Search PubMed⌕ Search

Biomedical subjects

S Fukumoto

Publications and source records attributed to S Fukumoto.

At least 145 records · Page 8Linked to original sources
PubMed1995

[Current status and problems in the classification of parathyroid diseases].

Abnormalities in serum calcium level usually lead to the diagnosis of parathyroid diseases. Therefore, parathyroid diseases can be classified according to serum calcium levels of the patients. However, the present classification of the diseases have several problems. First, the existence of some of the historically wellknown parathyroid diseases is still under controversy at present. Second, recent studies using molecular and cellular biological approaches have uncovered several genetic abnormalities in some parathyroid tumors, suggesting that parathyroid adenoma or cancer is not a homogeneous disease entity. Third, there remain many unanswered problems to explain the pathogenesis of various parathyroid diseases including pseudohypoparathyroidism. Further elucidation of the pathogenesis of parathyroid diseases should enable us to establish a better classification of these diseases.

Calcium↗
PubMed1994

Regulation of plasminogen activator inhibitor-1 (PAI-1) expression by 1,25-dihydroxyvitamin D-3 in normal and malignant rat osteoblasts.

In rat calvarial osteoblast-like cells and in clonal osteogenic sarcoma cells (UMR 106-01), 1,25-dihydroxyvitamin D-3 (1,25(OH)2D3) enhanced plasminogen activator (PA) activity and decreased PA inhibitor-1 (PAI-1) production over the same concentration range. Steady-state levels of mRNA for PAI-1 were also decreased by 1,25(OH)2D3 in a dose-dependent manner, without significant effects on mRNA for either tissue-type PA (tPA) or urokinase-type PA (uPA). When protein synthesis was inhibited by cycloheximide treatment in UMR 106-01 cells, the action of 1,25(OH)2D3 on PAI-1 mRNA was abolished, as was observed previously with parathyroid hormone (PTH) treatment. In osteoblast-like cells however, 1,25(OH)2D3 and PTH actions differed, in that 1,25(OH)2D3 had no effect on either PAI-1 or uPA mRNA levels under conditions of protein synthesis inhibition, whereas PTH decreased PAI-1, and increased uPA mRNA. Identification of proteins involved in these actions may help to explain differences in molecular regulation by PTH and 1,25(OH)2D3, two agents which have similar actions on osteoblasts, but employ different signal transduction pathways.

Animals↗
PubMed1994

Hepatitis may precede the occurrence of precore region mutation in hepatitis B virus genome during infection in young carriers.

To understand when the mutation with a stop codon of precore region in hepatitis B virus genome occurs, the prevalence of the mutation of viral DNA clones propagated from sera of school-age carriers was investigated with respect to hepatitis B e antigen (HBeAg)/anti-HBe and sequential changes of mutants along HBeAg seroconversion were analyzed. Of 32 carriers aged 8-18 years, 14 HBeAg(+) patients had 2.2% mutant clones, whereas 8 patients with low titer anti-HBe had a higher rate of 18.1% (P < 0.01) and the highest rate of 61.3% was found in 10 patients with high anti-HBe titer (P < 0.001). By contrast, the amount of viral DNA decreased significantly in patients with anti-HBe. Sequential analysis in six cases revealed three types of seroconversion with time difference of the emergence and increase of mutant clones. It is concluded that mutation occurs at a relatively young age and increases along time and/or HBeAg seroconversion. Hepatitis might precede or accelerate the emergence and increase of mutant population which might be predictive of sustained resolution of the disease.

Adolescent↗
PubMed1994

Alpha-fetoprotein-producing early gastric cancer accompanying liver cirrhosis: a case report.

A rare case of alpha-fetoprotein (AFP)-producing early gastric cancer with liver cirrhosis is presented. A 61-year-old man was admitted to Shimane Medical University Hospital in 1988 because of abnormal liver function test results suggestive of liver cirrhosis with mild elevation of AFP. Liver cirrhosis was confirmed laparoscopically and histologically. Gastric cancer was found in fluoroscopic and endoscopic studies. After partial gastrectomy, the serum AFP level fluctuated transiently within normal limits, and then gradually increased soon after the operation. Therefore, complication of hepatocellular carcinoma was suspected, but no tumor in the liver was detected by any imaging examination, including angiography. Two years after the operation, swelling of abdominal periaortic lymph nodes was noted at a periodic checkup, but still no hepatic tumor was found. At this point, AFP-producing gastric cancer was suspected, and an AFP staining test was carried out on the tissue of the resected specimen. AFP-positive cells were recognized immunohistochemically. Thus, we diagnosed the condition as post-operative recurrence of an AFP-producing gastric cancer accompanying liver cirrhosis.

Adenocarcinoma↗
PubMed1994

Precore region mutation in hepatitis B virus genome in early stage of infection: a study in hepatitis B e antigen-positive young carriers.

To determine when the precore mutation at the 83rd nucleotide occurs, leading to the formation of a stop codon in the hepatitis B virus genome in carriers, which would indicate the presence of antibody to hepatitis B e antigen (anti-HBe), we investigated this mutation by direct sequencing and subcloning in 22 young hepatitis B antigen (HBeAg) (+) carriers. These subjects were 7-17 years old and were found during a survey for hepatitis B surface antigen (HBsAg) in three elementary schools, a junior high, and a senior high school. None of these carriers had clinical manifestations, although one-third of them had elevated serum alanine aminotransferase levels. All were HBeAg-positive by radioimmunoassay (RIA), and 6 of them had preserved titers of anti-HBe at the same time. Precore mutations were found in 4 subjects (18.2%), with predominance of the wild type. Although 3 of these 4 had preserved titers of HBeAb, the other had no HBeAb titers. In an other 3 subjects with preserved titers of HBeAb, the precore mutation was not detected, even after the subcloning of viral DNA. The remaining 15 subjects with HBeAg showed no precore mutation. Subjects with ALT levels exceeding 100 IU/l were all HBeAg-positive without the mutation. It was clear that the precore mutation itself occurred in the subjects at an early age during the course of infection. However, the chronological relationship between the emergence of the precore mutation and the onset of hepatitis requires further study.

Adolescent↗
PubMed1994

Treatment of malignancy-associated hypercalcemia with YM175, a new bisphosphonate: elevated threshold for parathyroid hormone secretion in hypercalcemic patients.

The effect of a new third generation bisphosphonate, YM175 (cycloheptylamino-methylene bisphosphonate), on serum calcium (Ca) and intact PTH levels was examined in 79 malignancy-associated hypercalcemia patients with serum Ca levels higher than 2.75 mmol/L. A single infusion of 2.5, 5, and 10 mg YM175 reduced serum Ca levels in a dose-dependent manner. YM175 was about 6 times more potent than 3-amino-hydroxypropylidene-1,1-bisphosphonate. Among 23 patients treated with 10 mg YM175, serum Ca decreased by more than 0.5 mmol/L in 20 patients and was normalized in 11 patients. Serum intact PTH was subnormal in all of these patients before treatment and remained subnormal in 12 patients (suppressed PTH group), but was elevated to normal or high levels after treatment in the remaining 11 patients (responsive PTH group). Serum Ca was significantly higher throughout the study period in the suppressed PTH group, and mean serum Ca at the nadir did not decrease below 2.90 mmol/L in this group. However, the rate or magnitude of reduction in serum Ca was not different in the two groups. Polynomial regression analysis revealed that the threshold of serum Ca for PTH secretion was elevated to 2.75 mmol/L in the responsive PTH group, whereas it was about the upper limit of normal when both groups were combined (2.59 mmol/L). Furthermore, in the responsive PTH group, the threshold for PTH secretion during the decreasing serum Ca phase (days 4 and 6) was higher than that during the increasing serum Ca phase (days 10 and 14). The changes in the threshold for PTH secretion were also observed in patients treated with lower doses of YM175. These results demonstrate that YM175 is one of the most potent currently available bisphosphonates, and that the threshold for PTH secretion is elevated in at least some malignancy-associated hypercalcemia patients. In addition, there appears to be a difference in the threshold for PTH secretion between the decreasing and increasing serum Ca phases similar to the previously reported hysteresis phenomenon.

Adult↗
PubMed1993

Inflammation of the liver causes mutations in duck hepatitis B virus genome.

To investigate whether hepatitis causes mutation in the viral genome, DNA sequences in the pre-core region of duck hepatitis B virus (DHBV) DNA were analyzed in both ducks with hepatitis and without hepatitis. Five DHBV carrier ducks were injected with DHBV particle proteins purified from duck serum with Freund's complete adjuvant (FCA) intrahepatically from 14 day posthatch for 9 weeks (immunized group). Serum was drawn at the end of the 1st and 4th week after the 1st injection of DHBV particle protein and ducks were killed at the end of the 9th week to obtain the liver. Another five ducks without treatment were used as controls. All ducks of the immunized group showed moderate to severe hepatitis at the 9th week. All ducks in the immunized group showed one mutation except one duck that showed two mutations only at the 9th week. Mutations were observed in the 5th, 13th, 21st, 22nd, and 28th codon of the pre-core region. All of them were point mutation at the 3rd base in the triplets. The frequency of mutation was different in each duck from 20% to 60% but not 100%. There was no mutations in ducks in control group. These results suggest that hepatitis causes mutation in the pre-core lesion genome of duck hepatitis B virus.

Animals↗
PubMed1993

Transforming growth factor beta stimulation of parathyroid hormone-related protein (PTHrP): a paracrine regulator?

The regulation of PTHrP expression and production by transforming growth factor-beta (TGF beta) has been investigated in an epidermal squamous cancer cell line COLO 16. TGF beta 1 treatment increased steady-state levels of PTHrP mRNA and concentrations of PTHrP immunoreactivity in conditioned medium in a time- and dose-dependent manner with a half-maximal effect at 40 pM. An effect of TGF beta 1 on PTHrP mRNA was observed first after 4 h treatment and continued to increase up to 48 h with a concomitant increase in PTHrP immunoreactivity in the culture medium. TGF beta 1 was found to stabilize PTHrP mRNA as assessed by actinomycin C1 experiments. In addition, a direct effect of TGF beta to increase PTHrP transcription was indicated by nuclear run-on and transient transfection experiments using a CAT promoter/expression construct encompassing the region -1100 bp to -20 bp from the initiating AUG of the human PTHrP gene. The conditioned medium from COLO 16 cells was also shown to contain both latent and active TGF beta at concentrations of 160 pM and 16 pM, respectively, in 72 h conditioned medium. A neutralizing antibody to TGF beta 1 (and TGF beta 2) decreased the level of immunoassayable PTHrP in the medium.

Base Sequence↗
PubMed1993

Clinical results of fractionated proton therapy.

PURPOSE: Preliminary results of a multi-site Phase I-II clinical trial investigating the efficacy of high-energy proton beams in a wide variety of human malignancies are reported. METHODS AND MATERIALS: Since 1983 proton radiotherapy using 250 MeV proton beams produced by a booster synchrotron of the National Laboratory for High Energy Physics has been carried out at Proton Medical Research Center, University of Tsukuba. As of September 1990, a total of 147 patients received a partial or full treatment with proton beams with curative intent; 92 patients (63%) were treated with proton beams alone and 55 patients (37%) with combined photon and proton beams. There were 91 males and the mean age was 61.8 years old. The follow-up observation period ranged from 10 to 97 months. With regard to a total tumor dose, nearly 80% of patients received 70 Gy or more and 53% received 80 Gy or more. While dose-fractionations used depended upon tumor sites, the large majority of patients received substantially high radiation doses in terms of larger total doses (> 70 Gy) and larger fraction sizes (> 2.5 Gy) than those traditionally used. This fractionation regimen has been used because of limited availability of the accelerator or a shortage of machine time (27-30 weeks/year, 3-3.5 hr/day), and also by the expectation that the superior dose distribution possible with protons will permit administration of high radiation doses without increasing morbidities. In connection with this, we have determined the target volume by setting margins around the tumor boundary as practically small as possible, ranging from 5 to 10 mm. RESULTS AND CONCLUSIONS: The current trial has been based on a site and dose searching program, hence a wide variety of tumor sites including the aerodigestive organs has been treated. So far, our judgment is that proton therapy has proven of potential advantage in treatment of the lung, esophageal, liver, uterine cervix, prostate, and head and neck malignancies; and of possible value in treatment of high-grade gliomas, and gastric, urinary bladder, and pediatric tumors.

Adolescent↗
PubMed1993

The plasminogen activator and inhibitor system in bone remodelling.

The neutral protease, plasmin, is generated by plasminogen activators, and is ascribed an important role in several physiological and pathological circumstances characterized by tissue remodelling and cell motility. The two types of plasminogen activator, tissue-type (tPA) and urokinase-type (uPA), are produced by osteoblasts, as is the specific PA inhibitor, PAI-1. Some hormones which activate bone resorption increase PA activity produced by osteoblasts, by decreasing the production of PAI-1. The increased PA activity has been suggested to facilitate bone resorption by activating latent collagenase, thus preparing the bone surface for osteoclastic resorption. Targeted and regulated production of plasmin might also contribute to the coupling of bone formation to resorption, by activating latent TGF beta in bone, and activating IGF-1 by freeing it from association with inhibitory binding protein. TGF beta itself is a powerful inhibitor of PA activity, an effect achieved by enhancing mRNA and protein for PAI-1. Thus the PA system is a potentially important regulatory system in bone remodelling, whose local activity is controlled through concerted actions of hormones and locally generated growth factors and cytokines.

Animals↗
PubMed1993

[Giant calcified meningioma after radiation therapy for previous ependymoma: a case report].

We presented a case of secondary giant meningioma with dense calcification (brain stone) after radiation therapy for primary ependymoma removed 25 years before. A 31-year-old man was referred to our hospital because of generalized convulsion. He had received extirpation of an ependymoma in the left frontoparietal region and postoperative radiation therapy 25 years before. Skull X-ray and CT revealed a giant brain stone in the left parietal region. It was totally removed en bloc. Photomicrograph of the specimen showed proliferation of arachnoid cell-like tumor cells in narrow spaces surrounded by marked calcified lesions which showed partial ossification. The etiology and therapy of this tumor were discussed.

Adult↗
PubMed1993

[The effects of Ara-A on viral markers in duck hepatitis B virus carrier ducks].

Duck hepatitis B virus (DHBV) carrier ducks of one week old were injected with Ara-A (adenine arabinoside) of different dose including 2.5 (11 ducks), 5.0 (11), 10.0 (10) and 20.0 (10) mg/kg for 14 days. This antiviral effect showed dose-dependence up to 5.0 mg/kg and this dose seemed effective to obtain significant antiviral effect. Viral DNA and DNA polymerase activity were reduced significantly from the 1st week after starting the administration of Ara-A. This antiviral effect was maintained even at the 1st week after discontinuation of the drug. These findings were quite similar to those observed in HBV carriers. With the increasing necessity of Ara-A treatment in patients who will not respond to interferon therapy, DHBV seemed a suitable model for the investigation of the dose and antiviral effect of Ara-A treatment in humans.

Animals↗
PubMed1992

Synthesis and thromboxane A2/prostaglandin H2 receptor antagonistic activity of phenol derivatives.

Consideration of possible structural similarities between thromboxane A2 and the hydroquinone form of (R)-(+)-7-(3,5,6-trimethyl-1,4-benzoquinon-2-yl)-7- phenylheptanoic acid (R-(+)-AA-2414) led to the development of a new series of thromboxane A2/prostaglandin H2 (TXA2/PGH2) receptor antagonists, namely 7-(4-fluorophenyl)-7-(2-hydroxyphenyl)heptanoic acids (I). These compounds were found to be potent TXA2/PGH2 receptor antagonists. Compounds having either a carbonyl or a hydroxymethyl group at the para-position of the phenolic hydroxy group exhibited most potent activities in this series. Compounds 14, 15, 18, and 26 inhibited the specific binding of [3H]U-46619 to guinea pig platelet membranes (IC50 = 4.4, 80, 32, and 13 nM, respectively), and also inhibited U-46619-induced human platelet aggregation (IC50 = 310, 69, 79, and 78 nM, respectively). Comparison of the UV spectra of the compounds with a carbonyl group at the para-position of phenolic hydroxy group revealed that the activity tended to increase in accordance with a decrease in the torsional angle between the carbonyl group and the phenol ring. These results suggested that the spacial location of the carbonyl and hydroxymethyl oxygen are important for significant increase in activity and that the carbonyl and hydroxymethyl oxygen at the para-position of the phenolic hydroxy group might interact with one of the TXA2/PGH2 receptor sites.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1992

Plasminogen activator regulation in osteoblasts: parathyroid hormone inhibition of type-1 plasminogen activator inhibitor and its mRNA.

In order to determine the mechanism by which parathyroid hormone (PTH) stimulates plasminogen activator (PA) activity in rat osteoblasts, we investigated the effect of human PTH(1-34) [hPTH(1-34)] on the synthesis of mRNAs for tissue-type PA (tPA), urokinase-type PA (uPA), and PA inhibitor-1 (PAI-1), and on release of PA activity and PAI-1 protein in both normal rat calvarial osteoblasts and UMR 106-01 osteogenic sarcoma cells. hPTH(1-34) (0.25-25 nM) decreased PAI-1 mRNA and protein, and increased PA activity in both cell types in a dose-dependent manner with ED50 of about 1 nM for both responses. Forskolin and isobutylmethylxanthine also stimulated PA activity and decreased PAI-1 protein and mRNA in both cell types. hPTH(1-34) did not show any consistent effect on tPA and uPA mRNA in calvarial osteoblasts, but a modest (two-fold) increase of both mRNAs was observed in UMR 106-01 cells treated with 25 nM hPTH(1-34). However, when protein synthesis was inhibited with 100 microM cycloheximide, the increase of tPA and uPA mRNA by hPTH(1-34) was enhanced in UMR 106-01 cells and became evident in calvarial osteoblasts. Fibrin autography also revealed that hPTH(1-34) increases tPA and uPA activity, especially after cycloheximide treatment in UMR 106-01 cells. These results strongly suggest that PTH increases PA activity predominantly by decreasing PAI-1 protein production through a cyclic adenosine monophosphate (cAMP)-dependent mechanism in rat osteoblasts. The reduction of PAI-1 protein by PTH results in enhanced action of both tPA and uPA, and would contribute to the specific roles of these PAs in bone.

Animals↗
PubMed1992

Glucocorticoid regulation of plasminogen activator inhibitor-1 messenger ribonucleic acid and protein in normal and malignant rat osteoblasts.

Glucocorticoids exert potent inhibitory effects on bone formation. We have previously shown that glucocorticoids suppress plasminogen activator (PA) activity in normal and malignant rat osteoblasts. To clarify the mechanism of this suppression, we investigated the effects of dexamethasone on PA inhibitor-1 (PAI-1), tissue-type PA (tPA), and urokinase-type PA (uPA) expression and also on PAI-1 protein and PA activity in both normal rat calvarial osteoblasts and a clonal osteogenic sarcoma cell line, UMR 106-01. Dexamethasone increased PAI-1 mRNA and protein in both cell types. The increase in PAI-1 protein and the decrease in PA activity were obtained over the same concentration range, with a half-maximally effective concentration of dexamethasone of about 10(-9) M. The increase in PAI-1 mRNA caused by dexamethasone was retained with cycloheximide treatment, but abolished with actinomycin-D. Dexamethasone had no effect on tPA or uPA mRNA in either cell type. The glucocorticoid antagonist RU 486 prevented the effects of dexamethasone on PA activity and PAI-1 protein. Dihydrotestosterone, progesterone, and 17 beta-estradiol did not influence PA activity or PAI-1 formation. Although tPA and uPA protein could not be measured, these results suggest that glucocorticoids suppress PA activity predominantly by increasing PAI-1 synthesis in rat osteoblasts. Suppression of PA activity through actions on PAI-1 formation by glucocorticoids could contribute to the mechanisms by which glucocorticoids inhibit bone formation.

Animals↗
PubMed1992

Comparison of isozyme patterns between Spirometra erinacei and Spirometra mansonoides by isoelectric focusing.

No differences were observed in the isozyme patterns of 4 enzymes examined between fresh samples stored at -80 C and samples stored at room temperature for 10 days after lyophilization, which supports the validity of comparing lyophilized samples to fresh frozen tissue. Mature proglottids as well as plerocercoids of Spirometra erinacei from Japan and Australia were indistinguishable by comparison of isozyme patterns after isoelectric focusing. The isozyme patterns of acid phosphatase, glucosephosphate isomerase (GPI), and mannosephosphate isomerase from plerocercoids of Spirometra mansonoides were distinctly different from those of plerocercoids of S. erinacei. The adenylate kinase isozyme patterns of the mature proglottids of S. mansonoides were also distinctly different from those of the mature proglottids and the plerocercoids of S. erinacei. The GPI isozyme pattern of the mature proglottids of S. mansonoides was also distinguishable from the GPI patterns of those of S. erinacei. These electrophoretic data suggest that the S. erinacei from Japan and Australia are closely related, if not identical, but that S. mansonoides is genetically distinct from S. erinacei.

Acid Phosphatase↗