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Biomedical subjects

S Tomioka

Publications and source records attributed to S Tomioka.

At least 19 recordsLinked to original sources

Synaptic potentials produced in jaw-closer and jaw-opener motoneurons by palatal stimulation.

Excitation and inhibition of temporal and digastric motoneurons (Temp. and Dig. Mns) during transient jaw closing, the so-called jaw-closing reflex, were studied in cats. Application of diffuse pressure stimulation to the posterior palatal surface produced the jaw-closing reflex and it was found that mechanosensory inputs from the posterior palatal mucosa produce depolarizing potentials on the Temp. Mns responsible for jaw closure during the jaw-closing reflex. We have demonstrated that in one-third of 27 explored Temp. Mns the initial bursts of spikes were elicited before the onset of jaw closure, suggesting that these cells contribute to initiate jaw closure during the jaw-closing reflex. The remaining cells probably contributed to maintain the occlusal phase. Furthermore, it was found that mechanosensory inputs from the posterior palatal mucosa produce a hyperpolarization-depolarization sequence in the Dig. Mns responsible for the jaw-closing reflex. In addition, when pressure stimulation was applied to the anterior palatal mucosa, sustained jaw opening was elicited and an increase of firing frequency of Dig. Mns occurred 40 ms before the onset of jaw opening and continued for 80 ms.

Animals

Intrapair differences of physical aging and longevity in identical twins.

The genetic and environmental contributions to physical aging (hair graying, balding, presbyopia) and longevity (age at death) were examined by within-pair comparison in monozygotic (MZ) and dizygotic (DZ) twins in later adulthood. Physical aging was investigated on 135 pairs of adult twins aged over 50. Hair graying and hair loss (baldness) showed significantly higher rates of concordance in the MZ twins than in the DZ twins. The intrapair difference of the degree of hair graying was negligible in 79%, slight in 15% and striking in 5% among the MZ pairs; while negligible in 40%, slight in 50% and striking in 10% among the DZ pairs. The intrapair difference of the degree of hair loss was negligible in 92%, slight in 8% (and striking in none) among the MZ pairs; while negligible in 69%, slight in 25% and striking in 6% among the DZ pairs. The age at onset of presbyopia showed a slightly higher rate of concordance in the MZ than in the DZ pairs. Longevity (age at death) was surveyed on 184 pairs of twins who died at over 40 years of age. The intrapair difference of longevity was 6.65 +/- 5.6 years (maximum 18.0; minimum 0.04) in the MZ pairs, and 8.66 +/- 7.2 years (maximum 18.6; minimum 2.9) in the DZ pairs. The MZ pairs showed a slightly smaller within-pair difference of longevity than the DZ pairs.

Aged

Risk factors for cognitive aging in adult twins.

Monozygotic (MZ) and dizygotic (DZ) twins in later adulthood were studied in order to examine genetic and environmental contributions to the decline of cognitive performance. In this study, 118 twin pairs took a comprehensive medical examination at a university hospital. Cognitive function was measured by the Wechsler Adult Intelligence Scale (WAIS). The intraclass correlation coefficients on Digit Span (D) and Digit Symbol (DS) subtests of the WAIS did not show any significant difference between MZ and DZ twins although Block Design (BD) showed a significant difference. The values of the intraclass correlation coefficients were mostly around 0.5 and showed significant within-pair similarity of test scores. The mean score of D, DS and BD declined with advancing age. The intraclass correlation coefficients for D, DS and BD were around 0.2 in the MZ twins reared apart, and around 0.6 in the MZ twins reared together. These results indicated a significant environmental influence on cognitive aging in later adulthood.

Aged

Excitation and inhibition of trigeminal motoneurons by palatal stimulation.

Excitation and inhibition of jaw-closing motoneurons (Masseteric and Temporal Motoneurons, Mass. and Temp. Mns) during transient jaw closing, the so-called jaw-closing reflex, and prolonged jaw opening elicited by palatal stimulation were studied. By pressing the anterior palatal surfaces sustained jaw opening was elicited, suggesting that sustained jaw opening results from inhibition of tonic background activity of jaw-closing motoneurons by inhibitory postsynaptic potentials (IPSPs) elicited by mechanical stimulation of the anterior palatal mucosa. Recordings showed that the onset of IPSPs was 80 ms earlier than the onset of jaw opening. Application of diffuse pressure stimulation to the posterior palatal surfaces elicited bursts of spikes triggered on excitatory postsynaptic potentials (EPSPs), suggesting that mechanosensory receptors from the posterior palatal mucosa send excitatory synaptic inputs to jaw-closing motoneurons. Furthermore, it is suggested that mechanosensory inputs from the posterior palatal mucosa may excite neurons in the central pattern generator and provide the motor patterns responsible for jaw closure during the jaw-closing reflex. We have demonstrated that excitation of Mass. Mns innervating the deep masseter muscle mainly contributed to maintaining the occlusal phase of jaw closure during the jaw-closing reflex. However, the onset of EPSPs was 100 to 160 ms (n = 27) earlier than the onset of jaw closure. In studies on spontaneously occurring jaw closure it was demonstrated that there was a proportional increase in the number of spikes of the Temp. Mn and the mechanical response (jaw closure).

Animals

Synaptic efficacy of inhibitory synapses in the reinnervating hypoglossal motoneurons.

The synaptic efficacy of inhibitory synapses in tongue protruder motoneurons reinnervating the tongue retractor muscle was studied in cats. We have demonstrated that the percentage magnitude of a short- and a long-lasting inhibitory postsynaptic potential in the inhibitory postsynaptic potentials produced in the tongue protruder motoneurons, whose axons had been cut but allowed to regenerate to make functional contact with the tongue retractor muscles, by lingual nerve or inferior alveolar nerve stimulation, was rearranged to appear like that exhibited by the tongue retractor motoneurons that normally supply that muscle. In addition, the peak amplitude of the summated afterhyperpolarization in a tongue protruder motoneuron on operated cats at nine months axon-union was in the normal range.

Action Potentials

Synaptic efficacy of inhibitory synapses and repetitive firing in the reinnervating trigeminal and hypoglossal motoneurons.

The synaptic efficacy and repetitive firing in masseteric motoneurons after the self-union operation and in tongue protruder motoneurons after their cut axons were reunited to tongue retractor muscles, the styloglossus muscle, were studied in cats. To ensure the correct identification of reinnervating motoneurons, the muscle response produce by an induced spike in a motoneuron by intracellularly injected depolarizing current was recorded. In both masseteric and tongue protruder motoneurons there were no differences on the patterns of postsynaptic potentials produced in reinnervating and non-reinnervating motoneurons by peripheral nerve stimulation, suggesting that the recovery of the synaptic efficacy of inhibitory synapses is time-dependent rather than muscle reinnervation. However, the present study demonstrated that the recovery of processes that control rhythmical firing of motoneurons is probably dependent on muscle reinnervation.

Animals

Synthesis and antiarrhythmic activity of 5,11-dihydro[1]benzoxepino[3,4-b]pyridines.

During further modification of the new antiulcer agent 5 (KW-5805), a 5,11-dihydro[1]benzoxepino[3,4-b]pyridine derivative, we found that some new derivatives had antiarrhythmic activity. So we continued synthesis and evaluation of a series of 5-substituted 5,11-dihydro[1]benzoxepino[3,4-b]pyridines for antiarrhythmic activity in chloroform-induced ventricular arrhythmias in mice and in ouabain-induced ventricular arrhythmias in dogs. In chloroform-induced ventricular arrhythmias, the 7-methoxy group played an important role in activity and the type of terminal side chain at position 5 had not obvious effect on potency. On the other hand, in ouabain-induced ventricular arrhythmias, the structure-activity relationship was highly specific and only four compounds, 9, 30, 34, and 35, were effective. Compound 9,5-[[2-(diethylamino)ethyl]amino]-7-methoxy-5,11-dihydro[1] benzoxepino[3,4-b]pyridine 1.5-fumarate, which exhibited low affinity for muscarinic acetylcholine receptors and a high ED100(mydriasis)/ED50(antiarrhythmic activity) ratio, was selected for further development and clinical evaluation as KW-3407. The synthesis and antiarrhythmic activity of optically active 9 is described. The order of potency of antiarrhythmic activity in ouabain-induced ventricular arrhythmias in dogs was (-)-9, (+/-)-9, and (+)-9.

Animals

[Immunological diagnosis of multidrug resistant cancer in urological malignancies].

A monoclonal antibody, MRK16, recognizing specifically an epitope of P-glycoprotein (P-GP) was used to determine the degree of expression of P-GP in kidney and urinary bladder cancers. Immunohistochemistry, immunoelectronmicroscopy, and immunoprecipitation were used for this study. Expression of P-GP was found in 6 of 20 kidney cancers treated without anticancer drugs. Also expression of P-GP was found in 17 of 47 urinary bladder cancers. 11 of 31 in primary cases, 0 of 5 in recurrent cases treated without anticancer drugs, and 6 of 11 in recurrent cases treated with anticancer drugs were positively expressed. These results indicate that a certain proportion of kidney and urinary bladder cancers intrinsically acquired multidrug resistance, and also that prior administration of anticancer drugs may induce P-GP in initially negative tumors. We also succeeded to detect MDR1 mRNA by means of in situ hybridization. From our present data, our methods to detect P-GP and MDR1 mRNA appeared to be very useful from the point of clinical application.

ATP Binding Cassette Transporter, Subfamily B, Mem

[Survivals of incidental renal cell carcinoma].

Between January 1987 and July 1988, 151 cases of renal cell carcinoma were nephrectomized at out institutions. Among them 41 cases (27.2%) were diagnosed incidentally. The ratio of incidental carcinoma has been increasing steadily in the past decade. Thirty-four of these cases (82.9%) were detected by ultrasound, 4 by computerized tomography, and three by excretory urography. Twenty-eight of these cases were found serendipitously during examination for other diseases, while others had no symptoms at all. Only 8 of these cases (19.5%) showed microscopic hematuria. The stage and the grade of these incidental carcinoma were significantly lower than those of symptomatic carcinoma (p less than 0.001). The survival rate of the former was better than that of the latter (p less than 0.01), especially in patients with pT1-2b tumors (p less than 0.05) or with tumors smaller than 10 cm in diameter (p less than 0.05).

Adult

[Factors influencing the prognosis of grade 1 renal cell carcinoma].

Between 1960 and 1988, 65 patients with grade 1 renal cell carcinoma were nephrectomized in our institutions. To delineate potentially curable cancer, the host and tumor factors influencing the prognosis were analyzed. Factors that had unfavorable effects were the presence of tumor thrombi in renal veins, fever, and elevation of erythrocyte sedimentation rate (ESR), serum alpha 2-globulin and C-reactive protein (CRP). Patients who were under 39-years-old or with pT1-2a tumor had excellent prognosis. The ratio of tumor thrombi, pT, fever, ESR, serum alpha 2-globulin and CRP levels all increased with age. In conclusion, patients with normal levels of fever, ESR, serum alpha 2-globulin, CRP and no tumor thrombi and/or with pT1-2a tumor were considered to be the potentially curable cancer patients.

Adolescent

Determinations of the DNA sequence of the mreB gene and of the gene products of the mre region that function in formation of the rod shape of Escherichia coli cells.

The 6.5-kilobase mre region at 71 min in the Escherichia coli chromosome map, where genes involved in formation of a rod-shaped cell form a gene cluster, was analyzed by in vivo protein synthesis in a maxicell system and by base sequencing of DNA. An open reading frame that may code for a protein with an Mr of about 37,000 on sodium dodecyl sulfate-polyacrylamide gels was found and was correlated with the mreB gene. N-terminal amino acid sequencing of the hybrid mreB-lacZ protein confirmed the production by mreB of a protein of 347 amino acid residues with a molecular weight of 36,958. The amino acid sequence of this protein deduced from the DNA sequence showed close similarity with that of a protein of the ftsA gene which is involved in cell division of E. coli. Three other contiguous genes that formed three proteins with Mrs of about 40,000, 22,000, and 51,000, respectively, were detected downstream of the mreB gene by in vivo protein synthesis. The mreB protein and some of these three proteins may function together in determination of cell shape.

Amino Acid Sequence

Thermosensitive omsA mutation of Escherichia coli that causes thermoregulated release of periplasmic proteins.

A mutant of Escherichia coli with a thermosensitive defect, possibly in the outer membrane (omsA mutant), was isolated from E. coli K-12 by mutagenization and selection for thermosensitivity and beta-lactam supersensitivity of growth. The mutant also showed very high sensitivity to other antibiotics, such as macarbomycin, midecamycin, rifampin, and bacitracin. The mutation was recessive to the wild type and was mapped at about 4 min on the E. coli chromosome between fhuA and metD. The mutation caused rapid release into the medium of periplasmic enzymes such as RTEM penicillinase but practically no cytoplasmic enzyme when cells grown at 30 degrees C were transferred to 37 or 42 degrees C. Electron microscopic observations showed many large double-layered vesicles attached to the surface of cells incubated at 42 degrees C. We conclude that the mutant had a mutation that caused a temperature-dependent defect in the outer membrane structure or its assembly (named an oms mutation). The omsA mutant may be useful for production of periplasmic proteins, which it releases into the culture medium on shift up of temperature.

Bacterial Outer Membrane Proteins

Influence of collateral ventilation on single-breath washout curves.

To examine the relationship between airway closure and collateral ventilation, Ar bolus single-breath washout tests were performed in the supine position in 10 mature dogs (animals with a well-developed collateral ventilation). Transpulmonary pressure was measured simultaneously to obtain the volume above residual volume of the inflection point in the pressure-volume curve (VIP). In pigs, closing volume (CV/VC%, mean 27.4%, where VC is vital capacity) equaled the volume of inflection (VIP/VC%, mean 35.1%) when the dead space (0.07 liter) was accounted for, indicating simultaneous onset. In dogs, closing volume (CV/VC%, mean 48.1%) was greater than the volume of inflection (VIP/VC%, mean 27%). Furthermore, as closing volume increased, so did the volume exhaled between closing volume and the volume of inflection [(CV-VIP)/VC%]. These increases were strongly age related, with the oldest dogs showing the greatest differences between closing volume and volume of inflection. These results support the previous suggestion that this difference is a measure of the degree of collateral ventilation. We defined a concavity index (CI) of phase IV by measuring the ratio of the end-to-mid phase IV height above extrapolated phase III (no concavity implies CI = 2). Whereas pigs had a low CI (mean 3.3), dogs had a high CI (mean 10.6). In dogs, the CI correlated well with closing volume (CV/VC%) and the volume exhaled between closing volume and volume of inflection [(CV-VIP)/VC%]. Again, this relationship was strongly dependent on age, suggesting that the CI is also a valid indication of the degree of collateral ventilation.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging

Gravitational independence of single-breath washout tests in recumbent dogs.

To examine the mechanisms of lung filling and emptying, Ar-bolus and N2 single-breath washout tests were conducted in 10 anesthetized dogs (prone and supine) and in three of those dogs with body rotation. Transpulmonary pressure was measured simultaneously, allowing identification of the lung volume above residual volume at which there was an inflection point in the pressure-volume curve (VIP). Although phase IV for Ar was upward, phase IV for N2 was small and variable, especially in the prone position. No significant prone to supine differences in closing capacity for Ar were seen, indicating that airway closure was generated at the same lung volumes. The maximum deflections of phase IV for Ar and N2 from extrapolated phase III slopes were smaller in the prone position, suggesting more uniform tracer gas concentrations across the lungs. VIP was smaller than the closing volume for Ar, which is consistent with the effects of well-developed collateral ventilation in dogs. Body rotation tests in three dogs did not generally cause an inversion of phase III or IV. We conclude that in recumbent dogs regional distribution of ventilation is not primarily determined by the effect of gravity, but by lung, thorax, and mediastinum interactions and/or differences in regional mechanical properties of the lungs.

Animals

Protective effect of human granulocyte colony-stimulating factor on bacterial and fungal infections in neutropenic mice.

The in vivo effects of purified natural human granulocyte colony-stimulating factor (h G-CSF) on bacterial and fungal infections were examined in mice treated with cyclophosphamide (CPA). Induction of severe neutropenia was prevented by repeated daily injections of h G-CSF at a dose of 2.5 micrograms/day for 4 days after the CPA treatment. Although control mice died shortly after the bacteria inoculation at day 4, most of the mice in whom the numbers of blood neutrophils were restored by h G-CSF injections were saved from death. At the site of the bacteria inoculation in the h G-CSF-treated mice many mature neutrophils were observed to migrate in a dose-dependent way. Furthermore, the dose of antibiotics required for elimination of infections was proved to be much less in the h G-CSF treated mice than that in the non-treated mice. These findings indicate that h G-CSF can be used efficiently for prevention and treatment of bacterial and fungal infections, particularly in patients with neutropenia.

Agranulocytosis

Lifestyle factors affecting intrapair differences of serum apoproteins and cholesterol concentrations in adult identical twins.

83 pairs of twins, aged 50-74 years, were studied with respect to their serum apoproteins (A-I, A-II, B, C-II, C-III and E) and cholesterol concentrations. Each of the variables showed a higher intraclass correlation in the MZ twins than in the DZ twins. HDL cholesterol showed the highest intraclass correlation among the variables and indicated strong heritability. In the MZ pairs discordant for alcohol consumption, the higher consumers within the pair showed a significantly higher level of apo A-I and HDL cholesterol, and a lower level of apo B concentration. In the MZ pairs discordant for cigarette smoking, the higher consumers within the pair showed a significantly lower level of apo C-III. In the MZ pairs discordant for obesity, the heavier twins within the pair showed higher levels of non-HDL cholesterol, total cholesterol, apo B, apo C-II and apo C-III. In the MZ pairs discordant, for occupation, the twins of 'heavy work' showed significantly higher levels of apo B, total cholesterol and non-HDL cholesterol than the twins of 'light work'.

Aged