasing the rate of C2H4 release in response to short-term exposures to varying CO2 levels does not decline after prolonged growth at high CO2. When leaves, whole plants, and model canopies of tomato plants are exposed to exogenous C2H4 a reduction in the rate of photosynthesis can, in each case, be attributed to the classical effects of C2H4 on plant development and morphology. The effect of C2H4 on CO2 gas exchange of plant canopies is shown to be dependent on the canopy leaf area index.

[Clinical study of carfecillin in chronic urinary tract infection (author's transl)].

1. Ten patients with chronic urinary tract infection by Pseudomonas aeruginosa or Proteus species were treated with carfecillin. Excellent response was seen in one case, fairly good in 5 cases and clinical effective rate was 60%. 2. The recurrence suppression effect of carfecillin was examined in two patients suffering from complicated urinary tract infection. In both cases, recurrence was not found when carfecillin was administered for a week after the effective pretreatment of carbenicillin, but found when administered for two weeks. 3. Side effects were observed in 3 cases (itching, tinnitus, diarrhea).

[Tunica albuginea cyst: a case report].

A 47-year-old male visited our hospital complaining of painless swelling of the right scrotum. Ultrasonography demonstrated hydrocele and a 13 x 12 x 10 mm cystic space along the margin of the right testis. Hydrocelectomy and simple resection of the cyst were performed. Pathologic examination of the excised cyst showed a serous cyst lined with simple flattened epithelium. Ultrasonography is useful for the diagnosis of tunica albuginea cyst.

[Clinical evaluation of cernilton in the treatment of the benign prostatic hypertrophy].

Cernilton was given clinically to 30 patients with benign prostatic hypertrophy. Cernilton was given orally at least for 12 weeks at a daily dose of 6 tablets in three divided doses. The overall clinical efficacy on subjective symptoms was 80%, and that on objective signs, 43%. During the administration period of Cernilton, no serious untoward effects were observed in either the clinical or laboratory findings. It is, therefore, suggested that, from the clinical point of view, Cernilton is a useful and safe drug in the treatment of benign prostatic hypertrophy.

[A case of hydronephrosis caused by renal stones with elevated serum levels of CA-19-9 and CA-125].

A case of hydronephrosis caused by renal stones with elevated serum levels of carbohydrate antigens 19-9 (CA-19-9) and 125 (CA-125) is reported. A 74-year-old woman was hospitalized with pyelonephritis. The results of computerized tomography and endoscopy suggested that the patient did not have pancreatic or ovarian cancer, but laboratory tests were significant for serum CA-19-9 greater than 1,000 U/ml (normal less than 37) and serum CA-125 78 U/ml (normal less than 35), which are markers for such tumors. Abdominal X-ray films showed stones in the pelvis of the right kidney. Excretory urography showed that the right kidney was not functioning. Computerized tomography showed severe right hydronephrosis with a thin renal cortex. Complete obstruction of the ureteropelvic junction of the kidney was seen by retrograde pyelography. During percutaneous pyelography, aspiration of the pelvic urine was done, and the sample had a high concentration of CA-19-9 (250,000 U/ml), but no cancer cells. The patients underwent right nephrectomy. The pelvic urine was tested for both CA-19-9 and CA-125 this time, and both were high (190,000 U/ml and 5,100 U/ml, respectively). Pathological evaluation showed no evidence of a malignant tumor. The epithelium lining the renal pelvis was stained for both CA-19-9 and CA-125 using the avidin-biotin-peroxidase complex method. Serum levels of the markers returned to normal after nephrectomy.

[Clinical study of terodiline hydrochloride for the treatment of urinary frequency and urinary incontinence, and its cardiovascular adverse effects].

We evaluated the effectiveness and side effects of terodiline hydrochloride in 109 patients with urinary frequency and urinary incontinence. The drug was administered at a dose of 24 mg once a day or 12 mg twice a day for 4 weeks. Symptoms such as urinary frequency and urinary incontinence were alleviated in 101 out of 109 patients (92.7%). Mild side effects such as thirst, dysuria, sense of residual urine, orthostatic hypotension and arrhythmia were observed in 9 out of 109 patients (8.2%). Side effects such as orthostatic hypotension and arrhythmia were observed on the 28th day or the 20th day of the administration, but these symptoms disappeared with discontinued use of this medicine. The results obtained from this study suggest that terodiline hydrochloride may be greatly useful for the patients with urinary frequency and urinary incontinence. But we must take account of the side effects such as orthostatic hypotension and arrhythmia.

[Clinical study on cefmenoxime (CMX) in urology].

Basic and clinical studies were made on Cefmenoxime (CMX), a new cephalosporin antibiotic, and the following results were obtained. The serum concentration of CMX was examined in four healthy adults after administration of 250 mg of CMX by intramuscular injection, intravenous injection and one-hour intravenous drip infusion (cross over). In the case of intramuscular injection, the peak value of 5.9 micrograms/ml was obtained 30 minutes after administration, and the half-life in serum was 1.41 hours. In the case of intravenous drip infusion, injection, a concentration value of 11.1 micrograms/ml on the average was obtained after 15 minutes of administration, and the half-life in serum was 1.26 hours. In the case of intravenous drip infusion, the concentration was 12.4 micrograms/ml upon completion of drip infusion, and CMX disappeared from serum at a half-life of 0.94 hour. The urinary recovery up to 6 hours was from 60 to 70% in each The efficacy rate of this preparation was 100% for 4 cases of acute simple cystitis. The efficacy rate of CMX was 70% for 10 cases of complicated urinary tract infection; the 3 cases in which CMX was not effective were patients with a residual catheter and Pseudomonas persisting or appearing as superinfection. It was noted that Serratia, which was resistant to the conventional cephalosporin antibiotics, became negative. No subjective side effects due to the administration of this preparation were observed. As for abnormal laboratory findings, a slight and transient rise in transaminases was observed in one case. On the basis of the above-mentioned results, it was concluded that CMX is an effective preparation for the treatment of urinary tract infections.

[Endocrine chemotherapy for prostatic cancer].

We carried out a randomized joint study on endocrine therapy and endocrine chemotherapy for prostatic cancer at our department and 17 affiliated institutions. Of 80 patients entered, 39 patients were treated with chlormadinone acetate alone (group A) and 41 patients were treated with chlormadinone acetate in combination with UFT (group B). After excluding 10 inappropriate patients, Stage C was observed in 14 patients in group A and 13 in group B, and stage D in 20 patients in group A and 23 in group B. Side effects were observed in 8.8% (3/34) in group A and 22.2% (8/30) in group B without a significant difference. The anti-tumor effects (response rate) and clinical effects with respect to each item did not significantly differ between the two groups. The non-recurrence rate and survival rate were significantly higher in group B than in group A. These findings suggest the usefulness of endocrine chemotherapy using UFT.

[Results of Kock pouch construction fully utilizing an auto-suture instrument].

From March 1987 to the end of February 1991, we performed Koch pouch construction as a urinary diversion on 20 patients who had undergone radical cystectomy due to bladder cancer. The operation was done according to the method of Skinner et al. We fully utilized an auto-suture instrument to ensure safe and stable suturing of the ileum and to shorten the operating time. It was of great concern that the staples placed at several portions might cause stone formation or aggravate infection. However, stone formation was observed only in one patient (5%) at the tip of a nipple valve in which a staple became the nucleus of the stone. Staples are usually not regarded as an obstacle as they are usually covered by the mucous membrane. In all patients, the maximum capacity of the pouch was more than 500 ml, intra-pouch pressure was kept low even when the pouch was inflated up to the maximum capacity, and reflux of urine into the upper urinary tract was not observed. As for complications, there was a slight degree of obstructive uropathy in 4 patients (20%), difficulty in catheter insertion was noted in 3 patients (15%), and stress incontinence-like urinary leakage was present in one patient when the capacity exceeded 500 ml. However, there were no complications which necessitated reoperation. In terms of blood chemistry, although there was a tendency towards a slight increase in BUN or hyperchloremia, no specific treatment was necessary as far as the kidney function was normal.(ABSTRACT TRUNCATED AT 250 WORDS)