Tumor necrosis factor-alpha (TNF-alpha)-induced and interleukin-1 beta (IL-1 beta)-induced shedding of TNF receptors from gingival fibroblasts.

Tumor necrosis factor-alpha (TNF-alpha) exerts its functions by binding two different receptors (TNFR55 and TNFR75). Both TNFR55 and TNFR75 exist in cell-associated and soluble forms. Soluble TNF receptors (sTNFR), sTNFR55 and sTNFR75, are proteolytically shed upon inflammatory stimuli and then modulate various TNF-alpha bioactivities. As human gingival fibroblasts (HGF) can be potential targets for TNF-alpha in inflamed gingiva, we hypothesized that HGF partially modulate the cellular responses to TNF-alpha by regulating their own TNFR. In this study, the kinetics of expression of cell-associated and soluble forms of both receptors from cultured HGF in response to proinflammatory cytokines TNF-alpha and interleukin-1 beta (IL-1 beta) were investigated in vitro. Both TNF-alpha and IL-1 beta upregulated the gene expression of TNFR75 and did not affect that of TNFR55. TNF-alpha and IL-1 beta decreased binding of [(125)I]TNF-alpha to HGF. Moreover, TNF-alpha and IL-1 beta upregulated the release of sTNFR75 from HGF but not that of sTNFR55. These results suggest that HGF under inflammatory conditions may contribute to the inactivation of circulating TNF-alpha through the preferential induction and shedding of TNFR75.

GM-CSF- and IL-3-dependent CD34 expressing myeloid cell line (SAS-1) established from CD7 and CD34 expressing acute myeloblastic leukemic cells.

A novel factor-dependent human myeloid leukemia cell line (SAS-1) was established from a 69-year-old Japanese male suffering from CD7 and CD34 expressing acute myeloblastic leukemia (AML M2 in FAB classification). Morphological and cytochemical staining showed that SAS-1 cells were round with basophilic cytoplasm which is positive for peroxidase. Analysis of surface markers revealed that SAS-1 cells were myeloblasts derived from an immature progenitor origin, which express CD34. The consensus karyotype of the cell line was 41 XY 5q-, -7, 11p-, 12p+, -13, -14, -16, -17, -19, -22, with two markers. The proliferation of SAS-1 cells was dependent on the presence of either granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3), and GM-CSF- and IL-3-induced proliferation was dose dependent. Neither, stem cell factor (SCF) nor granulocyte colony-stimulating factor (G-CSF) alone supported the growth of SAS-1 cells, but supported their viability for more than 4 days and arrested them in the G0/G1 phase. SCF also enhanced GM-CSF- or IL-3-induced growth, but other cytokines did not have this synergistic effect. Clonogenic assays revealed that SAS-1 cells formed 36.0 +/- 5.7 or 41.5 +/- 0.7 colonies/1000 cells in the presence of GM-CSF or IL-3, respectively. SCF also increased the number of colonies formed by GM-CSF or IL-3 treatment, while SAS-1 cells did not form colonies in the presence of SCF alone. SAS-1 cells may prove to be a useful tool for studying the regulation of the cell cycle, myeloid proliferation, and differentiation.

Intravesical instillation of adriamycin for bladder tumors.

In the present series of trials, Adriamycin (ADM) intravesical instillation therapy was found to be effective against tumors of papillary morphology measuring less than 10 mm in diameter that were of low pathological stage and low histological grade. The rate of complete disappearance increased in proportion to the concentration of ADM and the duration of retention of the drug, although the efficacy rates were almost the same in each trial. On the other hand, side effects on the bladder were reduced when the instilled solution was lower in concentration and the retention time was short.

Comparative analysis of short-term and long-term prophylactic intravesical chemotherapy of superficial bladder cancer. Prospective, randomized, controlled studies of the Japanese Urological Cancer Research Group.

The Japanese Urological Cancer Research Group has conducted three randomized clinical studies on intravesical chemoprophylaxis of superficial bladder cancers. This paper presents a comparative analysis of the first and second of these. The protocol used in the first study was a so-called short-term schedule in which drugs (for group A, ADM 30 mg/30 ml; group B, ADM 20 mg/40 ml; group C, MMC 20 mg/40 ml; and group D, control) were administered twice a week for 4 weeks after transurethral resection (TUR), and in the second study a long-term schedule was used, in which drugs (for group E, ADM 30 mg/30 ml; group F, ADM 20 mg/40 ml; group G, MMC 20 mg/40 ml; and group H, control) were administered twice a week for 1 week, every 2 weeks for 7 weeks, monthly for 8 months, and finally once every 3 months for 1 year. In the first study 575 patients were evaluated and followed up for 5 years. The second study started 28 months later, and 607 patients were evaluated. A generally good prophylactic effect was obtained in the second study when the patients' backgrounds were adjusted in combination with the history and number of the tumors. The second study did not reveal any promoting or inhibitory effect on the progression of the recurrent tumors. There were no significant side effects in either study. The indications and the schedule for prophylactic intravesical chemotherapy should be more carefully studied.

Long-term results of intravesical chemoprophylaxis of superficial bladder cancer: experience of the Japanese Urological Cancer Research Group for Adriamycin.

Long-term results were analyzed in terms of tumor progression and survival in patients with superficial bladder cancer who were enrolled in the second intravesical chemoprophylactic study of the Japanese Urological Cancer Research Group for Adriamycin, which was started in July 1982. This study was a prospective, randomized, controlled trial conducted on primary tumors treated with a long-term instillation regimen that involved control versus intravesical instillations of Adriamycin or mitomycin C given once a week for the first 2 weeks, once every other week for 14 weeks, once a month for 8 months, and once every 3 months for 1 year, for a total of 21 instillations in 2 years. An analysis of the prophylactic effects of such treatment on bladder tumors after TUR has previously been performed, and the results have been published elsewhere. The present study represents a follow-up of the above trial. Of the 671 cases previously analyzed with regard to tumor prophylaxis, 158 cases (23.5%) were eligible to be followed for tumor progression and survival. A detailed comparison of the background factors between these 158 patients and the other 513 cases revealed no statistically significant difference. Thus, the 158 evaluable cases might reasonably be considered to represent all patients enrolled in the second study, and the results were thought to be reasonable enough to reflect the long-term efficacy of the long-term instillation regimen adopted in this study. The median follow-up for these 158 cases was 6.6 years. Tumor progression in terms of the disease stage and/or grade occurred in 43 of 127 patients who received prophylactic instillations and in 12 of 31 control cases. No significant difference in the incidence of tumor progression was found between the treatment and the control groups. In addition, no difference in survival was observed between the treatment group and the control group. Survival was also compared between patients who showed tumor progression and those who did not. All patients whose tumors did not progress survived, whereas the 7-year survival of those exhibiting tumor progression was less than 90%.

Direct determination of E2020 enantiomers in plasma by liquid chromatography-mass spectrometry and column-switching techniques.

High-performance liquid chromatography with column switching and mass spectrometry (MS) was applied to the on-line determination and resolution of the enantiomers of E2020 (acetylcholinesterase inhibitor) in plasma. This system employs two avidin columns and fast atom bombardment (FAB)-MS. A plasma sample was injected directly into an avidin trapping column (10 mm x 4.0 mm I.D.). The plasma protein was washed out from the trapping column immediately while E2020 was retained. After the column-switching procedure, E2020 was separated enantioselectivity in an avidin analytical column. The separated E2020 enantiomers were specifically detected by FAB-MS without interference from metabolites of E2020 and plasma constituents. The limit of quantification for each enantiomer of E2020 in plasma was 1.0 ng/ml and the intra- and inter-assay relative standard deviations for the method were less than 5.2%. The assay was validated for enantioselective pharmacokinetic studies in the dog.

Diagnostic accuracy and its limitations in prostatic cancer by means of transrectal ultrasonotomography.

We evaluated transrectal ultrasonotomography performed on 97 cases of prostatic cancer and obtained the following results: Transrectal ultrasonotomography was far more accurate in the diagnosis and staging of prostatic cancer than palpation. However, diagnosis is rarely difficult in cases with a symmetric and non-deformed prostatic shape. Though transrectal ultrasonotomography is very sensitive in the detection of extracapsular cancer infiltration, under-estimation of staging may still occur in some instances.

Ultrasound findings in urolithiasis in the lower ureter.

Thirty-two cases of urolithiasis in the lower ureter, difficult to detect by ordinary X-ray studies, were diagnosed accurately by ultrasound. Stonelike echoes were easily detected on the ultrasonograms when the ureter of the affected side was dilated. Patients should be examined by ultrasound prior to invasive retrograde pyelography.

Efficacy of a new hemostatic device, Adapty , after transradial coronary angiography and intervention.

A novel hemostatic device, Adapty (Medikit, Tokyo, Japan), was developed to achieve effective and comfortable hemostasis following transradial procedures. The device consists of a pad fixed to a transparent plastic plate and a self-adhesive strap. The catheter sheath is removed from the radial artery after the pad has been positioned precisely over the puncture site, with the strap attached to the plate. Compression pressure then is adjusted with the self-adhesive strap, as is required with occlusive clamps. Patients do not need to maintain hyperextension of the wrist after the procedure. The wrist can be mobilized immediately after application. The efficacy of Adapty was evaluated in prospective observations of 200 patients. The device was successfully applied in all patients immediately after sheath removal. No patient required interruption of compression because of pain, congestion or ischemia. Complete hemostasis was obtained in 199 patients (99.5%), and the device caused no vascular complications. This study demonstrates that Adapty is highly effective for achieving hemostasis after transradial procedures.

Resolution of 4-(4-chlorobenzyl)-2-(hexahydro-1-methyl-1H-azepin-4yl)-1(2H)-phthalazi none enantiomers in plasma with frit-FAB LC-MS using a conalbumin column.

A new column-switching method for analysis of drug enantiomers in plasma has been developed with liquid chromatography-frit fast atom bombardment mass spectrometry in combination with a chiral resolution column, which consists of conalbumin (egg-white glycoprotein) immobilized on silica gel and can be used in the reversed-phase separation mode. This method makes it possible to inject a large volume of deproteinized plasma and obtain resolution of drug enantiomers with high sensitivity. The optimum mobile phase, including a non-volatile buffer such as phosphate buffer, for separation of drugs from a large amount of endogenous compounds can be used, because of inclusion of a trapping column with a desalting function. This method is very simple and rapid, and should be very powerful in studies requiring high-sensitivity analysis with chiral separation of drugs from biological samples such as plasma.

Portal-hepatic venous shunt through a portal aneurysm complicated by hepatic encephalopathy and pulmonary hypertension.

We report a rare case of portal-hepatic venous shunt through an enormous portal aneurysm complicated by pulmonary hypertension. A 66-year-old woman was admitted to our hospital for hepatic encephalopathy. Chest roentgenography revealed pulmonary hypertension. Computed tomography and ultrasound examination demonstrated a shunt between the portal and hepatic veins through an enormous portal aneurysm. The diagnoses of portal-hepatic venous shunt and pulmonary hypertension were confirmed by hepatic venous catheterization and cardiac catheterization. Pulmonary hypertension might result from the effects of vasoconstrictive agents, which should be metabolized by the liver in normal subjects, passing through the intrahepatic shunt into the lung.

Sarcoidosis after interferon therapy for chronic active hepatitis C.

Sarcoidosis is characterized by multisystemic granulomatous lesions of unknown etiology. A 62-year-old woman developed sarcoidosis after treatment with alpha-2a interferon (IFN) for 24 weeks (total dose: 522 million units) for chronic hepatitis C. She developed complete atrioventricular block and multiple noncaseating granulomatous lesions in the lung. IFN therapy, which may disturb cellular immune activation in some patients, may have contributed to the onset and progression of sarcoidosis.

[Repair of intrathoracic visceral damage using video-assisted thoracoscopic surgery for blunt chest trauma and rib fixation at the site of mini-thoracotomy].

We treated three patients with intrathoracic visceral damage caused by severely dislocated fractured ribs resulting from blunt trauma by using video-assisted thoracoscopic surgery (VATS) and rib fixation through a mini-thoracotomy. Under general anesthesia and unilateral respiration, the thoracic cavity was inspected with a thoracic video scope through the port inserted through the thoracic drainage opening which was made upon arrival at hospital. As the visceral damage seemed restorable under VATS, a mini-thoracotomy was positioned just above the rib fracture. Two thoracic ports were inserted through the site of rib fracture or through the intercostal space and then VATS was performed using three ports. After the restoration of intrathoracic visceral damage, the fractured rib was fixated using a bioabsorbable poly-L-lactide rib fixation pin or a marlex mesh. Lung injuries were sutured and ligated under VATS in two of our cases and a spur of the fractured rib was shaved in one case. Only severely dislocated ribs were fixated through the mini-thoracotomy in all cases. Air leakage stopped just after this procedure and there were no complications. The rib fixation and bone regeneration were excellent after this procedure. The advantages of this method are the visceral restoration under VATS through a mini-thoracotomy and the ability to perform rib fixation without injuries to the intercostal muscle, artery, vein or nerve. This operative procedure is recommended for intrathoracic visceral damage caused by severely dislocated rib fracture.

[Recent advances of pediatric urology--diagnosis and treatment of urinary tract diseases detected in the new-born infant period].

Recent technological advances of diagnostic modalities, such as ultrasonography, have realized the early detection of urinary tract diseases in the neonate and new-born infant. Accordingly, it is very important to study the problems deriving under such a situation. In this symposium, the views for diagnosing and treating urinary tract diseases detected in the early infant period are proposed and discussed.

[Detection of early prostatic cancer in mass screening program].

Since 1975 up to 1988, we have performed a mass screening program (MS) for prostatic diseases using transrectal ultrasonography (TRS) in the primary study. In our study, 42 cases of prostatic cancer (0.6%) was detected among 6,674 examinees. Out of 42 cases of cancer, 24 (57.1%) were diagnosed as early prostatic cancer (Stage A 1, Stage B 23). The detection rate of cancer in MS and the ratio of early stage of cancer among them were higher than those in the outpatient clinic of our department. Diagnostic accuracy of TRS, palpation and tumor markers in MS were studied respectively through our series of MS. TRS was useful for MS especially in low false negative rate. On the other hand, palpation was characteristic in low false positive rate. Prostatic specific antigen (PSA) among tumor markers was effective to detect early prostatic cancer. However, there were some problems about distinguishing early prostatic cancer from BPH, because of the high false positive rate.

[Clinical study of cinoxacin in acute simple cystitis].

Cinoxacin (CINX) was administered twice a day for 7 consecutive days (400 mg X 2/day) to 34 female patients suffering from acute simple cystitis. The overall clinical efficacy was excellent in 15 cases (94%) and moderate in one case (6%) according to the criteria for clinical evaluation by the UTI committee. The efficacy was not determined in 18 cases. Bacteriological examination revealed 11 cases of single infection by E. coli, 2 cases of single infection by P. cepacia and S. epidermidis and one case of single infection by S. sunguis. MIC of E. coli ranged from 3.13 to 6.25 micrograms/ml. MIC of P. cepacia was 3.13 micrograms/ml and MIC of S. epidermidis more than 100 micrograms/ml. All the strains were eradicated with the efficacy of 100%. There was no relapse of acute simple cystitis in 16 cases after 7 days treatment of CINX. No serious side effects were recognized except for slight general fatigue and heart burn in 2 cases. It was thus concluded that CINX is clinically effective and safe for acute simple cystitis caused by E. coli and P. cepacia.

[Clinical studies for genitourinary anomalies with anorectal malformations].

Anorectal malformations involve genitourinary anomalies frequently. In this study, the treatment and prognosis for genitourinary anomalies in 8 patients with anorectal malformations were discussed. All patients were men (range 1 to 14 years). Seven of them showed high types of anorectal malformations and one low type. Five patients were managed surgically. Among them, 3 were treated successfully, but the outcome was not good for 2 patients. These 2 patients have been followed up under careful observation. The treatment could not be performed on one patient with poor bowel function. In this series, successful results were obtained on patients with a low degree of anomalies. However, there were hazard problems in patients with a high degree of anomalies. Neurogenic bladder was included among these problems. It is difficult to diagnose and treat genitourinary anomalies on a newborn baby with anorectal malformations, when these anomalies might be complicated with other severe anomalies such as congenital heart diseases. In such cases, genitourinary anomalies should be treated as conservatively as possible until the patient's condition has improved.

[Time-resolved-fluoroimmunoassay for the determination of prostate-specific-antigen in capillary-blood spotted on filter paper and its clinical significance in prostate cancer patients].

Prostate-specific-antigen (PSA) has recently become widely recognized as an important tumor marker for prostate cancer. For relieving the examinee from pain and saving the time in blood collection, we developed a new method, based on time-resolved fluoroimmunoassay (TR-FIA), using a dried disc paper to collect capillary-blood. The standard curve ranged from 1.0 to 300 ng/ml, the intraassay (CV% was 4.09 to 6.36 (n = 10), while the interassay CV% was 3.45 to 8.87 (n = 2, k = 7). The diluted linearity and analytical recovery (91.5 to 98.2%) seemed to be satisfactory for routine use. All the samples from 30 healthy male adults had non-detectable serum PSA less than 1.0 ng/ml. When the cut-off value was set at 3.4 ng/ml (MEAN + SD of BPH), the positive rate in prostate cancer cases was 85.7% (12/14), in BPH cases was 20.0% (2/10) and in other benign urological disease was 0.0% (0/20). The clinical sensitivity was 85.7%, the specificity 93.3% and the efficacy 90.9%, accordingly. In conclusion, the newly developed TR-FIA method using dried disc paper to collect capillary-blood was quantitatively suitable as a routine test for prostate cancer, because of its simplicity in blood collection and less invasiveness to the examinee.

[Analgesic effect of calcitonin in patients with metastatic bone lesions from urogenital cancer].

The analgesic effect of eel-calcitonin (Elcitonin) was evaluated in 10 patients with metastatic bone lesions from urogenital cancer. Five patients had renal cell carcinoma, while the remaining 5 patients had prostatic cancer. Eel-calcitonin was injected intravenously to each patient at a dose of 80 units every day. The drug was markedly effective for 3 patients, effective for 4 patients and ineffective for 3 patients. The effect was better for prostatic cancer than renal cell carcinoma.

[Puncture technology and selective renal biopsy].

An experimental study of puncture technology for the kidney: We investigated the strength characteristics of tissues which are penetrated by the puncture needle for the kidney using a tension test. The tensile strength of the fascia, the muscle, the renal capsule, the renal parenchyma and the renal pelvis were 13.9, 1.1, 29.5, 0.5 and 21.4 kg/cm2, respectively. As the strengths differ, the needles for each tissue clearly need to be changed. Needle tip shape and needle material for kidney puncture were investigated by compression test, acryl resin injection into the renal vasculature, stereo-microscopy and scanning electron microscopy. These investigations revealed that the most suitable needle tip was a sharp cone shape, and material with a smooth surface and some flexibility such as Derlin seemed to be the most appropriate for the puncture needle for the kidney. Using the acryl resin injection method, stereo-microscopy and scanning electron microscopy, we studied the relative safety of single stage puncture and the repeated dilatation method to establish percutaneous nephrostomy. Single stage puncture seems to cause less damage to the kidney than the repeated dilatation method. Selective renal biopsy: A new puncture system using real-time ultrasound was developed at our clinic in 1978. The puncture procedure is monitored in 2 dimensional real-time images by a mechanical sector scanner equipped with an attachment for needle guidance. The application of the system to percutaneous renal biopsy is called "selective renal biopsy" because the specimen can be obtained selectively from any portion of the kidney.(ABSTRACT TRUNCATED AT 250 WORDS)