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Biomedical subjects

Y Higashi

Publications and source records attributed to Y Higashi.

At least 217 records · Page 12Linked to original sources

[The effects of preoperative insertion of double-J catheter in transurethral lithotripsy (TUL)].

Transurethral lithotripsy (TUL) was performed in the cases in which the ureteral calculi were not destroyed by the extracorporeal shock-wave lithotriptor (Dornier HM-3, EDAP LT 01). Preoperative placement of double-J ureteral catheter (D-J catheter) caused ureteral dilation, allowing smooth insertion of the ureteroscope. We divided the 55 TUL cases into two groups, those with (27) or without (28) a D-J catheter placed preoperatively, and compared requirement of ureteral bougination, difficulty of ureteroscope insertion and duration of operation between the two groups. In all cases with a D-J catheter, ureteral bougination was not necessary, the insertion of ureteroscope was easier and the duration of operation was shorter than the cases without a D-J catheter. Bladder irritable symptoms were seen in some cases with a D-J catheter but did not require removal of the D-J catheter. On the follow-up term after TUL, there was no difference in the incidence of postoperative fever or postoperative ureteral stenosis, between the cases with and those without a D-J catheter.

Adult↗

Activation of aspartase by site-directed mutagenesis.

To elucidate the role of sulfhydryl groups in the enzymatic reaction of the aspartase from Escherichia coli, we used site-directed mutagenesis which showed that the enzyme was activated by replacement of Cys-430 with a tryptophan. This mutation produced functional alterations without appreciable structural change: The kcat values became 3-fold at pH 6.0; the Hill coefficient values became higher under both pH conditions; the dependence of enzyme activity on divalent metal ions increased; and hydroxylamine, a good substrate for the wild-type enzyme, proved a poor substrate for the mutant.

Amino Acid Sequence↗

Structures of regulatory regions in the human cytochrome P-450scc (desmolase) gene.

The mechanism of regulatory expression of human cytochrome P-450scc gene by cAMP was investigated in a transient expression system using Y-1 cells (mouse adrenal tumor cell line) and a chimeric DNA composed of the structural gene for bacterial chloramphenicol acetyltransferase and the 5' flanking upstream sequence of the cytochrome P-450scc (cholesterol desmolase) gene which was revealed to contain a DNA element(s) responsive to cAMP [Inoue, H. et al. (1988) Eur. J. Biochem. 171, 435-440]. Introduction of deletions and point mutations in the upstream regulatory sequence demonstrated that three regions were mainly required for response to cAMP. These regions contained a short similar sequence. All of them have a 5-bp motif GTCAT (or ATGAC) in common, and have at least two motifs which conserve four out of five base pairs of the consensus sequence of the cAMP-responsive element (CRE), CGTCA (or TGACG). They are all apparently necessary for regulation by cAMP. Gel mobility shift assays suggested that a binding factor(s) to these regions was present in the nuclear extracts of Y-1 cells and adrenal cortex tissues and appeared to be different from the somatostatin CRE-binding protein. Deletion analysis also suggested that the region around -44 was essential to the basal transcriptional activity. This region shows some similarity to the CTF NF-1 binding site [Johnson and McKnight (1989) Annu. Rev. Biochem. 58, 799-839].

Animals↗

High efficacy of monomethoxypolyethylene glycol-conjugated L-asparaginase (PEG2-ASP) in two patients with hematological malignancies.

Two patients with hematological malignancies were successfully treated with monomethoxypolyethylene glycol-conjugated Escherichia coli L-asparaginase (PEG2-ASP), which reportedly lacks both antigenicity and immunogenicity but retains catalytic activity as well as slow clearance in an experimental animal model. A 20-year-old male patient with leukemic lymphoma was refractory to conventional chemotherapy but responsive to L-asparaginase (L-ASP) followed, however, by severe adverse effects. On relapse, an intravenous infusion of 100-200 IU/day dose of PEG2-ASP alone led to a complete remission 2 months later without hypersensitivity or other significant adverse reactions. Surprisingly, he remained in a complete remission for over one year with a regular weekly infusion of PEG2-ASP, combined with a weekly small dose of Ara-C. During this period, blood asparagine was not detectable. The other patient, a 64-year-old woman with chronic myelogenous leukemia in blast crisis achieved, within 6 weeks, a complete remission with twice-weekly infusions of PEG2-ASP. Thus, PEG2-ASP is a highly effective antitumor agent overcoming the limitations in therapeutic use of L-ASP.

Adult↗

Effects of individual mutations in the P-450(C21) pseudogene on the P-450(C21) activity and their distribution in the patient genomes of congenital steroid 21-hydroxylase deficiency.

Recent observations have suggested that the pathological mutations in human P-450(C21) deficiency are generated through gene conversion-like events between the functional gene [P-450(21)B] and the pseudogene [P-450(C21)A]. To address this point more extensively, we investigated the effects of the base changes in the A pseudogene on the P-450(21) activity by using the COS cell expression system. In addition to the defective mutations found previously in the pseudogene, four single base changes with amino acid substitutions of Pro(30), Ile(172), Val(282), or Arg(356) were further identified as causing complete [Arg(356)] or partial [Pro(30), Ile(172), and Val(282)] inactivation of P-450(C21). Blot hybridization analysis of patient DNAs using oligonucleotide probes specific for these mutations revealed that the splicing mutation in the 2nd intron was distributed most frequently in both simple-virilizing and salt-wasting forms. The mutation Ile(172) seemed to be frequent in patients with the less severe simple-virilizing form, whereas the mutation Arg(356), together with other most serious mutations reported previously, was preferentially associated with salt-wasting, the most severe form of the disease. In combination with the present results of the effects of various mutations on the P-50(C21) activity, a survey of the distribution of the various mutations in the patient genomes so far reported suggests that the heterogeneous clinical symptoms of this genetic disease are somehow related to the degree of attenuation of the activities of the mutated gene products.

Adrenal Hyperplasia, Congenital↗

Cavernous lymphangioma of the breast: case report with electron microscopic and immunohistochemical investigations.

A rare case of cavernous lymphangioma of the breast in a 16-year-old Japanese girl was investigated by light and electron microscopies, and immunohistochemistry. The patient, who had a soft breast tumor measuring 16 x 14 cm, had undergone a tumorectomy two years after she noticed the tumor. Histologically, the tumor was composed of numerous narrow spaces containing amorphous fluid lined with a monolayer of endothelial cells. Abundant collagen fibers and numerous fibroblasts were found beneath the endothelium. Histological findings confirmed a diagnosis of lymphangioma of the breast. Immunohistochemically, the endothelium showed negative immunoreaction for factor VIII-related antigen, but the discontinuous basal lamina was positive for laminin. Ultrastructurally, numerous microfilaments and pinocytotic vesicles were found in the cytoplasm of the endothelial cells, and intermediate junctions were recognized between adjacent cells. In addition, a discontinuous basal lamina was seen beneath the endothelium. Electron microscopic and immunohistochemical investigations are thus useful in confirming a diagnosis of cavernous lymphangioma of the breast.

Adolescent↗

In vitro and in vivo transferrable beta-lactam resistance due to a new plasmid-mediated oxyiminocephalosporinase from a clinical isolate of Proteus mirabilis.

A new plasmid-mediated beta-lactamase (FPM-1) with an isoelectric point of 7.2 and a molecular weight of 26,000 was found in a cefuroxime-resistant clinical isolate of Proteus mirabilis strain 6003. FPM-1 can be classified as a type I oxyimino-cephalosporinase on the basis of its substrate specificity and inhibition pattern by clavulanic acid etc., and its conferred resistance on both the strain and transconjugants against most oxyme-type cephalosporins as well as the older ones but not against cefamycins and a few exceptional oxyme-type cephalosporins such as ceftizoxime, ceftazidime and cefixime. In a murine systemic infection model, only these FPM-1-stable drugs exhibited protective activity against the FPM-1-producing P. mirabilis 6003 similar to that against a nonproducing derivative strain. The FPM-1-mediated cefuroxime resistance in P. mirabilis 6003 was transferred to co-infected Escherichia coli 7004 at frequencies between 3.8 x 10(-3) and 4.0 x 10(-2) in a murine ascending urinary tract infection model. In the same infection model due to the FPM-1-producing E. coli transconjugant, FPM-1-stable cefixime was significantly more effective than FPM-1-labile cefteram pivoxil, although both drugs had similar therapeutic effect against its FPM-1-nonproducing counterpart strain.

Animals↗

Study on brain uptake of local anesthetics in rats.

Brain uptake of local anesthetics under steady-state plasma condition and/or following intravenous bolus administration was investigated in rats. All ester-type anesthetics examined such as ethyl (Et), propyl (Pr), butyl (Bu) esters of p-aminobenzoic acid (PABA), and procaine disappeared rapidly from plasma in a dose-dependent manner. Plasma profiles of these compounds were well explained by a 2-compartment model with a Michaelis-Menten type elimination process from a central compartment. On the other hand, lidocaine, amide-type anesthetic, showed a linear pharmacokinetic characteristic and its half life in the elimination phase was far longer than those of ester type agents. Extents of brain uptake (brain-to-plasma partition coefficient, Kp value) of these drugs were determined at 3 different steady-state plasma concentrations (1-15 microM). The Kp value of each drug was similar under the three different steady-state plasma concentrations. The Kp value increased in the following order; procaine (1.1) less than PABA-Et (1.9) less than lidocaine (2.2) less than PABA-Pr (2.7) less than PABA-Bu (3.6). A linear relationship was observed between the Kp value and the logarithmic value of the partition coefficient obtained in n-heptane/water or n-octanol/water partition system. The value of PABA-Et and PABA-Bu following intravenous bolus administration were varied with time elapsed but the mean values were almost same with those obtained under steady-state plasma conditions.

4-Aminobenzoic Acid↗

[Macroscopic tumor thrombus in renal cell carcinoma].

Prognosis of 114 patients treated for renal cell carcinoma from 1972 to 1988 was investigated to evaluate intravenous tumor extension as a prognostic factor. Those in whom presence or absence of macroscopic tumor thrombus was not confirmed were not included in the current patient group. Tumor stages were evaluated according to TNM criteria except that intravenous tumor thrombus was not counted for local staging. Incidence of T3 and T4 tumors, distant metastasis and grade 3 anaplasia (G3) were higher in V+ group (V1 + V2) than in V0 group, which appeared to be a major difference of background making 5-year actuarial survival rates in V1 and V2 patient groups worse than in V0. Therefore, 5-year actuarial survival rates in N0 and M0 cases receiving radical nephrectomy were compared and found 83.3% in V2 group, 54.4% in V1 and 87.3% in V0. Since V1 group included G3 tumors more frequently than the other two groups, 5-year survival rates were further compared after excluding those with G3 tumors and found to be identical among V0, V1 and V2 groups. The current results indicate that macroscopic intravenous extension of renal cell carcinoma is an accompanied phenomenon secondary to high grade and invasive tumors and therefore, not a primary risk factor for prognosis. Accordingly, it is questionable to regard macroscopic tumor thrombus itself as a risk factor for clinical staging.

Adult↗

[The pitfall of ESWL].

The pitfall of extracorporeal shock-wave lithotripsy (ESWL), such as complications of ESWL, problems of focus and results of stone disintegration are discussed. The progress of ESWL today is mainly due to the development of new generation lithotripters and endourological support, which has broadened the indications of ESWL. The necessary shock-waves have been selected, and complications have been reduced. Post ESWL stone street is now easier to treat. We expect more improved lithotripters such as by incorporation of X-ray and echo focusing systems. Endourological techniques including laser lithotripsy also should be improved.

Autonomic Nervous System Diseases↗

Enhanced rectal and nasal absorption of human epidermal growth factor by combined use of the absorption promoter and the synthetic polymer in rats.

Previously, the presence of sodium carboxymethylcellulose (CMC Na) in addition to an absorption promoter, sodium caprate (C10 Na), in the dosing solution was found to be necessary for the enhancement of the rectal absorption of human epidermal growth factor (hEGF). In the present study, other synthetic polymers and absorption promoters were examined for their ability to enhance the rectal and nasal absorption of hEGF in rats. The effect of polymers in combined use with 100 mM C10 Na on the rectal absorption of hEGF was in the following order: 1% methylcellulose 1% hydroxypropylmethylcellulose 0.1% polyacrylic acid 1% CMC Na. Other absorption promoters such as N-lauroyl-alanine (C12-A) and dihydroxy-bile salts also enhanced the rectal absorption of hEGF in combined use with CMC Na. In order to confirm the increased rectal absorption of hEGF, the disappearance of hEGF from the rectal loop was examined. When hEGF in a 1% CMC Na solution (200 ug/kg) was administered in the rectal loop, the disappearance percent of hEGF during 60 min was 13.9% of the dose, although hEGF was not detected in the plasma. The presence of promoters such as 10 mM C10 Na or 15 mM C12-A in 1% CMC Na increased the disappearance percent to about 50% in a dosing range of hEGF from 100 to 500 ug/kg. On the other hand, a markedly enhanced nasal absorption of hEGF by 100 mM C10 Na was observed even in the absence of any polymer in a dising solution. However, addition of CMC Na into the dosing solution accelerated the rate of nasal absorption of hEGF in early phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Acrylic Resins↗

[A case of malignant pheochromocytoma of the urinary bladder].

A 31-year-old man was admitted to our hospital because of miction pain and gross hematuria in August, 1988. Cystoscopic examination revealed a solid mass in the bladder. The histological diagnosis was pheochromocytoma of urinary bladder by biopsy. He had a history of syncope on urination several times. Abnormal elevation of serum noradrenaline was observed in hormonal studies and abnormal accumulation was seen in the bladder by 131I-MIBG scintigraphy. Total cystectomy, lymphadenectomy and urinary diversion were performed in November, 1988. Pathological diagnosis was pheochromocytoma of the urinary bladder with metastasis to both iliac lymph nodes.

3-Iodobenzylguanidine↗

[Clinico-pathological comparative study between brainstem encephalitis of Iizuka type and neuro-Behçet's disease].

We experienced one necropsy case of brainstem encephalitis of Iizuka type (BSE) and one necropsy case of the brain-stem syndrome (BSS) of typical neuro-Behçet's disease, and compared them clinically and neuropathologically. Clinically both of these cases showed chronic progressive mental disturbance, pseudobulbar paresis, spastic tetraparesis, cerebrospinal fluid pleocytosis, increased protein, and brainstem atrophy observed by X-CT. Neuropathologically, irregular, boundary-indistinct demyelinating lesions and obsolete softening lesions were sporadically found, associated with perivascular lymphocytic infiltration and gliosis centering on the brainstem. In this way, both cases were similar in many points except for the presence or absence of cutaneo-muco-ocular signs specific for Behçet's disease. Also BSE and BSS reports in the literature showed that both diseases were similar not only in clinical findings consisting of mental disturbance and brainstem signs but also in neuropathological findings with similar topographical distribution of the same histopathological changes, including the variations and diversity of these characteristics. Especially of much interest is their similarity in characteristic mental disturbance. In discriminating BSE from multiple sclerosis and other diseases with exclusive involvement of the brainstem, it is important to understand their clinical characteristics. The characteristic mental disturbance includes damage to memory and sentiment, a change in personality, and lowering in spontaneity, but calculation ability and orientation are comparatively preserved. Of course the similarity in clinical and neuropathological findings does not necessarily mean the identical etiopathogenesis. However, it is possible to consider that neuro-Behçet's disease (syndrome) may form a wide spectrum with BSE and typical neuro-Behçet's disease at the both ends, regarding the time and spatial diversity of the appearance of cutaneo-muco-ocular signs.

Atrophy↗

[Quantitative measuring method for fibers using image processing and analysis].

Previously, the radioisotope labeling and morphometric techniques have been used for the quantitative determination of growth of mandibular condyle by measuring the DNA synthesis or the increased number of cells. However, it is difficult to analyze the dynamics of ESFs (Elastic System Fibers) in the mandibular condyle related to aging, because of changes in the amount, distribution, number of fibers, and density of ESFs. In the present study, therefore, the video-scanning image analyzing technique was used for the quantitative measurement of ESFs in the mouse mandibular condyle. The objects under selected suitable illumination are scanned and focused by the TV camera and lens. The focused image is converted and amplified to obtain the most reliable electric signal by sequential scanning with the relative electronic beam. The original shaded image (electric signals) generated and converted by photo electric converter was filtered by the input slope (detective sensitivity) to detect the relative objects. Next, by inputted contrast, a secondary black-and-white image was detected. Meanwhile, a suitable compensation was also used to eliminate electric noise and dusts by inputting size discrimination. The next step was designed to obtain various quantitative data by measuring areas and diameters of the relative objects after treatment and analyzing of the secondary image, which was outputted from the photo electric converter. The connected LED display showed the measured and counted data, and at the same time the obtained data was automatically printed out for recording. There are many samples that are impossible to distinguish without using specific staining methods, like the ESFs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[A case of infantile Sertoli cell tumor].

A case of infantile Sertoli cell tumor of the testis is presented. A 2-year-old child visited our hospital with the complaint of painless swelling of the left scrotal content. A solid tumor was demonstrated in the left testis by scrotal echography. Physical and laboratory examinations were within normal limits and alpha-fetoprotein and beta-HCG were not elevated. The left testis was removed. The tumor sized 3.0 x 3.0 x 2.2 cm and weighted 14.5 g. Pathohistological diagnosis was benign Sertoli cell tumor. Tumor cells were vimentin positive and TM-1 reactive antigen positive and revealed electronmicroscopically some features of Sertoli cells such as intermediated microfilament, rich lysosomes and interdigitation between adjacent cells. The patient was well with no evidence of diseases one and a half years after the operation.

Age Factors↗