Biomedical subjects

M Fujikawa

Publications and source records attributed to M Fujikawa.

At least 19 recordsLinked to original sources

PubMed2004

Elevated bone resorption markers in a patient with hypercalcemia associated with post-partum thyrotoxicosis and hypoadrenocorticism due to pituitary failure.

A 36-yr-old woman began to suffer from headache, anorexia and general fatigue at 35 weeks' gestation. About 2 or 3 months after the delivery, fever, tachycardia and generalized musculoskeletal disorder appeared. Thereafter, they worsened rapidly, accompanied by a disturbance of consciousness and hypercalcemia. Thyrotoxicosis, due to a post-partum thyroiditis, and glucocorticoid deficiency, due to a pituitary failure, probably associated with lymphocytic hypophysitis, were also observed. All the symptoms and hypercalcemia disappeared after the glucocorticoid replacement therapy and the normalization of thyroid hormone levels. Serum and urinary bone resorption markers, such as urine pyridinoline (U-Pyr), urine deoxypyridinoline (U-DPD), urine amino-terminal telopeptide of type I collagen (U-NTx) and serum carboxy-terminal telopeptide of type I collagen (ICTP), were extremely high at the hypercalcemic state. In this case, they were 10 to 20 times higher than the normal upper limits, and then markedly decreased in a normocalcemic state, thereby showing an extreme acceleration of bone resorption in a state of both thyrotoxicosis and glucocorticoid deficiency.

Adrenal Insufficiency↗

PubMed2002

Measurements of cosmic-ray low-energy antiproton and proton spectra in a transient period of solar field reversal.

The energy spectra of cosmic-ray low-energy antiprotons ( *p's) and protons ( p's) have been measured by BESS in 1999 and 2000, during a period covering reversal at the solar magnetic field. Based on these measurements, a sudden increase of the *p/p flux ratio following the solar magnetic field reversal was observed, and it generally agrees with a drift model of the solar modulation.

Journal Article↗

PubMed2001

Evaluation and structure-activity relationship of synthesized cyclohexanol derivatives on percutaneous absorption of ketoprofen using artificial neural network.

The effect of 35 newly synthesized O-ethylmenthol (MET) derivatives on percutaneous absorption of ketoprofen was investigated in rats. In order to understand the relationship between the structure of compounds and promoting activity (structure-activity relationship), an artificial neural network (ANN) was employed. In the in vivo percutaneous absorption study, male Wistar rats, weighing 160-180 g, were used. The apparent penetration rate (Rp) was estimated based on a pharmacokinetic model with a constant rate of penetration through the skin after a lag time. As an index of the promoting activity of each compound, an enhancement factor (Ef), defined as follows, was used: Ef=Rp(with enhancer)/Rp(without enhancer). An irritation evoked on rat skin was microscopically judged at the end of the in vivo percutaneous absorption experiment and evaluated as a total irritation score (TIS). Ef and TIS were selected as output variables to determine the ANN structure. Calculated logP, molecular weight, steric energy (SE), van der Waals area, van der Waals volume, dipole moment, highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) were used as factors to determine the structural nature of cyclohexanol derivatives. Among these parameters, logP, SE and LUMO significantly affected the prediction of Ef and TIS. The predicted values of Ef and TIS coincided well with in vivo percutaneous absorption experimental values. However, results observed with a linear regression method were poor compared with the ANN approach. The contribution index of logP was approximately 50% in the prediction of Ef, suggesting that lipophilicity among physicochemical properties contributes most of the promoting activity of these compounds.

Animals↗

PubMed2001

Simultaneous optimization based on artificial neural networks in ketoprofen hydrogel formula containing O-ethyl-3-butylcyclohexanol as percutaneous absorption enhancer.

The influence of the amounts of additives including 1-O-ethyl-3-n-butylcyclohexanol (OEBC), diisopropyl adipate (DIA), and isopropanol (IPA) on the penetration rate (R(p)) of ketoprofen from hydrogels through rat skin in vivo was investigated. Skin irritation evoked by the application of hydrogels was evaluated based on a microscopic observation of skin cross-sections. Both optimization techniques incorporating an artificial neural network (ANN) and a second-order polynomial regression analysis were applied to the optimization of ketoprofen hydrogel formulations. Findings indicated that the R(p) and total irritation score (TIS) of the skin were predicted quantitatively as a function of quantities of OEBC, DIA, and IPA, employing ANN. In contrast, the prediction ability of the polynomial regression equation was somewhat poorer compared with that of ANN. The observed results of R(p) and TIS in the optimal formulation coincided well with the predictions in the simultaneous optimization technique incorporating ANN.

Animals↗

PubMed2001

Multiple intracranial recurrent tumors with hyperprolactinemia combined with a parasellar malignant fibrous histiocytoma long after transfrontal surgery and irradiation to a pituitary adenoma.

We herein describe a 40-year-old woman with hyperprolactinemia, an empty sella and two extrasellar intracranial recurrent tumors which were revealed 23 years after the first transfrontal craniotomy and 18 years after the second transfrontal surgery and irradiation to a provable prolactin-producing pituitary macroadenoma. One recurrent tumor was in the right orbital apex causing right oculomotor nerve palsy, and the other tumor was in the right apex partispetrosae and foramen jugulare. Although her serum prolactin level decreased after the administration of bromocriptine mesilate, and the size of the two tumors remained unchanged, a malignant fibrous histiocytoma, which might have been induced by the irradiation 18 years before, grew rapidly in the right suprasellar-prepontine cistern to the right pedunculus cerebralis, leading to a poor prognosis. This case confirmed the importance of the life-lasting follow-up of pituitary adenomas treated with surgery and/or irradiation therapy. Not only ectopic recurrence of the primary tumor but also post-irradiation tumors may become apparent long after the removal of the primary tumor.

Adult↗

PubMed2001

Interaction of TIP26 from a hyperthermophilic archaeon with TFB/TBP/DNA ternary complex.

Interactions of TBP-interacting protein (TIP26), TBP, and TFB from a hyperthermophilic archaeon Thermococcus kodakaraensis KOD1 with TATA-DNA were examined by electrophoretic mobility shift assay. Tk-TFB formed a ternary complex with Tk-TBP and TATA-DNA. Tk-TIP26 did not inhibit the formation of this ternary complex, but interacted with it to form a TIP26/TFB/TBP/DNA quaternary complex. This interaction is rather weak, and a large excess of Tk-TIP26 over Tk-TBP is required to fully convert the TFB/TBP/DNA ternary complex to the quaternary complex. However, determination of the concentration of Tk-TIP26 and Tk-TBP in KOD1 cells by Western blotting analysis indicated that the concentration of Tk-TIP26 is approximately ten times that of Tk-TBP, suggesting that the quaternary complex might also form in vivo.

Amino Acid Sequence↗

PubMed2001

Breast reconstruction using a deepithelialized rectus abdominis musculocutaneous flap.

There are many methods for breast reconstruction. Using implants can achieve good results without conspicuous scarring, but this method has disadvantages, such as infection, exposure, and capsular contracture. The rectus abdominis musculocutaneous (RAM) flap has become a standard technique because of its safety and abundant volume, but its main problem is the lack of a color and texture match between the skin paddle and the skin around the flap. To overcome such shortcomings, the authors perform breast reconstruction using tissue expansion and a RAM flap. First a tissue expander is inserted superficially to the pectoralis major muscle at the time of or after mastectomy, and is expanded to a size larger than the contralateral breast. The expander is replaced with the deepithelialized RAM flap. Scar revision is performed if the expander is inflated satisfactorily. The authors used this technique in 11 patients and obtained good results without severe complications.

Adult↗

PubMed2001

Enzyme immunoassay for 6-amino-5-chloro-1-isopropyl-2-(4-methyl-1-piperazinyl)benzimidazole, a novel 5-HT3 receptor antagonist.

An enzyme immunoassay (EIA) has been developed for determination of 6-amino-5-chloro-1-isopropyl-2-(4-methyl-1-piperazinyl) benzimidazole (KB-6806), a novel 5-HT3 receptor antagonist. Anti-KB-6806 antiserum was elicited against the KB-6806-bovine serum albumin (BSA) conjugate prepared by a diazo coupling reaction through the inherent 6-amino group. Beta-galactosidase-labeled 6-amino-5-chloro-1-isobutyl-2-(4-methyl-1-piperazinyl)benzimidazole was similarly prepared by diazo coupling reaction as an enzyme-labeled antigen with a hapten heterologous combination of antiserum. The modification at the 4-methyl group of the piperazine moiety of KB-6806 significantly decreased the binding affinity to the antibody. This method could quantitate KB-6806 in dog plasma in the concentration range of 0.078-10 ng/ml with good accuracy and precision. The EIA method has been successfully applied to the determination of KB-6806 in plasma after intravenous administration of KB-6806 to dogs.

Animals↗

PubMed2001

A case of an ameloblastic fibro-odontoma arising from a calcifying odontogenic cyst.

This case report describes an ameloblastic fibro-odontoma arising from a calcifying odontogenic cyst (COC) in the mandible of a twenty-three-year old male. The patient was referred to the Department of Oral Surgery, Tokyo Dental College, on March 30th, 2000, complaining of a painful swelling, which had appeared three weeks earlier on his left mandibular molar region. In a pathological view, the lesion was a round cyst the size of a chicken-egg, dark red in color, and surrounded by a thick membrane. The cyst had an epithelium of varying thickness which included many ghost cells and an enamel-like structure on the inside, and a thick wall of connective tissue with an ameloblastic fibro-odontoma on the outside. Enamel organ-like epithelial islands were structured radially in the form of strands with immature dentin. Cytokeratin 19 was strongly immunoreactive in the epithelium of the lesion; osteopontin and osteocalcin reacted in the mesenchymal cells and weakly in the epithelial element of this tumor.

Adult↗

PubMed2000

Formula optimization of theophylline controlled-release tablet based on artificial neural networks.

Formulation of the controlled-release tablet containing theophylline was optimized based on the simultaneous optimization technique in which an artificial neural network (ANN) was incorporated. As model formulations, 16 kinds of theophylline tablets were prepared. The amounts of Controse, the mixture of hydroxypropylmethyl cellulose with lactose, cornstarch and compression pressure were selected as causal factors. The release profiles of theophylline were characterized as the sum of the fast and slow release fractions. The initial weight, the rate constant in the fast release fraction and the rate constant in the slow release fraction were estimated as release parameters. A set of release parameters and causal factors were used as tutorial data for ANN and analyzed using a computer. Based on the plasma concentration profiles of theophylline predicted by the pharmacokinetic analysis in humans, a desirable set of release parameters was provided. The simultaneous optimization was performed by minimizing the generalized distance between the predicted values of each response and the desirable one that was optimized individually. The optimization technique incorporating ANN showed a fairly good agreement between the observed values of release parameters and the predicted results.

Chemistry, Pharmaceutical↗

PubMed2000

Precision measurement of cosmic-Ray antiproton spectrum

The energy spectrum of cosmic-ray antiprotons ( &pmacr;'s) has been measured in the range 0.18-3.56 GeV, based on 458 &pmacr;'s collected by BESS in a recent solar-minimum period. We have detected for the first time a characteristic peak at 2 GeV of &pmacr;'s originating from cosmic-ray interactions with the interstellar gas. The peak spectrum is reproduced by theoretical calculations, implying that the propagation models are basically correct and that different cosmic-ray species undergo a universal propagation. Future BESS data with still higher statistics will allow us to study the solar modulation and the propagation in detail and to search for primary &pmacr; components.

Journal Article↗

PubMed1999

Formula optimization based on artificial neural networks in transdermal drug delivery.

The promoting effect of O-ethylmenthol (MET) on the percutaneous absorption of ketoprofen from alcoholic hydrogels was evaluated in rats in vitro and in vivo. Furthermore, a novel simultaneous optimization technique incorporating an artificial neural network (ANN) was applied to a design of a ketoprofen hydrogel containing MET. When a small quantity of MET (0.25-0.5%) was added to the hydrogels, the permeation of ketoprofen increased remarkably, compared with the control. On the other hand, little change in permeation was observed when small amounts of menthol were used (<1%), and at least 2% menthol was required to obtain a promoting efficiency comparable with 0.25% MET. The partitioning of ketoprofen from the hydrogel to the skin was improved by the addition of a small amount of MET, whereas the diffusivity of the drug was enhanced at higher concentration of MET (0.5-1%). For the optimization study, the amount of ethanol and MET were selected as causal factors. A rate of penetration (R(p)) and lag time (t(L)) and total irritation score (TIS) were selected as response variables. A set of causal factors and response variables was used as tutorial data for ANN and fed into a computer. Nonlinear relationships between the causal factors and the response variables were represented well with the response surface predicted by ANN. The optimization of the ketoprofen hydrogel was performed according to the generalized distance function method. The observed results of R(p) and TIS, which had a lot of influence on the effectiveness and safety, coincided well the predictions.

Animals↗

PubMed1999

Increased sensitivity to thyroid hormone replacement therapy followed by hyponatremia and eosinophilia in a patient with long-standing young-onset primary hypothyroidism.

We describe a 51-year-old woman with long-standing young-onset primary hypothyroidism. Serum cortisol, adrenocorticotropin, and arginine vasopressin levels were normal, but urinary excretion of 17-hydroxycorticosteroid was decreased. Administration of a very small initial dose of thyroid hormone induced severe acute complications including fever, palpitation, and sweating associated with a rapid decrease in serum thyrotropin level, a dramatic increase in serum alkaline-phosphatase level, and a decrease in serum total cholesterol level. A week later, the late complications of nausea, severe hyponatremia, and eosinophilia occurred. Serum cortisol level decreased slightly but remained within normal limits during this hyponatremic period. This rare case suggests that increased sensitivity to thyroid hormone can occur in long-standing primary hypothyroidism with biphasic clinical course of acute thyrotoxic complications followed by severe hyponatremia resembling hypoadrenocorticism.

17-Hydroxycorticosteroids↗

PubMed1999

Application of rapid random stimulation (RRS) to visual evoked potentials in children.

The present study was performed to examine the effects of regular (1 Hz) and modified rapid random stimulation (RRS) (6 and 12 Hz) on visual evoked potentials (VEPs), by simultaneously recording negative waves around 100 ms, wave IV-latency, positive waves around 60 ms, wave III-latency, and amplitudes calculated from peak to peak, without causing impairment of visual acuity, in 44 patients aged 5-17 years. The wave IV-latencies of VEPs obtained by 6 and 12 Hz RRS were easily determined, and the latencies were not significantly changed compared to those obtained by previous 1 Hz regular stimulation. On the other hand, the amplitudes decreased in a frequency-dependent manner (1 < 6 < 12 Hz). These results were found to be similar in both preschool and school children. The examination time of VEPs determined by RRS is one-tenth shorter than that of 1 Hz regular stimulation. Thus, this method has the benefit of shortening the examination time, which decreases fatigue and inattention of the subjects, suggesting that modified RRS is a practically useful method for children.

Adolescent↗

PubMed1999

Hepatitis G virus infection in a high-risk subgroup of hospitalized dental patients.

OBJECTIVE: The prevalence of hepatitis G virus infection was evaluated in dental patients whose clinical laboratory test results were positive for hepatitis C virus antibody, hepatitis B virus surface antigen, or elevated serum alanine transaminase concentrations. STUDY DESIGN: Frozen serum samples from patients with hepatitis C virus antibody (n = 63), hepatitis B virus surface antigen (n = 20), or alanine transaminase concentrations greater than 100 IU (n = 14) were assessed for GB virus C (GBV-C)/hepatitis G virus RNA by a reverse transcriptase-polymerase chain reaction. RESULTS: Six of 63 patients with hepatitis C virus antibodies had serum hepatitis G virus RNA (9.5%), and 2 of 20 subjects with hepatitis B virus surface antigen had hepatitis G virus RNA (10.0%). None of 14 patients whose alanine transaminase concentration was greater than 100 IU/L had hepatitis G virus RNA. Of 4 subjects with both hepatitis C virus antibody and hepatitis B virus surface antigen, 2 had hepatitis G virus RNA (50%). In the total study population (N = 92), 6 subjects (6.5%) had hepatitis G virus RNA. All hepatitis G virus-infected patients also had hepatitis C virus antibody. Neither serum alanine transaminase nor aspartate transaminase concentrations were different between subjects with and subjects without hepatitis G virus RNA. The lack of a relationship between hepatitis G virus infection and elevation of alanine transaminase and aspartate transaminase might suggest that this virus is not truly a hepatitis virus. CONCLUSIONS: Hospitalized dental patients are infected with hepatitis G virus at a prevalence similar to or slightly higher than that seen in the general population. Dentists should pay close attention to infection control with respect to the potential new hepatitis virus known as hepatitis G virus.

Adolescent↗

PubMed1999

Artificial neural network as a novel method to optimize pharmaceutical formulations.

One of the difficulties in the quantitative approach to designing pharmaceutical formulations is the difficulty in understanding the relationship between causal factors and individual pharmaceutical responses. Another difficulty is desirable formulation for one property is not always desirable for the other characteristics. This is called a multi-objective simultaneous optimization problem. A response surface method (RSM) has proven to be a useful approach for selecting pharmaceutical formulations. However, prediction of pharmaceutical responses based on the second-order polynomial equation commonly used in RSM, is often limited to low levels, resulting in poor estimations of optimal formulations. The aim of this review is to describe the basic concept of the multi-objective simultaneous optimization technique in which an artificial neural network (ANN) is incorporated. ANNs are being increasingly used in pharmaceutical research to predict the non-linear relationship between causal factors and response variables. The usefulness and reliability of this ANN approach is demonstrated by the optimization for ketoprofen hydrogel ointment as a typical numerical example, in comparison with the results obtained with a classical RSM approach.

Chemistry, Pharmaceutical↗

PubMed1999

Relapsing polychondritis diagnosed by Tc-99m MDP bone scintigraphy.

PURPOSE: Relapsing polychondritis is a generalized recurring disease of cartilage that involves joints, trachea, bronchi, laryngeal cartilages, costal cartilages, and cartilages of the ear and nose. It is associated with autoimmune diseases, including Hashimoto disease in some cases. METHODS: The authors evaluated a 29-year-old man with relapsing polychondritis who had symptoms and signs of a common cold for 2 months and anterior chest pain near the sternum for 1 month. RESULTS: After the diagnosis, the authors found that the patient had a history of thyroid therapy for hyperthyroidism 15 years before. Tc-99m MDP bone scintigraphy performed to evaluate anterior chest pain showed diffusely increased accumulation of radioactivity in all costocartilages and sternoclavicular joints. Based on that information, relapsing polychondritis was diagnosed. Ga-67 citrate scintigraphy was preformed to determine the optimum biopsy site of the cartilage. The diagnosis was histologically supported by the results of the open biopsy. CONCLUSIONS: In this case, Tc-99m MDP bone scintigraphy was useful for diagnosing relapsing polychondritis, and Ga-67 citrate scintigraphy was helpful in determining the biopsy site.

Adult↗

PubMed1999

Repair of the mandibular nerve by autogenous grafting after ablative surgery of the mandible.

In this paper, we introduce our original method of autologous nerve grafting for substitution of the mandibular nerve after mandibular resection in three subjects. The lateral cutaneous nerve of the forearm served as a donor nerve, and the graft was imbedded microsurgically at the junctures using an epineurial nerve suture technique. Oversized grafts were chosen in order to insert them without tension in a space between the stumps of the recipient nerve and the regeneration zone of the bone. In all three subjects, sensibility of the lower lip and chin recovered completely after about ten months.

Case-Control Studies↗