Search PubMed⌕ Search

Biomedical subjects

N Tamura

Publications and source records attributed to N Tamura.

At least 235 records · Page 13Linked to original sources

Human immunoglobulin preparation for intravenous use induces elevation of cellular cyclic adenosine 3':5'-monophosphate levels, resulting in suppression of tumour necrosis factor alpha and interleukin-1 production.

We previously showed that human immunoglobulin preparation for intravenous use (IGIV) suppresses the in vitro production of tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) by rabbit peritoneal exudate cells (PEC) stimulated with lipopolysaccharide (LPS). In this study we investigated the mechanism of the suppression. IGIV treated at pH4 (pH4-G) was used as IGIV. Fc fragments of pH4-G, as well as untreated pH4-G, suppressed TNF-alpha and IL-1 production by rabbit PEC stimulated with LPS. The interaction of pH4-G with PEC also resulted in generation of cyclic adenosine 3':5'-monophosphate (cAMP), known to be an intracellular second messenger. N6, 2'-0-dibutyryl cAMP (BtcAMP), a lipid-soluble derivative of cAMP, and cholera toxin (CT), an adenylate cyclase activating agent, also suppressed the production of TNF-alpha and IL-1. Further N-[2-(methylamino) ethyl]-5-isoquinolinesulphonamide dihydrochloride (H-8), an inhibitor of cAMP-dependent protein kinases, abrogated the suppression by pH4-G of the productions. These results indicate that the binding of IGIV to PEC via Fc gamma receptors (Fc gamma R) induces the elevation of intracellular cAMP levels, resulting in the suppression of LPS-induced TNF-alpha and IL-1 productions.

Animals↗

[Fibromyalgia (fibrositis) syndrome--a case report].

A 25-year-old woman was admitted in our hospital with back pain and both hip joint pain. Pain was abruptly occurred from the beginning of March 1990. Physical examination revealed wide spread pain (occipital area, both shoulder, lumber area, bilateral gluteal area, inguinal area, both Achilles-plantar area) and more than 12 tender points (occiput, trapezius, second rib, supraspinatus, gluteal, greater trochanter, hip joints, pubic bone). Laboratory examination showed no abnormal findings except ANF (1:160). Any examination including X-ray, bone scintigraphy, CT and MRI did not disclose spondylitis, sacroiliitis and enthesopathy. She was diagnosed as primary fibromyalgia/fibrositis syndrome. Treatment with maprotine hydrochloride (30 mg/day) and phenobarbital (120 mg/day) brought approximately 1/3 reduction of pain and tenderness. Psychoanalysis revealed that she had psychological conflicts against her parents and her colleagues at the work. EEG showed a borderline record with irregular basic pattern and 14 & 6 Hz positive burst at the sleep stage. Although the newly proposed criteria for the classification of fibromyalgia was proposed by ACR, fibromyalgia/fibrositis syndrome has been seldom discussed in the Japanese literature. As this syndrome is frequently associated with various rheumatic diseases, hypothyroidism and malignant diseases, we should pay much more attention to understand this syndrome.

Adult↗

[A case of adrenoleukodystrophy presenting large lesion of the cerebellar white matter and dentate nuclei on brain CT and MRI].

A 17-year-old male was admitted to our hospital complaining of slowly progressive gait disturbance. His initial symptoms were behavioral change and mental deterioration starting at age 16. One year later, unstable gait and speech disturbance appeared. On admission, neurological findings included slight dementia, visual loss, scanning speech, dysdiadochkinesis, pathological reflexes, spastic and ataxic gait. Brain CT scan showed symmetrical low density areas in the dentate nuclei and cerebellar white matter, atrophy of the brain stem and cerebellum, and dilatation of the fourth ventricle. These findings were also confirmed by MRI. One year after admission, atrophy of the frontal, temporal, parietal lobes was noted by CT scan and MRI. The cervical and thoracic cord was observed to be atrophic by MRI. Motor nerve conduction study showed decreased velocity, suggesting the presence of peripheral neuropathy. Fatty acids analysis of plasma sphingomyelin revealed marked increased in very long chain fatty acids, which was compatible with a diagnosis of adrenoleukodystrophy (ALD). However, the term "adrenoleukomyeloneuropathy (ALMN)" was considered more preferable, since the spinal cord and peripheral nerves were involved in this case. Prominent changes in the cerebellar white matter and dentate nuclei at early stage on CT and MRI were not described in the previous publications. Our paper, hence, may be the first one to report such findings and may contribute to early recognition of ALD or ALMN.

Adolescent↗

[Central acetylcholine receptor function in patients with myasthenia gravis].

There are some reports on central nervous system involvements in patients with myasthenia gravis, such as abnormal EEG, and memory disturbance. Myasthenia gravis is considered to be an autoimmune disease with antibodies against the skeletal nicotinic acetylcholine receptor (n-AChR). ACh is a neurotransmitter in osmoregulation. Neuronal n-AChR plays an important role in this regulation. In order to investigate the function of neuronal n-AChR in patients with myasthenia gravis, we performed a 5% hypertonic saline infusion test on 9 patients and 9 healthy volunteers. We also carried out an orthostatic stress test (50 degree passive head-up tilt) on 6 patients with myasthenia gravis and 5 healthy controls to evaluate arginine-vasopressin (AVP) release via baroreceptors. Three of the 9 MG patients showed exaggerated plasma AVP secretion, and one revealed a blunt response to hypertonic stimulation. Both patients and controls did not differ significantly in terms of plasma AVP response to orthostatic stress. To conclude, we suggest the possibility that function of neuronal n-AChR in the central nervous system is impaired in patients with myasthenia gravis.

Adult↗

Diversity in junctional sequences associated with the common human V gamma 9 and V delta 2 gene segments in normal blood and lung compared with the limited diversity in a granulomatous disease.

The T cell receptor (TCR) junctional regions (N regions) of the common human V gamma 9 and V delta 2 gene segments were sequenced from the blood and lung of normal individuals (195 transcripts) and a group of individuals with sarcoidosis (220 transcripts), a granulomatous disease in which increased numbers of V gamma 9+ gamma/delta + T cells are often observed. In normal individuals, the vast majority (86%) of blood V gamma 9 transcripts used the J gamma P gene segment. In contrast to this restriction of J region usage, there was a large diversity of the junctional region, with less than 20% of blood V gamma 9 junctional regions showing identical sequences for any one normal individual. For the blood V delta 2 transcripts in normal individuals, there was restriction of J region usage, with 93% using J delta 1. The junctional regions were even more diverse than for V gamma 9, with a unique sequence observed in each transcript examined. Compared with blood, sequences from the normal lung showed a small increase in identical junctional regions, particularly in one individual where 46% of V gamma 9 transcripts examined were identical, suggesting a response of some gamma/delta T cells to antigens found in the lung in the normal state. In marked contrast to normals, some individuals with sarcoidosis had large numbers of V gamma 9 transcripts, as well as V delta 2 transcripts, sharing identical sequences. For V gamma 9 blood transcripts, two individuals showed 84 and 56% of junctional region sequences to be identical, respectively. Similarly, blood V delta 2 transcripts showed 43, 33, and 25% identical junctional region sequences in three individuals. In the sarcoid patient with the most striking over-representation of blood V gamma 9 junctional sequences, lung V gamma 9 transcripts showed increased (67%) use of the same junctional region sequence as in blood. This limited diversity of TCR junctional regions among some individuals with sarcoidosis suggests a response from specific stimuli, possibly antigenic, and that gamma/delta T cells may play a specific role in granuloma formation in sarcoidosis, as has been suggested in other granulomatous diseases.

Adult↗

Biased accumulation of T lymphocytes with "memory"-type CD45 leukocyte common antigen gene expression on the epithelial surface of the human lung.

Expression of alternatively spliced products of the CD45 leukocyte common antigen gene identifies two populations of blood T cells: "naive" T cells (containing CD45R-IV mRNA transcripts, CD45 220, 205 kD surface proteins detected with antibody 2H4) that respond poorly to recall antigens, and "memory" T cells (containing CD45R-0 mRNA transcripts, expressing CD45 180 kD protein, detected with antibody UCHL1) that respond promptly to recall antigens. While blood contains approximately equal numbers of "naive" and "memory" T cells, it is known that UCHL1+ "memory" T cells accumulate at sites of chronic inflammation. To test the concept that "memory" T cells are a feature of the T lymphocyte populations present in tissues chronically exposed to antigens in normals as well as in individuals with chronic inflammation, we evaluated T lymphocytes obtained from blood and the epithelial surface of the lower respiratory tract of normal individuals for the expression of specific CD45 surface protein isoforms and corresponding mRNA transcripts. Flow cytometric analysis of CD45 220, 205, and 180 kD surface proteins demonstrated that lung T cells of normals are dominated by UCHL1+ "memory" cells (86 +/- 2%) while autologous blood T cells have equal proportions of "memory" UCHL1+ and "naive" 2H4+ T cells. In addition, polymerase chain reaction analysis of CD45 mRNA transcripts revealed that the lung cells expressed CD45R-0 mRNA transcripts but 17-fold fewer CD45R-IV mRNA transcripts than autologous blood T cells (p less than 0.01). The pattern of lung T cells being dominated by CD45R-0 mRNA+, UCHL1+ "memory" T cells was also observed in individuals with chronic beryllium disease, an example of a chronic inflammatory disease in which antigen-specific T cells accumulate on the pulmonary epithelial surface. Like the normals, the lung T cells of the beryllium disease patients were dominated by CD45R-0 mRNA transcript+, UCHL1+, T cells. However, on a quantitative basis, the beryllium patients contained far greater numbers of T cells, i.e., the T cell populations on the surface of the normal and inflamed lung are similar in character ("memory" T cells) but differ in numbers (there are far more in the chronic inflammatory state). Thus, T cell populations on the epithelial surface of the normal lung likely reflect the chronic exposure to a diverse set of antigens, with a pattern that is qualitatively similar to that observed among T cells accumulating in response to a single antigen.

Adult↗

Autonomic function and unmyelinated fibers in chronic inflammatory demyelinating polyradiculoneuropathy.

Because autonomic function may be abnormal in some demyelinating peripheral neuropathies, it has been studied with a number of noninvasive and invasive tests in 14 patients with chronic inflammatory demyelinating polyradiculoneuropathy. There were abnormalities of the 30:15 ratio in 3 patients and an abnormal thermoregulatory sweat test in 5 patients. These findings are indicative of mild parasympathetic and sympathetic dysfunction. Minor pathological changes in unmyelinated fibers were demonstrated on morphometric examination of sural nerves of 10 patients.

Adolescent↗

Characterization and genotoxicity of DNA adducts caused by 2-naphthyl isocyanate.

Calf thymus DNA and M13mp9 RF DNA were modified with [ring-3H]2-naphthyl isocyanate (NIC) and analyzed by reverse-phase HPLC following enzymatic hydrolysis. In each case, essentially, a single radioactive component, which co-chromatographed with authentic N4-2-naphthyl-carbamoyl-2'-deoxycytidine (NCdC), was detected. In order to explore the biological potential of this adduct, mp9 RF DNA modified with NIC was introduced into Escherichia coli strains using a calcium chloride technique. The plaque-forming efficiencies of DNA decreased with increasing adduct level, and the decreases were more pronounced in Uvr endonuclease-deficient strains (i.e. AB1886, uvrA; AB1885, uvrB; AB1884, uvrC) as compared to JM103 (Uvr endonuclease proficient) and JM101 RH03 (recA). These results suggest that these lesions, NCdC adducts, can be removed by the Uvr endonuclease repair system. Mutations were detected as the loss of ability of the bacteriophage to complement the defective beta-galactosidase of the host cells. Induction of SOS functions in the host cells enhanced the mutation frequency to 0.089%, i.e. greater than or equal to 4-fold greater than in non-SOS-induced cells, in transfections with RF DNA that contained 100 adducts/molecule. The mutagenic potency of this cytidine lesion is lower than that of the guanine-C8 adducts of 2-aminofluorene and 2-acetylaminofluorene as reported previously for this mutagenesis system.

Cyanates↗

Comparative survival of aminobiphenyl- and aminofluorene-substituted plasmid DNA in Escherichia coli Uvr endonuclease deficient strains.

pBR322 plasmid DNA, randomly substituted with arylamine moieties, was introduced into Escherichia coli Uvr endonuclease deficient strains. Plasmid survival was determined by selection in the presence of ampicillin. Modification of plasmid DNA with N-acetoxy-N-trifluoroacetylaminobiphenyl yielded primarily N-(deoxyguanosin-8-yl)-4-aminobiphenyl residues. Reaction of DNA with N-acetoxy-N-acetylaminobiphenyl produced only N-(deoxyguanosin-8-yl)-4-acetylaminobiphenyl adducts. The aminobiphenyl (ABP) and acetylaminobiphenyl adducts reduced the ability of the plasmid DNA to transform E. coli to approximately the same extent in a wild-type strain. In uvrA, uvrB and uvrC, i.e. Uvr endonuclease deficient strains, both adducts produced equivalent decreases in survival, however, the reduction in survival was much more pronounced in the uvr- cells than in the wild-type strain. A similar pattern of toxicity was observed with plasmids carrying N-(deoxyguanosin-8-yl)-2-acetylaminofluorene adducts, although the acetylaminofluorene adduct was approximately 5-fold more effective in reducing the biological activity of the plasmid. In contrast, the deacetylated aminofluorene (AF) lesion, N-(deoxyguanosin-8-yl-2-aminofluorene, exhibited relatively little effect on plasmid survival in uvrA and uvrB cells as compared to the wild-type strain, even though the survival of both ABP and AF adducts was essentially similar in the uvrC and wild-type strains. These data demonstrate that (i) both the deacetylated and acetylated lesions are subject to repair by the Uvr endonuclease complex, and (ii) the presence of the N-acetyl group is not the sole determinant of the differential effects of arylamine adducts in uvr cells. These observations provide indirect evidence that both the N-acetyl and aryl moieties of these adducts alter the conformation of DNA.

Acetylation↗

Suppression of tumor necrosis factor alpha production by a human immunoglobulin preparation for intravenous use.

We investigated the effect of a pH 4-treated human immunoglobulin preparation for intravenous use (pH4-G) on the production of tumor necrosis factor alpha (TNF-alpha) in vivo. The level of TNF-alpha in the sera of rabbits receiving pH4-G before lipopolysaccharide (LPS) injection was lower than that in rabbits receiving only LPS. Similarly, the in vitro production of TNF-alpha was suppressed by pH4-G. Rabbit peritoneal exudate cells stimulated with LPS in the presence of pH4-G produced less TNF-alpha than did those stimulated only with LPS. pH4-G, however, had no effect on various TNF-alpha activities, such as cytotoxicity against tumorigenic murine fibroblasts (L929 cells), induction of interleukin-1 production, or fever induction. These results indicate that pH4-G suppresses TNF-alpha production without affecting TNF-alpha activities. A suppressive effect on the expression of TNF-alpha mRNA was also observed.

Animals↗

Synthesis and antibacterial activity of lactivicin derivatives.

The chemical modification of the 4-acetylamino group on the cycloserine moiety of lactivicin (1a) was carried out. The lactivicin derivatives (1d, k--p and w) having heterocyclic acylamino groups which have been often utilized in beta-lactam antibiotics showed potent antibacterial activities. Ester prodrugs (7a--d) of lactivicin derivatives were also prepared in order to improve the bioavailability on oral administration. The pivaloyloxymethyl (POM) esters (7a and 7b) and 1-ethoxycarbonyloxyethyl (EOE) ester (7c) were found to have slightly improved protective effect in vivo compared with their parent compounds 1c and 1k.

Anti-Bacterial Agents↗

[Effects of alminoprofen on the allergic reactions].

The effects of alminoprofen, a nonsteroidal anti-inflammatory agent, on the experimental animal models of allergic reactions were examined and compared with those of ibuprofen. Alminoprofen at 30 mg/kg given intraduodenally significantly suppressed passive anaphylactic bronchoconstrictions, while ibuprofen did not at the same doses. In vitro studies revealed that alminoprofen, in contrast to ibuprofen, exerted an inhibitory effect on arachidonate 5-lipoxygenase activity which initiates the bio-synthesis of leukotrienes. Alminoprofen inhibited arachidonic acid-induced ear edema in mice and homologous passive cutaneous anaphylaxis in rats at high doses, while ibuprofen did not at the high doses. From its characteristic feature of inhibitory effects on 5-lipoxygenase activity and the experimental model of type I allergic reaction, it is suggested that alminoprofen is a new type of nonsteroidal anti-inflammatory agent.

Animals↗

Glomerular filtration response to acute loading with protein from different sources in healthy volunteers and diabetic patients.

To evaluate the effects of acute protein loading on the glomerular filtration rate, albumin excretion rate and concentration of plasma amino acids, ten healthy volunteers and six type 2 diabetic patients with normoalbuminuria were studied before and after eating 0.7 g/kg body weight of tuna fish, boiled egg white, cheese or tofu (bean curd) on separate days. Furthermore, to study the possible role of glucagon, growth hormone, atrial natriuretic peptide and kallikrein in the responses of glomerular filtration rate to protein, these substances were measured before and after ingestion of tuna fish or egg white in six healthy volunteers. In healthy subjects, glomerular filtration rate increased significantly (p less than 0.01) from 98.1 +/- 4.2 ml/min during the baseline period to 129.9 +/- 6.6 ml/min after ingestion of tuna fish. No significant differences were seen between glomerular filtration rate before and after ingestion of egg white, cheese or bean curd. No significant differences were observed between the baseline albumin excretion rate and that after loading with any of the four kinds of protein. Plasma concentrations of alanine, glycine and arginine (amino acids known to induce glomerular hyperfiltration) increased to a greater degree after ingestion of tuna fish than after administration of the other meals. Diabetic subjects and healthy volunteers had similar responses. Plasma glucagon and growth hormone concentrations increased after ingestion of the tuna fish meal or egg white. Plasma atrial natriuretic peptide concentration and urinary kallikrein excretion were unaffected by ingestion of these two kinds of protein. These findings suggest that responses of glomerular filtration rate to acute protein loading may differ depending on the protein ingested, and that these responses may not be directly induced by glucagon, growth hormone, atrial natriuretic peptide or kallikrein.

Adult↗

[Nosological correlation between autonomic failure with Lewy bodies and Parkinson's disease--comparative assessment of clinical features in both diseases].

Autonomic failure with Lewy bodies (AF-LB) was first described by Fichefet et al. in 1965, and more than ten cases have been reported to date. AF-LB and Parkinson's disease (PD) share the neuropathological findings characterized by widely distributed Lewy bodies in the central nervous system including the substantia nigra and locus coeruleus. However, clinical manifestations of AF-LB are far different from PD in which autonomic dysfunction, if present, is not a predominant feature. In the present study, clinical features were comparatively analysed in AF-LB and PD to investigate the nosological relation between PD and AF-LB. The subjects were 94 patients with PD and 11 reported cases of AF-LB in the literature. A test of 70 degrees passive head-up tilt was performed upon the patients with PD in our laboratory. Based on the results in tilting test, the patients with PD were divided into two groups; PD-I (69 cases) with an orthostatic fall of systolic blood pressure less than 30 mmHg, and PD-II (25 cases) with a fall of 30 mmHg or more. Autonomic dysfunctions were more extent in PD-II than in PD-I, because the incidences of anhidrosis, impotence, neurogenic bladder and constipation were higher in PD-II. All of the cases of AF-LB were contained in the previous literatures with reasonably full clinical descriptions. Mean age at onset of the disease was 62.1 +/- 8.7 (mean +/- SD) years old in PD-I, 64.5 +/- 7.5 years old in PD-II and 63.9 +/- 9.0 years old in AF-LB, and no significant differences were found among the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Cardiovascular alpha- and beta-adrenoceptor sensitivities in orthostatic dysregulation].

Orthostatic dysregulation (OD), originally a German-Scandinavian term partially corresponding to an Anglo-American concept of sympathotonic orthostatic hypotension, is characterised by altered cardiovascular control on standing, and its clinical features include dizziness, palpitation and, occasionally, orthostatic hypotension. The symptomatology suggests presence of cardiovascular adrenoceptor dysfunction, although the aetiology of OD has not been elucidated. The above situation prompted us to investigate autonomic nervous function in OD. The subjects were 8 patients with OD (20 +/- 2 years old; mean +/- SD), all of them fulfilled the diagnostic criteria accepted in Japan, and 6 healthy controls (17 +/- 3 years old). Noradrenaline and isoproterenol infusion tests and conventional haemodynamic functional tests (70 degrees passive head-up tilt, cold pressor test, Valsalva manoeuvre and Aschner's eye-ball pressure test) were carried out upon the subjects under the continuous measurement of blood pressure, pulse rate and respiration. Plasma vasoactive substances (noradrenaline, adrenaline, arginine-vasopressin and renin activity) were also determined in supine position and at 15 minutes after the 70 degrees passive head-up tilt. In noradrenaline infusion test, different doses (0.01 microgram/kg, 0.02 microgram/kg, 0.05 microgram/kg and 0.1 microgram/kg) of noradrenaline were administered by means of intravenous bolus injection, and a degree of subsequent rise in blood pressure was used as an index for the cardiovascular alpha-adrenoceptor sensitivity. In isoproterenol infusion tests cardiovascular beta 1- and beta 2-adrenoceptor sensitivities were assessed, respectively, by a degree of an increase in pulse rate and a degree of a fall in blood pressure following bolus injection of the drug (0.001 microgram/kg, 0.002 microgram/kg, 0.005 microgram/kg and 0.01 microgram/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗