Biomedical subjects

N Murakami

Publications and source records attributed to N Murakami.

At least 145 records · Page 8Linked to original sources

PubMed1998

Removal of endotoxin and cytokines by plasma exchange in patients with acute hepatic failure.

OBJECTIVES: To compare the circulating concentrations of endotoxin and cytokines in patients with fulminant hepatitis and patients with the severe form of acute hepatitis, and to assess the effects of plasma exchange on the circulating concentrations of these inflammatory mediators in patients with acute hepatic failure. DESIGN: Prospective, consecutive entry study of patients meeting fulminant hepatitis criteria and the severe form of acute hepatitis criteria. SETTING: University hospital, intensive care unit. PATIENTS: Five patients with fulminant hepatitis, eight patients with the severe form of acute hepatitis, two patients with acute-on-chronic hepatic failure, and one patient with postoperative hepatic failure. INTERVENTIONS: Plasma endotoxin, serum tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6 were determined on admission in five patients with fulminant hepatitis and eight patients with the severe form of acute hepatitis. Circulating concentrations of the inflammatory mediators were measured before and after a single course of plasma exchange in eight patients with acute liver failure, including five patients with fulminant hepatitis, two patients with acute-on-chronic hepatic failure, and one patient with postoperative hepatic failure. MEASUREMENTS AND MAIN RESULTS: TNF-alpha and IL-6 in patients with fulminant hepatitis were significantly higher than in patients with the severe form of acute hepatitis, whereas endotoxin concentrations did not differ between patients with fulminant hepatitis or the severe form of acute hepatitis. IL-1beta was not detectable in patients with either fulminant hepatitis or the severe form of acute hepatitis. Plasma endotoxin concentrations decreased immediately after plasma exchange. Serum concentrations of TNF-alpha and IL-6 were significantly lower after plasma exchange than before plasma exchange. CONCLUSION: TNF-alpha and IL-6 may be important in the pathogenesis of the clinical symptoms that differentiate fulminant hepatitis from the severe form of acute hepatitis, and plasma exchange removes these inflammatory mediators from the circulation of patients with severe liver disease.

Adolescent↗

PubMed1998

Accumulation of tau in autophagic vacuoles in chloroquine myopathy.

Long-term administration of chloroquine to rats induces a vacuolar myopathy, which is specifically termed chloroquine myopathy (CM). In CM, tau mRNA levels were transiently upregulated in the early phase, while tau itself slowly accumulated in the late phase. The temporal profiles of tau mRNA levels and its accumulation were very similar to those of beta-amyloid protein precursor (APP) and its carboxyl-terminal fragments, both of which have been known to be degraded in lysosomes. Immunocytochemistry showed that tau progressively accumulated in the rimmed vacuoles exhibiting increased acid phosphatase activities, and immunoelectron microscopy demonstrated that tau was located within autophagic vacuoles. These results suggest that the accumulation of tau in CM is due to defective tau degradation in the lysosomal compartment in the muscle.

Acid Phosphatase↗

PubMed1998

Novel point mutations and allele loss at the RET locus in sporadic medullary thyroid carcinomas.

Germline mutations in the RET proto-oncogene have been shown to be the underlying cause of multiple endocrine neoplasia type 2 (MEN 2A and 2B) and familial medullary thyroid carcinoma (FMTC). Some cases of sporadic medullary thyroid carcinoma (sporadic MTC) are reported to have specific codon 918, 883 and 768 mutations of the RET gene in tumor tissues. We examined RET gene mutations in 40 Japanese cases who had previously undergone surgery for sporadic MTC. DNA extracted from formalin-fixed tumor tissues and corresponding normal thyroid tissues or peripheral blood leukocytes was analyzed for mutations of exon 10, 11, 13, 14 and 16 of the RET gene by DNA sequencing and by mutation-specific restriction enzyme analysis. Germline RET point mutations were found in six of 40 cases (15%), cysteine residues at codon 618 in two, codon 634 in three and valine residue at codon 804 in one, and were newly identified as heritable MTC. Of the remaining 34 sporadic MTC cases, four (12%) had tumor-specific RET point mutations. Two were found in exon 16; one case showed an ATG to ACG (Met to Thr) mutation at codon 918, and the other showed two point mutations, ATG to ACG (Met to Thr) at codon 918 and GCA to GTA (Ala to Val) at codon 919 with loss of the wild-type allele, suggesting that both alleles at the RET locus were altered. The other two were found in exon 13; one case showed a CCG to TCG (Pro to Ser) mutation at codon 766 and the other showed a silent mutation, GTC to GTT (Val) at codon 778 with loss of the wild-type allele. There was no association of sporadic mutations with recurrence or prognosis in patients with sporadic MTC. The low rate of somatic RET mutation at codon 918 in our sporadic MTC suggests that as yet unknown factors may be involved. Genetic alterations in both alleles may have an important role in small fraction of sporadic MTCs.

Adult↗

PubMed1998

[Clinical analysis on 127 cases of fungemia in Fukuoka University Hospital between 1984 and 1994].

A clinical analysis on 127 cases out of 140 cases presenting with fungemia at Fukuoka University Hospital between 1984 and 1994 was done. The number of the positive blood cultures during the same period was 1188 and the rate of fungemia was 11.8%. The rates generally increased in recent years, 9.0% (1984-1986), 10.2% (1987-1989) and 13.6% (1990-1994), but decreased after 1992. C. albicans has shown a tendency to decrease while C. parapsilosis and C. glabrata have increased in recent years thus suggesting the effect of the prevalence of intravenous hyperalimentation (IVH) and azole antifungal agents. Only 3.9% of the fungemia were preceded by bacteremia. In addition to the known risk factors for fungemia such as IVH (89.0%) and the antibacterial agents, H2-receptor antagonists were used in 58.3% of the cases. 14 cases of the fungemia were observed during the prophylactic use of antifungal drugs. Therefore, fungemia should always be kept in mind regarding the differential diagnosis for bacteremia when an indwelling venous catheter is used. The prompt extubation of the catheter in addition to the adjustment of the dosage of antifungal drugs in response to the status of the host defense system are thus considered to be important in the treatment of fungemia.

Adolescent↗

PubMed1998

Cardiovascular and humoral responses to sustained muscle metaboreflex activation in humans.

The cardiovascular and humoral responses to sustained muscle metaboreflex activation were examined in eight male volunteers while they performed two 24-min exercise protocols. Each of these consisted of six 1-min bouts of isometric handgrip exercise (the left and right hands being used alternately) at 50% of maximal voluntary contraction; after each bout, there was either 3-min postexercise occlusion (occlusion protocol) or 3-min rest (control protocol). In the occlusion protocol, mean arterial blood pressure was approximately 25 mmHg higher than during the control protocol, indicating that the muscle metaboreflex was activated during occlusion. During the control protocol, plasma renin activity, plasma vasopressin, and adrenocorticotropic hormone values were not significantly different from the values at rest. During the occlusion protocol, however, plasma renin activity, plasma vasopressin, and adrenocorticotropic hormone were all significantly increased at 25 min. These data demonstrate that, in humans, the sustained activation of the muscle metaboreflex causes the secretion of several hormones originating from different regions.

Adult↗

PubMed1998

A case of atypical chronic myeloid leukemia regarded as MDS with myeloproliferative features.

We report a case of atypical chronic myeloid leukemia (aCML) who showed marked neutrophilia without dysplastic features, basophilia or monocytosis. These findings diverged somewhat from the FAB criteria for aCML. The patient's erythroid cells and megakaryocytes were dysplastic. His marrow cells formed no spontaneous colonies, as shown by cell culture. The cells formed many small-sized neutrophil colonies with G-CSF stimulation. Interestingly, they formed mainly neutrophil colonies with GM-CSF stimulation. These findings were different from those of chronic myelomonocytic leukemia cells and chronic granulocytic leukemia cells. This aCML case showed the cytological features of myelodysplastic syndrome.

Humans↗

PubMed1998

Anti-inflammatory, analgesic and anti-pyretic effects of d-2-[4-(3-methyl-2-thienyl)phenyl]propionic acid (M-5011), a new non-steroidal anti-inflammatory drug, in rats and guinea pigs.

Anti-inflammatory, analgesic and anti-pyretic effects of d-2-[4-(3-methyl-2-thienyl)phenyl]propionic acid (M-5011), a new non-steroidal anti-inflammatory drug (NSAID), were compared with those of indomethacin, diclofenac sodium and ketoprofen in rats and guinea pigs. Anti-inflammatory effect of M-5011 on ultraviolet-induced erythema in guinea pigs was 11.7 and 1.8 times more potent than that of indomethacin and ketoprofen, respectively. Inhibitory effect of M-5011 on carrageenin-induced paw edema was 2 and 1.5 times more potent than that of indomethacin and diclofenac sodium, respectively. Analgesic effect of M-5011 on dry yeast-induced hyperalgesia or adjuvant-induced arthritic pain was equipotent to that of indomethacin, diclofenac sodium or ketoprofen. Anti-pyretic effect of M-5011 on yeast-induced pyrexia in rats was 4.2 and 4.6 times more potent than that of indomethacin and ketoprofen, respectively. Inhibitory effect of M-5011 on prostaglandin E2 production in the exudate of air-pouch inflammation induced by carrageenin was 1.75 times more potent than that in the non-inflamed site (stomach). As a result, gastric ulcerogenic activity of M-5011 was half that of indomethacin in rat. These results suggest that M-5011 shows more potent anti-inflammatory and anti-pyretic effects and equipotent analgesic effect with low gastro-ulcerogenic activity compared with classical NSAIDs.

Analgesics, Non-Narcotic↗

PubMed1998

Relationship between plasma testosterone concentrations and age, breeding season and harem size in Misaki feral horses.

Jugular vein blood samples were collected from 23 young and sexual mature feral stallions to examine the relationship between plasma testosterone concentration and age, breeding season or harem size. Testosterone concentration increased with the age of the stallions until they formed their own harems, at about 4 to 6 years old. Seasonal variations in testosterone concentrations were observed, and found to be significantly higher (P<0.001) throughout the breeding season than non-breeding season, from 3 years of age. Testosterone levels were correlated with harem size for individual stallions. It can be inferred from these results that there is a relationship between plasma testosterone concentration and age, breeding season and harem size.

Age Factors↗

PubMed1998

Post-operative thyroid status of patients with Graves' disease is determined by the responsiveness of thyrocyte to TSH under the present thyroid gland remnant.

In order to determine whether thyrocyte responsiveness to TSH is correlated with post-operative thyroid status, thyrocytes obtained from 51 patients with Graves' disease were cultured for 3 days. This was followed by culture with 10 mU/mL of TSH (TSH group) or without TSH (control group) for 3 additional days. On the 8th culture day, the amount of thyroglobulin (Tg) secreted into the culture medium was assayed and the Tg ratio (amount of Tg from the stimulated group/amount of TG from the control group) was calculated. Log10 (the Tg ratio) was used for the statistic study. The post-operative status of the patient was determined based mainly on the serum concentration values of free T3 and T4 obtained between 5 and 16 months after surgery. Multivariate analysis revealed that among age, gender, TSH-binding inhibitory immunoglobulin (TBII) obtained before the surgery, estimated weight of the thyroid gland remnant, and Log10 (Tg ratio), only Log10 (Tg ratio) was statistically significant (P=0.008). When the Log10 (Tg ratio) value was small, most patients showed signs of as post-operative hypothyroidism, and as the value became larger as the number of euthyroid and/or hyperthyroid patients increased.

Adult↗

PubMed1998

Supra- and extrasellar pituitary microadenoma as a cause of Cushing's disease.

There has been accumulating evidence that pituitary adenomas which cause Cushing's disease are located not only in sella turcica but also in various extrasellar and intracranial regions. We describe a case of Cushing's disease caused by a supra- and extrasellar ACTH-producing microadenoma, which originated in the anterior pituitary and extended upward without connecting to the stalk. The pituitary microadenoma was identified and removed by transsphenoidal microsurgery. After the surgery the patient experienced complete remission. This type of pituitary microadenoma is considered to be rare, but in order to accomplish successful surgical treatment, it is necessary to consider that pituitary adenomas which cause Cushing's disease may be located in such an unusual position.

Adenoma↗

PubMed1998

Hereditary angioneurotic edema and thromboembolic diseases: I: How symptoms of acute attacks change with aging.

Localized edema of the larynx and pharynx leading to death from asphyxia has long been recognized as a characteristic symptom of hereditary angioneurotic edema (HANE). Long-term follow-up of younger HANE patients has revealed that transient localized acute attacks of edema affect tissues where the microcirculation maintains the blood supply. However, with aging, HANE attacks precipitate disseminated intravascular coagulation (DIC) or multiple organ failure (MOF). Substitution with a C1-inhibitor (C1-INH) has resulted in a fulminant lethal end with a rapid and profound decrease in antithrombin-III (AT-III) activity. A possible mechanism is as follows: Exogenous stimuli activate plasma proteinase systems with the generation of plasma kallikrein that activates the tissue factor pathway (TF) and liberates bradykinin (BK). In younger patients, BK enhances vascular permeability. In the elderly, activated TF is controlled by tissue factor pathway inhibitor (TFPI) and generates thrombin, which is the target enzyme of AT-III and precipitates DIC or MOF. In elderly patients, the characteristic symptom of HANE is hypercoagulation by age-related changes in the biosynthesis of AT-III or TFPI.

Acute Disease↗

PubMed1998

Maternal Brachial Arterial Waveforms in Gestational Hypertension: Analysis Using a Laplace Transform Technique.

> Objective: A pilot study was designed to investigate whether maternal brachial arterial Doppler shift waveforms analyzed using a Laplace transform analysis technique could distinguish women with gestational hypertension and preeclampsia from women who remained normotensive during their pregnancy. Methods: We examined 50 pregnant women in total. They were divided into two groups. The first was a group of 21 normotensive women, and the second was a group of 29 women with gestational hypertension or preeclampsia, not on medication at the time of study. A Doppler shift waveform of the right and left brachial artery was obtained and analyzed using the conventional parameters of resistance index (RI) and pulsatility index (PI) and Laplace transform analysis. Results: The systolic and diastolic blood pressures and the mean arterial blood pressure at presentation were significantly higher in group 2 as expected. The results of the Laplace transform parameters showed significant differences in the resonant frequency, real pole, c coefficient, and alpha between the two groups. There was no difference in the PI between the two groups, but the differences in RI just reached significance. The Laplace transform parameters in the group with gestational hypertension were consistent with peripheral vasoconstriction, which has been suggested as part of the hemodynamic abnormalities in this condition. Conclusion: Analysis of maternal brachial arterial Doppler shift waveforms by Laplace transform analysis detects differences between normotensive and hypertensive patients. These differences may also reflect some of the hemodynamic changes occurring in gestational hypertension.

Journal Article↗

PubMed1997

Extracapsular invasion of lymph node metastasis is an indicator of distant metastasis and poor prognosis in patients with thyroid papillary carcinoma.

BACKGROUND: In patients with thyroid papillary carcinoma, age and the presence or absence of distant metastasis are regarded as the main prognostic factors. However, the histologic characteristics of thyroid papillary carcinoma that develops distant metastasis have not yet been clarified. METHODS: The histologic findings and prognosis of 50 patients with thyroid papillary carcinoma who later developed distant metastasis (metastatic group) were compared with those of 50 patients without local recurrence or distant metastasis (control group). The age, tumor size, and gender ratio of the control group were matched with those of the metastatic group. Univariate analyses (chi-square test and/or Fisher's exact test) and multivariate analyses (logistic regression) were performed. RESULTS: Univariate analyses showed that the incidence of nonpure papillary carcinoma, absence of bone at the periphery of the tumor, invasion of the perithyroidal muscle, large lymph node deposits, and extranodal invasion were significantly higher in the metastatic group. Multivariate analyses revealed that only extranodal invasion was statistically significant (P = 0.0045) and that the odds ratio of extranodal invasion in distant metastasis was 9. Moreover, the risk of death from thyroid carcinoma was higher among the patients with extranodal invasion than those without (P <0.01). CONCLUSIONS: The presence of extranodal invasion in patients with thyroid papillary carcinoma is an indicator of distant metastasis and poorer prognosis.

Adult↗

PubMed1997

Relationship between brainstem MRI and pathological findings in progressive supranuclear palsy--study in autopsy cases.

The relationship between the features of MRI in brainstem and pathological findings was investigated in eight autopsy cases with progressive supranuclear palsy (PSP). Features of T1-weighted images at midbrain level were atrophy of tegmentum and tectum, and dilatation of aqueduct. Histologically, these findings were consistent with atrophy of periaqueductal gray matter, quadrigeminal plate, and tegmentum. In these lesions, we detected neuronal loss, decrease in density of myelinated fibers, gliosis, rarefaction of tissues, and tau-positive structures such as neurofibrillary tangles (NFTs), glial fibrillary tangles (GFTs) and neuropil threads. At pons level, atrophy of tegmentum, atrophy of pontine base, and dilatation of prepontine cistern were found. Tau-positive structures were observed not only in tegmentum but also in pontine base. The density of the tau-positive structure was closely related to the severity of atrophy. Features of T2-weighted images were high intensity in the periaqueductal lesion and tegmentum in pons. In these lesions, severe histological findings were detected. The MRI features in brainstem were closely related to the histological findings as PSP.

Aged↗

PubMed1997

Daily injections of melatonin entrain the circadian activity rhythms of nocturnal rats but not diurnal chipmunks.

It is well known that daily injections of melatonin entrain the free-running rhythms of nocturnal rodents (rats and hamster) and diurnal sauropside (birds and lizard). Here, we asked whether daily injections of melatonin entrain the free-running rhythm of the chipmunk, a diurnal rodent, and, if they do, is the phase relationship between the time of injection and onset of the activity interval similar to that in sauropside rather than that of nocturnal rodents? Contrary to our expectations, daily injections of melatonin did not entrain the free-running rhythm in 9 of 10 chipmunks, even when a high dose of melatonin (1 mg/kg, b.wt.) was used. These results indicate that the entraining effect of daily injections of melatonin on free-running rhythm varies among mammalian species.

Animals↗

PubMed1997

Individual pineal cells in chick possess photoreceptive, circadian clock and melatonin-synthesizing capacities in vitro.

Chick pineal cells express a circadian rhythm of melatonin release under light-dark (LD) cycles, with an increase during the dark period and a decrease during the light period, and this rhythm persists under constant darkness (DD). We cultured individual single pineal cells with 15 microl of medium per well in a Terasaki plate and measured melatonin secretion every 12 h under LD, DL and DD. Individual cells secreted more melatonin during the dark period than during the light period under both LD and DL conditions, and those rhythmic secretions persisted under DD. These results suggest that individual pineal cells in chick have photoreceptive, circadian clock and melatonin-synthesizing capacities.

Animals↗

PubMed1997

Tumor necrosis factor receptors in the pituitary cells.

To clarify the site and mode of action of tumor necrosis factor (TNF) in the pituitary, we studied the effects, binding sites of TNF and its receptor mRNA in the two types of mouse pituitary-derived cell lines, AtT-20, ACTH-producing cells and TtT/GF, folliculo-stellate (FS)-like cells. First, we examined the expression of TNF receptor mRNA in these cells. Using Northern blot analyses with radiolabeled cDNA to murine TNF receptor p60 and p80 mRNAs as probes, we identified both types of mRNA in the poly(A)-containing RNA prepared from AtT-20 cells and p60 TNF receptor mRNA from TtT/GF. The identified mRNA were compatible in size with those detected in the immune-competent cells. Next, we studied the TNF-binding sites on these cells. Scatchard plot analysis of the significant binding of [125I]TNF revealed a single type of binding site with a Kd (dissociation constant) of 210 pM and 131 binding sites/cell on AtT-20. Similarly on TtT/GF, [125I]TNF showed 353 binding sites/cell with a Kd of 900 pM. [125I]TNF binding on both types of cells competed with TNF and lymphotoxin (TNF beta) in an equimolar fashion. Third, TNF stimulates ACTH synthesis in AtT-20 cells, while TNF increases immunoreactive interleukin (IL)-6 release from TtT/GF cells. These findings demonstrate that AtT-20 and TtT/GF cells are equipped with fully functional TNF receptor system, and suggest that ligand of the receptor, TNF alpha and/or TNF beta, can modulate ACTH synthesis and release as a direct hormonal effector on corticotrophs or indirect modulator through another paracrine mediator, such as IL-6 from FS cells.

Animals↗

PubMed1997

Evaluation of learning and memory dysfunction and histological findings in rats with chronic stage contusion and diffuse axonal injury.

We previously reported a modified fluid percussion device capable of consistently producing experimental cortical contusion (CC) and diffuse axonal injury (DAI) in separate groups of rats by lateral and midline fluid percussion, respectively. The purpose of the present study was to compare the differences in learning acquisition and memory retention impairments between these two types of injured rats in the chronic stage using the Morris water maze technique. We also compared the histological differences between these two different types of traumatic brain injury. The results showed a statistically significant difference in learning acquisition impairment between the sham and CC rats and also between the sham and DAI rats. However, a significant difference in memory retention impairment was observed only between the sham and DAI rats. Histologically, the neuronal cell loss of CA3 pyramidal cells in the hippocampus was observed on the ipsilateral side in the CC and bilaterally in DAI. The neuronal cell loss was seen in bilateral entorhinal cortex layer II in DAI, but it was not seen in CC. From these results, we speculate that the marked cell loss in the hippocampus CA3 region in both CC and DAI rats was related to the impairment of spatial learning acquisition. The marked cell loss in entorhinal cortex layer II in DAI rats may be one of the important factors in the impairment of spatial memory retention.

Animals↗