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Biomedical subjects

K Akai

Publications and source records attributed to K Akai.

At least 37 records · Page 2Linked to original sources
PubMed1992

Effects of alpha and beta adrenergic blockade on coronary arterial microvessels in the beating canine heart.

OBJECTIVE: The aim was to clarify the effects of alpha and beta adrenergic blockade on coronary arterial microvessels and to assess the role of alpha and beta adrenergic tone in normally beating hearts. METHODS: 47 anaesthetised open chest dogs were studied. The diameters of epicardial arterial microvessels were measured in beating hearts using an incident light fluorescence microscope equipped with a floating objective. Drugs were infused into the left anterior descending coronary artery keeping the heart rate and aortic pressure at control levels. To examine the effect of alpha adrenergic blockade, phentolamine (100 micrograms.kg-1) was given in the absence or presence of beta adrenergic blockade (propranolol 50 micrograms.kg-1). To examine the effect of beta adrenergic blockade, propranolol (50 micrograms.kg-1) or three doses of ICI 118,551 (a selective beta 2 antagonist, 0.1, 0.5, and 1.0 microgram.kg-1.min-1) was given. RESULTS: Coronary arterial microvessels were divided into three groups according to the control diameters (D) of small (D less than 100 microns), medium (100 less than or equal to D less than 200 microns) and large (D greater than or equal to 200 microns) groups. In the absence of beta adrenergic blockade, phentolamine significantly dilated all vessel groups: small +19.6 (SEM 5.6)%, medium +5.8(2.3)%, large +5.3(0.9)%. In the presence of beta adrenergic blockade, the vasodilator effect of phentolamine was completely abolished. Propranolol constricted all vessel groups: small -3.6(1.1)%, medium -4.8(1.0)%, large -3.5(1.0)%. ICI 118,551 significantly constricted the large vessel group [-2.5(0.6)%] at the mid dose, and the medium and large vessel groups [medium -3.1(0.8)%, large -3.5(1.3)%] at the highest dose. CONCLUSIONS: These data indicate that (1) the vasodilator effect of phentolamine is induced by beta adrenergic stimulation; (2) resting alpha adrenergic tone of coronary arterial microvessels is minimal in normally beating hearts, and (3) resting beta adrenergic tone may play a physiological role in coronary arterial microvessels, and beta 2 adrenergic tone predominates in arterial microvessels greater than 100 microns in diameter.

Adrenergic alpha-Antagonists↗
PubMed1992

Microvascular sites and mechanisms responsible for reactive hyperemia in the coronary circulation of the beating canine heart.

Our aim was to elucidate the site and mechanism responsible for reactive hyperemia in coronary circulation. In in vivo beating canine hearts, microvessels of the left anterior descending coronary artery (LAD) were observed through a microscope equipped with a floating objective. Flow velocity of the LAD was measured with a suction-type Doppler probe. The LAD was occluded for 20 or 30 seconds and then released, and reactive hyperemia was observed before and after 8-phenyltheophylline (7.5 mg/kg i.v.) or glibenclamide (200 micrograms/kg into the LAD) infusion. During the occlusion, only arterial microvessels smaller than 100 microns in diameter dilated. Dilation of those vessels was partially attenuated by 8-phenyltheophylline and completely abolished with glibenclamide. In the early phase of reactive hyperemia, all arterial microvessels dilated, and the magnitude of peak dilation was greater in vessels smaller than 100 microns compared with those larger than 100 microns. Vasodilation during reactive hyperemia ceased within 60 seconds in vessels smaller than 100 microns but was sustained for more than 120 seconds in those larger than 100 microns. 8-Phenyltheophylline did not change peak dilation of arterial microvessels but reduced dilation after the peak. Glibenclamide remarkably attenuated dilation of all arterial microvessels in the whole phase of reactive hyperemia. These results indicate that all arterial microvessels are responsible for reactive hyperemia after coronary artery occlusions of 20-30 seconds, but there is greater participation of vessels smaller than 100 microns in the early phase of reactive hyperemia. Dilation of vessels larger than 100 microns assumes an important role in the later phase. ATP-sensitive K+ channels mediate dilation of arterial microvessels both in brief ischemia and reactive hyperemia.

Adenosine↗
PubMed1991

Effects of site-directed removal of N-glycosylation sites in human erythropoietin on its production and biological properties.

Erythropoietin (Epo) has three N-linked sugar chains. Codons for asparagine at N-glycosylation sites in genomic human Epo DNA were replaced with those for glutamine. The wild-type Epo gene and seven mutants that lacked N-glycosylation sites in every possible combination were introduced into baby hamster-kidney cells. To study the role of the N-linked sugars in Epo biosynthesis, Epo protein expressed transiently was measured by an enzyme-linked immunoassay. The elimination of all three N-glycosylation sites decreased Epo production to 10% of that of the wild-type Epo. Wild-type and mutant Epos produced by stably transfected cells were partially purified to investigate their properties. Removal of N-glycosylation sites changed affinity of Epo to the receptor. The in vitro activity of Epo that lost all N-glycosylation sites was comparable with that of the wild-type Epo, while the in vivo activity severely decreased. These results indicate that N-linked sugars of Epo have two major functions; N-linked sugars are important for 1) proper biosynthesis and/or secretion and 2) expression of the in vivo activity probably by enhancing survival in the circulation. N-Linked sugars of Epo affect binding affinity of the ligand to the receptor but do not play a key role in expression of the in vitro activity.

Base Sequence↗
PubMed1991

Absence of association of HTLV-I infection with type 1 neurofibromatosis in the United States or Japan.

An HTLV-I tax transgenic mouse model develops a syndrome with similarities to type 1 neurofibromatosis (NF-1). To investigate possible associations between this human retrovirus and NF-1, we have analyzed 67 neurofibromas from Japan (where HTLV-I infection is endemic) and compared them with 21 cases from the United States. We were not able to identify virus in tumor tissue in either group. This suggests that HTLV-I infection is not commonly associated with NF-1.

Amino Acid Sequence↗
PubMed1991

[Clinico-histological study of low-density non-enhancing glioma].

Some gliomas are not noticeably enhanced on initial computer tomography (CT) scans. Such low-density non-enhancing gliomas have a relatively long period between onset and surgery ranging from 5 to 25 months. The mechanism causing the low density over a certain period of time in the sequential CT findings was retrospectively investigated. Characteristic histological findings associated with such low-density areas were microcystic formation, necrosis, intratumoral edema, infiltrative growth, and absence of capillary proliferation. Proliferation of capillary vessels is characteristic of CT enhancement.

Adolescent↗
PubMed1990

[Assay of nuclear triiodothyronine receptors in the precentral gyrus in patients with amyotrophic lateral sclerosis].

Abnormality in the receptor of the cell might have some bearing on the selective cellular damage in systemic degenerative diseases. In relation to deranged metabolic turnover of the folate cycle in amyotrophic lateral sclerosis (ALS), we have measured nuclear triiodothyronine receptors (NT3R) in the precentral gyrus, stored at -80 degrees C after autopsy, of 4 ALS patients and 8 patients with non-neurological diseases. Cell nuclei were separated in bulk from about 1 g of grey matter by the method of Løvtrup-Rein & McEwen, and T3-binding assay was carried out by the method of Silva et al. DNA was measured by the method of Giles & Myers based on Burton's method. Specific bindings comprised more than 85% of total bindings. Scatchard analysis showed that the maximal binding capacity, namely the density of NT3R was significantly reduced in ALS, compared to that of the controls. The dissociation constant, namely the affinity was not different between the two groups. The present investigation suggests that NT3R may be reduced in the motoneuron of ALS patients, although the result might merely indicate the loss of nerve cells from the ALS motor cortex. This point should be clarified, but the bulk separation of pure nerve cell nuclei from autopsied human brain has not so far been successful in our laboratory. Action of thyroid hormone in the mature brain has not fully been clarified. Meanwhile, some investigators suggest that the metabolic state of the central nervous system of ALS has a tendency of hypothyroidism. Therefore, the relevance of thyroid hormone to pathogenesis or pathophysiology of ALS will be an important subject in future study.

Aged↗
PubMed1989

Demonstration of microglial cells in and around senile (neuritic) plaques in the Alzheimer brain. An immunohistochemical study using a novel monoclonal antibody.

A monoclonal antibody, termed AD11/8, reactive to microglial cells, was produced by immunization of mice with partially purified amyloid fibrils of senile (neuritic) plaques. With immunoperoxidase staining on human tissues, AD11/8 also recognized macrophages in the red pulp of the spleen, Kupffer cells in the liver, and macrophages in the bone marrow. The results show that AD11/8 recognizes the antigens associated with mononuclear phagocytes lineage. In normal brains a few resting microglial cells were stained in gray matter, and less frequently in white matter. In senile dementia of the Alzheimer type numerous microglial cells were stained intensively and they often formed clusters in gray matter. By double immunostaining with AD11/8 and a polyclonal antibody against synthetic amyloid beta-protein, clustered microglial cells were observed in and around senile plaques with amyloid deposits. Some amyloid plaque cores were surrounded by microglial cell processes. These results indicate that microglial cells may play an important role in senile plaque formation.

Aged↗
PubMed1989

Characterization and use of monoclonal antibodies directed against human erythropoietin that recognize different antigenic determinants.

We have established four hybridoma cells that produce monoclonal antibodies (MoAbs) R2, R4, R6, and R12 directed toward recombinant human erythropoietin (rHuEPO). MoAbs R2, R4, and R6 bound to EPO with high affinities (kd = approximately 2, 4, and 1 nmol/L, respectively) but MoAb R12 had a low affinity (240 nmol/L). These antibodies inhibited the biological activity of rHuEPO and EPOs from humans, rats, mice, and rabbits. This inhibition was due to the blocking of EPO binding to the target cells. The fully deglycosylated rHuEPO bound to the MoAbs, indicating that they recognized peptide sequences of the antigen but not the carbohydrates attached to the antigen. An immunosorbent column with the immobilized MoAb R2 was effective for the rapid purification of EPO. MoAb R6 bound to EPO at a site(s) different from those to which other MoAbs bound. Based on this finding, a sensitive and rapid enzyme-linked immunosorbent assay of EPO, in which EPO was sandwiched between two MoAbs (R2 and R6), was developed. The assay measured plasma levels of EPO as low as 5 mU/mL within several hours.

Animals↗
PubMed1989

[Morphologic findings and biologic behavior in the high grade glioma--a postmortem study of 22 cases].

Morphologic features of the autopsied specimen of 22 cases with supratentorial gliomas treated by surgery, radiation and/or chemotherapy were analysed, and the characteristics of recurrence of gliomas were searched for. The cases consisted of anaplastic 12 astrocytoma and 10 glioblastoma. The results were as follows: 1) Characteristic CT findings before death were regrowth of the tumor mass or the occurrence of a new enhanced lesion in 21 out of 22 cases. The enhanced lesion showing regrowth of the tumor located in the same site as the previous tumor mass in 21 cases. The new enhanced lesion resulting from a trans-or subependymal tumor spread, was seen in the ventricular wall, and these findings were a characteristic feature of the recurrence of gliomas. 2) Modes of extension of the tumor were subdivided into 3 types. One was the expansive or infiltrative type caused by regrowth of the residual tumor. In the second pattern, a spread of tumor cells occurred along the myelinated fiber tracts to the brain stem (60%), or to the contralateral cerebral hemisphere through the corpus callosum (50%). The third mode of tumor propagation was cerebrospinal fluid seeding with intraventricular or subarachnoid tumor regrowth (45%). 3) Characteristic histological findings shown in the original tumor bed were those of increased cellularity with endothelial proliferation, widespread necrosis with occlusion of the blood vessels, occurrence of the gemistocytic astrocytes and large bizarre cells. Thickening of wall of the blood vessels due to effect by radiation was followed by occlusion of the blood vessels. Large necrosis in the tumor tissue was caused by those process and others. Necrotic area was mainly circumscribed and corresponded to the territory of the vessels. One of the specific findings in the morphological changes of the tumor cells was giant cell formation which were monstrous cell, giant cell (12 cases out of 22), and gemistocytic cell (in all cases). These specific cells were supposed to the degenerative changes of the tumor cells exposed while withstanding such adverse conditions as hypoxia, radiation and chemotherapy. 4) Infiltration distant from the primary lesion which were defined only by microscopical examination was demonstrated as both through myelinated fiber tracts in 8 cases and through perivascular spaces in 2 cases. Reinvasion of the tumor cells from the subarachnoid spaces to the brain parenchyma was along the Virchow-Robins spaces of the penetrating blood vessels in the latter cases.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1989

Neuropathological study of the nucleus basalis of meynert in alcoholic dementia.

Intellectual impairment and mental disorders occurring in association with long periods of alcohol abuse are often irreversible; those persons who have difficulty leading normal daily lives because of such disorders are considered to have alcoholic dementia. We investigated this condition from the standpoint of pathomorphology. The subjects were nine autopsy cases of alcoholic dementia; three alcoholic autopsy cases of about the same age level but without dementia were also studied as a control group. In these two groups, the nucleus basalis of Meynert in the substantia innominata was selected as fixed site and nerve cells were counted; strict anatomical measurements were performed on this fixed site, and every effort was made to minimized artifacts in each case. The nucleoli of the nerve cells at this site were calculated in a fixed area on the basis of a fixed magnification; this was repeated in serial sections, and the number of nerve cells on a fixed volume was thus obtained. The "t" distribution test within the two groups was investigated; a probability value of less than 0.05 was obtained and the null hypothesis abandoned. Mean values were found to be different. The results obtained were compared with those found in literature, and important findings concerning lesions in alcoholic dementia were noted.

Alcoholism↗
PubMed1988

Comparative structural study of N-linked oligosaccharides of urinary and recombinant erythropoietins.

The structures of the N-linked oligosaccharides of the urinary erythropoietin (u-EPO) purified from urine of aplastic anemic patients were analyzed and compared with those for recombinant erythropoietin (r-EPO) prepared with baby hamster kidney (BHK) cells. Asparagine-linked neutral oligosaccharides were released from each EPO protein by N-oligosaccharide glycopeptidase (almond) digestion. The reducing ends of the oligosaccharide chains thus obtained were aminated with a fluorescent reagent, 2-aminopyridine, and the mixture of pyridylamino derivatives of the oligosaccharides was separated by high-performance liquid chromatography (HPLC) on an ODS silica column. More than 8 and 13 kinds of oligosaccharide fractions for u-EPO and r-EPO (BHK), respectively, were completely separated by the one-step HPLC procedure. The structure of each oligosaccharide thus isolated was analyzed by a combination of sequential exoglycosidase digestion and another kind of HPLC with an amide-silica column. Furthermore, high-resolution proton nuclear magnetic resonance (1H NMR) spectroscopy and methylation analyses were carried out in the case of r-EPO (BHK).(ABSTRACT TRUNCATED AT 250 WORDS)

Carbohydrate Sequence↗
PubMed1987

Normal pressure hydrocephalus. Neuropathological study.

The pathological changes in the brains of seven patients who had been clinically diagnosed as normal pressure hydrocephalus (NPH) are described and the possible etiological mechanisms are discussed. The pathological findings in all cases consisted of demyelination akin to Binswanger's type of encephalopathy, especially in the frontal lobes. Arteriosclerosis accompanied by occasional organized thrombi and scattered microinfarcts in the periventricular white matter were seen. Focal leptomeningeal fibrosis, diminution of arachnoidal granulations, and non-specific aging processes were noted. Among the above of particular interest, was the degeneration of both periventricular and deep white matters with microinfarcts, and moderate to severe arteriosclerosis. On the basis of these observations, we assume that the degeneration in the white matter is not merely a secondary change due to the result of enlargement of ventricle, but plays an important role in the development of NPH. The development of NPH requires not only the disturbance of cerebrospinal fluid, but also the pre- or coexisting vulnerability in the white matter caused by variables such as ischemia, hypoxia, and trauma.

Adolescent↗