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Biomedical subjects

N Yamazaki

Publications and source records attributed to N Yamazaki.

At least 19 recordsLinked to original sources

Muir-torre syndrome with intriguing squamous lesions: a case report and review of the literature.

Muir-Torre syndrome (MTS) is an autosomal, dominantly inherited disorder characterized by sebaceous neoplasms and visceral malignancies. We report a 56-year-old woman who underwent resections of extraocular sebaceous carcinoma, sebaceous epithelioma, actinic keratosis, and keratoacanthoma (KA)-like squamous cell carcinoma (SCC) with venous invasion metachronously over a 9-year period. Because of the mixed, unusual features of the skin lesions, and her history of endometrial and colorectal cancers that had been resected 12 years and 1 year, respectively, before the present event, a possible diagnosis of Muir-Torre syndrome was suggested. Immunohistochemical studies revealed loss of hMSH2 expression in all the cutaneous lesions including the actinic keratosis, and also in the endometrial and colorectal cancers. This patient presented with intriguing squamous lesions including keratoacanthoma-like squamous cell carcinoma that showed venous invasion and actinic keratosis, and associated loss of hMSH2 expression, in addition to the sebaceous neoplasms typical of Muir-Torre syndrome.

Adenocarcinoma, Sebaceous↗

Alpha 2 integrin +807 polymorphism in drug-induced gingival overgrowth.

Alpha2 integrin on fibroblasts is reported to play an important role in the induction of drug-induced gingival overgrowth, which is characterized by excessive accumulation of type I collagen in gingival connective tissue. Silent polymorphism 807 T/C within the alpha2 integrin gene is associated with high/low alpha2 integrin expression. The aim of this study was to test the hypothesis that expression of alpha2 integrin 807 T/C polymorphism correlates with drug-induced gingival overgrowth. A case-control study comparing 136 subjects taking calcium channel blockers (72 with vs. 64 without drug-induced gingival overgrowth) demonstrated that the frequency of the +807 C allele was significantly higher in the case group than in the controls (odds ratio, 3.61; 95% confidence interval, 2.14 - 6.10; P < 0.05). The present findings suggest that the alpha2 +807 C allele is one of the genetic risk factors for drug-induced gingival overgrowth.

Adolescent↗

Morphology of microphase separated domains in rod-coil copolymer melts.

We investigate the morphology of microphase separated domains in diblock copolymers where each chain consists of a stiff rod block and a flexible coil block. A simplified phenomenological model system is introduced, which is coarse-grained in terms of the local concentration difference between the two blocks and the local director field of the rod part. Computer simulations of this set of time-evolution equations in two dimensions show in the weak segregation regime that the elastic energy in the rod-block rich domains affects drastically the structures of microphase separated domains. A coil-to-rod transition is incorporated into the model system to examine the elastic and anisotropic effects. The effects of the external electric field are also investigated to control the domain morphology.

Journal Article↗

Primary cutaneous aspergillosis caused by Aspergillus ustus following reduced-intensity stem cell transplantation.

A 19-year-old woman with myelodysplastic syndrome underwent reduced-intensity stem cell transplantation [RIST: (cladribine 0.11 mg/kg for 6 days, busulfan 4 mg/kg for 2 days, and rabbit antithymocyte globulin)] from her one HLA-mismatched mother. Prophylaxis against graft-versus-host disease (GVHD) was performed with cyclosporine A (CSA) alone. Severe acute GVHD in the skin, gut, and liver developed concurrently with stable engraftment, and methylprednisolone was administered (1-2 mg/kg per day, then pulse therapy with 1 g/day for 3 days) until day 40 of transplant, when a necrotic lesion of 10 mm in diameter appeared on the right cheek. The initial skin biopsy of the affected area showed a nonspecific inflammatory change. Routine X-ray and computed tomography examinations of the sinuses, chest, and abdomen disclosed no particular abnormalities. Despite intensive antibiotic therapy, the lesion rapidly extended to form an ulcer. A second biopsy specimen obtained from the lesion showed massive septa hyphae, suggesting mold infection. Although we immediately started amphotericin B, she died of multiorgan failure on day 68. Postmortem DNA sequence analysis of the specimen using the polymerase chain reaction identified Aspergillus ustus. Although this is an extremely rare complication after transplantation, this case highlights that we should pay more attention to primary cutaneous aspergillosis in severely immunosuppressed patients.

Adult↗

Radioiodination of glycoprotein-conjugated liposomes by using the Bolton-Hunter reagent and biodistribution in tumor-bearing mice.

We have developed a suitable radiolabeling method for our new type of glycoprotein-liposome conjugate (GCL), in order to investigate its potential utility as a drug carrier that can target the cellular functions of carbohydrate-binding proteins. In order to obtain radiolabeled GCL with high labeling efficiency, we introduced p-hydroxyphenylpropyl groups into the liposome membrane through the amine moiety of a constitutive phospholipid, dipalmitoylphosphatidylethanolamine (DPPE) by using Bolton-Hunter reagent (BHR). Radioiodination of the introduced tyrosyl groups was performed by the Chloramine-T method. The labeling efficiency of the BHR-treated liposome conjugate was high in comparison with that of the BHR-untreated liposome conjugate. An in vitro inhibition study showed that the binding affinity of 125I-labeled BHR-treated GCL (125I-F3S-BH) with lectin was twice as high as that of untreated conjugate (125I-F3S). The biodistribution of 125I-F3S-BH in mice was considerably different from that of 125I-F3S. 125I-F3S-BH was more rapidly taken up by the liver and was more rapidly excreted from the liver than 125I-F3S. Moreover, 125I-F3S-BH accumulated more rapidly into the kidneys, which resulted a lower radioactivity in the blood circulation at an earlier time point than in the case of 125I-F3S. The characteristics of tumor accumulation of 125I-F3S-BH and 125I-F3S were similar to those in blood. If F3S is to be employed as an in vivo targeting ligand in biodistribution studies, BHR would be a suitable tool for radiolabeling because it allows GCL to retain the biological activity and characteristics of the unmodified conjugate.

Animals↗

Evaluation of 5-S-cysteinyldopa as a marker of melanoma progression: 10 years' experience.

5-S-Cysteinyldopa (5-S-CD) has been used as a biochemical marker of melanoma progression. In this study, we measured serum levels of 5-S-CD in 2648 samples taken from 218 patients in order to evaluate the usefulness of this parameter in following melanoma progression and prognosis. 5-S-CD levels were significantly elevated above the upper limit of the normal range (10 nmol/l) in stage IV melanoma patients. The sensitivity of elevated serum 5-S-CD levels in detecting distant metastasis was 73%, while the specificity was 98% and the positive predictive value 94%. The sensitivity was improved to 77% when cases of amelanotic melanoma were excluded. Patients without metastases had elevated 5-S-CD values in 5% of the 1480 serum samples. Changes in serum 5-S-CD levels were followed during disease progression until the end stage in 49 patients. In 33% of the patients, elevation of serum 5-S-CD levels preceded clinical detection of visceral metastases, and in 37% elevation of 5-S-CD levels occurred at the same time as visceral metastasis. Patients with elevated 5-S-CD levels before or after surgical treatment had significantly shorter survival times than those with normal levels. These results show that the level of 5-S-CD in the serum is a sensitive and specific marker in predicting distant metastases. Elevated serum levels of 5-S-CD, before or after surgical treatment, is associated with a poor prognosis.

Adolescent↗

NAD/NADH models with axial/central chiralities: superiority of the quinoline ring system.

Precursors of NAD model compounds 1c and 3a,b were successfully resolved into their atropisomers with respect to carbamoyl rotation. Atropisomers of quinoline derivatives are much more stable than pyridine derivatives as determined by cyclic voltammetry and X-ray crystallography. The 1,4-reduction of NAD model compound 4 was successfully achieved, affording novel NADH model compound 5. The rotational properties of the side chain of 5 were investigated by means of dynamic NMR. The rotational rate and syn/anti ratio, which indicate the orientation between carbonyl oxygen and hydrogen at the 4-position, are significantly affected by addition of magnesium ion. In the rotational transition state, the double-bond character of the C(carbonyl)-N(amide) bond is disrupted judging from the activation parameters. The oxidation of chiral 5 with p-benzoquinone in the presence of magnesium ion catalyst gave predominantly one enantiomer of 4. On the other hand, oxidation of 5 with p-chloranil (tetrachloro-p-benzoquinone) in the absence of magnesium ions affords the opposite enantiomer of 4 as the major product. The product enantiomer ratio is parallel to the syn/anti ratio in the starting material, indicating the importance of ground state conformation to stereochemistry of the reaction.

Crystallography, X-Ray↗

Expression of NAD(+)-dependent isocitrate dehydrogenase in brown adipose tissue.

cDNA clones significantly expressed in brown adipose tissue (BAT) but not in white adipose tissue (WAT) of rats were isolated by use of a PCR-select cDNA subtraction kit. Of the isolated clones, structural features of two of them, 2-58 and 2-67, were studied in detail. The results indicated that these clones were cDNAs encoding alpha- and beta-subunits of rat NAD(+)-dependent isocitrate dehydrogenase (NAD(+)-ICDH). Previous biochemical study suggested the importance of NAD(+)-ICDH in metabolism in BAT; however, transcript levels of individual subunits of this enzyme in BAT had never been analyzed. In the present study, using these newly isolated cDNAs, we clearly demonstrate that the expression of three subunits of NAD(+)-ICDH was the most remarkable in BAT among the various tissues analyzed.

Adipose Tissue, Brown↗

Total synthesis of (-)-stellettamide B and determination of its absolute stereochemistry.

[figure: see text] The first total synthesis of (-)-stellettamide B has been achieved by a sequence based on amide coupling of the chiral 1-(aminomethyl)-indolizidine fragment, prepared by TiCl4-mediated asymmetric allylation of the tricyclic N-acyl-N,O-acetal, with the chiral trienoic acid fragment. This synthesis led to revision of the published relative stereochemistry of the natural product and established its absolute stereochemistry to be 1S,4S,8aR,6"R.

Alkaloids↗

Generation of human bipedal locomotion by a bio-mimetic neuro-musculo-skeletal model.

To emulate the actual neuro-control mechanism of human bipedal locomotion, an anatomically and physiologically based neuro-musculo-skeletal model is developed. The human musculo-skeletal system is constructed as seven rigid links in a sagittal plane, with a total of nine principal muscles. The nervous system consists of an alpha motoneuron and proprioceptors such as a muscle spindle and a Golgi tendon organ for each muscle. At the motoneurons, feedback signals from the proprioceptors are integrated with the signal induced by foot-ground contact and input from the rhythm pattern generator; a muscle activation signal is produced accordingly. Weights of connection in the neural network are optimized using a genetic algorithm, thus maximizing walking distance and minimizing energy consumption. The generated walking pattern is in remarkably good agreement with that of actual human walking, indicating that the locomotory pattern could be generated automatically, according to the musculoskeletal structures and the connections of the peripheral nervous system, particularly due to the reciprocal innervation in the muscle spindles. Using the proposed model, the flow of sensory-motor information during locomotion is estimated and a possible neuro-control mechanism is discussed.

Foot↗

Heparin-stimulated expression of extracellular-superoxide dismutase in human fibroblasts.

Extracellular-superoxide dismutase (EC-SOD) is the major SOD isozyme in the arterial wall and may be important for antioxidation capability of the vascular wall and normal vascular function. EC-SOD is expressed in various cell types in the vascular wall such as fibroblasts, smooth muscle cells and macrophages, and the synthesis of EC-SOD by human fibroblasts is known to be highly responsive to various inflammatory cytokines, although there is no response to oxidative stress. Heparin is a highly sulfated glycosaminoglycan with many functions such as antithrombotic, antilipemic and antiatherosclerotic effects. Another less well-known function of heparin is regulation of protein synthesis. In this study, we measured the induction of EC-SOD after treatment with heparin to understand the role of heparin in the antiatherosclerotic response of fibroblasts. Heparin induced EC-SOD expression at both the mRNA and protein levels. Heparin showed the greatest stimulatory effect and heparan sulfate showed moderate effects. The effect of chondroitin sulfate A was not clear. In contrast, desulfated heparin and chondroitin sulfate C did not increase EC-SOD expression. The stimulatory effect seemed to increase roughly with the degree of glycosaminoglycan sulfation. The enhanced expression of EC-SOD by heparin must contribute to the antiatherosclerotic effect of heparin.

Base Sequence↗

Predominant inner-half wall thickening of left ventricle is attenuated in dilated cardiomyopathy: an application of tissue Doppler tracking technique.

The importance of the inner half (IH) of the left ventricular (LV) wall has been reported in hearts that contract normally. However, it is difficult to verify this fact in an in vivo human heart with clinical echocardiography. By using a recently developed tissue Doppler tracking technique, we could assess the systolic wall thickening of the IH and outer half (OH) of the LV wall in 11 normal and 7 dilated cardiomyopathic hearts. Percent wall thickening and the fractional contribution of the IH and OH to the transmural wall thickening were calculated. In healthy subjects, percent wall thickening of the IH, OH, and transmural wall of the left ventricle were 75.8% +/- 24.1%, 39.4% +/- 14.4% (P <.001 versus IH), and 57.6% +/- 17.6%, respectively. In patients with dilated cardiomyopathy, those values were 31.3% +/- 17.1%, 31.2% +/- 20.1% (not significant versus IH), and 31.2% +/- 16.5%, respectively. On the other hand, the fractional contributions of the IH and OH were 66.2% +/- 7.7% and 33.8% +/- 7.7% (P &lt.01 versus IH) in healthy subjects and 50.5% +/- 11.8% and 49.5% +/- 11.8% (not significant versus IH) in patients with dilated cardiomyopathy. Specifically, the IH contributed to the transmural wall thickening nearly twice as much as the OH did in healthy subjects, however, the predominance of IH contribution was attenuated in dilated cardiomyopathy. The tissue Doppler tracking technique is useful in assessing the IH and OH LV wall thickening separately in the clinical situation.

Adult↗

Malignant eccrine spiradenoma: a case report and review of the literature.

BACKGROUND: Eccrine spiradenoma is a well-differentiated benign tumor of the sweat glands. Malignant change arising within eccrine spiradenoma is rare. OBJECTIVE: We describe a patient with malignant eccrine spiradenoma exhibiting both carcinomatous and sarcomatous differentiation. METHODS: Case report and literature review. RESULTS: A 37-year-old woman noted enlargement of a left axillary tumor that had been present for 20 years. The tumor was resected and the specimen, measuring 3.0 cm x 1.5 cm, revealed an encapsulated benign eccrine spiradenoma as well as an undifferentiated carcinoma possessing both carcinomatous and sarcomatous components. A transition zone was evident between the benign eccrine spiradenoma and the undifferentiated carcinoma, suggesting that the latter had arisen from the benign tumor. The malignant areas consisted principally of undifferentiated carcinoma (70%), although squamous cell carcinoma (10%), adenocarcinoma (10%), and chondrosarcomatous (10%) components were also present. Numerous mitotic figures were noted within the areas of malignant change, suggesting that the tumor was aggressive in nature. The patient died of systemic metastases 7 months after diagnosis. CONCLUSION: Although eccrine spiradenomas are usually benign, they can, on rare occasions, undergo malignant transformation. This case report describes one such occurrence of malignant transformation of a benign eccrine spiradenoma that unfortunately resulted in the patient's death from systemic metastases 7 months after diagnosis.

Adenoma, Sweat Gland↗

Novel expression of equivocal messages containing both regions of choline/ethanolamine kinase and muscle type carnitine palmitoyltransferase I.

For characterization of the detailed gene structure of human muscle type carnitine palmitoyltransferase I (M-CPTI), we analyzed the 5'-upstream region of the M-CPTI transcripts. As a result, we found a cDNA clone containing a nucleotide sequence unexpected from the reported M-CPTI gene structure in the upstream region of its 5' end. Comparison of this nucleotide sequence with that of genomic DNA showed that this sequence was derived from the 3'-untranslated region of the gene encoding choline/ethanolamine kinase-beta (CK/EK-beta) located upstream of the M-CPTI gene. Southern blot analysis showed that there was no other region homologous to the CK/EK-beta gene in the whole human genome. Thus, the overlapping transcript was concluded to be produced from the functional genes of CK/EK-beta and M-CPTI. Furthermore, cDNAs containing both exons of these genes were detected by the polymerase chain reaction using the cDNA of human heart M-CPTI obtained by specific reverse transcription from its 3'-untranslated region as a template. From these results, the production and organization of these overlapping transcripts are discussed.

3' Untranslated Regions↗

NAD(P)+-NAD(P)H models. 90. Stereoselection controlled by electronic effect of a carbonyl group in oxidation of NAD(P)H analog.

4-Monodeuterated NAD(P)H model compounds (1,4,6,7-tetrahydro-1,6,11-trimethyl-5-oxo-5H-benzo[c]pyrido[2,3-e]az epin; 11Me-MMPAH) have been oxidized with a series of p-benzoquinone and its derivatives in the presence of Mg2+. The models have an axial chirality with respect to the orientation of carbonyl dipole, the dihedral angle of which is larger than 55 degrees out of the plane of dihydropyridine ring. Without Mg2+, the anti- (with respect to the carbonyl dipole) hydrogen is 3 to 32 times more reactive than the corresponding syn-hydrogen, whereas, when Mg2+ is present in the system, the selectivity is shifted toward the syn-preferency. Mg2+ plays the role of a Lewis acid catalyst to control the stereochemistry at the same time as it catalyzes the reaction.

Catalysis↗