Pneumocephalus causing pulsatile tinnitus. Case illustration.
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Drug Combinations↗
Biomedical subjects
T Kubo
Publications and source records attributed to T Kubo.
Targeted delivery of anticancer drugs with intravenously administered magnetic liposomes in osteosarcoma-bearing hamsters.
Although active targeting of anticancer drugs using magnetically responsive carriers is a very attractive treatment approach for solid tumors, successful results are limited. In particular, the therapeutic utility of intravenously administered magnetically responsive carriers has to date not been clearly established. The present study investigates magnetic liposomes designed to act as anticancer drug carriers, which can be effectively delivered to solid tumors via intravenous administration. Magnetic liposomes with incorporated adriamycin (magnetic ADR liposomes) were prepared by the reverse-phase evaporation method, and an in vivo study was carried out to assess the magnetic targeting of these liposomes to hamster osteosarcoma. The average diameter of liposomes thus prepared was 146 nm. Syrian male hamsters inoculated with osteosarcoma, Os515, in the right hind limb were studied 7 days after inoculation. After the hamsters had received an intravenous administration of either magnetic ADR liposomes or ADR solution (corresponding to 5 mg ADR/kg), the ADR concentrations in plasma, tumor, liver, lung, heart, and kidney were determined at designated time intervals. Administration of magnetic ADR liposomes under magnetic force using a permanent magnet (0.4 tesla) implanted in solid tumor produced an approximately 4-fold higher maximum ADR concentration in the tumor than did administration of ADR solution. The former administration modality induced an increase in ADR concentration in the liver and lung and a decrease in the heart compared with concentrations produced by the latter. The present results indicated that intravenously administered magnetic ADR liposomes can be used to effectively deliver ADR to osteosarcoma implanted with a magnet, as well as to the lung, a common site of metastases for osteosarcoma. Our results also suggest that this new treatment approach, which involves a combination of magnet implantation at the target site and intravenous administration of magnetic liposomes, can improve the clinical chemotherapy of solid tumors.
Animals↗
[Vestibular symptoms and ENG findings during periods of convalescence after endolymphatic sac drainage and steroid-instillation surgery (EDSS)].
Understanding the appearance of vestibular symptoms during periods of convalescence after surgery for the treatment of Meniere's disease is important for determining when a patient can return to work as well as the long-term results of the operation. We have treated 20 cases of intractable Meniere's disease with endolymphatic sac drainage & steroid-instillation surgery (EDSS) [Kitahara T, et al., Ann Otol Rhlnol Laryngol in press, 2000] and observed the subjective symptoms and objective vestibular findings using electronystagmogram (ENG) during the subsequent period of convalescence. The average postoperative durations of subjective static and evoked vestibular symptoms were 1.7 and 6.7 days, respectively. Those of spontaneous, positional and positioning nystagmus observed using ENG were 1.2, 2.0 and 7.9 days, respectively. In cases with a long history of Meniere's disease, postoperative static vestibular sensation and positional nystagmus lasted significantly longer than in cases with short histories. In cases with poorly developed temporal bony pneumatization in the area behind the posterior semicircular canal, postoperative evoked vestibular sensations and positioning nystagmus lasted significantly longer than in cases with well developed temporal bony pneumatization. Vestibular symptoms resulting from direct invasion during EDSS were considered to be slighter than those resulting from vestibular neurectomy or gentamicin treatment and almost the same as those resulting from endolymphatic sac surgery.
Adult↗
[Seven cases of tuberculous otitis media].
Tuberculous otitis media (TOM) is a variable and puzzling infectious disease that is sometimes confused with other chronic middle ear diseases. A series of 7 cases (9 ears) of TOM recently treated at Osaka Prefectural Habikino Hospital is reviewed to assess the recent features of the disease. In most cases, the pathogenetic mechanism was probably aspiration of tubercle bacilli through the eustachian tube. In most cases, abundant granulations were observed in the middle and external ears, but multiple perforations of the tympanic membrane were not seen. The manifestations were variable, such as otorrhea from the perforation and otitis media with effusion. In their early stage, most cases of TOMs due to transmission via the eustachian tube are tend to resemble otitis media with effusion. Smear tests, culture, PCR, and histopathological examinations, each of which has advantages and disadvantages, must be repeated to achieve a definitive diagnosis. Tuberculin tests can be unreliable, but a chest x-ray is indispensable whenever TOM is suspected. Antitubercular chemotherapy and 2% kanamycin earwash yielded good results. Since the classical criteria for the diagnosis of TOM are no longer valid, we propose a new criterion for diagnosis in the early stage of the disease.
Adult↗
[Endoscopic sinus surgery in flowing water].
A balloon has been developed that completely fills the choana, preventing water from leaking into the pharynx even when the water is entering into the nasal cavity at a rate of 1000 ml per minute. The balloon enables endoscopic sinus surgery (ESS) to be safely performed in "flowing water". This surgical technique is similar to that used in transurethral resections of the prostate because the tip of the endoscope is kept clean, and blood, debris and resected tissues are continuously removed by the water flow. In addition, the water pressure helps to suppress bleeding. This technique enables ESS to be performed with greater ease and efficiency. We have performed ESS in flowing water on 38 patients with chronic sinusitis under local anaesthesia. No complications, such as water leakage into the pharynx, were encountered, and only a few patients felt discomfort from the insertion of the balloon. Even if the balloon had burst, an emergency could have been easily prevented by withdrawing the endoscope from the nasal cavity and stopping the flow of water. Ultrasonography (USG) was used to examine the water-filled nasal cavity during surgery (SSD-2000 and Micro Tip Radial (ASU-101); Aloka, Ltd., Japan). Using USG, the middle turbinate, the inferior turbinate and the nasal septum could be visualized in a single coronal image. When the sensor was in the posterior ethmoid sinus, the orbit and its optic nerve could also be visualized. Since this surgery is performed under local anesthesia, eye movements can rapidly alter the position of the optic nerve. Thus, visualization of the optic nerve's exact position is extremely important. Unfortunately, USG is not very useful for localizing structures and guiding the surgeon to distant tumors or cysts located behind thick bones, since ultrasound can not penetrate hard masses or bones. In this situation, navigation systems are more reliable than USG. Nevertheless, USG is often useful for depicting surgical sites, especially during a crisis, if the medial wall of the orbit is thin or if the skull base has been broken, exposing the dura. USG can also provide early warning of an impending complication. USG also has several practical advantages over navigation systems: the cost of USG is much lower, preparation for surgery is unnecessary, visual information can be obtained in real time, and measurement accuracy (estimated to be about 2 mm for navigation systems) is not a consideration. Thus, USG can be easily used to avoid complications in most surgeries for chronic sinusitis. Flowing water also allows the nasal eavity to be completely washed and sterilized at the end of the surgery. This not only prevents post-operative infection, but enables sinus function to be more quickly recovered. In addition, the pressure from the balloon also prevents post-operative nasal hemorrhaging. This allows patients to be safely discharged from the hospital at an earlier time. The balloon can also be used for non-surgical purposes. For example, emergent epistaxis can be easily stopped by the insertion of this balloon, even if the doctor is not an otorhinolaryngologist. In addition, the balloon's soft pressure allows it to be left in the nose for long periods without any complications. We conclude that this simple balloon, which we have named the "Noda Balloon", is extremely useful for nasal treatments.
Adolescent↗
Gene delivery to human chondrocytes by an adeno associated virus vector.
OBJECTIVE: To investigate the efficiency of gene transduction to human chondrocytes using an adeno associated virus (AAV) vector. METHODS: We transduced green fluorescent protein (GFP) gene using AAV vector to primary human chondrocytes as well as human cartilage organ cultures, in which chondrocytes are surrounded by extracellular matrix. Expression of GFP gene was analyzed at various time points after transduction by fluorescence microscopy and immunohistochemistry. RESULTS: In primary chondrocytes, the percentages of GFP positive cells were 15.9% or 16.0% on Day 1 and 95.0% or 93.7% on Day 7 after gene transduction. In cartilage organ cultures, gene delivery was observed in cells located not only in the superficial layer but also in the deep layer within the cartilage tissue. Up to 45.3+/-7.4% or 46.0+/-3.9% of chondrocytes expressed GFP for at least 28 days. CONCLUSION: AAV vector could be useful for direct gene delivery to chondrocytes in situ.
Adenoviridae↗
Ex vivo gene delivery using an adenovirus vector in treatment for cartilage defects.
OBJECTIVE: To realize local selective gene expression in grafted chondrocytes for cartilage defect, we investigated the usefulness of an ex vivo gene delivery method using an adenovirus vector. METHODS: Beta-galactosidase gene (LacZ) was transfected using an adenovirus vector to chondrocytes isolated from rat joints. The cells were then embedded into collagen gel, and LacZ expression in the gel was examined using 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-gal) staining; beta-galactosidase activity was also measured. The collagen gel containing transfected chondrocytes was grafted to the experimental cartilage defects, and the expression of delivered gene was histologically examined after X-gal staining of the tissue containing the grafted area. RESULTS: X-gal positive chondrocytes in the gel accounted for 82% at one week and 55% at 8 weeks after gene delivery. Beta-galactosidase activity decreased with time, but its expression was maintained even at 8 weeks after gene delivery. Chondrocytes used in the allograft maintained their morphology, and the expression of delivered gene continued during the 8 week period. CONCLUSION: In this ex vivo method, delivered gene can be expressed efficiently for a long time; this method would be useful in allografts for cartilage defects.
Adenoviridae↗
[Molecular biology concerning to the honeybee sociality: how can we approach the evolution of insect sociality?].
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Animals↗
Angiolymphoid hyperplasia with eosinophilia of the orbit.
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Angiolymphoid Hyperplasia with Eosinophilia↗
Evaluation of radiological examination for sensorineural hearing loss.
The accuracy of radiological examinations has improved and their diagnostic ability has markedly increased. However, the cost of such examinations has also recently become an issue. In this study, the clinical significance of radiological examinations for sensorineural hearing loss (SNHL) was evaluated and the value of their utilization was reconsidered. A total of 1,276 ears of 724 patients who demonstrated unilateral or bilateral SNHL was studied retrospectively. Findings of radiological examinations such as plain X-ray (X-p), computed tomography (CT) and magnetic resonance imaging (MRI) of the brain or the temporal bone were investigated. Temporal bone X-p was usually performed to rule out acoustic tumors (AT). CT was further performed in 119 patients (16.4%) and MRI in 84 patients (11.6%) in total. The reasons or symptoms for further examination such as CT or MRI were X-p findings or auditory symptoms suspicious for AT or vertigo/dizziness suspicious for intracranial disease. Of five causes with AT, two with a small tumor exhibited normal findings for the internal auditory canal on temporal bone X-p. These small ATs were finally confirmed by MRI. MRI could also detect lacunar infarctions, cerebral atrophy and high jugular bulb which might be related to SNHL. These findings confirmed that MRI is very useful for detecting small ATs and suggested that MRI also reveals cerebral vascular insufficiency in patients with SNHL.
Adolescent↗
Eight UCA codons differentially affect the expression of the lacZ gene in the divE42 mutant of Escherichia coli.
In the divE mutant, which has a temperature-sensitive mutation in the tRNA1(Ser) gene, the synthesis of beta-galactosidase is dramatically decreased at the non-permissive temperature. In Escherichia coli, the UCA codon is only recognized by tRNA1(Ser). Several genes containing UCA codons are normally expressed at 42 degrees C in the divE mutant. Therefore, it is unlikely that the defect is due to the general translational deficiency of the mutant tRNA1(Ser). In this study, we constructed mutant lacZ genes, in which one or several UCA codons at eight positions were replaced with other serine codons such as UCU or UCC, and we examined the expression of these mutant genes in the divE mutant. We found that a single UCA codon at position 6 or 462 was sufficient to cause the same level of reduced beta-galactosidase synthesis as that of the wild-type lacZ gene, and that the defect in beta-galactosidase synthesis was accompanied by a low level of lacZ mRNA. It was also found that introduction of an rne-1 pnp-7 double mutation restored the expression of mutant lacZ genes with only UCA codons at position 6 or 462. A polarity suppressor mutation in the rho gene had no effect on the defect in lacZ gene expression in the divE mutant. We propose a model to explain these results.
Blotting, Northern↗
Effect of hyaluronan on chondrocyte apoptosis and nitric oxide production in experimentally induced osteoarthritis.
OBJECTIVE: Nitric oxide (NO) plays an important role in cartilage degeneration, and NO donors induce chondrocyte apoptosis. This study evaluated the effect of intraarticular injections of hyaluronan (HA) on chondrocyte apoptosis and NO production using an experimental osteoarthritis (OA) model. METHODS: Thirty-six New Zealand white rabbits underwent unilateral anterior cruciate ligament transection (ACLT), and were divided into 3 groups. Four weeks after ACLT, the HA group started intraarticular HA injections once a week for 5 weeks; the vehicle group started to receive the carrier of HA; the no injection group received no treatment. All ACLT knees were harvested at Week 9 and evaluated for OA severity. Culture supernatants of the cartilage were analyzed for nitrite concentration. Cartilage sections were analyzed by TUNEL for apoptosis and by immunohistochemistry for nitrotyrosine. RESULTS: OA in the HA group was less severe than the other 2 groups. The number of apoptotic chondrocytes was significantly lower in the HA group. HA injection did not influence NO production in cartilage. CONCLUSION: HA protects against chondrocyte apoptosis during the development of OA, while it may not have definite effects on NO production in the joints. These inhibitory effects of HA on chondrocyte apoptosis may play a role in its mechanism of action in chondroprotection.
Animals↗
Acetabular labrum in hip dysplasia evaluated by radial magnetic resonance imaging.
OBJECTIVE: To numerically express morphologic conditions and signal intensity in the acetabular labrum of the weight-bearing portion of hip joints in patients with hip dysplasia. METHODS: Using a radial magnetic resonance imaging (MRI) technique, where the planes are set radially centered on the midpoint of acetabulum, and which depicts the entire acetabular rim and acetabular labrum, we investigated 60 hip joints of 35 patients with hip dysplasia. RESULTS: The acetabular labrum was larger in dysplastic hips than in normal hips, and the size increased in the posterosuperior portion. All patients had portions with signal intensity changes within the labrum and had impairment on the labrum. When osteoarthrosis due to hip dysplasia was observed, signal intensity changes increased. The changes of intensity varied among the portions observed, and were stronger in the anterosuperior portions than in the superior and posterosuperior portions. CONCLUSION: Radial MRI numerically depicts morphologic conditions of acetabular labrum; the data were usable to evaluate the size difference in acetabular labrum due to hip dysplasia and the degree of impairment.
Acetabulum↗
Expression of differentiated phenotype in the pseudo-tendon sheath formed by a silicon rod.
We examined the cartilaginous gene expression in the inner layer of the pseudo-tendon sheath formed by an silicon rod. While cartilaginous gene expression was not detected in the outer layer of the tissue, gene expressions of aggrecan and type II collagen were detected in the inner layer of the the newly formed pseudo-tendon sheath around the silicon rod. Relative expression of aggrecan and Type II collagen were 0.15 and 0.28, respectively, compared to that of GAPDH. The expression of type II collagen was 0.57-folds of that of type I collagen. In these tissues, a sliding surface was formed by a silicon rod and the surrounding tissues, and its mechanical stress may induce cartilaginous gene expression. Mechanical stress together with various growth factors and cytokines may be critically important for the formation of more physiological tendon sheath structures. Therefore, we will further examine the changes detected in the tissues and evaluate mechanical stress for formation of the tendon sheath.
Adult↗
Effects of mechanical stress on expression of differentiated phenotypes of chondrocytes.
In the patients with dislocated hip arthropathy, cartilage gene expression was confirmed in weight-bearing inner layer tissues of the joint capsule. Because these inner layer tissues of the joint capsule formed joint-like structures with the femoral head for a long period, cartilaginous genes may have been expressed in the weight-bearing inner surface of the joint capsule. There was a difference in expression of the genes between weight-bearing and non-weight-bearing parts. From a quantitative comparison between GAPDH and aggrecan gene expression, aggrecan gene expression was 30-fold higher in the weight-bearing part than in the non-weight-bearing part. Aggrecan gene expression was not detected in outer layer tissues of the joint capsule. Type II collagen and TGF-beta genes were also detected, and both genes showed differences in expression between the weight-bearing and non-weight-bearing parts like the aggrecan gene. This may have been because mechanical stress caused cartilaginous differentiation in undifferentiated mesenchymal tissues in the inner layer of the joint capsule. Cell differentiation and proliferation caused by mechanical stress are indicate key role to osteoarticular tissues, and it is considered important for orthopedic treatment to evaluate the process in detail.
Aged↗
Apoptotic cell death in steroid induced osteonecrosis: an experimental study in rabbits.
OBJECTIVE: We investigated apoptosis, i.e., programmed cell death, in steroid induced osteonecrosis in a rabbit model. METHODS: Forty-four adult Japanese White rabbits were divided into 3 groups: Group A were untreated controls and had a subsequent 8 week no-treatment period; Group B received intramuscular injection of methylprednisolone 4 mg/kg once weekly for 4 weeks; and Group C received the same treatment and had a subsequent 8 week no-treatment period. At the end of each period, all animals were sacrificed and tissue samples were obtained from the femur and humerus for histopathologic examination. Terminal deoxynucleotidyl transferase (TdT) mediated deoxyuridine triphosphate (dUTP) biotin nick end labeling (TUNEL) was used to detect fragmented DNA known to be associated with apoptotic cell death. RESULTS: Group A rabbits did not develop osteonecrosis-like lesions (ONL) in the femur and humerus, and few TUNEL positive cells were observed in bone marrow cells. In Group B, ONL developed in 11/15 rabbits, and many TUNEL positive cells were found in the area surrounding ONL. In Group C, ONL were found in 6/10 rabbits, but only a few TUNEL positive cells were present around the lesion. CONCLUSION: These findings revealed that apoptosis occurs in the early stage of steroid induced osteonecrosis.
Animals↗
[Animal models, DOCA-salt hypertension].
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Animals↗
Plasma endothelin and LH-RH, LH, FSH, prolactin, progesterone, 17alpha-hydroxyprogesterone, estrone, 17beta-estradiol, delta4-androstenedione, testosterone, active renin, angiotensin-II and ANP levels in blood and LH, estrone and 17beta-estradiol and pregnanediol levels in urine of normal cycling women.
In order to investigate the endothelin (ET) levels and their relationship to various hormones during the menstrual cycle, we measured endothelin-1, -2 and -3 (ET-1, -2 and -3), big ET-1 and big ET-3 levels in 27 normally cycling women (mean age 27 years). Simultaneous determination of luteinizing hormone-releasing hormone (LH-RH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin, progesterone, 17alpha-hydroxyprogesterone (17-OHP), estrone, 17beta-estradiol, delta4-androstenedione, testosterone, active renin, angiotensin-II (A-II) and atrial natriuretic peptide (ANP) in blood, and LH, estrone and 17beta-estradiol and pregnanediol levels in urine was made in the same 27 women. The levels of ET-2 in plasma were found to be 20% of those of ET-1. In addition, ET-1 levels were measured in the endometrium of the normal uterus. Plasma ET-1 and ET-3 levels fluctuated during the menstrual cycle, with a peak at the luteal phase, but showed only a negative relationship (p < 0.01) to each other at the menstrual phase, whereas big ET-1 and big ET-3 levels showed no significant changes. Plasma ET-1 and ET-3 levels showed no significant relationship to the big ETs. As for the relationship to other hormones, plasma ET-3 had a negative relationship (p < 0.01) to prolactin and a positive correlation (p < 0.01) with ANP during the entire menstrual cycle. Plasma ET-1 and ET-3 showed a partial positive or negative correlation to LH, FSH, prolactin and ANP levels, depending upon the cycle phase, whereas plasma ETs and big ETs were unrelated to other hormones in the blood, and LH, estrone, 17beta-estradiol and pregnanediol in the urine throughout the menstrual cycle. At each menstrual stage, plasma ET-3 levels were more significantly related to LH, FSH, prolactin and ANP than ET-1, indicating a closer relationship between ET-3 and these circulating hormones during the menstrual cycle. The ET-1 level showed no significant change in the endometrium during the menstrual cycle.
Adult↗