Clinical usefulness of radionuclide angiography using 99mTc-DTPA-HSA in simultaneous cadaveric pancreas-kidney transplantation: a case report.
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Cadaver↗
Biomedical subjects
M Gotoh
Publications and source records attributed to M Gotoh.
Successful living donor liver transplantation in a patient with preoperative fungal infection.
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Adolescent↗
Locally expressed CTLA4-Ig in a pancreatic beta-cell line suppresses accelerated graft rejection response induced by donor-specific transfusion.
AIMS/HYPOTHESIS: This study examined whether locally expressed CTLA4-Ig can suppress the accelerated islet allograft rejection that is induced by donor-specific transfusion. METHODS: CTLA4-Ig-transfected or parental MIN6 cells were transplanted subcutaneously into the right flank of streptozotocin-induced diabetic C3H/Hej mice with or without donor-specific transfusion. For donor-specific transfusion, spleen cells from C57BL/6 mice were injected i.v. at the time of transplantation. In other experiments, CTLA4-Ig-transfected and parental MIN6 cells were transplanted separately into each flank, together with donor-specific transfusion. Rejection was defined as a blood glucose concentration of more than 300 mg/dl in two consecutive measurements, and graft survival was confirmed by hyperglycaemia after the grafts were removed. The effect of an anti-CTLA4 antibody on the survival of CTLA4-Ig-transfected MIN6 cells was also examined. RESULTS: In 7 of 12 donor-specific transfusion sensitised mice, CTLA4-Ig-transfected MIN6 cells remained viable 20 days after grafting, whereas all parental MIN6 cells ( n = 10) were rejected promptly, within 14 days. The prolonged allograft survival was observed even in the absence of detectable levels of serum CTLA4-Ig, while the surviving allografts continued to produce CTLA4-Ig in situ. This protection was abrogated by an anti-CTLA4 antibody, but not by a control antibody. Furthermore, six animals that maintained normoglycaemia after the separate transplantation of parental and CTLA4-Ig-transfected MIN6 cells into each flank all showed abrupt hyperglycaemia after the CTLA4-Ig/MIN6 graft was removed, suggesting that this protection operated locally. CONCLUSION/INTERPRETATION: A beta-cell line genetically engineered to secrete CTLA4-Ig can protect a graft locally from the alloimmune response induced by donor-specific transfusion.
Abatacept↗
Odontogenic infection pathway to the submandibular space: imaging assessment.
The aims of this study were to determine the pathways of odontogenic infection spread into the submandibular space and their relationship to the clinical symptoms. Computerized tomography (CT) and magnetic resonance (MR) images of 33 patients with submandibular involvement were analyzed. The spread of infection was evaluated by lateral asymmetry of the shape and density of the fascial spaces and tissues, and by obliteration of the interfascial fat spaces. Imaging findings were classified into three types: in 19 patients (57.6%), infection spread through the mylohyoid muscle or sublingual space (type I). In five patients (15.2%), infection spread through the bony structures of the mandible with periosteal reaction or perforation of the cortical plate (type II) and was associated with relatively mild symptoms. In four patients (12.1%), infection spread from the masticatory space (type III). Seven of 11 patients with dysphagia or fever showed submandibular involvement spreading into the parapharyngeal space. CT and MR imaging clearly demonstrated different pathways of the spread of odontogenic infection into the submandibular space, which influenced the manifestation of clinical symptoms.
Adipose Tissue↗
Two antiprothrombin antibodies against prothrombin and prothrombin-phosphatidyl serine show partial but not total identity.
Recently, an enzyme-linked immunosorbent assay (ELISA) using prothrombin (PT) as the antigen has become a widely used test. Two ELISA methods for the detection of antiprothrombin antibody have been used extensively: one method employs PT as an antigen (aPT), and the other employs PT and phosphatidyl serine (aPT/PS) as antigens along with Ca. However, the results obtained by the two methods are not necessarily consistent with each other even using the same samples, suggesting the possibility that aPT and aPT/PS are different antibodies. We conducted an investigation to determine whether aPT and aPT/PS are identical or different antibodies. Five patients who were positive for both tests become negative to aPT after absorption with an aPT-ELISA plate or fluid-phase PT; however, they retained reactivity to aPT/PS after the same absorption procedure. These results suggest that aPT and aPT/PS are partially identical, yet still different antibodies. However, further examination employing more samples may be needed to verify our hypothesis including clarification of the clinicopathological significance of these antibodies in the future.
Adult↗
Detection of genes expressed in primary colon cancers by in situ hybridisation: overexpression of RACK 1.
AIMS: The isolation of various genes that are expressed in a region specific manner is considered useful for research in molecular pathology. In situ hybridisation (ISH) was used in a screening procedure to isolate these genes efficiently, using colon cancer as a model. METHODS: Suppression subtractive hybridisation (SSH) between colon cancer tissue samples and corresponding non-cancerous tissues was performed. Genes showing high expression in the cancers were selected using macro-DNA array analysis. As a final screening procedure, conventional ISH was performed to isolate genes expressed specifically in colon cancers. RESULTS: Sixty nine clones were selected by SSH and macro-DNA array analyses. These clones were then analysed by ISH to examine their expression patterns. ISH screening revealed that all the clones screened showed more intense signals in colon cancers than in non-cancerous tissues. Among them, RACK 1, which is a protein kinase C receptor and a homologue of the G protein beta subunit, was expressed intensely in colon cancer cells. RACK 1 expression was evaluated in multiple samples by ISH, and the results confirmed that RACK 1 was universally overexpressed in cells of all 11 colon cancers examined. CONCLUSIONS: Many genes, including RACK 1, expressed in colon cancer cells can be isolated efficiently by this method, and their precise expression pattern can be evaluated. These results indicate that ISH is an excellent technique for systemic screening of genes expressed in a region specific manner.
Blotting, Northern↗
Octreotide-induced suppression of the hyperglycemic response to neostigmine or bombesin: relationship to hypothalamic noradrenergic drive.
Neostigmine (cholinesterase inhibitor) or bombesin, when injected into the third cerebral ventricle of awake rat, dose-dependently increased serum glucose with the simultaneous rise in hypothalamic noradrenergic neuronal activity (NAA). Co-administration of octreotide with neostigmine or bombesin suppressed the hypothalamic NNA response with the simultaneous inhibition of the hyperglycemic response. There was a close relationship between hypothalamic NNA and serum glucose in these studies. On the basis of the concept that hypothalamic noradrenergic drive plays an important role in mediating the hyperglycemic response to stressful stimuli, the present findings suggest that the hyperglycemic response to neostigmine or bombesin is mediated via the interaction with hypothalamic noradrenergic neurons.
Animals↗
Central suppressive effect of octreotide on the hyperglycemic response to 2-deoxy-D-glucose injection or cold-swim stress in awake rats: possible mediation role of hypothalamic noradrenergic drive.
Somatostatin (SRIH) and its analog have been reported to act within the central nervous system to suppress the hyperglycemic response to a variety of neural stimuli. On the other hand, the hyperglycemic response to 2-deoxy-D-glucose (2-DG) injection or cold-swim stress is well demonstrated to be closely associated with an increase in hypothalamic noradrenergic neuronal activity (NNA). To evaluate whether the suppression of the hypothalamic NNA response could be involved in the central mechanism whereby a SRIH analog inhibits the hyperglycemic response, octreotide, a clinically used long-acting octapeptide SRIH analog, was administered into the third cerebral ventricle of awake rats prior to the intraperitoneal injection of 2-DG or cold-swim stress. Hypothalamic noradrenaline (NA) and its neuronal metabolite, 3,4-dihydroxyphenylethyleneglycol (DHPG), were analyzed, and the ratio of DHPG to NA was used as an index of NNA. Intracerebroventricular (i.c.v.) pretreatment with octreotide suppressed the 2-DG-induced increase in hypothalamic NNA, accompanied by the inhibition of the serum glucose, NA and adrenaline responses. This suppressive effect of octreotide was dose-dependent. Similarly, i.c.v. pretreatment with octreotide prevented the hypothalamic NNA response to cold-swim stress, accompanied by a blockade of the increases in serum glucose, NA and adrenaline. A close relationship between hypothalamic NNA and serum glucose emerged from these studies. Intraperitoneal pretreatment with octreotide had no significant effect on the hyperglycemic or hypothalamic NNA response to 2-DG injection. These findings suggest that the inhibitory effect of octreotide on the hypothalamic NNA response to 2-DG injection or cold-swim stress is associated with the simultaneous suppression of the hyperglycemic response. Supporting the concept that hypothalamic NNA contributes to the modulation of blood glucose in stressful conditions, it is suggested that the suppression of the hypothalamic NNA response is, at least in part, involved in the central mechanism by which octreotide inhibits the hyperglycemic response to 2-DG injection or cold-swim stress.
Animals↗
Profenofos metabolites in human poisoning.
Profenofos and its metabolites were determined in a case of fatal poisoning. Little profenofos and large amounts of metabolites were detected by gas chromatography/flame photometric detection in the acid extracts of blood and urine after methylation with diazomethane. Four major metabolites containing phosphorus were identified with the synthesized metabolites, namely, despropylated profenofos, desethylated profenofos and des-S-propylated profenofos, respectively. 4-Bromo-2-chlorophenol (BCP), an aryl moiety of profenofos, was also determined in blood and urine with high performance liquid chromatograph (HPLC) as free or conjugated metabolites.
Aged↗
Effects of preconditioning on ischemia/reperfusion injury of hepatocytes determined by immediate early gene transcription.
Ischemia reperfusion (I-R) of the liver induces various events leading to cell death (apoptosis) and subsequent cells proliferation. Recent experimental studies have described the protective effect of ischemic preconditioning (IPC) on I-R injury of the liver. However, the mechanisms involved in this protection remain unknown. The protein products of immediate early genes (IEGs) behave as crucial transcriptional regulators not only in apoptosis but also in cell proliferation. Here, we evaluated the effects of IPC on IEG transcription after I-R injury, using a rat liver I-R injury model. Injury to hepatocytes was evaluated by measuring serum levels of aspartate transaminase (AST), alanine transaminase (ALT), and lactate dehydrogenase (LDH) and that to endothelial cells by plasma concentration of hyaluronic acid (HA). The extent of necrosis was evaluated by H&E staining, while cell proliferation and apoptosis were evaluated by proliferating cell nuclear antigen (PCNA) and terminal deoxy(d)-UTP nick end labelling (TUNEL) staining, respectively. Alterations in the transcription of IEGs (c-fos and c-jun) were examined by Northern blotting. Rats subjected to 40-min liver ischemia, preceded by 10-min preconditioning, showed significantly lower AST, ALT, LDH, and HA levels at 6 h after I-R than untreated animals (P < 0.05; n at least 5 rats per group). The percentage of necrotic areas at 24 h after I-R was significantly lower in IPC-treated animals than in the controls. The numbers of apoptotic cells at 24 h after I-R and the numbers of PCNA-positive cells at 24 and 48 h after I-R were significantly lower in IPC-treated rats than in controls. Transcription levels of IEGs were low in IPC-treated rats, particularly c-jun at 1 and 1.5 h after I-R (P < 0.05). Our results indicate that IPC provides a significant protective effect on for liver cells against I-R injury and that its effect is evidenced by a significant decrease in the transcription levels of IEGs following the insult.
Animals↗
Induction of immediate early genes after partial hepatectomy in cholestatic liver.
The protein products of immediate early genes (IEGs) behave as transcriptional regulators and play an important role in the regulation of gene expression associated with liver cell proliferation and apoptosis. The aim of this study was to examine whether the transcription of IEGs was induced by obstructive jaundice during liver regeneration after 70% partial hepatectomy, and to examine their association with animal survival, cell proliferation, and apoptosis. Obstructive jaundice (OJ) was induced in rats by common bile duct ligation (CBDL), and 70% partial hepatectomy was performed 5 days after CBDL (OJ group). Changes in the induction of the IEGs, c-fos and c-jun, were compared between control and OJ groups in relation to survival before and after partial hepatectomy. Cell proliferation and apoptosis were evaluated by proliferating cell nuclear antigen (PCNA) immunohistological staining and by an in situ TdT-mediated d-UTP-digoxigerin nick-end labeling (TUNEL) method. The 2-week survival in the OJ group (2/7) was significantly less that of the sham operation (control) group (7/7). Enhanced induction of IEGs was evident in the OJ group after partial hepatectomy compared with findings in the control group. The PCNA-labeling index (LI) in the OJ group was increased after partial hepatectomy, but only minimally, compared with that in control animals. Apoptotic cells appeared in bile ducts and surrounding hepatocytes after partial hepatectomy in the OJ group, although apoptotic cells were rare in the control group. IEG transcription does occur after partial hepatectomy in jaundiced liver but it is enhanced and sustained, and leads to apoptosis rather than leading to the efficient proliferation of hepatocytes.
Animals↗
C4d and C4bp deposition along the glomerular capillary walls in a patient with preeclampsia.
Complement (C) 4d and cofactor C4b binding protein (C4bp) are detected in the glomerular capillary walls of a patient with preeclampsia. A 32-year-old nullipara had proteinuria of 1.2 g/d and edema at the 33rd week of pregnancy. Gradually the urinary protein excretion increased, reaching 5.1 g/d at the 37th week. The patient also showed hypertension at this stage. After normal mature delivery, the level of the urinary protein excretion remained at 3 to 4 g/d. Renal biopsy performed by means of light and electron microscopy, 15 days after delivery, showed almost normal glomeruli and modest subendothelial widening. Immunohistochemistry indicated that immunoglobulin (Ig) A, IgG, C1q, C3c, and C4c were not deposited in the glomeruli, whereas weakly positive IgM and fibrin-related antigen (FRA) were observed. Conversely, C4d, C3d, and C4bp were strongly deposited. Protein S (PS) also was observed, with a similar distribution pattern to that of C4bp. Immunoelectron microscopy showed the deposition of C4d along the capillary walls and of C4bp in the subendothelium. These findings suggest that the C4 activation process as well as the regulation process of C system and of the inflammatory coagulation axis by C4bp and PS may play an important role in the pathophysiology of preeclampsia, so-called glomerular capillary endotheliosis (GCE).
Adult↗
Vascular endothelial growth factor (VEGF) expression in the subacromial bursa is increased in patients with impingement syndrome.
Vascular endothelial growth factor (VEGF), which is known to be an angiogenetic factor, plays an important role in the inflammation of synovial tissue. To investigate the relationships between VEGF and clinical symptoms in rotator cuff disease, VEGF expression was examined using RT-PCR and immunohistochemical analysis in 50 patients with this disease (26 with full-thickness cuff tear, 12 with partial-thickness tear, and 12 with subacromial bursitis). VEGF mRNA expression was detected in 40 out of 50 patients by RT-PCR. VEGF mRNA expression was found more frequently in the patients with motion pain (39 out of 41) than in those without motion pain (1 out of 9) with statistical significance (Fisher's test, P < 0.001). Thirty-one out of 33 patients with synovial proliferation showed VEGF mRNA expression, whereas the expression of this transcript was found in 9 out of 17 patients without synovial proliferation. This association with synovial proliferation was also significant (Fisher's test, P = 0.0013). Thirty out of 41 patients with motion pain had synovial proliferation but 3 out of 9 patients without motion pain had synovial proliferation. In all these 30 patients with both motion pain and synovial proliferation, VEGF mRNA expression was detected. This association between motion pain and synovial proliferation was also significant (Fisher's test, P < 0.05). The mean vessel count and area in subacromial bursa expressing VEGF was significantly higher than in those without VEGF (Mann Whitney's U test, P < 0.01). These results suggested that VEGF expression is associated with vascularity, synovial proliferation and shoulder motion pain in the rotator cuff disease.
Acromion↗
Healing of full-thickness tears of avian supracoracoid tendons: in situ hybridization of alpha1(I) and alpha1(III) procollagen mRNA.
Although clinically significant, much remains unknown about the healing of the torn rotator cuff tendon, because of unavailability of appropriate animal model. The human supraspinatus tendon faces the subacromial bursa superiorly, and the joint capsule inferiorly, while the digital flexor tendon is surrounded by the synovium. We hypothesized that the supraspinatus tendon heals by the process which is different from that observed with digital flexor tendons, in which epitenon cells migrate into the torn portion circumferentially. The avian supracoracoid tendon was adopted for this experiment because of its similarity to the human supraspinatus tendon. We developed a full-thickness tendon laceration followed by primary suture. The objective of this study was to detect localization of the responsible cells for repair of the tendon. We examined the process using histology and in situ hybridization. Starting at week 1 the peritendon cells of the bursal side proliferated and migrated into the laceration site. At week 6, the tendon stumps were continuous with new connective tissue. High-level expression of procollagen mRNA in the proliferating peritendon cells on the bursal side demonstrates to contribute to the reparative process, which progressed to the joint side. This mode of repair is different from that of the digital flexor tendon.
Animals↗
Successful recovery from human immunodeficiency virus (HIV)-associated haemophagocytic syndrome treated with highly active anti-retroviral therapy in a patient with HIV infection.
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Acquired Immunodeficiency Syndrome↗
Blood flow in and around the masseter muscle: normal and pathologic features demonstrated by color Doppler sonography.
OBJECTIVE: The purpose of this study was to clarify the normal findings of arteries in and around the masseter muscle and to present their pathologic changes with the use of color Doppler sonography. STUDY DESIGN: The vascular appearances were examined for the 4 main arteries feeding the masseter muscle in healthy volunteers (n = 38) and patients with inflammation (n = 5) and intramuscular hemangioma (n = 3). The features of these arteries were investigated together with the flow diameter, flow velocities, and arterial resistances. The symmetry indices were also calculated to assess the pathologic changes. RESULTS: The detection rates of the branch from the transverse facial artery, the masseter artery, and the branch from the maxillary or external carotid artery were 98.7%, 21.1%, and 84.2% in healthy volunteers, respectively. The facial artery that feeds the muscle from the inferior part represented 2 patterns according to anatomic variant: the masseteric branch (22.4%) and the main trunk itself (77.6%). The means of the flow diameter, maximum and minimum velocities, resistive index, and pulsatility index in healthy subjects were 1.8 mm, 24.6 cm/s, 5.1 cm/s, 0.80, and 2.51, respectively. In most of the patients with symptoms, the symmetry indices of all measurement values increased in comparison with those of healthy volunteers. CONCLUSION: Color Doppler sonography is useful in describing the arteries in and around the masseter muscle and has the potential of being used to depict the pathologic changes.
Adult↗
Doppler sonography of the deep lingual artery.
PURPOSE: To clarify the Doppler sonographic features of the lingual artery in normal subjects and to evaluate those of patients with cancer of the tongue. MATERIAL AND METHODS: Sixty-seven volunteers and 12 patients with cancer and/or leukoplakia of the tongue were examined with an intraoral sonographic probe. The visibility of the deep lingual artery was determined on transverse and anteroposterior images. On the transverse images, the vascular index, which was defined as the number of colored pixels, was measured on bilateral lingual arteries. Thereafter, the degree of symmetry was evaluated for normal subjects and patients. RESULTS: In normal subjects, between younger and older volunteers, there were no significant differences in visibility of the trunk but differences were found between the two groups for the dorsal branches. The vascular indices of the right and left sides were not different. The characteristic Doppler sonographic feature was vasculature in and around the tumors in the patients with cancer of the tongue. The symmetry indices of the cancer patients were significantly different from those of normal subjects. CONCLUSION: Doppler sonography should be an important procedure for evaluation of tongue neoplasms.
Adult↗
Interleukin-1-induced subacromial synovitis and shoulder pain in rotator cuff diseases.
OBJECTIVE: To determine the relationship between the expression of interleukin-1beta (IL-1beta) and IL-1 receptor antagonists (IL-1ra) in the subacromial bursa and shoulder pain in rotator cuff diseases. METHODS: Synovial specimens were analysed using various methods including reverse transcriptase-polymerase chain reaction (RT-PCR), immunohistochemistry and in situ RT-PCR. Thirty-nine patients with rotator cuff diseases were candidates. The degree of their shoulder pain was evaluated using a visual analogue scale. RESULTS: The mRNA expression levels of the cytokines were significantly correlated with the degree of pain [IL-1beta: r=0.782; secreted IL-1ra (sIL-1ra): r=0.756; intracellular IL-1ra (icIL-1ra): r=0.806, P<0.001, respectively]. The combined results of immunohistochemistry and in situ RT-PCR analysis indicated that both synovial lining and sublining cells produce IL-1beta, while synovial lining cells predominantly produce icIL-1ra and sublining cells secrete sIL-1ra. CONCLUSIONS: The differential regulation of the two forms of IL-1ra mRNAs may play an important role in shoulder pain in rotator cuff diseases, regulating IL-1-induced subacromial synovitis.
Adult↗