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Biomedical subjects

M Shimoda

Publications and source records attributed to M Shimoda.

At least 91 records · Page 5Linked to original sources
PubMed1997

Molecular analysis of minimally differentiated acute myeloid leukemia with chromosome 16 inversion.

We report a 3-year-old girl with minimally differentiated acute myeloid leukemia and chromosome 16 inversion (inv 16). Inv 16 is generally associated with acute myelomonocytic leukemia with dysplastic eosinophils in the bone marrow (AML-M4Eo). Recently, molecular analysis showed that a fusion gene is generated by this inversion between the CBFB gene on the q arm and the MYH11 gene on the p arm. Using reverse transcriptase-polymerase chain reaction analysis, we tried to detect CBFB/MYH11 chimeric mRNA in blasts from our patients, however, were unable to detect any chimeric mRNA in the blasts: The absence of CBFB/MYH11 transcripts in this case suggests that rare chimeric products might be formed as a result of inv 16 that could not be detected by the primer sets used in this study. Another possibility is that different genes are rearranged on the chromosome 16 with the inv 16. More detailed molecular analysis of this case might be necessary in order to elucidate these possibility. Analyzing leukemias with inv 16 which do not have a typical CBFB/MYH11 chimeric mRNA might lead to understanding an alternative pathogenesis for acute leukemia with inv 16.

Acute Disease↗
PubMed1997

Surgical indications in patients with an intracerebral hemorrhage due to ruptured middle cerebral artery aneurysm.

In this retrospective study, the authors analyzed surgical outcomes in patients who suffered an intracerebral hemorrhage (ICH) as a result of a ruptured middle cerebral artery aneurysm. They studied 47 patients who underwent early aneurysm surgery and hematoma evacuation within 24 hours after onset of ICH. The types of ICH were classified into three groups according to their appearance on computerized tomography scanning: 1) temporal ICH; 2) intrasylvian hematoma; and 3) ICH with diffuse subarachnoid hemorrhage (SAH). Overall, 25 patients (53%) achieved a favorable outcome and 18 (38%) died. Factors that could be used to predict a favorable outcome included age less than 60 years, temporal ICH, World Federation of Neurological Surgeons Grade II or III, absence of a surgical complication, and a hematoma volume less than 25 ml. In the patients with temporal ICH, eight of nine patients achieved a good recovery and no patient developed a surgical complication or delayed ischemic deficit. The significant prognostic factor in patients with an intrasylvian hematoma was surgery within 6 hours after onset of symptoms. In patients with temporal ICH or intrasylvian hematoma, the results of the initial neurological examination did not accurately predict outcome. On the other hand, in patients with ICH and diffuse SAH, those patients who developed an ICH with a volume greater than 25 ml had a poor prognosis. These results indicate that aggressive surgical treatment should be performed in patients with a temporal ICH or an intrasylvian hematoma, regardless of the neurological findings on admission; in patients with ICH and diffuse SAH, a careful review of surgical indications is required.

Aged↗
PubMed1997

[Expression of matrix metalloproteinases and tissue inhibitor of metalloproteinase by myofibroblasts--morphological study on corneal wound healing].

The matrix metalloproteinases (MMPs) and the tissue inhibitor of metalloproteinases (TIMPs) regulate the extracellular matrix and are important in the process of connective tissue remodeling. In this study, we investigated the expression of MMPs and TIMP-2 by myofibroblasts (MF) originating from keratocytes during the healing of alkali-burned and lacerated rabbit corneas. In light and/or electron microscopic immunohistochemistry, the MMP-1, 2, 9 and TIMP-2 antibodies reacted with MF in both types of corneal wounds. The clear expression of MMP-1 and the relatively faint immunoreaction of MMP-2 were observed in both types of healing from one week after wounding, while MMP-9 appeared from 3 weeks after injury. In addition, the levels of MMP-2 and 9 were increased from 4 weeks after alkali-burned injury. The clear expression of TIMP-2 was observed from 1 week after both types of wounds. These findings indicate that MF is deeply involved in degrading some of the key matrix proteins (such as type I collagen), and may play an important role in tissue remodeling in corneal wounds through production of MMPs and TIMP.

Animals↗
PubMed1996

Early aneurysm surgery and dehydration therapy in patients with severe subarachnoid haemorrhage without ICH.

We prospectively analysed treatment results in patients with severe subarachnoid haemorrhage (SAH) who underwent early aneurysm surgery, and were managed by dehydration therapy. We studied a total of 31 patients with poor-grade SAH including 18 in grade IV, and 13 in grade V according to the WFNS classification system. Patients who were older than 70 years of age, or those with an intracerebral haemorrhage or absent brainstem response were excluded from this study. At surgery, clot evacuation from the peri-brainstem cisterns with/without external decompression was performed following obliteration of the aneurysmal neck. In the early postoperative period, patients were maintained in negative water balance using osmotic diuretics. When delayed ischaemic deficits had manifested themselves, the pulmonary wedge pressure and/or central venous pressure was immediately increased by the rapid injection of albumin until hypovolaemia reverted to normovolaemia with the continuous administration of dobutamine. The outcome at 3 months was good recovery in 16 (52%) patients, moderate disability in 3 (10%), severe disability in 5 (16%), a vegetative state in 1 (3%), and death in 6 (19%). We though that early aneurysm surgery and postoperative dehydration therapy in the acute stages of brain oedema resulting from primary brain damage are effective in the treatment of patients with severe SAH but reversible primary brain damage.

Adult↗
PubMed1996

Implication of altered levels of plasma alpha(1)-acid glycoprotein and its derived sialic acid on plasma protein binding of trimethoprim in pigs in physiological and pathological states.

In growing pigs (0 to 158 days after birth), pregnant sows (0 to 90 days), and in pigs suffering from respiratory disease (Actinobacillus pleuropneumoniae), the plasma levels of alpha(1)-acid glycoprotein (AGP) and its derived sialic acid were determined, as was the meaning of their altered levels on the plasma protein binding of trimethoprim. The AGP level was very high immediately after birth (more than 10,000 mu g/ml), decreased markedly during 2 weeks after birth (about 700 mu g/ml) and thereafter stayed at a constant level (about 400 mu g/ml). Pregnant sows had a low AGP level with a narrow variation throughout pregnancy (about 190 to 260 mu g/ml). Pigs infected with A. pleuropneumoniae showed an increased AGP level (mean value; 732 mu g/ml) with a wide variation (range: 170-1,840 mu g/ml). N-acetylneuraminic acid (NANA) and N-glycolylneuraminic acid (NGNA) were sialic acid subtypes detected in porcine plasma. In growing pigs, the time course of changes in NANA concentrations was consistent with that of AGP, whereas that of NGNA was different, implying that NANA is a sialic acid subtype derived from porcine AGP, in contrast to NGNA. The relationship between AGP and NANA levels in growing pigs could be expressed by the following equation: NANA=0.14 x AGP + 159 mu g/ml, whereas that in pigs with respiratory disease could be expressed by NANA=0.O67 x AGP + 357 mu g/ml, indicating a low fraction of NANA in AGP in diseased pigs. The regression lines between the AGP level and the plasma protein binding of trimethoprim < or = 2,000 mu g of AGP/ml were similar as follows: binding(%)=0.O23 x GP + 34 in growing pigs and binding(%)=0.O22 x GP+29 in diseased pigs, implying a minor role of sialic acid residues in the binding of basic drugs to AGP. In conclusion, the wide change in plasma AGP levels in diseased pigs as well as during the initial growth phase can alter the plasma protein binding of basic drugs such as trimethoprim, probably leading to a change in drug disposition. The low sialylation of AGP in diseased pigs may not have a great influence on the binding of basic drugs to AGP, implying the quantitative importance of AGP.

Actinobacillus Infections↗
PubMed1996

Contribution of alpha 1-acid glycoprotein to plasma protein binding of some basic antimicrobials in pigs.

Protein binding kinetics of basic antimicrobials including trimethoprim (TMP), erythromycin (EM), lincomycin (LM) and clindamycin (CM) were studied using porcine plasma, albumin and alpha 1-acid glycoprotein (AGP). Rosenthal plots of these basic drugs in porcine plasma suggest saturable and non-saturable binding. Dissociation constants (kd) and binding capacity (Bmax) for saturable binding were as follows: TMP, kd = 8.58 mumol/L, Bmax = 5.26 mumol/L; EM, kd = 2.72 mumol/L, Bmax = 3.06 mumol/L, LM, kd = 3.96 mumol/L, Bmax = 6.58 mumol/L and CM, kd = 4.43 mumol/L, Bmax = 21.7 mumol/L. The proportionality constants (Bmax2/kd2) for non-saturable binding were 0.29 in TMP, 0.52 in EM, 0.17 in LM and 3.2 in CM. The kds of the drugs in porcine AGP solution were determined by a fluorescence quenching method, using 1-anilino-8-naphthalene sulphonate (ANS) as a fluorescent probe: 9.51 mumol/L in TMP, 1.89 mumol/L in EM, 4.48 mumol/L in LM and 9.69 mumol/L, in CM. Comparable kd values between porcine plasma and AGP solution indicated that AGP is a major saturable binder in porcine plasma. Binding property to porcine albumin presented linearity, showing the following proportionality constants: 0.23 in TMP, 0.38 in EM, 0.01 in LM and 0.76 in CM. The comparable proportionality constants of TMP and EM between porcine plasma and albumin solution indicate that albumin is a major non-saturable binder, whereas proportionality constants of LM and CM in albumin solution compared to those in porcine plasma were low, implying another non-saturable binder, i.e. lipoprotein. Simulation curve of drug-binding percentage vs. AGP concentrations showed that in pigs under a pathologic state, or during early growth stage with high AGP levels, AGP could be a main contributor to drug-plasma protein binding for all drugs examined. The increase of AGP from normal to pathological concentrations induced a decrease in the unbound fraction: LM > CM > EM > TMP in order of AGP contribution to drug binding. Therefore, the disposition and efficacy of basic antimicrobials which bind to AGP with high affinity could be markedly influenced by altered AGP levels, implying AGP contribution to pharmacokinetics and pharmacodynamics.

Anilino Naphthalenesulfonates↗
PubMed1996

Role of high-affinity folate-binding protein in the plasma distribution of tetrahydrofolate in pigs.

Stability and protein-binding properties of tetrahydrofolate (THF) in pig plasma were studied in vitro. THF in plasma was stable for more than 120 min when it existed in a bound form, whereas THF both in plasma ultrafiltrate and in plasma ultrafiltrate plus porcine albumin was degraded rapidly and disappeared soon after its addition. These results suggest that high-affinity folate-binding protein (HFBP) is related to the stability of THF. THF-protein binding kinetic analysis showed that porcine plasma had HFBP and low-affinity binding protein (albumin) for THF. Dissociation constant and maximal binding capacity of HFBP were calculated to be 0.4 and 70 nM, respectively, indicating that > 98% of endogenous plasma THF existed in bound form with HFBP. Porcine albumin was not essentially a protein that binds and protects endogenous THF from degradation. We conclude that most endogenous THF binds to HFBP and only the unbound form of THF is rapidly degraded in pig plasma. HFBP protects THF from degradation and allows THF to exist stably in pig plasma. In addition, HFBP may govern the species specificity of plasma folate distribution in pigs.

Animals↗
PubMed1996

Alteration of plasma folates in gestating sows and newborn piglets.

Plasma folates tetrahydrofolate (THF) and N5-methyltetrahydrofolate (5MF) were determined in nongestating, gestating, and lactating sows (2 to 4 yr old, 2-6 parities, n = 88) and in newborn, growing, and finishing pigs (0 to 158 days old, n = 191) with the use of high-performance liquid chromatography with an electrochemical detector. Plasma folates after folic acid injection (1 mg/kg iv) were also monitored in 2-day-, 2-wk-, and 2-mo-old pigs. In sows, plasma folates decreased significantly as pregnancy advanced. This was mainly due to the decrease of THF, which must be caused by the folate supply from the maternal body to the fetuses. In newborn piglets, levels of "total" plasma folates were much higher than those in adults (nongestating sows), and 5MF was the major folate content. This result may be related to the observation that, after folic acid injection, newborn piglets showed much higher metabolic activity of folic acid to 5MF than adults. Rapid and drastic decrease of plasma folate was observed during nursing in piglets, which is considered to be associated with the decrease of the metabolic activity of folic acid and rapid expansion of body volume together with negative folate intake during the nursing period.

Aging↗
PubMed1996

Familial amyotrophic lateral sclerosis with a two base pair deletion in superoxide dismutase 1: gene multisystem degeneration with intracytoplasmic hyaline inclusions in astrocytes.

We performed a comparative neuropathological study on two siblings with familial amyotrophic lateral sclerosis (FALS). The clinical course of the sister who died at age 46 was 18 months, and that of the brother who died at age 65, 11 years. The neuropathological findings of the female were compatible with FALS with posterior column involvement. Her brother had multisystem degeneration in addition to the motor neuron disturbance; Lewy body-like hyaline inclusions (LBHIs) were present in the affected neurons of the degenerative lesions. Eosinophilic inclusions were seen in many astrocytes of the affected areas of the male FALS patient. Immunohistochemical assays revealed that most astrocytic inclusions reacted with the antibodies against Cu/Zn-superoxide dismutase 1 (SOD1) and ubiquitin; immunoreactivity was essentially the same as that of the neuronal LBHIs. Ultrastructurally the astrocytic inclusions were composed mainly of 15- to 25-nm granule-coated fibrils and granular material, resembling LBHIs of the neurons. Despite the dissimilar neuropathological features, both patients had the same two base pair deletion in exon 5 of the SOD1 gene. These findings suggest that FALS due to an SOD1 gene mutation is potentially a multisystem degenerative disorder, affecting not only neurons, but also astrocytes.

Amyotrophic Lateral Sclerosis↗
PubMed1995

Aebi et al. reply.

Explore the source record for details and available documents.

Journal Article↗
PubMed1995

Shortened silent period produced by magnetic cortical stimulation in patients with Parkinson's disease.

Magnetic cortical stimulation can produce silent periods (SP) following excitatory motor responses. In patients with Parkinson's disease (PD), a shorter SP was observed. The shortened SP in PD patients improved after levodopa administration. This shortened SP in PD patients may be related to the hyperactivity of the motor cortex, and to the dopaminergic system. In control subjects, sound stimulation produced prolongation of the SP at a time interval of 100 ms between sound and magnetic cortical stimulation-increase in the inhibitory function. However, the prolongation of the SP after sound stimulation was not observed in PD patients lack of an increase in the inhibitory function. Even after levodopa administration, sound did not prolong the SP in PD patients. The change of the auditory effects on the SP may be due to the abnormal function of the reticular formation in PD. This change might be independent of the dopaminergic system.

Acoustic Stimulation↗
PubMed1995

Effective anticonvulsant therapy in a patient with limb shaking: a case report.

A case is described of a patient with limb shaking in whom anticonvulsant therapy was effective for inhibiting attacks. A 70 year old female developed rhythmical involuntary limb shaking of the right upper and lower limb in April 1986. She was diagnosed as having transient ischemic attacks and was followed up under treatment with an antiplatelet drug. Subsequently, anticonvulsant therapy was also initiated on an outpatient basis. In August 1991, she was admitted with shaking of the right upper and lower limbs. Low molecular dextran was ineffective for inhibiting limb shaking attacks, but intravenous injection of diazepam was effective. Phenytoin and phenobarbital was used in combination. No limb shaking attacks occurred thereafter. The involuntary movement was the same as that observed at the onset of the disease. Though no changes were observed in the pattern of the involuntary movement, anticonvulsant therapy was effective in preventing and inhibiting attacks. This finding is inconsistent with previous reports. It is possible that epileptic factors are involved in the development of this condition.

Aged↗
PubMed1995

Prolonged silent periods produced by magnetic cortical stimulation in patients with cerebellar ataxia.

Magnetic cortical stimulation can produce silent periods (SP) following excitatory motor responses. The SP in eight patients with cerebellar ataxia was examined. The onset latency of the SP in hand muscles after magnetic cortical stimulation was not different from that in control subjects. The duration of the SP was longer than that in control subjects, but the difference was not significant statistically. The end latency of the SP in patients with cerebellar ataxia was more prolonged than that in control subjects. Therefore, the inhibitory function may be enhanced in patients with cerebellar ataxia.

Aged↗
PubMed1995

Electrically induced blink reflex and clinical blinking ability in patients with amyotrophic lateral sclerosis.

A study of the electrically induced blink reflex was performed on 17 patients with amyotrophic lateral sclerosis (ALS), graded according to the voluntary and reflexive blinking ability. In the early stage, delay of bilateral R2 latencies, decrease of bilateral R2 amplitudes and disappearance of the contralateral R2 component occurred. Then, the ipsilateral R2 component vanished when the voluntary blinking was incomplete. In cases with the remaining R2 component, the recovery curves of R2 amplitude revealed the weakened influence of the central nervous system to the interneurons that constructed the R2 component. In highly impaired patients who had lost the reflexive blinking ability, the R1 component had disappeared. Electrically induced blink reflex is useful in assessing the degree of disability in the upper facial muscles.

Adult↗
PubMed1995

Morphology of defensin-treated Staphylococcus aureus.

Defensins are a family of broad-spectrum antimicrobial peptides found abundantly in the cytoplasmic granules of mammalian neutrophils and Paneth cells of the small intestine. Defensins are known to form ion channels on the membranes of target cells. These channel formations and the cytotoxicity of defensins are intimately linked. We showed the morphological effects of defensins on the cytoplasmic membranes of Staphylococcus aureus by transmission electron microscopy. S. aureus exposed to defensins developed characteristic mesosome-like structures but did not show remarkable changes in cell walls. Defensins induced such structural changes not only at high concentration but also at low concentrations that were not bactericidal. We also showed that increasing the concentration of NaCl in the reaction mixture completely inhibited the occurrence of membranous changes of target cells exposed to defensins. These findings are, to our knowledge, the first report of morphological changes in gram-positive bacteria treated with defensins. Our results indicate that the first effect of defensins in S. aureus is to damage cytoplasmic membranes directly; they also support previous reports that the cell membrane is the principal target of defensins.

Animals↗
PubMed1995

Enterohepatic circulation kinetics of bile-active folate derivatives and folate homeostasis in rats.

We examined the effect of enteric infusion of 5,10-methylenetetrahydrofolate (5,10-CH2-H4PteGlu), tetrahydrofolate (H4PteGlu), 10-formyltetrahydrofolate (10-HCO-H4PteGlu), and 5-methyltetrahydrofolate (5-CH3-H4PteGlu) on concentrations of plasma 5-CH3-H4PteGlu in rats. Concentrations of plasma 5-CH3-H4PteGlu rapidly decreased during continuous bile diversion, whereas initial levels of plasma 5-CH3-H4PteGlu were maintained by means of enteric infusion of 5-CH3-H4PteGlu at a dose of 3 nmol/h, which was approximately equal to total secretion of bile folates. Plasma 5-CH3-H4PteGlu levels were also maintained by the infusion of 5,10-CH2-H4PteGlu, H4PteGlu, or 10-HCO-H4PteGlu at the same dose as 5-CH3-H4PteGlu. The results indicate that folates secreted into the bile are reabsorbed through the intestine to regulate plasma concentrations of 5-CH3-H4PteGlu. We examined the secretion kinetics of bile folates after the intravenous injection of 5-CH3-H4PteGlu or folic acid (PteGlu) at 1 mg/kg body wt. When 5-CH3-H4PteGlu was injected, the bile secretion of folates other than 5-CH3-H4PteGlu increased by < 5 times the base level, whereas that of bile 5-CH3-H4PteGlu markedly increased by approximately 30 times. When PteGlu was given, the bile secretion of nonmethylated tetrahydrofolates markedly increased by 15-27 times, whereas that of 5-CH3-H4PteGlu increased by approximately 7 times. The results suggest that oxidized folates may be one of the sources for bile nonmethylated tetrahydrofolates. It is concluded that nonmethylated tetrahydrofolates in bile play an important role in folate homeostasis through enterohepatic circulation, together with 5-CH3-H4PteGlu.

Animals↗
PubMed1995

Effects of folic acid and pyrimethamine, a dihydrofolate reductase inhibitor, on intestinal absorption of folates in rats.

Oral co-administration of folic acid (pteroylglutamic acid, PteGlu) potentiates the decrease of plasma 5-methyltetrahydrofolic acid (5-CH3-H4PteGlu) concentration induced by pyrimethamine (PYR) in rats. To clarify the mechanisms of this potentiated decrease, we examined the effects of PteGlu and PYR on intestinal absorption of folates in rat jejunum loops, because plasma 5-CH3-H4PteGlu concentration is maintained by enterohepatic circulation of folates. The intestinal absorption of 5-[14C]CH3-H4PteGlu was inhibited by PteGlu, but not by PYR. The absorption of [3H]PteGlu was inhibited by reduced folates that exist in bile. These findings indicate that PteGlu competes with the bile reduced folates for the intestinal transport system. The bile secretion of reduced folates was also examined to observe the conversion of absorbed PteGlu to reduced folates in the liver in the presence of PYR. The bile secretion of reduced folates increased drastically after the administration of PteGlu alone, but not after the administration of PteGlu with PYR. These facts suggest that the absorbed PteGlu was not converted to reduced folates in the liver due to PYR. In conclusion, the potentiated decrease of plasma 5-CH3-H4PteGlu concentration must have resulted from a combination of the following two factors: the inhibition of reabsorption of bile reduced folates by PteGlu and the inhibition of PteGlu conversion to reduced folates in the liver by PYR.

Animals↗