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Biomedical subjects

S Kitahara

Publications and source records attributed to S Kitahara.

At least 37 records · Page 2Linked to original sources

Alterations of asparagine-linked sugar chains of N-acetyl beta-D-hexosaminidase during human renal oncogenesis: a preliminary study using serial lectin affinity chromatography.

Enzymatic properties and asparagine (Asn)-linked sugar-chain structures of N-acetyl beta-D-hexosaminidase A (Hex A) were compared in human tissues between normal renal cortex and renal cell carcinoma (RCC). No significant differences between the two Hex A preparations were observed with respect to enzymatic properties such as molecular mass, Michaelis-Menten value or optimal pH. With RCC preparations, relatively more Hex A passed through the concanavalin A (Con A) column, bound weakly to Con A, or bound strongly to Con A and also to the wheat germ agglutinin (WGA) column, than with preparations from normal renal cortex. In contrast, relatively less Hex A bound strongly to the Con A column, but passed through the WGA column with RCC preparations than with those from normal renal cortex. Asn-linked sugar-chain structures might apparently be altered during human renal oncogenesis.

Asparagine↗

Levels of free prostate-specific antigen (PSA) can be selectively measured by heat treatment of serum: free/total-PSA ratios improve detection of prostate carcinoma.

We studied a simple heat treatment method for measuring free prostate-specific antigen (PSA). Samples were incubated at 56, 58, and 60 degrees C for 5, 15, 30, 45, and 60 min. Then, 1 ml samples were fractionated on a Sephacryl S-200 gel filtration column to separate alpha1-antichymotrypsin-complexed PSA (ACT-PSA) and free PSA. Values of ACT-PSA decreased with increasing incubation temperature and time, whereas free-PSA remained relatively constant. The optimal temperature and time for incubation were 58 degrees C and 30 min. Using free/total-PSA ratios, we were able to distinguish between benign prostatic hyperplasia and prostate carcinoma in patients whose PSA was in the diagnostic 'grey zone', i.e. 4.1 to 10.0 ng/ml. Through receiver operating characteristic curve analysis, the area under the curve increased from 0.675 to 0.871 when comparing the performance of total PSA to the free/total-PSA ratio. Thus, clinical application of our present methodology may reduce the need to obtain prostatic biopsies in patients whose PSA level is within the diagnostic 'grey zone'.

Chromatography, Gel↗

CAG repeat length in the androgen receptor gene is enhanced in patients with idiopathic azoospermia.

OBJECTIVES: To determine whether the number of CAG repeats in the androgen receptor gene is enhanced in patients with idiopathic azoospermia. METHODS: Using the polymerase chain reaction, the number of CAG repeats was assayed in 41 patients with idiopathic azoospermia and in 48 normozoospermic fertile men. RESULTS: In the control group, the CAG repeat length ranged from 17 to 30 (mean 23.9 +/- 2.9); in the azoospermic group, the CAG repeat length ranged from 20 to 34 (mean 26.5 +/- 3.5). The difference between the two groups was statistically significant (P = 0.0013). None of the men in the control group had a CAG repeat length greater than 31; four of the azoospermic men had 34 CAG repeats. CONCLUSIONS: Results suggest that an increase in the number of CAG repeats in the androgen receptor gene to 31 or greater may be associated with the etiology of at least some cases of idiopathic azoospermia.

Adenosine↗

The operation of upper esophageal web in Plummer-Vinson syndrome: a case report.

Most cases of dysphagia associated with Plummer-Vinson syndrome are expected to improve with the oral administration of ferrous agents. When a web is the cause of the symptoms, surgical management is rarely necessary. However the surgical indication and technique for the web have been controversial. The patient was a 56-year-old woman who complained of restricted dietary habit because of an upper esophageal circumferential web associated with Plummer-Vinson syndrome. The circumferential and membranous web was resected with a surgical knife and scissors through the inner lumen of esophagus and the raw surface was sutured at five places with 4-0 proline thread under microlaryngosurgery. This surgical treatment resulted in diminished dysphagia and no recurrence of the web after the surgery.

Deglutition Disorders↗

Physicochemical properties of amorphous clarithromycin obtained by grinding and spray drying.

In order to characterize the amorphous clarithromycin (CAM) obtained by grinding and spray drying, physicochemical properties (crystallinity, thermal behavior, stability and solubility parameters) were evaluated. From powder X-ray diffraction, it was estimated that the crystalline state of CAM was changed into an amorphous state by grinding and spray drying. In differential scanning calorimetry measurements, both broad and sharp peaks for crystallization were observed in ground samples, whereas spray dried samples showed one broad peak due to crystallization. As to the stability test under high humidity, structural difference was confirmed between ground CAMs and spray dried CAM. The heat of dissolution of ground CAMs was greater than that of intact CAM. In the solubility parameter measurement, the increase of the special term, deltas, indicated that the energy change was due to the polarity of the surface energy of the powder particles by grinding.

Anti-Bacterial Agents↗

Prognosis after salvage chemotherapy for locally unresectable recurrent squamous cell carcinoma of the head and neck.

BACKGROUND: For locally unresectable recurrent squamous cell carcinoma of the head and neck, we investigated two salvage chemotherapy regimens as second-line chemotherapy. In our preliminary study, we observed that both regimens were active. In the present study we analyzed the prognosis of these patients. METHODS: Twenty-six patients with recurrent advanced head and neck cancer, were treated with one of two new regimens as second-line chemotherapy. The PEM regimen consisted of cisplatin 60 mg/m2 on day 1, etoposide 40 mg/m2 on days 1, 2 and 3 and mitomycin-C 7 mg/m2 on day 1. The long CF regimen consisted of cisplatin 8 mg/m2 on days 1-5, 8-12, 15-19 and 22-26 and 5-fluorouracil 300 mg/m2 as a 24 h infusion or oral administration of tegaful-uracil (UFT-E) 400 mg/m2 on days 1-28. Survival curves were calculated using the Kaplan-Meier method and compared by the log rank test. RESULTS: Of 24 patients evaluable for response, three complete responses (CR) and seven partial responses (PR) were achieved, with an overall response rate of 42%. Myelosuppression was the major side effect. One year survival was 100% for CR, 0% for PR and 20% for minor response (MR). All patients who failed to achieve a CR died within 12 months, except one patient with MR. CONCLUSION: Our data suggest that with these salvage regimens survival benefit was demonstrated only in CR patients.

Adult↗

Role of lentiviral lytic polypeptide I (LLP-I) in the selective cytotoxicity of gamma-glutamylcysteine ethyl ester against human immunodeficiency virus type 1-producing cells.

Selective cytotoxic effects of gamma-glutamylcysteine ethyl ester (gamma-GCE) against human immunodeficiency virus type 1 (HIV-1)-infected H-9 T lymphocytic cells were demonstrated previously. However, the mechanism of those effects remained unclear. Here, we report on enhanced cytotoxicity of the lentiviral lytic peptide I (LLP-I) of gp41, the envelope transmembrane glycoprotein of HIV-1, in the presence of gamma-GCE. Without gamma-GCE, the cytotoxic effect of LLP-I was transient, whereas with gamma-GCE, cell death induced by LLP-I remained continuous until termination. Of note, such effects by gamma-GCE were also observed with another unrelated amphipathic peptide toxin, melittin. These results suggest that the synergistic cytotoxic effect of gamma-GCE and LLP-I may play a central role in the molecular mechanism of the selective cytotoxicity of gamma-GCE in HIV-1-infected T lymphocytic cells.

Anti-HIV Agents↗

Allopurinol increases ear swelling and mortality in a dinitrofluorobenzene-induced contact hypersensitivity mouse model.

The immunomodulatory effects of allopurinol were investigated in a mouse contact hypersensitivity model. Allopurinol caused a time- and dose-dependent lethal effect in dinitrofluorobenzene (DNFB)-sensitized mice. Furthermore, allopurinol markedly increased ear swelling in the remaining mice. In contrast, TMX-67, a newly synthesized xanthine oxidase/xanthine dehydrogenase (XOD/XDH) inhibitor, had almost no effect on DNFB-sensitized mice. Allopurinol reduced both the spleen weight and white blood cell count in DNFB-sensitized mice without affecting the T cell subset of splenocytes. The production of interferon (IFN)-gamma, in the splenocytes of DNFB-sensitized mice was reduced by allopurinol administration. Death due to allopurinol was much lower in the non-sensitized mice than in the DNFB-sensitized mice. These findings indicate that allopurinol may interact with DNFB to enhance its toxicity and allopurinol might also modulate or enhance the inflammatory effect of DNFB. Also, DNFB may cause metabolic alterations via inflammation, leading to enhanced allopurinol toxicity.

Allopurinol↗

Effects of intravenous administration of high dose-diethylstilbestrol diphosphate on serum hormonal levels in patients with hormone-refractory prostate cancer.

The objective of this study was to elucidate the mechanism underlying the further suppression of serum testosterone (T) by diethylstilbestrol diphosphate (DES-DP) in patients with prostate cancer refractory to hormonal treatment. These patients received an LHRH agonist with or without a non-steroidal androgen-receptor blocker or a gestagen before DES-DP. We measured serum levels of total and free T, dihydrotestosterone (DHT), estradiol (E2), dehydroepiandrosterone sulfate (DHEA-S), dehydroepiandrosterone (DHEA), androstenedione, cortisol, aldosterone before and during intravenous administration of high doses of DES-DP (500 or 1000 mg/day). DES-DP administration suppressed the serum levels of FSH (p=0.04) and total T (p=0.02), and eliminated free T (p=0.04) and E2 (p=0.04) from serum, while reducing serum DHEA-S to approximately two-thirds of the pretreatment level (p=0.03). In contrast, serum levels of SHBG (p=0.02) and cortisol (p=0.02) were markedly increased after DES-DP administration. The latter had no significant effect on serum levels of LH, DHT, ACTH, 17alpha-hydroxypregnenolone, 17alpha-hydroxyprogesterone, DHEA, androstenedione, or aldosterone. The results suggest that the potent suppression of circulating total T by DES-DP is caused, in part, by the inhibitory effect of DES-DP on serum DHEA-S level. In most patients, high-dose DES-DP treatment completely suppressed the serum level of free T, while possibly elevating serum SHBG and decreasing serum total T. The mechanisms that maintain the serum level of serum DHT during DES-DP treatment require further elucidation.

Aged↗

[Clinicopathological evaluation of intralaryngeal ultrasonography].

We used a miniature ultrasonic probe to study its diagnostic application in the detection of laryngeal lesions. Using the immersion method and an extracted human larynx, we evaluated ultrasonic images, identified the layered structure of vocal folds, and examined clinical cases following the study of diagnostic application. By the immersion method, ultrasonic images revealed that the membranous vocal fold was separated into three layers. We identified the histological structures of these three layers by comparing the ultrasonic images with the corresponding histologies. The first layer (hyperechoic) was the epithelial and the superficial layer of the lamina propria; the second layer (hypoechoic) was the vocal ligament; and the third layer (hyperechoic) was the deep layer of the lamina propria. On the basis of this study, we then evaluated ultrasonographic images of clinical cases. Benign lesions such as vocal nodules or vocal polyps were noted on the layered structure of the mucosa, especially, polyps as hyperechoic images. Furthermore, glottic cancer lesions demonstrated hypoechoic images and sometimes revealed destruction of the layered structures. These results suggest that intralaryngeal ultrasonography can be useful as a clinical application for the detection of tumor involvement in the vocal folds.

Aged↗

Telomerase activity in renal cell carcinoma.

BACKGROUND: Telomerase activity has been shown to be increased in numerous tumors and cell lines, although to the authors' knowledge there has been no previous assessment of telomerase activity in renal cell carcinoma (RCC). To examine whether telomerase activity could be used as a biochemical parameter for predicting the behavior of RCC, telomerase activity was quantified in RCC samples and correlated with clinicopathologic findings. METHODS: Telomerase activity was quantified in 50 RCC samples and 21 samples of normal renal tissue using fluorescence-based telomeric repeat amplification. RESULTS: Telomerase activity was detected in 28 of 50 RCC samples (mean +/- standard deviation, 35.03 +/- 18.47 U/microg protein), whereas there was no telomerase activity in 21 normal renal tissue specimens. Telomerase activity in tumors classified as pT4 was significantly higher than in tumors classified as pT1 to pT3. Telomerase activity also correlated with patient age. CONCLUSIONS: Telomerase activity was increased in RCC samples compared with normal renal tissues. Although significant associations were observed between telomerase activity and clinicopathologic parameters, further study is required to determine whether telomerase activity affects the biologic and clinical behavior of RCC.

Adult↗

Secondary treatment failure without anti-human chorionic gonadotropin antibody in a patient with Kallmann syndrome.

A 29-year-old man with Kallmann syndrome suddenly developed decreased semen volume, azoospermia, and facial hair loss after 11 years of successful human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG) treatment. Anti-hCG antibody was not detected in the patient's serum. A high serum level of luteinizing hormone (LH) with nasal LH-releasing hormone analogue administration failed to increase serum testosterone to a sufficient level. Testosterone injection after cessation of hCG and hMG therapy was able to improve semen volume, but not azoospermia. Resumption of hCG and hMG therapy after 6 months cessation partially restored spermatogenesis. The secondary failure of hCG and hMG therapy suggests a decrease of testicular sensitivity to LH as well as hCG.

Adult↗

Novel inhibitory effects of gamma-glutamylcysteine ethyl ester against human immunodeficiency virus type 1 production and propagation.

The anti-human immunodeficiency virus type I (anti-HIV-1) effects of gamma-glutamylcysteine ethyl ester (gamma-GCE; TEI-2306) were examined in vitro. In initial studies using a vigorously HIV-1-producing human T-lymphocytic cell line, gamma-GCE displayed a novel biphasic repressive effect on chronic HIV-1 infection that was unlike that of other glutathione prodrugs or other reported antioxidants. In high doses, up to a concentration of 2.5 mM, at which neither glutathione (GSH) nor another GSH precursor has shown inhibitory effects, gamma-GCE potently inhibited the production of HIV-1 by a selective cytopathic effect against infected cells, while the viability and growth of uninfected cells were unaffected at the same gamma-GCE concentrations. At lower concentrations (200 to 400 microM), gamma-GCE significantly repressed the virus production from chronically HIV-1-expressing cells without affecting their viability. The discrepancy of the thresholds of the toxic doses between infected and uninfected cells was found to be more than 10-fold. Relatively high doses of gamma-GCE, utilized in acute HIV-1 infection of T-lymphocytic cells, entirely blocked the propagation of HIV-1 and rescued the cells from HIV-1-induced cell death. Furthermore, gamma-GCE at such concentrations was found to directly inhibit the infectivity of HIV-1 within 4 h. Repressive effects of gamma-GCE on acute HIV-1 infection in human primary human peripheral blood mononuclear cells were also demonstrated. Here, the anti-HIV-1 strategy utilizing gamma-GCE is removal of both HIV-1-producing cells and free infectious HIV-1 in vitro, in place of specific immunoclearance in vivo, which might lead to an arrest or slowing of viral propagation in HIV-1-infected individuals.

Anti-HIV Agents↗

Effects of head rotation on pharyngeal function during normal swallow.

This study quantified the effects of head rotation on pharyngeal swallowing in healthy subjects. Videofluoroscopic and oropharyngeal manometric examinations of pharyngeal swallowing were performed on seven volunteers with the head in neutral and rotated positions. Videofluoroscopic study revealed that head rotation swallow causes the bolus to lateralize away from the direction of head rotation. Pharyngeal manometric study indicated that the pharyngeal peak pressures toward the side of head rotation were significantly increased, whereas the pharyngeal pressures opposite the side of head rotation were not affected. Head rotation swallow produced a significant fall in upper esophageal sphincter (UES) resting pressure and a delay in UES closing. We concluded that the head rotation swallow in normal subjects not only alters the bolus pathway, but also has a useful effect on both pharyngeal clearance and UES dynamics.

Adult↗

[Studies of prostate-specific antigen (PSA) immunoassays--differences in characteristic of immunoreactivity and reference materials among the kits].

PURPOSE: We conducted this study to examine differences in characteristics of immunoreactivity for free PSA and alpha(1)-antichymotrypsin complex PSA (ACT-PSA) as well as in compositions and concentrations of PSA reference materials among commercially available PSA kits. METHODS: Fractionated serum samples using a Sephacryl S-200 column were measured by Tandem-R, Delfia-PSA, Ab bead PSA, ACS-PSA, Markit-M and gamma-seminoprotein (gamma-Sm) kits. The calibrators of Tandem-R, Delfia-PSA, Ab bead PSA and Markit-M were fractionated by the same method and measured by Tandem-R. The calibrators of Delfia-PSA, Ab bead PSA and Markit-M and control serums of ACS-PSA were measured by Tandem-R. RESULTS: Although the characteristic of immunoreactivity of Tandem-R, Delfia-PSA, and Ab bead PSA were found to be similar, they were not shown identical. ACS-PSA was proved to recognize free PSA greater than above three PSA kits, while Markit-M could scarcely detect free PSA. gamma-Sm recognized only free PSA. The calibrators of Tandem-R, Delfia-PSA, Ab bead PSA and Markit-M were proved to be only free PSA. The linear correlation was obtained between Tandem-R and Delfia-PSA or Ab bead PSA or Markit-M. The ratio of Delfia-PSA to Tandem-R, Ab bead PSA to Tandem-R and Markit-M to Tandem-R was 0.66, 0.93 and 2.2, respectively. With regard to relation of ACS-PSA and Tandem-R, two ratios of 0.22 and 0.25 were obtained between the two kits according to the different concentrations of control sera. CONCLUSION: The present studies suggest that the difference in PSA values among the commercial PSA kits results from (1) different characteristics of immunoreactivity for ACT-PSA and free PSA among PSA kits, (2) compositions of PSA calibrators among the kits, and (3) different concentrations of PSA calibrators among the kits.

Biomarkers, Tumor↗

Serum concentration of type I collagen metabolites as a quantitative marker of bone metastases in patients with prostate carcinoma.

BACKGROUND: Bone scans, widely used for the detection of bone metastases from prostate carcinoma, can neither quantitate metastatic lesions nor detect osteolytic lesions. METHODS: Serum concentrations of the carboxyterminal propeptide of Type I procollagen (PICP), the carboxyterminal pyridinoline cross-linked telopeptide of Type I collagen (ICTP), and prostate specific antigen (PSA) were measured by radioimmunoassays in 48 patients with benign prostatic hyperplasia (BPH), 25 patients with prostate carcinoma (PCA) without bone metastases, and 36 patients with PCA and bone metastases. RESULTS: Serum concentrations of PICP were significantly higher in patients with PCA with bone metastases than in patients with BPH or PCA without bone metastases. No significant differences were observed between patients with BPH and those with PCA without bone metastases. Serum ICTP concentrations were significantly higher in patients with PCA than in patients with BPH regardless of the presence or absence of bone metastases. Serum concentrations of PICP, ICTP, and PSA correlated significantly with Soloway's grading system for bone scans. The serum concentrations of PICP and ICTP in patients without bone metastases showed a significant downward trend in response to antiandrogen therapy. CONCLUSIONS: These observations suggest that the serum concentrations of PICP and ICTP are quantitative markers of bone metastases from PCA when followed serially in individual patients.

Age Factors↗

Serial lectin affinity chromatography with concavalin A and wheat germ agglutinin demonstrates altered asparagine-linked sugar-chain structures of prostatic acid phosphatase in human prostate carcinoma.

Differences between human prostate carcinoma (PCA, five cases) and benign prostatic hyperplasia (BPH, five cases) in asparagine-linked (Asn) sugar-chain structure of prostatic acid phosphatase (PAP) were investigated using lectin affinity chromatography with concanavalin A (Con A) and wheat germ agglutinin (WGA). PAP activities were significantly decreased in PCA-derived PAP, while no significant differences between the two PAP preparations were observed in the enzymatic properties (Michaelis-Menten value, optimal pH, thermal stability, and inhibition study). In these PAP preparations, all activities were found only in the fractions which bound strongly to the Con A column and were undetectable in the Con A unbound fractions and in the fractions which bound weakly to the Con A column. The relative amounts of PAP which bound strongly to the Con A column but passed through the WGA column, were significantly greater in BPH-derived PAP than in PCA-derived PAP. In contrast, the relative amounts of PAP which bound strongly to the Con A column and bound to the WGA column, were significantly greater in PCA-derived PAP than in BPH-derived PAP. The findings suggest that Asn-linked sugar-chain structures are altered during oncogenesis in human prostate and also suggest that studies of qualitative differences of sugar-chain structures of PAP might lead to a useful diagnostic tool for PCA.

Acid Phosphatase↗

Duodenal atresia in dizygotic twins.

The authors report duodenal atresia occurring in both members of dizygotic twins who showed no signs of Down's syndrome, and both had normal chromosomal constitutions. They both had the two unlinked end type of atresia in the second portion of the duodenum, and direct end-to-end duodenoduodenostomy was carried out. Their postoperative courses were smooth, and both babies were discharged 32 days after birth. Their mother underwent pituitary adenoma removal and partial parathyroidectomy for multiple endocrine neoplasia (MEN-type I). She had been given hormonal supplement therapy after surgery and became pregnant after exogenous gonadotropin therapy. Environmental factors may be responsible for some cases of duodenal atresia.

Diseases in Twins↗