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Biomedical subjects

T Morino

Publications and source records attributed to T Morino.

At least 19 recordsLinked to original sources

Delayed neuronal damage related to microglia proliferation after mild spinal cord compression injury.

In order to investigate the mechanism of delayed progressive or secondary neuronal damage after the spinal cord injury, we developed a mild-compression injury model in the rat thoracic spinal cord. Our compression device consists of a soft silicone point of contact to the dura, in order to prevent violent injury that may cause axonal tears or hemorrhages in the spinal cord. Since rats often assume a 'standing' posture, i.e. raising head with lifting their fore-limbs, damage to the thoracic spinal cord was evaluated by measuring the frequency of 'standing', which effectively indicates hind limb function. Twenty-four hours after compression by a 20 g weight for 10 or 20 min, the standing frequency of the injured rat was almost the same as that of sham animals that underwent laminectomy without compression. However, the standing frequency decreased with time; the frequency of standing at 72 h was approximately 30-50% that of sham animals. In the compressed spinal cord tissue, microglial cells, detected by lectin staining, proliferated with time. An enormous amount of microglia was observed at 48 and 72 h after compression, although only a small amount of cells were positive to lectin staining at 24 h after the compression. These results suggest that our mild-compression spinal cord injury model showed late-onset or delayed neuronal damage that may be related to pathological microglia proliferation.

Animals↗

Intraaneurysmal flow dynamics study featuring an acrylic aneurysm model manufactured using a computerized tomography angiogram as a mold.

OBJECT: To obtain precise flow profiles in patients' aneurysms, the authors developed a new in vitro study method featuring an aneurysm model manufactured using three-dimensional computerized tomography (3D CT) angiography. METHODS: A clear acrylic basilar artery (BA) tip aneurysm model manufactured from a patient's 3D CT angiogram was used to analyze flow modifications during one cardiac cycle. Stereolithography was utilized to create the aneurysm model. Three-dimensional flow profiles within the aneurysm model were obtained from velocity measurements by using laser Doppler velocimetry. The aneurysm inflow/outflow zones changed dynamically in their location, size of their cross-sectional area, and also in their shapes over one cardiac cycle. The flow velocity at the inflow zone was 16.8 to 81.9% of the highest axial velocity in the BA with a pulsatility index (PI) of 1.1. The flow velocity at the outflow zone was 16.8 to 34.3% of the highest axial velocity of the BA, with a PI of 0.68. The shear stress along the walls of the aneurysm was calculated from the fluid velocity measured at a distance of 0.5 mm from the wall. The highest value of shear stress was observed at the bleb of the aneurysm. CONCLUSIONS: This clear acrylic model of a BA tip aneurysm manufactured using a CT angiogram allowed qualitative and quantitative analysis of its flow during a cardiac cycle. Accumulated knowledge from this type of study may reveal pertinent information about aneurysmal flow dynamics that will help practitioners understand the relationship among anatomy, flow dynamics, and the natural history of aneurysms.

Acrylic Resins↗

Cascading glia reactions: a common pathomechanism and its differentiated control by cyclic nucleotide signaling.

A pathological glia activation, stimulated by inflammatory proteins, beta-amyloid, or brain ischemia, is discussed as a common pathogenic factor for progressive nerve cell damage in vascular and Alzheimer dementia. A critical point seems to be reached, if the cytokine-controlled microglial upregulation causes a secondary activation of astrocytes which loose the negative feedback control, are forced to give up their physiological buffering function, and may add to neuronal damage by the release of nitric oxide (NO) and by promoting toxic beta-amyloid formation. A strengthening of the cyclic adenosine-5',3'-monophosphate (cAMP) signaling exerted a differential inhibition of the stimulatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) released from cultured rat microglia, but maintained the negative feedback signal IL-6; cAMP inhibited also the release of free oxygen radicals (OR) but not of NO. Reinforcement of the NO-induced cyclic guanosine monophosphate (cGMP) increase by blockade of the phosphodiesterase (PDE) subtype-5 with propentofylline counterbalanced the toxic NO action that causes with OR neuronal damage by peroxynitrate formation. In rat cultured astrocytes, a prolonged cAMP elevation favored cell differentiation, the expression of a mature ion channel patter, and an improvement of the extracellular glutamate uptake. Cyclic AMP signaling could be strengthened by PDE blockade and by raising extracellular adenosine, which stimulates A2 receptor-mediated cAMP synthesis. Via an A1 receptor-mediated effect, elevated adenosine was found to overcome a deficient intracellular calcium mobilization resulting from an impaired muscarinic signaling at pathologically decreased acetylcholine concentrations. We suggest that pharmaca, which elevate extracellular adenosine and/or block the degradation of cyclic nucleotides, may be used to counteract glia-related neuronal damage in dementing processes.

Alzheimer Disease↗

Cloning of oxetanocin A biosynthetic and resistance genes that reside on a plasmid of Bacillus megaterium strain NK84-0128.

Bacillus megaterium strain NK84-0218 produces a potent antiviral antibiotic, oxetanocin A, which has an oxetanosyl-N-glycoside linkage to an adenine moiety. However, the oxetanocin A productivity of the original strain was unstable and low. In this study, oxetanocin A productivity and resistance was shown to be lost simultaneously when a 51.5-kb plasmid, pOXT1, was cured during cultivation. The deficiency of oxetanocin A productivity and resistance was restored by re-introduction of the pOXT1 plasmid into the cured strain. By a cloning experiment it was shown that a 6.8-kb BglI-D fragment of the pOXT1 plasmid was responsible for oxetanocin A productivity and resistance.

Adenine↗

Pavlik harness applications for congenital dislocation of the hip. How short can they be made?

We studied the results of different durations of application of the Pavlik harness for congenital dislocation or subluxation of the hip. For this, 110 hips in 106 patients were successfully reduced and examined when 6 years old. Dislocation and subluxation cases were divided into two groups: a long-term (4 months for dislocation and 3 months for subluxation) and a short-term (3 months for the former and 2 months for the latter) group. We compared them by roentgenographic analysis. The association between the long- and short-term groups was tested using statistical analyses. There were no significant differences between them, except for one item in subluxation. Therefore, we can say that the duration of application of the Pavlik harness should be reduced to 3 months for dislocation and 2 months for subluxation.

Braces↗

Stevastelins, a novel group of immunosuppressants, inhibit dual-specificity protein phosphatases.

BACKGROUND: Since the molecular target of the immunosuppressive reagents FK506 and cyclosporin A was revealed to be protein phosphatase PP2B (calcineurin), many researchers have been screening the protein phosphatase inhibitors from microbial metabolites to develop new immunosuppressive reagents. We isolated stevastelin B, which is composed of valine, threonine, serine and 3,5-dihydroxy-2,4-dimethyl stearic acid, and stevastelin A, which is a sulphonylated derivative of stevastelin B. To understand the action mechanism of stevastelins A and B, we synthesized a series of stevastelin derivatives and investigated their structure-activity relationships. RESULTS: A series of stevastelin derivatives have been systematically synthesized. Stevastelin B inhibited gene expression that is dependent on interleukin-2 (IL-2) or IL-6 promoters in situ, but it had no inhibitory activity against any protein phosphatases in vitro. In contrast, stevastelin A, which is a sulphonylated derivative of stevastelin B, inhibited the phosphatase activity of a dual-specificity phosphatase, VH1-related human protein (VHR), in vitro, but it had no inhibitory activity against gene expression or cell-cycle progression in situ. CONCLUSIONS: Stevastelin B is a novel immunosuppressant. It inhibited IL-2 or IL-6 dependent gene expression but did not inhibit the phosphatase activity of calcineurin. The structure-activity relationships show that the acidic functional group on the threonine residue and the stearic acid moiety in the stevastelin molecule are important for inhibitory effects on the dephosphorylation activity of VHR in vitro. Stevastelin B might be sulphonylated or phosphorylated after incorporation into the target cell, and then it interacts with protein tyrosine phosphatases and regulates cell-cycle progression.

Anti-Bacterial Agents↗

Transduction of a cosmid with the R4 phage cos sequence by heterogeneous actinophages, SPA10 and SPA38.

A cosmid, pR4C1, composed of the actinophage R4 cos sequence and Streptomyces plasmid pIJ365, was encapsidated in R4 phage particles in vivo. [T. Morino et al., Mol. Gen. Genet., 198, 228-233 (1985)] In this report a cosmid derivative, pR4C4, is shown to be also encapsidated by heterogeneous actinophages, SPA10 and SPA38, and transferred to Streptomyces lividans. Use of this transduction and conservation of the DNA packaging mechanism are discussed.

Antigens, Bacterial↗

Structural determination of stevastelins, novel depsipeptides from Penicillium sp.

Structures of novel immunosuppressants, stevastelin A, B and B3(1) were determined by their spectroscopic and chemical studies. Three stevastelins were shown to be cyclic depsipeptides composed of a fatty acid and three amino acid moieties. The sequence of these moieties was determined to be as 3,5-dihydroxy-2,4-dimethylstearylvalylthreonyl (or O-sulfonylthreonyl in stevastelin A)-O-acetylserine. Cyclic structures were shown to be formed by ester linkages between the carboxylic group of the O-acetylserine moiety and the 5-hydroxy group of the fatty acid moiety in stevastelin A and B, and the 3-hydroxy group of the fatty acid moiety in stevastelin B3.

Anti-Bacterial Agents↗

Absolute structural determination of stevastelin B.

Stevastelin B, obtained from a culture of a Penicillium sp. NK374186, is a novel depsipeptide containing three amino acids and 3,5-dihydroxy-2,4-dimethylstearic acid. The stereochemistry of the three amino acids was determined by HPLC analysis, and the relative configuration of the 3,5-dihydroxy-2,4-dimethylstearic acid was elucidated by chemical conversion and NMR analysis. The absolute stereochemistry of stevastelin B was determined by synthetic methods.

Anti-Bacterial Agents↗

Predictive factors for intrahepatic recurrence of hepatocellular carcinoma after partial hepatectomy.

To establish useful predictors of the intrahepatic recurrence of hepatocellular carcinoma (HCC) after partial hepatectomy, retrospective analyses of clinical and pathologic factors were done in 112 of 206 patients treated by partial hepatectomy. The absence or presence of intrahepatic recurrence was confirmed by a follow-up study. Cancer-free survival rates after 1, 2, 3, and 5 years were 54.8%, 36.7%, 32.5%, and 25.6%, respectively. The significant factors affecting recurrence were tumor size, number of tumors, cancer cell infiltration of the fibrous capsule of the tumor, portal involvement, and stage of the tumor, but the grade of anaplasia according to Edmondson-Steiner's classification and the severity of associated liver cirrhosis did not show a correlation with the incidence of recurrence. According to Akaike's Information Criteria (AIC), tumor number is useful for predicting early prognosis, and capsular infiltration is a good indicator of long-term survival. However, portal involvement gives much prognostic information throughout the entire postoperative period.

Adult↗

Clinico-pathological features of liver metastases from colorectal cancer in relation to prognosis.

Twenty-nine patients undergoing hepatic resection for colorectal metastases from 1980 to 1986 were studied. The overall cumulative survival rates were 82%, 63% and 32% at 1, 2 and 3 years, respectively. The possible prognostic factors, i.e., Dukes' staging of the primary lesion, the number of metastatic nodes, synchronous versus metachronous appearance of metastases, and curative versus non-curative resection were estimated. Evaluation of those categories did not provide any significant information for prognosis after hepatic resection for liver metastases. The growth patterns of the tumor boundary were classified into three types as sinusoidal, expansive, and mixed. There was no significant difference in the survival rates among these groups. The significant factor affecting prognosis was only whether the secondary tumors were encapsulated or not. Patients with encapsulated tumor of the interval longer than 2 years between colon resection and hepatic resection had a significantly better survival rate.

Adult↗

Clinicopathological features of malignancy in hepatocellular carcinoma.

The clinicopathological features showing the malignancy of hepatocellular carcinoma were investigated by retrospectively analyzing the postoperative prognosis after hepatic resection. The long-term prognosis was strongly affected by the existence of portal tumor invasion or intrahepatic metastasis as indicated by the following results. The 3-year cumulative survival rates were 61% and 38% for patients in portal vein tumor invasion groups (Vp0 and Vp1 (P less than 0.05). No patients with Vp2 or Vp3 could survive beyond 3 years after hepatic resection. Similarly, patients with intrahepatic metastasis IM0 showed a better prognosis, compared to those with IM2 or IM3 (P less than 0.05). In addition, the grade of tumor cell anaplasia to some extent affected the prognosis, but not the tumor growth pattern at the tumor/non-tumor boundary. The tumor growth rate, estimated by the alpha-fetoprotein doubling time, was not connected with venous invasion or intrahepatic metastasis, but it became shorter at the time of a recurrence. It is concluded that, from the standpoint of a long-term prognosis, the pathological features showing malignancy appear in venous invasion and intrahepatic metastasis.

Carcinoma, Hepatocellular↗