Biomedical subjects

K Doi

Publications and source records attributed to K Doi.

At least 325 records · Page 18Linked to original sources

PubMed1997

T-2 toxin-induced apoptosis in lymphoid organs of mice.

Lymphoid organs of male and female mice of 4 strains (ICR: CD-1, BALB/c, C57BL/6 and DBA/2) were histologically and biochemically examined at 24 hours after oral inoculation of T-2 toxin (0, 2.5, 5 and 10 mg/kg b.w.). Light microscopically, dose-dependent decrease in number of lymphocytes was observed in the thymic cortex and splenic follicles. The nuclei of lymphocytes showed pyknosis or karyorrhexis, and they were positively stained by the modified TUNEL method which detects fragmented DNA in situ. Electron microscopic characteristics of damaged lymphocytes were shrinkage of the cell body, nuclear chromatin condensation and fragmentation. Agarose gel electrophoresis of DNA extracted from the thymus showed DNA fragmentation into nucleosome units, i.e. ladder formation. The above-mentioned findings clearly showed that T-2 toxin could induce apoptotic cell death in the lymphoid organs of mice. These changes were more prominent in female BALB/c and C57BL/6 mice.

Administration, Oral↗

PubMed1997

T-2 toxin-induced apoptosis in intestinal crypt epithelial cells of mice.

The characteristics of T-2 toxin-induced cell damage in the intestinal crypt epithelia was investigated in mice. Following T-2 toxin-inoculation (0, 2.5, 5 and 10 mg/kg b.w.), dead cells showing pyknosis were sporadically observed in the crypt epithelia, and the nuclei of these cells were strongly stained by the modified TUNEL method which detects fragmented DNA in situ. Electron microscopically, the dead cells were characterized by shrinkage of the cell body and condensation of nuclear chromatin frequently along the nuclear membrane, and such nuclei were sometimes fragmented into small pieces. These morphological characteristics are well consistent with those of apoptosis. The mitotic index in the crypt epithelia drastically decreased at 6 hours after T-2 toxin-inoculation (6 HAI), but thereafter it recovered to almost the same value with that in control mice at 48 HAI. On the other hand, the apoptotic index in the crypt epithelia increased with the lapse of time. Clear mouse strain- and sex-differences were detected in the apoptotic index but not in the mitotic index. This is the first report that T-2 toxin caused apoptotic cell death in the intestinal crypt epithelial cells.

Animals↗

PubMed1997

TCR beta-independent development of CD4+ CD8+ thymocytes observed in a strain of scid mice.

Mice homozygous for severe combined immunodeficiency (scid) mutation usually halt their thymocyte development at the CD4-CD8- double negative (DN) stage due to their inability of TCR gene rearrangement. In this study, we report that SCID-bg mice, which were originally generated by mating CB-17-scid mice with KSN-bg mice, spontaneously develop dominant CD4+ CD8+ double positive (DP) thymocytes. Their thymi were mainly composed of DN, CD4-CD8+ and DP cells, and the majority of them did not present CD3. Similarly, they lacked TCR beta expression both on cell surface and in cytoplasm, which suggests that the thymocyte development to the DP stage observed in SCID-bg mice, was independent of CD3 and TCR beta expression. In spite of significant DP thymocytes in SCID-bg mice, the histology of their thymi was not so different from those of CB-17-scid mice. Analysis of bone marrow cells in SCID-bg mice showed that the development of B lineage cells was not altered when compared with CB-17-scid mice. These findings point out the fact that thymocytes in SCID-bg mice have a peculiar characteristic compared to CB-17-scid mice, and provide evidence of TCR beta-independent development of thymocytes to the DP stage.

Animals↗

PubMed1997

Characterization of CD4+CD8+ thymocytes observed in SCID-bg mice.

Previously, we reported that a strain of severe combined immunodeficient (SCID) mice, namely SCID-bg, spontaneously develop CD4+CD8+ double positive (DP) thymocytes despite their scid mutation. In the present study, we intend to further characterize the DP thymocyte population in SCID-bg mice with Southern hybridization and flow cytometry. Southern hybridization analyses of sorted DP thymocytes in SCID-bg mice showed rearrangement of T cell receptor (TCR) beta and TCR gamma gene segments, although the expression of TCR beta and gamma delta TCR molecules was absent. The phenotype of the DP thymocytes in SCID-bg mice was CD44- heat-stable antigen (HSA)+CD25-, and they did not express CD69. Interestingly, the expression of thymus leukaemia (TL) antigen was observed in the DP thymocytes of SCID-bg mice but not in their CD4-CD8- double negative (DN) fraction. Fas expression was higher and bcl-2 expression was down-regulated in the DP thymocytes as compared to the DN thymocytes in SCID-bg mice, suggesting that they are not immortalized cells having escaped from apoptosis. Taken together, these results show that the phenotype of the DP thymocytes in SCID-bg mice is similar to that of the earliest phase of the DP thymocytes in normal mice, although the expression of the molecules in the pre-TCR complex is absent.

Animals↗

PubMed1997

Modification of spontaneous renal lesion of APA hamsters by streptozotocin-induced diabetes.

Syrian hamsters of the APA strain (APA hamsters) develop spontaneous mesangial thickening in the renal glomeruli from an early age. They also develop focal and segmental glomerulosclerosis (FSG) at and after 6 months of age. In this study, histopathological, immunohistochemical and lectin histochemical examinations were conducted to clarify the modification of the spontaneous renal lesions of APA hamsters by streptozotocin(SZ)-induced diabetes. Histopathological analysis revealed that the expansion of the mesangial region was more prominent and the thickening of the glomerular basement membrane (GBM) was weaker in SZ-treated animals than in non-treated ones. Immunohistochemical analysis suggested that type IV collagen and laminin were involved in the expansion of the mesangial region and thickening of the GBM. In lectin histochemical analysis, podocytes, capillary endothelial cells, GBM and a part of mesangial region of SZ-treated animals were positive for RCA120 and GSL-I with neuraminidase-pretreatment although they were negative for these lectins in non-treated animals. These results suggest that the spontaneous glomerular lesion of APA hamsters is modified qualitatively and quantitatively by SZ-induced diabetes.

Animals↗

PubMed1997

An age-related change in susceptibility of rat brain to encephalomyocarditis virus infection.

Rats were inoculated intraperitoneally (i.p.) or intracerebrally (i.c.) with 1 x 10(4) plaque forming units (PFU)/animal of the D variant of encephalomyocarditis virus (EMC-D) at 2, 4, 7, 14, 28 or 56 days of age for virological and histopathological examination. In the i.p.-inoculation study, neither viral replication nor lesions were detected in the animals inoculated at 28 and 56 days of age. In the animals inoculated when younger than 14 days of age, lesions were restricted to the brain although viral replication was detected in the brain, heart and pancreas. The brain lesions were characterized by acute meningoencephalitis with neuronal necrosis in the cerebral cortex, hippocampus and thalamus, and viral RNA was detected in degenerated and/or intact neurons. In the i.c.-inoculation study, similar age-related changes in susceptibility of rat brain to EMC-D infection were observed, but a minor difference was that viral replication and lesions were still detected in the hippocampus of some animals inoculated at 28 days of age. These results suggest that an age-related decrease in the susceptibility of rat brain to EMC virus infection may reflect an age-related change in the susceptibility of neurons themselves as well as in maturation of the immune system.

Aging↗

PubMed1997

Hair follicles of young Wistar strain hairless rats: a histological study.

The histological changes in hair follicles in hairless rats derived from the Wistar strain (hW, hairless Wistar) were examined from birth to maturity and compared with those of age-matched normal Wistar rats. In the 1st hair cycle, the hair follicles of hW rats were shorter and less well developed than those of Wistar rats. In early anagen, eosinophilic bodies were observed in some hair follicles which showed immature histological features. By using Tdt-mediated dUTP nick end labelling (TUNEL) method and electron microscopic examination, these bodies were confirmed to be apoptotic bodies. These follicles seemed to disappear by abnormal regression. In late anagen phase, the follicles in which the apoptosis did not occur showed enlarged hair roots with hypertrophy of the inner root sheath. Subsequently, when the follicles in normal Wistar rats synchronously regressed in the catagen phase, most of the follicles in hW rats similarly entered the catagen phase, but a few follicles did not regress completely and showed aberrant hair root enlargement. Finally, both types of follicle in hW rats formed follicular cysts. These abnormalities in follicle development (abnormal follicular regression and follicular cyst formation) appear to be associated with the hairlessness in this rat strain.

Animals↗

PubMed1997

Vulval angiomyofibroblastoma. Clinicopathologic analysis of six cases.

Clinicopathologic, immunohistochemical, ultrastructural, and flow cytometric analyses were performed on vulvar angiomyofibroblastomas in six women (ages 32 to 46 years; average age, 41.3 years). The tumors were all well circumscribed, and measured 2 to 9 cm in greatest dimension. Five tumors were clinically diagnosed as Bartholin's gland cysts. At histologic analysis, the tumors were characterized by alternating hypercellular and hypocellular edematous areas with abundant blood vessels. The hypercellular areas showed a perivascular proliferation of spindle-shaped and round cells, which often formed small nests or epithelioid arrangements, and a short fascicular pattern of spindle cells. The proliferating vessels were thin-walled and capillary-sized. Cellular atypia and mitotic figures were absent. Two tumors contained an adipose element, and one showed a prominent vascular proliferation reminiscent of a capillary hemangioma. At immunohistochemical analysis, the tumor cells were strongly positive for vimentin and desmin. Some cells were weakly positive for HHF35 and alpha-smooth muscle actin. Ultrastructurally, one neoplasm showed fibroblastic differentiation. Flow cytometry revealed three tumors were DNA diploid and two were aneuploid. All tumors were excised, and none have recurred (average follow-up, 28.3 months). These results indicate that angiomyofibroblastomas contain heterogeneous components.

Adult↗

PubMed1997

Systemic inflammatory response syndrome and organ dysfunction following gastrointestinal surgery.

OBJECTIVES: Progression from systemic inflammatory response syndrome (SIRS) to sepsis, severe sepsis, and septic shock has been demonstrated in a variety of patients. However, the presence of SIRS alone was not helpful in predicting the development of multiple organ dysfunction syndrome (MODS) since SIRS includes many nonprogressive conditions. This study was conducted to investigate the clinical significance of SIRS in postoperative patients. DESIGN: Retrospective study. SETTING: The surgical department of a university hospital. PATIENTS: Two hundred ninety-two consecutive patients who received elective common gastrointestinal surgery (esophagectomy, pancreatoduodenectomy, hepatectomy, gastrectomy, colorectal resection, and laparoscopic cholecystectomy) between 1992 and 1995. INTERVENTIONS: Patients were analyzed for preoperative physiologic status, surgical stress parameters, and postoperative status of SIRS, complications, and end-organ dysfunction. MEASUREMENTS AND MAIN RESULTS: Duration of SIRS or positive criteria's number of SIRS after surgery significantly correlated with surgical stress parameters (blood loss/body weight and operation time) and peak serum C-reactive protein concentrations. SIRS that continued or reappeared after postoperative day 3 was an early sign of postoperative complications. SIRS continuing consecutively for 2 days after postoperative day 3 had a 70.6% positive predictive value and a 92.5% negative predictive value for postoperative complications. Septic complications and prolongation of SIRS were associated with MODS. Five of six patients who met the SIRS criteria for >30 days developed severe MODS, and three of them died. CONCLUSIONS: SIRS is a useful criterion for the recognition of postoperative complications and end-organ dysfunctions. Early recovery from SIRS may arrest the progression of organ dysfunction.

Aged↗

PubMed1997

Significance of elbow extension in reconstruction of prehension with reinnervated free-muscle transfer following complete brachial plexus avulsion.

Thirty-one patients with complete avulsion of the brachial plexus underwent reconstruction of elbow extension by intercostal nerve transfer following reconstruction of prehension with either a single or double free-muscle transfer. Long-term results of elbow extension were evaluated in 24 patients. Reinnervation of the triceps muscle took longer than that of the transferred muscle on serial electromyographic examinations, and the eventual strength of the triceps muscle was weak. None attained M5 grade, 2 achieved M4 grade, 4 achieved M3 grade, 8 achieved M2 grade, 5 achieved M1 grade, and another 5 achieved M0 grade. However, despite the weak recovery, 14 patients were able to obtain useful functional recovery of the triceps muscle, enabling it to stabilize the elbow joint against the transferred muscle, which acted as simultaneous elbow flexor and wrist or finger extensor. Elbow stability is imperative in order to obtain voluntary finger function following free-muscle transfer. Should the triceps muscle fail to recover following intercostal nerves neurotization, transferring the reinnervated infraspinatus to the triceps is an optional procedure to provide stabilization of the elbow.

Adolescent↗

PubMed1997

Experimental study on donor nerves for brachial plexus injury: comparison between the spinal accessory nerve and the intercostal nerve.

The spinal accessory nerve and intercostal nerves are widely used as donor nerves for neurotization in patients with brachial plexus injuries. However, the characteristic differences in reinnervation by the spinal accessory and intercostal nerves have not been investigated. The purpose of this study is to compare the resulting contractile properties of the biceps muscles following nerve-crossing procedures of spinal accessory nerve and intercostal nerves to the musculocutaneous nerves. In 10 beagle dogs, the spinal accessory nerve was used to reinnervate the left biceps muscle, and the second and third intercostal nerves were used to reinnervate the right biceps muscle. After 10 months, the reinnervated muscles were studied by measuring their force of contraction as well as by histochemical methods. Biceps muscles reinnervated by spinal accessory nerves (A transfers) acquired the properties of fast, fatigable muscles, whereas those reinnervated by intercostal nerves (IC transfers) acquired the properties of slow, fatigue-resistant muscles. Furthermore, histochemical studies showed that type II fibers were predominant in A transfers, whereas type I fibers were predominant in IC transfers. This study clearly demonstrates the differences between the spinal accessory nerve and intercostal nerves as donor nerves. This may lead us to select appropriate donor nerves for nerve-crossing procedures and free-muscle transfer depending on the desired functions to be reconstructed.

Accessory Nerve↗

PubMed1997

Tensor fasciae latae flap: alternative donor as a functioning muscle transplantation.

The functioning tensor fasciae late muscle was used for a patient with both a complete defect of the deltoid muscle and a defect of overlying skin. The configuration of the tensor fasciae latae including the length of the muscle belly as well as the muscle fiber arrangement was similar to that of the deltoid. In addition, the spatial relationship between the muscle, donor vessels, and motor nerve fulfilled the requirements for the recipient site of deltoid reconstruction. The transferred muscle successfully replaced the function of the deltoid and provided sufficient strength for elevation of the arm. Simultaneous skin coverage was also satisfactory. The case report here clearly indicates that the tensor fasciae latae muscle is a promising candidate for functioning muscle transplantation, and can also be applied for other disorders. However, several points such as limited motor nerve length should be considered when tensor fasciae latae is used as a functioning muscle.

Fascia Lata↗

PubMed1997

Endoscopic harvesting of the gracilis muscle for reinnervated free-muscle transfer.

Reinnervated functioning free-muscle transfer has proven to be invaluable in numerous reconstructive procedures. However, one problem that remains unsolved after transferring the muscle is the presence of a long and cosmetically unacceptable scar at the donor site. This scar has undermined patients' satisfaction with the procedure despite its excellent functional results. In an attempt to resolve this problem, the authors harvested the gracilis muscle endoscopically and now report their technique and results. To create an optical cavity in harvesting the gracilis muscle endoscopically, they devised a lifting apparatus, which is described. Comparative study showed that endoscopic harvesting of the gracilis produced a significantly shorter scar, but took 1.5 times longer than conventional method.

Adult↗

PubMed1997

Computerized analysis of interstitial disease in chest radiographs: improvement of geometric-pattern feature analysis.

We have been developing automated computerized schemes to assist radiologists in interpreting chest radiographs for interstitial disease based on texture analysis and geometric-pattern feature analysis. In this study, we attempted to improve the performance of the geometric-pattern feature analysis, because the current classification performance with geometric-pattern feature analysis is considerably lower than that of texture analysis. In order to improve the performance in distinguishing between normal lungs and abnormal lungs with interstitial disease, we attempted to remove rib edges in regions of interest (ROIs) by using an edge detection technique, and also to reduce false positives by using feature analysis techniques. In addition, the effects of many parameters on classification performance were investigated to identify proper threshold levels, and subsequently the specificity of the geometric-pattern feature analysis was improved from 69.5% to 86.1% at a sensitivity of 95.0%. Using a combined rule-based method with texture analysis and geometric-pattern feature analysis plus the artificial neural network (ANN) method for classification, a high specificity of 96.1% was obtained at a sensitivity of 95.0%.

Biophysical Phenomena↗

PubMed1997

Development of an improved CAD scheme for automated detection of lung nodules in digital chest images.

Lung cancer is the leading cause of cancer deaths in men and women in the United States, with a 5-year survival rate of only about 13%. However, this survival rate can be improved to 47% if the disease is diagnosed and treated at an early stage. In this study, we developed an improved computer-aided diagnosis (CAD) scheme for the automated detection of lung nodules in digital chest images to assist radiologists, who could miss up to 30% of the actually positive cases in their daily practice. Two hundred PA chest radiographs, 100 normals and 100 abnormals, were used as the database for our study. The presence of nodules in the 100 abnormal cases was confirmed by two experienced radiologists on the basis of CT scans or radiographic follow-up. In our CAD scheme, nodule candidates were selected initially by multiple gray-level thresholding of the difference image (which corresponds to the subtraction of a signal-enhanced image and a signal-suppressed image) and then classified into six groups. A large number of false positives were eliminated by adaptive rule-based tests and an artificial neural network (ANN). The CAD scheme achieved, on average, a sensitivity of 70% with 1.7 false positives per chest image, a performance which was substantially better as compared with other studies. The CPU time for the processing of one chest image was about 20 seconds on an IBM RISC/6000 Powerstation 590. We believe that the CAD scheme with the current performance is ready for initial clinical evaluation.

Adult↗

PubMed1997

Possible role of macrophage-derived soluble mediators in the pathogenesis of encephalomyocarditis virus-induced diabetes in mice.

Pancreatic islets from DBA/2 mice infected with the D variant of encephalomyocarditis (EMC-D) virus revealed lymphocytic infiltration with moderate to severe destruction of pancreatic beta cells. Our previous studies showed that the major population of infiltrating cells at the early stages of infection is macrophages. The inactivation of macrophages prior to viral infection resulted in the prevention of diabetes, whereas activation of macrophages prior to viral infection resulted in the enhancement of beta-cell destruction. This investigation was initiated to determine whether macrophage-produced soluble mediators play a role in the destruction of pancreatic beta cells in mice infected with a low dose of EMC-D virus. When we examined the expression of the soluble mediators interleukin-1 beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), and inducible nitric oxide synthase (iNOS) in the pancreatic islets, we found that these mediators were clearly expressed at an early stage of insulitis and that this expression was evident until the development of diabetes. We confirmed the expression of these mediators by in situ hybridization with digoxigenin-labelled RNA probes or immunohistochemistry in the pancreatic islets. Mice treated with antibody against IL-1beta or TNF-alpha or with the iNOS inhibitor aminoguanidine exhibited a significant decrease in the incidence of diabetes. Mice treated with a combination of anti-IL-1beta antibody, anti-TNF-alpha antibody, and aminoguanidine exhibited a greater decrease in the incidence of disease than did mice treated with one of the antibodies or aminoguanidine. On the basis of these observations, we conclude that macrophage-produced soluble mediators play an important role in the destruction of pancreatic beta cells, resulting in the development of diabetes in mice infected with a low dose of EMC-D virus.

Animals↗

PubMed1997

Photochemically induced colonic ischaemic lesions: a new model of ischaemic colitis in rats.

BACKGROUND: Recent clinical studies suggest that ischaemic colitis is caused by a microcirculatory disturbance that involves thrombosis of the colon. AIM: To establish a new model of photochemically induced ischaemic colitis in rats. METHODS: Thirty male Wistar rats were anaesthetised with amobarbital, the femoral veins were cannulated and laparotomies were performed. The serosal surface of the proximal colon was irradiated by using a krypton laser (wavelength 568 nm, 20 mW) for four minutes. An intravenous infusion of a photosensitising dye, rose bengal (20 mg/kg body weight), was administered over 90 seconds, beginning at the start of irradiation. Rats were killed immediately (n = 4), 12 hours (n = 2), 24 hours (n = 10), three days (n = 4), seven days (n = 4), 14 days (n = 2), or 28 days (n = 2) after irradiation. Two control rats received laser irradiation without dye infusion. Specimens of the irradiated sites were examined by using histopathology. RESULTS: Localised ulcers of the colon were present in rats killed at 12 hours, 24 hours, three days, and seven days after irradiation. Microscopy findings were consistent with the features of human ischaemic colitis. Reproducible ulcerative lesions were produced by photothrombosis of microvessels in the colon. CONCLUSION: This model may be useful for further investigation of the pathophysiology of ischaemic colitis.

Animals↗

PubMed1997

Digital chest radiography: effect of temporal subtraction images on detection accuracy.

PURPOSE: To improve early detection of disease in chest radiographs, the authors developed a digital processing technique that geometrically warps and subtracts a previous radiograph from a current radiograph to produce a temporal subtraction image. An observer test was performed to evaluate the effects of the temporal subtraction image technique on detection of interval change. MATERIALS AND METHODS: Fifty pairs of chest radiographs, including a baseline examination and a subsequent radiograph, were selected (25 cases in which potentially important new abnormalities had developed, and 25 in which there was no interval change). The baseline examination was chosen from multiple prior radiographs to minimize initial misregistration. By means of receiver operating characteristic (ROC) analysis, the ability of 11 observers to detect pathologic change when viewing the paired digitized baseline and subsequent radiographs was compared with their ability when viewing the same paired radiographs together with temporal subtraction images. Positive cases demonstrated focal new abnormalities that were greater than 1 cm in diameter. RESULTS: The mean area (Az) under the ROC curves increased from 0.89 without to 0.98 with the temporal subtraction images. When the paired digitized previous and current chest radiographs were viewed in conjunction with the temporal subtraction images, a significant improvement in detection of new abnormalities was achieved (P = .00004), whereas the mean interpretation time was reduced by 19.3% (from 52 to 42 seconds, including the time to record the score and to move to the next case) (P = .0019). CONCLUSION: The temporal subtraction technique can significantly improve sensitivity and specificity for detection of interval change in chest radiographs.

Humans↗