Biomedical subjects
Publications and source records attributed to Y Takeda.
Surgical procedures to correct malformations of the external auditory canal are associated with the risk of facial nerve injury. We operated on a 6-year-old boy with a stenotic external auditory canal using a Viewing Wand (ISG Technologies Inc., Mississauga, Ontario, Canada) for improved visualization. We present our experience using this imaging system for aural surgery.
We analyzed 29 pairs of primary and metastatic lung carcinomas obtained at autopsy for mutations in the p53 gene, using the polymerase chain reaction-single strand conformation polymorphism method (PCR-SSCP). We examined the relationship between p53 gene mutations and the development of metastasis, and the stability of p53 gene mutations during chemotherapy. The tumors consisted of six small cell carcinomas, 13 adenocarcinomas, eight squamous cell carcinomas, one large cell carcinoma, and one adeno-squamous cell carcinoma. PCR-SSCP analysis showed that three small cell carcinomas (50%), three adenocarcinomas (23%), two squamous cell carcinomas (25%), and one large cell carcinoma (100%) had p53 gene mutations. All these abnormalities were found between exon five and exon eight. The mutations in the primary tumors and the metastatic tumors were identical. These results suggest that p53 gene mutations occur before distant metastases develop, and that they may be stable during the process of metastasis. There were nine metastatic tumor samples that existed before the patients received chemotherapy. These samples showed identical p53 mutations as the corresponding primary tumor. This suggests that anticancer drugs rarely induce p53 gene mutations.
Two hundred and one folk remedies of West Anatolia derived from 91 plant species in 40 families and 2 animal species are presented, each with vernacular names, method of preparation of drugs and traditional uses.
The middle ear is derived from various embryonic tissues. Many experiments using teratogens have been performed, employing the difference of each tissue's sensitivity to the teratogen and the tissue's critical time of development. Triazene, a foliate metabolism antagonist, produced anomalies in fetuses that resembled those associated with thalidomide in humans, the so-called the first and second branchial syndrome. In our experiment, we administrated 3,3-dimethyl-1-phenyltriazene, an inductor of triazene, to pregnant mice at 7 to 14 days of gestation resulting in unique fetal anomalies. We examined the development of the stapes, stapedial artery, facial nerve, and oval window using an optical microscopic and three-dimensional reconstruction. Middle ear and facial nerve anomalies in mice depend on the gestation day when triazene is administrated. The stapedial artery, oval window, facial nerve (horizontal segment), stapes footplate, and styloid process are affected on the 9th to 11th administration day, the annular stapedialis on the 10th to 11th day, and the malleus and incus on the 9th to 11th day. The use of the Vox View/Mac, allowed us to create three-dimensional pictures from two-dimensional slides providing an improved understanding of the relationships between anatomical structures.
We proposed surgical indications for major operations on HIV-infected patients. According to our criteria, major surgery could be performed for HIV-infected patients as long as the surgical approach is preferred and surgery is not likely to exacerbate the subject's quality of life during the course of the disease.
Activity-guided fractionation of the stem bark of Annona senegalensis gave four bioactive ent-kaurenoids (1-4). Compound 2 showed selective and significant cytotoxicity for MCF-7 (breast cancer) cells (ED50 1.0 microgram/mL), and 3 and 4 exhibited cytotoxic selectivity for PC-3 (prostate cancer) cells but with weaker potencies (ED50 17-18 micrograms/mL). The structure of the new compound, 3, was deduced from spectral evidence.
The cell adhesion molecule L1 is a multifunctional protein in the nervous system characterizing cell adhesion, migration, and neurite outgrowth. In addition to full-length L1, we found an alternatively spliced variant lacking both the KGHHV sequence in the extracellular part and the RSLE sequence in the cytoplasmic part of L1. This L1 variant was expressed exclusively in nonneuronal cells such as Schwann cells, astrocytes, and oligodendrocytes, in contrast to the expression of the full-length L1 in neurons and cells of neuronal origin. To investigate the functions of the L1 variant, we established cell lines transfected with a cytoplasmic short L1 (L1cs) cDNA that lacks only the 12-bp segment encoding for the RSLE sequence. The promoting activities of homophilic cell adhesion, neurite outgrowth, and neuronal cell migration of L1cs-transfected cells (L4-2) were similar to those of full-length L1-transfected cells (L3-1), but the cell migratory activity of L4-2 itself was clearly lower than that of L3-1. In conclusion, the short form of L1 is a nonneuronal type, in contrast to the neuronal type of the full-length L1. Deletion of the four amino acids RSLE in the cytoplasmic region of L1 markedly reduced cell migratory activity, suggesting an importance of the RSLE sequence for the signaling events of neuronal migration mediated by L1.
The official methods for 'readily oxidizable substances (ROS)' in propionic acid as a food additive were compared. The methods examined were those adopted in the Compendium of Food Additive Specifications (CFAS) by the Joint FAO-WHO Expert Committee on Food Additives, FAO, The Japanese Standards for Food Additives (JSFA) by the Ministry of Health and Welfare, Japan, and the Food Chemicals Codex (FCC) by the National Research Council, USA. The methods given in CFAS and JSFA are the same (potassium permanganate consumption). However, by this method, manganese (VII) in potassium permanganate was readily reduced to colourless manganese(II) with some substances contained in the propionic acid before reacting with aldehydes, which are generally considered as 'readily oxidizable substances', to form brown manganese (IV) oxide. The FCC method (bromine consumption) for 'ROS' could be recommended because it was able to obtain quantitative results of 'ROS', including aldehydes.
Recently, we demonstrated that aldosterone is produced by human vascular cells, and that vascular aldosterone is linked to angiotensin II-induced hypertrophy of vascular smooth muscle cells. We therefore examined whether genes encoding steroidogenic enzymes responsible for aldosterone biosynthesis from cholesterol are expressed in vascular cells. Using polymerase chain reaction after reverse transcription, type I and II 3 beta-HSD (3 beta-hydroxysteroid dehydrogenase), P-450c21 (21-hydroxylase), and P-450c18 (18-hydroxylase/oxidase) genes were found to be expressed both in endothelial cells and smooth muscle cells cultivated from human pulmonary arteries. However, P-450scc (cholesterol side chain cleavage enzyme) and P-45011 beta (11 beta-hydroxylase) mRNAs could not be detected. These findings suggest that the enzyme system responsible for aldosterone production in human vascular cells is different from that found in the adrenal cortex and that vascular aldosterone may be synthesized from metabolic intermediates which originate from the circulation. Extra-adrenal 3 beta-HSD and steroid 21-hydroxylase occur in a wide variety of tissues. Thus, human vascular cells can retain the ability to produce aldosterone by expressing the P-450c18 gene.
In some mammalian genes, the paternally and maternally derived alleles are expressed differently: this phenomenon is called genomic imprinting. Here we study the evolution of imprinting using multivariate quantitative genetic models to examine the feasibility of the genetic conflict hypothesis. This hypothesis explains the observed imprinting patterns as an evolutionary outcome of the conflict between the paternal and maternal alleles. We consider the expression of a zygotic gene, which codes for an embryonic growth factor affecting the amount of maternal resources obtained through the placenta. We assume that the gene produces the growth factor in two different amounts depending on its parental origin. We show that genomic imprinting evolves easily if females have some probability of multiple partners. This is in conflict with the observation that not all genes controlling placental development are imprinted and that imprinting in some genes is not conserved between mice and humans. We show however that deleterious mutations in the coding region of the gene create selection against imprinting.
In order to develop orally active antitumor platinum complexes, several cyclohexanediamine-Pt(IV) complexes of a general formula trans,cis,cis-[Pt(IV) (OCOCnHn+1)2 (oxalato)(1R,2R-cyclohexanediamine)] were synthesized by derivatizing oxaliplatin [Pt(II)(oxalato)(1R,2R-cyclohexanediamine), I-OHP], which is a potent antitumor cyclohexanediamine-Pt(II) complex we have prepared and now undergoing clinical trials. The I-OHP derivatives were found to be stable, lipophilic and reduced to yield I-OHP, an active species, quantitatively by ascorbate in vitro. All the derivatives were antitumor active against mouse lymphocytic leukemia L1210 when given i.p. In particular, trans-bis-valerato-oxalato-1R,2R-dach-Pt(IV), C5-OHP, showed markedly high activity. C5-OHP also exhibited significant antitumor activity against L1210 when orally administered. C5-OHP was considered to be a suitable candidate for the oral cancer chemotherapy agent to be developed.
To identify the type of Verotoxins (VT) produced by Verocytotoxin-producing Escherichia coli (VTEC), a sensitive bead-enzyme-linked immunosorbent assay and polymerase chain reaction with common and specific primers to various VTs (VT1, VT2, VT2vha, VT2vhb, and VT2vp1) were developed. Together with colony hybridization tests with oligo- and polynucleotide probes, these methods were applied to VTEC isolates to type the VT produced. The toxin types of 26 of 37 strains were identified, but the reaction profiles in assays of the remaining 11 strains suggested the existence of new VT2 variants. The application of these identification procedures may be useful as a tool for clinical and epidemiological studies of VTEC infection.
Four Escherichia coli strains, isolated from cystitis patients, belonging to serotype 02:H- and possessing different combinations of urovirulence factors were examined in an experimental pyelonephritis mouse model to assess the relative importance of virulence factors in causation of urinary tract infections (UTI). The results suggest not only that the each virulence factor has a role in causation of UTI but also that the presence of P fimbriae and production of hemolysin significantly reduced the LD50 and ID50 of the strains in the mouse model. The results also demonstrate that the presence of additional virulence factors acts in an additive or synergetic fashion enhancing the cumulative impact of the strain.
Vibrio cholerae O139 isolated from different countries, as well as from different locations within a country, were examined using macrorestriction DNA analysis to determine the clonality of the O139 strains. NotI digests of genomic DNA of representative strains from Nepal, India, Bangladesh, China, Thailand, and Malaysia revealed very similar but not identical patterns. Examinations of the banding patterns generated by pulsed-field gel electrophoresis of strains isolated within countries revealed complete homogeneity. These results further reiterate the spread of an identical clone of V. cholerae O139 although it appears that genetic polymorphism among the O139 strains is becoming apparent.
An unusual case of malignant ameloblastoma which transformed a pre-existing benign lesion in the maxilla of a 63-year-old Japanese female is reported. In addition to the characteristic histopathological features of less-differentiated malignant ameloblastoma, dendritic-shaped cells containing various amounts of melanin pigment were distributed in the tumor nests invading bone and soft tissue around the maxillary antrum, and some tumor cells containing melanin granules in their cytoplasm were also noted. Neither melanocytes nor melanin pigments were seen within the stroma. Although no firm conclusion of the possible histogenesis of melanocytes in the present case could be drawn, this is the first case of odontogenic epithelial tumor with melanocytosis.
An unusual case of adenoid cystic carcinoma arising from the palatal minor salivary gland in a 63-year-old Japanese female is reported. In addition to the characteristic histopathologic features of adenoid cystic carcinoma, spindle- and dendritic-shaped cells containing excessive amounts of melanin pigment were densely and widely distributed in the stroma resulting in a blue nevus-like appearance. Neither melanocytes nor melanin pigments were seen within the parenchyma. The possible histogenesis of melanocytes in the stroma of the salivary gland carcinoma is discussed, although no firm conclusion could be drawn.
BACKGROUND: Urea-splitting microorganisms cannot always be detected by stone or urine culture in patients with infection stones. Detection of genetic elements within the calculi by the polymerase chain reaction (PCR) may be a useful alternative. In this study, we assessed the usefulness of the PCR method in detecting the urease gene specific to Proteus mirabilis in urinary calculi. METHODS: Thirty-eight metabolic stones (calcium oxalate and/or calcium phosphate, uric acid, or cystine) and 49 struvite stones were examined. The PCR was applied with DNA extracted by boiling pulverized stone pieces. RESULTS: Of the 87 stones, PCR demonstrated the presence of the P. mirabilis urease elements ureC1 and ureC2 in 17, all of which were struvite. Stone culture and urine culture had been performed in 22 and 46 struvite stone cases, respectively, and the PCR was positive in all of the 10 culture-positive calculi and also in two calculi from which P. mirabilis was not isolated. CONCLUSION: PCR was reliable and convenient for detecting P. mirabilis in desiccated struvite calculi. Study to detect other species such as Ureaplasma or Corynebacterium would be useful in elucidating the role of bacterial infection in the formation of these stones.
OBJECTIVE: To evaluate the role of plasminogen activators (tPA uPA) and inhibitor (PAI-1) in the pathogenesis of preeclampsia. STUDY DESIGN: tPA uPA and PAI-1 antigens were measured in amniotic fluid, maternal plasma, and placental homogenates in normal pregnancy by ELISA method and compared with that of preeclampsia. RESULTS: In normal pregnancy, tPA, uPA and PAI-1 levels increase as the gestation advance, but the increment of PAI-1 in amniotic fluid (28.3-fold) is larger than that of tPA and uPA (1.8-fold, 8.5-fold) (p < 0.001). Decidua homogenates contained larger amount of PAI-1 than villi. Whereas, villi had higher levels of tPA uPA than decidua (p < 0.01). In preeclampsia, the significantly higher levels of PAI-1 were observed in AF and decidua tissue as compared to the normals (p < 0.01), and the increment of PAI-1 in preeclampsia is larger than that of tPA, uPA. CONCLUSIONS: The elevated PAI-1 level is associated with the preeclampsia and the imbalance between the plasminogen activators (tPA, uPA) and the inhibitor (PAI-1) might be involved in the pathogenesis of preeclampsia.