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Biomedical subjects

K Teramura

Publications and source records attributed to K Teramura.

At least 19 recordsLinked to original sources

Malignant gastrointestinal stromal tumor showing remarkable whorl formations.

A case of malignant gastrointestinal stromal tumor (GIST) is reported. Histologically, spindle cell proliferation with remarkable whorl formations was predominant in the tumor. Immunohistochemically, the tumor cells were diffusely positive for CD117 (c-Kit) and vimentin and partially positive for CD34. Ultrastructurally, the desmosome-like structures and interdigitations occurred much more frequently in the areas with whorl formations. These organelles were considered to be closely associated with the whorl formations. Various kinds of cellular arrangements are revealed in GISTs, but remarkable whorl formations, such as in our case, are a rare variant pattern. Herein, we discuss the histopathologic differences between this and other tumors showing whorl formations and describe the meaning of this unique arrangement. GISTs are thought to be immature tumors, and, therefore, variations in histopathologic findings are recognized. Finally, the ultrastructural study of GISTs is useful for understanding the mechanisms forming whorl formations and the differentiation or pathogenesis of GISTs.

Aged↗

Effects of interferon-alpha on peripheral neutrophil counts and serum granulocyte colony-stimulating factor levels in chronic hepatitis C patients.

Granulocytopenia is commonly observed in interferon-alpha (IFN-alpha) therapy. Granulocyte colony-stimulating factor (G-CSF) has been identified as a primary cytokine that regulates neutrophil production, but the kinetics of G-CSF in IFN-alpha-induced granulocytopenia remains unclear. We investigated the effects of IFN-alpha on serum G-CSF levels and peripheral neutrophil counts (NC) in 15 chronic hepatitis C patients treated with standard-dose (10 MU) recombinant IFN-alpha for 24 weeks by using a chemiluminescent enzyme immunoassay for G-CSF. The time course of change after a single IFN-alpha injection showed that mean serum G-CSF levels and NC increased significantly compared with pretreatment values (p < 0.05), and were statistically correlated (r = 0.914, p = 0.0015). On repeating IFN-alpha administration, this change gradually became unclear, and granulocytopenia occurred, accompanied by a significant increase in serum G-CSF (p < 0.01). Both values reached a plateau within 2 weeks after starting treatment, and recovered rapidly after the cessation of therapy. Although continuous administration of IFN-alpha caused a time-dependent granulocytopenia, our results suggest that a single injection of IFN-alpha would be a potent inducer of G-CSF and NC in vivo as a short-term effect and that there would be negative-feedback regulation between them during long-term IFN-alpha therapy.

Adjuvants, Immunologic↗

[Subcutaneous phaeohyphomycosis of the right thumb].

Black fungi are a group of fungi that are characterized by the development of a pale brown to black color in the cell walls of their vegetative cells, conidia, or both. A mycotic infection caused by a member of black fungi can be subdivided into three clinical entities: phaeohyphomycosis, chromoblastomycosis, and mycetoma. Phaeohyphomycosis is distinguished from mycetoma by the absence of grain (organized, interwoven mycelial aggregates) formation, and from chromoblastomycosis by the absence of sclerotic bodies (thick-walled muriform cells). Phaeohyphomycosis is a rare disease and has been sporadically reported. In the present report, phaeohyphomycosis of the right thumb of a 72-year-old man was presented. A precipitating trauma of two months earlier at the site was recalled. A solitary mass, 10 mm in diameter, was gradually formed in the palm side of the distal right thumb and finally resected. Histological examination disclosed a solitary granulomatous lesion surrounded by an incomplete fibrous capsule. The lesion mainly involved subcutaneous tissue and was composed of multiple pyogranulomas. Pigmented branched septate hyphae and yeast-like cells were sparsely found in the periphery of the abscess and within histiocytic cells of the granulomas. No sclerotic cells were detected. When pigmentation of black fungi in tissue is as faint as in the present case, Fontana-Masson staining is useful to accentuate the presence of melanin-like pigment of fungal cell walls.

Aged↗

Effects of YM175, a new-generation bisphosphonate, on hypercalcemia induced by tumor-derived bone resorbing factors in rats.

YM175 (disodium cycloheptylaminomethylenediphosphonate monohydrate) is a new-generation bisphosphonate with stronger inhibitory activity on bone resorption than first-generation bisphosphonates. In the present study, the effect of YM175 on hypercalcemia induced in rats by single administration of either parathyroid hormone-related protein (PTHrP) or concomitant administration of PTHrP and interleukin 1beta (IL-1beta) was investigated. YM175 (0.01-1 mg/kg, i.v.) inhibited the increase in serum free calcium concentration induced by continuous administration of PTHrP alone (3 microg/rat/day, s.c., 7 days) dose-dependently. The inhibitory effect of YM175 appeared the day after administration and remained 3 days after administration. The effect of YM175 reached a maximum 2 days after administration, at which time the ED50 value of YM175 was calculated to be 0.041 mg/kg, i.v., revealing a potency approximately 50- and 10-fold stronger than those of either pamidronate or alendronate, respectively. In contrast, elcatonin (1-10 units/kg, s.c.) only transiently inhibited PTHrP-induced free calcium increase. YM175 (0.1-3 mg/kg, i.v.) also inhibited the increase in the serum free calcium concentration induced by continuous concomitant administration of both PTHrP and IL-1beta in a dose-dependent manner. These results indicated that YM175 is expected to be a useful drug for hypercalcemia associated with malignant tumors due to its efficacy and range of effect.

Animals↗

[Pagetoid spread of intratubular germ cell neoplasia into rete testis forming tumor-like mass].

Intratubular germ cell neoplasia (ITGCN) is the preinvasive phase of testicular germ cell tumors. ITGCN can spread into the rete testis in a pagetoid manner, but there are very few published data about this phenomenon. Furthermore, the tumor-like mass formed by ITGCN with pagetoid spread into the rete testis has not been documented to date, and the present case is the first to be reported. A tumor-like mass was found close to the superior pole of the left testis in a 39-year-old male and was unrelated to the epididymis. Three other nodules of seminoma surrounded by fibroconnective tissue existed next to the mass. Histological sections revealed ITGCN which was characterized by the presence of large and polygonal germ cells exhibiting clear cytoplasm with distinct cell borders. The cytoplasm was rich in glycogen and the cell membrane was immunohistochemically positive for placental alkaline phosphatase. The nuclei had less coarse chromatin than that of seminoma. ITGCN cells spread in between the lining epithelium of the rete and the basement membrane. This characteristic spread was consistent with pagetoid spread into the rete testis.

Adult↗

Neurotoxicity of serum components, comparison between CA1 and striatum.

In vasogenic brain edema, the neurotoxicity of extravasated serum components may contribute to neuronal damage. In the hippocampal CA1 sector and striatum, the neurotoxicity of serum was investigated. Rat serum was prepared as follows: Serum-1: whole serum, Serum-2: ultrafiltrated through a membrane with cut-off at molecular weight (MW) 100,000. Serum-3: through a membrane with cut-off at MW 20,000, and Serum-4: through a membrane with cut-off at MW 5,000. The infusion edema model was utilized for infusion of autologous serum into the brain. The brain tissue was histologically evaluated. The level of glutamate, total protein, and albumin was also measured in the sera used for infusion. The following results were obtained: 1) CA1 neurons were more vulnerable to all infused sera than striatal neurons, 2) there was a strong cellular response in the striatal site of infusion, but only a minimal in the CA1-sector, 3) the severity of damage of CA1 correlated with the glutamate concentrations of the infused sera, 4) further, there was a relationship between the degree of striatal neuronal loss and the amount of protein and albumin present in the infusate. It is, therefore, concluded that the neurotoxic properties of vasogenic edema fluid are also affected by specific features of the brain region of its extravasation. In addition, the pathological mechanisms associated with irreversible damage of neurons might be different in the CA1-sector and the striatum.

Animals↗

Drug disposition of incadronate, a new bisphosphonate, in rats with bone metastases.

1. Drug disposition of incadronate in the nude rat with bone metastases induced by A375 human melanoma cells was studied after intravenous administration. 2. The pharmacokinetics of incadronate (plasma concentration, urinary excretion and bone uptake) in rat with bone metastases was not markedly different from that in the control rat. This compound, however, was selectively taken up in the bone region around metastatic tumour nests. 3. Drug concentrations in the bone region around tumour nests were 3-10 micrograms/g, these levels being higher than the IC50 (0.35 microgram/ml) for the inhibitory effect of this drug on osteoclasts in vitro. 4. In contrast, concentrations in the tumour nest itself was < 0.7 microgram/g, being markedly lower than the IC50 (35 micrograms/ml) for the inhibitory effect on the proliferation of tumour cells in vitro. 5. These results strongly suggest that pharmacological action of incadronate in mouse with bone metastases (inhibitory effect on the growth of metastatic tumour in bone) is caused not by the direct action on the tumour cells but by the distribution of the drug in the perifocal bone region followed by inhibition of the activity of osteoclasts, resulting in inhibition of the osteolytic process, which is necessary for the progress of metastatic tumour.

Animals↗

Virus elimination and histologic improvement in patients with chronic hepatitis C treated with interferon alpha.

We evaluated the elimination of hepatitis C virus (HCV) by means of interferon alpha (IFN-alpha) by investigating both positive- and negative-stranded RNA forms in the peripheral blood mononuclear cells and liver tissue. We also assessed the long-term histologic improvement accompanying viral clearance. We studied 20 persons with HCV whose serum aminotransferase levels remained normal for more than 1.5 years after IFN-alpha treatment withdrawal. The presence of HCV RNA in their peripheral blood and of both positive and negative strands in the peripheral blood mononuclear cells and liver tissue was investigated using the reverse transcription polymerase chain reaction method. We examined the histologic findings using the European classification and the histology activity index scoring system. In 16 of 20 patients, both strands disappeared from the possible reservoirs. The histologic findings indicated reduced activity, and histology activity index scores (1, 2, 3, and total) also showed significant improvement. We confirmed that IFN-alpha therapy can induce the elimination of HCV RNA from the conceivable HCV reservoirs and effect histologic improvement. Therapy with IFN-alpha is effective for treating chronic hepatitis C.

Adult↗

Nemaline bodies of skeletal muscle fibers of the neck in a case of pharyngeal cancer.

Nemaline bodies were found in the regenerating muscle fibers of the neck of a 74-year-old Japanese male with pharyngeal cancer. Histologically, the nemaline bodies were needle-shaped structures and hematoxophilic with phosphotungstic acid-hematoxylin stain. Electron microscopic examination suggested that they arise as extensions of the Z bands. Although nemaline bodies occur in a variety of pathological conditions other than nemaline myopathy, their occurrence in regenerating skeletal muscle fibers invaded by cancer has not been reported previously. The pathogenesis of the nemaline body formation in the present case is discussed.

Aged↗

[Eumycotic mycetoma of the lower leg].

Eumycotic mycetomas are extremely rare diseases in Japan. Only four cases have been reported. In the present report, eumycotic mycetoma of right lower leg of a 44-year-old male of Thai origin, resident in Japan for more than five years, was presented. An induration was noticed on the antero-medial side beneath the knee. Computed tomography showed slightly high dense subcutaneous mass-like lesion at the medial side of the right tibia. Though no draining sinus was formed, histologic examination disclosed grains composed of septated hyphae with Splendore-Hoeppli material. Since more people from foreign countries tend to reside in Japan, physicians and pathologists should be aware of various infections which are not commonly found in Japan.

Adult↗

Substrate specificity of recombinant osteoclast-specific cathepsin K from rabbits.

A cDNA clone encoding the rabbit cysteine proteinase cathepsin K, which is predominantly expressed in osteoclasts and is closely related to cathepsins L (EC 3.4.22.15) and S (EC 3.4.22.27) [Tezuka K., Tezuka Y., Maejima A., Sato T., Nemoto K., Kamioka H., Hakeda Y., Kumegawa M., J. Biol. Chem., 269, 1106 (1994)], was expressed at high levels in Escherichia coli in a T7 expression system. The insoluble recombinant enzyme was solubilized in urea and refolded at an alkaline pH. Cathepsin K (37-kDa) was purified by gel filtration and its enzymatic characteristics were determined. The enzymatic activity of cathepsin K was strongly inhibited by cysteine proteinase inhibitors and its optimal pH was pH 5.5. Synthetic substrate benzyloxycarbonyl-Phe-Arg-7-(4-methyl)coumaryl-amide, which is hydrolyzed by cathepsins L and S, was also cleaved by cathepsin K. On the other hand, benzyloxycarbonyl-Gly-Pro-Arg-7-(4-methyl)coumaryl-amide was the most suitable substrate for cathepsin K, but was hardly hydrolyzed by cathepsin L. The substrate specificity of cathepsin K, as determined using various chemogenic substrates, showed different characteristics from cathepsins L and S.

Amino Acid Sequence↗

Effects of YM-51084 and YM-51085, new inhibitors produced by Streptomyces sp. Q21705, on cathepsin L.

The structures of YM-51084 and YM-51085, new protease inhibitors produced by Streptomyces sp. Q21705, were determined by 1H- and 13C-NMR and mass spectrometry. Both were characterized by the basic structures of an acyl-tripeptide. YM-51084 was elucidated to be isovaleryl-tyrosyl-valyl-phenylalaninal and YM-51085 was the reduced phenylalaninol form of YM-51084. These compounds proved to strongly inhibit human kidney cathepsin L; the IC50 values being 9.6 x 10(-9) M and 3.5 x 10(-7) M, respectively.

Carbon Isotopes↗

Effect of YM-47141, a new inhibitor produced by Flexibactor sp. Q17897, on elastase.

YM-47141, a peptidic compound recently isolated from Flexibactor sp. Q17897, strongly inhibited human leukocyte elastase (HLE) with Ki value 2.1 x 10(-7) M. Unlike other serine protease inhibitors, YM-47141 exhibited relatively weak effects on cathepsin G and alpha-chymotrypsin and its inhibitory Ki values were 9.2 x 10(-4) M and 1.3 x 10(-6) M, respectively. It had little, or no inhibitory effect on plasmin, thrombin, trypsin and kallikrein (IC50 > 10(-4) M). The inhibition of HLE by YM-47141 was reversible and of a mixed type.

Animals↗

Relationship between age and nephrotoxicity following single low-dose cisplatin (CDDP) injection in rats.

We studied nephrotoxicity following a single injection of cisplatin (CDDP) at low dose (1 mg/kg) in two groups of rats aged 52 weeks (adult, A group) and 9 weeks (young, Y group). Renal platinum (Pt) was detectable in both groups 3 h after the CDDP injection, and, from 6 h to 3 d after injection, its level in the A group was higher than that in the Y group. Compared with the levels in age-matched normal rats (non-treated rats examined at time zero), the plasma urea nitrogen and creatinine levels in the A group were significantly increased, beginning 3 d after CDDP injection, while those in the Y group showed little change for 10 d after injection. Beginning 3 d after CDDP injection, the level of renal metallothionein in the Y group increased, while that in the A group decreased remarkably. The renal tissue levels of the heavy metals Zn, Cu, Mn showed similar patterns. There were no significant changes in the renal lipid peroxide (LPO) level in either the A and Y group at any time measured after CDDP injection compared with the value in the respective age-matched untreated group. Morphological evaluation demonstrated degeneration of the proximal tubules in the A group 3 d after CDDP injection. These results suggested that the renal disorders observed following CDDP injection in the A group were caused by mechanisms other than LPO such as decreased tissue metabolic function associated with aging.

Aging↗

Experimental quantitative evaluation of transvascular removal of unnecessary substances in brain edema fluid.

We developed a model by which the transvascular removal of unnecessary substances in brain edema fluid could be measured quantitatively and chronologically. Brain stab wounds were produced in Wistar rats by insertion of paired microdialysis probes in the unilateral caudatoputamen. Homovanillic acid (HVA) was administered by microdialysis from one probe, and the HVA clearance was measured by HPLC analysis of perfusate from the other probe. Using this model, we evaluated the site of removal and whether the removal processes were affected by anesthesia or an elevated plasma concentration of the substance. As a result, 1) Probenecid did not change HVA clearance although this inhibits HVA removal via subarachnoid vessels. Therefore, HVA removal in this model was considered mainly due to intraparenchymal transvascular efflux. 2) There was no alteration in HVA removal induced by anesthesia or intravenous HVA injection. Consequently, this efflux mechanism seems to be a rather stable protective process, and seems to play a considerable role in brain microenvironmental homeostasis.

Animals↗

Auditory sound agnosia without aphasia following a right temporal lobe lesion.

A 55-year-old right-handed man showed inability to recognize the meaning of non-verbal sounds without impairment of language comprehension after a cerebrovascular accident. His auditory acuity was intact and no other sign of agnosia, apraxia or aphasia was detectable. His errors on a test of sound recognition were acoustic rather than semantic. Brain CT scan showed a small lesion in the posterior part of the right temporal lobe. This case suggests that auditory sound agnosia without language disorder can ensure a lesion confined to the right hemisphere, and that the deficit is discriminative rather than associative in nature.

Agnosia↗

Hypothalamo-pituitary dopaminergic system in patients with myotonic dystrophy.

We studied the function of hypothalamo-pituitary dopaminergic system in 15 myotonic dystrophy (MyD) patients whose growth hormone (GH) responses to insulin or arginine had been normal. We obtained the following findings: (1) basal levels of plasma GH and prolactin (PRL) were normal, although the latter levels were slightly lower than controls, (2) both GH and PRL responses to L-dopa or bromocriptine were significantly blunted compared with controls, (3) PRL response to sulpiride was also significantly low compared with controls. These results indicate that hypothalamic dopaminergic neuron and its postsynaptic dopamine receptors relating to GH secretion might be impaired. It was also suggested that the dopamine receptors of pituitary PRL cells might be impaired and the PRL reserve of pituitary cells might be decreased in some case.

Adolescent↗