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Biomedical subjects

N Murakami

Publications and source records attributed to N Murakami.

At least 307 records · Page 17Linked to original sources

Increase in [3H]cAMP binding sites and decrease in Gi alpha and Go alpha immunoreactivities in left temporal cortices from patients with schizophrenia.

To search for possible alterations in second messenger systems in the temporal cortex (Brodmann's area 22) of patients with schizophrenia, we measured the binding activities of [3H]adenosine 3',5'-cyclic monophosphate ([3H]cAMP) and [3H]4 beta-phorbol 12,13-dibutyrate ([3H]PDBu) which can label the regulatory subunit of cAMP-dependent protein kinase (protein kinase A) and the regulatory domain of Ca2+/phospholipid-dependent protein kinase (protein kinase C), respectively. We also immunoquantified the variable subunits of guanine nucleotide binding proteins (G-proteins), using specific polyclonal antisera against Gs alpha, Gi alpha and Go alpha. Brains were obtained at autopsy on 10 patients with schizophrenia and 10 age-matched control subjects. Representative Scatchard plots for specific [3H]cAMP bindings to the soluble fraction consisted of a single component with high affinity (Kd = 2.36 nM, Bmax = 737 fmol/mg protein). Among the tested adenyl and guanyl nucleotides, or neuroleptics, cAMP alone potently inhibited the binding (Ki = 4.95 nM). The binding sites for [3H]cAMP were discretely localized, and were in the order of: cerebral cortex = hypothalamus = amygdala > hippocampus = neostriatum = thalamus = nucleus accumbens > globus pallidus = cerebellum. Specific [3H]cAMP bindings to the soluble fractions were about 30% greater in the left temporal cortices of schizophrenic patients, as compared to findings in the right side of the patients and the left side of the control subjects, no control brain showed this asymmetry. The specific [3H]PDBu binding in schizophrenic and control groups did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Studies on onset patterns in antithyroid drug-induced agranulocytosis].

We studied the patterns of the onset of antithyroid drug-induced agranulocytosis. From 1975 to 1990, 19,050 patients with Graves' disease receiving treatment with antithyroid drugs were seen at our clinic. For all patients with Graves' disease treated with an antithyroid drug, a routine white blood cell count was done every 2 weeks until euthyroid state was gained, and a count was done once every moth thereafter. Of these, 70 were found to have agranulocytosis. Agranulocytosis was defined as a granulocyte count of 500/mm3 or less. In only 19 of the 70 was agranulocytosis detected after the occurrence of infection (symptomatic: classical agranulocytosis). The remaining 51 patients were asymptomatic when agranulocytosis was detected during routine white blood cell and granulocyte count monitoring. However, 17 of the 51 patients became symptomatic several days after the withdrawal of antithyroid drug treatment (shifted from asymptomatic to symptomatic agranulocytosis). Thirty-four patients had no symptoms of infection throughout the course of the disease (asymptomatic agranulocytosis). In conclusion, 1) We found three patterns in the onset of antithyroid drug-induced agranulocytosis: classical (symptomatic), a shift from asymptomatic to symptomatic, and asymptomatic agranulocytosis, 2) Unexpectedly, classical (symptomatic) agranulocytosis was seen in only 19 of the 70 patients, 3) We were again remained of the importance of routine white blood cell and granulocyte count monitoring.

Adolescent↗

Organum vasculosum laminae terminalis (OVLT) in rabbit and rat: topographic studies.

The microcirculation and fine structure of the rabbit and rat organum vasculosum laminae terminalis (OVLT) were examined by light microscopy and scanning and transmission electron microscopy. In both animals, the microcirculation is composed of a superficial and a deep vascular bed but the system is more complex and extensive in the rabbit. This was particularly true of the deep vascular bed. In the rabbit, the deep bed is composed of fenestrated capillaries, which are arranged in glomerular tufts surrounded by very wide perivascular spaces (PVS). In contrast, the deep vascular bed of the rat OVLT usually consists of only one or two small vessels. These are either fenestrated and surrounded by a PVS or lined by continuous endothelium with only a few fenestrae and without a dilated PVS. A corresponding difference was seen in the contours of the ventricular surface. It is much more irregular in the rabbit than in the rat and numerous bulges reflect the underlying vascular tufts and pockets of PVS in the rabbit. Supraependymal cells are present in both species and two sizes of them occur in the rabbit. The results demonstrate that the microcirculation of the OVLT is more elaborate and more highly developed in the rabbit than in the rat. We suggest that this might result in a different neurohemal microenvironment and, ultimately, in functional differences.

Animals↗

Granulocyte colony-stimulating factor treatment of antithyroid drug-induced granulocytopenia.

The primary objective of this study was to ascertain the effectiveness of granulocyte colony-stimulating factor in the treatment of antithyroid drug-induced granulocytopenia of varying degree. Sixteen patients with Graves' disease with antithyroid drug-induced granulocytopenia (granulocyte counts < 1.0 x 10(9)/L) each received a daily dose of 75 micrograms of granulocyte colony-stimulating factor administered subcutaneously. Within 24 hours of the first injection, the granulocyte count increased (0.6 to 12.3 x 10(9)/L) in all 10 patients with mild granulocytopenia (granulocyte counts between 0.5 and 1.0 x 10(9)/L) and all three with moderate granulocytopenia (granulocyte counts < 0.5 x 10(9)/L). The three remaining patients with severe granulocytopenia (agranulocytic), whose granulocyte counts were zero, did not recover from granulocytopenia until the 6th, 7th, and 14th days of treatment with granulocyte colony-stimulating factor. Examination of bone marrow taken at the onset of the disease in all three agranulocytic patients showed a prominent decrease in granulocytic series, while identical examination in six of eight patients with mild to moderate granulocytopenia showed close to normal granulocytic series. There was no elevation of serum granulocyte colony-stimulating factor concentration in four patients with mild granulocytopenia and one with moderate granulocytopenia at the onset of their disease, whereas those of the remaining three patients with severe granulocytopenia (agranulocytic) increased at onset of agranulocytosis. This information led us to conclude that: (1) granulocyte colony-stimulating factor is effective in the treatment of antithyroid drug-induced mild to moderate granulocytopenia and (2) in severe agranulocytic cases, granulocyte colony-stimulating factor is not effective. Accordingly, we were again reminded of the importance of early diagnosis and treatment of antithyroid drug-induced agranulocytosis.

Adult↗

Changes in expression of nonmuscle myosin heavy chain isoforms during muscle and nonmuscle tissue development.

Anti-human platelet myosin antibodies and two anti-peptide antibodies, anti-peptide IIA and anti-peptide IIB, which recognize macrophage-type (MIIA) and brain-type (MIIB) isoforms of nonmuscle myosin heavy chain, respectively, were used to study expression of nonmuscle myosin isoforms in various tissues of mice during development. Tissue-specific changes in the relative isoform concentrations were observed by performing immunoblots of crude myosin extracts from nonmuscle and muscle tissues. In fetal and neonatal mouse tissues, the anti-peptide IIB antibodies stained a single band, called MIIB2, while the anti-peptide IIA and anti-platelet myosin antibodies stained a band that migrated faster than MIIB2. In brain, a slower moving band, MIIB1, started to appear at 2 weeks after birth, and in the adult cerebellum it was at least as abundant as MIIB2. In thymus, MIIB2 decreased selectively shortly after birth, while in liver both MIIB2 and MIIA rapidly disappeared, but the isoform(s) detected by anti-platelet myosin antibodies (MIIApla) remained constant. The MIIB2 and MIIA as well as MIIApla found in striated muscles from fetal and neonatal mice decreased to levels that were below the limit of detection by 3 weeks of age. In cryosections of skeletal and cardiac muscles, MIIB2 was localized within the muscle cells, while MIIA and MIIApla were primarily in the blood vessels and capillaries.

Aging↗

Oculomotor nuclear pathology in amyotrophic lateral sclerosis.

We examined the oculomotor and/or trochlear nuclei of 27 amyotrophic lateral sclerosis (ALS) patients and 10 controls by histological and immunohistological methods. Their neurons were relatively well preserved. In 7 of 22 sporadic ALS patients (including 3/3 ALS with ophthalmoplegia) and in 4 of 5 ALS patients with dementia, some morphological changes similar to those in anterior horns (Bunina bodies, ubiquitin-positive skein-like inclusions, Lewy body-like inclusions, conglomerate inclusions and spheroids) were rarely, but clearly seen. These changes were not observed in controls. Our results suggest that the oculomotor and trochlear nuclei in ALS patients are slightly affected in a manner similar to that in the anterior horns, but the degree is less than that necessary for development of ophthalmoplegia in the majority of ALS patients.

Adult↗

Changes in myosin heavy chain isoform expression of overloaded rat skeletal muscles.

1. The effect of functional overload produced by tenotomy of synergistic gastrocnemius muscle on the expression of myosin heavy chain (MHC) isoforms in the plantaris and soleus muscles of the rat was studied using gradient sodium dodecyl sulfate-acrylamide gel electrophoresis. 2. Five weeks tenotomy, the plantaris and soleus muscle weights induced by tenotomy of the gastrocnemius muscle were 44.3% (P < 0.005) and 37.4% (P < 0.005), respectively, heavier than the contralateral control muscles. 3. Although four types of MHC isoforms were observed in both control and experimental plantaris, the percentage of MHC isoforms in the control and experimental muscles differed; the hypertrophied plantaris muscle contained more HCI (P < 0.05), HCIIa and HCIId (P < 0.05) and less HCIIb (P < 0.05) than the control muscle. 4. The control soleus muscle contained two MHC isoforms, HCI and HCIIa. However, there was only a single HCI isoform in the hypertrophied soleus muscle. 5. These results indicate that overloading a skeletal muscle by removing its synergists produces not only the muscle hypertrophy but also the changes in the expression of MHC isoforms.

Animals↗

Ubiquitin-positive inclusion in anterior horn cells in subgroups of motor neuron diseases: a comparative study of adult-onset amyotrophic lateral sclerosis, juvenile amyotrophic lateral sclerosis and Werdnig-Hoffmann disease.

This report concerns the expression of ubiquitin in anterior horn cells of various subgroups of adult and infantile motor neuron disease (MNDs); immunohistochemical techniques were employed. Ubiquitin-positive skein-like inclusions (SLIs) were found in all cases of adult-onset amyotrophic lateral sclerosis (ALS), including 16 cases with sporadic ALS, two cases of familial ALS with posterior column degeneration and Lewy body-like hyaline inclusions (LBHIs), two sporadic ALS cases with LBHIs, and three cases of sporadic ALS with dementia. SLIs were not found in anterior horn cells of 5 cases with Werdnig-Hoffmann disease (WHD). However, granular ubiquitin-positive deposits were seen in ballooned neurons of WHD patients. No ubiquitinated materials were found in the perikarya of two sporadic juvenile ALS patients with basophilic inclusions (BIs), but granular ubiquitin-immunoreactive deposits were occasionally observed in the BIs. These results suggest that ubiquitin-positive SLIs are characteristic features of various forms of adult-onset ALS and that aggregated ubiquitinated granules are characteristic of ballooned neurons of WHD. Ubiquitinated structures and their distribution patterns may reflect degenerative processes of anterior horn cells, and may be useful for classifying subgroups of motor neuron diseases.

Adult↗

Cerebrospinal fluid 28-kDa calbindin-D as a possible marker for Purkinje cell damage.

To examine the clinical value of 28-kDa calbindin-D (CaBP) in cerebrospinal fluid (CSF) as a marker for the damage to Purkinje cells, we measured CSF CaBP levels using an enzyme immunoassay method in 107 patients with cerebellar and other neurological diseases, and 26 controls. The mean CaBP level was markedly elevated in patients with cerebellar diseases, and the elevation of CaBP level was more frequent in the diseases involving Purkinje cells, such as multiple system atrophy (MSA) and subacute cerebellar degeneration in association with lung cancer. Further, in MSA patients, the CaBP levels decreased with duration of illness. The mean levels of CaBP were also elevated in some of the other diseases. We conclude that the elevations of CaBP levels are not specific for cerebellar diseases, but CSF CaBP may be a useful marker for examining the Purkinje cell involvement in cerebellar diseases.

Adolescent↗

Effects of electrical stimulation or local anesthesia of the rabbit's hypothalamus on the acute phase response.

The effects of electrical stimulation of the rostral hypothalamic region on the acute phase response (APR) were examined in rabbits. As indicators of APR, we measured changes in the plasma concentrations of iron, zinc, copper, and fibrinogen and changes in the red and white blood cell counts. Electrical stimulation of the rostral hypothalamic region near the preoptic and anterior hypothalamic region did not induce any aspect of the APR. However, stimulation near the anteroventral portion of the third ventricle (AV3V) induced responses that were, in part, opposite to those observed in the APR: an increase in the plasma concentration of zinc and a decrease in the circulating leukocyte count. Microinjections of procaine into the brain regions near the AV3V did not induce any changes in the plasma levels of trace metals and fibrinogen but increased the circulating leukocyte count. These results suggest that nonspecific stimulation or inhibition of the rostral hypothalamic region does not induce APR.

Acute-Phase Reaction↗

Immunohistological differentiation of benign thyroid follicular cell tumors from malignant ones: usefulness of anti-peroxidase and JT-95 antibodies.

An immunohistological investigation using anti-thyroid peroxidase (PO) and JT-95 (JT) antibodies was conducted on surgical specimens of papillary carcinoma (n = 12), follicular carcinoma (n = 8), follicular adenoma with prominent papillary structure (n = 12), follicular adenoma (n = 8) and adenomatous goiter (n = 8). In benign lesions, follicle-forming and papillae-forming epithelia showed positive staining with anti-PO antibody. In 26 of 28 benign lesions, PO-positive areas covered 50% or more of the cut surface area of the lesions. However in carcinomas, PO-positive areas were non-existent (13/20) or only focal (7/20) and the papillae did not stain. The incidence of JT-positive cases was higher in papillary carcinomas (12/12) than in other lesions (13/36). JT-positive areas were much wider than PO-positive areas in papillary carcinomas, whereas in benign lesions, PO-positive areas were wider than or at least roughly equal to, JT-positive areas. Follicular carcinomas did not stain or stained only focally with these antibodies. In conclusion, these two antibodies seem useful in differentiating benign from malignant follicular cell tumors.

Adenocarcinoma, Follicular↗

Pathological mineralization in a serially passaged cell line from rat pulp.

The ultrastructure of crystal formation in association with dental pulp cells isolated from rat incisor was studied in vitro. A clone, RPC-K, was obtained and incubated with Na-beta-glycerophosphate (BGP). Growing pulp cells showed low alkaline phosphatase (ALP) activity, which began to increase with cell proliferation. Pulp cells formed cell multilayers after day 14 of culture. Mineralized tissues were observed within cell multilayers on day 28 of culture. Vesicular structures were found around degenerate and necrotic cells. Some of these vesicles contained needle-like crystals. Organic structures appeared at the periphery of mineralized tissues with a post-embedding demineralization and staining method. Electron diffraction patterns of the newly formed crystals revealed a pattern consistent with hydroxyapatite (HAP). These findings suggest that the RPC-K cell line might be useful for a model system to investigate pathological mineralization.

Alkaline Phosphatase↗

The central role of corticotrophin-releasing factor (CRF-41) in psychological stress in rats.

1. We investigated the central role of corticotrophin-releasing factor (CRF-41) in psychological stress-induced responses, including cardiovascular, thermoregulatory and locomotive activity in free-moving rats. 2. Psychological stress was induced by cage-switch stress. After rats were placed in the novel environment, blood pressure, heart rate, body temperature and locomotive activity significantly increased. The intracerebroventricular (I.C.V.) injection of alpha-helical CRF(9-41), a CRF-41 receptor antagonist, significantly attenuated the stress-induced hypertension, tachycardia, hyperthermia and increase in locomotive activity. However, in unstressed rats, the I.C.V. injection of alpha-helical CRF(9-41) had no effect on physiological parameters measured in this study. 3. In unstressed rats, the I.C.V. injection of CRF-41 (1 microgram and 10 micrograms) increased blood pressure, heart rate, body temperature and locomotive activity in a dose-dependent manner. The changes in these responses were quite similar to those observed during cage-switch stress. 4. The results suggest that central CRF-41 plays an important role in psychological stress-induced hypertension, hyperthermia, tachycardia and increase in locomotive activity. However, it is likely that central CRF-41 does not contribute to normal cardiovascular and body temperature regulation when rats are free from stress.

Animals↗

[Epidemiology of sporadic pediatric enteritis patients due to verotoxin-producing Escherichia coli].

We tried to isolate verotoxin-producing Escherichia coli (VTEC) from 323 sporadic pediatric enteritis patients who came to three clinics in the Fukuoka area. We used the sorbitol-MacConkey medium for the isolation of VTEC O157:H7. For non-O157 VTEC strains we used the V1/PECS method. VT/PECS method was applied. VTEC strains were isolated from three patients (0.9%). None of the patients were seriously, ill or developed the hemolytic uremic syndrome. The three patients were all seen in the summer season, July and August. O157:H7 strains were isolated from two patients, and O145:NM from one. This study showed that sporadic enteritis cases due to VTEC exist in the Fukuoka area. In the future a rapid and easy method for the detection of VT or VTEC should be developed and commercialized to proceed with epidemiological studies of VTEC infections throughout Japan.

Bacterial Toxins↗

Levator palpebrae superioris muscle: MR evaluation of enlargement as a cause of upper eyelid retraction in Graves disease.

Sympathetic stimulation of the Müller muscle may be responsible for most of the medically reversible cases of eyelid retraction in patients with Graves disease. The authors studied 21 patients with class I Graves ophthalmopathy (GO), 32 patients with Graves disease without ophthalmopathy (GD), and 12 control subjects. T1-weighted spin-echo magnetic resonance (MR) imaging was performed with a 0.5-T superconducting system. The thickness of the levator palpebrae superioris muscle was determined from sagittal MR images. The thickness of the levator muscles in patients with GD did not differ from the thickness in control subjects, but the levator muscles in patients with GO were significantly thickened (P < .01). The thickness of the levator muscles in patients with GO was significantly greater than in those of patients with GD (P < .01). In 64 orbits of patients with GD, 3% of levator muscles were thickened. In 33 of 40 (83%) orbits of patients with GO presenting with upper eyelid retraction, the levator muscles were thickened. Sagittal MR imaging demonstrated thickening of the levator muscles in patients with persistent upper eyelid retraction. The authors conclude that a thickened levator muscle probably causes upper eyelid retraction in patients with GO.

Adult↗

Effects of alpha- and beta-adrenergic antagonists on rise in body temperature induced by psychological stress in rats.

We investigated the effects of intraperitoneal injection of alpha- and beta-adrenergic antagonists on psychological stress-induced responses in free-moving rats. Psychological stress was induced by immersion in 2-cm-deep water. The intraperitoneal injection of the alpha-adrenergic blocker, phentolamine (10 mg/kg), attenuated the stress-induced rise in body temperature and hypertension but enhanced tachycardia. In contrast, intraperitoneal injection of the beta-adrenergic blocker, propranolol (1 mg/kg), suppressed tachycardia but had no effect on rise in body temperature and hypertension during stress. The intraperitoneal injection of both blockers had no effect on the increase in metabolic rate (O2 consumption) induced by stress. The intravenous injection of propranolol (1 mg/kg) suppressed the stress-induced rise in body temperature. We then examined the effect of intracerebroventricular injection of propranolol on the stress-induced rise in body temperature and found that intracerebroventricular injection of propranolol (50 micrograms) suppressed the stress-induced rise in body temperature. These results support the following hypotheses: 1) Systemic injection of phentolamine suppresses the psychological stress-induced rise in body temperature by facilitating heat-loss; 2) Peripheral beta-adrenergic stimulation probably does not contribute to psychological stress-induced rises in body temperature; and 3) central beta-adrenergic receptors are important in stress-induced increases in body temperature.

Adrenergic alpha-Antagonists↗

Febrile and metabolic tolerance to endotoxin and human recombinant interleukin-1 beta in rabbits.

We investigated whether or not tolerance of the febrile and metabolic responses to human recombinant interleukin-1 beta (IL-1 beta) develops in rabbits. Febrile tolerance to bacterial endotoxin was induced by daily injections of lipopolysaccharide (LPS, 5.0 micrograms/kg iv). In LPS-tolerant rabbits, the second phase of the biphasic fever induced by intravenous injections of LPS (5.0 micrograms/kg) or IL-1 beta (2.0 micrograms/kg) was significantly reduced. However, the first phase was almost the same as that observed in normal rabbits. Five daily injections of IL-1 beta (2.0 micrograms/kg iv) resulted in the development of tolerance of the febrile response to IL-1 beta. In IL-1 beta-tolerant rabbits, the second peak of the biphasic fever was significantly reduced. In addition, decreases in leukocyte count and plasma zinc induced by intravenous injections of LPS or IL-1 beta were significantly reduced in LPS- or IL-1 beta-tolerant rabbits. However the monophasic fever induced by a smaller dose of IL-1 beta (0.5 microgram/kg iv) and the first peak of the IL-1 biphasic fever were almost the same as those observed in normal rabbits. Febrile responses induced in LPS- or IL-1 beta-tolerant rabbits by intracerebroventricular injections of LPS (5.0 ng) or IL-1 beta (2.0 ng) were similar to those observed in normal rabbits. The present results suggest that tolerance of the febrile and metabolic responses to IL-1 beta is developed after repeated injections of IL-1 beta and that reduced responsiveness to IL-1 beta is partly involved in the development of LPS tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗