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Biomedical subjects

Yasuhiro Suzuki

Publications and source records attributed to Yasuhiro Suzuki.

At least 109 records · Page 6Linked to original sources

Immunohistochemical evaluation of hormone receptor for routine practice of breast cancer: highly sensitive procedures significantly contribute to the correlation with biochemical assays.

Immunohistochemical evaluation of hormone receptors for breast cancer has been performed parallel to biochemical assays. Recently, immunohistochemistry has tended to substitute the biochemical method in Japan. To clarify the factors concerned and problems to be resolved, we reviewed our evaluation system for hormone receptors by immunohistochemistry from 1990. A total of 861 breast cancer samples were examined by immunohistochemistry and biochemistry. In 3 main periods, phase 1 (1990-1993), phase 2 (1995-1998), and phase 3 (1999-2001), increasing sensitivity of the immunohistochemical method was provided by commercially available staining systems and shown to range from 83.6% (phase 1) to 92.0% (phase 3). The highly sensitive procedures of the antigen retrieval and peroxidase-conjugated polymer method are main contributing factors. The authors examined how these procedures influenced the distribution of positive cell population; concordance rate, including sensitivity and specificity; cutoff points; and evaluation categories. The correlation between biochemistry and immunohistochemistry was extensively studied in the 1980s and 1990s. In reference to the progress achieved in the United States and United Kingdom to control the current situation in Japan, it should be recognized that recently developed, highly sensitive procedures boost the immunoreactivity, which will affect the basic factors for technical validation.

Breast Neoplasms↗

Forensic discrimination of lead-tin solder based on the trace impurity analysis by ICP-AES.

Trace impurities in lead-tin solders were determined using inductively coupled plasma atomic emission spectrometry (ICP-AES) for the forensic discrimination of solder samples from different origins by a comparison of the concentration for each element. After about 10 mg of sample was accurately measured and taken into a glass tube, 1 ml of HNO3 was added. The tube was capped and heated at 80 degrees C for 10 min. After cooling to the room temperature, 1 ml of HCl and 2 ml of purified water were added. It was then agitated until the sample was completely dissolved, followed by dilution to 10 ml. Five elements (Sb, Bi, Cu, As and Ag) in this solution were determined by ICP-AES. The observed values for these elements in the NIST Standard Reference Material 1131 showed good agreement with the certified ones. Eighteen kinds of solder samples could be distinguished from each other, since all of the pairs among these samples provided remarkable difference in the concentration of the trace elements. The copper concentration should have been excluded from the comparison when it increased after melting by a soldering iron made of copper.

Journal Article↗

Duplex Doppler ultrasonography of subclavian steal syndrome--three case reports.

Three cases of subclavian steal syndrome were detected by duplex Doppler ultrasonography. Ultrasonography demonstrated retrograde flow with to-and-fro pattern in the right vertebral artery in two cases, and reflux with diastolic flow deceleration in one case. Interventional treatment with stenting was successfully performed in two cases and conservative treatment was given in one case. Ultrasonography is an effective noninvasive method for the evaluation of the vertebral artery, and should become a routine part of cerebrovascular examinations.

Aged↗

Venous infarction resulting from sacrifice of a bridging vein during clipping of a cerebral aneurysm: preoperative evaluation using three-dimensional computed tomography angiography--case report.

A 67-year-old woman presented with a ruptured aneurysm of the left internal carotid artery bifurcation. Three-dimensional computed tomography angiography (3D-CTA) demonstrated the first segment of the basal vein of Rosenthal passing in front of the internal carotid artery and the anastomosis with the cavernous sinus, the partially hypoplastic second segment, and the superficial sylvian vein entering the lateral side of the sphenoparietal sinus. Dissection of the sylvian fissure toward the distal direction enabled transfer of the superficial sylvian vein to the temporal side, but the bridging vein had to be sacrificed to secure adequate operating space. Postoperative CT demonstrated hemorrhagic infarction at the left caudate head and surrounding region. Postoperative venous infarction is not an uncommon complication of various approaches. 3D-CTA can provide important information about the venous anatomy indispensable for avoiding postoperative venous infarction.

Aged↗

Heterogeneous gene alterations in primary breast cancer contribute to discordance between primary and asynchronous metastatic/recurrent sites: HER2 gene amplification and p53 mutation.

The aim of the present study was to clarify differences in genetic events between primary breast cancers and asynchronous metastatic/recurrent lesions, by examining HER2 gene amplification and p53 mutation. The subjects were 44 breast cancer patients with asynchronous metastasis or recurrence. Synchronous metastases were excluded. HER2 overexpression and gene amplification were examined using immunohistochemistry and fluorescent in situ hybridization (FISH). P53 point mutation was examined by immunohistochemistry, laser-captured microdissection, PCR-single-strand conformation polymorphism, and a direct sequencing method. Immunohistochemistry showed that, for HER2, p53, ER and PgR, discordance rates between primary and recurrent tumor were 2 (4.5%), 1 (2.3%), 7 (15.9%) and 10 (22.7%), respectively. Two primary tumors with discordant HER2 overexpression were composed of at least two populations of carcinoma cells, with and without HER2 gene amplification. Distribution of HER2 gene amplification was consistent with protein overexpression. Corresponding recurrent tumors consisted of carcinoma cells without HER2 gene amplification. Of 6 recurrent tumors in which the primary carcinoma had a p53 point mutation, 3 tumors had identical mutations, 1 tumor had a different point mutation, and 2 tumors had no mutation. It was suspected that the latter 3 recurrent tumors comprised a minor component of the primary tumor. In the present study, we examined a large series of asynchronous recurrent tumors. A limited number of these tumors showed discordance between primary and recurrent tumors. Detailed observations revealed that cell populations present in recurrent tumors were also present in the primary tumors, although they comprised a minor component of the primary tumor. Heterogeneity of the primary tumor apparently contributed to discordance.

Breast Neoplasms↗

[Cardiovascular complications in oncology patients].

Cancer patients receiving chemotherapy have an increased risk of developing cardiovascular complications even if they have normal hearts, and the risk is greater if there is known history of heart disease. Various clinical cardiac complications that have been reported are arrhythmias, cardiomyopathy, vaso-occlusion or vasospasm resulting in angina or myocardial infarction. It is well know that cardiovascular complications in oncology patients is caused by anthracyclines. The trastuzumab as the new treatment option for the metastatic breast cancer may be associated with the development of a clinically significant cardiotoxicity. We described and reviewed the cardiotoxicity in oncology patients.

Antineoplastic Agents↗

[A case presenting with hydrocephalus and posterior fossa subdural effusion].

We report a case of hydrocephalus due to posterior cranial fossa subdural effusion. The patient was a 4-year-old boy, presenting headache and nausea, with a medical history of viral meningitis 2 months before. Cerebrospinal fluid provided no evidence of infection, and symptoms caused by increased intracranial pressure gradually deteriorated, although glycerol infusion was effective temporarily. Computed tomography revealed marked ventriculomegaly with subdural effusion in the right posterior cranial fossa. The subarachnoid space in the posterior fossa was very tight, and the cerebellum and brain stem were compressed anteriorly. Magnetic resonance imaging demonstrated stenosis of the aqueduct and foramens of Luschka and Magendie. The cerebeller tonsil was dislocated inferiorly, indicating impending herniation, so an emergency operation was performed. Ventriculoperitoneal shunt was undertaken after implantation of an Ommaya reservoir for the posterior fossa subdural effusion. The patient's postoperative course was uneventful, and the symptoms were improved. Although hydrocephalus and subdural effusion following viral meningitis is rare, neuroimaging studies such as CT and MRI should be examined when a young child suffers from symptoms of increased intracranial pressure.

Catheters, Indwelling↗

[An autopsy case of cryptococcal meningoencephalitis: correlation of MRI and pathologic findings].

A comparative study of MRI and pathology was performed on a case of cryptococcal meningoencephalitis. An 11-year-old female presented with confusion and vomiting. On admission, CSF examination revealed spherical fungal cells with mild pleocytosis, decreased glucose and elevated protein level. MRI showed multiple punctate lesions in the basal ganglia with high intensity on T2-weighted image, while enhanced MRI revealed diffuse meningeal involvement. Post-mortem examination disclosed that the T2-weighted lesions found in the basal ganglia were aggregated small cystic lesions consisting of a cryptococcal invasion of Virchow-Robin spaces, termed "soap bubble lesions", characteristic findings of cryptococcal meningoencephalitis. Thus MRI findings of the basal ganglia and meninges may help to diagnose cryptococcal meningoencephalitis.

Brain↗

[Pathophysiology of hypercalcemia and the therapeutic role of bisphosphonates].

When hypercalcemia is found in patients with malignancy, it is necessary to measure circulating parathyroid hormone -related peptide concentrations and to search for bone lesions. Because accelerated bone resorption mainly contributes to malignancy associated hypercalcemia, bisphosphonates, which strongly suppress osteoclastic resorption, is most effective. Upon administration of bisphosphonates, serum calcium begins to fall within two days, reaches the bottom after one week, and the effects disappear after two or three weeks. In case of need to lower the serum calcium concentration rapidly, calcitonin should be used at the same time.

English Abstract↗

Characterization of a holin (HolNU3-1) in methicillin-resistant Staphylococcus aureus host.

The gene encoding holin protein HolNU3-1 from a clinical isolate of methicillin-resistant Staphylococcus aureus (MRSA) NU3-1 was cloned and expressed in S. aureus RN4220. HolNU3-1 encoded by the holNU3-1 gene, which is located upstream of the deleted endolysin gene, was functional. Expression of the holNU3-1 gene induced a decrease in culture turbidity and formation of translucent (empty ghost) cells in S. aureus. We found heterogeneity of the holin genes and diversity of the two-component lysis system, which consists of holin and endolysin, in MRSA hosts. We suggest that this diversity is important in the identification of the evolution of clinical isolates of S. aureus.

Amino Acid Sequence↗

Immunopathogenesis of cerebral toxoplasmosis.

Interferon (IFN)-gamma is an absolute requirement for resistance against acute acquired infection with Toxoplasma gondii and development of toxoplasmic encephalitis (TE) during the late stage of infection. Multiple populations of both T and non-T cells are important sources of IFN-gamma in resistance. In the absence of IFN-gamma-producing non-T cells, T cells cannot prevent TE. Interleukin-12, Bcl-3, NF-kappaB(2), and CD40-CD40L ligand interaction are important for up-regulation of IFN-gamma production. T. gondii infects a variety of host cells, and IFN-gamma-mediated immune responses control the parasite in both phagocytic and nonphagocytic cells through at least five different mechanisms, most likely depending on the types of cells responding to IFN-gamma. Such effector functions involve production of NO by iNOS, tryptophan degradation by the enzyme IDO (indolamine 2,3-dioxygenase), unidentified mechanism(s) mediated by 47- to 48-kDa proteins encoded by an IFN-gamma responsive gene family, limiting the availability of intracellular iron to the parasite, and production of reactive oxygen intermediates.

Animals↗

Genistein, an isoflavone included in soy, inhibits thrombotic vessel occlusion in the mouse femoral artery and in vitro platelet aggregation.

Diet can be the most important factor that influences risks for cardiovascular diseases. Genistein included in soy is one candidate that may benefit the cardiovascular system. Here, we investigated the inhibitory effects of genistein on thrombotic vessel occlusion in the mouse femoral artery using a photochemical reaction, and in vitro platelet aggregation in whole blood measured by single platelet counting. Genistein (10 mg/kg), intravenously administered 10 min before the rose bengal injection, significantly prolonged the thrombotic occlusion time from 6.1+/-0.4 to 8.4+/-0.8 min (P<0.05). Genistein at doses higher than 30 microM significantly (P<0.01) inhibited in vitro platelet aggregation induced by collagen (1 and 3 microg/ml). When 10 mg/kg genistein was intravenously administered, ex vivo platelet aggregation induced by collagen (1 and 3 microg/ml) was significantly suppressed (P<0.01). In conclusion, genistein prevented in vivo thrombogenesis and suppressed in vitro platelet aggregation. These results suggest that dietary supplementation of soy may prevent the progression of thrombosis and atherosclerosis.

Analysis of Variance↗

Effects of various forms of surfactant protein C on tidal volume in ventilated immature newborn rabbits.

Surfactant protein (SP)-C is characterized by alpha-helix structure and palmitoyl groups attached to two cysteine residues. We examined the function of palmitoylation and dimerization in promotion of tidal volume in immature newborn rabbits. Reconstituted surfactants were made from a mixture of synthetic phospholipids and porcine SP-B (basic mixture) by adding various forms of SP-Cs: normal SP-C isolated from porcine lungs and monomeric or dimeric forms of SP-C. These latter two were isolated from patients with pulmonary alveolar proteinosis and were less palmitoylated. Animals were ventilated at an inspiratory pressure of 25 cmH2O. Median tidal volumes were <2 ml/kg in nontreated controls, 7.7 ml/kg in animals receiving the basic mixture without SP-C, and >18 ml/kg in animals treated with reconstituted surfactants containing 3% normal or 2% dimeric SP-C (P < 0.05 vs. basic mixture). The physiological effect of basic mixture was not improved by monomeric SP-C. We conclude that palmitoyl groups are important for the physiological effects of SP-C and that the dimeric form also improves physiological effects.

Animals↗

SM-20220, a Na(+)/H(+) exchanger inhibitor: effects on ischemic brain damage through edema and neutrophil accumulation in a rat middle cerebral artery occlusion model.

The Na(+)/H(+) exchanger (NHE) is activated during ischemia-reperfusion in an effort to restore intracellular pH to normal levels. The NHE is recognized to exist as a distinct protein in the plasma membranes of a variety of cells. We investigated the pharmacological effects of a Na(+)/H(+) exchanger inhibitor, SM-20220 (N-(aminoiminomethyl)-1-methyl-1-H-indole-2-carboxamide methanesulfonate), on ischemic brain damage, edema and neutrophil accumulation at 72 h after middle cerebral artery (MCA) occlusion in a rat MCA occlusion model. SM-20220 was intravenously administered as a bolus injection immediately after occlusion, followed by a continuous infusion over 2.5 h. At 72 h after occlusion, the infract area was measured using hematoxylin-eosin staining and, using the same slices, neutrophils in the brain were immuno-stained with anti-myeloperoxidase (n=11). In a separate study, rat behavior was scored and scaled, and brains removed for the determination of water content by the dry-weight method. SM-20220 significantly (P<0.05) attenuated cerebral infarct volume, water content, and the neutrophil accumulation at 72 h after the MCA occlusion, and ameliorated neurological deficits. SM-20220, an NHE inhibitor prevented the progress of cerebral ischemic damage and edema following MCA occlusion in rats though a possible mechanism that may be due to the inhibition of neutrophil accumulation. The NHE in neutrophils may enhance the progress of cerebral damage following cerebral ischemia-reperfusion.

Amides↗

Host resistance in the brain against Toxoplasma gondii.

Interferon (IFN)-gamma-dependent, cell-mediated immunity plays the major role in resistance against development of toxoplasmic encephalitis (TE). Humoral immunity also participates in controlling Toxoplasma gondii in the brain. Resistance is operative under collaboration among T and B cells, IFN-gamma-producing non-T cells, microglia, astrocytes, and dendritic cells. A number of cytokines, including IFN-gamma, mediate interactions between these cells and activation of effector cells that prevent intracellular replication of the parasite. The L(d) gene confers resistance against development of TE in mice. In humans, the HLA-DQ1 and -DQ3 genes are involved in regulating the resistance and susceptibility. Since these genes are a part of the major histocompatibility complex, which regulates the immune responses, the regulation of the responses by these genes appears to be important for determining host resistance to this disease. Strains of T. gondii also affect development of TE. Genotypes of the parasite may be an important factor for determining development of TE.

Animals↗

In vivo nitric oxide transfer of a physiological NO carrier, dinitrosyl dithiolato iron complex, to target complex.

Dinitrosyl dithiolato iron complex (DNIC) has been identified as an endogenous NO carrier, yet in vivo mechanisms of NO donation remain undefined. Transnitrosylation, in which a coordinated NO group is transferred to another metal complex, has been observed in transition-metal-nitrosyl chemistry. In this study, we used three kinds of iron dithiocarbamate complexes (Fe-DTCs) as NO acceptors to elucidate in vivo transnitrosylation of diglutathionyl dinitrosyl iron complex [DNIC-(GS)(2)]. Fe-DTCs were administered to mice after the injection of DNIC-(GS)(2) and electron paramagnetic resonance (EPR) spectra were measured both in the resected organs and in the upper abdomen of living mice. The spectral feature gradually changed from an initial DNIC-(GS)(2) signal to mononitrosyl iron dithiocarbamate one, suggesting that NO-Fe-DTC was formed through in vivo reaction of DNIC-(GS)(2) with Fe-DTC. The spectral results in in vitro and in vivo systems indicate that NO-Fe-DTCs can be formed not only by the transfer of coordinated NO-group(s) in DNIC-(GS)(2) but also by the abstraction of Fe-NO group in DNIC-(GS)(2) by free DTC ligands. Transnitrosylation proceeded more rapidly in blood than in liver and kidney; and more efficiently in kidney than in liver. Further, the ability to accept NO from DNIC was dependent on water-solubility of Fe-DTCs. Thus, in vivo transnitrosylation from DNIC to exogenous iron complex could be observed and this reaction was influenced by biological constituents and properties of iron complex. These results demonstrate that the transnitrosylation from DNIC to intrinsic NO acceptors like metalloproteins has a probable significance in in vivo NO transfer process.

Animals↗

Hypercholesterolemia induces regression in neointimal thickening due to apoptosis of vascular smooth muscle cells in the hamster endothelial injury model.

OBJECTIVE: Hypercholesterolemia is a major risk factor in the development of atherosclerosis. Although matrix metalloproteinase may play a key role in plaque rupture, apoptosis of vascular smooth muscle cells (VSMCs), which is induced by cholesterol and its oxides may also contribute to instability and rupture of plaque. Thus, we investigated the roles of hypercholesterolemia in vascular remodeling following endothelial injury in the hamster femoral artery. METHODS: The endothelium was injured by photochemical reaction between green light and the photosensitizer dye, Rose Bengal. Photochemical reaction is routinely used in our laboratory to produce endothelial injury without mechanical stretching in experimental animals. RESULTS: In normocholesterolemic hamsters (NCH), neointimal thickening gradually progressed within a 3-week observation period after endothelial injury. In hypercholesterolemic hamsters (HCH), neointimal thickening gradually progressed until the second week after endothelial injury. In contrast, at the third week neointimal thickening regressed and was thinner than that at the second week. There was no significant difference in in vivo proliferation of VSMCs detected by in vivo BrdU uptake between HCH and NCH. Apoptotic cells in the neointima and the media were observed in HCH from 2 to 4 weeks after endothelial injury, but not in NCH. At 2 weeks after endothelial injury, the numbers of TUNEL-positive VSMCs in HCH were significantly higher than those in NCH (neointima; 1.2 +/- 0.3 vs. 0.3 +/- 0.1%, P<0.05, media; 2.9 +/- 0.6 vs. 0.6 +/- 0.2%, P<0.01). Cholesterol deposit, which is detected by oil red O staining was observed in a neointimal or medial area in HCH, but not in NCH. CONCLUSIONS: These findings suggest that hypercholesterolemia with endothelial injury may induce VSMC apoptosis, followed by the regression of neointimal thickening, further hypercholesteremia might play a role in inducing plaque rupture through apoptosis of VSMC.

Animals↗

Retinoids in liver fibrosis and cancer.

Pathobiological functions and metabolism of retinoids (vitamin A and its derivatives) in liver fibrosis and hepatocellular carcinoma (HCC) are discussed in the present review. Retinoic acid (RA, active metabolite) exacerbates liver fibrosis that is not accompanied by hepatic necroinflammation, in which RA acts directly on hepatic stellate cells (HSCs); RA enhances plasminogen activator/plasmin levels and thereby induces proteolytic activation of latent transforming growth factor-beta (TGF-beta), a strong fibrogenic cytokine, resulting in enhanced collagen production. We have developed a protease inhibitor, camostat mesilate, that suppresses TGF-beta activation and thereby inhibits the transformation of HSCs, leading to reduced matrix production by the cells. The compound is effective not only in preventing but also in reducing hepatic fibrosis in rats when administered orally. HCC is refractory to RA due to its local depletion in the tumors and also due to malfunction of its nuclear receptor, retinoid X receptor-alpha (RXRalpha) Oral supplementation of a synthetic retinoid named acyclic retinoid led to the disappearance of serum lectin-reactive alpha-fetoprotein (AFP-L3) and subsequently suppressed posttherapeutic recurrence of HCC in cirrhotic patients. These results suggest eradication of AFP-L3-producing latent malignant clones from the liver by the retinoid. We propose the concept of "clonal deletion" therapy for cancer chemoprevention, a new category of cancer chemotherapy.

Animals↗