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Biomedical subjects

Y Hamanaka

Publications and source records attributed to Y Hamanaka.

At least 19 recordsLinked to original sources

Suppression of PI3K/mTOR pathway rescues LLC cells from cell death induced by hypoxia.

Cancer cells in solid tumors are challenged by various microenvironmental stresses, including hypoxia, and cancer cells in hypoxic regions are resistant to current cancer therapies. To investigate the mechanism of resistance to hypoxia in cancer cells, we examined mouse Lewis lung carcinoma (LLC) cells, which died due to necrosis at high density under hypoxic but not under normoxic conditions. Levels of mammalian target of rapamycin (mTOR), a central regulator of cellular energy, are reported to be suppressed in hypoxia. We found that phosphorylation of two molecules downstream to it, ribosomal p70 S6 kinase (S6K) and ribosomal protein S6, was markedly suppressed by hypoxia. Overexpression of the active form of S6K increased the sensitivity of LLC cells to hypoxia. On the other hand, inhibition of PI3K or mTOR dramatically reduced hypoxia-induced cell death under hypoxic conditions. Under hypoxic conditions, blockade of the PI3K or mTOR pathway increased levels of intracellular ATP and delayed decreases in pH and glucose level in culture medium, without affecting the cell cycle.

Adenosine Triphosphate↗

[Evaluation of the proximal stenosis of native coronary vessels after coronary artery bypass grafting].

This study was designed to evaluate proximal native coronary stenosis (PNCS) after coronary artery bypass grafting (CABG). In 36 patients undergoing postoperative coronary arteriography, the PNCS bypassed with internal thoracic artery (ITA), saphenous vein graft (SVG) and right gastroepiploic artery (RGEA) progressed in 9 of 23 vessels (39%), in 15 of 28 vessels (53%), in 4 of 11 vessels (36%), respectively. Stenosis of no grafted coronary vessels progressed in 3 of 26 vessels (11%). Twelve native coronary vessels (9: 99% and 3: 90% stenosis vessels) bypassed with grafts were obstructed. This study confirms that the PNCS progresses significantly by CABG just after the operation and that it tends to progress highly with SVG in comparison with arterial grafts such as ITA or RGEA. Because operative mortality for repeated CABG is approximately twice as high as that for primary CABG, it is important to decide whether early postoperative percutaneous transluminal angioplasty is needed or not, in considering of future graft failure and stenosis progression of the native coronary vessels by CABG.

Aged↗

[Prospective study of systemic inflammatory response syndrome after cardiac surgery as a effective indicator].

This prospective study was designed to elucidate the meaning of systemic inflammatory response syndrome (SIRS), the mechanisms that lead to the protraction of SIRS, and whether SIRS is potentially a simple and effective postoperative indicator or not in patients who are operated on with cardiopulmonary bypass (CPB). We studied the duration of SIRS in 90 patients. Our data showed that 83 (92%) of the 90 patients met 2 or more criteria for SIRS and that significant relationship between the protraction of SIRS and the duration of aortic clamping time, CPB time, operation time, and the risk of postoperative organ damage and complication. Those results suggest that SIRS after cardiac surgery with CPB can be regarded as right criteria and highly valuable indexes of preparatory state of organ dysfunction.

Adult↗

[Clinical evaluation of risk factors for respiratory failure after coronary artery bypass grafting with cardiopulmonary bypass].

The relationship between the duration of postoperative mechanical ventilation and pre-, intra- and just post-operative factors was studied in 48 patients undergoing coronary artery bypass grafting with cardiopulmonary bypass. The patients were divided into 2 groups on the basis of the duration of mechanical ventilation: group A with less than 24 hours (n=35) and group B with more than 24 hours (n=13). Investigation of the perioperative parameters which significantly correlated with the duration of mechanical ventilation revealed that emergency case, cardiac dysfunction, high dose administration of cathecolamine, high left atrial pressure (LAP), low serum albmin, and renal dysfunction after transfer to intensive care unit (ICU) were found to be increased risks of postoperative respiratory failure.

Aged↗

Thymic carcinoids in multiple endocrine neoplasia-type 1.

We report a case of a 45-year-old man with thymic carcinoids in multiple endocrine neoplasm-type 1. Extended total thymectomy was performed through a median sternotomy, and the mediastinal regional lymph nodes and fibroadipose tissue were dissected. Multiple endocrine neoplasm-type 1 related thymic carcinoids are rare and have a poor prognosis. The efficacy of radiotherapy and chemotherapy for prolonging survival is limited, and an aggressive surgical approach with complete excision of the tumor with resection of the peripheral tissues and dissection of the mediastinal lymph nodes seems to be the best available treatment today. We have found that this practice of thymectomy at an early stage in combination with genetic and effective radiological treatment can be effective for multiple endocrine neoplasm-type 1 patients.

Carcinoid Tumor↗

Hand-assisted thoracoscopic resection for anterior mediastinal masses.

We report three cases of anterior mediastinal disease (pericardial cyst, thymoma, and myasthenia gravis) in which we used a hand-assisted method in combination with thoracoscopic resection via an infrasternal approach in order to improve the maneuverability and safety of the operation. This technique combines the advantages of both thoracoscopic and incisional resection. It shows promise of becoming a less invasive operation that can be used to treat certain mediastinal tumors, both malignant and benign.

Humans↗

Video-assisted thoracic lobectomy by the substernal hand-assisted method for a metastatic lung tumor.

In lobectomy by video-assisted thoracic surgery (VATS), the surgeon is required to have experience and a high degree of skill in performing the operation. We applied substernal hand-assisted thoracoscopic lobectomy to remove a metastatic lung tumor that originated from colon cancer in one patient and obtained satisfactory results. This method compensates for a current limitation of VATS lobectomy, namely, the fact that the surgeon cannot touch the lesion. The reported method is safe and useful for thoracoscopic surgery. It can be performed easily, even if the surgeon is not experienced in performing VATS lobectomy.

Colonic Neoplasms↗

The sympathetic nervous system promotes carbon tetrachloride-induced liver cirrhosis in rats by suppressing apoptosis and enhancing the growth kinetics of regenerating hepatocytes.

Norepinephrine is considered to possess potent anti-apoptotic action in regenerating hepatocytes. To clarify the role of the sympathetic nervous system in apoptosis that occurs in chronic liver damage and following the promotion of liver cirrhosis, we studied a carbon tetrachloride (CCl4)-induced liver injury model, using spontaneously hypertensive rats (SHR), Wistar-Kyoto rats (WKY), and chemically sympathectomized WKY. At 24 h after CCl4 administration. acute damage, characterized by vacuolated hepatocytes in the centrilobular zone, was greater in SHR than in WKY. This vacuolated change in WKY hepatocytes was significantly reduced by chemical sympathectomy with 6-hydroxydopamine (6-OHDA). After 48 h, the acute damage was dramatically improved in each animal, without significant differences between the three groups. In chronic damage after weekly repetition of CCl4 treatment for 4 weeks, fibrosis was evident in SHR, while in the other groups there was only scant fibrosis in the centrilobular zone. After 8 weeks' repetition of CCl4, liver cirrhosis was seen only in SHR. The incidence of apoptotic cells in areas of both acute and chronic damage in WKY, detected by terminal deoxynucleotidyl transferase-dUTP nick end labeling, was significantly increased in comparison with that in SHR, and was further increased by 6-OHDA pretreatment. In contrast, there was significantly greater enhancement of the growth of hepatocytes in SHR than in WKY in both acute and chronic damage. Moreover. hepatocyte growth kinetics in WKY was significantly inhibited after sympathectomy in acute injury, as evidenced by immunohistochemistry for proliferating cell nuclear antigen (PCNA). In vitro, the amount of hepatocellular apoptosis induced by transforming growth factor-beta1 was significantly decreased by incubation with norepinephrine. These findings suggest that the anti-apoptotic effect of the sympathetic nervous system increases cell growth kinetics and promotes liver cirrhosis in this animal model.

Animals↗

High-output heart failure caused by a huge renal arteriovenous fistula after nephrectomy: report of a case.

Postnephrectomy renal arteriovenous fistula (AVF) with an aneurysmal lesion is a rare clinical entity that may cause high-output heart failure. In this report, we describe the case of a 68-year-old man who had undergone nephrectomy for renal tuberculosis 43 years previously, in whom an acquired large renal AVF presenting as an aneurysm caused congestive cardiac failure. We also discuss the hemodynamic, hormonogenic (human arterial natriuretic polypeptide; hANP), and radiographic findings before and after surgery for the AVF. The AVF with an aneurysmal lesion was clearly visualized by three-dimensional-computerized tomographic (CT) scanning, and proximal ligation of the renal artery was followed by an uneventful recovery. This procedure can produce good results when a fistula is too large to allow safe embolization and when excision would be hazardous due to inflammation surrounding the fistula.

Aged↗

Expression of tyrosine kinase receptors Tie-1 and Tie-2 in giant cell tumor of the tendon sheath: a possible role in synovial proliferation.

We have recently demonstrated that Tie-1 and Tie-2 are expressed in synovial cells from rheumatoid arthritis (RA). To elucidate the possible involvement of Tie receptors in synovial proliferation, we analyzed their expression by immunostaining in five cases of giant cell tumor of tendon sheath (GCTTS), which represents a proliferating lesion of synovial cells. Strong immunoreactivity for both Tie-1 and Tie-2, regardless of the individual patient's profile, was observed in all cases of GCTTS. Six sets of double immunohistochemical stainings for Tie-1/Tie-2 and fibronectin, CD68, or CD34 were carried out to determine the phenotype of Tie-1 and Tie-2-positive tumor components. In these studies, both Tie-1 and Tie-2 immunoreactivity were widely observed in the fibronectin-positive fibroblastic and the CD68-positive histiocytic mononuclear cells, as well as in the osteoclast-like giant cells. In tumor vasculature, Tie receptors were expressed in the CD34-positive endothelial cells possessing proliferating cell nuclear antigen (PCNA) immunoreactivity. We also evaluated the correlation of Tie-1/Tie-2 expression and proliferating cells in GCTTS by using double staining of Tie-1/Tie-2 together with PCNA. Overexpression of PCNA immunoreactivity was frequently found in Tie receptors-positive cells with no obvious differences in the expression pattern of Tie-1 and Tie-2. These findings suggest the possible involvement of Tie receptors in the pathogenesis of GCTTS other than solely via their involvement in angiogenesis and subsequent vascularization. It was demonstrated that Tie-2 immunoreactivity was restricted to the fibroblastic, but not histiocytic, phenotype in RA synovium, suggesting different regulatory control of Tie-2 expression in GCTTS and RA synovium. Overexpression of Tie receptors in GCTTS may imply a biological role for these receptors in synovial proliferation.

Adult↗

Expression of human beta-defensin 2 (hBD-2) in Helicobacter pylori induced gastritis: antibacterial effect of hBD-2 against Helicobacter pylori.

BACKGROUND: Human beta-defensin 2 (hBD-2) plays a role in the innate defence system at mucosal surfaces. Colonisation of Helicobacter pylori in the stomach is an important pathological factor in gastrointestinal illnesses, including gastritis, peptic ulcer, and gastric adenocarcinoma. AIMS: To evaluate the antibacterial role of hBD-2 against H pylori infection in the gastric mucosa. SUBJECTS: Biopsied gastric mucosa specimens from H pylori positive (n=6) and H pylori negative (n=6) individuals were used. H pylori was determined by the presence of urease activity and microscopic examination. METHODS: The specimens were examined for hBD-2 expression by reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry, and in situ hybridisation. The antibacterial effect of hBD-2 against H pylori was evaluated by the number of colony forming units of H pylori after incubation with 0, 10(-9), 10(-8), 10(-7), 10(-6), or 10(-5) M of hBD-2 peptide. RESULTS: All six H pylori positive specimens expressed a high level of hBD-2 mRNA while hBD-2 mRNA was not detected in the H pylori negative specimens by RT-PCR. Immunohistochemistry using anti-hBD-2 antiserum revealed that hBD-2 was expressed in the surface epithelium of H pylori infected specimens. In gastric specimens obtained after H pylori eradication, hBD-2 immunoreactivity had dramatically decreased. In situ hybridisation confirmed that hBD-2 transcripts were localised in the epithelium of H pylori infected gastric specimens. Incubation with hBD-2 reduced the growth rate of cultured H pylori in a dose dependent manner, and incubation with 10(-5) M hBD-2 completely inhibited the proliferation of H pylori. CONCLUSIONS: H pylori infection induces hBD-2 expression in the human gastric epithelium. hBD-2 inhibited the growth of H pylori in vitro, suggesting that hBD-2 plays an antibacterial role in H pylori induced gastritis.

Aged↗

Mitral valve plasty for mitral regurgitation after blunt chest trauma.

A 21 year-old woman was admitted to our hospital because of chest and back pain after blunt chest trauma. On admission, consciousness was clear and a physical examination showed labored breathing. Her vital signs were stable, but her breathing gradually worsened, and artificial respiration was started. The chest roentgenogram and a subsequent chest computed tomographic scans revealed contusions, hemothorax of the left lung and multiple rib fractures. A transthoracic echocardiography (TTE) revealed normal left ventricular wall motion and mild mitral regurgitation (MR). TTE was carried out repeatedly, and revealed gradually progressive MR and prolapse of the posterior medial leaflet, although there was no congestive heart failure. After her general condition had recovered, surgery was performed. Intraoperative transesophageal echocardiography (TEE) revealed torn chordae at the posterior medial leaflet. The leaflet where the chorda was torn was cut and plicated, and posterior mitral annuloplasty was performed using a prosthetic ring. One month later following discharge, the MR had disappeared on TTE.

Accidents, Traffic↗

Comparison of various biochemical measurements with bone mineral densitometry and quantitative ultrasound for the assessment of vertebral fracture.

We have retrospectively studied postmenopausal elderly Japanese women (n = 288; age range, 60-75 years, 65.8 +/- 4.5 [mean +/- SD]) for the evaluation of biochemical measurements in assessment of bone mass and vertebral fracture, comparing with several bone mineral measurements and quantitative ultrasound (QUS) measurement. Several biochemical parameters [red cell count (RBC), hemoglobin (HB), albumin (ALB), and cholesterol (CHO)] positively correlated with bone mass parameters, but only serum cholesterol showed association with the presence of vertebral fracture. Urinary deoxypyridinoline (DPYD) and n-telopeptide (NTx) showed moderate negative correlation with bone mass parameters, and DPYD showed association with vertebral fracture. All bone mineral measurements (lumbar spine, total body, femoral neck by DXA, calcaneal bone by SXA, distal radius by pQCT) and QUS measurement (os calcaneus by two different QUS machines) showed a higher odds ratio and high chi2 value in logistic regression analysis for association with vertebral fracture. Thus, bone mass measurement is the principal method for assessment of fracture risk, and biochemical measurement should be used for motivation of further bone mass measurement. In biochemical measurements, measurement of serum cholesterol is cheap and easy, and thus might have an advantage, although further study is necessary.

Absorptiometry, Photon↗

[A case of saccular aneurysm of the coronary artery post PTCA].

We experienced a 48-year-old man who was diagnosed as having a saccular aneurym of the coronary artery by CAG after an otherwise uneventful percutaneous transluminal coronary angioplasty (PTCA). At the time of operation, the aneurysm, measured 15 mm, and arose from the 3rd segment of the right coronary artery. Aneurysmal formation after successful PTCA is not rare and is related to the overinflating balloon. It is necessary to evaluate the coronary artery after PTCA by IVUS. There were no symptoms after the operation and he was discharged at 21th postoperative day.

Angioplasty, Balloon, Coronary↗

Induction of human beta-defensin-2 mRNA expression by Helicobacter pylori in human gastric cell line MKN45 cells on cag pathogenicity island.

Helicobacter pylori is an etiological agent of gastritis, peptic ulcer, and gastric cancer. Human beta-defensin-2 (hBD-2) is an antimicrobial peptide which belongs to one of the most important host defense systems against bacterial infection in several epithelial tissues. We studied the effect of H. pylori on the expression of hBD-2 mRNA in MKN45 gastric mucosal cells. H. pylori, but not culture filtrate, increased the hBD-2 mRNA level in MKN45 cells; the inductive effect of H. pylori was not detected with Intestine 407 cells. Among H. pylori strains, strain OHPC0002, which lacks a cag Pathogenicity Island (PAI), did not induce hBD-2 mRNA in MKN45 cells. These results suggested that H. pylori cag PAI is critical for the induction of hBD-2 mRNA in MKN45 cells. Exposure of MKN45 cells to Salmonella typhimurium, S. enteritidis, S. typhi, and S. dublin, but not Escherichia coli ML35, also resulted in induction of hBD-2 mRNA.

Blood Bactericidal Activity↗

Comparison of bone mineral density at various skeletal sites with quantitative ultrasound parameters of the calcaneus for assessment of vertebral fractures.

This study investigated the role of quantitative ultrasound (QUS) for evaluation of fracture risk in comparison with bone mineral density (BMD) measurement. Our subjects were postmenopausal Japanese women (n = 260; age, 67 +/- 6.1 years) who were examined for bone densitometry, QUS, and spinal X-ray examination at our department between 1992 and 1996. The subjects were categorized into three groups by the number of atraumatic fractured vertebrae: NF, no vertebral fractures: F1, one vertebral fracture; F2, two or more vertebral fractures. We compared the measured parameters to determine their association with the number of fractured vertebrae. Differences among groups were compared and analyzed by Student's t-test. Odds ratios were also calculated after age adjustment, as well as age and lumbar or calcaneal parameters. Between NF and F1, lumbar BMD and BMD of the Ward's triangle showed more significant differences than other values, while between F1 and F2, whole-body BMD and QUS parameters showed more significant differences. Lumbar BMD also showed the highest age-adjusted odds ratio in differentiating F1 from NF. Although QUS parameters showed no power to differentiate between NF and F1, these values showed higher odds ratios than other measurements for discriminating between F1 and F2. Adjustment for bone density did not totally abolish the association between QUS parameters and vertebral fracture. Additionally, the combination of lumbar BMD and QUS ("stiffness") clearly showed a high power to discriminate NF from F1 + F2. In conclusion, we showed that QUS measurement is effective in evaluating fracture risk in advanced osteoporosis, while lumbar dual X-ray absorptiometry is effective in evaluating risk in early osteoporosis.

Aged↗

Relationship between skeletal uptake of 99mTc-HMDP and bone mineral density in elderly women.

The relationship between bone mineral density in elderly women and the pattern of skeletal uptake of 99mTc-HMDP, especially in regard to skull uptake, was investigated. The whole-body skeletal uptake (WBSU) and whole-body skeletal tracer distribution patterns were studied in 86 disease-free women on bone scintigraphy with 99mTc-hydroxy-methylene-diphosphonate (HMDP). Bone scans were quantified by setting regions of interest (ROI) and bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry in all patients. WBSU and the skeletal distribution pattern were compared with bone mineral densities of the entire skeleton as well as selected regions. WBSU was high in the elderly and negatively correlated with regional bone mineral densities (r = -0.403 to -0.534). Among the regions, uptake by the skull increased with age more than in other regions in women and had the highest negative correlation with the bone mineral density. The skull uptake correlated negatively with total body BMD (r = -0.583) and with lumbar BMD (r = -0.561, p < 0.0001). Our results show that increased radionuclide uptake in bone scintigraphy, especially skull uptake was associated with decreased bone mineral density in elderly women, so that, increased skull uptake in elderly women would be a scintigraphic sign of post-menopausal or senile osteopenia.

Absorptiometry, Photon↗