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The study investigates lower lumbar segments (L4-5, L5-S1) with disc herniation with respect to posterior vertebral shifts, the orientation of facet joints, age, sex, and body mass index. Decubitus lumbar radiographs as well as magnetic resonance imagings of 173 patients (226 segments) were analyzed. The results support biomechanical considerations, that the posterior vertebral shifts lead to the migration of herniated disc at L4-5.

Aims To evaluate the action mechanism of α1-receptor blockers in improving nocturia, we have studied effectiveness of tamsulosin hydrochloride (TAM) in the patients with nocturia associated with lower urinary tract symptoms/benign prostatic hyperplasia (LUTS/BPH). Methods LUTS/BPH patients with nocturia (nocturnal frequency ≥2 times per day) were administered TAM (0.2 mg/day) for 8 weeks. A frequency volume chart (FVC), the International Prostate Symptom Score (I-PSS), quality of life (QOL) index, post-void residual, and uroflowmetry were recorded before and after TAM administration for the patients. The parameters affected by TAM were examined. Results The FVC and I-PSS of the 160 patients analyzed revealed significant clinical improvements in the nocturnal frequency. On the basis of the FVC, the patients were divided into two groups: the responder group comprising 97 patients with significantly improved nocturnal frequency and the non-responder group comprising 63 patients with less improvement in the nocturnal frequency. Significant differences between groups were observed in the following parameters: the hours of undisturbed sleep (HUS), the interval between the time of sleeping and the first instance of nocturnal voiding, the volume of urine in the first nocturnal voiding episode, nocturnal urine volume, nocturnal polyuria index, daytime urine volume, maximum and average flow rates, and post-void residual. Conclusions TAM improved the QOL of LUTS/BPH patients by significantly reducing the nocturnal frequency and increasing HUS; moreover, it improved nocturia by decreasing the nocturnal urine volume. Neurourol. Urodynam. 29:1276–1281, 2010. © 2010 Wiley-Liss, Inc.

We reported a rare case of severe OPLL in an adult case of vitamin-D resistant rickets.The case was 56-year-old female. We started 50-150 thousand units of vitamin-D treatment about 16 years ago.About 2 years before operation, she was complaint of gait disturbance and dysuria.X-ray examination showed a severe OPLL from C1 to Th2 (max. stenosis 79%, C1, 2).We performed a surgery of canal-expansive laminoplasty and suboccipital craniectomy.

Malignant myoepithelioma of the head and neck usually arises in the salivary glands. We experienced a rare case with malignant myoepithelioma in the maxillary sinus. A 47-year-old woman with malignant myoepithelioma in the maxillary sinus underwent partial maxillectomy. However, local recurrence occurred 28 months after surgery and she was subsequently treated with radiation therapy with proton beams. The recurrent tumor showed complete response and the patient was alive with no evidence of disease 30 months after irradiation. No therapy-related severe toxicities were observed. A rare case with malignant myoepithelioma in the maxillary sinus was successfully treated with radiation therapy.

Peripheral pulmonary arterial aneurysm has rarely been reported, and although most cases show symptoms of hemoptysis. We experienced a case of idiopathic peripheral pulmonary arterial aneurysm in the asymptomatic period noted on medical examination. The patient was a 49-year-old man with coin lesion which was 15 mm in diameter in the right lower lung field on chest X-ray film at the 1st visit. It was strongly stained on enhanced computed tomography in the right S4 and continuity with the pulmonary arteries was suggested. The right middle lobectomy was performed under the diagnosis of peripheral pulmonary arterial aneurysm. Histological examination of the resected specimen revealed that the prominent thinning in the arterial wall, however, there was no evidence of specific chronic inflammation. The postoperative course was good. The patient has been well without new pulmonary arterial aneurysm for 2 years after the surgery.

Leiomyomatosis peritonealis disseminata (LPD) is a rare benign smooth muscle tumour located in the peritoneal cavity. Increased oestrogen exposure appears to be an aetiological factor for LPD. We report two cases of LPD after leiomyomectomy and assisted reproductive technology pregnancy, which can cause a high serum concentration of oestrogen. CT and MR scanning demonstrate many intraperitoneal well-demarcated nodules of varying size that mimic widespread intraperitoneal malignancy.

Dickkopf 3 (Dkk3) is a protein expressed at a very early stage of hepatogenesis. In this study, we examined whether Dkk3 was related to a premature or dedifferentiated nature in hepatoblastomas (HBLs) and hepatocellular carcinomas (HCCs). It was demonstrated that Dkk3 was overexpressed in HBLs and HCCs and that its expression was more frequent in the former than in the latter, being consistent with the fact that most HBLs show an embryonal or fetal hepatic histology, whereas there was no distinct relationship between Dkk3 expression and clinical data or histology. All of the HBLs expressed Dkk3, alpha-fetoprotein (AFP), or both proteins, suggesting that, similar to AFP, Dkk3 is another potentially useful biomarker detecting a wide range of HBLs. Furthermore, Dkk3 and AFP were expressed reciprocally in the tumors. These results suggest that Dkk3 may be related to the premature or dedifferentiated nature of HBLs and HCCs, whereas AFP may be related to a more differentiated nature. Thus, assessment of Dkk3 and AFP may be useful in the diagnosis of hepatic tumors.

Two patients with severe iron deficiency anemia and gastric antral vascular ectasia (GAVE) are reported. The anemia caused by the chronic blood loss from the abnormally dilated mucosal and submucosal capillary veins in the gastric antrum was unresponsive to oral iron supplementation. However, one of the patients was successfully treated with intramuscular injection of (Asu1,7) eel calcitonin. The other one was treated by oral prednisolone with resulting improvement iron deficiency anemia. The possible mechanisms of successful calcitonin and prednisolone treatments on chronic blood loss from GAVE is discussed.

The diagnostic accuracy of myelography, CT and MRI for the diagnosis of lumbar herniated nucleus pulposus is compared in 32 patients, all of whom underwent surgical exploration. The accuracy rates in these patients were 76.5% for myelography, 85.3% for CT, 79.4% for MRI, and 94.1% for CT and MRI. Although CT and MRI can be viewed as an alternative to the invasive myelography in diagnosing lumbar disk herniation, myelography was more sensitive to change of nerve root. Further advances in MRI technology can be expected to be primary noninvasive diagnostic technique for evaluation of lumbar spine intervertebral disk disease.

Seventy-two patients were treated with posterior lumbar interbody fusion (PLIF) by total facetectomy (TF), using intervertebral spacer (i. e. AW glassceramic, hydroxyapatite), for lumbar degenerative disorders. Patients were followed clinically and radiographically from four months to over two years. Fusion was achieved in 95.8% of the cases, and good clinical improvement was shown in the JOA score for most patients. Especially, spinal fusion by PLIF was useful in relieving low back pain. PLIF by TF provides wide decompression, prevents iliac pain caused by picked bone and offers spinal surgeons numerous advanteges for the treatment of lumbar diseases. Use of the intervertebral spacer also provides good support and good filling-up for bone graft.

The possibility of in vivo gene transfer into the rat bladder by electroporation (EP) was evaluated. The bladder was exposed through an abdominal midline incision in 8-week-old male rats. Plasmid DNA of marker genes, green fluorescent protein (GFP) and luciferase, and the neuronal nitric oxide synthase (nNOS) gene were then injected into the subserosal space of the bladder and EP was applied. At 72 h after gene transfer, GFP and luciferase were assayed in the isolated bladder, and immunohistochemical staining was used to detect nNOS. NOx released from isolated bladder strips was also assessed using microdialysis procedure. From the luciferase assay, 45 V, 1 Hz, 50 ms, and 8 pulses were selected as the optimum conditions for EP. Bladder specimens with GFP genes injected by EP showed numerous bright sites of GFP expression in the smooth-muscle layer. In rats with the nNOS gene injected by EP, there was marked nNOS immunoreactivity, and NOx released from bladder strips was significantly greater than that in the control groups. These results suggest that EP is a useful technique for in vivo gene transfer into rat bladder smooth muscles, and that the nNOS gene transferred by this procedure functionally expresses and contributes to NO production.

To investigate the effects of M-1, a major active metabolite of propiverine on the bladder.We have evaluated the effects of M-1 on the contractions induced by carbachol, KCl, CaCl(2), and electrical field stimulation (EFS) in human detrusor smooth muscles, and pelvic nerve stimulation-induced bladder contractions in rats. The effects of M-1 were also compared with the effects of propiverine and tolterodine.Pretreatment with propiverine and tolterodine caused parallel shifts to the right of the concentration-response curves to carbachol. M-1 caused concentration-dependent reduction in the maximum contractile responses induced by carbachol. Although tolterodine did not inhibit the KCl- and CaCl(2)-induced contractions, M-1 and propiverine significantly inhibited these contractions. In the presence of atropine, M-1 and propiverine significantly inhibited the atropine resistant part of the contraction induced by EFS. On the other hand, tolterodine did not have significant inhibitory effects on atropine resistant contractions. Pelvic nerve stimulation induced bimodal phasic and tonic contractions in the rat bladder. M-1 mainly inhibited the phasic contraction. Tolterodine caused a significant inhibition in the tonic contraction, and propiverine had inhibitory effects on both contractions.The present results suggest that M-1 has inhibitory effects on the bladder smooth muscles through calcium antagonistic action. It is possible that the clinical effects of propiverine on the human bladder are based not only on the action of propiverine itself but also on one of its active metabolites, M-1.

The possibility of in vivo gene transfer into the rat bladder by electroporation (EP) was evaluated. The bladder was exposed through an abdominal midline incision in 8-week-old male rats. Plasmid DNA of marker genes, green fluorescent protein (GFP) and luciferase, and the neuronal nitric oxide synthase (nNOS) gene were then injected into the subserosal space of the bladder and EP was applied. At 72 h after gene transfer, GFP and luciferase were assayed in the isolated bladder, and immunohistochemical staining was used to detect nNOS. NOx released from isolated bladder strips was also assessed using microdialysis procedure. From the luciferase assay, 45 V, 1 Hz, 50 ms, and 8 pulses were selected as the optimum conditions for EP. Bladder specimens with GFP genes injected by EP showed numerous bright sites of GFP expression in the smooth-muscle layer. In rats with the nNOS gene injected by EP, there was marked nNOS immunoreactivity, and NOx released from bladder strips was significantly greater than that in the control groups. These results suggest that EP is a useful technique for in vivo gene transfer into rat bladder smooth muscles, and that the nNOS gene transferred by this procedure functionally expresses and contributes to NO production.

We reviewed 44 patients who had a bipolar prosthetic replacement from July 1982 to July 1989. There were 5 men and 39 women, whose ages ranged from 33 to 82 years (average, 58.0). They were re-evaluated one year to seven years postoperatively by questionnaire and roentgenograms. According to JOA Hip Score, preoperative score (mean, 45.0 points) was improved postoperatively (mean, 80.9 points). Roentgenographically central migration was observed in 5 hips 10.4%) and proximal migration in 3 hips (6.3%). Distal migration was observed in 11 hips (22.9%) and the sclerotic change at the tip of the stem in 23 hips (47.9%).

Six cases (six knees) of the painful bipartite patellae were treated by surgical method because conservative treatment wasn't effective. The first case was treated by an excision of the accessory ossification center, but the knee pain remained. So we tried to get osteosynthesis of the bipartite patellae by peg bone autograft and all of them were treated well. As surgical treatment for painful bipartite patellae, we recommend osteosynthesis by peg bone autograft when there is no subluxation of the patella. And when there is suluxation, at first we should think of reduction of the patella for example by transposition of the tibial tuberosity.

Benign prostatic hyperplasia (BPH) affects quality of life (QOL), and the goal of treatment is to improve lower urinary tract symptoms (LUTS), thus improving patient QOL. However, the international prostate symptom score (IPSS) used for evaluating LUTS does not always reflect the level of patient bother, and improvement in the IPSS score does not always reflect patient QOL. Therefore, in the present study, we observed the therapeutic effects of alpha(1)-blockers on IPSS, QOL index, and the bother score for individual symptoms. Ninety-three men diagnosed with BPH who had not yet been treated were enrolled (mean age 70 years). The IPSS, QOL index, and bother score for each symptom of IPSS (maximum 42 points, 7 grades, from 0 to 6: not at all bothersome, not bothersome, not much bother, neutral, a little bothersome, somewhat bothersome, very bothersome) were assessed in order to examine the correlation between LUTS and QOL. After treatment with tamsulosin hydrochloride 0.2 mg/day for 4 weeks, the change in each IPSS and bother score and the correlation was reassessed. Furthermore, the contribution of improvements in each symptom score and bother score to improvement in QOL index was examined using a path analysis model. On the IPSS at initial evaluation, the score was highest for slow stream. The bother scores were high for slow stream, nocturia, and daytime frequency. For slow stream, patients with a high IPSS score also had a high bother score, but for nocturia, there was a large discrepancy between the IPSS and bother score. After treatment, total IPSS, QOL and total bother scores were significantly improved (p0.01). Improvements in all individual symptom scores and bother scores were also observed (p0.01). The most predictable symptom for improvement in QOL after treatment was the improvement in the bother score for nocturia (F test; p0.01). Treatment with tamsulosin hydrochloride showed significant improvement of each IPSS and the bother score. For nocturia, there was a large discrepancy between the IPSS and bother score. After treatment, the improvement in bother score for nocturia showed the strongest contribution to improvement in QOL. The present study suggests that in addition to the IPSS, the evaluation of bother score for each symptom may be necessary in the management for patients with LUTS suggestive of BPH.

To investigate the effects of solifenacin on human detrusor smooth muscles, we evaluate the effects of solifenacin on the contractions induced by carbachol, KCl, CaCl2 and electrical field stimulation (EFS), and the EFS-induced acetylcholine release from detrusor smooth muscle strips by using the muscle bath and microdialysis technique. The effects of solifenacin were also compared with effects of other antimuscarinic agents (atropine, oxybutynin and propiverine). Pretreatment with various antimuscarinic agents caused parallel shifts to the right of the concentration-response curves to carbachol. The pA2 value of the Schild plots for solifenacin was similar to that for oxybutynin. Atropine did not inhibit the KCl- and CaCl2-induced contractions, while solifenacin, oxybutynin and propiverine significantly inhibited these contractions. EFS-induced contractions were inhibited by various antimuscarinic drugs in a concentration-dependent manner. In the presence of atropine, solifenacin tended to inhibit the residual atropine-resistant contractions induced by EFS, but it was not significant. However, oxybutynin and propiverine inhibited them under the same conditions. Although pretreatment with atropine and propiverine did not cause significant changes in EFS-induced acetylcholine release, solifenacin and oxybutynin caused significant decreases in acetylcholine release. The present results suggest that solifenacin inhibits contractions of human detrusor smooth muscles mainly by the antimuscarinic action and that the high concentration of solifenacin has Ca2+ channel antagonist action. Moreover, solifenacin may block not only postjunctional receptors, but also prejunctional receptors to modulate acetylcholine releases in cholinergic nerve endings in human detrusor smooth muscles. The findings support that muscarinic-receptor-inhibitory actions in human bladder mainly contribute to the usefulness of solifenacin as a therapeutic drug for overactive bladder.

Multidrug-resistant organism (MDRO) infections in critically ill patients are often life-threatening. To prevent nosocomial infections of MDRO, we made an infection control bundle in our ICU in 2013. In this study we evaluated the effect of our infection control bundle to prevent nosocomial MDRO transmission and infection.

NK4, a 4-kringle fragment of hepatocyte growth factor (HGF), is an HGF antagonist that also acts as an angiogenesis inhibitor. NK4 strongly inhibits the infiltration, metastasis, and tumor growth of pancreatic cancer. The aim of our study was to evaluate the antitumor effect of adenovirus-mediated NK4 gene transfer to the liver on hepatic metastasis of pancreatic cancer in vivo. We constructed recombinant adenoviral NK4 (Ad-NK4), which encodes a secreted form of human NK4. Intrasplenic injection of Ad-NK4 induced high and relatively maintained expression of NK4 protein in the liver and suppressed the number and growth of metastatic foci in the liver in a nude mouse model. Microscopically, central necrosis was found even in small metastatic foci in Ad-NK4 treated mice. Immunohistochemical analysis of metastatic tumors showed a remarkable decrease in microvessel density and an increase in the number of apoptotic tumor cells after treatment with Ad-NK4. These results indicate that intraportal injection of Ad-NK4 may be a useful therapeutic modality for the clinical control of hepatic metastasis in pancreatic cancer.

Percutaneous needle biopsy of a transplanted kidney is indicated as a diagnostic procedure in the evaluation of unexplained deteriorated renal function after renal transplantation. This procedure is not always without complications. We report a case of a subcapsular hematoma and hypertension following a percutaneous needle biopsy of a transplanted kidney. The cause of hypertension in this patient and the management of the subcapsular hematoma are discussed.

Muscarinic M3 (M3) receptor has been recognized as a major muscarinic receptor for smooth muscle contractions of the urinary bladder. Under the hypothesis that overexpression of M3 receptor in the urinary bladder would enhance urinary bladder contractions, we have transferred the M3 receptor gene into rat bladders using electroporation (EP) and evaluated the functional expression of the transferred gene.Plasmids expressing luciferase, a green fluorescence protein and M3 receptor were injected into the rat bladder and square-wave electric pulses were immediately applied. Two days after gene transfer, we analyzed gene expression. Immunohistochemical staining was performed and the contractile responses from isolated bladder strips, which were induced KCl, carbachol and electrical field stimulation (EFS), were evaluated.The optimal conditions of electroporation were 8 pulses, 45 voltages, 50 milliseconds/pulses and 1 Hz. Under these conditions, luciferase gene expression was enhanced approximately 300-fold, compared to an injection of DNA only. Regarding immunohistochemistry with an anti-M3 receptor, an increase in immunoactivity was observed in the M3 receptor gene transferred rat bladder, compared to the bladder of the control rat. In rats with the transferred M3 receptor gene, carbachol- and EFS-induced maximum contractile responses of bladder smooth muscle strips significantly increased.These findings suggest that an in vivo EP procedure is an useful method for gene transfer into the bladder and that an overexpression of M3 receptor in the rat bladder enhances bladder contractility. This technique may become a new treatment modality for detrusor underactivity.

Small pulmonary adenocarcinomas can be classified on the basis of their histological characteristics and prognosis, and when classified as such, the prognosis of replacing-type adenocarcinoma with active fibroblast proliferation is significantly worse than adenocarcinoma without fibroblast proliferation. In order to clarify the biological mechanisms of the key to the morphological changes associated with active fibroblast proliferation, we examined the activities of matrix metalloproteinase (MMP)-2 and MMP-9, which are important enzymes in the stromal invasion by cancers. The active MMP-2 and MMP-9 content of 40 pulmonary adenocarcinomas that were less than 20 mm in diameter was measured by the gelatin zymography method. The quantity of active MMP-2 in the pulmonary adenocarcinomas with active fibroblast proliferation was higher than in the pulmonary adenocarcinomas without proliferation (P < 0.001), but there were no correlations between the histological features and the activation of MMP-9. The presence of active fibroblast proliferation in small pulmonary adenocarcinomas suggests that the cancer cells have acquired the ability to invade through the action of active MMP-2, and this is thought to be one of the reasons for the worse prognosis of pulmonary adenocarcinoma with active fibroblast proliferation.

2003, 【要旨】

A girl with continuous urinary incontinence was successfully treated by angiographic embolization of a hypoplastic pelvic kidney with a single unilateral vaginal ectopic opening of the ureter. For this intervention, CT angiography was useful for detecting the corresponding renal artery of the hypoplastic kidney.

Hepatocyte growth factor (HGF) is a stromal-derived cytokine that plays a crucial role in invasion and metastasis of tumor cells through the interaction with HGF receptor, c-Met, which is frequently overexpressed in pancreatic cancer. The present study was designed to investigate the change in HGF receptor and HGF-mediated signaling after irradiation in pancreatic cancer cells. Six cell lines from human pancreatic cancer were included in the study. Gamma-radiation was used for irradiation treatment. The changes in expression levels of c-Met were evaluated by immunoblot and confirmed morphologically by indirect immunofluorescence staining. Whether the resultant alteration in c-Met would cascade as biologically usable signals upon HGF ligation was traced by receptor tyrosine phosphorylation analysis and mitogen activated protein kinase (MAP kinase or MAPK) activity assay. The various biological responses to HGF (including cell proliferation, cell scattering, migration and invasion) were evaluated as well. We also used a 4-kringle antagonist of HGF, NK4, to block the HGF/c-Met signaling pathway. Both immunoblot and immunofluorescent analysis showed moderate increased expression of c-Met in 3 of 6 pancreatic cancer cell lines after irradiation. The actions seemed to be dose-responsible, which began at 3 hr and reached its peak value at 24 hr following irradiation. The radiation-increased expression of c-Met could transform into magnifying receptor tyrosine phosphorylation reaction and MAP kinase activity once the ligand was added, fairly corresponding with alteration in the receptor. Sequentially, the cellular responses to HGF, including scattering and invasion but not proliferation, were enhanced. Also, in the presence of HGF, the elevated receptor could help to recover the radiation-compromised cell migration. A recombinant HGF antagonist, NK4 could effectively block these aberrant effects activated by irradiation both in molecular and cellular levels, thus suggesting the deep involvement of the c-Met/HGF pathway in the enhanced malignant potential after irradiation. These results suggest that radiation may promote HGF-induced malignant biological behaviors of certain pancreatic cancer cells through the up-regulated HGF/c-Met signal pathway. Selectively targeted blockade of the HGF/c-Met pathway could help to abolish the enforced malignant behavior of tumor cells by irradiation and therefore may improve the efficacy of radiotherapy for pancreatic cancer. © 2003 Wiley-Liss, Inc.

Sixty-five hybrid total hip replacements (THRs) in 58 patients with osteoarthritis (OA) and rheumatoid arthritis (RA) were analysed with regard to chinical and radiographical findings more than one year after surgery. The mean follow-up period was 22.2 months. Results are as follows; (1) Thigh pain occurred in 5.5% of OA cases (55 cases) and 10% of RA cases (10 cases). (2) Radiolucent lines were found in zone 1 (21.5%). (3) Bone cement gaps were found in 14.5% of OA cases and 0% of RA cases. (4) No osteolysis was found in any cases.

A multilocular-cystic and cavernous, retroperitoneal tumor was found in a 40-year-old man whose past medical history was unremarkable. On admission, he complained of a large and still growing intra-abdominal mass associated with dull pain and a low-grade fever. Laboratory findings revealed leukocytosis and C-reactive protein elevation, compatible with inflammation of the tumor. Percutaneous aspiration of the tumor was performed under transabdominal ultrasonographic guidance, and continuous drainage of fluid from within the tumor ameliorated his symptoms. From preoperative examinations, including radiological imaging, fluid aspiration, and endoscopy with biopsy, a diagnosis of retroperitoneal lymphangioma was made. Laparotomy revealed extensive adhesions between the tumor and both the duodenum and the pancreatic head. A pancreaticoduodenectomy was therefore performed. At 3-year follow-up, there was no sign of recurrence. Retroperitoneal lymphangioma is an uncommon disorder, and the cavernous type is extremely rare. The duodenal lesion was an important feature of the present case, and endoscopic biopsy of this lesion facilitated precise preoperative diagnosis of retroperitoneal lymphangioma.

A case in which malignant lymphoma occurred in association with a tuberculosis focus in a 70-year-old man is reported. Surrounding the epithelioid cell granulomas with caseous necrosis was a dense and diffuse monotonous infiltration of atypical lymphoid cells. Acid-fast bacilli were found in the granulomas and pulmonary tuberculosis was diagnosed. The infiltrating atypical lymphoid cells occasionally invaded the respiratory epithelium producing lymphoepithelial lesions. Immunohistochemically, the lymphoid cells were positive for CD20, and clonal rearrangement of the immunoglobulin heavy chain gene was demonstrated by polymerase chain reaction (PCR). We diagnosed the lesion as a pulmonary malignant lymphoma of bronchus-associated lymphoid tissue (BALT) occurring in the background of tuberculosis. This is the first reported case of pulmonary BALT lymphoma coexistent with pulmonary tuberculosis.

A previously uncharacterized yeast protein, YJL066c, was discovered in the membrane fraction although it has no hydrophobic stretch. The protein was partly solubilized by Triton X-100 in an oligomeric form, while it was insoluble in alkali or salt. By immunofluorescent microscopy, its localization coincided with the mitochondria. We therefore propose it should be named Mpm1 (mitochondrial peculiar membrane protein 1).

We evaluated the effects of nitric oxide (NO) on acetylcholine release and the contractile response induced by electrical field stimulation in rabbit bladder smooth muscles using a muscle bath and high performance liquid chromatography coupled with microdialysis. Electrical field stimulation (supramaximum voltage, pulse duration 0.5 ms, frequency 5 and 20 Hz) was applied to a smooth muscle strip isolated from rabbit bladder. With low-frequency (5 Hz) stimulation, pretreatment with N ω -nitro- l -arginine ( l -NNA) (100 μM) significantly increased electrical field stimulation-induced acetylcholine release and contractile response, which were reduced by the addition of l -arginine. Pretreatment with sodium nitroprusside in the absence or presence of l -NNA significantly decreased electrical field stimulation-induced acetylcholine release and contractile response. In contrast, with high frequency (20 Hz) stimulation, pretreatment with l -NNA and sodium nitroprusside had no significant effect on either contractile response or acetylcholine release. Pretreatment with sodium nitroprusside caused no significant changes in carbachol and ATP-induced contractile responses. Sodium nitroprusside and l -NNA had no significant effects on the atropine-resistant part of the contraction induced by electrical field stimulation in rabbit bladder smooth muscles. The results suggest that there is a NO-mediated mechanism inhibiting acetylcholine release from cholinergic nerve endings in rabbit bladder, which may contribute to bladder function.

A prospective study of 110 patients was carried out to determine the pathogenic significance of trauma to the upper body in the development of neural compressive irritation at the thoracic outlet. Twenty-nine patients were reviewed as cervical strain injuries (N group), 25 patients as probable neurogenic thoracic outlet syndrome (NTOS) (PT group), 39 patients as definite NTOS (T group), and 17 patients as NTOS associated with cervical disc disease (CD-T group). The time lapse between accident and diagnosis and the duration of treatment were significantly longer in T patients or CD-T patients than those in the N group. Radiography of NTOS patients also showed a higher percentage of cervical spine-length/height ratio. Traumatic NTOS would suggest two types related to direct damage of scalene muscles that included some physical aspects of cervical disc disease. Pathogenesis provided a key to the resolution of more complex posttraumatic problems of whiplash injury.

BACKGROUND Although the cytologic characteristics of advanced adenocarcinomas of the lung have been described, the unique cytologic features of early adenocarcinomas have not been established. METHODS Cytologic specimens from 193 patients with small-sized lung adenocarcinoma, up to 2 cm in dimension, were reviewed. Cytologic investigations were performed on sputum, bronchial brushings or washings, or fine-needle aspirates obtained from the patients preoperatively. The cytologic characteristics of early adenocarcinoma were confirmed with Image Processor for Analytical Pathology from Sumitomo Chemical Co., Ltd. RESULTS Nuclear size, variations in nuclear size, appearance of nucleolus, and nuclear atypia of the adenocarcinoma cells were found to differ between the various histologic subtypes of adenocarcinoma. The nuclei in small but advanced adenocarcinoma were generally larger and showed more variation in size than those in early adenocarcinoma (localized bronchioloalveolar carcinoma). CONCLUSIONS Surgically curable, early adenocarcinomas of the lung were found to have a unique cytologic appearance, including small nuclear size and slight variation in nuclear size. Using these unique characteristics, they can be distinguished easily from advanced adenocarcinomas. Cancer (Cancer Cytopathol) 2001;93:124–131. © 2001 American Cancer Society.

We evaluated the correlation among age, cholinergic and purinergic neurotransmissions in the electrical field stimulation-induced contractions in human isolated urinary bladder smooth muscles, using the muscle bath technique. Human bladder specimens were divided into three groups (G1, under 50years; G2, 51-70years; G3, over 70years old), and each muscle strip was suspended in a thermostatically controlled organ bath filled with oxygenated Krebs-Henseleit solution, connected to an isometric force displacement transducer, and an isometric tension development was recorded. The contractile responses induced by KCl, carbachol, adenosine triphosphate (ATP) and electrical field stimulation, and the effects of atropine and alpha, beta methylene ATP on electrical field stimulation-induced contractions were observed. The contractile response to KCl and concentration-response curves for carbachol and ATP, and frequency-response curves for electrical field stimulation were not significantly different among the three groups. The atropine sensitive and resistant parts of contraction induced by electrical field stimulation were decreased and increased with age, respectively. There are significant positive and negative correlations between age and the purinergic, and age and the cholinergic neurotransmissions in human isolated bladder smooth muscles, respectively. The age-related changes in neurotransmissions may contribute to the changes in bladder function in the elderly.

Clinical trials of BNCT for glioblastoma have been underway around the World. In Japan, the new reactor JRR-4 has been now reconstructed especially for therapeutic irradiation. From the clinical point of view, pathological studies are very important in understanding post BNCT clinical and MRI findings. However, pathological findings on target lesions, which received BNCT have scarcely been reported.1 We report an interesting and rare autopsy case of giant cell glioblastoma and compare MRI findings with autopsy findings, and discuss histopathlogical changes after BNCT

To evaluate the effects of tolterodine, vamicamide and temiverine, novel antimuscarinic drugs developed for the treatment of frequency and urinary incontinence, on human detrusor smooth muscle. Materials and methods Specimens of human urinary bladder were obtained from 20 patients who underwent total cystectomy for malignant bladder tumour. Using an organ-bath technique, the effects of various drugs on the contractions induced by carbachol, KCl, CaCl2 and electrical field stimulation in the detrusor strips were investigated.Carbachol (0.001-10000 micromol/L) caused concentration-dependent contractions in human detrusor smooth muscles. Tolterodine (0.01-10 micromol/L), vamicamide (0.01-10 micromol/L), temiverine (0.01-1 micromol/L) and atropine (0.001-1 micromol/L) caused parallel shifts to the right of the concentration-response curves to carbachol. All slopes for the regression line of Schild plots were close to unity, and the rank order of pA2 values was atropine = tolterodinevamicamidetemiverine. Tolterodine, vamicamide and atropine did not inhibit the maximum contractile responses to carbachol, while temiverine (10 micromol/L) significantly inhibited the maximum contractions. Tolterodine (0.001-1 micromol/L) and vamicamide (0.01-10 micromol/L) did not inhibit the KCl- (80 mmol/L) and CaCl2-induced (5 mmol/L) contractions, while temiverine (0.01-10 micromol/L) significantly inhibited the contractions. Electrical field stimulation (2-60 Hz) caused frequency-dependent contractions in human detrusor smooth muscles, which were significantly inhibited by various drugs. In the presence of 1 micromol/L atropine, tolterodine and vamicamide did not inhibit the contractions induced by electrical field stimulation at all frequencies, while temiverine (10 micromol/L) significantly inhibited the contractions.Tolterodine and vamicamide inhibited contractions of human detrusor smooth muscles only through their antimuscarinic action, while temiverine had both antimuscarinic and calcium-antagonist actions. Furthermore, these novel drugs have different efficacies and potencies for inhibiting human detrusor smooth muscle.

Clonal expansion of the germinal center B cells of human reactive lymph nodes was analyzed. By micromanipulation, 28 germinal centers were microdissected from three nonneoplastic lymph nodes that had been fixed with formalin. Immunoglobulin heavy chain variable (V) region gene rearrangement was examined by seminested polymerase chain reaction (PCR) using two sets of primers (FR2-J and FR3A-J). An oligoclonal development (one to five clones) was found in each germinal center. Depending on the primer used, four or five (16%) of the germinal centers showed a single rearrangement band. The average number of B-cell clones in each germinal center was approximately 2.5. Next, the authors analyzed 50 endoscopic biopsy specimens from 6 patients with non-mucosa-associated lymphoid tissue (MALT) type gastric lymphoma, 25 patients with chronic gastritis, and 19 patients with nonspecific colitis. In addition to the samples from the 6 patients with malignant lymphoma, 8 of 44 biopsy samples (18.2%) from patients diagnosed as having chronic gastritis or nonspecific colitis showed one or two amplified bands. These results indicate that PCR analysis of immunoglobulin heavy chain V region gene rearrangement in small biopsy specimens could be misleading, causing overdiagnosis of reactive lymphoid tissue as B-cell clonal proliferation.

The accuracy of the stress X-ray examination for the cruciate ligament deficient knee was studied. A stress device with the knee in 90 degrees of flexion was used. The examination was useful for the complete deficiency of the posterior Cruciate ligament. While for deficiency of the anterior cruciate ligament or imcomplete posterior ligament injury, this method was not accurate. For getting higher accuracy, we must use MRI, tomography of the cruciate ligament after arthrography and stress X-ray with the knee in 30-degree flexion position.

The p16 (CDKN2/MTS-1/INK4A) tumor-suppressor gene is frequently inactivated by DNA methylation in lung carcinomas. To clarify whether background anthracosis may play a role in DNA methylation and inactivation of the p16 gene, we examined DNA methylation of the p16-promoter region by methylation-specific polymerase chain reaction, and p16 expression immunohistochemically, and compared the results with the level of background anthracosis which was measured by an original quantitative method. At autopsy, DNA methylation of the p16 gene was observed in 6/19 tumors (32%) from patients who had died of pulmonary adenocarcinoma. The degree of background anthracosis (the effect of extrinsic carcinogenic factors) (mean absorbance value, A = 0.715) of the cases with p16-gene methylation was significantly higher than that without methylation (mean A value = 0.298). p16 expression was inactivated in all tumors with p16-gene methylation. The mean A value of black dust matter deposition in cases with normal expression of p16 (A = 0.151) was significantly lower than cases with abnormal expression of p16 (A = 0.531). These results indicate that the level of background anthracosis is closely associated with inactivation of p16 expression and also DNA methylation of the p16-gene promoter region in pulmonary adenocarcinogenesis. Int. J. Cancer (Pred. Oncol.) 84:609-613, 1999.

Tolterodine, (R)-N,N-diisopropyl-3-(2-hydroxy-5-methylphenyl)-3-phenylpropanamine+ ++, is an antimuscarinic drug developed for the treatment of overactive bladder with symptoms of frequency, urgency and urge incontinence. We investigated the effects of tolterodine and its major active metabolite, DD 01 (PNU-200577), (R)-N,N-diisopropyl-3-(2-hydroxy-5-hydroxymethylphenyl)-3-phenylpropa namine, on the contractions induced by carbachol, KCl, CaCl2 and electrical field stimulation in human isolated urinary bladder smooth muscles, using the muscle bath technique. Specimens of human urinary bladder were obtained from 20 patients who underwent total cystectomy due to malignant bladder tumor. The detrusor preparations were taken from the intact part of the dome region of the bladder. Carbachol (10(-9)-10(-2) M) caused concentration-dependent contraction of human detrusor smooth muscles. Tolterodine (10(-9)-10(-6) M), DD 01 (10(-9)-10(-6) M), oxybutynin (10(-8)-10(-6) M), propiverine (10(-8)-10(-6) M), atropine (10(-9)-10(-6) M), pirenzepine (10(-8)-10(-5) M), methoctramine (10(-8)-10(-5) M) and 4-diphenylacetoxy-N-methylpiperidine (4-DAMP) (10(-9)-10(-6) M) caused typical shifts to the right of the concentration-response curves for carbachol, except for higher concentrations (10(-5) M) of oxybutynin and propiverine, which caused a decrease of about 30% of the maximum contractile responses to carbachol. All the slopes of the regression lines of Schild plots were close to unity, and the rank order of pA2 values was: atropine = DD 01 = tolterodine = 4-DAMP = oxybutynin > propiverine = pirenzepine > methoctramine. Tolterodine (10(-9)-10(-6) M) and DD 01 (10(-9)-10(-6) M) did not inhibit the KCl-induced (80 mM) and CaCl2-induced (5 mM) contractions, while oxybutynin (10(-8)-10(-5) M) and propiverine (10(-8)-10(-5) M) significantly inhibited the contractions. Electrical field stimulation (2-60 Hz) caused frequency-dependent contraction of human detrusor smooth muscles, which were significantly inhibited by various drugs. In the presence of 10(-6) M atropine, tolterodine and DD 01 did not inhibit the residual contractions induced by electrical field stimulation at any of the frequencies, while oxybutynin (10(-5) M) and propiverine (10(-5) M) significantly inhibited the atropine-resistant part of the contractions. The results suggest that the inhibitory effects of tolterodine and DD 01 are mediated only by their antimuscarinic action, which is equal to that of oxybutynin and significantly greater than that of propiverine, and that tolterodine and DD 01 have neither Ca2+ channel antagonist action nor inhibitory effect on the atropine-resistant part of the contractions in human detrusor smooth muscles. These findings support the usefulness of tolterodine as a therapeutic drug for overactive bladder with symptoms of frequency, urgency and urge incontinence.