Search PubMed⌕ Search

Biomedical subjects

K Shigematsu

Publications and source records attributed to K Shigematsu.

At least 73 records · Page 4Linked to original sources

Partial characterization of insulin-like growth factor I in primary human lung cancers using immunohistochemical and receptor autoradiographic techniques.

We investigated primary human lung cancers resected surgically or obtained at autopsy. Included were squamous cell carcinoma (SQC) (five cases), adenocarcinoma (ADC) (six cases), large cell carcinoma (LCC) (four cases), and small cell carcinoma (SCC) (two cases). The objective of the study was to search for the presence of insulin-like growth factor I (IGF-I)-like immunoreactivity using immunohistochemical staining and for the localization of IGF-I binding sites, using in vitro quantitative receptor autoradiographic techniques. IGF-I-like immunostaining was present in all cases of SQC, ADC, and LCC, but not in cases of SCC. Strong immunostaining was observed in cases of SQC. On the other hand, ADC and LCC tissues showed a moderate or weak staining. Specific binding sites for IGF-I were present in all cases of SQC, ADC, LCC, and SCC examined. High densities of 125I-IGF-I binding sites were localized in cases of SQC and SCC. Low to high densities of the binding sites were found in LCC. Cases of ADC showed low densities of 125I-IGF-I binding sites. Specific binding obtained at a concentration of 80 pM 125I-IGF-I was competitively displaced by unlabeled IGF-I, with a 50% inhibitory concentration value of 1.84 +/- 0.31 x 10(-10) mol, whereas human insulin was much less potent in displacing the binding. This specificity profile is consistent with characteristics of IGF-I receptors. Scatchard analysis showed the presence of a single class of high affinity binding sites for IGF-I, with a Kd of approximately 1 nmol. Thus, the possibility that IGF-I may play a role in the growth of human lung cancers would have to be considered.

Adenocarcinoma↗

Specific [125I]brain natriuretic peptide-26 binding sites in rat and pig kidneys.

Specific binding sites for porcine brain natriuretic peptide-26 (BNP-26), a member of the atrial natriuretic peptide family (ANPs), were investigated in the kidney by using receptor autoradiographic and membrane binding techniques with [125I]BNP-26. The binding sites were discretely localized in rat and porcine kidney areas corresponding anatomically to the glomeruli and inner medulla. There were no differences between the localization of [125I]BNP-26 and [125I]alpha-rat ANP binding sites in the kidney. [125I]BNP-26 binding to solubilized membranes from isolated glomeruli of the rat kidney was saturable, and a single class of high-affinity sites was labeled with a KD of 372 pM. The radioligand bound to two sites in solubilized inner medullary membranes of the rat, a low-affinity site with a KD of 30 nM, and a high-affinity site with a KD of 33 pM. The rank order of potency to inhibit binding was BNP-26 = alpha-rat ANP-(1-28) greater than atriopeptin III (ANP-(103-126)) much greater than atriopeptin I (ANP-(103-123)) greater than des-Cys105,Cys121- ANP-(104-126). Thus, [125I]BNP-26 presumably recognizes ANP receptors in the kidney. The possibility that BNP-26 regulates, as a circulating hormone, kidney functions by binding to ANP receptors would have to be considered.

Animals↗

Neuropeptide Y (NPY) and peptide YY (PYY) receptors in rat brain.

1. Specific binding sites for neuropeptide Y (NPY) and peptide YY (PYY) were investigated in rat brain areas using quantitative receptor autoradiography with 125I-Bolton-Hunter NPY (125I-BH-NPY) and 125I-PYY, radioligands for PP-fold family peptides receptors. 2. There were no differences between localization of 125I-BH-NPY and 125I-PYY binding sites in the rat brain. High densities of the binding sites were present in the anterior olfactory nucleus, lateral septal nucleus, stratum radiatum of the hippocampus, posteromedial cortical amygdaloid nucleus, and area postrema. 3. In cold ligand-saturation experiments done in the presence of increasing concentrations of unlabeled NPY and PYY, 125I-BH-NPY and 125I-PYY binding to the stratum radiatum of the hippocampus, layer I of the somatosensory frontoparietal cortex, molecular layer of the cerebellum, and area postrema was single and of a high affinity. There was a significant difference between the affinities of 125I-BH-NPY (Kd = 0.96 nM) and 125I-PYY binding (Kd = 0.05 nM) to the molecular layer of the cerebellum. The binding of the two radioligands to the other areas examined had the same affinities. 4. When comparing the potency of unlabeled rat pancreatic polypeptide (rPP), a family peptide of NPY and PYY, to inhibit the binding to the areas examined, rPP displaced 125I-BH-NPY and 125I-PYY binding to the area postrema more potently than it did the binding to the stratum radiatum of the hippocampus, layer I of the somatosensory frontoparietal cortex, and molecular layer of the cerebellum. 5. Thus, the quantitative receptor autoradiographic method with 125I-BH-NPY and 125I-PYY revealed differences in binding characteristics of specific NPY and PYY binding sites in different areas of the rat brain. The results provide further evidence for the existence of multiple NPY-PYY receptors in the central nervous system.

Animals↗

Immunohistochemical expression of epidermal growth factor receptors in human adrenocortical carcinoma.

Epidermal growth factor (EGF) receptors were examined immunohistochemically in 64 adrenocortical carcinomas obtained at autopsy, and in 23 adrenocortical adenomas and seven pheochromocytomas obtained during surgery. In the nonneoplastic adrenal gland, EGF receptors were scattered to the zona glomerulosa, zona fasciculata, and zona reticularis. Adrenocortical carcinomas (63 of 64), more than adrenocortical adenomas (10 of 23) or pheochromocytomas (four of seven), stained positively for EGF receptors (P less than .01). The immunoreactivity was limited to the cytoplasm, cell membrane, and chromatin. When the antibody was immunoabsorbed with an excess of immunogen peptide, there was no evidence of immunostaining. The adrenocortical carcinomas could be classified into 16 cases of the well-differentiated type, 33 cases of the moderately differentiated type, and 15 cases of the poorly differentiated type. There was no relationship between histologic grading and staining intensity of the EGF receptors. On the other hand, more than 80% of the cases of adrenocortical carcinomas revealed a moderate to high intensity for EGF receptors. In 62 of the 64 patients, there was already metastases to other organs. We conclude that the expression of EGF receptors is associated with tumor growth and/or metastatic potential in adrenocortical carcinoma.

Adenoma↗

Restrictive cardiomyopathy following acute myocarditis--a case report.

A fifty-five-year-old man developed intractable heart failure four weeks after upper respiratory infection. His central venous pressure was as high as 300 mmH2O. Two-dimensional echocardiogram revealed no muscular hypertrophy of the ventricles, no pericardial thickness, and no pericardial effusion. On catheterization, hemodynamic data were compatible with restrictive cardiomyopathy. Transvenous endomyocardial biopsy of the left ventricle was performed. Histologic examination strongly suggested that cardiomyopathy developed after acute myocarditis.

Biopsy↗

Systemic effects of carteolol, a beta-adrenoceptor antagonist in stroke-prone spontaneously hypertensive rats.

The preventive effects of carteolol, a beta-adrenoceptor antagonist, on secondary lesions were pathophysiologically examined in stroke-prone spontaneously hypertensive rats (SHRSP) from 8 to 30 weeks of age. Carteolol was added to the drinking water in doses of 0.005% (8 to 18 weeks of age) to 0.01% (19 to 30 weeks of age) (3.8 and 6.0 mg/kg/d, respectively). These animals gained significantly more weight than the untreated control SHRSP, and their heart rate reduced from 14 weeks of age. Suppression of blood pressure rise was not definite, however, histology revealed prevention of the development or aggravation of secondary hypertension-related lesions, such as myocardial fibrosis, proliferative arteriolitis, necrotic arteriolitis and renal glomerular lesions. A decrease in non-esterified fatty acids in the serum was evident. Thus, carteolol has cardiac as well as renal protective effects, in the SHRSP.

Adrenal Glands↗

Evaluation of the neuroprotective action of WEB 1881 FU on hypoglycemia/hypoxia-induced neuronal damage using rat striatal slices.

Effect of WEB 1881 FU on hypoglycemia/hypoxia-induced brain damage in rats was evaluated and compared to findings obtained with idebenone. We used an in vitro model that facilitated the direct monitoring of dopamine release from striatal slices. The response to high K+ stimulation under perfusion of the slices with D-glucose-free Ringer solution (hypoglycemia) decreased at 40 min, and then practically disappeared. WEB 1881 FU at 10(-6) M or idebenone at 10(-6) M significantly protected against impairment of the striatal responses under the conditions of hypoglycemia. Hypoglycemic injury, evidenced by a remarkable neuron loss, necrosis and spongyosis was also ameliorated by these drugs. WEB 1881 FU at 10(-6) M had a protective action against the impairment of striatal responses evoked by NaCN (electron transport inhibitor at site 3) and oligomycin (inhibitor of mitochondrial ATP synthesis), but idebenone at 10(-6) M did not. In light of these observations, the possibility that WEB 1881 FU and idebenone exert neuroprotective actions against hypoglycemic/hypoxic brain injury by activating energy metabolism with different mechanisms from each other has to be considered.

Animals↗

[Postoperative pancreatitis following thoracoabdominal aortic aneurysmectomy--a case report].

Thoracoabdominal aortic aneurysmectomy with a temporary bypass from left axillary to right common iliac artery was successfully performed in a 57 year-old-female with an aneurysm involving celiac, superior mesenteric and renal arteries. An elevation of serum amylase level with a peak value on 7 POD was observed and ultrasonography revealed acute pancreatitis resulting from seventy minutes ischemia of celiac artery during the procedure. The patient was treated conservatively and discharged. It seems to be important to prevent pancreatic ischemia in thoracoabdominal aortic aneurysmectomy as well as to maintain renal and hepatic circulation.

Acute Disease↗

[A case of chronic progressive radiation myelopathy successfully treated with corticosteroid].

One patient who underwent radiation therapy for laryngeal cancer two years earlier developed chronic progressive radiation myelopathy and exhibited localized swelling of the cervical spinal cord at the C4 level and resultant blocking of the subarachnoid space on myelography and CT myelography. The condition responded markedly to the administration of corticosteroid except for persisting mild spasticity and sensory disturbances. On myelography and CT myelography half a year later, the cervical spinal cord showed no swelling. The corticosteroid therapy is considered to be useful for radiation myelopathy.

Aged↗

Neovascularization in kainic acid-induced lesions of rat striatum. An immunohistochemical study with laminin.

Vascular changes occurring after stereotaxic injection of the excitatory neurotoxin kainic acid (KA) into the rat striatum were studied at various time intervals after the lesion using laminin immunohistochemistry. Laminin immunohistochemistry revealed marked vascular changes, including presumed neovascularization, in the lesioned striatum. Vessels with increased laminin immunoreactivity were demonstrated from 2 days up to at least 5 months following the injection. The majority was capillary vasculature, which was distributed throughout the lesioned striatum, sometimes being arranged densely along the needle tract. Fine spike-like sprouts called streamers were also loaded with laminin immunoreactivity. In contrast, laminin immunoreactivity in vessels in the control striatum was negligible. Vascular changes detected by laminin immunohistochemistry preceded but then almost paralleled gliosis demonstrated by glial fibrillary acidic protein immunohistochemistry. These results indicate that striatal injection of KA causes marked vascular changes including neovascularizations which are demonstrable by laminin immunohistochemistry.

Animals↗

Specific 125I-endothelin-1 binding sites in the atrioventricular node of the porcine heart.

The quantitative receptor autoradiographic method we used revealed that specific 125I-endothelin-1 binding sites are highly concentrated in the atrioventricular node of the porcine heart. 125I-Endothelin-1 binding to the atrioventricular node, interatrial and interventricular septa was displaced by unlabeled endothelin-1 with Kd values of 53 pM, 2.03 nM and 3.48 nM, respectively. Knowledge of the existence of specific 125I-endothelin-1 binding sites in the porcine heart helps with understanding the physiology of endothelin, a possible endogenous Ca2+ channel agonist.

Animals↗

Monoamine oxidase-containing nerve fibers in the major cerebral arteries of rats.

The localization of monoamine oxidase (MAO) in nerve fibers associated with the major cerebral arteries in rats was studied using a new coupled peroxidation method modified by adding nickel ammonium sulfate at the electron microscopic level. MAO was, localized in some unmyelinated axons, both in the adventitia and in the periadventitial nerve bundles. Schwann cell cytoplasm encircling myelinated axons in the periadventitial nerve bundles also contained a MAO-reactive substance. The incidences of MAO-containing axons in the adventitial layer of the anterior cerebral, middle cerebral, internal carotid and basilar arteries were 32.3%, 29.5%, 29.6% and 21.1%, respectively. In the periadventitial nerve bundles, MAO activity was also demonstrated in 10.8% among unmyelinated axons. Preincubation with clorgyline, a specific inhibitor of MAOA, suppressed staining in the axons, both in adventitia and in periadventitial nerve bundles, but not in the Schwann cell cytoplasm. Conversely, preincubation with deprenyl, a specific inhibitor of MAOB, suppressed staining in the Schwann cell cytoplasm, but not in the axons. Therefore, MAO in the axons is regarded as MAOA and MAO in the Schwann cell cytoplasm as MAOB. In immunosympathectomized rats (anti-NGF-treated rats), MAO reactivity was suppressed in axons associated with cerebral arteries, but was retained in some Schwann cell cytoplasm. The results indicate that the MAO-containing unmyelinated axons coincide with the postganglionic noradrenergic ones. Thus, histochemical MAO staining may be utilized to study postganglionic sympathetic nerve fibers presumably innervating the major cerebral arteries at the electron microscopic level.

Adrenergic Fibers↗

Specific [125I]Bolton-Hunter substance P binding sites in human and rat skin.

[125I]Bolton-Hunter substance P [( 125I]BH-SP) binding sites in rat and human skin were investigated, using quantitative receptor autoradiographic and emulsion autoradiographic methods. [125I]BH-SP binding sites were discretely localized in skin areas anatomically corresponding to dermal papillae, sweat glands, and hair follicles. The highest density of the binding sites was in the dermal papilla of the finger, followed by the sweat gland. [125I]BH-SP binding to the dermal papillae of the human finger pad skin and rat paw pad skin was displaced by unlabeled SP, with a high affinity, and Kd values were calculated to be 744 pM and 297 pM, respectively. The existence of [125I]BH-SP binding sites supports the idea of the neurotransmitter role of substance P in skin dermal papilla.

Adult↗

Neovascularization of transplanted central nervous tissue suspensions: an immunohistochemical study with laminin.

Neovascularization of the dissociated central nervous tissue transplanted into the lateral ventricle of the rat was studied using laminin immunohistochemistry. A very high immunoreactive response to laminin was demonstrated in the presumably newly formed vessels within the transplants and the graft-host borders. The growing tips and fine spike-like sprouts called 'streamers' were also highly stained with laminin immunoreactivity. In contrast, laminin immunoreactivity was negligible in the vessels in the host brain. Therefore, these results indicate that laminin may be utilized as a marker for the newly formed vessels in neural transplantations.

Animals↗

Intracerebral transplantation of dissociated central nervous system tissue suspensions: use of phaseolus vulgaris leucoagglutinin as a cell marker.

Successfully transplanted neurons and their sprouting processes were demonstrated by Phaseolus vulgaris leucoagglutinin (PHA) marking. PHA is transported anterogradely and readily reveals the post-transplantation growth of the neuronal processes. Suspensions of fetal central nervous tissue, prepared by dissociation of embryonic rat brain, were marked with PHA and then transplanted into the striatum of nonimmunosuppressed young adult rats. At various intervals thereafter (1 day, 2 days, 1 week, 2 weeks, 1 month, and 2 months), the animals were sacrificed for histological examination with PHA and tyrosine hydroxylase (TH) immunohistochemistry. Up to 2 weeks after transplantation, PHA immunohistochemistry was capable of demonstrating grafted neurons and their presumably regenerated neuronal processes. However, at periods 1 month or longer after transplantation, PHA immunohistochemistry was unreliable. Thus, the PHA marking method has limitations in terms of its retention period, when applied to the intracerebral transplantation of dissociated cell suspensions. Nevertheless, the method presented here can be utilized to study neuronal regeneration as well as the relationship between transplanted neurons and the host tissue.

Animals↗

Receptor autoradiographic analysis of insulin-like growth factor-I (IGF-I) binding sites in rat forebrain and pituitary gland.

1. Specific 125I-labeled insulin-like growth factor-I [( 125I] IGF-I) binding sites in the rat forebrain and pituitary gland were investigated using quantitative receptor autoradiography. 2. High densities of [125I]IGF-I binding sites were present in the olfactory nerve layer, olfactory glomerular layer, choroid plexus, CA3 and CA4 of the hippocampus, basolateral amygdaloid nucleus, and endopiriform nucleus. Moderate to high binding densities were found in the cerebral cortex (II, VI), bed nucleus stria terminalis, accumbens nucleus, lateral septum, median preoptic nucleus, supraoptic nucleus, paraventricular hypothalamic nucleus, and ventroposterior thalamic nucleus. In the circumventricular organs, subfornical organ, vascular organ of the lamina terminalis, and median eminence, the binding sites were numerous. High densities of [125I]IGF-I binding sites were also observed in the anterior pituitary gland. 3. In kinetic experiments, [125I]IGF-I binding sites in the olfactory glomerular layer, choroid plexus, median eminence, and anterior pituitary gland were found to be single and of a high affinity. 4. Noteworthy was the difference in the potency of insulin in inhibiting the binding among the areas examined, a finding which suggests heterogeneity of IGF-I receptors. 5. The possibility that IGF-I plays the role of a neurotransmitter and/or neuromodulator in the central nervous system warrants further investigation.

Animals↗

Specific insulin binding sites in snail (Helix aspersa) ganglia.

1. Insulin binding sites were characterized and quantified in snail (Helix aspersa) ganglia by incubation of tissue sections with 125I-porcine insulin, autoradiography with [3H]Ultrofilm, image analysis coupled to computer-assisted microdensitometry, and comparison with 125I-standards. Cellular localization was performed in the same sections by emulsion autoradiography. 2. Specific insulin binding sites were demonstrated in discretely localized groups of neurons of the cerebral, pleural, parietal, visceral, and pedal ganglia and in nerves. Scatchard analysis performed with consecutive sections from single animals revealed a single class of high-affinity insulin binding sites (Kd, 0.13 +/- 0.01 nM; Bmax, 157 +/- 10 fmol/mg protein). 3. Our results suggest that insulin may play a role as a neurotransmitter or neuromodulator in snail ganglia.

Animals↗