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Biomedical subjects

K Kaneko

Publications and source records attributed to K Kaneko.

At least 307 records · Page 17Linked to original sources

Formation of new capillary-like tubes in a three-dimensional in vitro model (aorta/collagen gel).

Direct sprouting (angiogenesis) does not occur during the formation of capillary-like tubes in an aorta/ collagen gel in the in vitro model. However, emigration of cells which stretch, arrange themselves side by side, form contacts (unspecific, tight and gap junctions), develop a lumen and show differentiation of endothelial cells (including the formation of a lamina densa and the appearance of pericytes) have been observed, i.e. vasculogenesis occurs. The origin of long, stretched cells is not known with certainty. They possibly represent smooth muscle cells. In addition, other cell types have been found, such as fibrocyte-like and fibroblast-like cells, elastoblasts, fat cells, monocytes and macrophages. All these cells are able to produce factors that promote the formation of new capillaries. Hence, a knowledge of these cells appears to be important for the analysis of in vitro systems. Moreover, the occurrence of these cell types must be considered when assessing possible effects.

Animals↗

Continuous brachial plexus infusion of butorphanol-mepivacaine mixtures for analgesia after upper extremity surgery.

We have recently reported that continuous administration of butorphanol into the brachial plexus neurovascular sheath provided superior analgesia compared with that obtained with continuous i.v. administration. Furthermore, we found that analgesia was most pronounced when a mixture of mepivacaine and butorphanol was given and that butorphanol alone ranked next. In this study, we increased the dose of butorphanol, compared with that used in our previous reports, and an initial bolus dose of butorphanol was administered into the brachial plexus neurovascular sheath just after surgery had ended. Thereafter, postoperative pain relief was estimated. In patients undergoing upper extremity surgery with continuous axillary brachial plexus block, group A received a bolus of 1 ml of physiological saline with 1.5% mepivacaine, 10 ml into the brachial plexus sheath followed by a continuous brachial plexus infusion of 0.5% mepivacaine with butorphanol 6 mg at a rate of 144 ml/ 72 h. Group B was given a bolus of butorphanol 1 mg (1 ml) with 1.5% mepivacaine, 10 ml into the brachial plexus sheath and a continuous brachial plexus infusion of 0.5% mepivacaine with butorphanol 6 mg at a rate of 144 ml/72 h. After operation, VAS scores did not differ between the two groups. The time to first use of supplementary analgesia did not differ significantly between the two groups and there were no significant differences in the number of patients who required supplementary analgesia. These results indicate that continuous butorphanol 2 mg day-1 with 0.5% mepivacaine provided sufficient postoperative analgesia after upper limb surgery.

Analgesia↗

ACE inhibition reduces left ventricular mass independent of pressure without affecting coronary flow and flow reserve in spontaneously hypertensive rats.

Systemic and regional (including coronary) hemodynamics were studied in spontaneously hypertensive and normotensive Wistar Kyoto rats after 3 weeks of treatment with one of the three doses of the angiotensin converting enzyme inhibitor, ramipril. The effects of respective treatments on cardiovascular mass and systemic, coronary, and regional hemodynamics (at rest, during maximal treadmill exercise, and during dipyridamole infusion) then were evaluated in conscious rats using radiomicrosphere techniques. Low-dose ramipril (10 micrograms/kg/day by gavage) neither decreased arterial pressure nor reduced cardiac mass. However, medium (100 micrograms/kg/day) and high (1 mg/kg/day) doses reduced total cardiac and left ventricular masses to the same extent in spontaneously hypertensive rats, despite a much greater fall in arterial pressure with a high dose. Resting cardiac index, and myocardial and all other organ blood flows remained unchanged in both strains. When compared with Wistar Kyoto rats, coronary circulation was impaired in untreated spontaneously hypertensive rats (ie, reduced coronary flow and flow reserve and increased minimal coronary vascular resistance during dipyridamole infusion). This remained unchanged by ramipril. Furthermore, significant (and comparable) increases in cardiac index and myocardial blood flow and decreases in coronary vascular resistance were produced by maximal treadmill exercise in both strains. This also was unaffected by ramipril. These data showed that angiotensin converting enzyme inhibition with suboptimal and optimal hypotensive doses of ramipril reversed left ventricular hypertrophy in spontaneously hypertensive rats, but coronary flow, flow reserve, and minimal coronary vascular resistance remained unchanged despite left ventricular hypertrophy reversal.

Angiotensin-Converting Enzyme Inhibitors↗

Neutrophil elastase inhibitor, ONO-5046, modulates acid-induced lung and systemic injury in rabbits.

BACKGROUND: Acid instillation leads to direct lung and to secondary systemic organ injury, probably via activated macrophages and neutrophils. This study investigated the effects of neutrophil elastase on organ injury after unilateral lung acid instillation by administrating a specific neutrophil elastase inhibitor, ONO-5046, before acid instillation. METHODS: Three groups of anesthetized rabbits (n = 12 in each group) underwent tracheostomies, and instillations were made into their right lower lobe airspaces with either phosphate buffered saline (pH, 7.4; volume, 1.2 ml/kg; n = 12) or HCl (pH, 1.25; volume, 1.2 ml/kg; n = 24). In half of the acid-instilled rabbits, ONO-5046, 10 mg/kg, was given intravenously 15 min before the HCl instillation, and then 10 mg x kg(-1) x h(-1) of the drug was continuously infused throughout the experiment. The other groups of animals received the vehicle intravenously. Anesthesia and mechanical ventilation was continued for 8 h, whereas arterial blood gases were sampled intermittently. Eight hours after saline or acid instillation, the animals were killed, and their lungs, heart, kidneys, liver, and small intestines were harvested. Wet-to-dry weight ratios (W/ D) and myeloperoxidase (MPO) assays of these organs were done, and elastase assays on the bronchoalveolar lavage fluids (BALF) obtained from each lung also were performed. RESULTS: Pretreatment with ONO-5046 attenuated the physiologic changes seen in the vehicle-treated animals. Significant decreases in W/D of the noninstilled lungs and of the small intestine and normalization of the oxygenation of the experimental animals occurred. The ONO-5046 pretreatment did not affect the neutrophil sequestration in the lungs or in the other organs as determined by neutrophil counts in BALF and by the MPO assays. CONCLUSIONS: A neutrophil elastase inhibitor, ONO-5046, administered immediately before acid instillation attenuated the physiologic changes seen in the vehicle-treated animals. The drug blocked neutrophil elastase but did not block neutrophil sequestration in the lungs, although the drug improved measurements of lung injury.

Animals↗

Small hepatocellular carcinoma on magnetic resonance imaging. Relation of signal intensity to angiographic and clinicopathologic findings.

RATIONALE AND OBJECTIVES: The authors discuss the clinicopathologic features and angiographic vascularity of various signal intensity patterns on magnetic resonance (MR) imaging of small hepatocellular carcinomas (HCCs). METHODS: Magnetic resonance images of 88 resected HCCs (< or = 3 cm) were obtained using T1- and T2-weighted spin-echo images and T1-weighted images after gadolinium (Gd)-DTPA administration. Images were compared with angiographic and histopathologic findings. RESULTS: Forty HCCs (45%) were depicted on T1-weighted images, 51 (58%) on T2-weighted images, and 41 (49%) on T1-weighted images after Gd-DTPA administration. Overall, 64 (76%) were found on at least one image. On T1-weighted images, hyperintense HCCs histologically showed fatty metamorphosis and portal tracts within the tumor. On T2-weighted images, HCC hyperintensity correlated with expansive growth, peliotic change, and hypervascularity. By contrast, HCCs that were undetected or hypointense on T2-weighted images were well differentiated with replacing growth and portal tracts. On T1-weighted images after Gd-DTPA, hyperintense HCCs had peliotic change; undetected HCCs were well differentiated and hypovascular. CONCLUSIONS: Histologic grade, vascularity, portal tracts and peliotic change correlate with MR signal intensity. For hyperintense HCCs on T1-weighted images and hypo- or isointense HCCs on T2-weighted images, treatment methods must be assigned with the consideration that HCCs may be receiving transsinusoidal and portal blood supplies.

Adult↗

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↗

Complement partially mediates acid aspiration-induced remote organ injury in the rat.

BACKGROUND: Acid aspiration into one lung is known to cause both a local as well as remote organ injury characterized by neutrophil sequestration and subsequent edema. This study investigated investigated the role of the complement cascade in the development of acid aspiration-induced local lung and remote organ injuries using K-76 COONa (K76), an anticomplement agent that inhibits the complement pathway at the C5 step, and its usefulness as a treatment drug. METHODS: Anesthetized rats underwent tracheostomy and insertion of a cannula. K76 was intraperitoneally administrated prior to or immediately after the instillation of 0.1 ml of HCl (0.1N) or phosphate buffer solution (PBS) into the left lung. Inflammatory responses were evaluated by tumor necrosis factor alpha (TNF alpha) in the plasma and the bronchoalveolar lavage fluid (BALF) (n = 4), tissue myeloperoxidase (MPO), wet-to-dry weight ratio (W/D ratio) (n = 6), and protein concentration in the BALF (n = 6). RESULTS: Acid instillation caused an increase in the plasma TNF alpha, which was significantly attenuated by the administration of K76 prior to or after the acid instillation. Acid instillation to the left lung resulted in an increase of MPO and W/D ratios of the left lung, the right lung, and the small intestine. The administration of K76 inhibited the increase of MPO in these organs. K76 inhibited the increase of W/D ratios of the right non-instillated lung and the small intestine. Acid instillation led to increased protein concentration in the BALF of the left lung, which was not inhibited by K76. K76 administrated after the acid instillation had the same effects. TNF alpha in the BALF was not detected in all groups. CONCLUSION: These results suggest that localized acid aspiration induces, through the C5a step of the complement system-dependent mechanisms, TNF alpha formation and neutrophil sequestration, which caused the increase of endothelial permeability of the systemic organs. K76 is effective as a treatment drug in modulating some of the injuries caused by the acid instillation, but further investigations is warranted as to its potential as a therapeutic agent.

Animals↗

Analgesia after upper abdominal surgery using extradural administration of a fixed dose of buprenorphine in combination with lignocaine given at two infusion rates: a comparative study.

BACKGROUND: Extradural administration of combinations of local anaesthetics and opioids are frequently employed for postoperative pain relief. There is a scarcity of data on the analgesic effects of variations of the dose of local anaesthetic drug admixed to a fixed dose of opioid. METHODS: Twenty-four patients were investigated after elective upper abdominal surgery. During closure of the abdomen, 2% mepivacaine (8 ml) with buprenorphine 0.1 mg (0.5 ml) was given extradurally. After extubation, patients were randomly allocated to receive continuous extradural infusion of a fixed dose of buprenorphine (0.017 mg/h) in combination with 2% lignocaine at either 2.1 ml/h (low rate group, n = 14) or 6.3 ml/h (high rate group, n = 10). Postoperative pain at rest was assessed using visual analogue scale (VAS) scores and pain at movement by Prince Henry Pain Scale (PHPS) scores. Venous plasma lignocaine concentrations were measured. RESULTS: VAS scores at rest were similar in the two groups at 3 h postoperatively, whereas at 6-24 h postoperatively, VAS scores were higher in the low rate group than in the high rate group. PHPS scores were similar in the two groups at 3 h and at 18 h postoperatively, whereas at 6, 9, 12 and 24 h postoperatively, PHPS scores were higher in the low rate group than in the high rate group. Plasma lignocaine concentrations were higher at 23 h postoperatively in the high rate group than at 16 h in both groups, and at 23 h in the low rate group. At 3 h postoperatively, both the systolic and diastolic arterial pressures were higher in the low rate group than control values obtained on admission. Side effects were observed in one patient in the low rate group who complained of dizziness, and in one patient in the high rate group who complained of nausea. CONCLUSIONS: When added to a fixed dose of buprenorphine, continuous extradural infusion of 2% lignocaine at high rate provides better postoperative analgesia than when given at low rate without producing significant side effects.

Abdomen↗

Follicular dendritic cell sarcoma complicated by hyaline-vascular type Castleman's disease in a schizophrenic patient.

Follicular dendritic cell (FDC) sarcoma is an exceedingly rare neoplasm of unknown pathogenesis. A case of FDC sarcoma complicated by the hyaline-vascular type Castleman's disease occurring in a schizophrenic male is presented. Swelling of the left cervical lymph node appeared in a 44-year-old male schizophrenic who had been medicated with major tranquilizers for 20 years. He had had a history of cervical lymphadenopathy 14 years before, for which a diagnosis of hyaline-vascular type Castleman's disease had been made. The present specimen, obtained from the same site, was an enlarged lymph node heavily infiltrated with oval to spindle-shaped atypical cells but was uninvolved at the periphery. The infiltrating cells showed nodular or sheet-like growth, occasionally taking fascicular or storiform patterns. Follicular involvement was also common. Peculiarly, various amounts of small lymphocytes were intermingled with the neoplastic cells. The atypical cells expressed two FDC-specific antigens, DRC-1 and Ki-M4 antigen, together with a few other markers that are shared by FDC, including CD21 and HLA-DR. These findings clearly show the tumor to be FDC sarcoma. In addition, a peculiar fibro-hyalinous change in the lymph follicle, which is compatible with hyaline-vascular type Castleman's disease, was noted at the periphery of the lymph node where neoplastic cells had not infiltrated. Surprisingly, similar hyaline-vascular changes were observed in the previous biopsy taken 14 years ago. Meanwhile, Kaposi's sarcoma-associated herpesvirus, which is often identified from generalized Castleman's disease, was not identified in the present case by polymerase chain reaction study. Thus, this case is unique in two aspects: (i) the overlap of FDC sarcoma with hyaline-vascular type follicular changes; and (ii) its occurrence in a schizophrenic patient.

Adult↗

Lingual cyst in infancy: importance of palpation for diagnosis.

Two infants, 5 and 12 weeks of age, with lingual cysts were presented. Histological findings were compatible with a salivary retention cyst in one and a thyroglossal duct cyst in the other. Both infants were admitted to our hospital because of severe stridor that had developed from one to two weeks of age. Their lingual cysts were easily recognizable by simple palpation and were confirmed by non-invasive imaging techniques, such as ultrasound sonography, computed tomography and magnetic resonance imaging. Lingual cyst in infancy may be large enough to cause stridor and dyspnea, and occasionally result in sudden infant death, although once diagnosis is made a radical operation can be easily performed. Therefore, it is important that palpation in the oral cavity should be performed with all infants with persistent stridor as a part of a physical examination.

Cysts↗

Sex difference in the metabolism of pirmenol in rats.

The in vitro metabolism of pirmenol (cis-alpha-[3-(2,6-dimethyl-1-piperidinyl)propyl]-alpha-phenyl-2-pyri dinemethanol) and glucuronidation of its metabolites, a 4-hydroxylated derivative of pirmenol (M3) and 3-methylether of M3 (M5), were investigated using a hepatic 9000 x g supernatant and microsomes, respectively, of female and male rats in order to elucidate the higher urinary excretion of M3G and M5G (glucuronides of M3 and M5, respectively) in females previously observed in in vivo metabolism. Pirmenol delta1' iminium ion (M2) and M3 were formed by the oxidation of pirmenol in both sexes; however, M2 was the main metabolite in males, while M2 and M3 were formed at nearly the same level in females. On glucuronidation of M3 and M5, the Vmax values of both compounds were higher in female rats, consistent with the results in vivo. In addition, the sex difference in the urinary excretion ratio of M5G to M3G (1.1 in female, 2.5 in male) might reflect the lower availability of M3 for glucuronidation in male rats in vivo. The chromatographic separation of diastereomers of M5G was also described.

Animals↗

Ventricular septal defect secondary to non-penetrating chest trauma.

A 52-year-old man acquired a ventricular septal defect following non-penetrating chest trauma. Four days after the traumatic accident, he showed signs of congestive heart failure. Imaging techniques using echocardiography and left ventriculography were helpful in diagnosing the condition. Surgical repair by patch closure of the ventricular septal defect was accomplished 7 days after the traumatic accident.

Heart Septal Defects, Ventricular↗

Splenectomy in biliary atresia patients with recurrent jaundice following partial splenic embolization.

Splenectomy was performed for three patients with biliary atresia because of re-exacerbation of their jaundice following treatment by partial splenic embolization (PSE). The subjects' red blood cell count and hemoglobin, serum level of hepatic enzymes (glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, gamma-glutamyl transpeptidase, alkaline phosphatase, and lactic dehydrogenase), and total bilirubin (TB) were evaluated both before and after splenectomy in order to analyze the effects of splenectomy on these patients. The TB decreased significantly within 3 months after splenectomy in all three patients (13.0 +/- 1.6 mg/100 ml to 5.4 +/- 0.3 mg/100 ml, p < 0.05). The red blood cell count and hemoglobin increased gradually. There was a statistically significant correlation between the TB and the red blood cell count, and/or concentration of hemoglobin. The hepatic enzymes after splenectomy were not significantly different from those before splenectomy. The change in TB following splenectomy was essentially similar to that following PSE. These results suggested that the postoperative improvement in jaundice following splenectomy may not be due to improved hepatic function but merely a reflection of decreased red blood cell turnover. Splenectomy is a useful palliative procedure for jaundice in patients with biliary atresia for whom PSE is no longer effective.

Biliary Atresia↗

Anatomy and clinical importance of cholecystic venous drainage: helical CT observations during injection of contrast medium into the cholecystic artery.

OBJECTIVE: The purpose of this study was to use helical CT to elucidate the anatomy and clinical importance of cholecystic venous drainage. SUBJECTS AND METHODS: We performed helical CT of the upper abdomen during injection of contrast medium through a superselectively catheterized cholecystic artery (cholecystic artery CT) in 28 patients, all of whom were surgical candidates for suspected hepatobiliary abnormality. In nine of these patients, CT during arterial portography (CTAP) was also performed. RESULTS: Cholecystic venous blood most frequently entered peripheral portal branches of hepatic segment V (27 of 28 patients, 96%) and segment IV (26 of 28, 93%). In order of decreasing frequency, cholecystic venous blood also drained to segments I, VI, VIII, III, and VII. Cholecystic venous blood subsequently drained into the middle hepatic vein (21 of 28, 75%) or right hepatic vein (20 of 28, 71%). In two patients with adenocarcinoma involving the gallbladder associated with multiple liver metastases, cholecystic venous drainage was seen around each metastatic focus. In the nine patients in whom both cholecystic artery CT and CTAP were performed, nontumorous portal perfusion defects were attributable to cholecystic venous drainage. CONCLUSION: Recognition of cholecystic venous drainage as a possible pathway for spread of disease from the gallbladder to the liver and also as one of the causes of non-tumorous portal perfusion defects seen on CTAP is important.

Aged↗

Cell-specific regulation of IRS-1 gene expression: role of E box and C/EBP binding site in HepG2 cells and CHO cells.

Insulin receptor substrate 1 (IRS-1) is one of the major substrates of insulin receptor tyrosine kinase and mediates multiple insulin signals downstream. We have previously shown that the levels of IRS-1 mRNA varied in different tissues. To elucidate the molecular mechanisms of the tissue specific regulation of IRS-1, we have studied the cis-acting elements and transacting factors in CHO and HepG2 cells. Using the chloramphenicol acetyltransferase (CAT) assay with the various deletion mutants of the IRS-1 promoter-CAT fusion plasmids, several regions responsible for positive or negative regulation in each cell line were identified. A region from -1645 to -1585 bp, which regulated expression negatively in CHO cells and positively in HepG2 cells, was further analyzed. Within this region a fragment from -1645 to -1605 bp upregulated the IRS-1 promoter only in HepG2 cells, whereas a fragment from -1605 to -1585 bp downregulated only in CHO cells. In the gel mobility shift assay, several nuclear proteins that bind to these fragments were detected, and among them, two nuclear proteins that bind to a potential E box (nucleotide [nt] -1635 to -1630) and two nuclear proteins that bind to a potential C/EBP binding site (nt -1599 to -1591) were identified in HepG2 and CHO cells, respectively. CAT assays using promoters mutated at the E box or at the C/EBP binding site revealed that these sequences were responsible for cell-specific regulation of the IRS-1 gene. We therefore concluded that the two nuclear proteins that bind to the E box regulate IRS-1 gene expression positively in HepG2 cells and the two nuclear proteins that bind to the C/EBP binding site regulate it negatively in CHO cells.

Animals↗

Impact of natural IRS-1 mutations on insulin signals: mutations of IRS-1 in the PTB domain and near SH2 protein binding sites result in impaired function at different steps of IRS-1 signaling.

Insulin receptor substrate-1 (IRS-1) is one of the major substrates of insulin receptor tyrosine kinase and mediates various insulin signals downstream. In this study, we have examined the impact of three natural IRS-1 mutations identified in NIDDM patients (G971R, P170R, and M209T) on insulin signaling. G971R is located near src homology 2 protein binding sites, and P170R and M209T are located in the phosphotyrosine binding domain of IRS-1. 32D-IR cells, stably overexpressing human insulin receptor, were transfected with wild-type human IRS-1 cDNA (WT) or three mutant IRS-1 cDNAs and analyzed. All the cell lines expressing mutant IRS-1 showed a significant reduction in [3H]thymidine incorporation compared with WT. Upon insulin stimulation, cells expressing G971R showed a 39% decrease (P < 0.005) in phosphatidylinositol 3-kinase (PI 3-kinase) activity, a 43% decrease (P < 0.01) in binding of the 85-kDa regulatory subunit of PI 3-kinase, and a 22% decrease (P < 0.05) in mitogen-activated protein kinase activity compared with those expressing WT. Cells expressing P170R and M209T showed slight but significant decreases in PI 3-kinase activity (17 and 14%, respectively; both P < 0.05) and in binding of p85 (22 and 16%, respectively; both P < 0.05) and a greater decrease in mitogen-activated protein kinase activity (41 and 43%, respectively; both P < 0.005) compared with WT. After insulin stimulation, cells expressing P170R and M209T showed significant decreases in IRS-1 phosphorylation (37 and 42%, respectively; both P < 0.05) and in IRS-1 binding to the insulin receptor (48 and 53%, respectively; P < 0.01) compared with WT. G971R showed no changes in IRS-1 phosphorylation and in IRS-1 binding to the insulin receptor compared with WT. These data suggest that the impaired mitogenic response of P170R and M209T was mainly due to reduced binding to the insulin receptor, whereas the impaired response of G971R was mainly due to reduced association with PI 3-kinase p85.

Animals↗