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Biomedical subjects

T Nomoto

Publications and source records attributed to T Nomoto.

At least 19 recordsLinked to original sources

Sparse and wavy hair: a new model for hypoplasia of hair follicle and mammary glands on rat chromosome 17.

Mutant animals in the skin and hair have been used to identify important genes in biomedical research. We describe a new mutant rat, sparse and wavy hair (swh), that spontaneously arose in a colony of inbred WTC rats. The mutant phenotype was characterized by sparse and wavy hair, which was most prominent at age 3-4 weeks, and was inherited in an autosomal recessive manner. The swh/swh rats showed impaired gain of body weight, and their hair follicles were reduced both in number and size, associated with hypoplasia of the sebaceous glands and the subcutaneous fat tissue. Female swh/swh rats were unable to suckle their offspring. Their mammary glands were hypoplastic, and differentiation of mammary epithelial and myoepithelial cells was impaired. Linkage analysis of 579 backcross rats localized the swh locus to a .35-cM region between D17Rat131 and D17Rat50 in the distal end of rat Chr 17. The swh locus spanned the 3.7-Mb genomic region where 24 genes have been mapped and corresponded to the centromere region of the mouse Chr 2 or the region of the human Chr 10p11.1-p14. None of the genes or loci described in mouse or human hair and skin diseases mapped to these regions. These findings suggest that the rat swh is a novel mutation associated with impaired development of the skin appendages, such as hair follicles, sebaceous glands, and mammary glands, and will provide an experimental model to clarify a gene and mechanisms for development of skin appendages.

Animals↗

Spontaneous healing of chyle leakage after lymphangiography.

We report a 34-year-old man with the complication of chylous ascites after retroperitoneal lymphadenectomy that was refractory to various conservative therapies. Because surgical treatment for chylous ascites was considered, lymphangiography was performed to identify the area of leakage of chyle, after which the chylous ascites spontaneously healed.

Adult↗

[Early and late results and problems of coronary artery bypass grafting in patients over 80-year-old].

This study evaluated the validity of coronary artery bypass grafting (CABG) in patients over 80-year-old investigating the early and late result, patient's opinion to the surgery, and change of activities of daily living scale. From July 1993 to September 2002, consecutive 94 patients over 80-year-old were performed CABG in our institution. The group consisted of 43 female patients, and mean age of 82.6 years. Of these patients, 36 were operated conventional CABG (CABG group) and 58 patients were operated with off-pump CABG (OPCAB) group. There were no significant differences between 2 groups in preoperative characteristics except for anemia and hypertension. Operative results, including mortality, number of distal anastomoses, operative time had no significant differences between 2 groups. But maximum CK-MB fraction was higher in CABG group. There were 4 operative deaths, indicating operative mortality was 4.3%. Late results showed overall survival rate at 3 years was 81.1% and cardiac event free survival rate at 3 years was 88.8%. Questionnaire revealed over 80% patients were satisfied with the surgery but less than 40% patients felt activities of daily living (ADL) scale was improved. Operative results of CABG in octogenarians were satisfied, but more efforts to remain patient's high ADL were mandatory.

Activities of Daily Living↗

Adeno-associated virus vector-mediated interleukin-10 gene transfer inhibits atherosclerosis in apolipoprotein E-deficient mice.

Inflammation is a major contributor to atherosclerosis by its effects on arterial wall biology and lipoprotein metabolism. Interleukin-10 (IL-10) is an anti-inflammatory cytokine that may modulate the atherosclerotic disease process. We investigated the effects of adeno-associated virus (AAV) vector-mediated gene transfer of IL-10 on atherogenesis in apolipoprotein E (ApoE)-deficient mice. A murine myoblast cell line, C2C12, transduced with AAV encoding murine IL-10 (AAV2-mIL10) secreted substantial amounts of IL-10 into conditioned medium. The production of monocyte chemoattractant protein-1 (MCP-1) by the murine macrophage cell line, J774, was significantly inhibited by conditioned medium from AAV2-mIL10-transduced C2C12 cells. ApoE-deficient mice were injected with AAV5-mIL10 into their anterior tibial muscle at 8 weeks of age. The expression of MCP-1 in the vascular wall of the ascending aorta and serum MCP-1 concentration were decreased in AAV5-mIL10-transduced mice compared with AAV5-LacZ-transduced mice. Oil red-O staining of the ascending aorta revealed that IL-10 gene transfer resulted in a 31% reduction in plaque surface area. Serum cholesterol concentrations were also significantly reduced in AAV5-mIL10-transduced mice. To understand the cholesterol-lowering mechanism of IL-10, we measured the cellular cholesterol level in HepG2 cells, resulting in its significant decrease by the addition of IL-10 in a dose-dependent manner. Furthermore, IL-10 suppressed HMG-CoA reductase expression in the HepG2 cells. These observations suggest that intramuscular injection of AAV5-mIL10 into ApoE-deficient mice inhibits atherogenesis through anti-inflammatory and cholesterol-lowering effects.

Adenoviridae↗

Development and characterization of an antisense-mediated prepackaging cell line for adeno-associated virus vector production.

One of the limitations of recombinant adeno-associated virus (rAAV) vector systems for gene therapy applications has been the difficulty in producing the vector in sufficient quantity for adequate evaluation. Since the AAV Rep proteins are cytotoxic, it is not easy to establish stable cell lines that express them constitutively. We describe a novel 293-derived prepackaging cell line which constitutively expresses the antisense rep/cap driven by a loxP-flanked CMV promoter. This cell line was converted into a packaging cell line expressing Rep/Cap for rAAV vector production through adenovirus-mediated introduction of a Cre recombinase gene. Without the introduction of the Cre recombinase gene, the cell line was shown to produce neither Rep nor Cap. rAAV vector was produced (1 x 10(9) genome copies/3.5-cm dish) 4 days after the transduction with Cre-expression adenovirus vector together with transfection of AAV vector plasmid. We further showed that the addition of Cap-expression adenovirus vector caused a 10-fold increase in the yield of rAAV vector. This system is also capable of producing rAAV as a transfection-free system by using a small amount of rAAV instead of vector plasmid.

Adenoviridae↗

Linkage disequilibrium pattern in the L-myc gene in Italian and Japanese non-small-cell lung-cancer patients.

Italian and Japanese non-small-cell lung-cancer patients were genotyped for an intragenic L-myc EcoRI restriction site polymorphism previously reported to be associated with lung-tumor prognosis in Asian populations but not in Caucasians. Screening of the L-myc sequence in Italian samples allowed identification of 2 additional 3'-UTR SNPs, located 2.3-3.0 kb from the EcoRI polymorphism, but no coding polymorphism was found. No significant association was found between any of the 3 SNPs and lung-tumor prognosis in Italian patients, consistent with the reported difference between Caucasian and Asian populations. Moreover, the newly discovered polymorphisms in the Italian group were not present in Japanese patients. Significant LD between EcoRI and the 2 other SNPs was detected in the Italian population, whereas no significant LD between the 2 3'-UTR markers was detected despite their close proximity (0.7 kb). Thus, the disparate conclusions about the role of L-myc polymorphism in tumor prognosis among different populations may rest in population-specific LD between the functional gene and the L-myc polymorphism.

Adenocarcinoma↗

Initial effects of the left ventricular repair by plication may not last long in a rat ischemic cardiomyopathy model.

BACKGROUND: Long term effects of left ventricle (LV) repair surgery (LVR) for ischemic cardiomyopathy are not well understood. METHODS AND RESULTS: Sixty-nine rats developed ischemic cardiomyopathy with large akinetic LV area 4 weeks after the left anterior descending artery was ligated. In a second surgery 4 weeks later, 33 rats underwent LVR by plication of the akinetic LV area (LVR group), and 36 underwent rethoracotomy alone (sham group). No medication was used in either group. All rats survived the second surgery. LV end-diastolic dimension as measured by echocardiography, LV fractional shortening, and the maximal end-systolic pressure-volume relationship (E(max)) as calculated from the data by catheter-tipped manometer and echocardiography improved in the LVR group after the second surgery, but LV end-diastolic dimension and E(max) gradually deteriorated as time passed. LV end-diastolic pressure improved 1 week after LVR but rose significantly 4 weeks after LVR. Brain natriuretic peptide mRNA was lower in the LVR group than in the sham group 1 week after LVR but not 4 weeks postoperatively. CONCLUSIONS: Initial improvement in LV function and neurohormonal status after LVR did not last for 4 weeks in this rat model when untreated medically. The mechanism of deterioration should be elucidated to improve long-term results of LVR.

Animals↗

Alternative splicing isoforms of hippostasin (PRSS20/KLK11) in prostate cancer cell lines.

BACKGROUND: Hippostasin is a kallikrein-like protease (PRSS20/KLK11), which is expressed preferentially in the hippocampus and prostate. We have reported that alternative splicing variants of human hippostasin are regulated in a tissue-specific manner. Brain-type hippostasin consists of 250 amino acids including a typical signal sequence, and is expressed in the brain and prostate. The prostate-type hippostasin, which has 32 extra amino acids at the N-terminal end, is expressed only in the prostate. METHODS: We analyzed the expression and localization of hippostasin in normal prostate tissue, BPH tissue, and prostate cancer cell lines. We performed northern blotting, in situ hybridization, immunohistochemistry, and RT-PCR. RESULTS: Hippostasin mRNA is expressed preferentially in the normal prostate and weakly in the testis. It was detected in prostate secretory epithelium. Hippostasin protein was localized in the prostate secretory epithelium, and western blotting showed that hippostasin was present in semen. All tested prostate cancer cell lines, including PSA-negative cell lines, expressed hippostasin. Interestingly, all the prostate cancer cell lines expressed only brain-type but not prostate-type hippostasin, while normal prostate and BPH expressed both types of hippostasin CONCLUSIONS: Our results suggest the possibility that hippostasin may be a useful marker by which prostate cancer and BPH can be distinguished.

Biomarkers, Tumor↗

Surgery for acute type A aortic dissection using retrograde cerebral perfusion.

OBJECTIVE: We reviewed the surgical management of acute type A aortic dissection between 1989 and 1998. METHODS: Subjects were 28 consecutive patients (mean age: 61.8 +/- 10.7 years) with acute type A aortic dissection were studied. The mean duration between aortic dissection onset and surgery was 17.5 +/- 17.0 hours. In surgery, aortic pathology and flow patterns in dissected aortic channels were evaluated using transesophageal and epiaortic echo. Simple, safe combination of profound hypothermic circulatory arrest with retrograde cerebral perfusion and open aortic anastomosis was used for brain protection. Hypothermic circulatory arrest was 46.9 +/- 24.8 minutes. Aortic repair consisted in ascending aortic replacement in 5 patients, with hemiarch repair in 17, and total arch repair in 6. Intimal tears were resected in all but 2 patients. Concomitantly resuspension of the aortic valve was done in 9 and aortic root replacement in 2. RESULTS: No operative (30-day) deaths occurred, although 2 died from unrelated hepatic failure during hospitalization or late-stage pancreatic cancer in the late stage. In cerebral sequellae, 1 patient suffered a stroke and 2 patients developed temporary neurologic dysfunction. CONCLUSION: Our experience demonstrated that the simplified conjunction of hypothermic circulatory arrest with retrograde cerebral perfusion and open aortic anastomosis, associated with real-time assessment by transesophageal and epiaortic echo, is safe and useful during emergency aortic repair for acute type A aortic dissection.

Acute Disease↗

Aortic arch repairs through three different approaches.

OBJECTIVES: The outcome of aortic arch repairs by means of three different approaches between 1990 and January 2000 was reviewed. METHODS: In total 39 patients aged 71.5+/-6.2 years were operated on. The three different surgical approaches depended on the anatomical positions of the aneurysms and on their proximal or distal extension; a median approach was employed in 23 patients, whereas a left postero-lateral approach was used in eight patients. More recently, in eight cases a left antero-lateral approach was applied. All patients underwent open aortic anastomosis without any clamp on or around the aortic arch. During the procedure, the brain was protected by a combination of profound hypothermic circulatory arrest and several techniques of retrograde cerebral perfusion. RESULTS: Permanent cerebral dysfunction occurred in four patients: two in the median approach and two in the left postero-lateral approach. There were two hospital deaths (5.3%) and six late deaths, all of which belonged either to the median group or to the postero-lateral group. The antero-lateral approach did not produce any cerebral dysfunction, early death, or late death. CONCLUSIONS: The outcome of aortic arch repairs using profound hypothermic circulatory arrest and variable techniques of retrograde cerebral perfusion, by means of three different approaches, was satisfactory. Of the three approaches, the antero-lateral approach can be employed easily, whether aneurysms extend proximally or distally.

Aged↗

Primary racemose hemangioma of the bronchial artery.

A 44-year-old woman was admitted to our hospital for repeated hemoptysis. Selective angiography of the bilateral bronchial arteries showed them to be enlarged and convoluted, and revealed shunts between the bronchial and pulmonary arteries. The patient was diagnosed as having racemose hemangioma of the bronchial artery. Although embolization of the bronchial artery with gelatin sponges was performed, hemoptysis emerged again about one year later. Finally, segmentectomy of the right lower lung was performed and primary racemose hemangioma of the bronchial artery was histopathologically confirmed.

Adult↗

[Surgery for thoracic aortic aneurysms involving the distal arch through a left thoracotomy].

Surgical outcome for thoracic aortic aneurysms involving the distal arch via a left thoracotomy using retrograde cerebral perfusion combined with profound hypothermic circulatory arrest was reviewed. Twelve patients with a atherosclerotic aortic aneurysm between 1994 and 1997 were involved. A proximal aortic anastomosis was made by means of an open aortic technique. For the first four patients, oxygenated arterial blood from cardiopulmonary bypass was perfused retrogradely through a venous cannula positioned into the right atrium. In the last eight cases, venous blood provided by a low-flow perfusion of the lower half body via the femoral artery, which was still oxygen-saturated, was circulated passively in the brain in a retrograde fashion with the descending aorta clamped. Prosthetic replacement was done between the distal arch and the proximal descending aorta in 6 patients and from the distal arch to the entire descending thoracic aorta in 6 patients. The median duration of hypothermic circulatory arrest and continuous retrograde cerebral perfusion was 36 minutes and 33 minutes respectively. The overall outcome was satisfactory without early mortality--all patients survived, although an octogenarian died of respiratory failure 1 year postoperatively. Another octogenarian with a ruptured aneurysm developed delay of meaningful consciousness, and other two patients with a severely atherosclerotic aneurysm suffered permanent neurological dysfunction (stroke) presumably due to an embolic episode. The safe and simple combination of profound hypothermic circulatory arrest, retrograde cerebral perfusion, and open aortic anastomosis protects the brain adequately and produces satisfactory results in surgery for aortic aneurysms involving the distal arch through a left thoracotomy.

Aged↗

[Combined surgery for valvular and ischemic heart disease].

Combined coronary artery bypass (CAB) and valve surgery is one of the most challenging surgical procedures, but the operative results have improved over the years. We discuss several important points in combined surgery. The first point is cardioplegia, which should be perfect in such complex operations. Sufficient antegrade cold blood cardioplegia should be used in combined CAB and mitral valve surgery. Continuous retrograde cardioplegia is required in CAB and aortic valve surgery. The second point is the prosthesis and grafts. A mechanical prosthesis and arterial grafts should be used in younger patients, while a bioprosthesis and vein grafts with a left internal thoracic artery graft should be used in older ones. Finally, the choice of valve repair or replacement must be considered in mitral surgery with CAB. Valve repair is the choice in patients with mitral prolapse due to chordal rupture, because a perfect repair can be achieved using a well-known procedure. In cases in which repair appears difficult, replacement must be carried out as soon as possible. In mitral valve replacement the continuity between the papillary muscles and the mitral ring must be preserved for good left ventricular performance.

Aortic Valve↗

Population-based mapping of pulmonary adenoma susceptibility 1 locus.

Pulmonary adenoma susceptibility 1 (Pas1), the major locus affecting inherited predisposition to lung tumor development in mice, maps near the Kras2 gene. We previously reported a significant association between a KRAS2/RsaI polymorphism and the risk and prognosis of lung adenocarcinoma (ADCA) in the Italian population. In the present case-control study, we examined 269 lung ADCA patients, 121 squamous cell lung carcinoma patients, and 632 healthy individuals (general population controls) in the Japanese population with genetic markers spanning approximately 1200 kb in the KRAS2 region. Allele-specific oligonucleotide hybridization revealed the same KRAS2/RsaI polymorphism associated with risk and prognosis as in Italian lung ADCA patients; the polymorphism was significantly associated with clinical stage (P < 0.001) and survival rate (log rank = 0.0014), confirming the mapping of PAS1 and pointing to the role of this locus in human lung cancer.

Adenocarcinoma↗

beta-blocker therapy in patients after aortic valve replacement for aortic regurgitation.

BACKGROUND: beta-blocker therapy for dilated or ischemic cardiomyopathy is now an accepted and effective treatment. However, little is known about its efficacy in patients with postoperative impaired left ventricular function. This retrospective study was designed to assess the effects of beta-blocker therapy in patients after aortic valve replacement (AVR) for aortic regurgitation (AR). METHODS: A total of 59 patients who underwent AVR for chronic AR were assigned to four groups. Twelve patients were treated with both ACE inhibitors and beta-blockers, 12 patients with only ACE inhibitors, eight patients with only beta-blockers, and 27 patients without beta-blockers or ACE inhibitors. A postoperative echocardiographic study was performed one year after surgery. RESULTS: The heart rate was significantly reduced in patients with beta-blockers despite the use of ACE inhibitors after surgery. Postoperative left ventricular volume was more significantly decreased in beta patients than in non-beta patients despite the use of ACE inhibitors. There were also significant reductions in left ventricular mass index in ACE+beta patients compared to ACE+non-beta patients. However, there were no significant differences in NYHA functional class and survival rate between beta patients and non-beta patients. CONCLUSIONS: beta-blocker therapy may improve cardiac performance by reducing cardiac volume and mass in patients with impaired LV function after AVR for AR.

Adrenergic beta-Antagonists↗