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Biomedical subjects

K Shigematsu

Publications and source records attributed to K Shigematsu.

At least 91 records · Page 5Linked to original sources
PubMed1989

Receptor autoradiographic localization of insulin-like growth factor-I (IGF-I) binding sites in human fetal and adult adrenal glands.

We report here the first evidence of insulin-like growth factor-I (IGF-I) binding sites in human fetal and adult adrenal glands, obtained at autopsy. Sections of tissue were incubated with 0.1 nM [125I]IGF-I and analyzed using [3H]Ultrofilm autoradiography with image analysis coupled to computerized microdensitometry. Specific binding sites of [125I]IGF-I were found to be localized in the definitive zone, fetal zone, and fetal medulla of the fetal adrenal glands. In the adult adrenal glands, the entire cortex and medulla were specifically labeled with [125I]IGF-I. Specific binding obtained at a concentration of 0.1 nM [125I]IGF-I to areas in the fetal and adult human adrenal glands was competitively displaced by unlabeled IGF-I, with an IC50 value of 0.34-2.54 nM, and 0.38-0.73 nM, respectively, whereas insulin was much less potent in displacing the binding. Acquisition of this knowledge will aid in studies on cell growth and steroid-catecholamines biosynthesis of the human adrenal gland.

Adrenal Cortex↗
PubMed1989

[Antihypertensive effect of bopindolol on stroke-prone spontaneously hypertensive rats (SHRSP)].

The antihypertensive effect of bopindolol, a long-acting beta-adrenoceptor blocking agent, was investigated in stroke-prone spontaneously hypertensive rats (SHRSP). One group received tap water during the period of 8 to 32 weeks of age. The average dose of bopindolol administered was calculated from water intake to be approximately 1.4 mg/kg/day. The lowering effect in blood pressure of bopindolol was apparent at the age of 14 weeks, and this continued up to the end of the experiment. Bopindolol significantly reduced the heart rate. Plasma levels of urea nitrogen (BUN), triglyceride, and phospholipid of SHRSP treated with bopindolol were lower than those of the control SHRSP. One of the 8 control SHRSP died, and no rats treated with bopindolol died during the experiment. The histopathological study revealed that three of the control SHRSP had cerebral apoplexy, whereas there was no evidence of cerebral apoplexy in the treated SHRSP. Chronic treatment of bopindolol clearly alleviated myocardial fibrosis and hypertrophic changes in the left ventricular wall of the heart. Decreases in the incidence of proliferative arteritis and malignant nephrosclerosis in the kidney and necrotizing arteritis of the mesenteric arteries were observed in SHRSP treated with bopindolol. The data presented indicate that bopindolol is a powerful antihypertensive agent.

Administration, Oral↗
PubMed1989

Characterization of insulin-like growth factor I and epidermal growth factor receptors in meningioma.

Receptors for insulin-like growth factor I (IGF-I) and epidermal growth factor (EGF) were localized and characterized in eight samples of human meningioma (four fibrous, two meningothelial, and two angioblastic types), using quantitative autoradiographic techniques. Effects of both growth factors on deoxyribonucleic acid (DNA) synthesis in the cultured meningioma cells were examined. High numbers of specific binding sites for both IGF-I and EGF were homogeneously present in tissue sections derived from fibrous and meningothelial types of meningiomas, whereas binding sites for these growth factors were not detectable in adjacent leptomeninges. While relatively large numbers of IGF-I binding sites were located in the wall of the intratumoral vasculature, the number of binding sites in the stromal component was lower in angioblastic-type meningiomas, including a low number of EGF binding sites detected only in the stromal portion. Scatchard analysis revealed the presence of a single class of high-affinity binding sites for both IGF-I and EGF in the meningiomas examined (dissociation constant (Kd) = 0.6 to 2.9 nM, and the maximum number of binding sites (Bmax) = 16 to 80 fmol/mg for IGF-I; and Kd = 0.6 to 4.0 nM, Bmax = 3 to 39 fmol/mg for EGF). Both growth factors increased the synthesis of DNA, in a dose-dependent manner, as measured by 3H-thymidine incorporation. The combination of IGF-I and EGF synergistically stimulated the synthesis of DNA, and the effects seen with 10% fetal bovine serum could be reproduced at a concentration of 10(-10) M. These observations can be interpreted to mean that both IGF-I and EGF may be involved in the growth modulation of meningiomas, possibly through paracrine or autocrine mechanisms.

Adult↗
PubMed1989

[Two cases of amylase-producing lung cancer].

In 1951, Weiss et al. first reported a case of an amylase-producing lung cancer. Since then, reports on immunohistochemical, ultrastructural, and biochemical studies have been published. We recently have experienced two autopsy cases of lung cancer that manifested high amylase activity in the serum, urine, and pleural effusions. Histologically, both lung cancers were classified as being well differentiated adenocarcinomas, and immunohistochemically, the tumor cells showed positive immunoreactivity for amylase. This paper discusses the histogenesis of amylase-producing lung cancers and cases found in the literature.

Adenocarcinoma↗
PubMed1989

"Parallel array" of tubules with pipe-like structure in the mitochondria of glomerulosa cells of adrenal cortex. Ultrastructural and freeze-fracture replica studies.

We found "parallel array" of tubules with a pipe-like structure in the mitochondria of glomerulosa cells of the adrenal cortex of the rats treated with atrial natriuretic factor (ANF) that inhibits aldosterone production. This structure was characterized by the regular parallel arrays of tubules running straight along the mitochondrial long axis, representing a pipe-like structure. The cross section exhibited the round shape with an electron lucent core measuring about 40 nm and dual thick membranes measuring 10 nm in thickness. Some of these tubules were connected with the mitochondrial inner membrane. Freeze fracture replica represented round particles distributed on the surface membrane of these tubules, indicating protein particles. This particular structure was considered to be one of the changes occurring in the mitochondrial inner membrane on which structural proteins were localized. These tubules probably appeared in connection with the impaired mitochondrial protein synthesis in the process of the biosynthesis of mineralcorticoid, because this structure was found only in the glomerulosa cells under the decreased and increased aldosterone production.

Aldosterone↗
PubMed1989

[Expression of insulin-like growth factor I receptors in human brain tumors: comparison with epidermal growth factor receptor by using quantitative autoradiography].

By using quantitative autoradiographic techniques, receptors for insulin-like growth factor I (IGF-I) and epidermal growth factor (EGF) were analyzed in 13 samples of human brain tumors (4 low grade astrocytomas, 7 glioblastomas, 1 anaplastic ependymoma and 1 medulloblastoma). High number of specific binding sites for IGF-I and EGF were homogeneously present in tissue sections derived from glioblastoma. In low grade astrocytoma, relatively high numbers of binding site for EGF were observed, but there was no significant difference in concentrations of IGF-I binding sites between tumors and control cortex. In medulloblastoma, only IGF-I binding sites were present. These observations might indicate that both IGF-I and EGF are involved in the growth modulation of human gliomas possibly through paracrine or autocrine mechanisms. Antagonists to growth factors or monoclonal antibody against those receptors could have the way for therapeutic application for gliomas.

Astrocytoma↗
PubMed1988

Receptor autoradiographic evidence of specific brain natriuretic peptide binding sites in the porcine subfornical organ.

Specific binding sites of brain natriuretic peptide (BNP), a newly discovered peptide in the subfornical organ (SFO) of porcine brain were investigated, following incubation of related tissue sections with 125I-BNP, then using autoradiography and an image analysis coupled with computer-assisted microdensitometry. Specific 125I-BNP binding sites were found to be localized in the SFO, an area densely labeled by 125I-alpha-rat atrial natriuretic peptide and 125I-(Sar1,Ile8)-angiotensin II. Specific 125I-BNP binding to the SFO was displaced by unlabeled BNP, with a high affinity, and was calculated to be Ka = 0.385 x 10(-9) M and Bmax = 40.1 fmol/mg using a LIGAND computer program. Acquisition of these present findings enhances our knowledge of the physiology of BNP, atrial natriuretic peptides and angiotensin II system in the SFO.

Animals↗
PubMed1988

[Metastatic calcification associated with malignancy].

From 1975 to 1986, 15 cases (2%) of metastatic calcification associated with an underlying malignancy were found in a review of 702 autopsied cases with histories of malignancy. These underlying malignancies included 7 cases of lung cancer, 6 cases of malignant lymphoma, one case of breast cancer, and one of urinary bladder cancer. Squamous cell carcinoma was of the histological type most often associated with metastatic calcification in lung cancer, and ATL in malignant lymphoma. Hypercalcemia was found in 10 (83%) out of cases, and almost all were accompanied by renal dysfunction. Calcium deposits were most frequently observed in the kidneys and the lungs. It has been suggested that metastatic calcification in the lungs and kidneys of a patient with a history of malignancy showing hypercalcemia is sometimes accompanied by respiratory and renal dysfunction, causing the patient's condition to deteriorate.

Adult↗
PubMed1987

Localization and characterization of atrial natriuretic peptide binding sites in discrete areas of rat brain and pituitary gland by quantitative autoradiography.

Atrial natriuretic peptide [rat (r) ANP6-33 or ANP99-126] binding sites were localized in discrete areas of rat brain and pituitary gland using quantitative autoradiographic techniques. High numbers of rANP6-33 binding sites were concentrated in the circumventricular organs (the organon vasculosum laminae terminalis, organon subfornicalis, and area postrema) and selected hypothalamic nuclei (the nucleus supraopticus, nucleus preopticus medianus and nucleus paraventricularis). High binding was also present in the choroid plexus and the bulbi olfactorii (laminae medullaris interna). A relatively low number of rANP6-33 binding sites was observed in other olfactory, limbic and brainstem areas (the nucleus tractus solitarii, nucleus motoris dorsalis vagii and nucleus hypoglossi), the eminentia mediana and the pituitary gland (anterior and posterior lobes). High-affinity rANP6-33 binding sites were demonstrated in the organon subfornicalis and the area postrema after incubation of consecutive sections from individual rat brains with 125I-rANP6-33 in concentrations from 20 to 400 pM. rANP6-33 binding sites were concentrated in areas associated with angiotensin II and/or vasopressin, suggesting an interaction among these peptides in the central nervous system.

Animals↗
PubMed1987

Dopamine D1 receptor in rat brain: a quantitative autoradiographic study with 125I-SCH 23982.

We report the regional distribution and characteristics of 125I-SCH 23982 binding to D1 receptors in rat brain using a quantitative autoradiographic technique. The substantia nigra pars reticulata, the caudate putamen, the nucleus accumbens and the olfactory tubercle had a single class of high affinity binding sites for 125I-SCH 23982. Binding sites were also present in a discrete, continuous band connecting the caudate putamen with the substantia nigra.

Animals↗
PubMed1987

Localization of angiotensin II receptors along the anteroventral third ventricle area of the rat brain.

Autoradiographic techniques were utilized to localize and to quantify angiotensin II (ANG) binding sites in rat forebrain. Specific, localized ANG binding sites were demonstrated in midline sagittal sections, corresponding to the entire anteroventral third ventricle (AV3V) area, including the nucleus preopticus medianus and the subependymal area of the anterior third ventricle from the nucleus preopticus medianus to the organon vasculosum laminae terminalis. A continuous band of ANG receptors extended dorsally from the nucleus preopticus medianus along the subependymal area of the third ventricle to the organon subfornicalis. Scatchard analysis performed with consecutive sections from single animals revealed a single class of high-affinity ANG receptors in both the organon subfornicalis and the organon vasculosum laminae terminalis. In addition, ANG receptors were localized in areas anatomically and physiologically related to the AV3V area, including the nuclei paraventricularis and periventricularis and the eminentia mediana. These results support the idea that ANG may act as both a hormone and a neurotransmitter in the central regulation of fluid balance and cardiovascular function, and suggest that the circumventricular organs are the most likely sites for an interaction between the peripheral and central ANG systems.

Angiotensin II↗
PubMed1987

125I-iodinated benzazepines bind to melanin: implications for the noninvasive localization of pigmented melanomas.

Both the 5-R and the 5-S enantiomers of [125I]2,3,4,5-tetrahydro-8-iodo-3-methyl-5-phenyl-1H-3-benzazepin- 7-ol bind to melanin. The interaction between the 5-R enantiomer and melanin permits visualization of melanomas in mice with a noninvasive imaging procedure. Two lines of evidence suggest that the interaction between iodinated ligands and melanin is not related to the D-1 dopamine receptor, a known target for the 5-R enantiomer: first, melanin binds both enantiomers of the 125I-iodinated benzazepine while the D-1 receptor binds only the 5-R enantiomer; second, the melanin binding site displays only a 5-fold difference in affinity towards the R- and S-enantiomers of SCH 23390 while the D-1 receptor displays a 100-fold difference in affinity towards these two molecules. Because both enantiomers of the iodinated benzazepine bind to a human pigmented melanoma, we propose that such compounds may be of use in the diagnosis of pigmented melanoma: in addition, we discuss the possible application of these molecules as a supplement to existing technology for the localization of pigmented melanomas.

Animals↗
PubMed1987

Alterations in substance P binding in brain nuclei of spontaneously hypertensive rats.

Substance P binding sites were characterized in brain nuclei of young (4-wk-old) and adult (16-wk-old) spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto (WKY) control rats by quantitative autoradiography. Young SHR presented higher affinity constants (KA) than young WKY. The changes were restricted to the locus coeruleus, the area postrema, the dorsal motor nucleus of the vagus, and to discrete areas located in lobes 9 and 10 of the vermis cerebelli of SHR. There were no differences in the maximal binding capacity (Bmax) except in the nucleus ambiguus where the Bmax was lower than in WKY. Conversely, the number of substance P binding sites was higher in the locus coeruleus, the nucleus tegmentalis dorsalis, the nucleus ambiguus, the dorsal motor nucleus of the vagus, the hypoglossal nucleus, the inferior olivary nucleus, and lobes 9 and 10 of the vermis cerebelli of adult SHR when compared with adult WKY. Our results support the hypothesis of a role for brain substance P in blood pressure regulation and in genetic hypertension in rats.

Aging↗
PubMed1986

Specific substance P binding sites in rat thymus and spleen: in vitro autoradiographic study.

Substance P binding sites were localized in rat thymus and spleen by incubation of tissue sections with [125I]Bolton-Hunter substance P, [3H]Ultrofilm autoradiography with image analysis coupled to computerized microdensitometry and comparison with 125I standards. The tissue localization of the binding sites was determined with emulsion autoradiography. A single type of specific, saturable, high affinity binding sites was found associated with the vasculature in the medulla of the thymus and the marginal sinus of the spleen, with a Kd of 0.10 and 0.14 nM, respectively. Of all the unlabeled tachykinins tested (substance P, physalaemin, substance K, eledoisin, kassinin, and neuromedin K) substance P was the most potent inhibitor of [125I]Bolton-Hunter substance P binding, with an IC50 of approximately 0.5 nM, indicating the presence of substance P-P binding sites. Our results support the hypothesis of a role for substance P in the modulation of the immune system.

Animals↗
PubMed1986

Angiotensin II binding sites in the anteroventral-third ventricle (AV3V) area and related structures of the rat brain.

Angiotensin II binding sites were localized in the rat brain by incubation of sagittal sections with 125I-[Sar1]-angiotensin II, followed by [3H]Ultrofilm autoradiography. Binding sites were localized in the subfornical organ and the entire anteroventral-third ventricle (AV3V) area, including the subependymal area of the anterior third ventricle, the median preoptic nucleus and the organon vasculosum laminae terminalis. Binding sites were also present in the paraventricular and periventricular nuclei and in the median eminence. These findings support the hypothesis of an extensive involvement of angiotensin in the neuronal circuits connecting the subfornical organ, the AV3V area, the paraventricular nucleus and the median eminence, and in the regulation of fluid balance, blood pressure and pituitary secretion.

Animals↗
PubMed1986

Increased density of substance P binding sites in specific brainstem nuclei of spontaneously hypertensive rats.

Substance P binding sites were quantitated in 16-week-old spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto rats by incubation of brain sections with 125I-Bolton-Hunter substance P, autoradiography and microdensitometry. The maximum binding capacity (Bmax) was significantly increased in the dorsal motor nucleus of the vagus, in the hypoglossal, ambiguus and inferior olivary nuclei, and in lobes 9 and 10 of the vermis cerebelli of SHR.

Animals↗
PubMed1986

Localization of atrial natriuretic peptide, ANP-(99-126) binding sites in the rat thymus and spleen with quantitative autoradiography.

Binding sites for atrial natriuretic peptide, ANP-(99-126) were studied in lymphoid organs of the rat with quantitative autoradiography. Tissue sections were incubated in the presence of 0.13 nM 125I-ANP-(99-126) followed by autoradiography using [3H]-Ultrofilm, and the results were analyzed by computerized densitometry and comparison to 125I-standards. Specific ANP binding sites were localized in the medulla and the cortex of the rat thymus and in the white pulp of the rat spleen, with apparent binding sites concentrations of 93, 65, and 126 fmol/mg protein, respectively. The presence of ANP binding sites in areas related to the maturation and function of lymphocytes, and to the production of thymic hormones, suggests the possibility of a role of circulating ANP in the modulation of the immune response.

Animals↗