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Biomedical subjects

Y Yoshikawa

Publications and source records attributed to Y Yoshikawa.

At least 37 records · Page 2Linked to original sources
PubMed2001

Retention and transit of intestinal mucoadhesive films in rat small intestine.

The retention and transit characteristics of intestinal mucoadhesive film systems have been studied after intraduodenal administration in rats. Small size four layered film preparations, 0.5x0.5 mm, were prepared, where the backing layer (45.1+/-2.9 microm thick) was made of a water-insoluble polymer, ethylcellulose (EC), the surface layer was made of enteric pH-sensitive polymers, Eudragit L100, S100 or HP-55 and the middle layer was made of cellulose membrane. The surface layer was attached to the middle layer with an adhesive layer composed of carboxyvinyl polymer (Hiviswako(R) 103). After administration of ten films to the duodenum, the rats were sacrificed hourly and the distribution of the films in the whole small intestine was directly observed after abdominal incision. The HP-55, Eudragit L100 and S100 film systems were found to adhere to the upper, middle and lower part of the small intestine after 1, 2 and 4 h, respectively, for 2-3 h. Direct inspection study suggests that intestinal mucoadhesive film system has functions of: (1) pH-dependent intestinal adhesion site specificity; (2) adhesion to the intestinal wall; and (3) retention in the small intestinal adhesion site for at least 2 h. Intestinal mucoadhesive film system has been suggested to be a targeting system for drugs to the gastrointestinal tract.

Adhesiveness↗
PubMed2001

Genomic organization of the Shc-related phosphotyrosine adapters and characterization of the full-length Sck/ShcB: specific association of p68-Sck/ShcB with pp135.

The Shc gene family is an emerging family, containing at least three members designated Shc/ShcA, Sck/Sli/ShcB, N-Shc/Rai/ShcC in mammals. In this study, we determined the genomic organization of the mouse Shc family. Coding regions of ShcA, B, and C each comprised 12 exons, spanned approximately 6, 20, and 65 kb, and located on chromosome 3, 10, and 13, respectively. Based on this genome analysis, we determined the full-length structure of mouse Sck/ShcB as a 68-kD protein. We found that the 68-kD full-length Sck/ShcB was more efficiently phosphorylated upon EGF treatment than the previously-analyzed CH2-deleted form. We also found that Sck specifically interacted with a 135-kD phosphoprotein (pp135) through its SH2 domain following membrane depolarization. The Sck-pp135 interaction was reduced by Src kinase inhibitors. These results suggest that Sck, but not N-Shc nor Shc, transmit signals in conjunction with pp135 following Src activation and/or calcium entry in the cell.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Mitosis and apoptosis in postnatal auditory system of the C3H/He strain.

The mouse auditory neurons, hair cells and their supporting cells in the cochlea are considered to be generated mainly in the embryonic days and to be sustained throughout the whole life. In the present study, however, we observed that auditory ganglion cells in the spiral ganglia undergo apoptosis and mitosis in the suckling mouse (1- to 2-week-old C3H/HeJ mice) with a normal auditory system. In spiral ganglia at postnatal days 7 (P7) and 10 (P10), TUNEL (TdT-mediated dUTP nick-end labeling)-positive and morphologically apoptotic ganglion cells were found. Furthermore, by bromodeoxyuridine labeling, mitosis of auditory ganglion cells was found at P10 to P14. In a functional study of auditory brainstem response, we demonstrated that the C3H/HeJ mouse acquires the ability to hear airborne sound at P12 and this is the same time as the opening of their external acoustic meatus (EAM). These results indicate that C3H/HeJ auditory ganglion cells have the ability to proliferate even after opening of the EAM and the initial input of airborne sound. We found that postnatal apoptosis and mitosis after P7 also occurred in the greater epithelial ridge (GER) which is an important organ for maturation of the organ of Corti and is located around the inner hair cells. This indicates that GER cells are not only degenerated but also regenerated until their disappearance around P12. This is the first report on mammals to demonstrate that neuronal mitosis of spiral ganglion cells and that of GER cells occur not only in embryonic and neonatal development but also in postnatal development of the normal auditory system.

Age Factors↗
PubMed2001

Evaluation of an intestinal pressure-controlled colon delivery capsules prepared by a dipping method.

A new method for preparation of large amounts of empty pressure-controlled colon delivery capsules (PCDCs) by a dipping method has been developed. Empty PCDCs are composed of two polymer membranes. The inner one was a water-insoluble polymer membrane, ethylcellulose (EC). The outer one was an enteric polymer membrane, hydroxypropylmethylcellulose phthalate (HPMCP) or hydroxypropylmethylcellulose acetate succinate (HPMCAS). By consequently dipping into an ethanolic EC solution and an alkalized enteric polymer solution, empty PCDCs were obtained after both the capsule body and cap were adjusted to the size of #2 capsules. With each enteric polymer, two types of empty PCDCs of different thickness were prepared. Fluorescein (FL) was formulated with suppository base, PEG1000, and used as a model drug. FL/PEG1000 suspension was introduced into empty PCDCs which were then sealed with enteric polymer solution. The PCDCs were evaluated by an in vivo experiment using beagle dogs. After oral administration of the test PCDC preparations containing 30 mg of FL, blood samples were obtained from the jugular vein and serum FL levels were measured. The thickness of the EC membrane layer varied in both the capsule body and cap. HPMCAS PCDCs had 62.1+/-5.0 (S.E.) microm (body) and 49.7+/-3.3 microm (cap) with thicker ones and 55.7+/-6.6 microm (body) and 46.8+/-6.2 microm (cap) with thinner ones. HPMCP PCDCs had 28.1+/-3.3 microm (body), 30.9+/-1.0 microm (cap) with thinner ones and 43.1+/-9.8 microm (body), 42.4+/-8.2 microm (cap) with thicker ones. The mean T(i) values, the first appearance time, of FL in the serum of HPMCAS PCDCs were 2.0+/-0.7 h for thicker ones and 3.8+/-0.5 h for thinner ones, while the mean T(i) values of HPMCP PCDCs were 2.0+/-0.0 h for thinner ones and 3.5+/-0.7 h for thicker ones. Since the colon arrival time in beagle dogs was 3.5+/-0.3 h as determined by a sulfasalazine test, thinner HPMCAS PCDCs and thicker HPMCP PCDCs were thought to deliver FL to the colon.

Animals↗
PubMed2001

Caspase-3-deficiency induces hyperplasia of supporting cells and degeneration of sensory cells resulting in the hearing loss.

Caspase-3 is one of the cystein proteases that play essential roles in programmed cell death. As such, brain development is profoundly affected by caspase-3-deficiency, resulting in hyperplasia and abnormal cell organization (Kuida et al., Nature 1996;384:368-372). In the present study, we used caspase-3 (-/-) mice to show that caspase-3 deficiency results in severe hearing loss, hyperplasia of supporting cells and degeneration of sensory hair cells. The greater epithelial ridge, a remnant of the primordial organ of Corti, persists throughout all of the turns of cochlea in 2-week-old caspase-3 (-/-) mice, which indicates that the morphology of the cochlea is immature. The number of border cells, that develop from the greater epithelial ridge and are one of the supporting cells of the inner hair cell, increase significantly in both 2- and 5-week-old caspase-3 (-/-) mice. On the other hand, abnormal fused stereocilia can be seen in both 2- and 5-week-old caspase-3 (-/-) mice, and disarrangement and loss of sensory hair cells are observed in 5-week-old caspase-3 (-/-) mice. Taken together, both hyperplasia and degeneration occur simultaneously in the inner ear of the caspase-3 (-/-) mice, suggesting that caspase-3-dependent apoptosis is necessary for the development and formation of a properly functioning auditory system in mammals.

Animals↗
PubMed2001

Fractal analysis of senile plaque observed in various animal species.

In the present study, the fractal dimension (FD), a concept to determine morphological complexity, was applied to morphological estimation of animal and human senile plaque using a computer-aided method. The FDs of mature plaque in a 17-year-old dog were significantly higher than those of diffuse plaque in 11- to 16-year-old dogs. In both types of plaque, the FD tended to increase as the size expanded and there was a significant difference between the slope values of the approximate line for diffuse and mature plaque. In humans, there was also a significant difference in FD value between diffuse and mature plaque. No significant differences were observed between the two types of plaque in a bear or a cynomolgus monkey. The FD of feline diffuse plaque was significantly lower than that of a camel, bear and monkey. These results indicated that the diffuse and mature plaque of the dog might form in a different manner, and similar events may occur in human senile plaque formation. In addition, specific shapes and different FD values of the diffuse plaque among animals suggested that the original conditions for plaque formation would be different.

Aging↗
PubMed2001

Insulinomimetic bis(maltolato)zinc(II) complex: blood glucose normalizing effect in KK-A(y) mice with type 2 diabetes mellitus.

High blood glucose levels of KK-A(y) mice with type 2 diabetes mellitus were normalized by daily intraperitoneal (ip) administration of a zinc(II) complex, bis(maltolato)zinc(II) (Zn(Mal)(2)) with a Zn(O(4)) coordination mode, following the finding of strong in vitro insulinomimetic activity in isolated rat adipocytes treated with epinephrine in terms of the inhibition of free fatty acid release. The blood glucose level was maintained in the normal range during administration of the Zn(Mal)(2) complex for 14 days and improvements in the glucose tolerance were confirmed by an oral glucose tolerance test.

Adipocytes↗
PubMed2001

Congenital diverticulum of the left ventricle.

We present a case of a congenital left ventricular diverticulum of fibrous type that was surgically repaired. Considering the potential risks such as rupture, systemic thromboembolism, and arrhythmia, an early surgical intervention should be employed for this rare abnormality even in a child without clinical symptoms.

Child↗
PubMed2001

Results of performing mesh plug repair for groin hernias.

The simplicity and good postoperative results of mesh plug repair for groin hernias have been reported in numerous articles. We have been performing this procedure in our department for more than 5 years, and the present study was conducted to reexamine its clinical outcome from our viewpoint. A total of 224 patients with a collective 244 groin hernias underwent mesh plug repair between March 1993 and August 1998. There were 155 (63.5%) indirect hernias, 79 (32.4%) direct hernias, 2 (0.8%) femoral hernias, and 8 (3.3%) compound hernias; 27 (11.1%) were recurrent hernias. Two plugs were inserted in all the compound hernias and in two of the direct hernias with a diffuse weak inguinal floor. The mean operating time was 32.2min. The complications that developed during this study were continuous pain in four patients, seroma in two, and hematoma in one. The rates of recurrence were 0% for indirect hernias and 12.7% for direct hernias. The patients in whom recurrence developed underwent mesh plug repair again and have had no further recurrence. Our experience showed mesh plug repair to be an excellent technique for indirect hernias or recurrent hernias after mesh repair, but it might be unsuitable for direct hernias with a diffuse bulging weakness in the floor of the inguinal canal.

Adult↗
PubMed2001

Genome structure of Ebola virus subtype Reston: differences among Ebola subtypes. Brief report.

We determined the complete genome sequence of Ebola virus subtype Reston (EBO-R) in the Philippines in 1996. The deduced transcriptional signals were highly conserved among Ebola viruses except for the stop signal of L genes. The intergenic regions were composed of 4 to 7 nucleotides, and of 2 characteristic overlaps and a long intergenic region. The glycoprotein (GP) had several amino acid differences from EBO-R isolated in 1989 and 1992. The variety of GP sequences strongly suggests the independent introduction of EBO-R from unknown natural reservoirs in 1996.

Amino Acid Sequence↗
PubMed2001

Renewal of the Fontan circulation with concomitant surgical intervention for atrial arrhythmia.

BACKGROUND: Atrial arrhythmia remains one of the major complications in the longer term after the Fontan procedure. METHODS: Conversion to total cavopulmonary connection was carried out concomitantly with surgical intervention for atrial arrhythmia in 4 patients undergoing the Fontan procedure by atriopulmonary connection and having continual atrial fibrillation or flutter in the longer term after the initial procedure. RESULTS: The surgical intervention restored sinus rhythm. Transient atrial fibrillation occasionally occurred after the reoperation in 1 patient in whom duration of preoperative arrhythmic period had been 6 years, and defibrillation was needed twice. In the other 3 patients, no episodes of paroxysmal arrhythmia have been noted. Subsequent to renewal of the Fontan circulation, cardiac index increased, with systemic venous pressure decreasing. All 4 patients are currently doing well with their functional status of New York Heart Association functional class I. CONCLUSIONS: Combination of conversion to total cavopulmonary connection and concomitant surgical intervention for atrial arrhythmia is effective, when used appropriately and in a timely manner in patients with atrial arrhythmia in the longer term after the initial Fontan procedure by atriopulmonary connection.

Arrhythmias, Cardiac↗
PubMed2001

Extended unroofing procedure for creation of a new ostium for anomalous left coronary artery.

A modified procedure to create an alternative ostium for the left coronary artery was successfully carried out in a patient having anomalous origin of the left coronary artery from the right coronary sinus of the aorta. The proximal portion of the artery had an intramural course. The newly constructed orifice was widely patent and functioning well 44 months later, without episodes of myocardial ischemia or aortic regurgitation.

Adolescent↗
PubMed2001

Double inlet right ventricle versus other types of double or common inlet ventricle: its clinical characteristics with reference to the Fontan procedure.

OBJECTIVE: To determine the clinical features in patients with double inlet right ventricle (DIRV) and separate atrioventricular (AV) valves in terms of the Fontan procedure. METHODS: Surgical procedures were carried out in 31 patients with this rare malformation. Their clinical characteristics were compared with similar features in 45 patients with double inlet left ventricle (DILV), 93 with common inlet right ventricle (CIRV), and 20 with common inlet left ventricle (CILV). RESULTS: Pulmonary atresia with the right and the left pulmonary arteries being confluent was seen in 58% of patients with DIRV, and pulmonary atresia with non-confluent pulmonary arteries in 15% (P=0.0001). The incidence of these findings was significantly higher when compared with DILV (P=0.0001). Reflecting these morphologic features, constructions of systemic-to-pulmonary shunts and extensive plasty to the pulmonary arteries were more frequently needed in patients with DIRV than in the others (P=0.04, 0.0001). The AV valves have become moderately or severely regurgitant in three with DIRV (10%). The Fontan procedure has thus been employed in 21 with DIRV (64%), this incidence being significantly higher than that seen in the CIRV (37%) group (P=0.01). Survival rate of 95% at 10 years in this group was as excellent as that in the DILV group, and obviously better than that in either CIRV or CILV (P=0.002). CONCLUSIONS: Although multiple palliative procedures might be frequently needed to maintain pulmonary perfusion, the Fontan circulation can be justifiably established in patients with DIRV, and regurgitation across the AV valves was not very common.

Child↗
PubMed2001

Continuous systemic perfusion improves outcome in one stage repair of obstructed aortic arch and associated cardiac malformation.

OBJECTIVE: To determine whether continuous systemic perfusion is of effective use when establishing primary repair of the aortic obstruction and associated cardiac malformations. METHODS: Since 1991, 56 infants have undergone reconstruction of interrupted (in 28) or coarctated (in 28) aorta, concomitantly with closure of ventricular septal defects in 37, and repair of other malformations in the remaining 19. Of these, total circulatory arrest (30+/-11 min) was employed in 23. In another 21 patients, perfusion was maintained for the carotid arteries with the descending aorta cross-clamped (31+/-15 min). The bodily organs were perfused throughout the operative procedures by placing dual aortic cannulae in the remaining 12 patients. RESULTS: The postoperative courses were less eventful in the non-circulatory arrest group than other groups of patients undergoing total or partial circulatory arrest, although these groups were operated in different time periods, and consequently, a general progress might be one reason for improvements in the surgical outcomes. All patients undergoing no circulatory arrest survived the primary repair, could have the sternum primarily closed, and had no episodes of cerebral bleeding. Prolonged tracheal intubation was needed just in one patient of this group. The amount of urine output during cardiopulmonary bypass was significantly greater in the non-circulatory arrest group than in the others. The maximal concentrations of urinary beta-microglobulin, serous creatinine, creatine phosphokinase, and glutamic oxaloacetic transaminase were lower in this setting. CONCLUSIONS: Continuous systemic perfusion was considered less invasive when concomitantly repairing the obstructed aorta and intracardiac malformations.

Alanine Transaminase↗
PubMed2001

Anatomic biventricular repair by intraatrial and intraventricular re-routing in patients with left isomerism.

OBJECTIVE: To determine the efficacy of anatomic biventricular repair by a combination of intraatrial and intraventricular re-routing in patients with isomerism of the left atrial appendages. METHODS: Anatomic biventricular repair by means of combined intraratrial and intraventricular re-routing was achieved in 5 of the 63 patients with left isomerism in whom we attempted a definitive surgical procedure. The inferior caval vein was interrupted in 3. The Mustard procedure was chosen for intraatrial redirection of blood in 4, and the Senning procedure in the other. Intraventricular re-routing was carried out via a right ventriculotomy in all patients, using an external conduit to reconstruct the morphologically right ventricular outflow tract. RESULTS: One patient died one month after the procedure because of low cardiac output and bronchial bleeding. Obstruction across the superior caval venous channel occurred after the Senning procedure in this particular patient, related to the interrupted inferior caval vein draining via the azygous vein. The other 4 patients are currently doing well. Postoperative catheterization showed excellent cardiac performance, with no obstruction across the venous channels or the ventricular outflow tracts in these 4. No episode of significant arrhythmia has been noted, all patients having a regular atrial rhythm, although the P wave vector was unusual in each patient. Reoperation has been needed thus far in one patient, 128 months after the initial repair, because of obstruction of the external conduit. CONCLUSION: With precise recognition of the morphologic features, a combination of intraatrial and intraventricular re-routing can successfully be established in patients with isomeric left atrial appendages, with functional results in the intermediate term being reasonable.

Atrial Appendage↗
PubMed2001

Repair of double outlet right ventricle with doubly-committed ventricular septal defect.

OBJECTIVE: To investigate our surgical results of intraventricular rerouting in patients having double outlet right ventricle with doubly-committed ventricular septal defect. METHODS: We undertook repair in 8 patients with this particular feature. Of these, 2 patients had pulmonary stenosis, and another had interruption of the aortic arch. The subarterial defect was unequivocally related to both the aortic and the-pulmonary orifices in all, albeit slightly deviated towards the aortic orifice in one, and towards the pulmonary orifice in another. Intraventricular rerouting was carried out via incisions to the right atrium and the pulmonary trunk. To ensure reconstruction of an unobstructed pulmonary pathway, a limited right ventriculotomy was made in 5. RESULTS: All patients survived the procedure, and are currently doing well, with follow-up of 25 to 194 months, with a mean of 117+/-68 months. Catheterization carried out 16+/-6 months after repair demonstrated excellent ventricular parameters. Mean pulmonary arterial pressure was 16+/-7 mmHg, being higher than 20 mmHg in 2 patients. No significant obstruction was found between the right ventricle and the pulmonary arteries. A pressure gradient across the left ventricular outflow tract became significant in one patient in whom a small outlet septum was present, and a heart-shaped baffle had been used for intraventricular rerouting. Reoperation was eventually needed in this patient for treatment of the obstruction, which proved to be progressive. CONCLUSION: Precise recognition of the morphologic features is of paramount importance when choosing the optimal options for biventricular repair in patients with double outlet right ventricle and doubly-committed interventricular communication.

Adult↗