Search PubMed⌕ Search

Biomedical subjects

Y Harada

Publications and source records attributed to Y Harada.

At least 379 records · Page 21Linked to original sources

A novel metalloprotease/disintegrin-like gene at 17q21.3 is somatically rearranged in two primary breast cancers.

From chromosomal region 17q21.3, where a tumour suppressor gene(s) for breast and ovarian cancers is thought to be present, we have isolated a novel gene from a cosmid clone that revealed somatic rearrangements in two breast cancers. The gene (MDC) encodes a 524-amino acid metalloprotease-like, disintegrin-like and cysteine-rich protein with sequence similarity to members of the snake-venom metalloprotease/disintegrin family and guinea-pig sperm-surface protein PH-30. These proteins have been implicated in cell-cell or cell-extracellular matrix interactions. Rearrangements in both tumours involve multiple exons and disrupt the coding region of the new MDC.

Amino Acid Sequence↗

The effect of protease inhibitor on reperfusion injury after unilateral pulmonary ischemia.

Reperfusion injury is a large problem in the early stage after lung transplantation. Its prevention by protease inhibitor was evaluated experimentally. Warm ischemic models were made with the left lungs of adult mongrel dogs. The time for the warm ischemic procedure was set at 2 hr, and the lungs were reperfused for 2 hr. The experimental group was divided into a control group, a UTI (urinary trypsin inhibitor) group and a GM (gabexate mecilate) group. To the UTI group, 10,000 units/kg of UTI was administrated during reperfusion, and to the GM group, 20 mg/kg of gabexate mecilate was administrated similarly. In the control group, the pulmonary vascular resistance and the lung tissue wet and dry weight ratios (W/D ratios) increased significantly, and thickened interstitium and infiltration of neutrophils were observed histologically after reperfusion. In the GM group, W/D ratios increased significantly, and histological appearances were similar to the control group. In the UTI group, the pulmonary vascular resistance increased slightly, but the W/D ratio did not increase significantly, and no changes were seen histologically after reperfusion. In the survival experiment, only two of the five dogs survived for more than seven days in the control and GM groups, while all five dogs survived for more than seven days in the UTI group. These results indicate that UTI significantly attenuates reperfusion injury, perhaps by inhibiting neutrophil proteases.

Animals↗

Effect of protease inhibitor on ischemia/reperfusion injury of the rat liver.

The purposes of this study were to clarify the role of neutrophilic proteases in the pathogenesis of hepatic ischemia/reperfusion injury and to determine whether urinary trypsin inhibitor (UTI) pretreatment attenuated liver ischemia/reperfusion injury in rats. Livers from male Sprague-Dawley rats were subjected to 90 min of no-flow warm ischemia followed by 120 min of reperfusion. Rats were divided into a UTI group and a control group. In the control group, 120-min reperfusion of the liver produced a significant increase in myeloperoxidase activity, a significant decrease in ATP and energy charge, and a marked increase in the serum aspartate aminotransferase, alanine aminotransferase, and lactic dehydrogenase levels. In the UTI group, the myeloperoxidase activity was significantly attenuated (P < 0.01), ATP and energy charge were significantly improved (P < 0.01 and P < 0.05, respectively), and the elevation in serum aspartate aminotransferase, alanine aminotransferase, and lactic dehydrogenase was also markedly suppressed (P < 0.05, P < 0.01, and P < 0.05, respectively) compared with the control group. Sections through the livers of control rats showed severe hepatocyte necrosis with neutrophil infiltration. In the UTI group, there was slight congestion and hepatocyte necrosis. The survival rate after 90-min liver ischemia was significantly improved compared with that in the control group (P < 0.05). The results of this study suggest that pretreatment with UTI significantly attenuates liver reperfusion injury, perhaps by inhibiting neutrophil proteases.

Adenosine Triphosphate↗

Normal levels of IgG subclass in childhood determined by a sensitive ELISA.

Normal values of all IgG subclasses were determined using a sensitive ELISA in children aged from newborn to 14 years. The upper and lower limits of normal values of all IgG subclasses were obtained in all the age groups using 29 umbilical cord blood samples from full-term newborns and 308 venous blood samples from normal infants and children. The trends in the levels of IgG1, IgG2 and IgG3 with age were almost similar to previous reports. IgG4 levels decreased gradually until reaching the lowest level at 7 to 12 months and increased gradually with age, reaching a plateau at 12 to 14 years of age. Thus, the lower limit of serum IgG4 levels was determined using our method.

Adolescent↗

The effect of nifedipine on monocrotaline-induced pulmonary hypertension in rats.

Effective drug therapy for pulmonary hypertension has not yet been developed. This study was designed to estimate the long-term hemodynamic and histopathological effects of nifedipine on severe pulmonary hypertension using animal models. Injection of one dose of monocrotaline produced subacute pulmonary hypertension in 7 week old Sprague-Dawley rats. Nifedipine (10 mg/kg) was administered intraperitoneally every day. For 5 weeks, bodyweight and hemodynamic parameters were measured, and right ventricle (RV) and left ventricle with septum (LV + S) were weighed separately. Medial thickness of the small pulmonary arterial wall was calculated by Suwa's method. Compared with the control group, the increase in right ventricular systolic pressure, total pulmonary resistance index, weight ratio of RV/(LV + S and medial hypertrophy in the nifedipine-treated rats were significantly limited without causing systemic hypotension. These results suggest that treatment with nifedipine may also be effective in attenuation of pulmonary hypertension when applied to humans.

Acute Disease↗

Norepinephrine prolongs tetracaine spinal anesthesia in surgical patients: a preliminary study.

We conducted a double-blinded examination of the effects of norepinephrine as a vasoconstrictor on the onset and duration of tetracaine spinal anesthesia in 80 surgical patients. The patients were randomly allocated to four groups (n = 20 in each group). Each patient received 10 mg of tetracaine in a volume of 2.0 mL which contained either 0 micrograms/mL, 5 micrograms/mL, 10 micrograms/mL, or 15 micrograms/mL of norepinephrine. The onset of spinal anesthesia was determined by the time to reach Th-10 level as well as by the time required to obtain the highest level of sensory analgesia. The time for two-segment regression and full-motor recovery were defined as the duration of spinal anesthesia. The time to reach Th-10, the highest analgesia level, and the time to obtain the highest analgesia level did not differ among the groups. Two-segment regression was prolonged significantly by 175%, 103%, and 106% as compared with the plain tetracaine group, in 5 micrograms/mL, 10 micrograms/mL, and 15 micrograms/mL of norepinephrine groups, respectively. Motor recovery also was extended significantly by 111%, 152%, and 121% as compared with the plain tetracaine group, in 5 micrograms/mL, 10 micrograms/mL, and 15 micrograms/mL of norepinephrine groups, respectively. There were no differences in the changes of arterial blood pressure and heart rate associated with the addition of norepinephrine among the groups. We conclude that norepinephrine provides a clinically meaningful prolongation of the duration of tetracaine spinal anesthesia.

Abdomen↗

Contribution of the vestibular primary neuron and the sensory cell to posture recovery.

The right vestibular nerve of the frog was cut peripherally to the vestibular ganglion. The frog sustained a tilting posture toward the right side. This tilting disappeared and the frog returned to normal posture. Based on this finding, the following experiments were done: In experiment I, the right vestibular nerve was again cut after posture recovery. The tilting angle was smaller and the recovery period shorter than after the 1st neurectomy. In experiment II, the left nerve was cut after posture recovery. The tilting angle toward the left was greater than that of the 1st neurectomy. In experiment III, the frog underwent bilateral neurectomy. A piece of the bone was inserted into the cut ends of the right nerve to inhibit nerve regeneration. The frog slowly developed tilting toward the right side. The above results indicate that both reactivation of the endorgan and the central compensatory mechanism play essential roles, for postural recovery after vestibular neurectomy.

Animals↗

Three-dimensional observation of the Golgi apparatus in the vestibular (Scarpa's) ganglion cell.

Ultrastructure of the Golgi apparatus and GERL was observed three-dimensionally from the functional view point of lysosome formation. GERL directly continues with rough endoplasmic reficulum. There are at least two systems for lysosome formation, i.e. dependent and not dependent systems on the Golgi stack respectively. GERL also continues with a trans Golgi saccule, indicating that GERL is a part of the Golgi apparatus.

Animals↗

The presence of two sites of action of endothelins in the isolated rabbit iris sphincter and dilator muscles.

The contractile activity of endothelins (ETs) and their effect on twitch contraction evoked by electrical field stimulation were studied in the isolated rabbit iris sphincter and dilator muscles using the isometric tension recording method. ET-1, ET-2 and ET-3 caused slow contractile response of the sphincter as well as the dilator muscles, with sphincter muscle EC50 values of 37.3, 58.0 and 84.3 nM, and dilator muscle values of 31.7, 69.0 and 224.4 nM, respectively. These contractile responses were not affected by atropine (1 microM), prazosin (1 microM) or indomethacin (1 microM). ET-1 and ET-3 slightly but significantly inhibited the fast cholinergic component of twitch contraction of the sphincter muscle evoked by field stimulation, without affecting the response to carbachol. However, ET-1 did not affect the slow substance P-ergic component of twitch contraction of this preparation. In the dilator muscle, ET-1 and ET-3 had little effect on the contraction induced by phenylephrine but reduced the amplitude of the twitch contraction evoked by the field stimulation. The inhibitory effect of ETs on the dilator muscle was antagonized by pretreatment with BQ-123 (100 nM), which is a selective ETA receptor antagonist. Pretreatment with indomethacin (1 microM) also attenuated the inhibitory effect of ETs on the twitch contraction. These results suggest that ETs may have two sites of action, pre- and post-synaptic effects, on the rabbit iris sphincter muscle as well as the dilator muscle. All three ET isopeptides may have direct contractile activity on the smooth muscles of the sphincter as well as the dilator without mediation by prostaglandins or neuronal mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[The effect of calcium ion on ampullary nerve potential].

The effect of calcium ion (Ca2+) in the endolymphatic and/or perilymphatic space of the posterior semicircular canal (p.s.c.) nerve response was studied. When both endolymph and perilymph contained no Ca2+, no p.s.c. nerve response was observed. When only the endolymph contained Ca2+ and the perilymph was Ca2+ free, again no nerve response was observed. On the other hand, when only the perilymph contained Ca2+, p.s.c. nerve response was evoked. Therefore, Ca2+ in the perilymph was considered to be essential for maintaining the function of the p.s.c. as a mechanoreceptor.

Action Potentials↗

[Tissue culture of guinea pig middle ear epithelium--morphological characterization and proliferative activities of cultured cells on fibroblast-reorganized collagen gels].

Long-term culture of the middle ear epithelium of guinea pigs was carried out on reconstituted floating collagen matrix. Fibroblasts established from the abdominal skin dermis of allogenic animals were used to reorganize hydrated collagen gels into a dermal-like matrix. The explants placed on the surface of these matrices were composed of pseudostratified columnar cells with polygonal flat outgrowth sheets, which could be maintained for up to one month. In contrast, with simple hydrated collagen gel, no lysis of the substrate was observed regarding this reorganized collagen gel. In order to examine the growth pattern of these culture cells, 5-bromodeoxyuridine (BrdU) was added to the medium during the entire culture period. The specimens were immunohistologically stained using monoclonal antibodies. Noticeable changes were observed in the marginal portion of the explant where the cell shape changed from cuboidal to squamous. In this transitional area, most cells showed positive staining and consequently high proliferative activity. In the central area of the explants, however, the number of positive cells decreased and the main observation was a few labeled basal cell nuclei. It was suggested that the same regenerative process which usually occurs in normal respiratory epithelia after mechanical injury or other insults, was replayed in this culture system.

Animals↗

Three-dimensional cytoskeletal structures of the chinchilla organ of Corti: scanning electron microscopy application of the polyethylene glycol method.

We describe the application of a polyethylene glycol (PEG) embedding technique to examine the sensory and supporting structures of the inner ear. The chinchilla organ of Corti was exposed by cracking PEG embedded cochleas. A range of PEG molecular weights (2000-8000) were utilized; PEG 2000, with a melting point of 57 degrees C was preferred. After removal of the PEG, the three-dimensional aspects of intracellular structures were observed using scanning electron microscopy. Filamentous elements in the hair cell cuticular plate and in the supporting cells were clearly observed, as was the meshwork of cross-linked actin filaments in the cuticular portion of sensory hair cells. Microtubule and microfilament alignment patterns in pillar and Deiters cells were also clearly demonstrated. Characteristic structures in the outer hair cell synaptic region, such as the post-synaptic cistern and synaptic body, were well preserved using the PEG method.

Actin Cytoskeleton↗

[Effect of hemodynamics on transdiaphragmatic central venous pressure: experiments with rapid bleeding and rapid infusion].

Effects of hemodynamics which would be a possible problem in monitoring diaphragm function through transdiaphragmatic central venous pressure were studied experimentally. Mongrel dogs were anesthetized and allowed to breath spontaneously. (1) Rapid exsanguination (30 ml/kg. body), (2) rapid infusion (15 ml/kg. body) were performed. Superior vena cava mean pressure (PSVC) and inferior vena cava mean pressure (PIVC) were measured and pressure changes during respiration (delta P) were recorded. Changes in the transdiaphragmatic central venous pressure (delta PDI = delta PIVC - delta PSVC) were calculated. And hemodynamic parameters (heart rate, cardiac output, mean arterial pressure, PSVC, PIVC) were measured simultaneously. The delta P and hemodynamic parameters were measured before and after (1) or (2). As the results, no significant changes were observed in delta PDI even if hemodynamics changed. The results suggest that measurement of transdiaphragmatic central venous pressure can be employed clinically as a parameter for monitoring diaphragm function to detect hemodynamic changes which are less serious than those appeared by mass bleeding or excess fluid transfusion.

Animals↗

Vestibular endorgan of the frog after the space flight and postural alteration of the neurectomized frog--its morphological and functional resilience.

The vestibular organ of frogs returned from space were observed by SEM. Morphology of the sensory epithelia was normal, including ultrastructure, such as tip links and side links. The frogs' behavior and vestibular morphology after various types of vestibular neurectomy were studied. Vestibular neurectomy resulted in tilting posture toward that side. This tilting gradually decreased to zero and the nerve regenerated. When the same nerve was cut again after postural recovery, the tilting angle was smaller and recovery period was shorter than after the first neurectomy. When the bilateral nerves were cut and neural regeneration was inhibited on one side, tilting slowly developed toward that side. These results show that frogs' postural change is modified by both central compensation and peripheral vestibular function.

Animals↗

[Tetralogy of Fallot with absent pulmonary valve--a successful surgical case at 40 days after birth].

A markedly symptomatic patient with tetralogy of Fallot and absent pulmonary valve underwent operation at 40 days after birth. The baby had severe cardiopulmonary insufficiency at neonatal period and needed surgical intervention. The operation is consisted of patch closure of ventricular septal defect, partial resection of dilated pulmonary artery, and right ventricular outflow reconstruction with unicusped prosthetic patch. The patient is growing and is well more than 2 years and 8 months after operation.

Echocardiography↗

Tissue culture of middle ear epithelium using fibroblast-reorganized collagen gels.

The middle ear epithelium of the guinea pig has been cultured on a modified floating collagen matrix. Fibroblasts harvested from abdominal skin dermis of allogenic animals were used to reorganize hydrated collagen gels into a dermal-like matrix. Within two days, the explants placed on the surface of these matrices showed proliferation of polygonal "outgrowth cells" which could be maintained for up to one month. During the first two weeks of the culture period, dividing cells were frequently identified. These cells were especially abundant in the marginal area of the explants and consisted of pseudostratified columnar cells. The reorganized collagen gel matrix was stable and did not dissolve even after the "outgrowth cells" became confluent. The present system should allow further elucidation of the growth and differentiation mechanisms of middle ear epithelial cells.

Animals↗

[Full thickness chest wall resection for recurrent breast cancer with reference to prognostic factors].

Full thickness chest wall resection surgery has been carried out in 16 patients with local recurrence after previous mastectomy. Seven of 16 patients had isolated chest wall recurrence, but 9 had mediastinal invasion and/or distant metastasis of carcinoma. Recurrent breast carcinoma involving the bony chest wall was resected, and the chest wall defects were reconstructed with myocutaneous flaps using rectus abdominis or latissimus dorsi, or breast flap. Marlex mesh was utilized under the flap in 10 patients. The 3 year survival probability was 79% and the 5 year one was 57% with mean follow-up period of 43 month. Local recurrence was classified into 3 types according to cancer infiltration; i.e., demarcated, scattered and diffuse types. The patients with demarcated type showed better prognosis than those with diffuse type. Patients who received curative surgery showed better prognosis than those receiving palliative surgery. A disease free interval (DFI) after mastectomy longer than 5 years correlated well with a long survival rate after chest wall resection. Thus, local recurrence presenting demarcated tumor with possible curative surgery as well as a longer DFI after mastectomy is a favorable prognostic factor for full thickness chest wall resection.

Adult↗

[A case of chronic neutrophilic leukemia associated with polycythemia vera].

A 74-year-old male patient was seen on December 15, 1980 because of right shoulder pain and leukocytosis. The spleen and the liver were enlarged, and palpable, 3 and 4 fingerbreadths below the costal margin respectively. The red blood cell count (RBC) was 899 x 10(4)/microliters, hemoglobin (Hb) 20.6 g/dl, reticlocyte (Ret) 7/1000, platelets (Plt) 34.2 x 10(4)/microliters, the white blood cell count (WBC) 26,800/microliters with 86% neutrophils. A bone marrow aspiration showed the nucleated cell count (NCC) to be 16.5 x 10(4)/microliters, and the myeloid/erythroid ratio (M/E) 2.0. The patient was treated with venesection and later with carboquone. Since September 1990 he has not been treated with any agents because of erythrocytopenia. In July 25, 1991, the spleen was enlarged, and palpated 8 fingerbreadths below the costal margin. The RBC was 456 x 10(4)/microliters, Hb 12.5 g/dl, Ret 9/1000, Plt24.2 x 10(4)/microliters, the WBC41,500/microliters with 90% neutrophils. Bone marrow aspiration showed the NCC to be 16.5 x 10(4)/microliters, M/E14.3, with no atypical cells. Chromosome studies of marrow cells revealed no Ph1 chromosome. Many hematologic malignancies have been occasionally associated with polycythemia vera (PV), but chronic neutrophilic leukemia associated with PV is a very rare condition.

Aged↗