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Anti-alphabeta T cell receptor monoclonal antibody (R73) has been reported to be a potent immunosuppressant. The suppressive effects of this antibody on allograft rejection after corneal transplantation are unknown.Orthotopic rat penetrating keratoplasty was performed using Lewis rats as recipients and Brown Norway and Fisher rats as donors. The treated groups received R73 intraperitoneally until day 12 after the transplantation. In grafted rats with or without R73 treatment, cytokine expression of the aqueous humor, corneal-infiltrating cells, draining lymph nodes, and splenocytes was determined. Delayed-type hypersensitivity (DTH) responses were compared.All allografts in the untreated controls of Fisher-to-Lewis or BN-to-Lewis rat combinations were rejected within 14 days. In contrast, indefinite survival rates of the postoperative R73-treated group increased to 86% in the Fisher-to-Lewis and 23% in the Brown Norway-to-Lewis combinations, respectively. Interferon-y, interleukin (IL)-2 (T helper [Th]1), and IL-10 (Th2), but not IL-4 (Th2), expression of the eye and DTH responses in the control group were suppressed in the R73-treated group. Both IL-2 and IL-10 expression after mixed lymphocyte culture in the R73-treated group were significantly lower than those of the naive and untreated control group.alphabeta T cell receptor-targeted therapy prevents allograft rejection in rat corneal transplantation as evidenced by suppression of DTH responses. The cytokine profile after R73 treatment was characterized by low interferon-gamma, IL-2, and IL-10, and high IL-4 expression.

S-8921 (methyl 1-(3,4-dimethoxyphenyl)-3-(3-ethylvaleryl)-4-hydroxy-6,7,8-trimeth oxy-2- naphthoate, CAS 151165-96-7) is a novel hypocholesterolemic agent which was found to inhibit ileal Na+/bile acid cotransporter. In this report, the pharmacokinetic profile of S-8921 was studied in rats and dogs. After dosing of 14C-S-8921 to rats at 1 to 25 mg/kg as 0.5% methylcellulose (MC) suspension, tmax was observed during 5-6 h, and AUCs increased with the dose, but not proportionally. The elimination half-lives were around 38-41 h for the doses examined. The apparent absorption ratio of 5 mg/kg of 14C-S-8921 as MC suspension was about 14%. Most of the radioactivity (98% of dose) was excreted into the feces and only 1-2% into the urine. Biliary excretion of radioactivity after dosing of 1, 5 or 25 mg/kg was 22, 20, 15%, respectively. Saturation of the absorption process was suggested. Even in case of intravenous dosing, about 88% was excreted into the bile. Enterohepatic circulation of biliary metabolites was also observed in rat. Its extent was small (6%), but, it may be contribute to the slow elimination of S-8921 from rat. The highest radioactivity was observed in the liver, with other tissues showing similar radioactivity profiles to that of plasma. The elimination half-lives of radioactivity from tissues were very long, e.g. 68 h for the liver and 58 h for the kidney. After 14 days multiple dosing, most tissues showed about two times higher radioactivity than that after a single dose. The simulation curves of liver and plasma showed a good fit with those of the observed values. These results suggested that there is no serious accumulation of radioactivity in tissues by multiple dosing of 14C-S-8921 in rats. The plasma radioactivity after oral dosing of 5 mg/kg of 14C-S-8921 to dogs as an MC suspension reached maximum concentration (c.a. 33 ng/ml) at 2 h, then decreased very slowly with a half-life of 169 h. The apparent absorption ratio was 4.6% for MC suspension. The excretion of radioactivity into bile, feces and urine after oral dosing of 14C-S-8921 at 5 mg/kg as an MC suspension were 3.0%, 94.6% and 0.3%, respectively. Even in the case of intravenous dosing, urinary excretion was very small (2.2%) and most of the radioactivity was excreted very slowly into the feces. The major metabolite of S-8921 in rat bile was its glucuronide. Other minor metabolites identified were the demethylated forms of 7-methoxy and 4'-methoxy moieties of S-8921. They were also excreted into bile as their glucuronides.

1. S-1153, a non-nucleoside agent that is under development in the USA as a new anti-HIV agent, has potent antiviral activity based on the inhibition of reverse transcriptase. 2. S-1153 was incubated with rat liver microsomes and NADPH, and seven metabolites were formed. The main metabolites were identified as the S-oxide, N-oxide and sulphone of S-1153. 3. Two other minor metabolites were assumed to be S-1153 hydroxylated on the isopropyl moiety. 4. Our findings confirmed the existence of at least three oxidative metabolic pathways of S-1153.

In 1986 an albino mouse with cream yellow coat color was discovered in a breeding colony of strain CAL20, which is an IgH-C congenic strain of BALB/c mice, supported by the Institute for Experimental Animals, Faculty of Medicine, Kanazawa University. Genetic analysis revealed that the cream yellow coat color phenotype was controlled by a single recessive mutant gene on chromosome 13. A preliminary study with biochemical and histologic examinations showed that cream yellow hair contained more fatty acid than unaffected normal hair and a large number of lipid droplets accumulated in parenchyma cells of the liver in mutant mice, as early as the age of 32 days old, suggesting that the cream yellow coat color was due to unusual lipid metabolism. The locus was designated cream fur locus and was given the gene symbol crf. In addition, it was found that recombination frequencies in the vicinity of the region of the crf locus were markedly different between male and female meiosis.

Although prostate-specific antigen (PSA) is a valuable marker of prostate cancer, some untreated patients with advanced prostate cancer have normal PSA values. Over a period of 5 years, we reviewed pretreatment serum PSA levels in 131 patients with advanced prostate cancer (stages C and D). Ten patients (7.6%) had normal PSA values. The histological type of prostate cancer associated with normal PSA values was variable and the prognosis was not so poor. Immunostaining for PSA was performed on the resected prostate tissue of the 10 patients. PSA staining was positive in 5 cases, negative in 3 cases, and equivocal in the remaining 2 cases. In conclusion, PSA is not always useful, especially for following patients with normal PSA values.

There have been few reports concerning the cytotoxic effects of fluoroquinolone antibiotics on transitional cell carcinoma. This investigation was designed to study the cytotoxic effects of fleroxacin and ciprofloxacin on transitional cell carcinoma quantitatively in vitro.Two transitional cell carcinoma cell lines, MBT-2 and T24, were used in this study. The effects of fleroxacin and ciprofloxacin on cell proliferation were determined by counting the number of living cells and by colorimetric MTT assay.Two fluoroquinolones, fleroxacin and ciprofloxacin, significantly inhibited cell proliferation in a dose-dependent manner at a concentration of 50-800 microg/mL in both cell lines. Compared with the cytotoxic effects of the two antibiotics, the inhibitory activity of ciprofloxacin on cell proliferation significantly exceeded that of fleroxacin in the MBT-2 cell line. However, the two fluoroquinolones did not have significantly different effects on the T24 cell line.Fleroxacin and ciprofloxacin significantly affect cell proliferation in transitional cell carcinoma cell lines. The results encourage further study of the possibility of clinical application of some fluoroquinolones to prevent recurrence of urinary bladder tumors because the urinary excretions after oral administration of these drugs are quite high.

A double-blind study was conducted to evaluate the efficacy, safety and usefulness of cimetropium bromide (DA3177) in the patients with pain caused by upper urinary calculus at a daily dose of 75 mg t.i.d. (Group D, 97 patients) in comparison with scopolamine butylbromide at a daily dose of 60 mg t.i.d. (Group B, 101 patients). According to patient's impression, the rate of "moderately improved" or better was significantly higher in Group D (68.7%) than in Group B (53.5%; Wilcoxon 2 sample test: p = 0.0044). For pain, the rate of "moderately improved" or better was 69.1% in Group D and 60.4% in Group B. In global improvement, the rate of "moderately improved" or better was significantly higher in Group D (70.1%) than in Group B (61.4%; Wilcoxon 2 sample test: p = 0.0469). The rate of "no problem in safety" showed no significant difference between Group D (91.5%) and Group B (93.3%). Adverse reactions occurred in 8.5% in Group D and 6.7% in Group B. The major adverse reactions were "dry mouth", "abdominal distension", "constipation" and "nausea". The rate of "useful" or better was 68.7% in Group D, and 60.4% in Group B. In conclusion, DA3177 was confirmed to be a useful drug for patient with pain caused by upper urinary calculus.

We studied the effect of recombinant murine interferons (rMuIFNs) on the growth of Orientia (formerly Rickettsia) tsutsugamushi Gilliam in mouse L929 cells. Rickettsial growth was measured by flow cytometry. rMUIFN-gamma inhibited the growth of O. tsutsugamushi at the concentrations of 100 i.u./ml and 1,000 i.u./ml in accord with previous reports. Relatively low concentrations (10 i.u./ml and 100 i.u./ml) of rMUIFN-beta also inhibited the growth of O. tsutsugamushi. On the other hand, high concentrations (1,000 i.u./ml and 10,000 i.u./ml) of rMuIFN-beta enhanced the growth of the rickettsia. This enhancement of rickettsial growth was blocked by anti-murine IFN-beta monoclonal antibody (MoAb). rMuIFN-beta also enhanced the growth of Rickettsia sibirica 246 in L929 cells to some extent.

Wild measles virus isolated in a marmoset lymphoblastoid B95a cell line induced rashes and Koplik's spots when inoculated parenterally in cynomolgus and squirrel monkeys. Marked leukopenia. associated with transient decrease in the CD4(+)-to-CD8+ T-cell ratio also was induced. Virus growth, as well as histologic lesions of necrosis and giant cell formation, was observed in the lymphoid tissues. Thus clinical signs of acute measles were successfully induced in monkeys by inoculation with cell-culture-grown measles virus. These nonhuman primate models of measles will be useful for study of the pathogenesis of acute measles virus infection in terms of generalized clinical signs of disease, leukopenia, and changes in the lymphocyte subsets.

The present investigation was designed to study interactions between Madin-Darby canine kidney (MDCK) cells and calcium oxalate monohydrate (COM) crystals and to clarify the significance of these crystal-cell interactions in stone pathogenesis. MDCK cells cultured in the presence of COM crystals showed a time-dependent uptake of crystals; this was specific for COM crystals. In the dynamic model system designed to study these phenomena under more physiological conditions, COM crystals adhered to the cell surface and were subsequently internalized. In this endocytotic process, the microvilli of the cell appeared to play an important role. The observation by scanning electron microscopy of complexes consisting of aggregated COM crystals and cell debris led us to speculate that adhesion and endocytosis of crystals might provide the calculus nidus for aggregation and retention of crystals in the renal tubule. Furthermore, glycosaminoglycans and the macromolecular fraction of human urine were shown to have the ability to inhibit the cellular uptake of crystals. Evidence that similar processes may also occur in vivo was obtained using an experimental stone model in rats. Our experiments revealed that most of the COM crystals adhered to the tubular cells and some crystals were endocytosed by the cell. Thus, these crystal-cell interactions might be one of the earliest processes in the formation of kidney stones. Further elucidation of the mechanism and the regulatory factors involved in this process may provide new insight into stone pathogenesis.

Antihydrogen may be confined by radio frequency cavity mode fields at sufficiently low temperature, estimated to be T

The notion that oligonucleotides can modulate gene-specific expression was established more than a decade ago. Recent advances in molecular genetics have broadened the armamentarium used to manipulate gene expression in biological systems including triplex DNA, antisense RNA/DNA, and ribozymes (catalytic RNA). These oligonucleotides demonstrated important early application to the elucidation of cellular signaling pathways. More recently, studies with these agents have probed their utility as potential therapeutic agents, especially in the realm of cancer. With the implementation of gene therapy in early clinical trials, oligonucleotide-mediated suppression of gene expression has emerged as an important strategy for gene therapy. This review will discuss the current knowledge in this field, focusing on the biology of triplex DNA, antisense oligonucleotides, and ribozymes.

One hundred and sixty one patients with upper urinary stones were examined for antimicrobial prophylaxis following extracorporeal shock wave lithotripsy (ESWL). They were divided into two groups, the low-risk group (n = 133) and high-risk group (n = 28), according to the risk factors of urinary tract infection. The patients in the low-risk group were further randomized into two groups which were orally given ofloxacin for 7 days after ESWL (Group A, n = 66), no antimicrobial (Group B, n = 67). The patients in the high-risk group were randomly subdivided into three groups which were given flomoxef intravenously for 2 or 3 days and ofloxacin for 4 or 5 days thereafter (Group C, n = 10), flomoxef only for 2 or 3 days and no drugs later (Group D, n = 10), ofloxacin for 7 days (Group E, n = 8). In all of the patients in the low-risk group, during the 7 days after ESWL, fever elevation was observed in only 1.5% of patients, and bacteriuria in 10.0% on the 7th day. There was no difference in frequency of fever elevation and bacteriuria following ESWL between Group A and Group B. These findings indicate that prophylactic antimicrobial after ESWL treatment is not necessary for low risk patients with urinary tract infections. In the high-risk group, the over-all rates of fever elevation and bacteriuria were 21.4% and 24.0% respectively. The difference of effectiveness among the prophylactic regimens of the three groups (Group C, D, E) was not shown.(ABSTRACT TRUNCATED AT 250 WORDS)

Numerical stability of the two-fluid model when the high-order upwind difference method is applied was systematically clarified using a single linear model equation. The results of the examination were verified using an actual two-fluid model. It was confirmed that the high-order methods tend to yield unstable numerical solutions compared with the first-order upwind difference method, and the method which includes an explicit diffusion term in a basic equation was proposed in order to conduct numerically stable calculation with the high-order method. It was also demonstrated by calculating a faucet flow problem that the high-order method gives a more accurate numerical solution than the first-order method.

A joint multi-institution study was conducted on the efficacy of Sairei-to, centering on urinary tract fibrosis. The subjects consisted of 18 patients with retroperitoneal fibrosis (including 3 women), 77 patients with plastic induration of penis, 5 patients with sclerotic lipogranuloma (all men), and 67 patients with hemorrhagic cystitis (including 6 men). As a rule, Sairei-to was administered in monotherapy for periods of 4 weeks or longer. Efficacy was most pronounced in the patients with sclerotic lipogranuloma and plastic induration of penis, with overall improvement rates (percentage of patients with ratings of effective or better) of 80% in the former and 77.9% in the latter group. The overall improvement rate in the patients with retroperitoneal fibrosis was 61.1%. In the above diseases, there were numerous patients concurrently administered drugs such as antiinflammatory enzyme preparations and corticoid preparations, and the improvement rates were somewhat higher in these patients treated concurrently with other drugs. Outstanding efficacy was also seen in hemorrhagic cystitis. Dividing the patients into irradiation and non-irradiation groups, respective overall improvement rates of 77.8% and 82.8% were obtained, with the non-irradiation group showing a slightly higher rate. The non-irradiation group showed slightly higher improvement rates in the subjects treated concurrently with drugs such as antibacterial drug. Conversely, the irradiation group showed significantly superior rates for monotherapy. Side effects such as mild gastrointestinal disturbances were seen in only 13 of 167 patients (7.8%), and the utility of this drug in treatment of the above diseases should be held in high regard.

The TOSOH II PA (AIA-PACK PA in the U.S.A.) monoclonal immunoenzyme assay was used and the clinical usefulness of prostate specific antigen (PSA) was evaluated in 39 men with prostatic cancer and 32 men with benign prostatic hyperplasia (BPH) confirmed pathologically. We evaluated the lower limit of detection in this assay by the mean PSA level plue 3 standard deviations in 5 separate experiments with a zero control sera as well as the mean PSA level minus 3 standard deviations in 5 separate experiments with serial dilutions of a known concentration of PSA. PSA concentrations of 0 to 0.25 ng/ml could not be distinguished from the zero control. Therefore, we set the lower limit of detection for the assay as 0.25 ng/ml. At our laboratory, the normal standard value was determined by the mean PSA level plus 3 standard deviations in 79 healthy men as 2.3 ng/ml. Of patients that underwent radical cystoprostatectomy for bladder cancer, all had PSA levels less than 0.25 ng/ml, while only 6% had PAP levels less than 0.11 ng/ml, the lower limit of detection in the TOSOH II PAP assay. We compared TOSOH II PA with Markit PA, a commonly used assay in Japan. Although there was a close linear correlation (r = 0.90) between the TOSOH II PA and Markit PA, the difference of slope in the linear regression lines was great, it was thought due to anti-PSA antibodies in each assay recognizing different epitopes of PSA in the blood.(ABSTRACT TRUNCATED AT 250 WORDS)

OBJECTIVE To study the change in lymphocyte subsets of a renal allograft recipient who acquired human immunodeficiency virus (HIV) infection. PATIENT AND METHODS A 53-year-old Japanese man who acquired HIV infection at the time of renal transplantation and died from opportunistic infection 3 years later was studied. Lymphocyte subsets were examined serially throughout his clinical course. RESULTS The numbers of CD4 positive cells were severely decreased but those of CD8 positive cells were stable; the CD 4/8 ratio was extremely low. The numbers of B cells were also decreased but production of immunoglobulin was increased. In spite of this immunosuppressive state, graft rejection was noted when the patient's immunosuppressive medication was reduced. CONCLUSION The lymphocyte subsets of renal transplant patients with HIV infection should be closely observed, as should the nature and timing of opportunistic infection in relation to transplantation, and the administration of immunosuppressive medication.

An early phase II study of irinotecan (CPT-11) in patients with advanced or recurrent breast cancer was undertaken by a cooperative study group of 15 institutes in Japan. CPT-11 was administered by intravenous drip-infusion. The administration schedules were 100 mg/m2 weekly (regimen A), 150 mg/m2 biweekly (regimen B), and 200 mg/m2 every 3-4 weeks (regimen C). There were 4 partial responses (PRs), 12 cases with no changes (1 minor response) and 9 cases of progressive diseases with a response rate of 16% (4/25). One out of 7 patients on regimen A and 3 patients out of 15 patients on regimen C achieved PR with a response rate of 14% and 20%, respectively. In three out of 4 PRs, prior chemotherapy, endocrinotherapy or radiotherapy had failed. Major adverse reactions were leukopenia 28/33 (85%), neutropenia 19/25 (76%), anemia 15/33 (46%), nausea/vomiting 28/33 (85%), anorexia 25/33 (76%), diarrhea 22/33 (67%) and alopecia 20/33 (61%). The incidence of leukopenia and thrombocytopenia seemed to be higher in regimen C than regimen A, and diarrhea was also more severe in regimen C than regimen A. The recovery of leukopenia was delayed in some patients on regimen C. The results suggested that CPT-11 was effective against advanced or recurrent breast cancer. The recommended administration schedule for a late phase II study was thought to be 100 mg/m2 weekly, considering efficacy and safety.

Recently, interactions of crystals and tubular cell of the kidney have been extensively examined on inner medullary collecting duct epithelial cells in primary culture by Wiessner et a11 and Riese et al2, 3. However, the exact and specific processes that mediate attachment of stone crystals to tubular epithelium are not yet known.

The present investigation was designed to study adhesion of calcium oxalate crystals on the surface of intact MDCK cells quantitatively, and to estimate the effects of glycosaminoglycans (GAGs) and cell injuries on these adhesions. Calcium oxalate monohydrate (COM) crystals adhere to the cell surface by an active force, and the attachment is in a time and concentration dependency with plateau. Pre-treatments with low concentration of GAGs (chondroitin sulphate C, hyaluronic acid, heparan sulphate, heparin and sodium pentosan polysulphate) produce significant reductions of the adhesion. There are significant decreases of the adhesions with pre-treatments of Triton-X100, 0.1 N HCl and gentamicin. These phenomena might be induced by some alterations of cell surface structures or characters. The current quantitative system on MDCK cells should serve as a useful model for the investigations of interactions with crystals and tubular cells. Our studies may also support the hypothesis of attachment of microcrystals to the cellular membrane, which is one of the most important and the earliest process of the pathophysiology of kidney stone.

A planar array of microspheres was deposited on the surface of a surface-acoustic-wave (SAW) device. Arrays of polymer microspheres with mode number m=1 and 2 were observed to resonate with the acoustic wave, thus absorbing or scattering the wave such that transmission is reduced at the resonant frequency. Comparing the quality factor determined from the transmission spectra (Q~15) and that determined from rapid pulse shut-off experiments (Q15) also indicated that the surface wave was either scattered by the array or absorbed via enhanced coupling to the atmosphere.

The patient was a 20-month-old girl. She visited some pediatric clinic with the chief complaint of voiding difficulty and miction pain from October 5, 1991. Excretory urogram, abdominal ultrasound and computed tomographic scan revealed a retrovesical mass which compressed the urinary bladder antero-superiorly. She was referred to our hospital for further evaluation. Physical examination disclosed a fist-sized tumor in her lower abdomen, which persisted after bladder emptying. Cystoscopy revealed elongation of the urethra and elevation of the bladder base. Tumor markers and endocrine examination were normal. Magnetic resonance imaging at 2 weeks after admission revealed that the retrovesical tumor had been translocated cranial to the bladder. Operation was done on October 29, 1991. The tumor originated from the right ovary and was 6.2 x 5.0 x 5.0cm in size and 60g in weight. The cut surface of the surgical specimen included the fatty tissue and hair, and the pathological diagnosis was an ovarian dermoid cyst. This is the youngest case of ovarian dermoid cyst presenting as urinary retention in the Japanese literature. The mechanism of urinary retention due to infantile gynecological disease is discussed.

Nineteen cases of pheochromocytoma were experienced at our department between 1979 and 1990. Nine patients were males and 10 females with an average of 42.4 years old. In 18 patients the tumor was located in the adrenal gland (9 in right, 5 in left and 4 in bilateral adrenal gland), while in one patient whose original tumor had been resected 15 years earlier, the tumor had recurred in the extra-adrenal gland and was surgically extirpated revealing a malignant pheochromocytoma by histological examination. Hypertension was seen in 16 patients; 14 had paroxysmal and 2 had sustained hypertension. In 3 patients, hypertension was not observed. Familial pheochromocytoma was seen in 5 patients. Three patients had Sipple syndrome. Computed tomographic scan and magnetic resonance imaging were very useful techniques in preoperatively localizing the tumor. Even in the cases treated with alpha- or beta-blocker agents preoperatively, significant hypotension was observed immediately after resection of the tumor and treatment with norepinephrine or rapid blood transfusion or both was needed. Although meticulous care with alpha- and beta-blockers is important, surgical treatment of pheochromocytoma should spare the surgeon of unnecessary anxiety.

As part of a joint study on preoperative radiotherapy for developing an optimal mode of rectal cancer therapy, ACNU sensitization was studied in a total of 120 cases, with the cooperation of 48 facilities participating nationwide. The following results were obtained. Improvement in depth of invasion was more distinct in the combination preoperative therapy-ACNU group than in the preoperative radiotherapy group, with no other significant differences between the two. This finding suggests that dose and administration method could be improved. White blood cells and platelets were reduced in some cases of the ACNU combination group, but these reductions were not serious enough to impede surgical procedures. In addition, no significant difference in complications was noted between the two.

We report a case of retrovesical fibrosarcoma with severe hypoglycemia. A 67-year-old man was admitted to our hospital with second recurrence of the retrovesical tumor with hypoglycemia. The episodes of hypoglycemia were accompanied by the advance of tumor size. Complete tumor resection with total cystectomy was performed on December 21, 1989, and the tumor was diagnosed histopathologically as fibrosarcoma. Soon after removal of the tumor, hypoglycemia disappeared and the patient has been well without local recurrence or distant metastasis for more than 20 months.

A 60-year-old man had been administered diphenylhydantoin (DPH) for prevention of convulsive seizures following clipping of an aneurysm of the middle cerebral artery. About one month after the commencement of DPH administration, he developed cough and low grade fever. He was treated with various antibiotics, but his condition increasingly worsened. Chest X-ray film revealed bilateral interstitial processes throughout the entire lung fields. Transbronchial lung biopsy was performed and the obtained specimen showed histological findings compatible with drug-induced pneumonitis. Administration of DPH was stopped immediately and 50 mg/day of prednisolone was started. The patient's condition rapidly improved, and the abnormal shadows on chest X-ray film gradually diminished. The lymphocyte stimulation test by DPH was positive with a stimulation index of 282%.

The response of serum citrate to the oral citrate load was studied in seven healthy subjects. Serum citrate was significantly elevated from 15 to 60 min post-load with some individual variations. In 27 stone-formers serum citrate and the response to the oral citrate administration was studied and compared with the results obtained on healthy subjects. The serum citrate concentration of stone-formers was 1.99 +/- 0.49 mg/dl as compared to 1.61 +/- 0.35 mg/dl in healthy subjects. After citrate administration serum citrate increased significantly in both groups, but no significant difference was shown in response to the oral citrate load between these two groups (3.44 +/- 0.94 mg/dl in stone-formers, 3.16 +/- 0.38 mg/dl in healthy subjects). In Sprague-Dawley rats each weighing about 200 g urinary citrate and calcium excretion were studied after administration of sodium citrate or calcium chloride or both. The concomitant equimolar administration of sodium citrate and calcium chloride did not have significant influence on urinary citrate or calcium excretion as compared when citrate or calcium was given alone. However, the calcium excretion was significantly decreased with the administration of citrate and calcium ata molar ratio of 1:2.

Prenatal stress in the last trimester of pregnancy induces permanent disorders in sex-specific differentiation of the brain in rats. In order to determine the neuroendocrine response of the fetal hypothalamus to the maternal stress, we investigated the temporal change in fetal hypothalamic catecholamines when their mothers were exposed to an acute stress. On day 20 of gestation, pregnant rats were subjected to forced immobilization and sacrificed at 0, 30, 60, 120 and 180 minutes. Plasma corticosterone reached a peak at 60 minutes of stress in mothers and fetuses. Hypothalamic norepinephrine and epinephrine decreased at 120 and 180 minutes of stress in mothers, whereas in fetuses, hypothalamic norepinephrine decreased at 120 and 180 minutes of stress, and dopamine also showed a tendency to decrease. These results suggest that maternal stress in late pregnancy decreases fetal hypothalamic norepinephrine which is involved in androgen-dependent sex differentiation of the brain.

A tumor mass covered with scrotum-like skin on its tip was found on the perineal region of 3-year-old boy since his birth. The mass was diagnosed as congenital lipoma, which was resected, because of its gradual enlargement. Histopathological findings of the tumor indicated perineal lipoma, and the scrotum-like portion was diagnosed as an accessory scrotum. In the Japanese literature, 7 congenital perineal lipomas (6 males, 1 female) have been reported and all male cases except 1 case (no description about scrotum) were accompanied with an accessory scrotum. We conclude that there may be a close relationship between congenital perineal lipoma and accessory scrotum.

An early Phase II study of CTP-11, a new derivative of Camptothecin, in gynecologic cancers was carried out by a cooperative study group of 9 institutions. Forty-six patients were enrolled, and there were 14 cases of ovarian cancers, 7 of cervical cancer, 6 of uterine body cancers and 1 of endometrial stromal sarcoma which satisfied study criteria. The response rate in ovarian cancers was 21.4%, and in cervical cancers 42.9%, among an overall rate of 21.4%. Three out of 6 patients with objective response had undergone previous chemotherapies including cisplatin, suggesting that CPT-11 was effective for patients with no response or refractory to these therapies. Leukopenia was a major adverse reaction with an incidence of 60.0% (grade 2 or more). Gastrointestinal symptoms such as nausea vomiting, anorexia and diarrhea were frequently observed (grade 2 or more; 13.3-43.3%). These were generally tolerable except in a few cases. Besides these reactions, alopecia was also observed (33.3%), but severe adverse reactions such as nephropathy were not. These results suggested that CPT-11 was effective against ovarian cancer and cervical cancer. The recommended dose regimen for a late phase II study is considered to be 100 mg/m2 once weekly and 150 mg/m2 once every 2 weeks.

The microwave absorption of certain water soluble polymers (polyethylene glycol, polyvinyl pyrrolidone, proteins, and DNA) in solution is composed of three parts: absorption in the free water, absorption in the substance, and absorption in the hydration layer. Ethanol, sucrose, glycerol, and sodium acetate, which form weak hydrogen bonds or have an ionic nature in aqueous solutions, also have microwave absorption signatures similar to polymers that form hydration layers. The frequency-dependent absorption of the free water and of the hydration layer water is described by a simple Debye relaxation model. The absorption per unit sample volume attributable to the hydration layer is solute concentration dependent, and a simple model is used to describe the dependence. The hydration-layer relaxation time was found to vary from substance to substance and with solute concentration. The relaxation time was also found to be independent of solute length.

The clinical usefulness of Z-100 (Z group) for the treatment of leukopenia caused by radiotherapy for malignant tumors was evaluated by comparing it with that of L-cysteine (L group) by the double-blind method. For 178 complete cases, there were no significant differences in the time-course of the WBC during radiotherapy between the two group. However, for cases with a large field of irradiation (15 X 15 cm = 225 cm2), the mean WBC count in the L group decreased more than that in the Z group. The Z group showed comparable or superior efficacy for the treatment of leukopenia in the L group although there were no significant differences. Adverse reactions were observed in 5.66% and 2.94% in the Z and L groups, respectively, without any significant difference between the groups. The utility rate, useful or better, was 73.9% and 69.2% in the Z and L groups, respectively, showing a slightly higher rate in the Z group than in the L group, although the difference between the two groups was not significant. These results confirmed that Z-100 has comparable or superior efficacy to L-cysteine for the treatment of leukopenia caused by large field radiotherapy for malignant tumors.

The clinical efficacy of Z-100 for the treatment of leukopenia caused by radiotherapy for malignant tumors was evaluated in an early clinical study using three doses, 2, 10 and 20 micrograms. According to the evaluation by investigators and time-course of WBC, the highest effective rate was achieved by 20 micrograms. Adverse reactions occurred in all groups, but there were no serious or clinically relevant reactions. These results suggested that Z-100 is clinically useful for the treatment of leukopenia caused by radiotherapy.

A retrospective clinical study of 41 patients with prostatic carcinoma relapsing after endocrine therapy at Wakayama Medical College from 1972 to 1987 was reported. Patient's age was from 51 to 80, with an average of 69.8 years. Initial clinical stage was A in 2 patients, C in 12, D in 26 patients and unknown in one. Pathological grade at the first visit was well-differentiated cell type in 4 patients, moderately differentiated in 13, poorly differentiated in 23 patients and unknown in one. Of 41 patients, 32 had a local progression and 26 had an appearance or progression of metastasis. Several factors which might be related to the interval between initial endocrine therapy and relapse were analysed. Following factors such as poorly differentiated cell type, stage D, high Gleason score and increase in acid phosphatase level were revealed to be related to the short interval. Chemotherapy consisting of various agents and their combination has not been able to improve the survival of the patients with relapsed prostatic carcinoma. 1-year survival rate of all cases after relapse was 41.3% and none of the patients survived over 3 years.

Radially localized sheared toroidal flow may be driven in a toroidal plasma by using ion cyclotron heating to assymmetrically trap ions.

A soliton is the wave which propagates in the form of stable bulk with concentrated energy. Zabusky and Kruskal discovered it in 1965 by solving numerically the K-dV equation, and consequently a variety of analytical methods were established for studying its physical property to introduce the new field of modern physics. This paper succeeds in demonstrating computationally interaction of solitons concerning recurrence of the initial state suggested by Zabusky and Kruskal where ambiguity about their numerical analysis has prevented us from obtaining stable solution representing recurrent phenomenon for a long time. Here numerical experiment enables us to examine instability occasioning in the leapfrog method with a function of the initial condition which served as a key parameter. It is clarified that: (i) this finite difference approximation is available to describe only weakly coupled interaction of solitons, (ii) on linear analysis point of view, instability results from increasing unstable numerical mode of the higher Fourier components which was attributed to dispersive property of this difference method and (iii) instability originates in a sharp solitary wave which was standing still at the point of its birth.