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Biomedical subjects

Shinya Kobayashi

Publications and source records attributed to Shinya Kobayashi.

At least 19 recordsLinked to original sources

Heterotopic pancreas in the stomach which caused obstructive stenosis in the duodenum.

The patient, a 43-year-old Japanese man suffering from duodenal ulcer and reflux esophagitis, was admitted to our hospital because of submucosal tumor in the antrum and obstructive stenosis of duodenum. Several imaging tests could not rule out the possibility of malignant disease. Therefore, the patient was surgically treated. Pathohistological examination of resected tissue demonstrated Heinrich type I heterotopic pancreas in the gastric lesion and submucosal abscess in the duodenal lesion with stenosis. In this case, it was considered that the heterotopic pancreas caused chronic inflammation to form the gastric tumor, and submucosal abscess leading to the severe duodenal stenosis.

Abscess↗

ROCK inhibition produces anxiety-related behaviors in mice.

RATIONALE: The role of Rho/Rho-associated kinase (ROCK) in regulating dendritic and axonal morphology during development has gained much attention. Very little is known, however, about the role of the Rho/ROCK pathway in emotional behavior. OBJECTIVE: To investigate the role of ROCK in emotional behaviors. We examined how the ROCK inhibitor Y27632 affects the performance of mice on three behavioral tests that measure anxiety-related behaviors. RESULTS: In the elevated plus-maze test, Y27632 (10 nmol, intracerebroventricular) induced a significant decrease in the percentage of time spent in the open arms and in the percentage of entries into open arms. In the fear conditioning test, Y27632-treated mice froze significantly more often and longer than did saline-treated mice. In the hole-board test, Y27632 significantly suppressed head-dipping behavior in Y27632-treated mice than in saline-treated mice. On the other hand, Y27632 did not produce on spontaneous alteration performance in the Y-maze test. These results indicate that ROCK inhibition increased anxiety-related behaviors. CONCLUSION: Our findings suggest that the ROCK pathway is involved in the expression of anxiety- and fear-related behaviors. Furthermore, we propose that if the Rho/ROCK pathway plays an important role in mediating anxiety-related behaviors in humans, it may prove to be a novel system for anxiolytics to target.

Amides↗

Uroselectivity in male dogs of silodosin (KMD-3213), a novel drug for the obstructive component of benign prostatic hyperplasia.

AIMS: Our main aim was to compare the prostatic selectivity of silodosin with that of other alpha(1)-adrenoceptor (AR) antagonists. METHODS: We examined uroselectivities in two sets of experiments namely, in vitro and in vivo functional studies using male dogs. In the in vitro study, after evaluating the inhibitory effects of silodosin on noradrenaline (NA)-induced contractions in the isolated prostate and isolated carotid artery using the Magnus method, we calculated prostatic selectivity. In the in vivo study, we examined the effects of drugs on the hypogastric nerve stimulation (HNS)-induced increase in intraurethral pressure (IUP) and on blood pressure. The uroselectivity of silodosin was compared with those of tamsulosin and naftopidil. RESULTS: In vitro, all drugs antagonized NA-induced contraction in both prostate and carotid artery. The prostatic selectivity of silodosin (79.4) was much higher than those of tamsulosin (1.78), naftopidil (0.55), BMY 7378 (0.115), and prazosin (0.01). In vivo, intravenously (i.v.) administered silodosin dose-dependently inhibited the HNS-induced increase in IUP with much less hypotensive effect than either tamsulosin or naftopidil, the uroselectivity (ED(15)/ID(50)) of silodosin (237) being significantly higher than those of tamsulosin (1.21) and naftopidil (2.65). CONCLUSIONS: Our results clearly demonstrate that silodosin is a potent and highly selective alpha(1A)-AR antagonist. A selective alpha(1A)-AR antagonist such as silodosin may have good potential as a less-hypotensive drug for the treatment of urinary dysfunction in benign prostatic hyperplasia patients.

Adrenergic alpha-1 Receptor Agonists↗

Alveolar soft-part sarcoma of the retroperitoneum.

A 33-year-old woman was referred to Iida Municipal Hospital because of left back pain. Computed tomography showed a tumor (17 x 11 x 10 cm) in the left retroperitoneal space. T1- and T2-weighted magnetic resonance imaging showed an inhomogeneous mass with marginal blood vessels. The tumor was resected via lumbar oblique incision with the thoraco-abdominal approach. The tumor weighed 1800 g and consisted of nests of 5-100 large, loosely arranged, polygonal cells, surrounded by capillaries, resembling alveoli. The tumor cells were rich in cytoplasm, containing periodic acid-Schiff- and diastase-positive granules and typical crystals. The pathological diagnosis was alveolar soft-part sarcoma (ASPS). Alveolar soft-part sarcoma is a rare soft-tissue tumor that accounts for approximately 0.5-1% of soft-tissue sarcomas. Such tumors originating in the retroperitoneal space are extremely rare. Herein is reported a case of ASPS of the retroperitoneum with radiological and pathological findings.

Adult↗

[Effect of silodosin on intraurethral pressure increase induced by hypogastric nerve stimulation in dogs with benign prostatic hyperplasia].

We compared the urethral and cardiovascular effects of silodosin (selective alpha(1A)-adrenoceptor antagonist), a novel medication for benign prostatic hyperplasia (BPH), with those of tamsulosin (selective alpha(1A)/alpha(1D)-adrenoceptor antagonist) and naftopidil (selective alpha(1D)-adrenoceptor antagonist). We evaluated the effects of these three drugs on the increase in intraurethral pressure (IUP) induced by electrical stimulation of the hypogastric nerve in anesthetized dogs with spontaneous BPH. All three drugs dose-dependently reduced both the increase in IUP and the mean blood pressure (MBP). The rank order of potencies was tamsulosin>silodosin>naftopidil for the reductions in both IUP and MBP. However, the uroselectivity (ED(15) value for hypotensive effect/ID(50) value for reduction in IUP) of silodosin (uroselectivity, 19.8) was about 21 and 4 times higher than that of tamsulosin (0.939) and naftopidil (4.94), respectively. These data suggest that silodosin might be one of the most useful medications for dysuria in BPH patients.

Adrenergic alpha-1 Receptor Antagonists↗

[A case of alcoholic liver cirrhosis associated with intramuscular hematoma].

We reported a rare case of spontaneous intramuscular hematoma associated with alcoholic liver cirrhosis patient. A 60-year-old man with alcoholic liver cirrhosis was admitted to our hospital for pneumonia. It was improved by conservative treatments, however, he was complaint of severe pain in right hip and thigh. MRI revealed intramuscular hematoma at acute phase. Resting and anticoagulant therapy reduced it, but liver functions were not improved. After a few months, he received another intramuscular hematoma in the left thoracic muscles, and then died because of liver failure. It seems important to consider intramuscular hematoma as a complication of alcoholic liver cirrhosis.

Fatal Outcome↗

Annular rectal constriction due to infiltration by bladder cancer.

Invasive bladder cancers frequently show lymphatic or hematogenous metastasis. Furthermore, aggressive local invasion into adjacent structures is also commonly observed. However, the occurrence of rectal stricture due to infiltration by bladder cancer is relatively rare. Here, we report three patients with aggressive bladder cancer causing rectal obstruction.

Aged↗

53BP2 induces apoptosis through the mitochondrial death pathway.

The p53 binding protein 2 (53BP2) has been identified as the interacting protein to p53, Bcl-2, and p65 subunit of nuclear factor kappaB (NF-kappaB). The TP53BP2 gene encodes two splicing variants, 53BP2S and 53BP2L, previously known as apoptosis stimulating protein 2 of p53 (ASPP2). We found that these 53BP2 proteins are located predominantly in the cytoplasm and induce apoptosis as demonstrated by cleavage of poly ADP ribose polymerase (PARP) and annexin V staining. Furthermore, we demonstrate that 53BP2 is located in the mitochondria and induces apoptosis associated with depression of the mitochondrial trans-membrane potential (DeltaPsim) and activation of caspase-9. From these findings we conclude that 53BP2 induces apoptosis through the mitochondrial death pathway.

Apoptosis↗

Inhibition of the 53BP2S-mediated apoptosis by nuclear factor kappaB and Bcl-2 family proteins.

The p53 binding protein 2 (53BP2) has been identified independently as the interacting protein to p53, Bcl-2, and p65 subunit of nuclear factor kappaB (NF-kappaB). It was demonstrated that over-expression of 53BP2 (renamed as 53BP2S) induces apoptotic cell death. In this study we explored the effect of NF-kappaB activation elicited by a physiological NF-kappaB inducer, interleukin-1beta (IL-1beta), and anti-apoptotic Bcl-2 family proteins on the 53BP2S-mediated apoptosis. We found that both NF-kappaB activation and Bcl-2 family proteins could prevent the 53BP2S-mediated depression of mitochondrial transmembrane potential, activation of caspase-9, cleavage of poly ADP ribose polymerase (PARP), and cell death. These observations suggested that 53BP2S/Bbp and its directly or indirectly interacting proteins might play crucial roles in the regulation of apoptosis and contribute to carcinogenesis. It is also suggested that 53BP2S/Bbp induces apoptosis through the mitochondrial death pathway presumably by counteracting the actions of anti-apoptotic Bcl-2 family proteins. The regulatory network of the 53BP2S-mediated apoptosis cascade including its interacting proteins is discussed.

Apoptosis↗

Female para-urethral adenocarcinoma: histological and immunohistochemical study.

BACKGROUND: Female urethral cancer with a diverticular form is assumed to originate from the para-urethral duct, which is embryologically homologous to the male prostate gland. The purpose of the present paper was to investigate the female para-urethral adenocarcinomas histologically and immunohistochemically. METHODS: Surgical specimens obtained from six female patients with para-urethral adenocarcinomas were examined histologically, and an immunohistochemical study using antibodies against carcinoembryonic antigen (CEA), prostate specific antigen (PSA), and chromogranin A was performed. RESULTS: On histologic examination, the female para-urethral cancers were divided into five cases of mucin-producing-type adenocarcinoma and one case of clear cell-type adenocarcinoma. All five mucin-producing-type adenocarcinomas were positive with anti-CEA, and two of them showed neuroendicrine differentiation. One of them showed a focally positive area with anti-PSA. The clear cell-type adenocarcinoma had no positive reactions to these antibodies. CONCLUSIONS: On the basis of histologic structure, positive CEA staining, and the presence of focal neuroendocrine differentiation, mucin-producing-type adenocarcinomas may arise from the proximal part of the para-urethral duct.

Adenocarcinoma, Clear Cell↗

Anatomical and histological studies of so-called Müllerian duct cyst.

BACKGROUND: We examined so-called Müllerian duct cysts both histologically and immunohistochemically with anatomical observation to investigate the etiology of the 'Müllerian duct cyst'. METHODS: Five cystic lesions located in the prostatic midline were obtained from surgical specimens. A communication between the cystic lesion and the urethra via the utricular orifice was looked for and the specimens were subjected to histological and immunohistochemical testing. RESULTS: A communication between the cyst and the urethra was confirmed in four cases, but not in one case. Histological and immunohistochemical examinations of the epithelium lining indicated that its characteristics were identical to those of the prostatic utricle in all cases. CONCLUSIONS: The so-called Müllerian duct cyst exhibits features comparable to those previously described in the prostatic utricle. There is no evidence that these cystic lesions originate from the Müllerian duct remnant, at least in the epithelial lining. We suggest that they should be termed a prostatic utricular cyst or cystic dilation of the prostatic utricle, depending on whether an outlet to the urethra is absent or present, respectively.

Aged↗

Clinical differences between primary sclerosing cholangitis and sclerosing cholangitis with autoimmune pancreatitis.

OBJECTIVES: Sclerosing cholangitis (SC) with autoimmune pancreatitis (AIP) is similar to primary sclerosing cholangitis (PSC) with regard to cholangiographic findings, but only the former responds well to steroid therapy. This report concentrates on the clinical differences between these diseases. METHODS: The presenting complaint or abnormality, associated disease, cholangiographic findings, pancreatic changes, treatment, and clinical course were studied for several cases of PSC (n = 27) and SC with AIP (n = 20). RESULTS: SC with AIP as a diagnosis occurs abruptly with obstructive jaundice compared with PSC where diagnosis is often based on findings of asymptomatic liver test abnormalities. In addition, inflammatory bowel disease is only associated with PSC. The most prominent features of cholangiograms for the SC with AIP cases were stenosis of the lower common bile duct. However, sclerosing changes in the intra- and extrahepatic bile ducts or hilar hepatic region were observed for half of the cases. Only PSC showed stage III or IV liver biopsy findings. IgG4 was significantly higher in SC with AIP. CONCLUSIONS: SC with AIP and PSC are different clinical entities.

Adult↗

[Case of uremic platelet dysfunction].

The present case was a 59-year-old woman who underwent a right nephrectomy at 30 years of age, and in whom renal dysfunction occurred at 51 years of age. In November 199X, when her creatinine level reached 7 mg/dl, renal replacement therapy was recommended. She refused this therapy and began her own diet therapy, which consisted of taking only supplement beverage, but no food. Afterwards she became unable to do daily work, and entered our hospital in July of the next year. On admission, her bleeding time was over 10 minutes, but coagulation function tests showed normal values. Platelet function tests showed that coagulation with the addition of ADP was mildly decreased and that coagulation with the addition of aggregation was severely decreased. These data and her bleeding tendency improved with hemodialysis. Therefore, a diagnosis of aggregation non-responsive uremic platelet dysfunction was made. On admission, we were not able to insert a catheter for hemodialysis because of her severe bleeding tendency. A platelet transfusion was made so that we could insert the catheter without severe bleeding. However, this hemostatic effect lapsed after about five to six hours. Six hours after insertion of the catheter, oozing from the orifice of the catheter was seen and a red blood transfusion was necessary. Three days after beginning hemodialysis, the bleeding tendency was no longer seen. Her platelet function and coagulation test results also improved. We can make two conclusions regarding this case. The first is when the physician's medical strategy cannot be carried out due to uremic platelet dysfunction, a platelet transfusion can temporarily eliminate the bleeding tendency. The second is that the pathophysiology of uremic platelet dysfunction involves suppression of the primary step of platelet aggregation with collagen. Experience with the present case revealed the appropriate therapeutic strategy for the pathophysiology of uremic platelet dysfunction.

Blood Platelet Disorders↗

Expression of 53BP2 and ASPP2 proteins from TP53BP2 gene by alternative splicing.

The p53 binding protein 2 (53BP2) has been initially identified as an interacting protein to p53 and subsequent studies have shown that it also interacts with Bcl-2 and NF-kappaB p65 subunit. We have previously found that the TP53BP2 gene encoding 53BP2 protein is a single copy gene and has been mapped to the long arm of chromosome 1 at q42.1. The subsequent studies revealed that TP53BP2 encodes two proteins, 53BP2 and ASPP2, of 1005 and 1128 amino acids, respectively. ASPP2 contains additional 123 amino acids to the N-terminus of 53BP2. In this study, we have examined the genomic organization of TP53BP2 transcripts and found that it encodes two mRNA species, either with (53BP2) or without exon 3 (ASPP2), by alternative splicing in various cell lines and tissues. Thus, we propose to call these proteins as 53BP2S (short) and 53BP2L (long), respectively.

Alternative Splicing↗

Cholangiography can discriminate sclerosing cholangitis with autoimmune pancreatitis from primary sclerosing cholangitis.

BACKGROUND: Sclerosing cholangitis with autoimmune pancreatitis has a cholangiographic appearance that is similar to that of primary sclerosing cholangitis, but only the former responds well to corticosteroid therapy. It, therefore, is necessary to distinguish between these two diseases. Cholangiography is the reference standard for the diagnosis of primary sclerosing cholangitis. The present study compared the characteristic findings for these two types of sclerosing cholangitis. METHODS: Cholangiograms from patients with primary sclerosing cholangitis (n = 29) and sclerosing cholangitis with autoimmune pancreatitis (n = 26) were studied with regard to length and region of stricture formation, and other characteristic findings. RESULTS: Band-like stricture, beaded or pruned-tree appearance, and diverticulum-like formation were significantly more frequent in primary sclerosing cholangitis. In contrast, segmental stricture, long stricture with prestenotic dilatation and stricture of the distal common bile duct were significantly more common in sclerosing cholangitis with autoimmune pancreatitis. Discriminant analysis based on these findings correctly identified 27 of 28 patients with primary sclerosing cholangitis and 25 of 26 patients with sclerosing cholangitis with autoimmune pancreatitis. It also identified a patient with an incorrect diagnosis of primary sclerosing cholangitis who proved, on review of a surgical specimen, to have findings consistent with lymphoplasmacytic sclerosing cholangitis. CONCLUSIONS: Characteristic cholangiographic features allow discrimination of sclerosing cholangitis with autoimmune pancreatitis and lymphoplasmacytic sclerosing cholangitis without pancreatitis from primary sclerosing cholangitis.

Adult↗

Calponin h1 expression in renal tumor vessels: correlations with multiple pathological factors of renal cell carcinoma.

PURPOSE: We determined whether the architecture of renal tumor vessels is immunohistochemically different from that of normal renal vessels and related to the various pathological factors that affect prognosis of renal cell carcinoma (RCC). MATERIALS AND METHODS: A total of 52 cases of primary RCC were selected. Tissues from radical nephrectomy specimens were stained with antibody to alpha-smooth muscle actin (alpha-SMA) and calponin h1. Immunostaining was evaluated semiqualitatively as 0-no staining to 3+-strong staining. Tumor cell proliferation was observed using proliferating marker Ki-67. Data were statistically compared with pathological factors, such as tumor size, histological pattern, growth pattern, cell type, nuclear grade, pathological stage and presence or absence of venous invasion. RESULTS: In normal renal tissues smooth muscle cells of the blood vessels showed strong immunoreactions with antibody to calponin h1 and alpha-SMA. Although alpha-SMA antibody showed similar strong immunoreactions in all types of renal tumor vessels, we observed qualitative alterations in the expression of calponin h1 in different types of RCCs. Strong to moderate immunoreactions with calponin h1 were observed in tumors with expansive growth and an alveolar pattern. Small tumors without venous invasion and chromophobe cell carcinomas also showed strong to moderate expression of calponin h1. Weak or absent expression of calponin h1 was observed significantly in infiltrating tumors, sarcomatous type, large, high grade and high stage tumors associated with significantly higher proliferating indexes. CONCLUSIONS: Our results strongly suggest that the renal tumor vessels are immunohistochemically different from normal renal vessels in respect to calponin h1 expression. We speculate that due to the decrease in or absence of calponin h1 tumor vessels do not develop adequate maturity to maintain vascular integrity. In addition, the distribution of calponin h1 significantly correlated with multiple pathological factors of RCC. Therefore, calponin h1 expression in renal tumor vessels could be a new, important pathological factor in RCC.

Adult↗

Anatomical reconsideration to renal area: lessons learned from radical nephrectomy or adrenalectomy through a minimal incision over the 12th rib.

BACKGROUND: To perform radical nephrectomy or adrenalectomy through a minimal incision over the 12th rib and to compare this with the traditional supracostal or transcostal approach. We review and clarify the related surgical anatomy through close observation. METHODS: We performed radical nephrectomy in six patients with upper urinary tract carcinoma through a minimal incision over the 12th rib and in five patients with renal cell carcinoma through a medium-sized incision, and adrenalectomy in five patients (bilaterally in one) again through a minimal incision over the 12th rib. During surgery, special points were noted to find out the differences between the new minimal-incision approach and the conventional approach. RESULTS: The procedures were accomplished smoothly with no complications through either a minimal or medium-sized incision. From our observation, it is clear that most of the procedures involved in the minimal-incision approach were and should be carried out within the space created in the retroperitoneum beneath the lateroconal fascia. CONCLUSION: Entering the correct anatomical planes posteriorly and anteriorly in the renal fasciae is a prerequisite for full mobilization of the kidney, together with the perinephric fat. To perform this, recognition of the lateroconal fascia and incising it along the correct lines are of the utmost importance for minimal-incision radical nephrectomy and adrenalectomy. Furthermore, this anatomical approach is also important for the conventional open approach and laparoscopic approach.

Adrenalectomy↗

Reconstruction of posterior urethral disruption: tips for success from our experience and from a literature review.

Repair of a posterior urethral disruption associated with a pelvic fracture is a challenge for urologic surgeons. Here, we provide surgical and strategic tips to facilitate the delayed surgical repair of urethral distraction defects. Nine patients each with a traumatic posterior urethral distraction defect underwent delayed transperineal or transperineoabdominal bulboprostatic anastomosis. Four patients had previously undergone multiple procedures. Seven patients regained satisfactory urination without incontinence, although one other patient is suffering from incontinence. In one patient, urethral disruption occurred again after removal of the urethral catheter, and he is being managed by suprapubic catheter. In our experience, the key to success is to perform a true bulboprostatic mucosa-to-mucosa anastomosis without tension. For this purpose, a transperineoabdominal approach is of particular importance when the healthy mucosa of the prostatic apex cannot be revealed through a perineal approach due to dense fibrous scar or fractured bone. A partial pubectomy may be necessary according to the situation. By the transperineoabdominal approach, the scar tissue can be bypassed through a broad sub-pubic-arch tunnel, and a reliable anastomosis achieved.

Adolescent↗