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Biomedical subjects

Y Nakazawa

Publications and source records attributed to Y Nakazawa.

At least 37 records · Page 2Linked to original sources

Angiographically documented coronary steal phenomenon evoked by the intracoronary infusion of bradykinin.

While studying flow-dependent coronary dilation using a Doppler flow velocity guidewire, total occlusion of a stenosed segment of the left circumflex artery during the intracoronary infusion of bradykinin was angiographically documented. Total occlusion was not demonstrated during intracoronary infusion of bradykinin after angioplasty. This is angiographic confirmation of the coronary steal phenomenon that has been previously described in the field of stress scintigraphy.

Aged↗

Primary sclerosing cholangitis complicated with idiopathic thrombocytopenic purpura.

We present a 66-year-old woman with primary sclerosing cholangitis (PSC) complicated with idiopathic thrombocytopenic purpura (ITP). Both PSC and ITP are considered to reflect an immunological disturbance. However, their coexistence is very rare and to the best of our knowledge this is only the second reported case. In Japan, PSC patients are rarely treated with liver transplantation. Fortunately, the present patient underwent successful hepatic transplantation from a brain-dead donor and simultaneous splenectomy. This case emphasizes the importance of liver transplantation as an effective treatment for primary sclerosing cholangitis.

Aged↗

[Efficacy of radiofrequency catheter ablation in a patient with sinus node reentrant tachycardia].

We performed electrophysiological study and catheter ablation on a 62-year-old patient with supraventricular tachycardia(SVT). This SVT was reproducibly initiated and terminated by atrial stimulation during the electrophysiological testing. The P-wave morphology and atrial activation sequence of intracardiac electrograms were identical to those in normal sinus rhythm. SVT was terminated with carotid sinus massage that increased vagal tone, and for this reason, the reentry circuit of SVT could be localized in sinus node. On the basis of these findings, the SVT was diagnosed as sinus node re-entrant tachycardia and was successfully eliminated by radiofrequency catheter ablation. Radiofrequency catheter ablation would be effective in patients with sinus node reentrant tachycardia refractory to anti-arrhythmic drugs. It should, however, be performed with careful consideration to the influence of the sinus node.

Catheter Ablation↗

Constituents and pharmacological effects of Eucommia and Siberian ginseng.

The bark and leaves of Eucommia ulmoides Oliv (Eucommiaceae) and "Siberian ginseng" (Ezoukogi in Japanese) prepared from the root bark or stem bark of Eleutherococcus senticosus Maxim (Acanthopanax senticosus Harms) have been used as tonic and anti-stress drug. The extracts of Eucommia showed anti-hypertensive, anti-complementary, anti-oxidative, and anti-gastric ulcer effects, and promoting collagen synthesis, accelating granuloma formation, and other pharmacological effects. The Siberian ginseng exhibited anti-fatigue, anti-stress, immuno-enhancing effect, CNS activity, and anti-depressive effect. By now, 40, 28, and 10 compounds have been isolated from Eucommia ulmoides bark, Eucommia ulmoides leaves, and Siberian ginseng, respectively, and their structures were elucidated. Their pharmacological activities were mainly due to lignans and iridoid glycosides.

Adjuvants, Immunologic↗

Retinoic acid is a negative regulator for the differentiation of cord blood-derived human mast cell progenitors.

We examined the effects of retinoids on the human mast cell development using a serum-deprived culture system. When 10-week cultured mast cells derived from CD34(+) cord blood cells were used as target cells, both all-trans retinoic acid (ATRA) and 9-cis RA inhibited the progeny generation under stimulation with stem cell factor (SCF) in a dose-dependent manner (the number of progeny grown by SCF plus RA at 10(-7) mol/L was one tenth of the value obtained by SCF alone). The early steps in mast cell development appear to be less sensitive to RA according to the single CD34(+)c-kit(+) cord blood cell culture study. The optimal concentration of RAs also reduced the histamine concentration in the cultured mast cells (3.00 +/- 0.47 pg per cell in SCF alone, 1.44 +/- 0.18 pg per cell in SCF+ATRA, and 1.41 +/- 0.10 pg per cell in SCF+9-cis RA). RT-PCR analyses showed the expression of RARalpha, RARbeta, RXRalpha, and RXRbeta messenger ribonucleic acid (mRNA) in 10-week cultured mast cells. The addition of an RAR-selective agonist at 10(-10) mol/L to 10(-7) mol/L decreased the number of mast cells grown in SCF, whereas an RXR-selective agonist at up to 10(-8) mol/L was inactive. Among RAR subtype selective retinoids used at 10(-9) mol/L to 10(-7) mol/L, only the RARalpha agonist was equivalent to ATRA at 10(-7) mol/L in its ability to inhibit mast cell growth. Conversely, the addition of excess concentrations of a RARalpha antagonist profoundly counteracted the retinoid-mediated suppressive effects. These results suggest that RA inhibits SCF-dependent differentiation of human mast cell progenitors through a specific receptor. (Blood. 2000;95:2821-2828)

Alitretinoin↗

Clinicopathological analysis of liver allograft biopsies with late centrilobular necrosis: a comparative study in 54 patients.

BACKGROUND: Centrilobular necrosis (CLN) in liver allografts can be a difficult lesion to interpret histologically. Although long recognized in association with developing chronic rejection, recent studies have described the lesion in association with a number of other disease processes. To clarify the histologic features that could allow a specific diagnosis to be made and to determine the outcome in different diagnostic groups, we assessed biopsies from 54 patients with CLN. METHODS: Biopsies were classified as CLN with acute cellular rejection (ACR), CLN with hepatitis, CLN with developing chronic rejection (CR), and CLN of other etiology. Histologic features were assessed and then compared between groups, and clinical outcomes were noted. RESULTS: Discriminating features for the different groups were as follows: CLN and ACR showed bile duct injury, endothelialitis, and acinar congestion. CLN and CR showed severe bile duct injury, bile duct loss, or centrilobular swelling. CLN and hepatitis was often a diagnosis of exclusion, although interface hepatitis was more common in this group. Cases of autoimmune hepatitis usually demonstrated plasma cell predominance in the portal and acinar inflammatory infiltrate. Significantly, there was considerable overlap in the histologic features between the groups, accounting for the diagnostic difficulty. Patients in whom the CLN was associated with CR or vascular complications generally required retransplantation or died, but in the groups with ACR and hepatitis, the outcome was more favorable. CONCLUSIONS: With regard to most liver allograft biopsies showing late CLN, it is possible to make a specific diagnosis despite overlapping histologic features; this allows specific therapy to be instituted. Ultimately this is likely to contribute to improved graft survival.

Acute Disease↗

Fibrous obliterative lesions of veins contribute to progressive fibrosis in chronic liver allograft rejection.

Fibrosis in liver allografts undergoing chronic rejection (CR) is variable and poorly understood. The temporal and spatial relationships of venous, arterial, and biliary lesions were studied to clarify their potential contributions to graft fibrosis. The severity, prevalence, and morphology of intimal lesions of vessels were analyzed and compared with the fibrosis stage. Three groups were found; group 1 (n = 5) with no hepatic vein (HV) lesions, group 2 (n = 5) with HV lesions only, and group 3 with lesions of both HV and portal veins (PV). The earliest lesion to develop, in 71% of grafts, was concentric intimal thickening of small HV. This was significantly more severe and frequent in grafts from group 3. With increasing frequency and severity of small HV sclerosis, fibrosis developed in medium/large veins. The morphology of larger vessel lesions suggested organized thrombus. Centrilobular fibrosis was significantly more severe in group 3 and developed unpredictably and sometimes rapidly. Conversely, portal fibrosis scores were significantly higher in grafts with ductular proliferation and did not correlate with venous lesions. This suggests that in CR, veno-occlusive-like lesions develop commonly in terminal hepatic venules, probably caused by immune-mediated damage. In only a proportion, with increased frequency and severity of the lesions, stasis and thrombosis in portal and larger veins occur and could result in loss of hepatic and portal venous outflow, which leads to ischemia and fibrosis. The stage of fibrosis did not correlate with foam-cell arteriopathy. A second pathway of portal fibrosis occurs in patients with longstanding biliary proliferation.

Adolescent↗

[Pathological examination for liver transplantation].

Liver biopsy plays an important role in the histopathological evaluation of the transplanted liver. In this review, we would like to describe the histological features of various forms of diseases such as allograft rejections occurring in transplanted livers. When severe steatosis is found in the donor liver, transplantation is contraindicated. Ischemic liver damage caused by transplant hypoperfusion is called harvesting or re-perfusion injury and characterized by the histological features of liver-cell ballooning, centrilobular cholestasis, and apoptosis of hepatocytes. Acute rejection occurring more commonly in the first few weeks after transplantation is defined by the diagnostic triad of portal inflammatory infiltrates, endothelialitis, and bile duct damage, whereas chronic rejection is characterized by the presence of ductopenia and foam cell arteriopathy. Obstruction of the hepatic artery leads to severe centrilobular necrosis of the allograft. Among viral infections affecting the allografts, cytomegalovirus infection occurs most frequently, and typical intranuclear or cytoplasmic inclusions are hallmarks of the infection. Post-transplantation lymphoproliferative disorders are closely associated with Epstein-Barr virus infection. Therapeutic drugs such as azathioprine and cyclosporin A also cause liver damage, but specific histological features of drug-induced injury have not yet been clarified. Recurrence of original diseases such as viral hepatitis or malignant tumors is also evaluated by the liver biopsy.

Acute Disease↗

Living-related liver transplantation for patients with fulminant and subfulminant hepatic failure.

The prognosis for patients with fulminant (FHF) or subfulminant hepatic failure (SFHF) has improved since the introduction of liver transplantation. However, the death rate of patients awaiting liver transplantation is high, possibly because of the difficulty in obtaining grafts in a timely manner, given the relative shortage of cadaveric donors. Between June 1990 and June 1999, 106 patients underwent living-related liver transplantation (LRLT) at Shinshu University Hospital. Among them, 8 patients had FHF and 6 had SFHF; these 14 patients are the subjects of this report. The graft volumes (GV) ranged from 231 mL to 625 mL, corresponding to 35% to 105% of the recipients' standard liver volume (SLV). The postoperative courses of all donors were uneventful. Following liver transplantation, all grafts functioned favorably, with normalization of serum total bilirubin within 3 to 5 days and normalization of coagulation profiles within 4 to 7 days. Thirteen of the 14 recipients are still alive. The actuarial 6-month, 1-year, and 5-year survival rates were 100%, 90%, and 90%, respectively. In the present study, when the ratio of the GV to the recipient's SLV was more than 35%, the graft was able to support the patient's metabolic demand after liver transplantation for FHF or SFHF. Because of the urgent nature of liver transplantation in this clinical condition, concerns over informed consent may be even greater than for elective LRLT. Nevertheless, the high success rate and low donor risk may justify this option for pediatric patients, as well as for a limited population of adult patients suffering from FHF or SFHF.

Adolescent↗

Zinc-dependent activation of the plasma kinin-forming cascade by aggregated beta amyloid protein.

Beta Amyloid proteins (Abeta) of 38, 40, and 42 amino acids long were assessed for their ability to activate the plasma kinin-forming cascade in vitro. Incubation with a mixture of Factor XII (Hageman Factor), prekallikrein, and high-molecular-weight kininogen (HK) led to conversion of prekallikrein to kallikrein that was dependent on zinc ion. No activation occurred if Factor XII was omitted. There was rapid generation of bradykinin equal to the molar HK input indicating complete cleavage. Incubation of aggregated Abeta with diluted human plasma also led to prekallikrein activation and HK cleavage. Activation of the cascade by Abeta (1-38) was dependent upon its preincubation time in buffer, suggesting that aggregation of Abeta is required, and studies with Abeta (1-40) revealed time-dependent aggregation by microscopy and augmented zinc-dependent binding of both Factor XII and HK to aggregated Abeta. These data demonstrate that aggregated Abeta can bind and activate proenzymes of the plasma kinin-forming cascade in a zinc-dependent reaction to release bradykinin and is of sufficient potency to do so at physiologic concentrations of each protein and in the presence of naturally occurring protease inhibitors.

Amyloid beta-Peptides↗

Clinicopathologic findings of recurrent primary sclerosing cholangitis after orthotopic liver transplantation.

Whether primary sclerosing cholangitis (PSC) occurs after orthotopic liver transplantation is controversial, largely because the pre-transplant diagnosis of PSC is based on nonspecific radiological and histological findings. We reviewed clinical, radiological, and histological records of 53 patients who underwent liver transplantation for PSC between 1985 and 1998. Three patients with patent hepatic arteries and no evidence of chronic rejection had radiological and histological findings that may have been due to recurrent PSC. Bile duct stricturing in these patients proved permanent and progressive and affected both the quality of life and graft survival. The first patient, who is 110 months after transplantation, has had repeated episodes of cholangitis for the last year. The second patient underwent excision of a strictured hepatic duct 45 months after transplantation and was ultimately retransplanted 95 months after initial transplantation. The third patient underwent left hemihepatectomy of an atrophied lobe 50 months after transplantation. Although the patient population assessed in this study is limited, putative recurrent PSC in the allografts has led either to graft loss or to clinically significant hepatobiliary complications of the graft.

Adolescent↗

First case of cadaveric liver transplantation in Japan.

The first case of liver transplantation from a brain-dead donor in Japan is described. The recipient was a 43-year-old man with familial amyloid polyneuropathy who manifested various neuropathic symptoms and autonomic dysfunction at the time of transplantation. The graft had three arteries, for which a single trunk was created at the back table. A side-to-side cavacaval anastomosis was performed as an outflow reconstruction. To avoid portal congestion, a temporary shunt between the right posterior branch of the portal vein and the vena cava was constructed, instead of a venovenous bypass. The graft preservation time was 7.2 h and the operation time was 12.2 h. Although sufficient blood flow in the hepatic artery, portal vein, and hepatic vein was confirmed intra- and postoperatively, using Doppler ultrasound, transient graft dysfunction was observed immediately after surgery, but there was spontaneous improvement. The patient was discharged 100 days after transplantation.

Adult↗

The role of laparoscopic US and laparoscopic US-guided aspiration biopsy in the diagnosis of multicentric hepatocellular carcinoma.

BACKGROUND: Detection of small hepatocellular carcinomas has become possible with improvements in various diagnostic imaging techniques. However, intraoperative US can detect lesions not visualized by any preoperative imaging study in which case it is difficult to determine whether the lesion is a hepatocellular carcinoma. METHODS: Nodular lesions detected by laparoscopic US in 186 patients with hepatocellular carcinoma were examined and we evaluated the diagnostic ability of laparoscopic US to detect multicentric hepatocellular carcinoma. RESULTS: One hundred thirty-four new nodular lesions were detected by laparoscopic US in 64 (34.4%) of 186 patients. Aspiration biopsy under laparoscopic US guidance was performed on the 134 nodules, and 28 nodules in 23 (12.4%) of the 186 patients were histologically diagnosed as hepatocellular carcinoma. Of these 23 patients, 18 had been diagnosed with solitary hepatocellular carcinoma before laparoscopic US. One hundred six of the newly detected lesions were initially diagnosed as noncarcinomatous nodules, but the diagnosis of 10 of these lesions was changed to hepatocellular carcinoma during follow-up that was as long as 96 months. CONCLUSIONS: Laparoscopic US is useful in the initial diagnosis of hepatocellular carcinoma and impacts treatment selection by more accurately defining the presence of multicentric hepatocellular carcinomas.

Biopsy, Needle↗

Prognosis of small hepatocellular carcinoma after laparoscopic ethanol injection.

BACKGROUND: Most patients with hepatocellular carcinoma have underlying cirrhosis, and this impairment of liver function makes hepatectomy difficult, prompting the use of other modalities such as transcatheter arterial embolization and percutaneous ethanol injection. METHODS: Laparoscopic ethanol injection was performed in 48 previously untreated patients with hepatocellular carcinoma smaller than 2 cm in diameter. Long-term survival was evaluated. RESULTS: In 12 patients, hepatocellular carcinoma was not detected by trans-cutaneous ultrasonography but could be demonstrated by laparoscopic ultrasonography. Laparoscopic ethanol injection did not cause serious complications in any patient. The mean hospital stay after ethanol injection was 8.6 days (4 to 15 days). The cumulative survival rate was 86.7% at 3 years and 60.0% at 5 years. According to the Child-Pugh classification, the cumulative survival rate at 5 years was 87.9% for class A, 65.7% for class B, and 28.6% for class C. CONCLUSIONS: The long-term prognosis for patients with small hepatocellular carcinoma treated solely by laparoscopic ethanol injection is satisfactory but still dependent on underlying liver function.

Adult↗

Interaction of factor XII and high molecular weight kininogen with cytokeratin 1 and gC1qR of vascular endothelial cells and with aggregated Abeta protein of Alzheimer's disease.

High molecular weight kininogen (HK) attaches to endothelial cells at separate sites on the heavy and light chains by a process which requires 15-50 microM zinc. Previously identified binding proteins include gClqR, cytokeratin 1, and the urokinase plasminogen activator receptor (U-par), however, their relative contribution to binding are not yet clarified. We have purified the binding proteins by affinity chromatography, in the presence of zinc ion, and identified cytokeratin 1 and gC1qR by amino acid sequencing of an internal peptide and by immunoblot as heavy chain and light chain binding proteins, respectively. Antibody to cytokeratin 1 inhibited HK binding to endothelial cells by 30%, antibody to gClqR inhibited HK binding to endothelial cells by 72%, and a mixture of both inhibited binding by 86%. The binding and activation of the proteins of the kinin-forming cascade along the cell surface is zinc-dependent. Similarly, proteins of the plasma kinin-forming cascade can be activated by binding to aggregated A(beta) protein of Alzheimer's disease. Activation of the cascade using purified proteins or upon addition of Abeta to plasma requires aggregation of A(beta) and the reactions are zinc-dependent. In plasma, HK is cleaved and bradykinin is liberated. The data demonstrate that aggregated A(beta) can bind and activate proenzymes of the plasma kinin-forming cascade to release bradykinin and these reactions are dependent on zinc ion.

Amyloid beta-Peptides↗

Effects of cyclopiazonic acid on contraction and intracellular Ca2+ in oesophageal striated muscle of normotensive and spontaneously hypertensive rats.

1. The effects of cyclopiazonic acid (CPA), a selective inhibitor of sarcoplasmic reticulum (SR) Ca2+-ATPase, on twitch contraction and on the resting state of tension and intracellular Ca2+ level ([Ca2+]i) of the oesophageal striated muscle of stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar Kyoto rats (WKY) were compared. 2. CPA (10 micronM) augmented the twitch contraction of oesophageal striated muscle preparations from both SHRSP and WKY, reducing the rate of relaxation (-dT/dt), and thus resulting in the prolongation of the time to 80% relaxation. The effect was significantly smaller in the SHRSP preparations. 3. In the resting state, CPA caused a sustained elevation of [Ca2+]i. The elevation was greater in the WKY preparations. Tension development accompanied by the elevation was observed in WKY preparations, but not in SHRSP preparations. 4. The sustained elevation of [Ca2+]i induced by CPA was eliminated by the removal of extracellular Ca2+. Both the elevated [Ca2+]i and tension in the preparations from WKY were reduced by flufenamic acid (100 micronM), mefenamic acid (100 micronM), lanthanum (La3+, 100 micronM), gadolinium (Gd3+, 100 micronM) and SK&F 96365 (100 micronM) but not by verapamil (10 micronM). 5. Thapsigargin (3 micronM), another SR Ca2+-ATPase inhibitor, produced similar effects on basal tension to those of CPA, although it reduced the amplitude of twitch contraction. 6. These results suggest that in the rat oesophageal striated muscle, (1) CPA extends the sequestrating time of Ca2+ into the SR, (2) CPA induces a Ca2+ influx mediated through verapamil-insensitive pathways, possibly nonselective cation channels, and (3) the mechanism of [Ca2+](i) modulation due to CPA-sensitive SR Ca2+-ATPase is deteriorated in the oesophageal striated muscle from SHRSP as compared with WKY preparations.

Animals↗