Hirokazu Kitamura

Lower Incidence of Inguinal Hernia: Minilaparotomy Radical Retropubic Prostatectomy Compared with Conventional Technique

Introduction: The purpose of the present study was to compare the incidence of inguinal hernias after conventional and minilaparotomy (minilap) radical retropubic prostatectomy (RRP). Patients and Methods: In this retrospective study, we review our experience with 70 consecutive patients with prostate cancer who underwent prostatectomy from April 1995 through March 2001. Of these, 35 patients had conventional RRP, and 35 patients had minilap RRP. Results: Conventional RRP and minilap RRP groups were similar in body mass index (mean 24.4 and 23.5), operative time (mean 260 and 241 min), previous lower abdominal operation record (mean 37.1 and 25.7%), and post-prostatectomy anastomotic strictures (mean 11.4 and 14.3%). The volume of the estimated blood loss was significantly less for minilap RRP (mean 1,220 ml) than for conventional RRP (mean 1,666 ml; p = 0.0194). The incidence of postoperative inguinal hernias was 17.1% (6 of 35), 2.9% (1 of 35), and 3.2% (1 of 31) in conventional RRP, minilap RRP, and unoperated groups, respectively. The incidence of inguinal hernias after minilap RRP was significantly lower than after conventional RRP (p = 0.0464). Seven patients with postoperative inguinal hernias had a high incidence of postoperative strictures (42.9%), while 63 patients without hernia had a low incidence (9.5%). There was a significant difference in developing postoperative strictures between patients with hernia and those without (p = 0.0124). While postoperative stricture and operative technique were different in the hernia and hernia-free groups on univariate analysis, multivariate logistic analysis revealed that the operative technique was an independent factor for the occurrence of inguinal hernias (p = 0.0419). Conclusion: Minilap RRP compares favorably with conventional RRP in view of the postoperative inguinal hernia development.

The endocrine pancreas of spontaneously diabetic db db mice: microangiopathy as revealed by transmission electron microscopy

Abnormalities in ultrastructures of islet capillaries were detected in db/db mice, with the visual inspection and morphometry of electron micrographs. The observed changes are: (1) capillary scarcity; (2) increase in the mean and diversity of capillary size; (3) pericapillary edema and fibrosis; (4) hypertrophy of the pericyte and abundance therein of actin-like microfilaments; and (5) luminal irregularity. Changes (2), (3) and (4) are conceived to indicate hyperperfusion, capillary hypertension and secondary vascular response. In particular, such pericyte changes were found to be shared by other organs whose capillaries are susceptible to diabetic complications.

Transformation of interstitial fibroblasts and tubulointerstitial fibrosis in diabetic nephropathy

 The developmental mechanism of tubulointerstitial fibrosis in diabetic nephropathy (DN) has not been elucidated. Tubulointerstitial fibrosis, as well as glomerulosclerosis, occurs in DN. Myofibroblasts which overproduce extracellular matrix are present in the renal interstitium in diabetics, although they are almost never seen in normal kidneys. The myofibroblasts appear to originate from interstitial fibroblasts. In addition, transforming growth factor-β1 (TGF-β1), which can evoke myofibroblast transformation, is detected in interstitial cells in the diabetic kidney, but not in the normal kidney. Taken together, these findings led us to speculate that TGF-β1 induces the transformation of interstitial fibroblasts into myofibroblasts, followed by tubulointerstitial fibrosis. Based on this speculation, we discuss the developmental mechanism of tubulointerstitial fibrosis in this review.

Vascular cell adhesion molecule-l expression in the renal interstitium of diabetic KKAy mice

To investigate the mechanism of interstitial inflammation in diabetic nephropathy, we used spontaneously diabetic KKAy mice. Twelve KKAy mice were divided into two groups; six mice were fed standard mouse chow ad libitum and six mice were placed on a diet (i.e. they received the same amount of chow as six control C57BL mice). Diabetic KKAy mice developed hypercholesterolemia and albuminuria. Animals were killed at 16 weeks of age and renal tissues were immunostained for vascular cell adhesion molecule-1 (VCAM-1). In diabetic KKAy mice, the renal interstitium was infiltrated by monocytes, lymphocytes, plasma cells, and other cells. The walls of venules near the infiltrating cells were more intensely stained for VCAM-1 when compared with other sites. In contrast, the VCAM-1 staining of arterioles and peritubular capillaries was not significantly increased. There was weak VCAM-1 staining of the infiltrating cells, including lymphocytes, monocytes, and other cells. Electron microscopy demonstrated immunolabeling for VCAM-1 on the cell surface and in the cytoplasm of both infiltrating cells and vascular endothelial cells. In KKAy mice placed on a diet, there was less staining for VCAM-1 and cellular infiltration was also decreased. Thus, increased expression of VCAM-1 by the endothelial cells of venules and VCAM-1 expression by infiltrating cells were demonstrated in the interstitium of kidneys from diabetic mice. These results suggest that increased expression of VCAM-1 by endothelial cells and infiltrating cells contributes to interstitial inflammation in diabetic nephropathy.

Organization of the lamina propria mucosae of rat intestinal mucosa, with special reference to the subepithelial connective tissue.

Light microscopy, scanning electron microscopy and transmission electron microscopy have been used to delineate the structure and function of the lamina propria mucosae in the rat jejunum. In silver-impregnated sections, the adepithelial surface of the lamina propria mucosae was framed by a sheet of reticular fibers (reticular sheet). Short-term (3-hour) immersion of jejunal tissues in 2 N NaOH solution enabled us to simultaneously view networks of reticular fibrils and fibroblasts residing in the subepithelial connective tissue under a scanning electron microscope. The reticular fibrils, which measured about 40 nm in diameter and were interwoven in dense networks, formed a sheet 2-3 microns thick. In the villi, this sheet contained numerous foramina ranging from 3 to 7 microns in diameter, through which lymphocytes, macrophages, basal extensions of epithelial cells and fat particles traversed. The reticular sheet in the domes of isolated lymphoid nodules was markedly porous, and many lymphocytes migrated into or out of the epithelium through the foramina. The formaina of the reticular sheet may participate in the communication between the intestinal epithelium and the lamina propria mucosae. It was noted that the foramina of the reticular sheet in the villi were surrounded by end feet of the cytoplasmic processes of fibroblasts. In addition, these fibroblasts were combined with lymphocytes or dendritic cells in the lamina propria mucosae.

Epiplakin accelerates the lateral organization of keratin filaments during wound healing

BACKGROUND Epiplakin (EPPK) belongs to the plakin family of cytolinker proteins and, resembling other members of the plakin family such as BPAG1 (an autoantigen of bullous pemphigoid) and plectin, EPPK has plakin repeat domains (PRDs) that bind to intermediate filaments. Elimination of EPPK by gene targeting in mice resulted in the acceleration of keratinocyte migration during wound healing. EPPK is expressed in proliferating keratinocytes at wound edges and, in view of its putative function in binding to keratin, we postulated that the keratin network in EPPK-null (EPPK(-/-)) mice might be disrupted during wound healing. OBJECTIVE To examine this hypothesis and to determine the precise localization of EPPK in relation to keratin filaments, we compared the non-wounded and wounded epidermis of wild-type and EPPK(-/-) mice. METHODS Non-wounded epidermis and wounded epidermis from wild-type and EPPK(-/-) mice were examined by immunofluorescence staining and electron microscopy before and after double immunostaining. RESULTS EPPK was colocalized with keratin 17 (K17) more extensively than with other keratins examined in wounded epidermis. The expression of K5, K10, K6, and K17 was the same in EPPK(-/-) mice after wounding as in normal mice, but diameters of keratin filaments were reduced in EPPK(-/-) keratinocytes. Electron microscopy after immunostaining revealed that EPPK colocalized with K5, K10 and K6 after wounding in wild-type mice. CONCLUSION Our data indicate that EPPK accelerates keratin bundling in proliferating keratinocytes during wound healing and suggest that EPPK might contribute to reinforcement of keratin networks under mechanical stress.

Changes in morphology of elastin fibers during development of the tunica intima of monkey aorta

SummaryThe normal development of elastin fibers in the thoracic aorta was studied in fetal, young, and adult monkeys. Tissue was examined by scanning electron microscopy (SEM) after NaOH treatment and by transmission electron microscopy (TEM). The NaOH treatment of fixed tissues effectively removed collagen fibers and enabled three-dimensional visualization of the elastin fibers. In intact fetal aortae, the internal elastic lamina (IEL) was situated immediately beneath the endothelium. This IEL consisted of superficial, longitudinally arranged bundles of elastin fibrils and an underlying solid sheet containing round fenestrations. In neonates, diffuse intimal thickening was observed. In the young and young-adult monkeys, the aortae exhibited intimal thickening with slender but split IEL. One of the most important findings of this study was that elastin fibers in the intimal thickening, as well as smooth muscle cells, ran in a longitudinal fashion. This was in contrast with the elastic laminae of the media which were mainly oriented circumferentially. Subendothelial elastin fibers in this intimal thickening combined with longitudinally arranged microfibrils which formed close associations with endothelial stress fibers. In some adult monkey aortae with well-developed intimal thickening, a complex meshwork of slender elastin fibers was also found beneath the endothelium. The development of the intimal elastin fibers is discussed in relation to hemodynamic forces.

Morphology of Lymphatics of the Mammalian Heart with Special Reference to the Architecture and Distribution of the Subepicardial Lymphatic System

The subepicardial lymphatic system in the rat and dog heart has been investigated by means of scanning electron microscopy. Following application of hydrogen peroxide, the epicardium was removed with a forceps under a dissecting microscope. The subepicardial region contained a well-developed lymphatic system which consisted of the main lymphatic trunks and lymphatic capillaries. The lymphatic trunks of large diameters ran from the apex of the heart to its base. The subepicardial lymphatic capillaries were ramified and anastomosed with each other to form a relatively dense network which extended over the entire surface of both ventricles. These networks joined the main lymphatic trunks. Further, some similar networks were connected with the underlying myocardial lymphatic capillaries.

Administration of antisense DNA for GPR39-1b causes anxiolytic-like responses and appetite loss in rats

The G protein-coupled receptor 39-b (GPR39-1b) is a splice variant of which is expressed in the central nervous and gastrointestinal systems. Previously, GPR39-1b was proposed to be the receptor for obestatin, but current evidence does not support this hypothesis. The purpose of the present work was to identify the role of GPR39-1b in anxiety and eating behaviors. Antisense oligonucleotides were infused at a constant rate into the cerebral lateral ventricles of rats and their effect on anxiety-like behavior and food intake was monitored. GPR39-1b antisense oligonucleotides produced anxiolytic-like effects in the elevated-plus maze test and in the black and white box test. Antisense oligonucleotides also decreased food intake. These results indicate that inhibition of GPR39-1b induces a decrease in anxiety-related behaviors and disturbs appetite.

A Clinical Approach to Brown Adipose Tissue in the Para-Aortic Area of the Human Thorax

Background Human thoracic brown adipose tissue (BAT), composed of several subdivisions, is a well-known target organ of many clinical studies; however, the functional contribution of each part of human thoracic BAT remains unknown. The present study analyzed the significance of each part of human thoracic BAT in the association between regional distribution, cellularity, and factors involved in the functional regulation of thoracic BAT. Methods We analyzed 1550 healthy adults who underwent medical check-ups by positron-emission tomography and computed tomography (PET–CT) imaging, 8 cadavers, and 78 autopsy cases in an observational study. We first characterized the difference between the mediastinum and the supraclavicular areas using counts of BAT detection and conditions based on PET–CT outcomes. The measurable important area was then subjected to systematic anatomical and immunohistochemical analyses using anti-uncoupling protein 1 (UCP1) antibody to characterize the cellularity in association with age and sex. Results In PET–CT scanning, the main site of thoracic BAT was the mediastinum rather than the supraclavicular area (P < 0.05). Systemic macroanatomy revealed that the thumb-sized BAT in the posterior mediastinal descending para-aortic area (paBAT) had feeding vessels from the posterior intercostal arteries and veins and sympathetic/parasympathetic innervation from trunks of the sympathetic and vagus nerves, respectively. Immunohistochemical analysis indicated that the paBAT exhibited immunoreactivity for tyrosine hydroxylase and vesicular acetylcholine transporter located in the pericellular nervous fibers and intracellular UCP1. The brown adipose cells of paBAT showed age-dependent decreases in UCP1 expression (P < 0.05), accompanied by a significant increase in vacuole formation, indicating fat accumulation (P < 0.05), from 10 to 37 years of age (P < 0.01). Conclusions paBAT may be one of the essential sites for clinical application in BAT study because of its visible anatomy with feeding vessels and sympathetic/parasympathetic innervation functionally affected by outer condition and senescence.