Biomedical subjects

Kanji Takahashi

Publications and source records attributed to Kanji Takahashi.

At least 19 recordsLinked to original sources

PubMed2006

[Status of measures against angiography room infection as determined by questionnaire].

Although the cleanliness of the angiography room and that of the operating room have long been equally attended to, the concept of Standard Precautions (including the basic measures and procedures to prevent infection) of the Centers for Disease Control and Prevention (CDC), 1996, as well as the introduction of transmission-based precautions, have been changing to preventive measures that are based on concrete measures. Therefore, a questionnaire was introduced in order to determine the actual status of countermeasures against infection used in the angiography room. The questionnaire was sent to 530 institutions, and 286 responded, a response rate of 54.0%. Its results significantly revealed the following: 1) unexpectedly low recognition of the need and importance for the CDC preventive measures against infection, 2) a considerable number of institutions continuing to perform the conventional preventive measures, 3) problems with education systems on preventive measures, and 4) handwashing, the most important measure against infection, failing to be adequately carried out noticeably among radiological technologists.

Angiography↗

PubMed2006

Design and synthesis of an orally active matrix metalloproteinase inhibitor.

A series of 4-(4-phenoxy)benzoylamino-4-methoxymethyloxymethyl butyric acid hydroxamates, which were derived from l-glutamic acid, were synthesized and evaluated as matrix metalloproteinase inhibitors. Most of the compounds listed in exhibited strong inhibitory activity against MMP-2 and MMP-9, as well as even stronger inhibitory activity against MMP-3, but showed relatively weak inhibition of MMP-1. Structure-activity relationships are discussed.

Administration, Oral↗

PubMed2006

Design and synthesis of novel metalloproteinase inhibitors.

A series of N-benzoyl 4-aminobutyric acid hydroxamate analogs were synthesized and evaluated as matrix metalloproteinase inhibitors. Synthetic work was focused on the chemical modification of the 4-aminobutyric acid part using easily available starting materials. As such, chemical modification was carried out using commercially available starting materials such as 4-aminobutyric acid, (+)- and (-)-malic acid, and D- and L-glutamic acid derivatives. Among the compounds tested, N-[4-(benzofuran-2-yl)benzoyl] 4-amino-4S-hydroxymethylbutyric acid hydroxamates derived from L-glutamic acid demonstrated more potent inhibitory activity against MMP-2 and MMP-9 compared with the corresponding 2S-hydroxy analogs or 3S-hydroxy analogs, respectively, which were derived from (-)-malic acid. Structure-activity relationship study is presented.

Benzofurans↗

PubMed2006

Discovery of a new chemical lead for a matrix metalloproteinase inhibitor.

A series of N-benzoyl gamma-aminobutyric hydroxamic acids were synthesized and evaluated as matrix metalloproteinase inhibitors. First, we focused on chemical modification of the N-benzoyl residue. Introduction of electron-rich para-substituents was effective to increase the inhibitory activity. Especially, some of the analogs with relatively more planar N-acyl residues, such as 10 and 11, demonstrated more potent activity. Second, chemical modification of the gamma-aminobutyric hydroxamic acid moiety was carried out to optimize the three-dimensional arrangement of the two pharmacophores (hydroxamic acid and N-acyl residues). Among the tested, the gamma-aminobutyric hydroxamic acid moiety was found to be the best spacer for connecting the above-mentioned two pharmacophores. Synthesis and structure-activity relationships are discussed.

Drug Design↗

PubMed2006

Clinical monitoring of innate cellular immunity of monocytes/macrophages by tumor necrosis factor alpha productivity in whole blood stimulated by lipopolysaccharide in patients with pancreatic cancer.

OBJECTIVE: The aim of this study was to evaluate the tumor necrosis factor alpha (TNF-alpha) releasing capacity in whole blood stimulated by lipopolysaccharide (LPS) in patients with pancreatic cancer during the perioperative period, and before and after chemotherapy. METHODS: The current study involved a total of 39 patients with pancreatic cancer (PC), who were further divided into a PC-Op group (n = 16, underwent pancreatectomy) and a PC-chemo group (n = 23, received chemotherapy). The control groups consisted of patients with hepatocellular carcinoma (n = 27, HCC group) and with benign diseases (n = 15, control group). Serial changes in TNF-alpha in whole blood stimulated by LPS were compared in various clinical settings. RESULTS: Preoperative TNF-alpha levels in the PC-Op group were significantly lower than those in the HCC and control groups (P = 0.034). The TNF-alpha variable surgical index (s-index) was defined as the ratio of the preoperative TNF-alpha level to postoperative level in the PC-Op and HCC groups. Although the TNF-alpha s-index in the PC-Op group was significantly decreased on postoperative day 1 and recovered on postoperative day 3 (P < 0.002), there were no significant changes in the TNF-alpha s-index in the HCC group. The TNF-alpha variable chemotherapeutic index (c-index) was defined as the ratio of the TNF-alpha level before to that after chemotherapy in the PC-chemo group. The TNF-alpha c-index in all 7 patients was reduced to less than 0.3 until leukopenia appeared. Patients who had an increase in TNF-alpha production (TNF-alpha c-index >1.0) on day 3 or 7 after chemotherapy had significantly better cumulative survival than those with no increase (P < 0.033). CONCLUSIONS: TNF-alpha production stimulated by LPS in the whole blood of patients with pancreatic cancer was low. Surgical stress and depressed immunocompetence might induce such profound decreases. A method of assessing the capability of leukocytes, particularly macrophages, to produce TNF-alpha could be useful for prognostis and for monitoring immunocompetence in patients with pancreatic cancer who have undergone chemotherapy.

Adult↗

PubMed2006

Less morbidity after pancreaticoduodenectomy of patients with pancreatic cancer.

OBJECTIVES: The pancreaticoduodenectomy with extended resection has been frequently performed in patients with pancreatic cancer in Japan. One result of this additional surgical stress may be that postoperative complications in patients with pancreatic cancer are more frequent than in patients with periampullary cancer. METHODS: The 198 patients with pancreatic and periampullary cancer underwent pancreaticoduodenectomy. The operative mortality and morbidity between patients with pancreatic and periampullary cancer were compared, and the risk factors of postoperative complications and in-hospital death were determined. RESULTS: Patients with pancreatic and periampullary cancer made up 52% and 48% of total patients. The duration of surgery and volume of intraoperative blood loss were significantly higher in patients with pancreatic cancer than in patients with periampullary cancer. Additional organ resections were frequently performed in patients with pancreatic cancer. However, significantly lower morbidity rates were observed in patients with pancreatic cancer. Among all complications evaluated, pancreatic fistula and abdominal abscess were found less frequently in patients with pancreatic cancer. Logistic regression analyses showed a positive correlation between periampullary cancer and an increased risk of complications, pancreatic fistula, and abdominal abscess. The in-hospital mortality rate has significantly reduced since 2000. When pancreatic fistula was clinically diagnosed, we immediately started a closed lavage using continuous administration of natural saline at 1000 to 4000 mL/d, after exchange of a nasogastric tube drain. CONCLUSION: Pancreaticoduodenectomy for patients with pancreatic cancer can be a safe procedure in spite of surgical stress. Further surgical strategies will be needed to reduce postoperative complications, especially in patients with periampullary cancer.

Abdominal Abscess↗

PubMed2006

[Bacterial endopathalmitis caused by B streptococcus endocarditis].

BACKGROUND: Bacterial endophthalmitis is often caused by a shift in the primary focus of infection in the patient's body. It is a high risk disease that can cause the loss of sight. Bacterial endophthalmitis with infectious endocarditis is very rare in Japan. CASE: A fifty-three-year-old woman visited our clinic complaining of pain, fever, and visual impairment in her left eye. OBSERVATIONS: The patient's left eye was blind, and showed hapopyon in the anterior chamber. She was admitted to our hospital with a diagnosis of endophthalmitis. Medical treatment with antibiotics was carried out, but the inflammation in her left eye increased. Her left eye was enucleated, and group B Streptococcus was found in the vitreous specimen. Echocardiography demonstrated vegetation of the posterior mitral valve. The diagnosis was made of endophthalmitis due to infectious endocarditis. CONCLUSION: We report an endophthalmitis patient with infectious endocarditis caused by group B streptococcus, based on histopathological findings. This is the first such case reported in Japan.

Endocarditis, Bacterial↗

PubMed2006

[Optical coherence tomographic findings of the retinal pigment epithelium tear in macular area preserving good visual acuity].

PURPOSE: It has been reported that the visual outcome of retinal pigment epithelial tear (RPE tear) in the fovea is worse than that of RPE tear sparing the fovea. We report optical coherence tomography (OCT) findings of 3 cases with RPE tear in the fovea who preserved good visual acuity. PATIENTS: All patients had serous retinal pigment epithelial detachment involving the macula. The RPE was torn and rolled RPE was observed in the fovea. In OCT findings, a fovea was observed on the RPE flap, and visual acuity was preserved after RPE tear repair. CONCLUSION: We considered that preservation of good visual acuity was due to the presence of a fovea on the RPE flap. We could precisely analyze the location of the fovea and RPE tear using OCT.

Aged↗

PubMed2006

[Evaluation of cases of polypoidal choroidal vasculopathy showing classic choroidal neovascularization in their natural course].

BACKGROUND: Some cases of polypoidal choroidal vasculopathy (PCV) in their natural course develop into classic choroidal neovascularization(CNV) as shown by fluorescein angiography (FA) findings. SUBJECTS AND METHOD: We evaluated 8 eyes of 8 PCV patients showing classic CNV by FA findings, using indocyanine green angiography (IA) and optical coherence tomography(OCT). RESULT: All patients showed subretinal grayish exudates, which were considered fibrinous. Five cases were recognized as true subretinal CNV according to IA and OCT findings. The other 3 patients showed polypoidal dilatation with vascular networks by IA, and a moderately reflective mass considered fibrinous over the polypoidal elevation of retinal pigment epithelium (RPE) by OCT. CONCLUSION: Both true CNV and PCV with fibrin are present in PCV patients showing classic CNV. It requires care to determine proper treatment.

Aged↗

PubMed2005

Surgical influence of pancreatectomy on the function and count of circulating dendritic cells in patients with pancreatic cancer.

BACKGROUND: Dendritic cells (DCs) are important for an immune surveillance. Myeloid DCs (DC1) are important for an effective antitumor immune system. The function and count of circulating DC1 (cDC1) in hosts with a malignant tumor would be defective. This study focused on analyzing the immunological features of cDC1 in patients with pancreatic cancer during the perioperative period. MATERIALS AND METHODS: Thirty-two pancreatic cancer patients who underwent pancreatectomy and 18 age-matched healthy individuals as controls were enrolled in this study. The perioperative cDC count, the stimulatory capacity of cDC1 against allogeneic T cells and TGF-beta1 level in the serum were measured. The cDC count was measured at 12 months after the operation. RESULTS: The preoperative cDC1/cDC2 ratio, cDC1 count, and stimulatory capacity of cDC1 were impaired in patients in comparison to controls (P<0.05). The serum TGF-beta1 level was significantly higher in patients than controls (P<0.001). The stimulatory capacity of cDC1 recovered after pancreatectomy (P<0.05). The serum TGF-beta1 level significantly decreased after the operation (P<0.05); however, they were still significantly higher than controls (P<0.05). Although the cDC1/cDC2 ratio and the cDC1 count did not increase after the pancreatectomy, they recovered as the controls' level at 12 months after the pancreatectomy in disease-free patients (P<0.05) and the serum TGF-beta1 level in those patients at 12 months after the operation significantly decreased compared with those at the postoperative period (P<0.05). CONCLUSION: Surgical resection of pancreatic cancer could be associated with improved cDC1 function. When a patient remained disease free, the recovery of cDC1 counts was observed approximately 12 months after pancreatectomy. Further strategy will be needed to improve immune function in patients with pancreatic cancer.

Aged↗

PubMed2005

Novel matrix metalloproteinase inhibitors: generation of lead compounds by the in silico fragment-based approach.

Generation of structurally new matrix metalloproteinase inhibitors was successfully carried out using an in silico technique. In order to identify the small fragment interacting with residues in the S1' pocket of MMP-1 through hydrogen bonds, we performed in silico screening using the LUDI program. As a result, acetyl-L-alanyl-(N-methyl)amide (Ac-L-Ala-NHMe) was selected to link with another fragment, hydroxamic acid that interacted with catalytic zinc. By this approach, the L-glutamic acid derivative 2b was discovered to be a new type of matrix metalloproteinase inhibitor. Further transformation to reduce its peptidic nature and improve activity yielded nonpeptidic lead compounds as inhibitors of MMP-1, -2, -3, and -9.

Magnetic Resonance Spectroscopy↗

PubMed2005

Bilateral orbital tumor as initial presenting sign in human T-cell leukemia virus-1 associated adult T-cell leukemia/lymphoma.

PURPOSE: To report a case of human T-cell leukemia virus type1 (HTLV-1)-associated adult T-cell leukemia/lymphoma (ATLL) whose initial sign was exophthalmos. DESIGN: Case report. METHODS: A 64-year-old Japanese man presented with exophthalmos and choroidal folds of the right eye without general symptoms and received ophthalmologic and laboratory examination, magnetic resonance imaging (MRI), and orbital biopsy. RESULTS: Antibodies against HTLV-1 were extremely high but atypical lymphocytes were not present in the peripheral blood. MRI showed multiple tumorous lesions in both orbits. Orbital biopsy revealed an orbital mass that consisted of atypical lymphocytes originally from T cells and established the diagnosis of lymphoadenopathy type of ATLL. CONCLUSION: Although ocular involvement by ATLL is extremely rare, ATLL can first present in the orbit, and only the results of a biopsy can provide definitive information for its diagnosis.

Antibodies, Viral↗

PubMed2005

Impaired function of circulating dendritic cells in patients with pancreatic cancer.

PURPOSE AND EXPERIMENTAL DESIGN: Dendritic cells (DCs) are important for immune surveillance and play a central role in protection against infection and malignancy. DCs comprise two subsets: DC1 (myeloid DC) and DC2 (lymphoid DC). The aim of this study is to determine whether the number and/or function of circulating DCs were decreased in patients with pancreatic cancer and to evaluate the effects of these changes in patients with locally advanced pancreatic cancer before and after chemoradiotherapy (CRT). We examined the circulating DC number and function using the peripheral blood from 29 patients with pancreatic cancer and 20 healthy control subjects. In patients who underwent CRT (n = 20), blood samples were taken before and after CRT. DCs were tested for the ability to stimulate allogeneic T lymphocytes in mixed leukocyte reaction (MLR). CD4/8, NK activity, PHA, and TGF-beta1 were also measured. RESULTS: The number and allostimulatory activity of circulating DC1s in patients were significantly lower than those in controls. In the patients who underwent CRT, the allostimulatory activity of DC1s at post-CRT was significantly increased as compared to those at pre-CRT. The level of TGF-beta1 was also significantly decreased at post-CRT as compared to pre-CRT. There were no changes in CD4/8, NK activity and proliferative response of T lymphocytes at the peri-CRT period. CONCLUSION: These data indicate that the number and function of circulating DCs were impaired in patients with pancreatic cancer. Chemoradiotherapy, however, improved DC function, which might be related to decreased immunosuppressive cytokine levels.

Aged↗

PubMed2004

Cholecystokinin-mediated suppression of feeding involves the brainstem melanocortin system.

Hypothalamic pro-opiomelanocortin (POMC) neurons help regulate long-term energy stores. POMC neurons are also found in the nucleus tractus solitarius (NTS), a region regulating satiety. We show here that mouse brainstem NTS POMC neurons are activated by cholecystokinin (CCK) and feeding-induced satiety and that activation of the neuronal melanocortin-4 receptor (MC4-R) is required for CCK-induced suppression of feeding; the melanocortin system thus provides a potential substrate for integration of long-term adipostatic and short-term satiety signals.

Animals↗

PubMed2003

Polypoidal choroidal vasculopathy: incidence, demographic features, and clinical characteristics.

OBJECTIVE: To clarify the incidence, demographic features, and clinical characteristics of polypoidal choroidal vasculopathy (PCV) in Japanese patients. METHODS: Consecutive patients with presumed neovascular age-related macular degeneration (AMD) who met the eligibility criteria were examined between January 1, 1999, and October 31, 2001. All patients underwent complete ophthalmologic examination and fluorescein and indocyanine green angiography. RESULTS: Among 471 eyes of 418 patients who met the criteria, 110 eyes (23%) of 100 patients were diagnosed as having PCV and 361 eyes (77%) of 318 patients as having neovascular AMD. Mean age of patients with PCV was 68.4 years, with a male preponderance (63% of patients); involvement was mostly unilateral (90% of patients), and polypoidal vascular lesions were located mainly in the macula (85% of eyes). Retinal manifestations of PCV were characterized by serous macular detachment (52% of eyes), submacular hemorrhage (30% of eyes), and retinal pigment epithelium degeneration (10% of eyes). There were few subretinal fibrovascular proliferations (7% of eyes). Mean visual acuity was 0.31 in eyes with PCV and 0.18 in eyes with AMD. The incidence of severe visual loss (0.2 or worse) was 35% in PCV and 53% in AMD. CONCLUSIONS: The incidence of PCV in Japanese patients is high, and the incidence and demographic features vary in different ethnic groups. The clinical manifestations of PCV and AMD resemble each other; however, PCV is characterized by low incidence of subretinal fibrovascular proliferation, slow progression of vascular abnormality, and minimal association with conventional choroidal neovascularization. These factors seem to lead to a more favorable visual outcome in PCV compared with neovascular AMD.

Age Distribution↗

PubMed2003

[A case of sympathetic ophthalmia secondary to silicone oil granuloma].

BACKGROUND: Sympathetic ophthalmia occurred after removal of silicone oil(SO) from a blind eye with chronic retinal detachment for 20 years. The enucleated eye was examined histopathologically. CASE: A 22-year-old man had been diagnosed with traumatic retinal detachment from blunt trauma to his left eye when he was 3 years old. Pars plana vitrectomy with SO injection was performed at that time, but he lost the sense of light in that eye. Twenty years later, he experienced ocular pain because of absolute glaucoma. Sympathetic ophthalmia has occurred after pars plana vitrectomy with removal of SO and cyclophotocoagulation. The left eye was enucleated and examined histopathologically. RESULT: Histopathological study of the enucleated eye revealed necrosis of the ciliary body due to cyclophotocoagulation. Multiple small round empty spaces which may have been SO droplets were observed in the preretinal membrane, the subretinal space, and the choroidal stroma. In the choroid, diffuse granulomatous inflammation which could be called "silicone oil granuloma" was observed. Calcified drusens were seen at the peripheral fundus. DISCUSSION: An eye containing injected SO for a long period might develop SO granuloma in the choroid and such condition could be the basis for subsequent sympathetic ophthalmia if a second operation with uveal damage was added.

Adult↗

PubMed2002

Polypoidal choroidal vasculopathy: natural history.

PURPOSE: The present study was performed to clarify the long-term natural history of polypoidal choroidal vasculopathy (PCV). DESIGN: Prospective, consecutive observational case series. METHODS: Fourteen eyes of 12 consecutive patients with PCV were prospectively followed in our clinic for at least 2 years without any treatment after a first visit to the clinic between February 1996 and November 1998. All patients underwent complete ophthalmologic examination, color fundus photography, and fluorescein and indocyanine green (ICG) angiography at regular intervals. Inclusion criteria were as follows: eyes had serous and/or hemorrhagic pigment epithelium detachment (PED) and retinal detachment in the posterior pole, and ICG angiography revealed a branching vascular network with polypoidal dilations at the terminals of the network. Exclusion criteria were as follows: other diseases such as exudative age-related macular degeneration, high myopia, angioid streaks, and presumed ocular histoplasmosis syndrome, and patients who previously underwent any ocular surgery. RESULTS: Patients were followed for mean of 39.9 months (range, 24-54 months). PCV was present in 10 (83%) men and two women and in the elderly (mean age 68.1 years), usually unilateral (83%) with vascular lesions located at the macula (93%). The PCV manifested in two patterns, exudative and hemorrhagic. In the exudative pattern, serous PED and retinal detachment were predominant at the macula. The hemorrhagic pattern was characterized by hemorrhagic PED and subretinal hemorrhage at the macula. ICG angiography revealed polypoidal choroidal neovascularization that was changeable in appearance and repeatedly grew and spontaneously regressed, but the vascular network persisted. In some eyes, a collection of small aneurysmal dilations of vessels resembling a cluster of grapes appeared and all of them had marked bleeding and leakage and worse outcome. CONCLUSION: Polypoidal choroidal vasculopathy is a long persistent chronic disease and the patients had a variable course. Fifty percent of the patients had a favorable course. In the remaining half of the patients, the disorder persisted for a long time with occasional repeated bleeding and leakage, resulting in macular degeneration and visual loss. Eyes with a cluster of grapes-like polypoidal dilatations of the vessels had a high risk for severe visual loss.

Aged↗

PubMed2002

Bone marrow-derived stem cells can differentiate into retinal cells in injured rat retina.

It has recently been shown that bone marrow cells can differentiate into various lineage cells including neural cells in vitro and in vivo. We therefore examined whether bone marrow stem cells can differentiate into retinal neural cells in adult rats. PKH-67-labeled stem cell-enriched bone marrow cells (BMCs) were injected into the vitreous space of eyes in which the retinas had been mechanically injured using a hooked needle. Two weeks after the injection of these cells, immunohistochemical examinations were carried out. The stem cell-enriched BMCs had been incorporated and had differentiated into retinal neural cells in the injured retina. The stem cell-enriched BMCs had accumulated mainly in the outer nuclear layer around the injured sites. The incorporated cells expressed glial fibrillary acidic protein, calbindin, rhodopsin, and vimentin. These results raise the possibility that stem cell-enriched BMCs have the ability to differentiate into retinal neural cells, and that the injection of stem cell-enriched BMCs into the retina would help repair damaged retinal cells.

Amacrine Cells↗