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Biomedical subjects

H Hatano

Publications and source records attributed to H Hatano.

At least 109 records · Page 6Linked to original sources

[Epidemiology of connective tissue diseases of the skin (scleroderma, dermatomyositis and polymyositis) in Japan].

An epidemiologic study of connective tissue diseases (scleroderma, dermatomyositis, and polymyositis) performed from 1973 to 1976 in Japanese university hospitals is reported. Data from 32 of 48 university hospitals revealed that a total of 659 cases were collected. There were 396 cases of progressive systemic sclerosis, 178 cases of dermatomyositis, and 85 cases of polymyositis. The following points were analyzed: relationship of regional incidence, sex, initial symptoms, laboratory findings, and statistical analysis of autopsies.

Adolescent↗

Proton magnetic resonance study of Streptomyces subtilisin inhibitor. pH titration and assignments of individual tyrosyl resonances.

This paper reports the pH titration at 25 degrees C and the assignment of aromatic proton resonances of three tyrosyl residues of each identical subunit of Streptomyces subtilisin inhibitor (Mr 23000) by high-resolution 1H NMR spectroscopy. The complete assignments of the specific tyrosyl resonances were made based on the results of the differential chemical modification of the tyrosyl residues with tetranitromethane followed by peptide analysis, independently of the knowledge of the crystal structure. pKa values of Tyr-7, -75, and -93 were determined in a 2H2O solution to be 10.95, 11.8, and greater than or equal to 12.6, respectively, at 25 degrees C, whereas pKa values of nitrated Tyr-7 and -75 were determined to be 7.3 and 7.9, respectively. Tyr-93 was not nitratable under normal conditions. The strong resistance to nitration, together with the extremely high pKa value and the high-field shifted positions of the ring proton resonances of Tyr-93 at neutral pH, strongly suggests that Tyr-93 takes part in a hydrogen bonding as a proton donor. Tyr-7 is more easily modified with tetranitromethane than Tyr-75, although in the crystal Tyr-75 is more exposed than Tyr-7. The result, together with the pKa value of Tyr-75 significantly higher than that of a normal tyrosine, indicates that the microenvironment of Tyr-75 is more restricted in solution than in solid. These results imply that structural details of a protein may be quite similar in solution to those in the crystal in the rigid hydrophobic region of the protein but that in the surface region of the protein local structures may well differ between the solution and the crystal.

Amino Acids↗

Acid denaturation steps of Streptomyces subtilisin inhibitor. A proton magnetic resonance study of individual histidine environment.

Resonance positions and intensities of the C(2) protons of histidyl residues (His 43 His 106) were followed in the NMR spectrum of a protein, Streptomyces subtilisin inhibitor (MW 23,000), in the pH range 2-9 at 30 degrees C, in order to clarify the microenvironment of the individual histidyl residues and the acid denaturation processes of the protein. The large difference in the 1H-2H exchange rate between the C(2) protons of the two histidyl residues indicates that, whereas His 106 is well exposed to the solvent, His 43 is highly shielded from the solvent. Protonation of His 106 occurs in the pH range 5-9, giving a pKa of 6.0 +/- 0.1. In contrast, His 43 can not be protonated in the native conformation, but is protonation occurs simultaneously with the acid denaturation of the protein in a narrow pH range 2.7-3.6, with pHmid of transition at 3.25. On the other hand, the denaturation of the His 106 environment starts at pH 5.0 and finishes at pH 2.7 with pHmid of transition at 3.7. The denaturation transitions are reversible with pH for both His 43 and His 106, but the rates of these transitions are slow (less than 25 s-1). The Hill coefficient for the His 106 transition was found to be 0.9 +/- 0.1 in the pH range 3.5-5.0, but to be distinctively larger than unity below pH 3.5. On the other hand, the Hill coefficient for the His 43 transition was found to be 4.4 +/- 0.6 for the whole range of transition (pH 2.7-3.6). These results combined with available information about the crystal structure lead us to conclude that the transition of His 106 in the pH range 3.5-5.0 represents a local denaturation caused by the protonation of one neighboring residue, probably Glu 102, whereas the transition of His 43 occurs as a result of cooperative protonation of several residues probably including Phe 113 and Asp 52, and is a denaturation step accompanied by the destruction of the major hydrophobic core.

Bacterial Proteins↗

Binding of bullous pemphigoid antibodies to basal cells.

Eight out of 12 serum samples from patients with bullous pemphigoid having basement membrane zone antibodies gave positive binding not only to the basement membrane zone but also to the basal cell membrane and/or cytoplasm as observed by complement immunofluorescence. Reaction of fluorescein labeled pemphigus vulgaris gamma-globulins, binding mainly to the lower intercellular spaces of the epidermis, was greatly reduced by the prior incubation of high-titered bullous pemphigoid sera having the reactivity to the basal cells, while that of fluorescein labeled pemphigus foliaceus gamma-globulins binding mainly to the upper and middle intercellular spaces, was not influenced by the prior application of these bullous pemphigoid sera. These results indicate that bullous pemphigoid antibodies are heterogenous and can be classified into 2 types and that some cross reaction is present between pemphigus antibodies and bullous pemphigoid antibodies having the reactivity to the basal cells.

Antigen-Antibody Reactions↗

A comparative study of seborrheic keratoses and basal cell epitheliomas by complement immunofluorescence and electron microscopy.

Eight cases of seborrheic keratosis (SK) and 7 cases of basal cell epithelioma (BCE) were studied comparatively by complement immunofluorescence using pemphigoid serum which was reactive not only to the basement membrane zone (BMZ) but also to the cell membrane or the intercellular space (CMICS) of basal cells in normal human epidermis. Positive immunofluorescence both at the BMZ and the CMICS of proliferating basaloid cells was observed in all cases of SK, whereas in BCE, immunofluorescence weaker than that in SK was observed only a the BMZ of tumor cell nests. These tumors were also examined by light and electron microscopy, and differences already described in the literature between SK and BCE were confirmed. These findings suggest that antigenic properties of the BMZ of the skin are affected by proliferating epithelial cells and that epithelial cells are involved in the formation of the BMZ.

Basement Membrane↗

Conformation of adenosine 3',5'-monophosphate in solution as studied by the NMR-desert method. II. Self-association and temperature-dependent glycosidic isomerization at pH 7.

A study has been made of the association and the temperature-dependent conformation of adenosine 3',5'-monophosphate (cyclic AMP) in a neutral aqueous (2H2O) solution by means of proton magnetic resonance chemical shift and relaxation. The concentration and temperature-dependent chemical shifts of H(1'), H(2), and H(8), have enabled us to estimate the self-association constant, Ka = 1.1 +/- 0.3 M-1 at 25 degrees C and thermodynamic parameters delta H = -5.8 +/- 1.5 kcal/mol and delta S (25 degrees C) = -19.0 +/- 3 cal/mol per degree. The NMR-DESERT (Deuterium Substitution Effect on Relaxation Times) method has been utilized for the determination of the syn-anti conformational equilibrium in the monomeric state and for the determination of the mutual orientation of the two adenine rings in the dimeric state of cyclic AMP. The molecules were found to coexist with nearly equimolarity or syn-anti conformers and thermal activation of the molecules perturbs the syn-anti conformational equilibrium to comprise the syn form in preference at higher temperature. The glycosidic isomerization (from anti to syn) was found to be characterized both by a positive enthalpy change and by a positive entropy change. The cyclic AMP molecules prefer to take a 'trans-stacking' conformation in the dimeric state where the two molecules are arranged in such a way that the H(2) of one molecule is close to the H(8) of the other.

Chemical Phenomena↗

Comparison of in vivo and in vitro capability of complement fixation by pemphigus antibodies.

Using complement immunofluorescence, the capability of complement fixation by bound antibodies in pemphigus lesional skin was compared with circulating intercellular antibodies of complement-fixing type in the same patient. Five lesional skin samples from 6 patients, containing bound IgG, gave positive binding of complement (C3) supplied from fresh guinea pig serum, while only one serum sample showed complement-fixing pemphigus antibodies in the circulation. These results support the view that complement-fixing pemphigus antibodies are rapidly localized to the skin and play a role on the production of acantholysis.

Antibodies↗

Solubilization of 6-oxybenzo(a)pyrene radical by caffeine and DNA as studied by magnetic resonance. Observation of intermolecular charge transfer.

Crystals of 6-oxybenzo(a)pyrene free radical, formed chemically from the hydroxy derivative of the carcinogen benzo(a)pyrene, can be solubilized in aqueous solutions of DNA and of caffeine. ESR spectral evidence indicate that the radicals exist as dispersed monomers associated with DNA and with caffeine. Comparison of NMR spin-lattice and spin-spin relaxation times in the protons of caffeine has given direct evidence that a part of the unpaired electron (at least 10(-4)) is transferred from the radical to the associated caffeine molecule. Simple consideration of Mulliken's charge transfer theory, however, leads to the conclusion that the intermolecular charge transfer is not likely to be a major source of stabilization energy of the complex.

Benzopyrenes↗

Multinucleate epidermal cells in non-neoplastic dermatoses.

Multinucleate epidermal cells (MEC) originated from keratinocytes were observed histologically in 92 of 197 cases of non-neoplastic dermatoses, such as lupus erythematosus (26 of 70), lichenoid eruptions (26 of 47), Hailey-Hailey disease (5 of 5), psoriasis vulgaris (20 of 49) and so on. Most of these cells had two nuclei, and a few had three nuclei. MEC usually showed perinuclear bands of eosinophilic material which also showed positive staining for epidermal fibres (tonofilaments). In all cases of Hailey-Hailey disease, close correlation between formation of MEC and dyskeratotic tendency was observed. From these findings, it is concluded that the mechanism of formation of MEC in these dermatoses may be similar to that of Bowen's disease, in which dyskeratotic tonofilaments become entangled with the spindles of the mitotic apparatus so that normal cell division cannot take place. It seems likely that MEC are a manifestation not only of malignant dyskeratosis but also of benign one.

Cell Nucleus↗

Complement-fixing pemphigus antibodies.

The serum of a patient with a typical case of pemphigus vulgaria contained complement-fixing intercellular autoantibodies (pemphigus antibodies). Complement-fixing pemphigus antibodies were demonstrated only during the untreated active stage of the disease and titrated lower than corresponding IgG autoantibodies, which paralleled well with the disease activity. Pemphigus lesional skin, which contained in-vivo-bound IgG, showed the capability of further binding C3 in vitro from normal human serum. It was suggested from these findings that the complement system may play an active role in pemphigus acantholysis through complement-fixing pemphigus antibodies.

Acantholysis↗