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Biomedical subjects

Y Nakayama

Publications and source records attributed to Y Nakayama.

At least 19 recordsLinked to original sources

[A case of esophageal carcinoma with hypercalcemia caused by PTH-rP--the effect of therapy on the bone and calcium metabolism].

The changes in the bone and in calcium metabolism during cisplatin or bisphosphonate administration is reported in a 50-year-old patient with esophageal carcinoma who had humoral hypercalcemia of malignancy (HHM). Laboratory findings on admission showed that ionized calcium was 1.65mmol/L, phosphorus was 2.4mg/dl, and PTH-rP was 151pmol/L, without any evidence of bone metastasis. After admission, cisplatin and/or bisphosphonate were administrated for hypercalcemia. These administrations ameliorated serum ionized calcium, urinary pyridinoline and hydroxyproline level within a few days. Although cisplatin administration decreased the serum osteocalcin level, bisphosphonate administration kept up the level, suggesting that bisphosphonate maintained bone formation and cisplatin decreased its formation. The discrepancy may be due to the coupling with the reduction of bone resorption and/or direct toxic effect on osteoblasts during cisplatin administration, and preservation of osteoblastic activity during bisphosphonate administration. Cisplatin and bisphosphonate may have different effects on bone formation. Serum 1,25(OH)2D level was slightly decreased or unchangeable after cisplatin administration, although the level was increased after bisphosphonate administration. Direct toxic effect on 1 alpha-hydroxylase of the kidney or increase in phosphrous level may explain the change of 1,25(OH)2D after cisplatin administration. These results suggested that cisplatin and bisphosphonate have the same effect of preventing bone resorption but different effects on bone formation and/or serum 1,25(OH)2D level.

Bone Resorption

Induction of human microvascular endothelial tubular morphogenesis by human keratinocytes: involvement of transforming growth factor-alpha.

Transforming growth factor-alpha(TGF-alpha), homologous to epidermal growth factor(EGF), is closely involved in hyperproliferation of human keratinocytes. Psoriasis is a common hyperproliferative skin disease characterized by hyperproliferation of keratinocytes and abnormal development of dermal capillary networks. In this study, we have examined whether keratinocytes could enhance angiogenesis. TGF-alpha or EGF efficiently stimulated formation of tubular-like structures of human omental microvascular endothelial(HOME) cells in type I collagen gels. Human keratinocytes produced TGF-alpha. To examine whether co-cultured keratinocytes could induce tubulogenesis of HOME cells in collagen gel, we have developed a co-culture system with human keratinocytes. Surprisingly, there appeared new development of many tubular-like structures of HOME cells in collagen gels when co-cultured with keratinocytes. This keratinocytes-dependent tubulogenesis was almost completely blocked when anti-TGF-alpha-antibody was present. The TGF-alpha molecules derived from keratinocytes appeared to enhance tubulogenesis of human microvascular endothelial cells. We propose the hypothesis that secretory TGF-alpha from human keratinocytes may promote an autocrine loop to proliferate the skin keratinocytes and also a paracrine loop to induce the skin angiogenesis.

Blotting, Northern

Central pressor actions of tachykinin NK-3 receptor in the paraventricular nucleus of the rat hypothalamus.

The central pressor actions of the tachykinin NK-3 receptor in the paraventricular nucleus (PVN) of the hypothalamus were examined in anesthetized rats. In forebrain-restricted animals, the selective tachykinin NK-3 receptor agonist senktide (10 micrograms, i.c.v.) increased the blood pressure, and this pressor response was more potent than in control animals. Injection of senktide into the PVN also increased the blood pressure, and this pressor response was inhibited by pretreatment with the vasopressin V1 receptor antagonist (10 micrograms/kg, i.v.). These results suggest that central injection of senktide stimulated the NK-3 receptor in the PVN of the hypothalamus, and increased blood pressure by inducing release of vasopressin from the pituitary gland.

Animals

Induction of 103-kDa gelatinase/type IV collagenase by acidic culture conditions in mouse metastatic melanoma cell lines.

Gelatinases/type IV collagenases have been shown to be involved in tumor invasion and metastasis. In this study, we examined the effect of culture medium pH on the secretion of the gelatinases from mouse B16 melanoma cell lines and human tumor cell lines using zymography analysis. The highly metastatic clone F10 of B16 melanoma did not secrete any gelatinase in neutral culture media (pH 7.1-7.3), whereas it secreted a high level of a 103-kDa gelatinase in an initial pH range of 5.4-6.1. The addition of an excess amount of glucose into a neutral culture medium also induced the gelatinase secretion from the cells by decreasing the medium pH during incubation. The extent of the acid-induced gelatinase secretion by the B16 melanoma cell lines was in the order of BL6 greater than F10 greater than F1 much greater than the parent B16 line, in good agreement with the order of their metastatic potentials. Two human cell lines (A549 and HT1080) secreted a higher level of a 90-kDa gelatinase at pH 6.8 compared with pH 7.3. The acid-induced gelatinase secretion from B16-F10 cells was blocked by cycloheximide, indicating that the enzyme induction was due to de novo synthesis. When in vitro tumor cell invasion was assayed in Boyden chambers, B16-F10 cells incubated in an acidic medium exerted a more active migration through type IV collagen gel than those in a neutral medium. These results suggest that the acidic environment formed around tumor tissues may be an important factor in invasion and metastasis of some types of tumors.

Animals

[Split-course radiation therapy in non-small cell lung cancer].

Split-course radiation therapy (Sp-RT) is based on theoretical differences between the kinetics of normal and malignant cells. A rest interval halfway through the course of treatment permits the normal tissues to recover, while the tumor shows vary little repopulation. Indeed, it shows mostly regression, resulting in shrinkage of the radiation field. From 1976 through 1985, 185 patients with localized but inoperable or unresectable (stage I-III) non-small cell carcinoma of the lung completed high-dose definitive RT delivered by continuous-course or split-course irradiation. Forty-seven patients who had large tumors or atelectases of the lung showing slow radioresponsiveness received Sp-RT over 60 Gy at 2 Gy per fraction. Rest periods were two or three weeks long in the interrupted schedules. The 5-year survival rate was 16% in the Sp-RT group and 13% in the continuous RT group. In the 33 patients that had differentiated epidermoid carcinoma with slow responsiveness to irradiation, the radiation fields could be shrunk by Sp-RT to the same extent as in the continuous group. Sp-RT was considered to be useful in the treatment of well-differentiated epidermoid carcinoma of the lung.

Adenocarcinoma

Role of NK-1 receptor in central cardiovascular regulation in rats: studies on a novel non-peptide antagonist, CP-96,345, of substance P NK-1 receptor.

CP-96,345[(2S,3S)-cis-2-(diphenylmethyl)-N-[(2-methoxyphenyl)- methyl]-1-azabicyclo [2.2.2] octan-3-amine] was recently discovered to be a nonpeptide substance P (SP) antagonist. We examined the effects of CP-96,345 on the central cardiovascular responses to tachykinin peptides in anesthetized rats. CP-96,345 (200 nmol, i.c.v.) inhibited the pressor responses of the NK-1 receptor-selective agonist GR 73632 (0.5 nmol, i.c.v.) and SP (7 nmol, i.c.v.). It also inhibited the increase in blood pressure elicited by neurokinin A (7 nmol, i.c.v.). However, it had no effect on the earlier pressor response induced by neuropeptide gamma (l nmol, i.c.v.) or by a selective NK-3 agonist senktide (1 nmol, i.c.v.). These findings suggest that SP (i.c.v.) induces pressor responses via the NK-1 receptor, and that the pressor response to neurokinin A may also be mediated by the NK-1 receptor in the brain.

Animals

Multivessel coronary revascularization with bilateral internal thoracic artery grafts.

Sixteen patients underwent coronary revascularization with bilateral internal thoracic artery (ITA) grafts between 1988 and 1989 at the Okayama University Hospital. A total 39 coronary grafts were performed, being an average of 2.4 grafts per patient. Each patient received bilateral ITA grafts, and in 5 patients an additional 7 grafts were constructed with 5 autologous veins and 2 gastroepiploic arteries. The right ITA was grafted as a free graft in 4 patients. The ITA graft patency rate was 96.8 per cent (31/32) at the time of hospital discharge. The postoperative morbidity included one reoperation for bleeding and one myocardial infarction. Coronary artery bypass grafting with bilateral ITA grafts can be safely performed and its application facilitates complete revascularization with arterial grafts.

Aged

Monoclonal antibody GOM-2 binds to blood group B-Le(y) active glycolipid antigens on human gastric cancer cells, KATO-III.

The antigen structure of a mouse monoclonal antibody, GOM-2, established by immunization with KATO-III human gastric cancer cells, was examined. GOM-2 reactive glycolipids were prepared from KATO-III cells and treated with endoglycoceramidase. Structural studies of ten GOM-2 reactive oligosaccharides by a combination of glycosidase digestions, methylation, and affinity chromatography on an Ulex europeus agglutinin I (UEA-I) column revealed that nine of them had a Y-related B-active difucosylated determinant (B-Le(y)) and one had a B-active determinant. Affinity chromatography of the purified and modified oligosaccharides on an immobilized GOM-2 column demonstrated that GOM-2 has a novel binding specificity: it binds tightly to the biantennary structure carrying the B-Le(y) determinant at the termini or the branched structure carrying the B-Le(y) structure at two nonreducing termini.

Antibodies, Monoclonal

Ultrastructural alterations of the conduction system in mice exhibiting sinus arrest or heart block during Coxsackievirus B3 acute myocarditis.

By light and electron microscopy we studied the sinus nodes and atrioventricular (AV) conducting tissue of six C3H/He mice having coxsackievirus B3 acute myocarditis. Sinus arrest was documented in all six mice, and second- or third-degree AV block was documented in three of the six mice. Although myocarditic changes in the conduction system, especially in the sinus node, were less than those in atrial and ventricular working myocardium, there were distinct abnormalities within both the sinus node and AV conducting tissue in all six hearts. Important ultrastructural alterations were inflammatory cell infiltrates and significant injury of specialized cells and of neural tissue. Specialized cells showed various features of degeneration and necrosis. Neural tissue damage included degeneration of axons and Schwann cells and disorganization of the neuromuscular junctions. Inflammatory cells, particularly macrophages, were often in intimate contact with injured specialized cells and neural tissue. Interstitial edema and bleeding and lymphatic vessel dilatation were also observed. These pathologic changes are considered to play an important role in the development of the documented disturbances of rhythm and conduction.

Animals

Polyoma middle T antigen or v-src desensitizes human epidermal growth factor receptor function and interference by a monensin-resistant mutation in mouse Balb/3T3 cells.

Epidermal growth factor (EGF)-induced down-regulation of its receptor is an obligatory pathway for cellular regulation of EGF-specific receptor (EGF-R) in normal and malignant cells. BNER4 cells are mouse Balb/3T3 cells transfected with the human EGF-R complementary DNA (cDNA). Polyoma middle T antigen-transfectants of BNER4, B4/MT-2, B4/MT-13, B4/MT-23, and B4/MT-24, showed diminished down-regulation of cell surface human EGF-R in response to EGF relative to the parental BNER4 cells. Also, the v-src-transfectants B4/SRC-13 and B4/SRC-24 showed much less down-regulation than BNER4 cells, whereas H-ras-transfectants of BNER4, B4/RAS-24 and B4/RAS-25, showed EGF-induced down-regulation of the cell surface EGF-R similar to that of BNER4. EGF induced DNA synthesis more than 20-fold in BNER4, but induced only about a 1.5- to 6-fold increase in the middle T antigen- and v-src-transfectants. EGF-Rs of the middle T antigen-transfectants were metabolically stable in the presence of EGF in comparison with their parental BNER4 cells. EGF-Rs of BNER4 cells degraded with half-lives of about 2 h in the presence of EGF, but those of the middle T antigen transformants were found to be highly stabilized in the presence of EGF. On the other hand, transfection with polyoma middle T antigen (MTAg) cDNA causes malignant transformation of Balb/3T3 cells, but not its monensin (an ionophoric antibiotic)-resistant mutant MO-5 cells, which have no significant EGF binding activity. Transfection of human EGF-R cDNA into MO-5 leads to the expression of high levels of human EGF-R in MNER31. Unlike the polyoma MTAg transfectants of BNER4, EGF-R in polyoma MTAg cDNA-transfectants into MNER31, M31/MT-13 and M31/MT-14, were down-regulated to levels similar to those of their parental MNER31. Exposure to EGF induced a more than 10-fold increase in DNA synthesis of quiescent BNER4, MNER31, M31/MT-13, and M31/MT-14 cells. Polyoma middle T antigen or v-src appears to modulate EGF-induced down-regulation of EGF-R, possibly through interaction of the receptor with the viral oncogenes, and this interaction may be altered in the mutant.

3T3 Cells

Effects of olfactory stimulation with jasmin and its component chemicals on the duration of pentobarbital-induced sleep in mice.

The effect of olfactory stimulation with jasmin and its component chemicals on pentobarbital sleep time was investigated using mice. In the present study we sought to determine which component of jasmin influences pentobarbital sleep time via olfactory stimulation. Sleep time was defined as the time elapsed between intraperitoneal pentobarbital administration and the first time that the animal was able to spontaneously right itself. Sleep time was significantly decreased by olfactory stimulation with jasmin, and also by one of the fractions obtained by fractional distillation at 150 degrees C and 0.1 mmHg. The fraction which influenced the sleep time was found to consist of benzyl benzoate, isophytol, geranyl linalool, phytol and phytyl acetate, which were identified using gas chromatography with mass and infrared spectrometry. In experiments using authentic samples of these components, phytol significantly shortened the pentobarbital sleep time, while the others had no effect. We conclude that phytol is the component of jasmin which reduces the duration of pentobarbital-induced sleep.

Animals

Establishment and characterization of monoclonal antibodies to carbohydrate antigens on peanut agglutinin receptor glycoprotein of gastric cancer KATO-III.

Eight mouse monoclonal antibodies, GOM-1, GOM-2, GOM-3, GOM-5, GOM-6, GOM-7, GOM-8 and GOM-9 were established that recognized carbohydrate antigens on the human gastric cancer cell line KATO-III. Their binding specificities were studied by enzyme-linked immunosorbent assay, cellular enzyme-linked immunosorbent assay, flow cytometry analysis and thin layer chromatography immunostaining. All these monoclonal antibodies bound to peanut agglutinin receptor glycoproteins and neutral glycolipids extracted from KATO-III cells, but they could be divided into three groups, namely GOM-1, -3, -9 group, GOM-5 and GOM-2, -6, -7, -8 group. GOM-3 specifically bound to the Le(a) structure, Gal beta 1-3 (Fuc alpha 1-4) GlcNAc beta 1-, and GOM-5 specifically bound to the Lec structure, Gal beta 1-3GlcNAc beta-. GOM-2 showed specific binding to KATO-III, but little or no binding to various other cell lines examined or to normal human leukocytic cells. It also did not bind to the synthetic glycoconjugates tested, carrying 10 different terminal sugar chains including T, Tn, Le(a), Lec and Le(x) structures. The binding specificity of GOM-2 was also different from those of the monoclonal antibodies anti-Le(x), anti-Leb and anti-Ley. These results suggest that GOM-2 recognizes a new carbohydrate antigen on KATO-III cells that is distinct from Le(a), Leb, Lec, Le(x), Ley, T and Tn structures.

Animals

Congenital absence of lumbosacral articular process: report of three cases.

Defective anomaly of the articular process of the lumbosacral region in three young women is reported. One had a bilateral defect at the lower facet of L1 with defect at L5 right lower and S1 right upper facets. Another had bilateral defects at L5 lower facets, and the third had a defect at the left lower facet of L5 with other anomalies of the lamina. Based on classification of 37 anomalies including those previously reported in the literature, it is concluded that unilateral defect at the lumbosacral apophyseal joint involving both upper and lower facets is the most common anomaly. The pathogenesis of all anomalies is apparently complex. The intervertebral instability caused by these defects may provoke occasional low-back pain, especially in younger persons with a unilateral L5/S1 anomaly.

Adolescent

Extracellular matrix formation in piecemeal necrosis: immunoelectron microscopic study.

Immunolocalization of Type I, Type III and Type IV collagens, laminin and prolyl hydroxylase (PH), a key enzyme in collagen synthesis, was examined to clarify the fibrotic process in chronic, active liver disease. In piecemeal necrosis of chronic, active hepatitis (CAH) and active liver cirrhosis (LC), fat-storing cells (FSCs) and transitional cells (TSCs), containing abundant rough endoplasmic reticulum (RER), were increased in number and stained intensely for PH. Immunodeposits of extracellular matrix (ECM) components were found in the RER, Golgi apparatus (GA) and vesicles of these cells, especially in cases with marked inflammation. On the other hand, in the periportal areas of chronic, persistent hepatitis (CPH) or inactive LC, immunoreaction of ECM components was seldom found in the RER of FSCs and TSCs. In the portal tract, immunodeposits of ECM components were seldom found in the organelles of fibroblasts, although ECM was increased there. These findings indicate that FSCs and TSCs in piecemeal necrosis might play a role in the production of ECM components in the progression of fibrosis during the development of chronic active liver disease. In addition, ECM component production by FSCs and TSCs is associated with marked inflammation.

Collagen

High-resolution CT of the temporal bone: a modified baseline.

High-resolution computed tomography (CT) of the temporal bone, particularly axial scanning on a baseline parallel to the orbitomeatal line, produces radiation exposure to the patient's lenses. The authors evaluated the radiation dose to the lens and the visualization of temporal bone structures with use of scanning along the orbitomeatal line and on a line parallel to the hard palate. Evaluation of visualization was performed by five radiologists, with high-resolution CT scans of 45 healthy patients, and the chi 2 test was performed for comparison. The change of the baseline from the orbitomeatal line to a line parallel to the hard palate decreased the radiation dose to the lens from 12.7 cGy to 0.274 cGy and improved visualization of the stapes superstructure and the tympanic portion of the facial nerve canal, although visualization of the incus body, incudostapedial joint, lateral semicircular canal, and oval window was of equal quality. Therefore, the authors recommend a new baseline parallel to the hard palate for use at high-resolution CT of the temporal bone.

Health Personnel