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Biomedical subjects

Y Mitsuhashi

Publications and source records attributed to Y Mitsuhashi.

At least 91 records · Page 5Linked to original sources
PubMed1990

Prediction of ACNU plasma concentration-time profiles in humans by animal scale-up.

Plasma concentration-time profiles of nimustine hydrochloride, 1-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-3-(2-chloroethyl)-3-nitrosour ea hydrochloride (ACNU), in the mouse, rat, rabbit, and dog were determined by high-performance liquid chromatographic analysis. The pharmacokinetic parameters for these four animal species and previously reported clinical data were analyzed for investigation of interspecies correlation. Log-log plots of body weight (W; kg) vs total plasma clearance (CLtot,p; ml/min) and steady-state distribution volume (Vd,ss; l) for the four animal species were linear, with high correlation coefficients (r 0.996 for both parameters), despite the fact that the nonrenal clearance was greater than 97% in these species. Linear regression on the plots excluding human data yielded allometric equations (CLtot,p = 50.6 W0.957; Vd, ss = 1.29 W1.03) that were extrapolated to predict ACNU pharmacokinetic parameters in humans. For both parameters, however, there were 3-fold differences between the predicted and observed parametric values. To investigate these discrepancies, we measured serum protein binding of ACNU in these animal species and in humans. The values of CLtot,p and Vd,ss were converted into those of CLutot,p and Vd,uss, which correspond to the parameters for unbound ACNU. In this case, correlation coefficients of the log-log plots excluding human data (CLutot,p = 71.7 W0.891; Vd,uss = 1.82 W0.966) were also high (r greater than or equal to 0.991). The extrapolated values vs those observed in a 70-kg human were the following: CLutot,p, 3,160 vs 2,290 ml/min; Vd,uss, 110 vs 106 l. Thus, the animal data were successfully extrapolated to yield better predictions of human pharmacokinetic parameters if the analysis was based on the unbound plasma concentration of ACNU. In addition, the predicted plasma concentration-time profile for humans also showed good agreement with the observed ones. These results suggest the importance of measuring unbound fractions of drugs for more accurate prediction of human pharmacokinetic parameters by extrapolation of animal data to the human situation.

Animals↗
PubMed1990

Enzymic method for the spectrophotometric determination of aspartame in beverages.

A sensitive spectrophotometric method for the determination of aspartame in beverages is described. The method involves the enzymic conversion of aspartame into formaldehyde by the alpha-chymotrypsin-alcohol oxidase system, followed by the formation of a chromophore with 4-aminopent-3-en-2-one. The calibration graph was linear in the range 2.0-30.0 micrograms ml-1 of aspartame. Many common ingredients of beverages do not interfere with the proposed method. The method was applied to the determination of the aspartame content of various real samples, and the results obtained were compared with those given by high-performance liquid chromatography.

Aspartame↗
PubMed1990

Nevus pigmentovascularis.

We describe a rare case of nevus pigmentovascularis, consisting of disseminated nevus spilus, mongolian-spot-like maculae, port-wine stains, bilateral nevus of Ota, and cavernous hemangioma. Although nevus pigmentovascularis is generally recognized as a congenital disease in Japan, we were unable to find a similar presentation of it in English textbooks on dermatology and plastic surgery.

Adult↗
PubMed1990

[Tuberculin skin test among medical college students].

The incidence of active tuberculosis in Japan has markedly decreased in the past few decades. It is also reported that the prevalence of tuberculosis infection in young population has been decreasing in accordance with the decline in the overall occurrence of tuberculosis. The above mentioned facts indicate that the younger population has a greater risk of developing tuberculosis once exposed to tuberculosis infection. Actually, the epidemics of tuberculosis among the adolescent population have often been reported in recent years. We performed a tuberculin skin test on our medical college students, who might be exposed to tuberculosis infection during their student clinical internship, in order to obtain the information about their present status of reaction to the tuberculin skin test. The data obtained from students between 18 and 25 years old were analyzed using Student's t test and Kruskal-Wallis's method. The mean size of erythema in the group of 23, 24 and 25 years old were significantly greater than that in the group of 20, 21 and 22 years olds. Similarly the latter was significantly greater than that in the group of 18 and 19 years olds. Furthermore, it was proven by the Kruskal-Wallis's method that the older a group was, the greater the chance of a large erythema. One explanation for this fact might be a decrease in the prevalence of tuberculosis infection in the younger generation as described above. Another explanation seems to be related to the revision of the Tuberculosis Prevention Law in 1974.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Anchoring fibrils and type VII collagen are absent from skin in severe recessive dystrophic epidermolysis bullosa.

Skin of patients with severe generalized recessive dystrophic epidermolysis bullosa (SGRDEB) was studied by immunoelectron microscopy and immunoblotting with antibodies to type VII collagen, a major structural component of anchoring fibrils. In normal skin, the protein was localized to the dermoepidermal junction zone below the basement membrane and was extractable from the papillary dermis after artificial epidermolysis. In SGRDEB skin, neither immunoreactive material below the basement membrane nor identifiable anchoring fibrils could be recognized and neither the tissue form nor the specific proteolytic fragments of type VII collagen were found in extracts of SGRDEB skin. Very low amounts of type VII collagen alpha-chains could be detected in cultures of SGRDEB-fibroblasts, whereas normal fibroblasts synthesized more of this collagen. These results suggest that a genetic defect in the correct synthesis, secretion, or in the molecular assembly of type VII collagen may underlie SGRDEB.

Adolescent↗
PubMed1988

Cell killing action of cell cycle phase-non-specific antitumor agents is dependent on concentration--time product.

Based on a pharmacokinetic model proposed by Jusko, which assumes that the cell killing action of cell cycle phase-non-specific agents occurs as a bimolecular reaction depending on drug concentration and cell density, we derived a cell kill kinetic equation for these drugs, including the decomposition constant in culture medium. This equation revealed that the cell killing activity of these drugs depends on the value of concentration x exposure time or the area under the drug concentration--time curve (AUC). It was also clarified that the curves for concentration--exposure time necessary for 90% cell kill on a log scale simulated on the basis of the equation differ according as whether drugs are stable or unstable in the culture medium, being expected to be linear with a slope of -1 in the former case, and to take the form of an asymptotic curve in the latter. For three cell cycle phase-non-specific agents, mitomycin C (MMC), 1-(4-amino-2-methylpyrimidine-5-yl)-methyl-3-(2-chloroethyl)3-nitrosoure a hydro-chloride (ACNU), and nitrogen mustard (HN2), we assessed the concentrations necessary for 90% cell kill (IC90) with various exposure times and the degradation rate constants under the culture conditions used. MMC was quite stable during the incubation, while ACNU and HN2 were unstable. When IC90's and exposure times were plotted on the above-mentioned graph, a linear relationship with a slope of -1 was seen for MMC, while for ACNU and HN2 the anticipated asymptotic curves resulted. We also ascertained that the decomposition constants for ACNU and HN2 expected on the basis of these curves showed a good agreement with the corresponding experimentally observed values. These results indicate that the cell killing action of cell cycle phase-non-specific drugs can be well described by a pharmacodynamic model and equation employing their decomposition constants and are dependent on the concentration-time product.

Animals↗
PubMed1988

Ultrastructural observations in port wine stains.

The cause for the progressive vascular dilatation in port wine stains remains unclear. We compared the histology and ultrastructure of lesional and adjacent normal skin in paired biopsy specimens of 12 and 8 patients, respectively (age range, 6 to 53 years). In semithin sections, the lesions of all patients showed ectatic vessels and a fine-fibrous or hyaline thickening of the walls of postcapillary venules, as well as in some instances a loosening of the surrounding connective tissue. Ultrastructurally, the wall material consisted predominantly of peripheral deposits of amorphous material interspersed with collagen fibrils (diameter, 35 +/- 4 nm); occasionally the number of basal laminae in the inner part was also increased. Cross-banded filamentous aggregates with a periodicity of 95 nm were observed in and around the walls. The endothelium of many patients displayed fenestrations and/or small gaps. Various kinds of alterations of the intervascular connective tissue were found. We conclude that structural alterations of the vascular and later also of the intervascular connective tissue are related to the dilatation of the vessels. These findings are in agreement with the immunopathologically demonstrated increase of basement membrane components in the same biopsy specimens, but are interpreted as secondary phenomena. Endothelial stability and permeability may also be affected.

Adolescent↗
PubMed1988

Lack of type VII collagen in unaffected skin of patients with severe recessive dystrophic epidermolysis bullosa.

Type VII collagen, the major structural component of the anchoring fibrils, was assayed in normal unaffected skin of patients with different forms of hereditary epidermolysis bullosa. Immunofluorescence staining with affinity-purified polyclonal antibodies to type VII collagen revealed a complete absence of staining in the skin of patients with severe dystrophic recessive epidermolysis bullosa. In all other forms, localized recessive dystrophic, dominant dystrophic, junctional and simplex forms there was an intense continuous linear staining of type VII collagen at the dermoepidermal junction. Also, obligate heterozygote carriers of the gene for severe dystrophic recessive form showed a normal pattern of staining. As internal controls and to define the clinical diagnosis, staining with antibodies to type IV collagen, laminin and bullous pemphigoid antigen was also performed. All these antibodies showed a normal staining pattern indicating an intact general morphology of the dermoepidermal junction zone. These results suggest that there is a defect of type VII collagen in patients with severe recessive dystrophic epidermolysis bullosa. The data also suggest that the group of recessive dystrophic epidermolysis bullosa may be heterogeneous not only clinically, but also at the molecular level.

Adolescent↗
PubMed1988

Immunohistological evaluation of endothelial markers and basement membrane components in port-wine stains.

As shown by an immunohistological study, the endothelial cells in the lesions of port-wine stains (PWSs), investigated for factor VIII-related antigen and Ulex europaeus agglutinin I lectin, were found to be swollen or flattened corresponding to mild or pronounced dilatation of vessels, respectively. Furthermore, dilated vessels in the lesional skin exhibited a broader staining for type IV collagen, laminin and fibronectin, which, however, was not considered to be of primary pathogenetic importance for vessel dilatation in PWSs. As concluded from the number of vessels, no vascular proliferation occurred, which indicates that PWS is not a true hemangioma but a special clinical type of telangiectasia.

Adolescent↗
PubMed1987

Determination of hydrogen peroxide in beverages by high-performance liquid chromatography with fluorescence detection.

A high-performance liquid chromatographic method is described for the determination of hydrogen peroxide in beverages. The method involves the enzymatic conversion of hydrogen peroxide into formaldehyde by catalase-methanol, followed by the derivatization of formaldehyde with 4-amino-3-penten-2-one. The reaction was carried out under the flow of nitrogen, which allows the detection of hydrogen peroxide without interference from reducing substances such as ascorbic acid. More than 90% of hydrogen peroxide spiked at the 2 ppm level was recovered from several beverages. The method exhibits good linearity, accuracy and precision, and the minimum detectable level was 0.05 ppm.

Ascorbic Acid↗
PubMed1987

Cryofibrinogenemic purpura.

A 50-year-old male patient had three episodes of acrally located purpura within 12 years without any other symptoms. The first two episodes which lasted several months coincided with the intake of beta-blockers; the third episode developed after a respiratory infection. A cryofibrinogenemia was found without any evidence of an underlying primary disease, especially not of a neoplasm. The clinical, histological, immunohistological, and electron microscopical findings, as well as the results obtained by intravital fluorescence videomicroscopy are presented.

Cryoglobulinemia↗
PubMed1987

[Pemphigus vulgaris with esophageal involvement. Case report and review of the literature].

A pemphigus vulgaris patient with esophageal involvement is presented, and eight well-documented cases from the literature are reviewed. The patient's skin had healed, but she still had acute gastroesophageal symptoms and persisting oral lesions. The antibody titers against intercellular substance were low. She thus presented the "classical" picture of pemphigus vulgaris with esophageal involvement.

Complement C3↗
PubMed1987

[Syringoma of the vulva].

A case of a 20-year-old white female patient is presented, who developed syringomas on the labia majora. The 12 cases that have previously been described in the literature are summarized. Syringomas should be considered in the differential diagnosis of papular lesions of the vulva and are probably more common than is reflected in the number of cases published.

Adenoma↗