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Biomedical subjects

T Tezuka

Publications and source records attributed to T Tezuka.

At least 19 recordsLinked to original sources

Phosphorylated cystatin alpha is a natural substrate of epidermal transglutaminase for formation of skin cornified envelope.

Both keratohyalin granules (KHG) and cornified envelopes were stained histochemically in an indirect immunofluorescent study by antiphosphorylated cystatin alpha antibody, indicating that phosphorylated cystatin alpha is a component of the cornified envelope proteins. When phosphorylated cystatin alpha (P-cystatin alpha) was incubated with epidermal transglutaminase (TGase) and Ca2+ ions, polymerized protein was produced by formation of epsilon-(gamma-glutamyl)lysine cross-linking peptide bonds between lysine residues of cystatin alpha and glutamine residues of suitable protein(s) in the enzyme preparation. However, phosphorylated and non-phosphorylated cystatins were polymerized to similar extents by the TGase. Immunofluorescent and immunoelectron microscopic observations revealed that P-cystatin alpha could be detected in vivo in the KHG and cornified envelopes. Treatment of sphingosine, a specific inhibitor of protein kinase C, markedly suppressed the incorporation of cystatin alpha into KHG. Thus phosphorylation of cystatin alpha by protein kinase C may play an important role in targeting cystatin alpha into KHG.

Animals

Case report: detection of varicella-zoster virus DNA in maternal breast milk.

A 27-year-old woman developed chickenpox postpartum. Her 2-month-old son who was breast fed also acquired chickenpox 16 days after the onset of the mother's illness. Varicella-zoster virus (VZV) DNA was detected in maternal breast milk by the polymerase chain reaction. These results suggest that transmission of VZV may occur via maternal breast milk.

Adult

Mild adrenal 3 beta-hydroxysteroid dehydrogenase deficiency in children with accelerated growth, premature pubarche and/or hirsutism.

We studied eight children (seven girls and one boy, of whom three are siblings) with accelerated growth, premature pubarche and/or hirsutism between the ages of 7 and 9.5 years. These patients were studied for the presence of adrenal steroidogenic defect by adrenocortico tropic hormone (ACTH) stimulation testing (Cortrosyn, 0.25 mg iv bolus dose). Baseline and stimulated 17-hydroxypregnenolone (delta 5-17P), 17-hydroxyprogesterone (17-OHP), dehydroepiandrosterone (DHEA), androstenedione (delta 4-A), testosterone, and cortisol levels were measured. Six children, including three siblings, were diagnosed with a mild form of 3 beta-hydroxysteroid dehydrogenase deficiency based upon the elevated response of serum delta 5-17P and the elevated ratio of delta 5-17P/17-OHP and of DHEA/delta 4-A to ACTH stimulation. Thus, a mild form of 3 beta-hydroxysteroid dehydrogenase deficiency may not be uncommon in children with accelerated growth, premature pubarche and/or hirsutism and routine assay of delta 5-steroid metabolites should be generally available.

17-alpha-Hydroxypregnenolone

[A case of complete response of locally advanced breast cancer to arterial infusion chemotherapy: cannulation through the right femoral artery and combined use of G-CSF].

We reported a case of locally advanced breast cancer who was cannulated into the right internal thoracic artery through the right femoral artery by Seldinger's method for intra-arterial chemotherapy and obtained good results. In general, aggressive chemotherapy is often accompanied by bone marrow suppression necessitating discontinuation of chemotherapy. However, this patient recovered from this complication by G-CSF. It was suggested that Seldinger's method is suitable for locally advanced breast cancer and that G-CSF has an immediate effect of bone marrow suppression caused by aggressive chemotherapy.

Administration, Oral

[Intra-arterial infusion chemotherapy with side-hole catheter for primary and metastatic liver, bile duct, and pancreas cancers].

Dislodgement and obstruction of catheter inserted into the artery are great hazards for the hepatic artery infusion chemotherapy. To prevent dislodgement, a new Anthron-coated catheter with a side hole was applied for the treatment of 32 patients with primary and metastatic liver cancer, bile duct cancer and pancreas cancer. The tip of the catheter was advanced deep into the gastroduodenal artery, proper or right hepatic artery, or splenic artery. Anti-cancer drugs were administered through the proximal side hole for targeting cancer. If necessary, the gastroduodenal artery was occluded with a metal coil. No dislodgement or obstruction of the catheter was noticed in the 32 patients thus treated. The new Anthron-coated catheter with a side hole proved to be useful for prevention of catheter dislodgement and accomplishment of long-term intra-arterial infusion chemotherapy.

Aged

Identification of hematoxylin-stainable protein in epidermal keratohyalin granules as phosphorylated cystatin alpha by protein kinase C.

The hematoxylin-stainable protein (HSP) in keratohyalin granules of the newborn rat epidermis was found to have the same amino acid composition and the same inhibitory and immunological properties as cystatin alpha. However, only its pI value (4.7) differed from that of cystatin alpha (5.3). Alkaline phosphatase treatment of HSP changed its pI value from 4.7 to 5.3. This pI change was inhibited by EDTA, an inhibitor of alkaline phosphatase. Furthermore, 32P from [gamma-32P]ATP was incorporated into recombinant cystatin alpha by a protein kinase C (PKC) preparation in the presence of phosphatidyl serine and Ca2+ ions as co-factors. The incorporation increased dose-dependently with the added cystatin alpha and was inhibited significantly by H-7, a specific inhibitor of PKC. SDS-PAGE autoradiography of the 32P-labeled proteins showed that 32P was incorporated into the cystatin alpha. This incorporation was not observed by the action of cAMP-dependent protein kinase. Therefore, it is highly possible that the HSP is a phosphorylated cystatin alpha and that the phosphorylation is catalyzed specifically by PKC.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine

[A case of neuroleptic malignant syndrome developed in liver cirrhosis patient addicted to alcohol].

A 55-year-old man with addiction of alcohol was admitted to our hospital with hematoemesis. After admission, the rupture of esophageal varices was observed and it was treated with endoscopic injection sclerotherapy. On the 3rd hospital day, the patient showed alcohol withdrawal syndrome and therefore haloperidol was administered intramuscularly and intravenously. After a half day of this treatment, high fever, diaphoresis, hypotension, tachycardia, muscular rigidity and tremor developed. With the laboratory data including high serum levels of CK, LDH, GOT and GPT, neuroleptic malignant syndrome (NMS) was suspected. Regardless of intensive care, hepatic failure, DIC and acute renal failure promptly developed, and he died on the 11th hospital day. Neuroleptics may cause serious side effects, such as NMS, when the physical status of patients was deteriorated. Especially in exhausted patient such as our case, even the small dose of neuroleptics caused NMS within short term. Thus, it seemed to be important for clinicians to pay attention to choice of neuroleptics.

Adult

Properties and nature of a cysteine proteinase inhibitor located in keratohyalin granules of rat epidermis.

The pI 4.7, 14.5 kDa hematoxylin-stainable protein (HSP) from rat epidermis inhibited the activities of the cysteine proteinases papain, ficin, cathepsins B, H and L with similar inhibitory characteristics as recombinant cystatin-alpha. Proteinases of other classes were not inhibited. The inhibitory activity of HSP was heat stable in the wide pH range of 3.0-10.0. Polyclonal antibodies against HSP cross-reacted with cystatin-alpha and the molecular mass of HSP was similar to that of cystatin-alpha, though its isoelectric point was different. The in vivo location of both HSP and cystatin-alpha is on keratohyalin granules in epidermis as detected by indirect immunofluorescence technique using individual antibodies. Therefore it is highly probable that HSP is a cystatin-alpha derivative or a very similar proteinase inhibitor belonging to a family of cystatins.

Amino Acids

Simple monochromatic refractometer for trans-epidermal water loss (TEWL).

We have developed a novel, portable refractometer (Noevir-Eva) for measuring transepidermal water loss (TEWL) which consists of a light emitting diode and a phototransistor. Cobalt chloride is used as an indicator of the amount of water. Filter paper, previously soaked with cobalt chloride solution and then dried, is attached to the skin with tape (3M Blenderm). Then, the monochromatic light (670 nm) which is yielded from the light-emitting diode is irradiated, reflecting on the above-mentioned filter paper, and the intensity of the reflected light is detected by a phototransistor. The amount of water evaporation from the surface of the skin is determined by the unit of reflected light intensity. The measured values by this new apparatus show a linear relationship with those of the commercially available apparatus (Evaporimeter EP-1). Accordingly, this new refractometer for the TWEL proved to be sensitive, dependable and also inexpensive.

Adult

Change in sphingomyelinase activity in human epidermis during aging.

We have investigated the change in activity of sphingomyelinase in human whole epidermis during aging. The sphingomyelinase activity gradually decreased with the aging process; that of people aged eighty decreased to one fourth of that of people aged twenty in same area. This result indicates that the lipid metabolism may be altered in the epidermis during aging.

Adolescent

Recurrent male herpes genitalis with two different strains of herpes simplex virus type 2.

A case of a 50-year-old man with recurrent herpes genitalis with two different isolated strains of herpes simplex virus (HSV) type 2 is reported. Morphologically, two types of cytopathic effects (CPE) induced by viruses were observed in the Vero cell cultures, one being a syncytial giant cell formation and the other a rounded cell formation without cell adhesion resembling the CPE induced by ordinary HSV type 2. In this case, it is clinically interesting that the patient complained of persistent pain on the glans and urethra without recurrence of herpetic lesions even after the involution of enanthema. The correlation between the persistent pain and neurovirulence of the two different HSV strains is discussed.

Animals

The 55-kd keratohyalin granule protein has the same epitope as the 43-kd stratum corneum membrane protein: immunofluorescence and immunoblotting studies using a monoclonal antibody to the 55-kd keratohyalin granule protein.

A monoclonal antibody (Ted-R-1) to the keratohyalin granules (KHGs) of the newborn rat epidermis was developed by immunizing mice with a pH 4.7 hematoxylin-stainable fraction of the extract in a 50 mM Tris-HCl buffer, pH 7.3, containing 10 micrograms/ml phenylmethylsulfonyl fluoride (PMSF) from the newborn rat whole epidermis. Using an indirect immunofluorescence technique, Ted-R-1 was located in two places: (a) the KHGs and (b) the cell membrane region of the stratum corneum. Under immunoelectron microscopy, the antigenic materials were located at the periphery of the KHGs. Immunoblotting analyses of the antigenic pH 4.7 fraction, the Tris-HCl extract from the stratum corneum, and the Tris-8M urea extract from freeze-dried whole skin demonstrated that there were 55 kd, 43 kd, and 78 kd polypeptides, respectively, with which Ted-R-1 reacts. No positive spot was seen in the dermal extract. The major amino acids of the 55 kd protein were glycine (24.4%), serine (17.3%), glutamic acid (14.1%), and alanine (7.7%), while the histidine residue was only 3.1%. On the basis of its amino acid composition, the 55 kd proteins is the third component of KHGs - in addition to histidine-rich and cystine-rich proteins.

Animals

The water-holding capacity of the stratum corneum measured by 1H-NMR.

The amount of bound water in the stratum corneum of the hairless rat was measured by using proton nuclear magnetic resonance (1H-NMR) spectrometry in the temperature range of -5 degrees C to -30 degrees C. A decrease in the bound water content was observed when the stratum corneum was extracted using water, a mixed solvent of chloroform:methanol (2:1), or a 1% sodium dodecyl sulfate (SDS) aqueous solution. However, extraction using a mixed solvent of acetone:ether (1:1) did not change the bound water content at temperatures above -20 degrees C. The lipids extracted by acetone:ether-extraction method consisted of sebaceous gland lipids, cholesterol, free fatty acids, and ceramides. In contrast, the lipids extracted by chloroform:methanol-extraction method contained more polar lipids such as sphingomyelin, which had the same amount of bound water in itself as that of the water-extracted stratum corneum. These results suggest that the polar lipids soluble in the chloroform and methanol mixture may contribute to enhance the bound water content. Therefore, it is hypothesized that the water-holding capacity of the stratum corneum is dependent on both the hygroscopic components such as the natural moisturizing factor (NMF) and the polar lipids, such as sphingolipids, existing in the intercellular spaces of the stratum corneum.

Animals