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Biomedical subjects

A Nishimura

Publications and source records attributed to A Nishimura.

At least 163 records · Page 9Linked to original sources

Isolation of temperature-sensitive aminoacyl-tRNA synthetase mutants from an Escherichia coli strain harboring the pemK plasmid.

The pem locus, which is responsible for the stable maintenance of the low copy number plasmid R100, contains the pemK gene, whose product has been shown to be a growth inhibitor. Here, we attempted to isolate mutants which became tolerant to transient induction of the PemK protein. We obtained 20 mutants (here called pkt for PemK tolerance), of which 9 were temperature sensitive for growth. We analyzed the nine mutants genetically and found that they could be classified into three complementation groups, pktA, pktB and pktC, which corresponded to three genes, ileS, gltX and asnS, encoding isoleucyl-, glutamyl- and asparaginyl-tRNA synthetases, respectively. Since these amino-acyl-tRNA synthetase mutants did not produce the PemK protein upon induction at the restrictive temperature, these mutants could be isolated because they behaved as if they were tolerant to the PemK protein. The procedure is therefore useful for isolating temperature-sensitive mutants of aminoacyl-tRNA synthetases.

Amino Acyl-tRNA Synthetases↗

A new animal model for split liver transplantation using an infrahepatic IVC graft.

An animal model of split liver transplantation using pigs is described herein. The donor liver was divided into two grafts, the right graft consisting of the right medial and lateral segments with the caudate lobe, and the left graft consisting of the left lateral and medial segments. To make implantation easier, a distal part of the donor's inferior vena cava (IVC) was isolated and attached to the left graft with an anastomosis between the orifice of the renal vein and the graft's hepatic vein. The left graft thereby contained a newly constructed retrohepatic IVC for anastomosis to the recipient. During the anhepatic phase, no conventional bypass procedure was used, but an abdominal aortic clamp in combination with general hypothermia was employed. Ten pigs were used as donors and a total 20 liver transplantations performed. No immunosuppressive drugs were given in this series. Ten of the 20 recipients survived for more than 2 days, the mean survival time being 4.7 days, with a range of 2-14 days. The mean survival time of the left grafts was much longer than that of the right grafts, although no technical problems such as kinking of the graft or occlusion of the hepatic vein were encountered in either. This model is the first report of split liver transplantation in animals. The advantages of using the infrahepatic IVC graft include stability of the graft and safe hepatectomy. This model will therefore be useful for the experimental study of split liver transplantation and may also be employed for clinical use in the future.

Animals↗

In vitro production of interleukin-1, interleukin-6, and tumor necrosis factor-alpha in insulin-dependent diabetes mellitus.

The in vitro production of interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) by monocytes was examined in patients with insulin-dependent diabetes mellitus (IDDM), in those with noninsulin-dependent diabetes mellitus (NIDDM), and in healthy volunteers. The production of IL-1 and IL-6 by monocytes was significantly lower in IDDM patients than in NIDDM patients and normal subjects whereas the TNF-alpha production by monocytes did not differ between IDDM patients and normal subjects. On the other hand, the TNF-alpha production was significantly higher in NIDDM patients than in IDDM patients and normal subjects. There was a significant correlation between IL-1 and IL-6 concentrations in culture supernatants of monocytes for IDDM patients but not for NIDDM patients and normal subjects. Neither glucose nor insulin showed any stimulatory effect on in vitro production of these monokines. In the serial observation lasting 3-18 months, the monocyte production of IL-1 was found to be consistently reduced in IDDM patients unrelated to the control state of diabetes, suggesting that the reduction of the IL-1 and IL-6 production by monocytes in IDDM patients may be intrinsically affected by immunological defects.

Adult↗

[Recent advances in the study on the mechanism of brain injury].

A cerebral contusion and DAI (diffuse axonal injury) are practically very important in a medico-legal case of the closed head injury. In this paper, we will report the epitome of the recent advances in the study on the mechanism of them. Coup contusion can be mainly attributed to the skull inbending and/or the skull fracture which develop in the impact region. As to the mechanism of the contrecoup contusion, several theories are reported. During rotational movement of the head, intracerebral shear strains would be produced because of brain lag (Holbourn's rotation theory). Anatomical features of the skull plays an important role (Gurdjian). Relative movement between a brain and a skull induces intracranial cavitation due to pressure gradient (Gross's cavitation theory). Brain is injured by deformation pressure induced by skull deformation and acceleration one done by a movement of the head (Lindenberg). The last one is Courville's transmitted waves of force theory. As to DAI, there is Gennarelli's theory. During a rotational movement of a brain caused by high rate of angular acceleration operating for a long period, intracerebral shear strains occur and injure a brain. As to the brain injuries which include a cerebral contusion and DAI, two theories are reported. Centripetal progression of strains to the core of a brain injuries the brain (Ommaya). Natural frequency of impact determines the nature of resulting injury to the brain (Willinger).

Biomechanical Phenomena↗

Histo-pathological findings of abraded skins in the cases of automobile dragging.

We histologically examined skin which had been abraded by automobile dragging. In the first case, the victim was a 57-year-old drunken male. He was hit by a passenger car while walking on a road and dragged for a distance of 30 m. He soon died from the pelvic bone fractures. Extensive and deep abrasions were observed on both shoulders and the back. In the second case, a 20-year-old drunken male was lying on a road. He was run over by a passenger car and dragged for a distance of 800 m. During the dragging the car's underbody strongly compressed his thoraco-abdominal region and killed him by causing insufficiency in breathing. Deep abrasions were found in the right temporal region and right back at the waist. In the third case, when a 50-year-old woman was riding a moped it collided with a passenger car at an intersection and she fell to the ground. Soon after, she was run over by another passenger car and dragged for a distance of 718 m. The cause of death was profuse bleeding from the crushed right axillary artery and vein. Autopsy revealed very extensive and severe abrasions in the right upper arm, right axilla, lateral surface of the right chest and abdomen, right back, back pelvic region, and lateral surface of the right lower leg and foot. Especially in the arm, axilla and chest, the skin and soft tissues were worn away, muscles and bones were exposed, and the right axillary artery and vein were crushed.(ABSTRACT TRUNCATED AT 250 WORDS)

Accidents, Traffic↗

[A case of death within 3 hours due to systemic embolism of fat from tibial fractures].

We experienced a case dying of systemic fat embolism shortly after a traffic accident. The man of 83 years old suffered an accident by a car while wheeling his bicycle on a lane through rice fields. His both legs were run over by a wheel of the car. He was fully conscious for some while after the accident. However, while he was taken to a hospital by an ambulance, he suddenly lost consciousness and died 2 hours and 45 minutes after the accident. The autopsy examination revealed the severely fractured tibiae in both legs. The left clavicle and sternum as well as the ribs of both sides were also fractured. Organs in the thoracic and abdominal cavities were slightly congested. The histopathological examinations revealed fat droplets in the small vessels in interlobular connective tissues and many alveolar capillaries of the lungs, many glomeruli of the kidneys and a few capillaries in parietal region of the cerebrum.

Accidents, Traffic↗

[Intra-arterial chemotherapy with 5-FU (weekly high dose 5-FU HAI) for the prevention of tumor recurrence in residual liver after hepatic resection of metastasis from colorectal cancer].

Intra-arterial cancer chemotherapy using an implantable reservoir was performed for the prevention of tumor recurrence in residual liver after resection of a metastatic tumor from colorectal cancer. Four cases of synchronous hepatic metastases and one case of metachronous hepatic metastasis, which were in H1 (2 cases) and H2 (3 cases), were treated. 5-FU was administered in a dose of 1,000 mg/m2 5 hours weekly (weekly high dose 5-FU HAI). The longest survival obtained is 1Y 11M. Other cases have survived for 1Y 7M, 1Y 12M, 9M, and 3M. Tumor recurrence was not observed in all cases except one. This case had a residual tumor because the complete resection was impossible. The tumor recurrence rate in patients treated with surgery alone at Nikko Memorial Hospital (n = 11) was 63.6%. The 1- and 2-year survival rate in these patients was 60.6% and 26.9%, respectively. As compared to these rates, the results of this study were very favorable. Although mild nausea and abdominal discomfort were observed in 1 patient, this adverse effect was reduced by administration of an anti-ulcer agent. Only a slight decrease of WBC and PLT counts was observed. Consequently, for residual liver after resection of hepatic metastasis from colorectal cancer, this intraarterial chemotherapy with 5-FU is considered to be effective to prevent tumor recurrence and thus to prolong survival.

Aged↗

[Traumatic primary brain stem injury and ambient cistern hematoma evaluated with magnetic resonance imaging].

Traumatic hemorrhage in the ambient cistern is thought to be an indirect indication of brain stem injury. In many cases such brain stem lesions cannot be clearly demonstrated by conventional CT scans. Magnetic resonance imaging (MRI) provides a more sophisticated display of the brain stem with improved contrast resolution of structures not appreciated on CT. We present four patients with traumatic ambient cistern hematoma on CT. They showed consciousness disturbance at the initial neurological examination and a Glasgow Coma Scale (GCS) of 7-10. All patients had hemothorax or clavicular fracture ipsilateral to the ambient cistern hematoma that suggested a severe mechanical force from the same direction. Axial, coronal and sagittal MRI scans were obtained with a super-conductive 1.5 T unit (Picker) within 6 days after trauma. Two standard pulse sequences were used; (1) Spin-echo (TR/TE = 500/20) or Inversion Recovery (TR/TI/TE = 3300/600/30) to obtain T1-weighted information and (2) Spin-echo (TR/TE = 2000/100) to obtain T2-weighted information. In case 1 (3-year-old girl) the hematoma which was thought to be located in the ambient cistern on CT was found to be present in the subpial region in the tegmentum on MRI. On T2 weighted image, a high signal intensity area was seen in the perifocal area. This area was demonstrated as a low density area on CT. This patient has remained in a persistent vegetative state 6 months after trauma. In case 3 (31-year-old man) CT demonstrated no abnormal findings in the brain stem. MRI demonstrated a high intensity area in the right cerebral peduncle and left tegmentum.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Parathyroid hormone inhibits 25-hydroxyvitamin D3-24-hydroxylase mRNA expression stimulated by 1 alpha,25-dihydroxyvitamin D3 in rat kidney but not in intestine.

Using a cDNA probe for rat renal 24-hydroxylase, expression of its mRNA was compared in the rat kidney and intestine. Vitamin D-deficient rats received a single injection of 1 alpha,25-dihydroxyvitamin D3. Expression of 24-hydroxylase mRNA was first detected in the kidney at 3-h post-injection and increased thereafter. Similarly, 24-hydroxylase mRNA was expressed in the intestine after 1 alpha,25-dihydroxyvitamin D3 injection. However, the dose level of 1 alpha,25-dihydroxyvitamin D3 required to induce the intestinal 24-hydroxylase mRNA expression was only 1/100 the amount required to induce renal 24-hydroxylase mRNA. Induction of intestinal 24-hydroxylase mRNA expression by 1 alpha,25-dihydroxyvitamin D3 was far more rapid than that of renal 24-hydroxylase mRNA. Thyroparathyroidectomy shortened the time required to induce expression of renal, but not intestinal, 24-hydroxylase mRNA. Administration of either parathyroid hormone or cAMP to vitamin D-deficient rats greatly reduced the expression of 24-hydroxylase mRNA in the kidney but not in the intestine. When rats were fed a vitamin D-repleted diet containing 0.7% (adequate) or 0.03% (low) calcium for 2 weeks, intestinal expression of 24-hydroxylase mRNA could be induced only in the low calcium group. In contrast, renal mRNA expression was preferentially stimulated in the adequate calcium group. These results clearly demonstrate that the expression of 24-hydroxylase mRNA is down-regulated by parathyroid hormone in the kidney but not in the intestine.

Animals↗

Neuroleptic malignant syndrome-like state in a patient with Down syndrome and basal ganglia calcification.

We report a case of rhabdomyolysis in a 13-year-old Down syndrome patient with progressive quadriplegia, choreoathetosis and dystonia. Cranial CT demonstrated bilateral basal ganglia calcification. He experienced the sudden onset of high fever, cloudiness of consciousness, muscle rigidity and severe opisthotonus. The diagnosis was made on the basis of the marked increases in serum creatine kinase and myoglobin. There was remarkable elevation of 5-hydroxyindoleacetic acid, homovanillic acid and methoxy-hydroxyphenyl glycol in the cerebrospinal fluid during hyperpyrexia. This case exhibited almost all the diagnostic criteria of the neuroleptic malignant syndrome. It was suggested that abnormalities of monoamines in the central nervous system may be related to the pathologic etiology of this state and rhabdomyolysis.

Adolescent↗

Correlation of a subset of the pLC plasmids to the physical map of Escherichia coli K-12.

We determined map positions of the Escherichia coli K-12 portions of a subset of the hybrid E. coli-ColE1 plasmids constructed by Clarke and Carbon. The probe DNA of pLC plasmids was labeled with digoxigenine-dUTP, hybridized to the 476 phage clones of the E. coli ordered clone bank miniset, which was adsorbed on a strip of nylon membrane filters, and detected by enzyme-linked immunoassay and a subsequent enzyme-catalyzed color reaction. The total number of Clarke-Carbon plasmids we analyzed was 518, for which chromosomal locations of 297 clones were newly determined in the present study. Another 180 plasmids gave results that agreed with those reported previously, and the remaining 41 plasmids gave map positions different from those described in the previous report. A chromosome map of E. coli which shows the locations of 518 pLC plasmids on it is presented, as well as a table which correlates the pLC plasmids with the clones of the E. coli ordered clone bank miniset on the basis of the hybridization data. We estimate that approximately one-half of the entire genome of E. coli was covered by the pLC plasmids used in this study.

Chromosome Mapping↗

Effects of the herbal medicine "Sai-rei-to" on in vitro interferon-gamma production of peripheral blood mononuclear cells.

The herbal medicine "Sai-rei-to" has been used in the treatment of swellings and edemas for about 3000 years in China. Recently, this drug has been prescribed as an adjuvant in the treatment of rheumatoid arthritis (RA) among Japan's western medicine doctors. It is thought to possess regulatory effects on the immune system, although its mode of action is not yet fully described. In the present in vitro study, we at first induced interferon-gamma (IFN-gamma) in the cultures of peripheral blood mononuclear cells of healthy volunteers by adding pokeweed mitogen (PWM), phytohemagglutinin (PHA), recombinant interleukin-2 (IL-2), or control medium. We then added "Sai-rei-to" to these cultures and investigated the effects of this drug on IFN-gamma production levels. The results demonstrated that "Sai-rei-to" had 2 different effects: (i) it inhibited the IFN-gamma production in cultures with PWM or PHA (which induced large volumes of IFN-gamma), and (ii) it increased IFN-gamma production in the cultures with IL-2 (IL-2 induced only small volumes of IFN-gamma). These findings indicate that "Sai-rei-to" possesses regulatory effects on the IFN-gamma production. IFN-gamma is an important cytokine in the immune system, and it has also attracted attention as a factor related to the pathogeneses of RA. Therefore, concomitant administration of such a medicine which can appropriately control IFN-gamma production in vivo could be beneficial for RA patients from the immunological viewpoint. Clinical experience in the past has shown that "Sai-rei-to" has a very low incidence of side effects, and can be administered orally for long periods. We expect that concomitant administration of "Sai-rei-to" with current therapy could be clinically useful in the management of RA patients.

Arthritis, Rheumatoid↗

Herbal medicine "sho-saiko-to" induces in vitro granulocyte colony-stimulating factor production on peripheral blood mononuclear cells.

The herbal medicine "Sho-saiko-to (Xiao-Chai-Hu-Tang)" has been used in China for about 3000 years for the treatment of pyretic diseases. This medicine is now available as one of the prescribing drugs approved by the Ministry of Health and Welfare of Japan, and has also been widely used for patients with chronic viral liver disease as one of biological response modifiers in the field of Japan's Western Medicine. However, its mode of action has not been fully described. In the present in vitro study, we added "Sho-saiko-to" (TJ-9, Tsumura, Tokyo) to the culture of peripheral blood mononuclear cells (PBMC) obtained from healthy volunteers, and observed a dose-dependent increase in the production of granulocyte colony-stimulating factor (G-CSF). The same experiment was conducted using other herbal medicines "Dai-saiko-to" (TJ-8) and "Saiko-keishi-to" (TJ-10) which showed similar effects, or "Sho-seiryu-to" (TJ-19) which consists of very different compounds and shows different efficacy. The increases of G-CSF production were similar when "Sho-saiko-to" (TJ-9) or one of the 2 reference drugs (TJ-8 and 10) was added, whereas the increase when the control drug "Sho-seiryu-to" (TJ-19) was added, was quite small. This result shows that G-CSF induction is not a common effect of herbal medicines, but a specific effect of TJ-8, 9, and 10. Among these 3 drugs the increase produced by "Sho-saiko-to" was the largest. Based on this result, we conclude that administration of "Sho-saiko-to" may be useful not only for the treatment of chronic liver disease, but also for malignant diseases and acute infectious diseases where G-CSF is efficacious.

Anti-Inflammatory Agents, Non-Steroidal↗

Effects of methylcobalamin (vitamin B12) on in vitro cytokine production of peripheral blood mononuclear cells.

Recently in Japan, one form of vitamin B12, methylcobalamin also known as methyl B12, has attracted the attention of physicians as a therapy for patients with rheumatoid arthritis. However, its immunological actions in vivo are still unknown. In this study, we induced the in vitro production of such cytokines as interleukin-6 (IL-6), interferon-gamma (IFN-gamma), and interleukin-1 beta (IL-1 beta) by adding various mitogens (phytohemagglutinin:PHA, concanavalin A: ConA, or pokeweed mitogen:PWM) as well as recombinant interleukin-2, and we investigated the effects of methyl B12 (final concentration, 8-8,000 ng/ml) on the production of these cytokines by peripheral mononuclear cells. As compared to the controls, IL-6 production induced by PHA and ConA on Day 4 of the culture was suppressed by an average 60-70% when methyl B12 (80-8,000 ng/ml) was added to the medium. IFN-gamma production decreased dose-dependently with methyl B12, i.e., it decreased to 46% of the control when this production was induced by rIL-2, and decreased to 56-66% when it was induced by mitogens. The effect of methyl B12 on IL-1 beta production on Day I of the culture was small. These findings indicate that methyl B12 suppresses mainly the cytokine production of T lymphocytes. Such suppressive effects as shown in the in vitro situation are expected to be expressed also in vivo in patients with rheumatoid arthritis, especially at articulation lesion sites.

Arthritis, Rheumatoid↗

Efficacy of a herbal medicine "sho-saiko-to" on the improvement of impaired cytokine production of peripheral blood mononuclear cells in patients with chronic viral hepatitis.

Peripheral blood samples were collected from normal subjects and chronic viral hepatitis patients, and the in vitro capability of the peripheral blood mononuclear cells to produce various cytokine (interleukin-1 beta, interleukin-6, interferon-gamma, and granulocyte-macrophage colony-stimulating factor) were analyzed by adding pokeweed mitogen. We then investigated the effects of a herbal medicine "Sho-saiko-to" on the levels of cytokine production. The production levels of the 4 cytokines were significantly lower in the peripheral blood mononuclear cells of the patients (Patient Group) than in those of normal subjects (Control Group). The addition of Sho-saiko-to to the Patient Group resulted in improved productions of those cytokines, as well as an remarkable improvement of interleukin-1 beta production. The results demonstrated that Sho-saiko-to acts to improve such immunological abnormalities as decreased cytokine productions. Administration of Sho-saiko-to to chronic viral hepatitis patients is also expected to have immunological benefits.

Anti-Inflammatory Agents, Non-Steroidal↗

Effects of the streptococcal preparation OK-432 on in vitro cytokine production of peripheral blood mononuclear cells in patients with chronic viral hepatitis.

We obtained peripheral blood mononuclear cells from 12 chronic hepatitis Type B patients, 12 Type C patients, and 15 healthy volunteers, and investigated the effects of OK-432, a streptococcal preparation, on in vitro production of 3 types of cytokines. Mononuclear cells in a concentration of 1 x 10(6) cell/ml were prepared in the culture medium. OK-432 (Chugai Pharmaceutical Co., Ltd., Tokyo) was added to this preparation and incubated for one to 4 days. Thereafter interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and interferon-gamma (IFN-gamma) levels in the culture supernatant were measured using enzyme-linked immunoassay kits. Cytokine production levels in cultures with OK-432 were significantly increased in the mononuclear cells of both patients and healthy volunteers. The largest increase was observed with IFN-gamma (p < 0.01), and then with IL-1 beta (p < 0.05). Responses of the cells from chronic hepatitis Type C patients to OK-432 were relatively good. When interferon (alpha and beta) treatment was first introduced, there were high hopes for a high efficacy. However, we now know 50-70% of patients with chronic hepatitis Type C do not respond satisfactorily to interferon. Some physicians suggest the necessity of using biological response modifier (BRM) as an adjuvant treatment for these patients. From our findings, OK-432 could be a useful BRM in patients with chronic hepatitis Type C.

Cells, Cultured↗

[Fracture of the cervical spine caused by blow in patient with ankylosing spondylitis--a report of an autopsy case].

Fracture of the cervical spine in a patient with ankylosing spondylitis is presented. A 43-year-old male was involved in a fight when drinking. He received blows to his face and the lower jaw, and fell backward on the street and died. The postmortem examination showed abrasions and subcutaneous hemorrhages on the face and the lower jaw. A transverse fracture was observed through the intervertebral disc space between the fifth and sixth cervical vertebrae. The cervical spinal cord was completely ruptured at the fracture site. Ossification of the supporting ligaments and anterior surface of dics were found. The spine was bony ankylosed. The alcohol levels of blood and urine were 2.95 and 3.84 mg/ml, respectively. The cause of death was paralysis of respiration. The victim had suffered from the ankylosing spondylitis for many years. His neck had no mobility. The X-ray films taken at age 42 showed complete ankylosis of the spine, so-called "bamboo" spine. It seemed that the blow to his face and the lower jaw caused hyperextension of the neck and easily caused the cervical fracture because of the loss of flexibility and fragility from osteoporosis in the ankylosed spine.

Adult↗