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Biomedical subjects

K Kamiya

Publications and source records attributed to K Kamiya.

At least 37 records · Page 2Linked to original sources

Staged vascular reconstruction along with repeatedly performed angiography to prevent ischemic limb loss with Buerger's disease: report of a case.

An aggressive approach to vascular reconstruction should be adopted in patients with Buerger's disease and peripheral ischemia who are often young and otherwise active. A patient with severe Buerger's disease is reported who was treated successfully by complete vascular reconstruction with staged bypass surgery while also performing repeated angiography to preserve the foot function. A 48-year-old man with Buerger's disease presented with necrosis of the foot. Angiography showed occlusion of the right distal external iliac artery and no runoff below the knee. Repeated angiography after performing a lumbar sympathectomy demonstrated patency of the distal portion of the deep femoral artery. Angiography was again performed after a reconstruction of the deep femoral artery and patency of the anterior tibial artery was observed. A staged bypass operation on the tibial artery was therefore able to achieve a prompt healing of both the toe ulcers and plantar wound.

Angiography↗

Flavonoid glucuronides from Helicteres isora.

Five flavonoid glucuronides were obtained from the fruit of Helicteres isora, three of which were previously unknown compounds: isoscutellarein 4'-methyl ether 8-O-beta-D-glucuronide 6"-n-butyl ester. isoscutellarein 4'-methyl ether 8-O-beta-D-glucuronide 2", 4"-disulfate and isoscutellarein 8-O-beta-D-glucuronide 2",4"-disulfate. The structures were determined on the basis of spectroscopy and hydrolysis experiments.

Flavonoids↗

Inflammatory solitary iliac artery aneurysms: a report of two cases.

Inflammatory abdominal aortic aneurysms are associated with atherosclerosis, which are characterized by specific clinical manifestation. We treated two patients with unilateral solitary iliac artery aneurysms with perianeurysmal fibrosis which compressed the ureter resulting in ipsilateral hydronephrosis. After the iliac artery aneurysm was repaired with a prosthetic graft, the hydronephrosis resolved. Microscopically, there was clear evidence of atherosclerosis in one case. There was a characteristic inflammatory reaction around the adventitia in both aneurysms. Localized iliac perianeurysmal fibrosis has not been particularly described. The clinicopathologic similarities between these cases and inflammatory abdominal aortic aneurysms suggest the same pathogenesis.

Aged↗

Exacerbatory mechanism responsible for water immersion stress-induced gastric lesions in aged rats compared with young rats.

1. The present study was designed to investigate whether or not ageing affects the development of water immersion stress-induced gastric lesions in rats. Effects of cetraxate, an anti-ulcer drug, were also examined. 2. Gastric lesions were induced by 6 h water immersion stress in rats. Gastric mucosal blood flow was determined by the hydrogen gas clearance technique and nitric oxide synthase (NOS) activity was measured enzymatically. 3. Early development of gastric lesions was observed in aged rats and exacerbation of gastric lesions was also found. Lowering of gastric mucosal blood flow and reduced NOS activity were observed in aged rats. 4. Cetraxate mitigated the development of gastric lesions in young rats and also increased gastric mucosal blood flow and NOS activity. However, these favourable effects were diminished in aged rats. 5. Decreased NOS activity may be an important exacerbatory factor to the development of gastric lesions in aged rats. 6. Effects of cetraxate differed between young rats and aged rats. 7. These results may explain the refractoriness and drug resistance in gastric ulcers encountered by elderly individuals.

Age Factors↗

Breast carcinomas with immunocytochemical detection of aromatase in fine-needle aspirates: report of three cases.

Three postmenopausal women with breast carcinoma underwent the fine-needle aspiration (FNA) preoperatively, and these specimens were stained by the antiaromatase antibody. We evaluated the identification of the aromatase immunoreactivity in breast carcinoma specimens obtained from both FNA and surgery. FNA specimens showed positive intracellular immunoreactivity of aromatase in these cases. The presence for aromatase in FNA specimens was identified with that in the surgical specimens. To our knowledge, the present cases are the first to report the aromatase staining of FNA specimens. The immunoreactivity of aromatase in FNA specimen may be useful to estimate the effectiveness of new aromatase inhibitors in patients with breast carcinoma. HUM PATHOL 32:348-351.

Aged↗

Identification of the critical spinal arteries with F wave-polysynaptic response complex monitoring: an experimental study.

PURPOSE: The main cause of paraplegia after surgery for descending thoracic aortic aneurysms and thoracoabdominal aortic aneurysms is spinal cord ischemia caused by ligation of the critical spinal arteries that are associated with the great radicular artery (GRA). In this experimental study, we attempted to identify the critical spinal arteries with F wave-polysynaptic response complex (FPC) monitoring. The FPC, which we are using as a monitor of spinal cord ischemia, is myogenic potentials evoked by the tibial nerve stimulation through the anterior horn cells. METHOD: In 18 rabbits, infrarenal lumbar arteries were clamped until there was an FPC amplitude reduction (FPCAR) of at least 60%. The rabbits were classified according to the number of arteries clamped to produce the FPCAR (group A, 1 artery; group B, 2 arteries; group C, 3 arteries). Selective angiography of each lumbar artery was performed in all rabbits. RESULTS: An FPCAR was observed in all 18 rabbits. In all nine rabbits in group A, the FPCAR was caused by the clamping of one particular lumbar artery. The GRA was shown by means of selective angiography to originate directly from this lumbar artery. In the nine rabbits in groups B and C, 11 FPCARs were observed. Of these, nine FPCARs in nine rabbits were caused by the clamping of lumbar arteries that included the vessel from which the GRA originated. CONCLUSION: Temporary clamping of lumbar arteries with FPC monitoring can be used as a means of detecting the critical spinal arteries from which the GRA originates.

Action Potentials↗

Prevention of hepatic and peritoneal metastases by the angiogenesis inhibitor fr-118487 after removal of growing tumor in mice.

We established a mouse rising dbl quote, left (low)primary tumor resection model" in which a transplanted tumor was resected after an orthotopic transplantation of colorectal cancer tissue to estimate the therapeutic effect of an angiogenesis inhibitor on metastasis. The angiogenesis inhibitor FR-118487 is a member of the fumagillin family. Here, 1 mg / kg / day of FR-118487 was subcutaneously administered to nude mice for 1 week, 2 weeks, or 4 weeks through an osmotic pump. Liver metastasis developed in 7 of 9 control mice, 2 of 6 mice that underwent the tumor resection 2 weeks after transplantation (early resection), and in all 7 of the mice that underwent the tumor resection 4 weeks after transplantation (late resection). In the short treatment trial, the FR-118487 administration immediately after the early resection completely inhibited both hepatic and peritoneal metastases, whereas its administration after the late resection had no effect on liver metastasis. In the prolonged treatment trial, inhibitory effects of prolonged treatment with FR-118487 on both hepatic and peritoneal metastases after the late resection were clearly demonstrated. The mice of the resection-alone group all died within 106 days after tumor inoculation, due to metastases of colon carcinoma. In contrast, half of the mice that underwent resection and then received antiangiogenic therapy were alive at the end of the observation period (160 days after transplantation). In conclusion, the combination of surgery and subsequent antiangiogenic therapy may be useful to prevent the distant metastasis of colorectal cancer and to improve the prognosis of patients with colorectal cancer.

Angiogenesis Inhibitors↗

Urokinase receptor and vascular endothelial growth factor are synergistically associated with the liver metastasis of colorectal cancer.

Considering recent findings that the urokinase plasminogen activation (PA) system is involved in invasion and vascular endothelial growth factor (VEGF) is involved in angiogenesis of colorectal cancer, we evaluated these factors in the liver metastasis of primary colorectal cancer. Cancer tissues from 71 colorectal cancer patients were assayed quantitatively for antigen levels of urokinase type plasminogen activator (uPA), uPA receptor (uPAR), and plasminogen activator inhibitor-1 and -2 (PAI-1, PAI-2), and were also assayed immunohistochemically for expression of VEGF protein. Among the PA system factors, both the levels of uPAR and PAI-1 were significantly higher in larger tumors than in smaller ones, and were also significantly higher in tumors that invaded subserosa, serosa or adjacent organs than in mucosal, submucosal tumors or in tumors that invaded the muscle layer. The uPAR levels were significantly higher in tumors with liver metastasis than in those without. VEGF overexpression was significantly more frequent in tumors with lymph node involvement or liver metastasis than in those without. Among the PA system factors, the uPAR levels were significantly higher in tumors with VEGF overexpression and a multivariate analysis revealed that high uPA level and VEGF overexpression were independent risk factors for liver metastasis. The combination of high uPAR level and overexpression of VEGF was associated with the worst prognosis in patients with colorectal cancer. These results suggest that uPAR and VEGF might contribute synergistically to the liver metastasis of colorectal cancer.

Colorectal Neoplasms↗

Effect of combination therapy with matrix metalloproteinase inhibitor MMI-166 and mitomycin C on the growth and liver metastasis of human colon cancer.

Several synthetic inhibitors of matrix metalloproteinases (MMPs) show antitumor, antimetastasis and antiangiogenesis effects in various models. Synergistic effects of combinations with conventional cytotoxic agents were reported previously. In this study, we examined the effects of a new selective MMP inhibitor, MMI-166, on tumor growth, angiogenesis and metastasis in a liver metastatic model of human xenotransplanted colon cancer (TK-4). We also investigated the synergistic effects of MMI-166 and a conventional cytotoxic agent, mitomycin C (MMC), in this model. Mice transplanted orthotopically with TK-4 were divided into 4 groups; a control group (treated with vehicle solution), an MMI-166 group in which MMI-166 was orally administered (p.o.) at a dose of 200 mg / kg, 6 days / week for 5 weeks, an MMC group in which MMC was administered intraperitoneally (i.p.) at a dose of 2 mg / kg / week for 5 weeks, and a combination group (treated with MMI-166 and MMC). MMI-166 did not inhibit transplanted tumor growth, but significantly inhibited liver metastasis compared with the control group and MMC group (P < 0.01). Significant antitumor and antimetastatic effects of the combination therapy were demonstrated. The microvessel density (MVD) detected by immunohistochemical staining with ER-MP12 antibody tended to be lower in the MMI-166 and the combination groups. These results suggest that MMI-166 has potential antimetastatic ability and a synergistic effect with MMC.

Animals↗

Carvedilol: molecular and cellular basis for its multifaceted therapeutic potential.

Carvedilol is a unique cardiovascular drug of multifaceted therapeutic potential. Its major molecular targets recognized to date are membrane adrenoceptors (beta 1, beta 2, and alpha 1), reactive oxygen species, and ion channels (K+ and Ca2+). Carvedilol provides prominent hemodynamic benefits mainly through a balanced adrenoceptor blockade, which causes a reduction in cardiac work in association with peripheral vasodilation. This drug assures remarkable cardiovascular protection through its antiproliferative/atherogenic, antiischemic, antihypertrophic, and antiarrhythmic actions. These actions are a consequence of its potent antioxidant effects, amelioration of glucose/lipid metabolism, modulation of neurohumoral factors, and modulation of cardiac electrophysiologic properties. The usefulness of carvedilol in the treatment of hypertension, ischemic heart disease, and congestive heart failure is based on a combination of hemodynamic benefits and cardiovascular protection.

Adrenergic alpha-Antagonists↗

Open channel block of HERG K(+) channels by vesnarinone.

Vesnarinone, a cardiotonic agent, blocks I(Kr) and, unlike other I(Kr) blockers, produces a frequency-dependent prolongation of action potential duration (APD). To elucidate the mechanisms, we studied the effects of vesnarinone on HERG, the cloned human I(Kr) channel, heterologously expressed in Xenopus laevis oocytes. Vesnarinone caused a concentration-dependent inhibition of HERG currents with an IC(50) value of 17.7 +/- 2.5 microM at 0 mV (n = 6). When HERG was coexpressed with the beta-subunit MiRP1, a similar potency for block was measured (IC(50): 15.0 +/- 3.0 microM at 0 mV, n = 5). Tonic block of the HERG channel current was minimal (<5% at 30 microM, n = 5). The rate of onset of block and the steady-state value for block of current were not significantly different for test potentials ranging from -40 to +40 mV [time constant (tau) = 372 +/- 76 ms at +40 mV, n = 4]. Recovery from block at -60, -90, and -120 mV was not significantly different (tau = 8.5 +/- 1.5 s at -90 mV, n = 4). Vesnarinone produced similar effects on inactivation-removed mutant (G628C/S631C) HERG channels. The IC(50) value was 10.7 +/- 3.7 microM at 0 mV (n = 5), and the onset and recovery from block of current findings were similar to those of wild-type HERG. Amino acids important for the binding of vesnarinone were identified using alanine-scanning mutagenesis of residues believed to line the inner cavity of the HERG channel. Six important residues were identified, including G648, F656, and V659 located in the S6 domain and T623, S624, and V625 located at the base of the pore helix. These residues are similar but not identical to those determined previously for MK-499, an antiarrhythmic drug. In conclusion, vesnarinone preferentially blocks open HERG channels, with little effect on channels in the rested or inactivated state. These actions may contribute to the favorable frequency-dependent prolongation in APD.

Alanine↗

Studies on the constituents of bark of Parameria laevigata Moldenke.

One new trimeric proanthocyanidin, epicatechin-(2beta-->O-->7, 4beta-->6)-epicatechin-(2beta-->O--->7, 4beta-->8)-epicatechin (5) and two new tetrameric proanthocyanidins, epicatechin-(2beta-->O-->7, 4beta-->8)-[epicatechin-(4beta-->6)]-epicatechin-(4beta-->8)-epicatechin, named as parameritannin A-1 (6), and epicatechin-(2beta-->O-->5, 4beta-->6)-[epicatechin-(2beta-->O-->7, 4beta-->8)]-epicatechin-(4beta-->8)-epicatechin, named as parameritannin A-2 (7), have been isolated from the bark of Parameria laevigata Moldenke (Apocynaceae) along with the two known dimers, proanthocyanidin A-2 (1) and proanthocyanidin A-6 (2), and two trimers, cinnamtannin B-1 (3) and aesculitannin B (4). These structures were elucidated by spectral and chemical evidence.

Anthocyanins↗

Age-dependent exposure to radioactive iodine (131I) in the thyroid and total body of newborn, pubertal and adult fischer 344 rats.

Female rats of the Fischer 344 strain at ages of 1, 4 and 9 weeks were exposed to 131I intraperitoneally with activities of 0.38, 1.03 and 3.42 kBq per gram of body weight under the condition of iodine deficiency. The absorbed doses in the thyroid increased linearly depending on the injected activities. Irradiation at 1 week old caused heavier exposure than those at 4 and 9 weeks old by 7.5 and 7.7 times, respectively; however, damage of the thyroid tissue was more obvious in the 4-week-old groups than in the 1-week-old groups. The absorbed doses in the total body were proportional to the square root of the injected activities. The one-week-old groups were exposed more heavily than the 4- and 9-week-old groups by 3.6 and 4.7 times, respectively, shown by the slow excretion of 131I with the values of effective half-life of 131I activity (Teff). An IDD-treatment was not so effective to enhance the 131I absorption in the total body, as in the thyroid. No matter how the iodine concentration in the blood changed, the 1-week-old groups could not react to normalize the level. We drew standard curves, which enabled us to estimate the absorbed doses in the thyroid and the total body in the case of the injected activities of 131I for the newborn, pubertal and adult rats.

Age Factors↗

Acute phase response in toxicity studies. I. Survey of beagle dogs subjected to single-dose toxicity studies.

In the field of routine single-dose toxicity studies, we occasionally meet with transient leukocytosis associated with an increase in fibrinogen in beagle dogs within a few days after treatment with the test article. Only a little is known, however, about the toxicological significance of these changes. However, these changes were thought to belong to the category of "Acute Phase Response, APR," which has been known for a long time in connection with injury, trauma or infection. Aiming at proper understanding of these experiences, we surveyed 25 single-dose toxicity studies (7 intravenous bolus, 5 intravenous infusion, 12 oral and 1 subcutaneous treatment, hereafter referred to simply as i.v. bolus, i.v. infusion, oral and s.c.) in beagle dogs, provided with data from hematological examinations. We set the following criteria as a positive response in the present survey: increases of 50% or more in either or both WBC or fibrinogen compared to the predosing value, transiently from Day 1 to Day 3 of the study. Among 25 studies surveyed, about 1/2 of the studies exhibited increases of 50% or more in either or both fibrinogen or WBC counts compared to the predosing values showing dose-dependency transiently on Day 1 or Day 2. These changes were remarkable after intravenous application. Oral application produced similar effects, although the incidence and severity were low compared to the i.v. routes. Regarding blood chemical and hematological changes other than changes in fibrinogen and WBC counts, there were no essential differences between the groups of studies with and without the changes in fibrinogen and WBC counts. These changes were thought to be characteristic and to have occurred as incidents unrelated to other changes. The reported changes seen in single-dose toxicity studies may belong to the category of APR as the non-specific mechanism of living bodies as stated by Burns et al. (1996).

Acute-Phase Reaction↗

[Effective combination chemotherapy for a recurrent case of carcinoma of the remnant stomach].

A 69-year-old-man underwent distal gastrectomy for gastric carcinoma in 1988. Another gastric carcinoma was discovered in the remnant stomach in March 1995. Total gastrectomy and lymph node dissection were performed. CEA was up and we detected a big left suprarenal mass by abdominal CT. Suprarenalectomy was performed in June 1997. The swelling of lymph nodes was detected by CT and CEA was up to 1,000. Combination chemotherapy with intermittent 5-fluorouracil (5-FU) and low-dose cisplatin (CDDP) was performed. CEA suddenly decreased and lymph node swelling was reduced.

Adenocarcinoma↗

Carvedilol and vesnarinone: new antiarrhythmic approach in heart failure therapy.

Carvedilol and vesnarinone are drugs attracting recent interest in the treatment of chronic heart failure. Electrophysiologic studies have revealed that these drugs cause a moderate prolongation of action potential duration (APD) of ventricular muscles with minimal "reverse frequency-dependence" through different ionic mechanisms. Carvedilol blocks L-type Ca2+ current (ICa), transient outward K+ current (Ito), and delayed rectifier K+ current (IK) preferentially for the rapidly activating component (IKr). Vesnarinone is a selective blocker of IK with a unique drug-channel interaction. From the voltage- and time-dependence of IK inhibition, vesnarinone is considered to bind the IK (mainly IKr) channel during the activated state and unbind during the closed state. These electropharmacologic profiles provide a new approach for the development of an ideal antiarrhythmic drugs in patients with structural heart diseases.

Action Potentials↗

Preservation of donor cornea prevents corneal allograft rejection by inhibiting induction of alloimmunity.

To determine whether preservation of the donor cornea prevents allograft rejection, orthotopic corneal transplantation was performed using corneas preserved in storage medium (Optisol-GS((R))). Donor corneas harvested from C3H/He (H-2(k)) mice and B10.D2 (H-2(d)) mice were preserved in storage medium for 0, 3, 7 and 14 days, and then transplanted into the corneal beds of the recipient BALB/c (H-2(d)) mice. Graft survival was determined clinically and histologically. The expression of major histocompatibility complex (MHC) molecules in the preserved corneas was analysed by immunohistochemistry and Western blotting. Donor-specific cytotoxic T lymphocyte (CTL) and delayed-type hypersensitivity (DTH) responses were assessed 3 weeks after grafting. Active suppression of DTH in the recipient mice was also examined 3 weeks after grafting. The survival of 14 day preserved allografts was significantly higher than that of the non-preserved allografts in both MHC and minor histocompatibility (H) antigens, and minor H only disparate combination. The recipients of the preserved allografts failed to induce both CTL and DTH. The active suppression of DTH was not acquired in these recipients. The expression of donor-derived MHC class I antigens was markedly reduced in the corneas after preservation. Preservation of the donor cornea had a remarkable effect on the prevention of corneal allograft rejection. Since the preserved allografts failed to induce donor-specific CTL and DTH, and active suppression of DTH was not acquired in the recipients, the prevention of allo-rejection is due to a failure of allo-sensitization. These results indicate that the reduction of MHC class I antigens and minor H antigens expression in the preserved grafts induces a failure of allo-sensitization and leads to the high rate of acceptance in corneal allografts.

Animals↗