Hyaluronic acid pretreatment for Sendai virus-mediated cochlear gene transfer.

Gene therapy with viral vectors is one of the most promising strategies for sensorineural hearing loss. However, safe and effective administration of the viral vector into cochlear tissue is difficult because of the anatomical isolation of the cochlea. We investigated the efficiency and safety of round window membrane (RWM) application of Sendai virus, one of the most promising non-genotoxic vectors, after pretreatment with hyaluronic acid (HA) on the RWM to promote efficient viral translocation into the cochlea. Sendai virus expressing the green fluorescent protein reporter gene was detected throughout cochlear tissues following application combined with HA pretreatment. Quantitative analysis revealed that maximum expression was reached 3 days after treatment. The efficiency of transgene expression was several 100-fold greater with HA pretreatment than that without. Furthermore, unlike the conventional intracochlear delivery methods, this approach did not cause hearing loss. These findings reveal the potential utility of gene therapy with Sendai virus and HA for treatment of sensorineural hearing loss.

Cutaneous mucormycosis.

The patient, a 59-year-old male, had been diagnosed as having alcoholic hepatopathy 20 years previously. He noticed localized swelling on his left leg after fishing in a river. The patient was diagnosed as having cutaneous mucormycosis upon histological and mycological examination of the skin. Gradual improvement of the symptoms was noted four weeks after administration of itraconazole and fruconazole; these were discontinued after five months.

Clinical phenotype of Bart's syndrome seen in a family with dominant dystrophic epidermolysis bullosa.

BACKGROUND: Bart's syndrome is one type of dominant dystrophic epidermolysis bullosa (EB). It is known that, in some familial cases of dominant dystrophic EB, the symptoms differ depending on the individual. We observed the way Bart's syndrome affected four generations in the same family. The proband was a newborn boy who showed congenital localized absence of skin (CLAS) and bullae on the anterior aspects of both legs. Histologically, the bullae were located subepidermally. The CLAS and bullae disappeared within 4 months after birth, leaving scars. His father retained scarring and scaling from the knees down along the anterior aspect of the legs, and the nails of the toes were either lacking or deformed. His paternal grandmother and great-grandmother also presented deformed nails of the toes, although they had not had CLAS or bullae on the legs at birth. The individuals in this family thus showed some heterogeneity depending on the sex: blistering and CLAS were seen on the legs soon after birth in the male family members, but the female members did not share this pattern of symptoms, suggesting that the expression of symptoms may differ depending on the sex of the affected individual.

Photo-enhanced modification of human skin elastin in actinic elastosis by N(epsilon)-(carboxymethyl)lysine, one of the glycoxidation products of the Maillard reaction.

Long-term incubation of proteins with glucose leads to the formation of advanced glycation end products (AGEs), which are characterized by fluorescence, brown color, and cross-linking. Formation of AGEs in vitro requires oxygen and is dependent on transition metal-catalyzed oxidation of glucose or Amadori products. AGEs are thought to be involved in aging and age-enhanced diseases such as diabetic complications, atherosclerosis, dialysis-related amyloidosis, and Alzheimer's disease. Chronic exposure of the skin to sunlight induces hyperplasia of the elastic tissue in the upper dermis known as actinic elastosis. Herein we used a monoclonal anti-AGE antibody (6D12) whose epitope is N(epsilon)-(carboxymethyl)lysine (CML), one of the glycoxidation products of AGEs, and demonstrated that the lesions of actinic elastosis were modified by CML. Further immunohistochemical and immunoelectron microscopic examination with 6D12 demonstrated CML accumulates predominantly in elastic fibers especially in the amorphous electron-dense materials corresponding to photo-induced degenerated area rather than the electron-lucent region. Immunochemical analyses with enzyme-linked immunosorbent assay (ELISA) of elastase-soluble fractions demonstrated that the CML levels of the sun-exposed area were significantly higher than those of the sun-unexposed area. We conclude that ultraviolet-induced oxidation may accelerate CML formation in actinic elastosis of photoaged skin.

Immediate allergy to rubber gloves: a questionnaire study of hospital personnel.

We conducted a questionnaire study of immediate allergy to natural rubber gloves among 2,408 medical workers who had used rubber gloves at Kumamoto University Hospital and allied hospitals. The response rate was 64.5% (1,321 workers). Among them, 8.5% (7.0-10.0% at 95% confidence limit) replied that they had experienced immediate allergy to rubber gloves. There were significant correlations among the frequency of rubber glove use, a history of atopic dermatitis or contact dermatitis, and the presence of skin lesions due to allergic reactions to rubber gloves. In 27 workers, skin lesions were associated with general symptoms. Of 59 workers who experienced immediate allergy and were tested for latex-specific IgE, 4 persons were positive. We conclude that the frequency of contact allergy to natural rubber products is substantially prevalent among Japanese hospital personnel and that education and awareness of this allergy are important.

Synthesis and antihypertensive activity of 3-acetoxy-2,3-dihydro-5-[2- (dimethylamino)ethyl]-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one (diltiazem) derivatives having substituents at the 8 position.

In order to improve the potency and duration of biological actions of diltiazem, a number of 1,5-benzothiazepine derivatives having the substituents at the 8 position were prepared and evaluated for their antihypertensive activity in spontaneously hypertensive rats. The introduction of methyl, ethyl, isopropyl, benzyl, methoxy, ethoxy, phenoxy, and methylthio groups increased the antihypertensive activity and prolonged duration of action, whereas cyclohexyl, cyclopentoxy, tolyloxy, p-methoxyphenoxy and phenylthio derivatives were less active than diltiazem. Among them, the 8-benzyl and phenoxy derivatives showed the most potent and long-lasting antihypertensive action.

Morphea profunda--a cutaneo-pulmonary variant with profuse sweating.

A 51-year-old Japanese male developed morphea profunda over a plaque of pigmented sweating skin on the left chest extending deeply into the lung. Eight years previously, he noted a brown pigmented spot on the left axilla which started to enlarge over the left chest in a band-like manner. Later, the involved skin hardened with profuse sweating. Chest X-ray examination and computer tomography revealed a thickening of the left chest wall and a nodular mass lesion in the left lower lung field. Biopsy specimens from lung, chest wall, and overlying skin revealed a granulomatous tissue in the parenchyma and a marked fibrosis extending from the deep dermis to the pleura. There were no findings suggestive of malignancy or chronic infectious disease. We assume that the process of morphea in this patient extended deeply from the skin to the lung.