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Biomedical subjects

S Ozeki

Publications and source records attributed to S Ozeki.

At least 55 records · Page 3Linked to original sources
PubMed1996

Biphasic changes in serum hepatocyte growth factor after transarterial chemoembolization therapy for hepato-cellular carcinoma.

To investigate the physiological significance of hepatocyte growth factor (HGF) after transcatheter arterial chemo-embolization (TACE), we measured serum HGF levels in 23 patients who underwent angiography (n = 3) or TACE (n = 20). HGF levels increased biphasically after TACE. It rapidly increased to 10-fold higher levels immediately after heparin-injection even before embolization. Serum HGF then decreased to below 1.0 ng/ml at 6 hours after the procedure. The second peak (a 2-fold increase) appeared 1-3 days after TACE. The first increase may be due to the injection of heparin which releases HGF from the cell-surface and extracellular matrix of the liver. Patients treated to a larger extent showed higher increase in serum HGF levels, and thus the impaired hepatic HGF clearance and size of regeneration may cause second elevation of serum HGF levels. Six out of eleven patients whose serum HGF levels before TACE were more than 0.5 ng/ml died in the follow-up period whereas no patients died with serum HGF under 0.5 ng/ml. Therefore, serum HGF levels before the procedure have the potential to be a good indicator of outcome.

Aged↗
PubMed1996

Induction of hepatocyte growth factor in the liver, kidney and lung following total body irradiation in rat.

Hepatocyte growth factor (HGF) has been shown to have a pleiotropic function to act as a potent organotropic factor in the regeneration of injury in various organs, including the liver, kidney and lung. To examine the involvement of HGF in radiation injury, the authors analysed the changes in HGF mRNA and HGF protein levels in the rat organs (liver, lung, kidney) and plasma following 6 Gy of total body irradiation. Expression of HGF mRNA in the liver and kidney increased 6-48 h after total body irradiation and returned to previous values 1 week later. HGF protein levels in lung and liver showed 1.3-2-fold elevations 1-2 weeks after irradiation (P < 0.05). HGF levels in plasma stayed at undetectable levels up to 1 month after total body irradiation. The labelling index determined 2 weeks and 1 month after total body irradiation indicated no enhancement of regeneration. Thus, total body irradiation induced transient HGF elevation in these organs without enhancement of regeneration.

Alanine Transaminase↗
PubMed1996

Quinolone-resistant Neisseria gonorrhoeae: correlation of alterations in the GyrA subunit of DNA gyrase and the ParC subunit of topoisomerase IV with antimicrobial susceptibility profiles.

Fifty-five clinical strains of Neisseria gonorrhoeae were examined for mutations in the gyrA and parC genes and for antimicrobial susceptibility profiles. The MICs of quinolones for 31 strains with alterations in GyrA were significantly higher than the MICs for 24 strains without such alterations. Eleven strains with alterations in both GyrA and ParC were significantly more resistant to fluoroquinolones than those with alterations in GyrA alone. The MICs of cephalosporins for these strains were also significantly higher than those for other strains.

Amino Acid Sequence↗
PubMed1996

Rapid detection of point mutations of the Neisseria gonorrhoeae gyrA gene associated with decreased susceptibilities to quinolones.

Mutations in the gyrA gene resulting in amino acid changes at Ser-91 and Asp-95 are significantly associated with decreased susceptibilities to quinolones in Neisseria gonorrhoeae. To detect these mutations, we developed a rapid and simple assay based on amplification of the region of the gyrA gene containing the mutation sites by PCR and digestion of the PCR product with a restriction enzyme. A naturally occurring HinfI restriction site was present in the region containing the Ser-91 codon, and an artificial HinfI restriction site was created in the region containing the Asp-95 codon by the method of primer-specified restriction site modification. The mutations generating alterations at Ser-91 and Asp-95 were detected as restriction fragment length polymorphisms of the PCR products digested with HinfI. Fifty-five clinical strains of N. gonorrhoeae were examined for mutations in the gyrA gene by this method. Mutations at Ser-91 and/or Asp-95 were detected in all the 31 strains in which the mutations had been confirmed by DNA sequencing. Our method allows simultaneous testing of a large number of strains and provides results within 8 h. This rapid and simple assay could be a useful screening device for genetic alterations associated with decreased susceptibilities to quinolones in N. gonorrhoeae and could facilitate epidemiological studies on clinical isolates of N. gonorrhoeae with decreased susceptibilities to quinolones.

Base Sequence↗
PubMed1996

Evidence that implicates the parathyroid hormone-related peptide in vascular stenosis. Increased gene expression in the intima of injured carotid arteries and human restenotic coronary lesions.

Proliferation of vascular smooth muscle cells (VSMCs) is considered to be one key event underlying the pathophysiology of restenosis after angioplasty. The parathyroid hormone-related peptide (PTHrP) and its receptor, a local autocrine and paracrine regulator of cellular growth in a variety of normal cell types, have been reported in the vicinity of VSMCs. To investigate how PTHrP might be involved in the process of neointimal formation after balloon angioplasty, we examined PTHrP expression in balloon-denuded rat carotid arteries and human coronary arteries that had been retrieved by directional atherectomy. In rat carotid arteries, the RNase protection assay and in situ hybridization demonstrated that PTHrP mRNA expression increased fourfold to sixfold 1 to 7 days after denudation and continued for 28 days, coincident with downregulation of PTH/PTHrP receptor mRNA expression. In situ hybridization and immunohistochemistry revealed that PTHrP expression in balloon-denuded carotid arteries was mainly localized to the neointima. To confirm the involvement of the PTHrP in human coronary artery restenotic lesions, immunohistochemical analysis of human coronary atherectomy specimens (23 primary and 10 restenotic lesions) was then performed. The number of intimal cells that expressed PTHrP protein was significantly higher in restenotic (407 +/- 53 cells/mm2; range, 143 to 739) than in stable angina (50 +/- 12 cells/mm2; range, 18 to 132; P<.05) or unstable angina (129 +/- 16 cells/mm2; range, 21 to 232; P<.05) specimens. These data demonstrate that PTHrP gene expression in VSMCs markedly increases during neointimal formation, supporting the hypothesis that PTHrP may play an important role in vascular stenosis as a regulator of VSMC proliferation.

Adult↗
PubMed1996

[Leiomyosarcoma of the scrotum: a case report].

A case of leiomyosarcoma of the scrotum is reported. A 44-year-old man referred to our hospital with the complaint of swelling of the left scrotal contents. The lesion was about 3 cm in diameter, isolated from testis, epididymis and spermatic cord. Ultrasonography revealed hypoechoic and slightly heterogenic area in the lesion. Surgical resection was easily done. Histological examination showed leiomyosarcoma. Adjuvant therapy was not performed. Three years after the resection, he is alive without any sign of recurrence or metastasis.

Adult↗
PubMed1996

Late local recurrence after radiotherapy for tongue and early glottic carcinoma.

BACKGROUND/AIM: Late local recurrence after radiotherapy for tongue and early glottic carcinoma is rarely discussed. In the head and neck cancer, approximately 90% of local recurrence occurred within 2 years after radiotherapy. However, we found that late local recurrence after radiotherapy for glottic cancer was not rare. Our aim was to evaluate the late local recurrence after radiotherapy for early glottic and tongue cancer. PATIENTS AND METHODS: From 1967 through 1982, 633 patients with tongue carcinoma and 330 patients with early (T1T2N0) glottic carcinomas were treated at the Department of Radiology, Osaka University Hospital. Of these 821 patients, 329 patients with tongue carcinoma and 221 patients with early glottic carcinoma survived at 5 years after radiotherapy without local recurrence. For tongue carcinoma, patients were divided by T category. For early glottic carcinoma, patients were divided by the tumor response at 40 Gy. RESULTS: Late local recurrence occurred in 23 of 329 patients (7%) with tongue carcinoma, and in 9 of 221 (4%) with early glottic carcinoma. For tongue carcinoma, late recurrence occurred in 19 of 249 patients (8%) in stage I and II, and 4 of 80 patients (5%) in stage III and IV. For glottic carcinoma, late recurrence occurred in 8 of 137 patients (6%) with tumor clearance at 40 Gy and 1 of 63 patients (2%) with tumor persistence at 40 Gy. The incidence of double cancer was also evaluated. Of 329 5-year survivors with tongue carcinoma, 39 patients (12%) had another malignancy, and 26 patients of 221 5-year survivors with early glottic carcinoma (12%) had also another malignancy. Of 39 double primaries of tongue carcinoma, 10 patients (26%) had head and neck malignancies, and none of 26 double primaries of early glottic carcinoma. CONCLUSION: Late local recurrence was not rare in tongue and early glottic cancer. Poor prognostic group showed lower incidence of late recurrence than good prognostic group. This result suggests that secondary tumor at the same site of primary tumor is late local recurrence.

Carcinoma↗
PubMed1995

Effect of dosing volume on gastrointestinal absorption in rats: analysis of the gastrointestinal disposition of L-glucose and estimation of in vivo intestinal membrane permeability.

The effect of the oral dosing volume (DV) on both gastric emptying and intestinal absorption was examined by analyzing the gastrointestinal disposition of a model solute, L-glucose, in rats. The amount of 14C-labeled L-glucose in the gastric and intestinal contents of sacrificed rats was measured at various times after administration, and the data were analyzed with a linear model, assuming first-order gastric emptying followed by first-order intestinal absorption. The gastric emptying rate constant (kg) rose from 0.025 to 0.072 min-1 by increasing DV from 0.1 to 3 mL/rat, whereas the intestinal absorption rate constant (ka) decreased from 0.031 to 0.015 min-1. This decrease in ka was attributed to an increase in the average intestinal lumen volume (Vav) from 24 to 39 microL/cm, assuming that the relationship ka = CLa,app/Vav holds (where CLa,app is the apparent intestinal membrane permeability clearance or the product of the apparent membrane permeability coefficient and surface area). The CLa,app (= kaVav), a measure of the in vivo intestinal membrane permeability, was 0.74 microL/cm/min for a DV value of 0.1 mL/rat and decreased only marginally by 20% for larger values of DV, suggesting an insignificant effect of DV on CLa,app. These results suggest that the accelerating effect of the increased kg, produced by the increased DV on the gastrointestinal absorption, may be canceled by the decrease in ka. A decrease in ka may lead to a decrease in the fraction absorbed. Finally, this study also provides a means for carrying out physiological modeling of drug absorption following oral administration.

Animals↗
PubMed1995

The proliferative activity in oral epithelial dysplasia analyzed by proliferating cell nuclear antigen immunostaining and argyrophilic nucleolar organizer region staining.

The proliferative activity of leukoplakia without dysplastic change (LP), epithelial dysplasia (ED), and squamous cell carcinoma (SCC) in the oral mucosa was examined by means of proliferating cell nuclear antigen (PCNA) immunostaining, silver-binding argyrophilic nucleolar organizer region (AgNOR) staining, and the frequency of mitotic figures. Significant differences in the labeling index of PCNA immunostaining (PI) and mitotic index (MI) were noted between LP and ED and between ED and SCC. The mean numbers of AgNORs (AI) significantly differed between ED and SCC. There was a significant positive correlation between PI and MI in samples of ED. However, there was no significant correlation between AI and other indexes. The number and the distribution of PCNA-positive cells in ED varied among samples. Five samples with higher PI and MI indexes than the mean values were selected from those of dysplasia based on the correlation between PI and MI. Their histological features symptomatic of oral ED as defined by the World Health Organization (WHO) Collaborating Centre in 1978, were investigated and compared with 10 samples with lower indexes. Histological findings, such as "loss of polarity of the basal cells," "an increased nuclear-cytoplasmic ratio," "cellular pleomorphism," and "enlarged nucleoli," were significant histological features of these five samples. This study showed that the four histological components described previously and the increased number of mitotic figures used as the index of proliferating activity were the main histological components related to severe ED of oral mucosa. They will provide a useful means of deciding the histopathological grade of oral ED.

Adult↗
PubMed1995

[A case report of prostate cancer resistant to endocrine therapy successfully treated with intra-arterial chemotherapy].

A 73-year-old male with low abdominal pain on urination and frequent urination was diagnosed as poorly differentiated adenocarcinoma of prostate. He received endocrine therapy with DESD and bilateral orchiectomy. This treatment was not effective, so he was given intra-arterial infusion chemotherapy with MTX, ADM and CDDP using the reservoir system. After 2 courses of this chemotherapy the regression rate was 75%, and the pathological examination after the chemotherapy revealed no cancer cells. There is no established chemotherapy for prostate cancer at present. Thus this case is very suggestive for the treatment of prostate cancer.

Adenocarcinoma↗
PubMed1994

Coronary atherosclerotic smooth muscle cells overexpress human parathyroid hormone-related peptides.

Parathyroid hormone-related peptide (PTHrP) was originally characterized as a tumor product responsible for hypercalcemia of malignancy and was subsequently found to be produced in many normal tissues. PTHrP is now suggested to play a critical role in the local modulation of vascular smooth muscle function. To elucidate the involvement of PTHrP in coronary atherosclerosis, we immunohistochemically examined coronary arteries obtained from 76 patients with various grades of atherosclerosis and compared the correlation between PTHrP staining and the percent stenosis. Smooth muscle cells at sites of coronary atherosclerosis overexpressed PTHrP, while cells from normal coronary arteries did not. The in situ hybridization using PTHrP riboprobe has also proven the overexpression of PTHrPmRNA in the affected lesions following atherectomy. The intensity of PTHrP expression by smooth muscle cells was significantly correlated with the degree of coronary artery stenosis. Coronary arterial PTHrP overexpression is closely related to the severity and/or progression of coronary atherosclerosis.

Adult↗
PubMed1994

Intra-arterial chemotherapy using a reservoir for endocrine-refractory prostate cancer.

For local control in patients with endocrine-refractory prostate cancer, an intra-arterial chemotherapy regimen comprising methotrexate (MTX), Adriamycin (ADM), and cisplatin (CDDP) was evaluated. A total of 19 patients having a mean age of 66.4 +/- 8.8 years and a mean performance status (PS) of 1.3 +/- 1.0 were enrolled. Of these patients, 3 had proved to be resistant to initial endocrine therapy and the remaining 16 had relapsed from disease stabilization after endocrine therapy. The catheter tip was placed in the internal iliac artery in 16 cases, in the common iliac artery in 2 cases, and in the aorta in 1 case after occlusion of the contralateral feeding artery. The intraarterial chemotherapy was performed mainly using MTX (30 mg/m2), ADM (30 mg/m2), and CDDP (50 mg/m2) as one course and was repeated for a mean of 2.9 +/- 2.3 courses. Then, in an outpatient clinic, 5-fluorouracil (5-FU), ADM, or MTX was given intra-arterially as maintenance chemotherapy until re-relapse. As based on the criteria for evaluation of nonsurgical therapy in prostate cancer proposed by the Japanese Urological Association, the prostatic lesion showed a partial response (PR) in 9 cases and no change (NC) in 10 cases. As judged from the response of prostate-specific antigen (PSA), a complete response (CR) was obtained in 6 cases, a PR, in 3 cases; and NC and progressive disease (PD), in 2 cases each. Therefore, the overall response rate was 63%. Improvement in the symptoms was observed in 83% of patients. The duration of the response was 15.1 +/- 10.5 months for the PR cases and 7.4 +/- 5.7 months for the NC cases. Furthermore, the mean survival time observed in the PR group was 38.9 months, which was better than that seen in the NC (16.4 months) and PD (10.5 months) groups. These results suggest that intra-arterial chemotherapy may become an option for the treatment of locally advanced and endocrine-refractory prostate cancers. Using a reservoir, this chemotherapy can be easily given in an outpatient clinic.

Abdominal Muscles↗
PubMed1994

Central squamous cell carcinoma of the mandible. Computed tomographic findings.

Five cases of central squamous cell carcinoma of the mandible were investigated with the use of computed tomography. Bucco-lingual extent and spread along the mandibular division of the trigeminal nerve were evaluated. Three patients with trismus showed involvement of the masseter or medial pterygoid muscle on computed tomography. Involvement of more than two landmarks along the trigeminal nerve were observed in cases with both paresthesia of the lower lip and severe pain that resembled neuralgia. Perineural invasion was confirmed histologically in four cases, and all of these patients had both severe pain and mandibular canal involvement that could be demonstrated with computed tomography. When localized soft tissue changes are evident along the course of the trigeminal nerve in the region between the mandibular foramen and foramen ovale, ascending perineural spread should be suspected. Computed tomography findings correlated well with clinical symptoms but added information about the spread of the lesion within the surrounding soft tissue.

Carcinoma, Squamous Cell↗
PubMed1994

New human oral squamous carcinoma cell line and its tumorigenic subline producing granulocyte colony-stimulating factor.

A new human carcinoma cell line, MISK81-5, was established from a metastatic lymph node of oral squamous cell carcinoma. Immunocytochemical and ultrastructural observations revealed an obvious epithelial origin of the cell line. Chromosome analysis revealed a hypertriploid karyotype with numerical and structural anomalies. MISK81-5 cells could form a tumor mass in the subcutaneous tissue of recipient BALB/c athymic mice only when coinjected with Matrigel. A stem cell assay revealed that conditioned medium (CM) of MISK81-5 contained granulocyte colony-stimulating factor (G-CSF) or interleukin-6 activity. Quantitation by ELISA disclosed a higher concentration of G-CSF in the CM of MISK81-5 than in the CM of other squamous and gastric carcinoma cell lines. The sMISK, that was derived from MISK81-5 as a subpopulation of the cell line having higher tumorigenicity, also showed a similar hematopoietic stimulating activity to that of MISK81-5. These characteristics of the MISK81-5 cell line and its subpopulation, sMISK will be useful for studying the biological behavior of oral squamous cell carcinomas and its relation to hematopoietic stimulating factors.

Aged↗
PubMed1994

Expression of parathyroid hormone-related peptide in relation to perturbations of gastric motility in the rat.

We studied the expression of PTH-related peptide (PTHrP) and its mRNA in rat gastric smooth muscle in relation to various gastric motility states. Male rats were divided into groups subjected to fasting, feeding ad libitum, cold restraint stress, pyloric ligation, and carbachol stimulation. Cold restraint stress induced abnormal contractions. Rhythmic and moderate contractions were produced by carbachol administration, and marked distension was induced by pyloric ligation. PTHrP mRNA expression was weak in the physiological fasting and feeding states, but was markedly increased by pyloric ligation and carbachol stimulation. PTHrP and its mRNA were localized to the proper muscle layer and muscularis mucosa, but not in the mucosa by immunohistochemistry and in situ hybridization. The gene expression of PTHrP receptor in the gastric tissue was confirmed by reverse transcription-polymerase chain reaction, but serum PTHrP levels did not increase in all groups. These findings suggest that PTHrP acts as an autocrine or paracrine factor in gastric smooth muscle that responds to muscle activity caused by distension and cholinergic stimulation. However, PTHrP gene expression was decreased by stress despite the presence of strong contractions, and the sufficient relaxation did not occur. PTHrP suppression by stress is caused by the increase in corticosterone, as pretreatment of metyrapone, an inhibitor of 11 beta-hydroxylation, enhanced PTHrP gene expression in association with serum corticosterone suppression. In conclusion, PTHrP might be an important gastrointestinal peptide that regulates gastric contractile activity and is influenced by the serum corticosterone level.

Animals↗
PubMed1994

Gastric emptying-limited oral absorption of alpha-linolenic acid administered as a milk fat-globule membrane (MFGM) emulsion in rats.

As a study to assess the potential application of milk fat-globule membrane (MFGM), which is of natural origin and expected to be a safer alternative to synthetic emulsifiers, to pharmaceutical dosage forms, the oral absorption of alpha-linolenic acid was evaluated by the analysis of gastrointestinal disposition after oral administration as an MFGM emulsion to rats. A linear model incorporated with first-order gastric emptying followed by first-order intestinal absorption was fitted to the data of the remaining fraction of alpha-linolenic acid versus time profiles for the stomach and small intestine to estimate the rate constants of gastric emptying (kg) and intestinal absorption (ka). The ka (0.045 min-1) was about 4 times larger than the kg (0.011 min-1). The kg was comparable to the apparent oral absorption rate constant estimated by the pharmacokinetic analysis of plasma concentration data. These results suggest that the oral absorption of alpha-linolenic acid administered as MFGM emulsion is gastric emptying-limited and, hence, any change in the intestinal absorption process would only modestly affect its oral absorption.

Animals↗
PubMed1994

Evaluation of milk fat-globule membrane (MFGM) emulsion for oral administration: absorption of alpha-linolenic acid in rats and the effect of emulsion droplet size.

The performance of milk fat-globule membrane (MFGM) emulsion as an oral dosage form was evaluated in rats using [14C]alpha-linolenic acid as a lipophilic model solute. For emulsions prepared by homogenization alone, the area under the plasma concentration versus time curve (AUC) after oral administration tended to be larger for MFGM emulsion, 35.0 +/- 2.5 micrograms eq.h/ml (mean +/- S.E., n = 3), than for Tween 80 emulsion, 28.5 +/- 0.6 micrograms eq.h/ml at p < 0.1, though the peak plasma concentration (Cmax) and the time required to reach Cmax (Tmax) were not significantly different. The absorption in the intestinal loop was not significantly different between the two emulsions, either. Thus, MFGM emulsion, compared with Tween 80 emulsion, did not show an obvious advantage or enhancement in the oral and intestinal absorption of alpha-linolenic acid, except for a slight increase in AUC. However, MFGM could be a good alternative to a synthetic emulsifier for oral use, considering that it is of natural origin and may be safer. In addition, it was shown that the AUC, as well as the absorption in the intestinal loop, was decreased for a MFGM emulsion in which the droplet size was reduced by sonication, presumably because of the observed decrease in alpha-linolenic acid concentration in the water phase, which was assumed to be the result of an increased distribution of alpha-linolenic acid, due to its amphipathic nature, to the increased oil-water interface.

Administration, Oral↗