Ca2+ sensitization in contraction of human bladder smooth muscle

PURPOSE: The role of Ca2+ sensitization in the contraction of human bladder urinary smooth muscle (UBSM) was investigated. MATERIALS AND METHODS: Simultaneous measurements of intracellular Ca2+ concentration ([Ca2+]i) and tension in fura-2 loaded intact strips and receptor coupled strips permeabilized with alpha-toxin were applied. Protein expressions was confirmed by Western blot analysis. RESULTS: In intact fura-2 loaded strips 1 microM carbachol (CCh) induced a greater contraction and a lower [Ca2+]i elevation than that induced by 60 mM K depolarization. In alpha-toxin permeabilized strips 1 microM CCh induced contraction at constant [Ca2+]i and produced a leftward shift in the [Ca2+]i-tension relationship. RhoA, Rho-associated kinase (ROCK) I, ROCK II and CPI-17 proteins were expressed in human UBSM. In intact fura-2 loaded strips the application of 3 microM Y-27632, a ROCK inhibitor, or 3 microM bisindolylmaleimide I (GF109203X), a protein kinase C inhibitor, during the sustained phase of contraction induced by 1 microM CCh induced relaxation without changing [Ca2+]i. In alpha-toxin permeabilized strips the application of 3 microM Y-27632 or 3 microM GF109203X during the sustained contraction induced by 0.3 microM Ca plus 10 microM guanosine triphosphate and 1 microM CCh induced relaxation at constant [Ca2+]i. CONCLUSIONS: These results indicate that in human UBSM CCh induces contraction, not only by increasing [Ca2+]i, but also by increasing the Ca2+ sensitivity of the contractile apparatus in a ROCK and protein kinase C dependent manner. Antagonism of Ca2+ sensitization pathways may represent an alternative target in the treatment of overactive bladder.     

Immune responses of graft mesenteric lymph node in small bowel transplantation

BACKGROUND: The high proportions of lymphoid tissues are thought to be one of the underlying factors inducing severe allograft rejection following small bowel transplantation. Mesenteric lymph nodes (MLN) contained in the intestinal graft are not only a source of donor-derived professional antigen-presenting cells, but also offer a field for immune interaction between donor and host cells. We investigated immune responses in graft MLNs with or without FK506 to develop a novel strategy to control small bowel allograft rejection. MATERIALS AND METHODS: Heterotopic small bowel transplantations were performed from Brown Norway donors to Lewis recipients. Changes in population of lymphocytes, expressions of costimulatory molecules, apoptosis, and cytokine profiles in graft MLNs were evaluated. RESULTS: The increase in apoptotic cells and cytokine responses relating to rejection in the graft MLNs developed prior to those in graft jejunum. While donor lymphocytes in graft MLNs were rapidly replaced to host-derived lymphocytes independent of FK treatment, increase in CD8(+) T cells in host population was seen only in recipients without FK506 treatment. The expressions of B7 molecules on donor cells in graft MLNs were significantly lower in the recipients with FK treatment. CONCLUSIONS: Immune responses in graft MLNs have significant impact on the outcome of the small bowel allograft. Apoptosis of graft MLN cells was well correlated with and ahead of progression of acute rejection. Modulation of costimulatory molecules on donor-derived MLN cells in the allograft and specific suppression of host CD8(+) T cells are possible ways to control severe rejection after allogeneic small bowel transplantation.     

Intraoperative ultrasound

Intraoperative ultrasound (IOUS) can provide various diagnostic information that is otherwise not available, and can guide or assist various surgical procedures in real time. With refinement of equipment, IOUS is currently used in a wide variety of surgical operations,such as hepatobiliary, pancreatic, endocrine, cardiovascular,and neurologic surgery. Our overview of IOUS, including instrumentation,techniques, indications, advantages, disadvantages,and future perspective, is described in this article. Being safe, quick, accurate, and versatile intraoperatively, IOUS is a valuable technique that surgeons are recommended to master to improve intraoperative decision making and surgical procedures.     

A case of transitional cell carcinoma of the renal pelvis with adenocarcinoma producing CEA and CA19-9

We report a case of invasive renal pelvic tumor with high serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9). An 86-year-old man presented with macrohematuria. Retrograde pyelography demonstrated a filling defect in right upper calyx, suspected of renal pelvic tumor. The levels of serum CEA and CA 19-9 were elevated to 28.0 ng/ml and 122 U/ml, respectively. No abnormalities were found in the gastrointestinal tract. Right nephroureterectomy was performed, and histopathological diagnosis was transitional cell carcinoma, grade 2>grade 3, accompanied with adenocarcinoma immuno-stained for CEA and CA19-9. A part of the tumor showed a tubular growth pattern. Both serum levels of CEA and CA 19-9 immediately decreased to the normal range after the operation, but increased again with lung and hepatic metastases.     

Sequential morphological change of Chiari malformation type II following surgical repair of myelomeningocele

Purpose

To document long-term morphological changes of Chiari type II malformation (CM-II) following closure of spina bifida manifesta (SBM).

Methods

We retrospectively evaluated postnatal magnetic resonance images of the CM-II and posterior fossa (PF) in 28 consecutive cases. We measured changes in vertebral level and length of the cerebellar peg (CP), cerebrospinal fluid (CSF) spaces anterior and posterior to the cerebrospinal junction, PF area, and the anteroposterior diameters of the foramen magnum (FM) and C1 vertebra. We examined the morphological differences between the cases with and without ventriculoperitoneal (VP) shunting and derived predicted means by nonlinear mixed-effect modeling.

Results

At birth, there were significant differences in CP length, PF area, and FM and C1 diameters between those who underwent VP shunting and those who did not. In cases with a CP below C1, VP shunting was required in every case but one. In those with visible CSF space at birth, VP shunts were not required. In 17 of 18 cases with a CP below C1, the vertebral level ascended by mean two vertebral levels (range 0–5 levels) within 4–6 months of delivery. In the remaining case, slowly progressive hydrocephalus and delayed CP descent required VP shunting at 8 months. Predicted mean CP length and FM and C1 diameters were greater in those who underwent VP shunting, but there was no difference in predicted mean PF area.

Conclusion

The morphology of CM-II and the presence of hydrocephalus influence each other in children who have undergone postnatal SBM repair.

     

Influence of dipyridamole on infarct size and on cardiac nucleoside content following coronary occlusion in the dog

Summary The effects of 3 different doses (0.02, 0.1, 0.5 mg/kg/h) of dipyridamole on myocardial infarct size were evaluated in pentobarbital anesthetized open-chest dogs following sequential coronary occlusion of two medium sized coronary arteries in the same heart. The first coronary occlusion produced a control infarct, the other a test infarct under the influence of the drug. Dipyridamole infusion was started 10 min before the second occlusion at a rate of 0.02 (group A, n=9), 0.1 (group B, n=10) or 0.5 (group C, n=9) mg/kg/h respectively and continued to the end of reperfusion (90 min). Biopsy samples were obtained at the end of each occlusion period and at the end of the second reflow period. Infarct size was determined using post mortem angiography and pNBT staining. Control and treated infarct sizes, expressed as a percentage of the perfusion area, were 21.9±5.4% vs. 25.2±7.7% in group A (n=9), 21.8±7.3% vs. 18.3±5.2% in group B (n=9), and 22.3±7.7% vs. 16.2±4.8% in group C (n=8). There were no significant differences between control and treated infarct sizes in the 3 groups. After 90 min coronary occlusion tissue adenosine contents in the ischemic myocardium were significantly higher (42±7 nmol/gww in group C and 40±5 nmol/gww in group B) than those in the nonischemic myocardium, and dipyridamole enhanced these levels (395±6 nmol/gww in group C: p<0.01, 55±10 nmol/gww in group B). Dipyridamole did not affect the tissue inosine levels in the ischemic myocardium after 90 min coronary occlusion. ATP and creatine phosphate levels were not affected by dipyridamole during ischemia or during reflow. The accumulated adenosine was not phosphorylated to AMP and on to ATP upon reperfusion.     

Organ-specific carcinogenicity of N-methyl-N-nitrosourea in F344 and ACI/N rats

Summary Male and female F344 rats were continuously administered N-methyl-N-nitrosourea (MNU) in their drinking water at concentrations of 200 or 100 ppm, and both sexes of ACI/N rats were given MNU at a concentration of 200 ppm. By the 42nd week of the experiment, high incidences of brain/spinal cord tumors were observed in both strains of rats. Histologically, many of them were astrocytomas or anaplastic astrocytomas. In addition, malignant neurinomas were also detected in the spinal nerve roots and trigeminal nerves, although their incidences were rather low. There was no difference in the type and incidence of these neurogenic tumors between the two strains of rats. Tumors of the tongue and esophagus were mainly observed in the high-dose group of F344 rats and those of the glandular stomach were observed in the low-dose group of F344 rats. In ACI/N rats, tumors of the heart and renal pelvis were detected. The organ-specific carcinogenicity of MNU in these two strains of rats was compared with that of MNU in Donryu rats. It was demonstrated that organ specificity of MNU given orally was influenced not only by the strain of rats but also by the dose level.Part of this work was presented at the 43rd Annual Meeting of the Japanese Cancer Association in Fukuoka, October 1984. This work was supported by grants-in-aid for cancer research from the Ministry of Education, Science and Culture     

Anaplastic and meningothelial meningiomas in a single tumor: A “dedifferentiated meningioma”?

The patient was a 74‐year‐old man, who developed progressive cognitive impairment and gait instability. Neuroradiological examination demonstrated a large and predominantly extra‐axial tumor spreading over the bilateral frontal base, indicative of olfactory groove meningioma. The greater part of the resected tumor consisted of a dense, patternless proliferation of large, round or polygonal cells, and compactly fascicular growth of spindle cells. Tumor cells showed markedly anaplastic cytological features. In small areas of the tumor, a typical meningothelial meningioma showing no cellular atypism was found. Both tumor components were closely juxtaposed and no pathological features of an intermediate grade (atypical meningioma) were noted. Shortly after the operation, the patient developed a local recurrence of the tumor and multiple metastases to the cerebrum, bone and skin. Anaplastic meningioma is a rare, highly malignant neoplasm which arises de novo or as a result of the progressive transformation of a low‐grade meningioma. The coexistence of anaplastic and low‐grade components in a single meningeal tumor has been rarely reported. This dimorphic appearance is reminiscent of “dedifferentiation”, a phenomenon infrequently seen in various mesenchymal and salivary gland neoplasms. We think that the term “dedifferentiated meningioma” can be appropriately applied to tumors such as that reported herein.     

Impact of an inflammation-based prognostic system on patients undergoing surgery for hepatocellular carcinoma: a retrospective study of 398 Japanese patients

BackgroundFew studies have investigated the Glasgow Prognostic Score (GPS) in patients with hepatocellular carcinoma (HCC).MethodsThis study compared the prognostic value of the GPS and Cancer of the Liver Italian Program (CLIP) score in patients undergoing surgery for HCC.ResultsA total of 398 patients were evaluated retrospectively. Kaplan–Meier analyses revealed that GPS (P < .001) and CLIP score (P < .001) were associated with overall survival. GPS could classify patients with low CLIP score (0 or 1) into 3 independent groups (P < .001). Univariate analyses selected GPS (P = .006) and CLIP score (P = .002) as the predictive factors associated with overall survival. Multivariate analysis using these 2 scoring systems disclosed that both GPS (P = .025) and CLIP score (P = .010) were associated with overall survival.ConclusionsGPS is not only an important predictor of overall survival after surgical treatment of HCC as well as CLIP score, but also is able to clearly divide patients with low CLIP score into 3 independent groups.     

A case of myxofibrosarcoma of the bladder

A 43-year-old woman presented to our hospital with the chief complaints of gross hematuria and dysuria. Cystoscopy and magnetic resonance imaging showed a tumor on the dome of the bladder and large blood clots. Computed tomography demonstrated no findings of distant metastasis. Following transurethral resection of the tumor, the tumor was histologically diagnosed as myxofibrosarcoma with muscular invasion, and partial cystectomy was performed in September 2009. There has been no evidence of recurrence or metastasis for 24 months postoperatively. In addition, the Japanese literature on myxofibrosarcoma of the bladder was reviewed and discussed.