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Biomedical subjects

T Iwanaga

Publications and source records attributed to T Iwanaga.

At least 235 records · Page 13Linked to original sources

Immunohistochemical demonstration of peptidergic nerve fibers associated with the central lacteal lymphatics in the duodenal villi of dogs.

Immunohistochemical demonstration was made of the peptidergic nerves distributed in the central lacteal lymphatics of the canine duodenal villi. The central lacteal-associating nerve fibers were predominantly immunoreactive for both substance P (SP) and calcitonin gene-related peptide (CGRP). Observation of doubly immunostained sections evidenced that both peptides were located in one and the same nerve fibers. The SP/CGRP-immunoreactive fibers were concentrated in the intermediate portion of the villus height. Ultrastructurally, the SP/CGRP-immunoreactive nerve fibers ran closely beneath the endothelial cells of the lacteal, some of them penetrating into the cytoplasm with knob-like swellings. The immunoreactive products were localized to large-cored vesicles in the sub- and intra-endothelial nerves. The occurrence of SP and CGRP in the nerve fibers distributed in the central lacteals which lack smooth muscles implies that these nerves may be sensory in nature. A mechanoreceptive function of the nerves is proposed on the basis of their peculiar knob-like projection into the lacteal endothelium.

Animals↗

Peptidergic nerve terminals associated with the central lacteal lymphatics in the ileal villi of dogs.

Nerve fibers in the villi of the canine ileum were studied with special reference to their relation to the central lacteal. Immunohistochemically demonstrable nerve fibers containing substance P (SP) and calcitonin gene-related peptide (CGRP) were rather more numerous in the villi of the ileum than in those of the duodenum, as observed in our previous study (Ichikawa et al., 1991). They were distributed beneath the epithelium and associated with smooth muscle fibers. Besides these localizations, immunoreactive fibers were gathered, especially at the middle of the height of the villus, close to the endothelial cells of the central lacteal. This particular distribution of nerves was more evident in the ileum than in the duodenum. Electron microscope observation indicated beaded fibers containing large cored (peptidergic) and small clear vesicles coursing closely under the lacteal endothelium, partly intercalated by a basement membrane and partly in direct contact. The nerve fibers often penetrated the endothelial cell, being directly surrounded by its cytoplasm. Although the above-described findings essentially coincide with our previous observations in canine duodenum (Ichikawa et al., 1991), the present study in the ileum demonstrated occasional nerve fibers protruding into the lacteal lumen with a knob-like swelling. It is suggested that the SP and CGRP-containing nerves in problem might be sensory in nature, possibly monitoring mechanical information from the lumen and wall of the central lacteal. At the same time, these nerves are suggested to be secretory in nature, releasing the peptides to exert unknown effects upon the lacteal wall and its vicinity, presumably in response to luminal and mural stimuli.

Animals↗

Immunohistochemical localization of laminin in the periodontal Ruffini endings of rat incisors: a possible function of terminal Schwann cells.

Ruffini endings in the periodontal ligament of rodents are ensheathed by a special type of terminal Schwann cell with a particularly developed rough endoplasmic reticulum and Golgi apparatus, and further enveloped by a characteristic multi-layered structure. In order to reveal the functional significance of the structures, localization of a laminin molecule in the periodontal Ruffini endings of rats was immunohistochemically investigated at the levels of light and electron microscopy. Immunostaining using an anti-laminin serum clearly demonstrated the profiles of the Ruffini endings as well as those of the blood vessels. Ultrastructurally, reaction products for laminin were deposited in the entire thickness of the multi-layered structure, supporting the idea that this structure is derived from the basal lamina. The basal lamina, immunoreacting with laminin antiserum, was penetrated by periodontal collagen fibers, possibly serving as an adhesive device between the Ruffini endings and surrounding collagen fibers. The laminin immunoreactive materials were also recognized in the vesicles and caveolae of the terminal Schwann cells which tended to gather at the interstitial surface of the cells. The terminal Schwann cells are therefore believed to be directly involved in the formation of the multilayered basal lamina through the active production of its materials.

Animals↗

GRP (gastrin-releasing peptide)-containing nerves in the rat stomach and stress-induced depletion of their synaptic vesicles. An electron microscope study.

Gastrin-releasing peptide (GRP)-containing nerves are extremely numerous in the mucosa of the gastric body. Our previous study demonstrated that depletion of GRP from the nerves occurred in close relation to ulceration in the stomach. The present study deals with the ultrastructure of the GRP-immunoreactive nerves under normal conditions and its changes induced by conditions of stress. The immunoreactivity for GRP was recognized selectively in large cored vesicles in the swollen axoplasm of the nerves. The same axoplasm further revealed immunonegative small clear vesicles which were believed to contain acetylcholine. In materials where the GRP-immunoreactive nerves markedly decreased in number, both large and small synaptic vesicles were depleted from the nerves. These findings suggest that GRP and acetylcholine coexist in single nerves in the oxyntic mucosa, and that by nerve stimulation, they are coreleased into the lamina propria.

Acetylcholine↗

[Percutaneous ethanol injection therapy (PEIT) and transarterial embolization (TAE) for recurrent hepatocellular carcinoma--report of 2 cases].

Two patients with recurrent hepatocellular carcinoma underwent reoperation following percutaneous ethanol injection therapy (PEIT) and transarterial embolization (TAE). In the first case, although the nodules where the accumulation of Lipiodol (LpD) was seen showed complete necrosis, viable cancer cells were seen in the areas with slight accumulation of LpD. One nodule with no accumulation of LpD where PEIT seemed to have been performed, developed necrosis. In the second case, the nodules with LpI) accumulation also showed almost complete necrosis. The area where PEIT was performed was mixed with necrosis and bleeding, where a small viable cancer nodule existed. The reason for incomplete anticancer effects by PEIT seemed to be the too small ethanol injection.

Aged↗

[Postoperative change of serum protease inhibitor and C-reactive protein level--with special reference to surgical resection of liver cirrhosis].

Changes in the activities of blood protease inhibitors and acute-phase reactive substances during surgical resection of liver cirrhosis were investigated by measuring the pre- and postoperative blood concentrations of alpha 1-antitrypsin (alpha 1AT), alpha 2-macroglobulin (alpha 2MG), pancreatic secretory trypsin inhibitor (PSTI), urinary trypsin inhibitor (UTI) and C-reactive protein (CRP), in patients with liver cirrhosis who underwent hepatectomy (Group A, n = 19), those without liver cirrhosis who underwent hepatectomy (Group B, n = 6) and those without liver cirrhosis who underwent surgeries other than hepatectomy (Group C, n = 5). On examining the preoperative blood levels of protease inhibitors, Group A had an increased level of alpha 2MG and a decreased level of UTI compared to Groups B and C. alpha 1AT and CRP began to increase on the first day following hepatectomy and formed peaks on the third postoperative day. The increases were significantly higher in Group B than Group A (p less than 0.01). To investigate factors causative of these differences, alpha 1AT and CRP on the third postoperative day were compared in relation to the time of operation, amount of intraoperative bleeding, weight of the resected liver and preoperative ICGR15. alpha 1AT and CRP were significantly correlated to only preoperative ICGR15. PSTI was increased postoperatively but showed no difference between Groups A and B.

Aprotinin↗

Abnormalities of growth factor systems in transformed airway epithelial cells.

The role of the peptide growth factors transforming growth factor alpha (TGF alpha) and transforming growth factor beta (TGF beta) in the regulation of proliferation of normal and transformed airway epithelial cells was studied. Normal as well as transformed rat tracheal epithelial (RTE) cell cultures secrete similar amounts of TGF alpha during logarithmic growth. Once normal RTE cell cultures reach the plateau phase of growth, they down-regulate TGF alpha expression at the RNA and protein level; in contrast, transformed cells do not down-regulate TGF alpha. Using neutralizing TGF alpha antiserum and a tyrphostin TGF alpha/EGF receptor tyrosine kinase inhibitor, we show that the secreted TGF alpha is utilized by both normal and transformed cells as an autocrine mitogenic factor. Normal RTE cells are highly sensitive to the growth inhibitory effects of TGF beta, particularly during early phases of logarithmic growth. At late logarithmic and plateau phases of proliferation, cultures of normal RTE cells secrete large amounts of TGF beta. That the endogenous TGF beta is exerting growth inhibitory effects can be demonstrated by adding TGF beta antisera to the cultures which causes a burst of proliferation. Many transformed RTE cell lines exhibit a markedly reduced sensitivity to the growth inhibitory effects of TGF beta. However, the cells remain responsive to regulation of ECM genes by TGF beta. The transformed cell lines examined secrete less than one tenth the amount of TGF beta of normal cells. Our studies show that the autocrine TGF beta growth restraining mechanism is inoperative in many of the RTE cell transformants. We conclude, therefore, that alterations in TGF alpha and TGF beta regulation of cell proliferation are important factors contributing to the abnormal growth behavior of transformed RTE cells.

Animals↗

[Prevention of local recurrence after sphincter-saving resection for rectal cancer].

The main cause of local recurrence after curative operation for rectal cancer is intra-operative implantation of viable shed cancer cells. The present study was undertaken to investigate whether irrigation of remnant rectum prior to anastomosis would prevent local recurrence in rectal cancer. Remnant rectum was irrigated 20 times with physiologic saline using 30 ml enema syringe. One hundred thirty-five patients with rectal cancer underwent sphincter-saving resection for cure. Twenty-six of these patients, received irrigation with physiologic saline, and the remainder received no irrigation. Viable cancer cells were still present in remnant rectum after irrigation 10 times, but absent after 20 times. Distribution by age, sex, stage and the distal clearance margin was similar in both groups. Local recurrence occurred in none of the irrigation-treated patients and in 11 percent of the untreated ones (p less than 0.05). Our results indicate that irrigation 20 times with 30 ml of physiologic saline of the remnant rectum prior to anastomosis is an effective method of preventing local recurrence after resection of rectal cancer.

Adult↗

Surgical management of lung metastases. Usefulness of resection with the neodymium:yttrium-aluminum-garnet laser with median sternotomy.

Between May 1969 and September 1989, 677 metastatic lesions were resected during 107 operations in 100 patients with pulmonary metastases from various primary sites at the Center for Adult Diseases, Osaka, Japan. Of those patients, 65 underwent conventional lateral thoracotomy, and 35 patients had median sternotomy. No significant difference existed in actuarial survival after the first operation to remove the metastases between the two patients groups. Furthermore, local excision of 418 lesions was performed in 25 patients with the neodymium:yttrium-aluminum-garnet (Nd:YAG) laser. Of those, 18 patients had undergone a one-stage operation for bilateral lesions through a median sternotomy approach. Although our study was not randomized, survival of the 25 patients treated with the Nd:YAG laser tends to be longer than survival of the 75 patients for whom the Nd:YAG laser was not used. We concluded that aggressive excision and evaporation of multiple lung metastases with the Nd:YAG laser under median sternotomy is a safe and promising variation in technique and that this approach will expand the scope of surgical indications for metastatic lung tumors. For a clearer demonstration of the influence of differences in surgical techniques on long-term survival it is necessary to conduct randomized prospective studies of the surgical techniques.

Adolescent↗

Expression of the human MHC, HLA-DQW6 genes alters the immune response in C57BL/6 mice.

In an attempt to obtain direct evidence for the critical role of HLA class II molecules in regulating the immune response, genomic genes for alpha- and beta-chains of HLA-DQw6 from HLA-Dw12 haplotype were introduced into the C57BL/6 (B6) strain of mouse and a line of HLA-DQw6 transgenic mouse was obtained. Tissue specificity of the expression of the transgenes was much the same as that of murine I-Ab genes. DQw6 molecules were expressed on B cells and macrophages in spleen cells and about 30 to 40% of the I-Ab+ spleen cells were positive for DQw6. The HLA-DQw6 transgenic B6 mouse became tolerant to the DQw6 molecules, as evidenced by the MLR and antibody production specific to the DQw6 molecules. The HLA-DQw6 transgenic B6 mouse showed a strong immune response to streptococcal cell wall antigen (SCW), whereas the B6 mouse was a low responder to SCW. The SCW-specific T cell line was established from the transgenic mouse and this T cell line recognized SCW in the context of HLA-DQw6 molecules expressed on the mouse L cell transfectant or on human monocytes. The proliferative response to SCW of primed lymph node T cells and the SCW-specific T cell line derived from the transgenic mice was inhibited by anti-HLA-DQ mAb. Thus, it is clear that the HLA-DQw6 genes acted as major histocompatibility genes in these transgenic mice.

Animals↗

[Combination therapy with 5'DFUR and MPA as a second line treatment for advanced/recurrent breast cancer].

As a second line therapy after failure to previous therapies, a combination therapy with MPA 1,200 mg po and 5'DFUR 1,200 mg po daily was given to 31 patients with recurrent breast cancer. At a median follow up period of 18 months, the overall response rate was 42%. The response rates for bone and visceral lesions were still good for the second line therapy. Patients previously exposed to tamoxifen (24 patients), 5-FU or its derivatives (21) and/or adriamycin (18) had response rates of 42%, 33%, 33%, respectively. The median duration of response in responders was 10 months. The overall median survival for the entire series was 9 months after start of the treatment. Thirteen (81%) of 16 patients with bone lesions were relieved from their bone pain. It is of special interest that the pain relief was also obtained in 7 out of 10 NC/PD patients with bone lesions, resulting in much improvement of their performance status. Side effects included obesity 52%, edema of the leg 35%, diarrhea 16% and so on. One patient developed venous thrombosis of her lower extremities and 4 were suspected to have the same condition. Fifty-five % of the patients underwent dose reduction of MPA at the 5th month of treatment in a median. This combination therapy is useful for recurrent disease even in late stages, so long as close observation is made for the occurrence of thrombosis.

Adult↗

Cholinesterase activity in terminal Schwann cells associated with Ruffini endings in the periodontal ligament of rat incisors.

A nonspecific cholinesterase activity was demonstrated in terminal Schwann cells associated with Ruffini endings in the periodontal ligament of rat incisors at the light and electron microscopic levels. The terminal Schwann cells are ultrastructurally characterized by a well-developed Golgi apparatus and rough endoplasmic reticulum. The cells in this study were positive for nonspecific cholinesterase, whereas ordinary Schwann cells associated with more proximal nerve fibers reacted negatively. The reaction products were densely deposited in the cisternae of the rough endoplasmic reticulum and along the nuclear envelop. A moderately intense labeling was found in the cytoplasmic extensions, in which the reaction products gathered in caveolae and vesicles. These findings indicate that nonspecific cholinesterase is a useful marker to distinguish terminal Schwann cells from ordinary Schwann cells and that the enzyme may be synthesized in the rough endoplasmic reticulum and conveyed toward the axon terminals. Since this enzyme has been known to be shared by the inner bulb of Pacinian corpuscles and the lamellar cells of Meissner's corpuscles, its possible involvement in mechanoreceptive functions in these specialized Schwann cells deserves further investigation.

Animals↗

Content and distribution of vasoactive intestinal polypeptide (VIP) in cavernous tissue of human penis.

Penile erection is controlled by a valvular structure in the helicine artery in humans. The opening and closing of this valve are believed to be regulated by the autonomic nervous system, especially through the release of vasoactive intestinal polypeptide (VIP). We determined the content of VIP in cavernous tissue in 18 impotent patients and in 5 normal controls by radioimmunoassay, and we examined the distribution of VIP-ergic nerve fibers in cavernous tissue by an immunohistochemical method. As a result, it was found that the lower penile VIP content was more frequent among patients with organic impotence than among the controls. Furthermore, VIP-ergic nerve fibers were seen to be diffusely and loosely distributed in a large number of organic impotence patients. These findings suggest that organic impotence in some patients may be due to decreases in the VIP content and in VIP-ergic nerve fibers.

Adolescent↗

Rapidly progressive bronchiolitis obliterans associated with Stevens-Johnson syndrome.

A middle-aged woman developed fulminant respiratory failure during recovery from Stevens-Johnson syndrome. Mechanical ventilation was difficult because of unusually high airway pressures, and she died one month later. Autopsy revealed not only the usual features of bronchiolitis obliterans, but also obstruction of cartilaginous bronchi. The histopathologic features suggested a relationship between bronchial obstruction and Stevens-Johnson syndrome.

Adult↗

Nerve terminals in human periodontal ligament as demonstrated by immunohistochemistry for neurofilament protein (NFP) and S-100 protein.

Nerve terminals in the human periodontal ligament were investigated by immunohistochemistry for neurofilament protein (NFP) and glia-specific S-100 protein. The human periodontal ligament was found to be innervated by NFP-immunoreactive nerve fibers, and contained free and specialized nerve endings; essentially all these nerve fibers were associated with S-100 protein-immunoreactive elements. Free nerve endings showing tree-like ramifications were frequently observed along the whole length of the tooth. The specialized nerve endings consisting of thick nervous elements were classified into four types as follows: Ruffini-like endings which were composed of expanded nerve terminals arranged in a dendritic fashion were found mainly around the root apex; coiled nerve endings were located in the mid-region of the periodontal ligament; spindle-shaped types, and expanded nerve endings, both rarely found near the root apex. Immunostaining for S-100 protein showed that no lamellated nerve terminals were found in the human periodontal ligament. The region-specific distribution of various nerve terminals demonstrated in this study seems to be suited to effectively receive mechanical stimuli to the teeth from various directions.

Humans↗

Gene conversion in steroid 21-hydroxylase genes.

The steroid 21-hydroxylase gene, CYP21B, encodes cytochrome P450c21, which mediates 21-hydroxylation. The gene is located about 30 kb downstream from pseudogene CYP21A. The CYP21A gene is homologous to the CYP21B gene but contains some mutations, including a C----T change which leads a termination codon, TAG, in the eighth exon. We found the same change in a mutant CYP21B gene isolated from a patient with 21-hydroxylase deficiency. Furthermore, a reciprocal change--i.e., a T----C change in the eighth exon of the CYP21A gene--was observed in the Japanese population and was associated with the two HLA haplotypes, HLA-B44-DRw13 and HLA-Bw46-DRw8. These changes may be considered the result of gene conversion-like events.

Adrenal Hyperplasia, Congenital↗

A sandwich-enzyme immunoassay for the quantification of lipoprotein lipase and hepatic triglyceride lipase in human postheparin plasma using monoclonal antibodies to the corresponding enzymes.

We have developed a sandwich-enzyme immunoassay (EIA) for the quantification of lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) in human postheparin plasma (PHP) using monoclonal antibodies (MAbs) directed against the corresponding enzymes purified from human PHP. The sandwich-EIA for LPL was performed by using the combination of two distinct types of anti-LPL MAbs that recognize different epitopes on the LPL molecule. The immunoreactive mass of LPL was specifically measured using a beta-galactosidase-labeled anti-LPL MAb as an enzyme-linked MAb, an anti-LPL MAb linked with the bacterial cell wall as an insolubilized MAb, and purified human PHP-LPL as a standard. The sandwich-EIA for HTGL was carried out by using two distinct anti-HTGL MAbs that recognize different epitopes on HTGL. The limit of detection was 20 ng/ml for LPL and 60 ng/ml for HTGL. Each method yielded a coefficient of variation of less than 6% in intra- and inter-assays, and a high concentration of triglyceride did not interfere with the assays. The average recovery of purified human PHP-LPL and -HTGL added to human PHP samples was 98.8% and 97.5%, respectively. The immunoreactive masses of LPL and HTGL in PHP samples, obtained at a heparin dose of 30 IU/kg, from 34 normolipidemic and 20 hypertriglyceridemic subjects were quantified by the sandwich-EIA. To assess the reliability of the measured mass values, they were compared with the corresponding enzyme activities measured by selective immunoinactivation assay using rabbit anti-human PHP-LPL and -HTGL polyclonal antisera. Both assay methods yielded a highly significant correlation in either normolipidemic (r = 0.945 for LPL; r = 0.932 for HTGL) or hypertriglyceridemic subjects (r = 0.989 for LPL; r = 0.954 for HTGL). The normal mean (+/- SD) level of lipoprotein lipase mass and activity in postheparin plasma was 223 +/- 66 ng/ml and 10.1 +/- 2.9 mumol/h per ml, and that of hepatic triglyceride lipase mass and activity was 1456 +/- 469 ng/ml and 26.4 +/- 8.7 mumol/h per ml, respectively. The present sandwich-enzyme immunoassay methods make it possible to study the molecular nature of LPL and HTGL in PHP from patients with either primary or secondary hyperlipoproteinemia.

Adult↗