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Biomedical subjects

M Shimamura

Publications and source records attributed to M Shimamura.

At least 163 records · Page 9Linked to original sources

A membrane-bound aminopeptidase isolated from monkey brain and its action on enkephalin.

A membrane-bound aminopeptidase which cleaves the tyrosine-glycine bond of enkephalin was purified about 1600-fold from monkey brain. This aminopeptidase hydrolyzed Leu-enkephalin with a Km value of 35 microM and also hydrolyzed basic, neutral and aromatic amino acid beta-naphthylamides. An apparently homogeneous enzyme consisted of a single polypeptide chain with a molecular weight of approx. 100 000. The optimum pH was in the neutral region. From the analysis of the reaction products, only aminopeptidase activity was detected. The enzyme was inactivated by metal chelators, but the activity could be restored by the addition of divalent cations, such as Co2+, Mg2+ and Zn2+. Puromycin, bestatin and amastatin, which are aminopeptidase inhibitors derived from microorganism, showed strong competitive inhibition of the enzyme, the most potent being amastatin, with a Ki value of 0.02 microM.

Aminopeptidases↗

A novel neutral oligosaccharide chain found in polysialoglycoproteins isolated from Pacific salmon eggs. Structural studies by secondary ion mass spectrometry, proton nuclear magnetic resonance spectroscopy, and chemical methods.

A novel carbohydrate chain possessing a hitherto unknown disaccharide unit, alpha-L-Fuc leads to D-GalNAc, has been isolated from salmon egg polysialoglycoproteins on alkali-borohydride treatment. Salmon egg polysialoglycoproteins contain O-glycosidically linked neutral pentasaccharide chains in addition to a number of oligosialosyl group containing sugar chains. Composition analysis of the neutral pentasaccharide gave fucose, galactose, 2-acetamido-2-deoxygalactose, and 2-acetamido-2-deoxygalactitol in a molar ratio of 1:2:1:1. The structure was determined to be alpha-L-Fuc(1 leads to 3)-beta-D-GalNAc-(1 leads to 3)-beta-D-Gal(1 leads to 4)-beta-D-Gal(1 leads to 3)-D-GalNAcol by the following three major procedures: First, the sequential order of the constitutional monosaccharides was determined by secondary ion mass spectrometry before and after permethylation. Second, linkages were established by methylation analysis and Smith degradation and hydrazinolysis-nitrous deamination studies. Third, anomeric configuration of the glycosidic linkages involved was deduced from 270-MHz proton nuclear magnetic resonance spectroscopy.

Animals↗

Discharge patterns of reticulospinal neurons corresponding with quadrupedal leg movements in thalamic cats.

To analyze the discharge patterns of the reticulospinal (R-S) neurons associated with four-limb movement, we recorded the unit spikes of 108 R-S neurons in 18 thalamic cats. (1) Unit spikes of R-S neurons exhibited alternating firings during leg movements, not only stepping on the treadmill but also upon passive flexion and extension movement by the experimenter's hand. (2) R-S neurons manifested firing patterns associated with diagonal, reciprocal and quadrupedal leg movements. About half of the neurons showed reciprocal patterns upon bilateral forelimb movements; spikes were increased when the ipsilateral forelimb was in a backward position; they were decreased when that leg was in a forward position. In contrast, the spikes were increased when the contralateral forelimb was placed forward and decreased when it was backward. About 15% of the R-S neurons showed discharge patterns correlated with quadrupedal leg movements. Firing increased when the left forelimb and right hindlimb were placed backward and the left hindlimb and right forelimb were forward. In contrast, when the position of all 4 limbs was reversed, firing rates decreased. (3) When brief touch stimulation was applied to the skin around the leg, bursting spikes were obtained; these were suppressed upon touching the skin of the contralateral limb. Even after transection of the muscle nerves, alternating firings were observed. (4) Local anesthesia to the shoulder joint resulted in a marked reduction of spontaneous discharges and alternating firings. (5) Our results indicate that afferents of joints and of cutaneous origins in individual limbs ascend to the brainstem reticular formation, that integrative action is organized as pattern generation in that region, and that this patterned information is sent to the spinal cord via the reticulospinal tracts.

Animals↗

Pharmacokinetics of cefotetan in normal subjects and patients with impaired renal function.

The elimination kinetics of cefotetan (YM09330), a new parenteral semisynthetic cephamycin derivative, were studied in eight healthy volunteers and 41 patients with renal insufficiency after the administration of a single 500-mg dose intravenously. Concentrations of cefotetan in serum and urine were determined by both bioassay and high-pressure liquid chromatography. The pharmacokinetic parameters for cefotetan were calculated on the basis of a two-compartment open model. Serum concentrations of cefotetan immediately after administration were approximately 180 micrograms/ml in all subjects regardless of function; however, serum concentrations during the beta-phase increased directly with the degree of renal impairment. The mean serum half-life during the beta-phase was 3.0 h in normal subjects as compared with 13.1 h in hemodialysis patients. There was a linear correlation (P less than 0.0001) between the elimination rate constant of cefotetan and creatinine clearance. The mean cumulative urinary recovery of cefotetan in the 24-h urine was 83.3% of the administered dose in normal subjects and decreased with reduced renal function.

Adult↗

Elimination kinetics of cefotaxime and desacetyl cefotaxime in patients with renal insufficiency and during hemodialysis.

The pharmacokinetics of cefotaxime, a new semi-synthetic cephalosporin for injection, was studied in 30 subjects with various degrees of renal function after a single 1-gram intramuscular injection. Serum and urinary concentrations of cefotaxime and desacetyl cefotaxime were determined by high pressure liquid chromatography. The pharmacokinetic parameters of cefotaxime were obtained using a one-compartment open model. The mean serum half-life of the parent compound (cefotaxime), 0.87 h in normal subjects, was prolonged to 2.35 h in hemodialysis patients. There was a significant linear correlation between the elimination rate constant of cefotaxime and creatinine clearance. The mean cumulative urinary recovery of the administered dose in the 24-hour urine was 51.7% as cefotaxime and 25.6% as desacetyl cefotaxime in normal subjects.

Adult↗

[Two cases of renal angiomyolipoma].

Two cases of renal angiomyolipoma without tuberous sclerosis are presented. The 1st case was a 33-year-old woman who had left flank pain and macroscopic hematuria on August 26, 1980. Physical examinations revealed a large left renal tumor, and selective renal angiograms showed the presence of a hypovascular mass located in the central to median lower part of the left kidney. Ultrasonography showed a high echogenic mass accompanied by a round low echogenic area in the left kidney. Computed tomography revealed a fatty density in the renal mass. The 2nd case was a 60-year-old woman who was incidentally diagnosed as having a right renal tumor by ultrasonography on February 18, 1982. The echogram showed a high echogenic mass in the right kidney, and the fatty density in the renal mass was determined by computed tomography. These patients underwent nephrectomy and the histological diagnosis was angiomyolipoma. The usefulness of ultrasonography and computed tomography in the preoperative diagnosis of this clinical entity and the possibility of association with renal cell carcinoma are discussed.

Adult↗

[Eosinophilic cystitis: a report of 2 cases].

Two patients with eosinophilic cystitis are presented in this report. The first case was a 39-year-old man who was admitted to our clinic with complaints of pollakisuria, pain on urination and hematuria for a month, which had not been relieved by antibiotic therapy. He had both a family and a personal past history of allergy. Excretory urograms showed a mild bilateral hydroureter and small bladder with irregular filling defects. Cystoscopic examination revealed velvety, ulcerated areas in the bladder mucosa, and we diagnosed these changes as eosinophilic cystitis after bladder biopsy. Steroid and antihistaminic therapy improved these symptoms. The second case was a 67-year-old woman who visited our clinic complaining chiefly of hematuria for 2 months. There was no predisposition to allergy, but she had a past history of uterine cancer which had been treated with irradiation. Cystoscopic examination disclosed a large amount of intravesical coagula, and erythematous and edematous areas with petechiae of the bladder mucosa. Bladder biopsy revealed hemangioma and eosinophilic cystitis. There was no recurrence of cystitis after the removal of the coagula without any other treatment.

Adult↗

Reticular neuron activities associated with locomotion in thalamic cats.

Unit discharges of the reticular neurons and EMGs of extensors and flexors were recorded in the 4 limbs of thalamic cats during stepping on a motor-driven treadmill to study the functional role of the spino-bulbo-spinal (SBS) reflex in locomotion. (1) Reticular neurons showed alterations of increased or decreased discharge rate depending on the phase of the step cycle; they were divided into input (ascending), output (reticulospinal, R-S) and internuncial neurons underlying the SBS reflex. (2) R-S neurons showed increased spikes from the end o the stance to the beginning of the swing phase; in this period, flexor muscle EMGS were obtained. The spikes decreased or disappeared when extensor EMGs were observed. To analyze the relationship between activity in R-S neurons and flexor muscles, R-S neuron spikes were used for triggering and post-spike EMGs were averaged. Averaged EMGs of the correlated flexor revealed a 12 and 6 ms latency for hind- and forelimbs, respectively. Most R-S neurons elicited EMGs of flexor in muscles of one ipsilateral leg, some elicited flexor EMGs of both the ipsilateral fore-and hindlimbs. (3) Input neurons of the reticular formation from spinal ascending tracts fired spikes upon touching of the skin over the correlated limb. During stepping, they showed two types of response patterns: a burst discharge appeared for the leg which was swinging and touching the belt, the other pattern was of continuous discharges at the end of stance and at the beginning of swing phases. (4) Internuncial neurons which relay impulses between the input and output neurons also showed alternate firings depending on the phase of the step cycle. Spikes could be elicited by touching the skin over the 4 limbs. (5) The relationship among the activities of the 3 groups of reticular neurons was analyzed by the post- or pre-spike averaging technique and appropriate latency responses were obtained. (6) The results indicate that flexor EMGs were excited by cutaneous afferents via the SBS reflex in cats stepping on the treadmill. The role of the SBS reflex in locomotion is discussed.

Afferent Pathways↗

Sensory evoked potentials and their changes with respiration in man and cat.

Cutaneously evoked cortical potentials were recorded in man and chloralosed cats, in order to analyse the neural mechanisms responsible for their fluctuation with respiration. From the Cz region of the human scalp, 2 components of potentials, early and late, were evoked following mechanical stimulation of a finger contralateral to the recording side. These potentials varied with the phase of respiration, the late component being larger in amplitude and longer in duration when the stimulus was applied during expiration. From the surface of the primary somatosensory cortex of the cat (gyri sigmoideus posterior), 3 components of potentials were evoked following mechanical stimulation of the skin around the contralateral hind limb. These were surface negative (N1), followed by positive (P) and delayed negative (N2) potentials. The respiratory fluctuations were mainly in the duration of N2, which was shortest at the end of the inspiratory phase, while it was longest at the shifting point from expiration to inspiration. The peak time of N2 was shortest at the end of the inspiratory phase and longest at the end of the expiratory phase. On the contrary, N1 and P potentials did not fluctuate. The results indicate that the late components of cutaneously evoked cortical potentials vary, depending on the respiratory phase. Each response was increased during expiration and decreased during inspiration. These fluctuations may possibly originate in the brain stem reticular formation.

Animals↗

Pharmacokinetics of cefroxadine in healthy volunteers and patients with impaired renal function.

The pharmacokinetics of cefroxadine, a new orally active broad-spectrum cephalosporin, was studied in healthy volunteers and patients with impaired renal function after a single oral dose of 500 mg. The pharmacokinetic parameters of cefroxadine were obtained by analysing the serum level data of the drug based on a one-compartment open model. The mean serum half-life of cefroxadine was 0.97 h in healthy subjects, and was prolonged to 41.7 h in patients with a creatinine clearance of less than 5 ml/min. There was a significant linear correlation (p less than 0.001) between the elimination rate constant of the drug and the creatinine clearance. In healthy subjects, 71% of the administered dose was excreted in the urine collected over the first 6 h.

Adult↗

IgE biosynthesis and IgE-bearing cells in atopic and normal peripheral blood.

The authors investigated the number of IgE-bearing cells in atopic and normal peripheral blood as well as IgE produced in vitro by mononuclear cells. The significant correlation between IgE produced in vitro and IgE in plasma (r = 0.91, P less than 0.001) or the number of IgE-bearing cells (r = 0.44, P less than 0.03) was observed. The data suggest that increased plasma IgE level in atopic patients is due mainly to conditions favoring increased production of IgE. The catabolic rate of IgE did not seem to exert an important effect on plasma IgE level.

Adolescent↗

Three types of reticular neurons involved in the spino-bulbo-spinal reflex of cats.

Reticular neuron activity was recorded in 28 chloralosed cats in order to analyze the reflex arc of the spino-bulbo-spinal (SBS) reflex. Three types of reticular neurons, types I (input), II(output) and III (relay), were identified by unit discharges in response to stimulation of the sural nerve. (1) Type I (input) neurons received spinal ascending volleys monosynaptically and responded to stimulation of the sural nerve with spikes of low amplitude and short latency. Unit spikes, however, were not produced by stimulation of the superficial radial nerve and the sensorimotor cortex. These input neurons were located in the dorsocaudal part of the medial bulbar reticular formation. (2) Type II (output) neurons were part of the reticulospinal tract, which sends axons to the spinal cord, since these neurons exhibited antidromic spikes following stimulation of the ventrolateral funiculus of the spinal cord. Unit spikes were evoked by stimulation either to the sural or superficial radial nerves. These neurons were located in the ventrocaudal part of the medial bulbar reticular formation. (3) Type III neurons included relay neurons. Unit spikes were evoked by stimulation of the sural nerve, superficial radial nerve and sensorimotor cortex. However, unit discharges were not obtained by antidromic stimulation to the reticulospinal tract. These neurons were distributed widely in the brain stem, both in the bulb and pons. (4) Latency difference of unit discharges between input and output neurons was 3.5--5 msec, indicating the presence of interneurons (relays) between input and output neurons. Spikes of output neurons with 3.8--4.2 msec latency were observed following stimulation of the region where input neuron activity was found. We may conclude that three kinds of reticular neurons, input, relay and output, were involved in pathways of the SBS reflex.

Afferent Pathways↗

Pharmacokinetics of cefmetazole in normal subjects and in patients with impaired renal function.

The pharmacokinetics of cefmetazole, a new cephamycin antibiotic, were examined after a 1-h intravenous drip infusion of 1 g to 5 healthy volunteers with normal renal function and 16 patients with impaired renal function. Peak serum concentrations were obtained at the end of the infusion in all subjects, regardless of their renal function. Approximately 70% of the infused dose was excreted in the urine within 6 h in healthy volunteers. The pharmacokinetic parameters of cefmetazole were derived by analyzing elimination data, with a one-compartment open model. The mean serum half-life of cefmetazole in healthy volunteers was 0.81 h. A significant correlation between the elimination rate constant and the creatinine clearance was demonstrated.

Adult↗

A histological study on hepatic changes induced by the administration of ATP, ADP and AMP.

Hepatic changes induced by the administration of ATP, ADP and AMP were observed histologically. After five administrations of each of these substances, once every other day, infiltration of mononuclear cells into Glisson's capsules was observed. These findings could be considered as a localized granuloma. The degree of these changes was most conspicuous in the groups that had received ADP, followed by the ATP and AMP groups, respectively. Hepatic cell degeneration was seen mainly in the ATP groups, but was slightly in the groups that had received ADP and AMP, respectively. Both these changes were related to the administered quantities and seemed greater when the administration period was longer, with the exception of the groups that had received ATP. These hepatic changes were clearly different from those observed in the experiments in which hemolysate had been administered.

Adenosine Diphosphate↗