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Biomedical subjects

M Goto

Publications and source records attributed to M Goto.

At least 307 records · Page 17Linked to original sources
PubMed1998

Kinetics of gentamicin uptake in the inner ear of Chinchilla langier after middle-ear administration in a sustained-release vehicle.

The search for a safe, effective treatment for the vertigo associated with Meniere's disease has long been an important topic in otolaryngology. In recent years many groups have begun using intratympanic gentamicin to treat this vertigo. Although reported cure rates are as high as 90%, many questions remain regarding this type of treatment. Current limitations are the necessity for repeated treatments and a lack of clear dosing guidelines. In addition, the gentamicin must be delivered in a manner that allows maximal vestibulotoxic effect without injury to hearing. Until investigators can control the exact amount of medicine that is placed in the ear and have an understanding of the kinetics of gentamicin absorption, adequate dosing guidelines will be difficult to establish, and therapy will continue to rely on empiric data. We describe the use of a fibrin-based sustained-release vehicle, impregnated with gentamicin, injected into the middle ear of chinchillas. This allows for a prolonged effect without repeated dosing. Using this model, we studied the absorption kinetics of gentamicin at time points ranging from 8 hours to 1 week after injection. We used our findings to create a kinetics curve of gentamicin absorption. We discuss the shape and characteristics of this kinetics curve and examine the effects of the fibrin-based sustained-release vehicle and gentamicin on the middle ear. We noted no absorption in the contralateral (untreated ear) or blood. Through better understanding of the actions of gentamicin in this animal model, we hope to facilitate safer use of intratympanic medicines in our patient population and initiate programs for the use of this sustained-release vehicle in human beings.

Animals↗
PubMed1998

A cadaveric study of maxillary sinus size as an aid in bone grafting of the maxillary sinus floor.

PURPOSE: This study measured maxillary sinus volume as an aid in determining graft bone volume before grafting of the maxillary sinus floor. MATERIALS AND METHODS: Maxillary sinus size was measured in 32 cadavers (59 sinuses) using casts of the maxillary sinus made using dental impression material. RESULTS: Anteroposterior length, height, width, and volume of the maxillary sinus (mean+/-SD) were 30.1+/-5.65 mm, 34.6+/-7.71 mm, 25.4+/-5.71 mm, and 11.3+/-4.60 cm3, respectively. When the sinus-lift procedure was simulated, inferior sinus volumes (mean +/- SD) were 3.51+/-1.23 cm3 for a 15-mm lift and 5.66+/-1.71 cm3 for a 20-mm lift. CONCLUSIONS: In bone grafting of the maxillary sinus floor, taking into consideration individual differences in maxillary sinus volume and resorption of the grafted bone, 4.74 cm3 or more of the graft is required for a 15-mm lift, and 7.37 cm3 or more is required for a 20-mm lift.

Aged↗
PubMed1998

Immunopharmacological studies on experimental allergic encephalomyelitis in DA rats.

The immunopharmacological profile of experimental allergic encephalomyelitis (EAE) in DA rats was compared to that in Lewis rats, which are commonly used for the study of EAE. DA rats showed higher susceptibility to EAE than Lewis rats. The immunological studies indicate that DA rats showed higher humoral and cellular immune response to myelin basic protein (MBP) than Lewis rats. This is probably due to the susceptible T cells to mitogen and autoreactive T cells to MBP in DA rats. In pharmacological studies, cyclosporin A, FK-506 and prednisolone suppressed the development of EAE in both strains in a similar manner. These results suggest the existence of two different types of T cells with respect to the onset of EAE in DA rats: one is highly reactive to mitogen and MBP; the other is regulated by cyclosporin A and FK-506.

Animals↗
PubMed1998

M3-type muscarinic receptors predominantly mediate neurogenic quick contraction of bovine ciliary muscle.

1. The present experiments were designed to investigate which subtypes of muscarinic receptors are involved in the neurogenic quick contraction of bovine ciliary muscle in connection to quick eye focal accommodation. 2. Transmural electrical stimulation (TES) produced a transient contraction, which was abolished in the presence of 3 x 10(-7) M tetrodotoxin and 10(-6) M atropine, but greatly augmented by 3 x 10(-7) M physostigmine. 3. The exogenously applied acetylcholine (ACh: 10(-9) to 3 x 10(-6) M) produced a concentration-dependent contraction, which was competitively antagonized by 10(-6) M atropine and augmented by 3 x 10(-7) M physostigmine, but unaffected by 3 x 10(-7) M tetrodotoxin. 4. The magnitude and time to peak of the maximal contraction produced by TES were significantly greater (1267.5 +/- 86.0 mg, P < 0.005) and shorter (9.0 +/- 0.2 sec, P < 0.005) than corresponding values (97.0 +/- 9.9 mg and 20.3 +/- 2.1 sec, respectively) of the phasic contraction caused by exogenously applied 10(-5) M ACh, at which concentration the agonist caused the maximal contraction. The velocity (140.6 +/- 7.8 mg/sec) of the transient contraction caused by TES was approximately 28-fold greater than that of the phasic contraction caused by ACh (5.1 +/- 0.9 mg/sec). 5. The contractions produced by TES were greatly attenuated by 4-diphenylacetoxy-N-methylpiperidine (4-DAMP) as an M3 antagonist and slightly by pirenzepine as an M1 antagonist (20.2 +/- 7.9% inhibition at the highest concentration), but not by methoctramine (MET) as an M2 antagonist. The IC50 value (-log M) for 4-DAMP was determined to be 7.17 +/- 0.14. 6. Scatchard plot analysis of [3H]-quinuclidinylbenzilate (QNB) binding revealed that the binding sites constituted a single population with a Kd of 31.2 +/- 0.8 pM and a Bmax of 895.5 +/- 93.2 fmol/mg protein. The activity in inhibiting [3H]-QNB binding was most potent with 4-DAMP (-log Ki = 7.98 +/- 0.02), but less potent with pirenzepine (-log Ki = 6.43 +/- 0.04) and MET (-log Ki = 7.32 +/- 0.16). 4-DAMP was approximately 35- and 5-fold more potent than pirenzepine and MET in terms of -log Ki values, respectively, suggesting the predominant localization of M3 receptor subtypes in the bovine ciliary muscle membrane. 7. These results suggest that TES produces a neurogenic quick contraction of the bovine ciliary muscle, which would be mediated mainly by ACh released from the intramural nerve terminals and subsequent excitation of M3 receptor subtypes localized on the ciliary muscle cells, and that neurogenic quick contraction of the ciliary muscle is possibly involved in part in eye focal accommodation.

Animals↗
PubMed1998

Hypocholesterolemic effects of the LDL receptor gene transcriptional upregulator CP-230821.

CP-230821 is a novel, potent LDL receptor gene transcriptional upregulator which decreases total plasma cholesterol level. Interestingly, this plasma LDL decrease does not alter hepatic lipid contents. A series of experiments was undertaken to study the molecular biology of this phenomenon. Twelve hours after CP-230821 treatment, the transcriptional activity and mRNA level of the LDL receptor gene in HepG2 cells were increased by 264% and 426%, respectively. Although treatment with the HMG-CoA reductase inhibitor compactin also increased LDL receptor gene transcription and mRNA, CP-230821 did not increase the level of HMG-CoA reductase gene transcription or mRNA. These results indicate that LDL receptor gene activity may play an important role in the decrease of plasma LDL level. These results further suggest that the LDL receptor gene and the HMG-CoA reductase gene are not strictly coordinately controlled.

Animals↗
PubMed1998

Application of pure pancreatic juice collection to the pancreatic exocrine function test.

We determined the usefulness of pure pancreatic juice collected by endoscopic procedures for assaying impaired pancreatic function in patients with chronic pancreatitis. The functional findings were compared with the degree of morphological change in endoscopic retrograde pancreatograms. Samples of pancreatic juice were collected from 23 patients with suspected chronic pancreatitis by endoscopic cannulation after a bolus intravenous injection of secretin, 100 IU, for 20 min in four 5-min samples. Volume and amylase and bicarbonate concentrations were measured. The maximum bicarbonate concentration (MBC) was found in fractions collected after 10 min. The MBC in patients with chronic pancreatitis (n = 7) was lower than in normal subjects (n = 10) (p < 0.05). When we regarded 125 mEq/L (mean - 1.5 SD) as the normal limit of MBC, the sensitivity, specificity, and overall efficiency of the pancreatic functional test using pancreatic juice to detect chronic pancreatitis were 86, 100, and 94%, respectively. In comparison with the group with normal pancreatogram findings (n = 10), the MBC, volume, amylase output, and bicarbonate output were lower in the combined group (n = 9) of Cambridge II and III (p < 0.05). MBC was the most reliable parameter in the evaluation of the exocrine pancreatic functional test using pancreatic juice samples.

Adult↗
PubMed1998

Quantification of human lithostathine S2-5 forms using the antibody to the N-terminal peptide region.

Lithostathine S2-5 inhibits in vitro crystal growth of CaCO3. We developed an antibody against the peptide region responsible for inhibitory effect to determine whether lithostathine S2-5 levels are different in the pancreatic juice of patients with and without chronic pancreatitis. The antibody against the synthetic peptide of the N-terminal end of lithostathine S2-5 detected lithostathine S2-5 but not lithostathine S1 or lithostathine extracted from pancreatic calculi. Lithostathine S2-5 was detected in samples of pancreatic juice protein by immunoblotting using the specific antibody. The concentration of lithostathine S2-5 was compared between control and chronic pancreatitis groups. The mean concentrations of lithostathine S2-5 were significantly (p=0.002) lower in chronic pancreatitis, 16.3 microg/mg of total protein, than in the control, 47.1 microg/mg of total protein. A decreased concentration of lithostathine S2-5 seems to increase the risk of stone formation in the ducts during the course of chronic pancreatitis because of insufficient inhibition of CaCO3 crystal growth.

Adult↗
PubMed1998

Autocrine/paracrine role of adrenomedullin in cultured endothelial and mesangial cells.

Adrenomedullin (AM), a potent vasorelaxant and natriuretic peptide isolated from human pheochromocytoma, is present in the kidney and secreted from endothelial cells (EC) and vascular smooth muscle cells (VSMC), but the functional role of AM is still unclear. To clarify the significance of AM as a local regulator, we investigated its secretion and action in cultured cells, and examined the effects of neutralization using a specific monoclonal antibody against AM. The prepared antibody directed against the ring structure showed a high affinity for human and rat AM. Using radioimmunoassay with this antibody, we found significant secretion from cultured rat mesangial cells (MC) of a 6-kDa mature form of AM as seen from EC and VSMC. The addition of AM into cultured cells dose-dependently increased cAMP production and potently inhibited PDGF-stimulated thymidine incorporation. Pretreatment with the monoclonal antibody completely abolished cAMP increase induced by exogenous AM. Moreover, antibody neutralization of endogenously secreted AM in cultured EC, but not in MC or VSMC, markedly (by approximately 70%) reduced basal cAMP production and significantly (1.7-fold) enhanced DNA synthesis. These results indicate that AM, acting as an autocrine/paracrine regulator, exerts an antiproliferative action on EC and MC, and suggest its role as a local modulator of endothelial and mesangial function.

Adrenomedullin↗
PubMed1998

Sp1-mediated transcription of the Werner helicase gene is modulated by Rb and p53.

The regulation of Werner's syndrome gene (WRN) expression was studied by characterizing the cis-regulatory elements in the promoter region and the trans-activating factors that bind to them. First, we defined the transcription initiation sites and the sequence of the 5' upstream region (2.8 kb) of WRN that contains a number of cis-regulatory elements, including 7 Sp1, 9 retinoblastoma control element (RCE), and 14 AP2 motifs. A region consisting of nucleotides -67 to +160 was identified as the principal promoter of WRN by reporter gene assays in HeLa cells, using a series of WRN promoter-luciferase reporter (WRN-Luc) plasmids that contained the 5'-truncated or mutated WRN upstream regions. In particular, two Sp1 elements proximal to the transcription initiation site are indispensable for WRN promoter activity and bind specifically to Sp1 proteins. The RCE enhances WRN promoter activity. Coexpression of the WRN-Luc plasmids with various dosages of plasmids expressing Rb or p53 in Saos2 cells lacking active Rb and p53 proteins showed that the introduced Rb upregulates WRN promoter activity a maximum of 2. 5-fold, while p53 downregulates it a maximum of 7-fold, both dose dependently. Consistently, the overexpressed Rb and p53 proteins also affected the endogenous WRN mRNA levels in Saos2 cells, resulting in an increase with Rb and a decrease with p53. These findings suggest that WRN expression, like that of other housekeeping genes, is directed mainly by the Sp1 transcriptional control system but is also further modulated by transcription factors, including Rb and p53, that are implicated in the cell cycle, cell senescence, and genomic instability.

Base Sequence↗
PubMed1998

Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro.

The morphogenesis and remodeling of bone depends on the integrated activity of osteoblasts that form bone and osteoclasts that resorb bone. We previously reported the isolation of a new cytokine termed osteoclastogenesis inhibitory factor, OCIF, which specifically inhibits osteoclast development. Here we report the cloning of a complementary DNA of human OCIF. OCIF is identical to osteoprotegerin (OPG), a soluble member of the tumor-necrosis factor receptor family that inhibits osteoclastogenesis. Recombinant human OPG/OCIF specifically acts on bone tissues and increases bone mineral density and bone volume associated with a decrease of active osteoclast number in normal rats. Osteoblasts or bone marrow-derived stromal cells support osteoclastogenesis through cell-to-cell interactions. A single class of high affinity binding sites for OPG/OCIF appears on a mouse stromal cell line, ST2, in response to 1,25-dihydroxyvitamin D3. An anti-OPG/OCIF antibody that blocks the binding abolishes the biological activity of OPG/OCIF. When the sites are blocked with OPG/OCIF, ST2 cells fail to support osteoclastogenesis. These results suggest that the sites are involved in cell-to-cell signaling between stromal cells and osteoclast progenitors and that OPG/OCIF inhibits osteoclastogenesis by interrupting the signaling through the sites.

Amino Acid Sequence↗
PubMed1998

Differential effects of cytotoxic drugs on mortal and immortalized B-lymphoblastoid cell lines from normal and Werner's syndrome patients.

We studied the effects of nine cytotoxic drugs on three groups of B-lymphoblastoid cell lines transformed by Epstein-Barr virus (EBV): group 1, mortal cell lines from normal individuals; group 2, immortalized cell lines from normal individuals with strong telomerase activity; group 3, mortal cell lines from Werner's syndrome (WS) patients. Aminoglycoside antibiotics and alkylating drugs showed significantly stronger cytotoxic effects on immortalized cell lines than on mortal cell lines or the cell lines before immortalization. In contrast, topoisomerase II inhibitors showed no difference or they tended to be less cytotoxic to immortalized cell lines. Mortal cell lines from normal individuals and WS patients showed no difference in sensitivity against all the drugs examined except for the topoisomerase I inhibitor, camptothecin, which had a stronger cytotoxic effect on WS cell lines than other cell lines. We discuss the mechanisms underlying these cytotoxic effects.

Aminoglycosides↗
PubMed1998

Bone and calcium metabolism in Werner's syndrome.

In order to compare the bone aging process in Werner's syndrome, a disease characterized by premature aging, and that in natural aging, we have assessed the bone status in a total of 19 cases (11 males and eight postmenopausal females) with Werner's syndrome. The spinal deformity index was determined for a total of 87 vertebral bodies from nine male patients and for a total of 61 vertebral bodies from six female patients. In the male patients, 15 vertebral deformities among 87 vertebrae in seven patients were observed, and the incidences of patients bearing deformity and deformed vertebrae were 77.8 (7/9) and 17.2% (15/87), respectively. In the female patients, the corresponding incidences were 50.0% (3/6) and 4.9% (3/61), respectively. The chi2-values for the incidences of patients bearing deformity and deformed vertebrae in the male and the female patients were 1.25 (P=0.26) and 5.24 (P<0.03), respectively. The metacarpal cortical thickness (MCI) was also measured on hand X-ray films, and the Z scores for MCI in the male (n=9) and female (n=3) patients were -0.8+/-0.3 and -1.6+/-0.3, respectively. This gender-based difference in the MCI was not statistically significant but, the Z scores for MCI in both the males and the females were significantly smaller than those of corresponding age-matched controls (P<0.05 and 0.01, respectively). The serum levels of calcium, intact PTH, 25-OH vitamin D and 1,25(OH)2 vitamin D in three male and three female Werner's syndrome patients were within the reference ranges with one exception. The serum intact osteocalcin levels in the male (2.2+/-0.6 ng/ml) and female (2.6+/-0.8 ng/ml) patients were lower than the age-matched control values (P<0.05 for males) and the postmenopausal control values (P<0.05 for females). In conclusion, the incidence of spinal bone deformity was higher in males with Werner's syndrome than that in female patients. The cortical bone thickness decreased in both the male and the female patients. A low serum intact osteocalcin level was a characteristic finding in the male and in post-menopausal Werner's syndrome, so that the bone changes such as vertebral fracture incidence and the serum intact osteocalcin level in Werner's syndrome may differ from those in normal aging in the general population.

Adult↗
PubMed1998

Protective effect of passive immunization against TNF-alpha in mice infected with Sendai virus.

TNF-alpha has been reported to be induced in mice infected with Sendai virus. We evaluated the role of TNF-alpha in the virus infection. TNF-alpha was induced locally in proportion to virus titers in the lung. The activity was correlated with suppression of body weight gain. Passive immunization against TNF-alpha improved body weight gain and ameliorated pneumonic lesions in infected mice, and prevented them from lethal infection, but lung virus induced emaciation, pneumonic lesions and death were mediated by TNF-alpha.

Animals↗
PubMed1998

Reconstruction of a congenital hypoplastic thumb with use of a free vascularized metatarsophalangeal joint.

Reconstruction of a Blauth type-IIIB hypoplastic thumb with use of a free vascularized metatarsophalangeal joint was performed in four patients (four hands). Several tendon transfers also were performed, either primarily or secondarily, to mobilize the reconstructed thumb. Three patients (three hands) were followed for at least two years after the reconstruction; the results for these three patients were compared with those for four patients (six hands) who had been managed with pollicization of the index finger because of a similar deformity of the thumb. The patients were evaluated with regard to grip strength, key-pinch strength, and the range of motion of the joints of the thumb in the operatively treated and contralateral hands as well as with regard to skill in performing activities of daily living as assessed with use of the Kobe hand-function test. Although the appearance of the thumb was closer to normal in the group that had had the pollicization procedure, total function of the hand and grip strength were greater in the group that had had the transfer procedure. We believe that reconstruction of an unstable hypoplastic (Blauth type-IIIB) thumb with use of a vascularized metatarsophalangeal joint is an acceptable alternative to pollicization of the index finger.

Activities of Daily Living↗
PubMed1998

Model-based surgical planning and simulation of cranial base surgery.

Plastic skull models of seven individual patients were fabricated by stereolithography from three-dimensional data based on computed tomography bone images. Skull models were utilized for neurosurgical planning and simulation in the seven patients with cranial base lesions that were difficult to remove. Surgical approaches and areas of craniotomy were evaluated using the fabricated skull models. In preoperative simulations, hand-made models of the tumors, major vessels and nerves were placed in the skull models. Step-by-step simulation of surgical procedures was performed using actual surgical tools. The advantages of using skull models to plan and simulate cranial base surgery include a better understanding of anatomic relationships, preoperative evaluation of the proposed procedure, increased understanding by the patient and family, and improved educational experiences for residents and other medical staff. The disadvantages of using skull models include the time and cost of making the models. The skull models provide a more realistic tool that is easier to handle than computer-graphic images. Surgical simulation using models facilitates difficult cranial base surgery and may help reduce surgical complications.

Adult↗
PubMed1998

[A case of systemic sclerosis complicated with pneumoperitoneum and pneumatosis cystoides intestinalis].

Here we report a case of systemic sclerosis (SSc) complicated with pneumoperitoneum and pneumatosis cystoides intestinalis (PCI). A 58-year-old woman who had been treated with oxygen therapy for chronic respiratory failure caused by interstitial pneumonia was admitted to Tokyo Metropolitan Ohtsuka Hospital because of abdominal fullness. On admission, laboratory data showed accelerated erythrocyte sedimentation rate, mild anemia, hypoalbuminemia, and elevated level of lactose dehydrogenase (LDH). Anti-nuclear antibodies, anti-RNP antibodies, anti-Topoisomerase I antibodies, anti-Ku antibodies, and rheumatoid factor were positive. Chest and abdominal roentgenograms showed free air under the diaphragm, dilatation of small intestine and colon, and multiple intestinal cysts. The diagnosis of pneumoperitoneum and PCI was made with laboratory findings and radiographic findings. Her symptoms did not respond to medications altering colonic motility and oxygen therapy. Finally, abdominal symptoms and radiographic findings caused by pneumoperitoneum and PCI disappeared three weeks after treatment with 1,500 mg/day of kanamycin sulfate. PCI is rarely associated with SSc. Possible pathogenic relationship between these diseases was discussed.

Female↗