Effect of interleukin-1 receptor antagonist on concanavalin A response of peripheral blood mononuclear cells from newborn calves.

The coexistence of interleukin (IL)-1beta with IL-1 receptor antagonist (ra) in bovine colostrum and the possibility of simultaneous transfer of these cytokines to neonates via colostrum have been demonstrated. In the present study, we investigated the effect of IL-1ra on the mitogenic response of calf peripheral blood mononuclear cells (PBMC) stimulated by concanavalin A (ConA), which was mediated by IL-1. Pretreatment of PBMC with recombinant bovine (rb) IL-1ra alone significantly suppressed the proliferation of ConA-stimulated cells. However, in the presence of rbIL-1beta, the suppressive activity of rbIL-1ra was counteracted. These results suggest that coexistence of IL-1ra with IL-1 in colostrum may have no effect on the activation of the neonatal immune system by IL-1beta.

Oral administration of IL-1 beta enhanced the proliferation of lymphocytes and the O(2)(-) production of neutrophil in newborn calf.

Recently, we demonstrated the presence of IL-1 beta in the colostral whey from dairy cows. Here, authors examined oral transmission of colostral IL-1 beta and its immunological effects on the neonatal calves. Biotin-labeled recombinant bovine (rb) IL-1 beta was administered orally to newborn calves and monitored in the serum. The results disclosed the passive transfer of colostral cytokines via the oral route, and a potent increase in white blood cell (WBC) count was observed in all calves administered with rbIL-1 beta. Oral administration of IL-1 beta significantly increased the proliferation of peripheral blood mononuclear cells (PBMCs) stimulated with concanavalin A, and the O(2)(-) production of stimulates neutrophils in newborn calves. These results suggest that the oral administration of IL-1 beta has an immunostimulatory activity in the newborn calf.

Detection of cytokines in bovine colostrum.

Colostrum contains factors that are protective for the neonate and may be a source of immunomodulary molecules that positively influence the immune status of the neonate. To confirm that colostrum contains a variety of cytokines with immunomodulatory properties, we established a bovine cytokine specific ELISA and five cytokines (IL-1 beta, IL-6, TNF-alpha, INF-gamma or IL-1 receptor antagonist, IL-1ra) in the whey samples from cows at different stages of lactation were monitored. The expression of cytokine mRNAs (IL-1 beta, IL-6, TNF-alpha and INF-gamma) in the colostral cells was detected by RT-PCR. The concentrations of cytokines in colostrum were significantly higher concentrations than those in the mature milk. A positive correlation was observed between the concentrations of IL-1ra and IL-1 beta in the colostrum samples. In conclusion, colostrum contains high levels of cytokines that could be produced and secreted in the mammary gland and that may have an immunomodulatory activity and influence neonatal immunity.

Tumor-targeted chemotherapy with SMANCS in lipiodol for renal cell carcinoma: longer survival with larger size tumors.

OBJECTIVES: To evaluate the anticancer effects of a lipophilic macromolecular anticancer agent, poly(styrene-co-maleic acid)-conjugated neocarzinostatin (SMANCS), dissolved in a lipid contrast medium (Lipiodol) given via the renal artery to patients with renal cell carcinoma. METHODS: Among 467 patients with renal cell carcinoma treated between April 1984 and March 1993, 191 were treated with SMANCS dissolved in a lipid contrast medium (a 3:2 mixture of Lipiodol F and Lipiodol Ultrafluid; Lpd). Selective arterial infusion of SMANCS/Lpd was performed at a dose of 1.0 or 1. 5 mg/mL. The infusion was repeated at intervals of about 2 weeks or longer, but the doses and the total number of infusions varied among patients, according to results of computed tomography analysis. RESULTS: Statistical analysis was performed for 415 patients who met the criteria of this study. Twenty-six surgical patients with metastases who underwent infusion therapy of SMANCS/Lpd for primary lesions showed 3 and 5-year survival rates of 23.0% and 12.8%, respectively; the rates were 19.3% and 9.7% in 31 patients who did not receive SMANCS infusion therapy. In 125 surgical patients without metastases who underwent SMANCS/Lpd infusion, the 5 and 10-year survival rates were 83.0% and 75.2%, respectively, whereas rates of 84.6% and 78.9% were observed in 199 surgical patients whose median tumor size was significantly smaller, however, than the SMANCS/Lpd infusion group. The maximal tumor diameter at the beginning of treatment was significantly larger (mean diameter 70.8 mm) in the SMANCS/Lpd infusion group than in the noninfusion group (59.1 mm). The survival rate was statistically better for patients with tumors of 100 mm diameter or larger in the SMANCS/Lpd infusion group (P <0.05): 5 and 10-year survival rates were 70.4% and 61.6%, respectively, for the infusion group and 64.6% and 50.9% for the group receiving no drug. In patients with larger tumor (greater than 110 mm), the survival rate at 13 years was 75% in the SMANCS/Lpd infusion group and 0% in the surgery group. CONCLUSIONS: Arterial infusion therapy with SMANCS/Lpd appears to be effective for large renal cell carcinoma without metastases in conjunction with surgery.

Successful treatment of radiation cystitis with hyperbaric oxygen therapy: resolution of bleeding event and changes of histopathological findings of the bladder mucosa.

To assess the effect of hyperbaric oxygen (HBO) therapy on radiation cystitis, clinical and histopathological characteristics were examined. Three women with radiation cystitis were treated with HBO therapy. Macrohaematuria was arrested in all patients. Cystoscopy demonstrated abnormal telangiectasia and inflammatory mucosa before treatment. After HBO therapy, the inflammatory mucosae were healed. However, abnormal vessels did not completely disappear. Histopathologically, the epithelium was atrophic and dilated lymph vessels and inflammatory cells were seen in the submucosa. These changes improved after treatment. HBO therapy is effective against radiation cystitis. With improvement of the clinical symptoms also the cystoscopic and histopathological findings changed favourably.

[Effects of gosha-jinki-gan on urinary bladder contraction in dogs].

The effects of Gosha-Jinki-Gan on the urinary bladder contraction in anesthetized dogs were studied to elucidate the mode of action. The bladder contraction was induced by electrical stimulation of the left distal end of the pelvic nerve under the bilateral pelvic nerve and hypogastric nerve transections, or by the infusion of acetylcholine (200 micrograms) in to the abdominal aorta. The bladder contraction induced by pelvic nerve stimulation was significantly inhibited by 10 and 100 mg/kg of intravenous Gosha-Jinki-Gan administration. A similar phenomenon was observed by the administration of atropine sulfate (0.1 mg). The acetylcholine-induced contraction was significantly inhibited by administration of 100 mg/kg of Gosha-Jinki-Gan. These findings suggested that Gosha-Jinki-Gan inhibits the urinary bladder contraction induced by the stimulation of cholinergic nerve.

Transurethral balloon laser enhanced thermotherapy in the canine prostate.

BACKGROUND AND OBJECTIVE: Hyperthermia is performed for prostate cancer. We examined the selective induction of coagulonecrotic changes in the objective area of the canine prostate in enhancing the effect of hyperthermia and treating the target area with transurethral balloon laser enhanced thermotherapy (TUBAL-ET) using a light absorbent material. STUDY DESIGN/MATERIALS AND METHODS: The heat exchange of ultrafine carbon particles after laser irradiation was observed in a phantom study using thermography. The carbon solution was injected at the right prostatic lobe in dogs and TUBAL-ET was performed. RESULTS: The charcoal absorbed the Nd:YAG laser energy and apparently converted it into thermal energy in the phantom study by thermographic observation. TUBAL-ET induced coagulonecrotic changes only at the area at which carbon had been injected in the prostate gland. The necrotic tissue was almost absorbed at four weeks after treatment. CONCLUSIONS: TUBAL-ET induces tissue damage at the target area in the prostate gland.

[Effects of Gosha-Jinki-Gan on the function of the urinary bladder in anesthetized dogs].

Gosha-Jinki-Gan is clinically used for the treatment of pollakiuria in patients with benign prostatic hyperplasia. The effect of Gosha-Jinki-Gan on the function of the urinary bladder in anesthetized dogs was examined. Gosha-Jinki-Gan (100 mg/kg) inhibited the rhythmic bladder contractions (RBC). However, the frequency of RBC increased resembling the effect of atropine (0.1 mg/body), and the amplitude decreased. On the cystometrogram, Gosha-Jinki-Gan caused an increase in maximum vesical volume (not significant). These findings indicated that Gosha-Jinki-Gan is a useful drug for the treatment of pollakiuria.

Serial changes in proximal urethral function after transurethral balloon laser hyperthermia of the prostate (TUBAL-H) in a canine model.

We performed transurethral balloon laser hyperthermia of the prostate (TUBAL-H) in 6 mongrel dogs. To evaluate the changes in proximal urethral function after TUBAL-H, the urethral cross sectional area (CSA, cm2) and urethral pressure (Pu, cmH2O) were measured using a balloon probe that allows their simultaneous measurement, and the urethral compliance (Comp, cm3/cmH2O) was calculated from these parameters and serially evaluated. In addition, the changes in Pu, CSA and Comp after administration of an alpha-adrenoceptor antagonist were evaluated before and 16 weeks after TUBAL-H. Before TUBAL-H, the mean Comp was 0.013, and the mean maximum CSA (MCSA) was 0.66. Eight weeks after TUBAL-H, the mean Comp was 0.038, and the mean MCSA was 1.39, showing a significant increase (p < 0.01). Sixteen weeks, after TUBAL-H, the mean Comp was 0.026, and the mean MCSA was 1.21, being lower than those at 8 weeks after TUBAL-H, but significantly higher than those before TUBAL-H (p < 0.05). After administration of the alpha-adrenoceptor antagonist, phentolamine (1 mg/kg), before TUBAL-H, the mean Comp significantly increased to 0.046 (p < 0.05), and the mean MCSA to 1.40 (p < 0.01). The mean Comp was significantly increased to 0.033 (p < 0.05), by phentolamine administration 16 weeks after TUBAL-H, but no other changes were observed. After TUBAL-H, urethral elasticity increased, and this increase persisted for 4 months. The responses of Comp and MCSA to alpha-adrenoceptor antagonist administration before and 16 weeks after TUBAL-H suggested that part of the effects of TUBAL-H is due to damage to alpha-adrenoceptors.

Transurethral balloon laser thermotherapy: effects of a directionally shielded balloon in canine prostates.

BACKGROUND: Transurethral balloon laser thermotherapy (TUBAL-T) improves objective, but not subjective, symptoms of benign prostatic hyperplasia (BPH). We studied whether or not an Nd:YAG laser beam with a shielded balloon could successfully irradiate the prostate during TUBAL-T in selective manner, to improve the subjective symptoms. METHODS: TUBAL-T was performed on canine prostates using the balloon with a laser probe, which was shielded anteriorly at 90 degrees (from the center of the balloon) and posteriorly at 90 degrees. RESULTS: At 20 watts laser power, the relative power density in the bilateral non-shielded areas was 17.4 and 17.8, and in the shielded area it was 1.0. Observation by thermography revealed that the temperature after laser radiation in a non-shielded area of a fish cake phantom was higher than in a shielded area. Following transurethral thermotherapy using a shielded balloon in dogs, a cavity was formed bilaterally around the urethra, and the tissues at the anteroposterior sides and the urethra were preserved. CONCLUSIONS: TUBAL-T, which has been performed in clinical cases of benign prostatic hyperplasia, might be useful in selective irradiation of adenoma if a shielded balloon is used.

Histological and immunohistochemical changes after transurethral balloon laser hyperthermia in the canine prostate.

Transurethral balloon laser hyperthermia (TUBAL-H) for the prostate was performed in a canine model. Eleven normal and hyperplastic prostates were heated at between 40 to 45 degrees C for 30 min. Compared to the pretreatment weight, the prostatic weight significantly increased immediately after treatment and significantly decreased at 4 weeks later, but was not significantly different after 8 weeks. Histologically, shedding of epithelial cells was observed immediately after treatment, although, coagulonecrotic tissue was not seen. After 8 weeks, atrophic changes of epithelial cells were observed at the inner portion of the prostate. By immunohistochemical analysis, epithelial cells expressing apoptosis related antigen (Ley) were observed at the inner portion of the prostate from immediately after treatment until 4 weeks later. The atrophic epithelia and the expression of apoptosis in the prostate gland were pathological changes induced by TUBAL-H. From the present data, it is suggested that TUBAL-H combined with radiation or administration of anti-cancer drugs may be effective for prostate cancer.

Changes in prostatic thickness and the location of ejaculatory ducts in autopsy prostates.

OBJECTIVE: To measure prostatic thickness and the depth of ejaculatory ducts from the urethral surface to prevent ejaculatory duct damage during transurethral balloon laser thermotherapy. MATERIALS AND METHODS: In 47 prostates obtained at autopsy, the prostatic thickness and the depth of ejaculatory ducts from the urethral surface were measured in eight directions from the centre of the urethra. RESULTS: The depth of ejaculatory ducts was approximately 6 mm from the urethral surface regardless of prostatic weight. Increase in prostatic weight was associated with increase in the thickness in all directions except the posterior one; the thickness ranged from 9 to 20 mm. The posterior thickness at the level of the transition zone was 10 mm regardless of prostatic weight. CONCLUSION: When benign prostatic hypertrophy is treated transurethrally, using laser or microwave equipment, care should be taken to avoid heating the posterior region of the prostate.

Transurethral balloon laser hyperthermia for chronic non-bacterial prostatitis: a clinical trial.

Transurethral balloon laser hyperthermia (TUBAL-H) was performed on five patients with chronic non-bacterial prostatitis who failed to respond to conventional treatment administered for more than two years. The prostatic interstitial temperature during treatment was measured and the safety and efficacy of this treatment was assessed. TUBAL-H was performed at a target temperature of 43 degrees C (5 mm depth) and at a laser power of 30 watts with urethral cooling for 20 min in the first three patients and for 30 min in the remaining two patients. The prostatic interstitial temperature at a depth of about 5 mm from the urethral surface ranged from 40.5 to 43.0 degrees C during treatment. The temperature of the urethra ranged from 31.5 to 39 degrees C and that of the rectum remained below 39.5 degrees C. After treatment, no abnormal findings were noted in any of the hematological and biological tests carried out, including prostatic specific antigen. The leukocyte count in expressed prostatic secretions fell to less than five cells per high-power field in four of the five patients after three months. A complete improvement in symptoms was observed in one patient, partial improvement in three, and no improvement in one. Based on these results, TUBAL-H was considered to be safe and a suitable treatment for patients with chronic prostatitis.

[Interstitial temperature measurement during balloon lasertherapy (Prostalase) of the canine prostate].

We examined the distribution of interstitial temperatures during balloon lasertherapy, using 4 mongrel canines. The laser equipment (CL50FS, SLT Japan Co. Ltd. Tokyo, Japan) consisted of Nd:YAG laser that produced 360 spindle-shaped radiation from a laser balloon (2 cm long) with a water-cooled circulation system. By measuring the temperature 3-5 minutes after the beginning of the treatment, we obtained following results. The temperature of the bladder neck and urethral sphincter remained below 42 degrees C except under extreme conditions. The temperature at a 6 mm depth from the prostatic urethra rose as laser energy increased, but was not affected by increased circulation of cooling water. The temperature at a 10 mm depth from the prostatic urethra was not affected by either increased laser energy or increased circulation of cooling water. We concluded that the limit of tissue cooling is within 6 mm and direct transmission of laser energy is within 10 mm. Distribution of the tissue temperature peaked at a 6 mm depth in the prostatic urethra. When cooling water was circulated at a 200 ml/min and laser-energy was generated at 30 W, the temperature distribution demonstrated that at a 4-10 mm depth from the prostatic urethra reached over 45 degrees C and at a 6 mm depth from the prostatic urethra, a peak of 52 degrees C was obtained. The possibility of thermotherapy of the prostate was suggested.

Prostalase: basic clinical research and preliminary clinical results with laser thermotherapy for symptomatic benign prostatic hyperplasia.

Prostalase¿ has a probe that emits a laser beam at 360 degrees . Targeted obstructive prostatic adenoma tissue was heated to above the cytotoxic threshold temperature of 45 degrees C. After successful canine prostate study, from September 1992 to April 1993, 45 patients were treated. This paper reports the 9 months results of this initial cohort of patients. Prostatic and periprostatic temperature mapping showed the mean temperature within the adenoma zone was 49 degrees C, while the periprostatic tissue remained within the safety level of less than 42.5 degrees C. The mean prostate volume reductions at 3, 6, and 9 months were 36, 33, and 38%, respectively. Those patients whose surgery was unsuccessful had prostatic tissue removed by TURP at 2 to 3 months. This tissue revealed a definite zone of coagulative necrosis. For the clinical assessment, patients were divided into urine retention (UR) and nonretention (NR) subgroups. At 9 months, 20 of the 32 UR subgroup and 10 of the 13 NR subgroup patients were available for assessment. Due to poor response or complications, 6 of the 26 UR patients (23%) required ancillary treatment. Hence, 20 of the 26 cases (77%) remained catheter free and their mean maximum uroflow +/- SE was 9.6 +/- 0.7 ml/sec. Based on a Siroky normogram only 7 of these 26 patients (27%) became unobstructed. Two of the 12 NR subgroup patients (17%) required ancillary treatment. The mean maximum uroflow +/- SE was 10.7 +/- 1.2 ml/sec.(ABSTRACT TRUNCATED AT 250 WORDS)

Production and induction of a novel cytotoxin (factor 2) by a human B-cell line.

The human B-cell line, Karpas 160, was found to produce Factor 1 and 2 (F1 and F2). F1 was found to be indistinguishable from tumor necrosis factor beta (TNF-beta), while F2 appears to be a new cytotoxin. We used several stimuli alone or in combination to trigger the 160b cells, a subclone of Karpas 160, to produce higher yield of F2. The optimal culture times, concentrations of cells and a range of stimuli were studied. We found that 20-25 ng/ml of phorbol myristate acetate (PMA) effectively induced the higher production of F2. Pretreatment of the cells with sodium butyrate enhanced F2 production. Production of TNF but not F2 was inhibited when the cells were cultured with tunicamycin and PDB. When ciprofloxacin or cycloheximide was added to the medium, F2 production in the presence of PMA was amplified. When 160b cells were cocultured with K562 cells, low levels of F2 induction were observed. We found that most types of human tumor cell lines were highly susceptible to F2, but less sensitive or even resistant to TNF. In contrast, normal human cell lines were not susceptible to F2. Therefore, it appears that F2 could be a new human cytotoxin.

[Clinical effect of Cernilton in chronic prostatitis].

Twenty-five patients with chronic prostatitis were given Cernilton tablets. Improvement of subjective symptoms and objective findings was noted in 96.0% and 76.0% of the cases. Sonographic findings in the prostate showed 33-100% improvement in four objective items. No side effects were observed in any case after Cernilton medication. Cernilton was judged to be an effective drug for chronic prostatitis.

Tumor-targeted chemotherapy with lipid contrast medium and macromolecular anticancer drug (SMANCS) for renal cell carcinoma.

Twenty-five patients with renal cell carcinoma were treated with a lipophilic macromolecular drug, poly(stylene-co-maleic acid)-conjugated neocarzinostatin (SMANCS) dissolved in lipid contrast medium (Lipiodol). The drug was injected by catheterizing the renal artery and another feeding artery in 24 patients, and in the common hepatic artery in 1 patient with metastases to the liver after a radical nephrectomy. The procedure of selective arterial administration of 3-20 mg/mL of SMANCS/Lipiodol was simple to perform and was required once every two to three weeks. Total dose of SMANCS for each patient varied from 3 to 57 mg. Both SMANCS and Lipiodol accumulated more selectively in tumor than in any other tissue and remained in the neovasculature and extracapillary space for a long time. CT pattern of the remaining oil contrast medium in the tumor was characterized by the high-density area localized mainly in the periphery of the tumor around the central necrosis. When hyperviscosity Lipiodol (Lipiodol HV) was used as lipid contrast medium, it remained more persistently in the tumor and disappeared more slowly than Lipiodol. Moreover, the pronounced anticancer effect was recognized when SMANCS/Lipiodol HV was administered compared with only SMANCS/Lipiodol. Severe side effects, such as myelosuppression, unendurable pain, paralytic ileus, etc., were not observed. This targeting chemotherapy may be of great significance for advanced renal cell carcinoma.

Branched-chain amino acid-supplemented nutritional support after gastrectomy for gastric cancer with special reference to plasma amino acid profiles.

Preoperative plasma aminograms constructed for 63 patients expected to undergo gastrectomy for gastric cancer at different stages showed markedly lower concentrations of many plasma amino acids in the Stage IV and recurrent cases. The amino acid levels were inversely proportional to tumor size. On the other hand, preoperative arteriovenous differences in free amino acid levels were positive in Stage I cancer but negative in Stage IV cancer, indicating that intake of amino acids by the skeletal muscles exceeded the outflow in Stage I, whereas there was a net loss of amino acids from the skeletal muscles in advanced cancer. The amount of amino acids actually lost from the skeletal muscles after muscular loading in Stage I cancer also surpassed that in Stage IV cancer. Administration of TPN solution supplemented with 31% branched-chain amino acids (BCAA) might favorably influence muscle protein metabolism in gastric cancer patients by inhibiting protein degradation and promoting synthesis, as treatment was more effective than 21% BCAA-enriched TPN.

Brain aromatase activity and behavioral consequences in the male rat treated in utero with 4-hydroxy-androstenedione.

Pregnant female rats were given daily injections of a potent aromatase inhibitor, 4-hydroxy-delta 4-androstenedione (4OHA), throughout the latter half of the pregnancy (days 11 to 22; the day of insemination was designated as Day O) and male fetuses and pups were obtained. Control animals were male offspring of mothers treated with oil vehicle. When measured by the tritium-water method, significant reductions in the aromatase activity were detected in the hypothalamic and preoptic continuum (HPOA) of the male fetuses and pups, over a period from day 16 of the pregnancy until a day after birth. All parturitions in the experimental as well as control animals occurred on day 22 of the pregnancy. Behavioral and anatomical consequences of the prenatal treatment were examined in adulthood. When mounted by stud male rats, the male litters of the 4OHA-treated mother showed lordosis at a significantly higher frequency both in terms of the number of positive test sessions (each consisted of a 20-min period in which the subject showed lordosis at least once) and the lordosis quotient (percent lordosis occurrence per 10 mounts). When placed with receptive female rats, the experimental animals were no less active in mounting or ejaculating than the control. No significant difference existed between the experimental and control animals in the weight of the testes or the accessorial genitalia, or the serum testosterone levels. Partial but significant intervention of behavioral defeminization of the brain was associated with decreased HPOA aromatase activity during the prenatal period.