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Biomedical subjects

H Shimizu

Publications and source records attributed to H Shimizu.

At least 91 records · Page 5Linked to original sources
PubMed2003

Disruption of the suprabasal keratin network by mutation M150T in the helix initiation motif of keratin 10 does not affect cornified cell envelope formation in human epidermis.

Keratin 10 (K10) is known to be tightly bound to the cornified cell envelope (CCE) and this binding is thought to play an important role in enhancing the structural integrity of the cornified cells. Bullous congenital ichthyosiform erythroderma (BCIE) is a genetic disorder of keratinization caused by gene mutations in the conserved sequences of keratin 1 (K1) or K10, which leads to abnormal suprabasal keratin network assembly. In BCIE patients' skin, the keratin network abnormalities make the upper spinous and granular keratinocytes fragile and result in blister formation. However, the exact pathomechanism of the hyperkeratosis seen in BCIE is still unknown. The involvement of the CCE in the pathomechanism of hyperkeratosis in BCIE is controversial. Abnormal CCE assembly may cause hyperkeratosis as reported in cases of lamellar ichthyosis. Binding of K10 to CCE is thought to be a vital connection between the suprabasal keratin filament network and CCE. We hypothesize that abnormal suprabasal keratin assembly caused by either K1 or K10 mutations can disrupt CCE formation, resulting in the hyperkeratosis observed in BCIE. To clarify whether K10 and keratin network defects affect CCE formation in vivo, the ultrastructural and immunohistological features of CCE were studied in the epidermis of two Japanese BCIE patients from two independent families carrying an identical missense mutation M150T in the helix initiation motif of K10. Ultrastructurally, a 15-nm-thick, dense, normal-appearing CCE was formed at the cell periphery of the keratinized epidermal cells. Light and electron microscopic immunolabeling revealed that the major CCE precursor proteins, involucrin and loricrin, were normally distributed and restricted to CCE of the epidermis. Immunofluorescent labeling showed that epidermal TGases, TGase 1, TGase 2 and TGase 3, were expressed normally in the epidermis. These findings suggest that a normal CCE is formed during the process of human epidermal keratinization, even if the suprabasal keratin filament network is disrupted as with this particular K10 mutation, M150T in BCIE.

Adult↗
PubMed2003

A novel homozygous mutation 371delA in TGM1 leads to a classic lamellar ichthyosis phenotype.

Malformation of the cornified cell envelope (CCE) arising from mutations of the transglutaminase (TGase) 1 gene (TGM1) is the cause of some cases of lamellar ichthyosis (LI). However, genotype/phenotype correlation in TGM1 mutations has not yet been fully clarified. We report a typical case of LI caused by a novel mutation in TGM1. The patient, a 33-year-old woman, showed thick, lamellar scales on the entire body surface. Immunofluorescence labelling with anti-TGase 1 antibodies was negative in the patient's epidermis. In situ TGase activity assay detected markedly reduced TGase activity in granular layers of the patient's epidermis. Electron microscopy revealed incomplete thickening of the CCE during keratinization in the epidermis. Sequencing of the entire exons and exon-intron borders of TGM1 revealed that the patient was a homozygote for a novel deletion mutation 371delA in exon 3. This mutation leads to a frameshift resulting in a premature termination codon 43 bp downstream from the mutation site. According to the protein modelling of TGase 1, the truncated protein from this mutated allele loses the entire catalytic core domain of TGase 1. Thus, the present homozygous mutation is expected to cause total loss of TGase 1 activity, resulting in large, dark, lamellar scales on the entire body, the classic phenotype of LI, in this patient.

Adult↗
PubMed2003

Squamous cell carcinoma developing in a 12-year-old boy with nonHallopeau-Siemens recessive dystrophic epidermolysis bullosa.

We report a 12-year-old boy with nonHallopeau-Siemens recessive dystrophic epidermolysis bullosa (nHS-RDEB) who developed two skin lesions of squamous cell carcinoma (SCC) on the left foot. The incidence of SCC in nHS-RDEB is much lower than in the HS-RDEB subtype. Furthermore, this boy is the youngest among 92 previously described patients with DEB to develop SCC. This study emphasizes the importance of vigilance in monitoring the possible development of SCC in DEB patients regardless of age or clinical severity.

Age of Onset↗
PubMed2003

Subcutaneous nodules on the buttocks as a manifestation of dialysis-related amyloidosis: a clinicopathological entity?

While beta 2-microglobulin amyloidosis occurring in patients undergoing long-term dialysis is frequently associated with joint involvement, skin lesions have rarely been encountered. We report a 57-year-old man with extensive subcutaneous amyloid deposition forming large nodules on the buttocks; the patient had been on maintenance dialysis for 28 years. Although this condition is rare, a review of the literature indicates that the majority of such lesions occur around the buttock region.

Amyloidosis↗
PubMed2003

The clinical spectrum of nonbullous congenital ichthyosiform erythroderma and lamellar ichthyosis.

Until about 20 years ago, the term lamellar ichthyosis (LI) represented all nonbullous autosomal recessive ichthyoses except for harlequin ichthyosis and ichthyosis syndromes. Since the 1980s, nonbullous autosomal recessive ichthyoses have been divided into two major clinical entities, nonbullous congenital ichthyosiform erythroderma (NBCIE) and LI. The nature of scaling and intensity of erythroderma are important clinical features that distinguish between NBCIE and LI. However, a considerable number of cases show an intermediate phenotype between the two classic clinical features. Histologically, parakeratosis and inflammatory cell infiltration are seen more frequently in NBCIE than in LI and the stratum corneum is usually thicker in LI than in NBCIE. However, neither histopathological findings nor ultrastructural features seem to help clearly distinguish between NBCIE and LI. Mutations in any of the three known causative genes, TGM1, ALOXE3 or ALOX12B, can lead either to NBCIE or LI. Candidate genes specific to either NBCIE or LI alone have not been identified. Based on these facts, it might be better to consider NBCIE and LI as variations of a single keratinization disorder, although the classification of these autosomal recessive congenital ichthyosis patients into NBCIE or LI depending on their clinical features is still useful for practical patient management.

Diagnosis, Differential↗
PubMed2003

Rapid remission of severe pruritus from angiolymphoid hyperplasia with eosinophilia by pulsed dye laser therapy.

A 48-year-old Japanese woman with angiolymphoid hyperplasia with eosinophilia (ALHE) was successfully treated with a flashlamp pulsed dye laser (585 nm, 450 micros pulse duration). The lesion was severely pruritic and had been enlarging slowly for 2 years but was resistant to conventional therapies, including topical, intralesional, and systemic corticosteroid, and cryotherapy. The severe pruritus immediately improved after the first treatment using the pulsed dye laser. The erythema and papules gradually improved without scarring and this was followed by further five treatments over approximately a 4-month interval. No clinical recurrences have been observed 1 year after completion of the treatment. We think that pulsed dye laser therapy is an effective treatment for ALHE in both Japanese as well as Caucasian patients. Pulsed dye laser therapy is also helpful in reducing the pruritus in ALHE patients.

Angiolymphoid Hyperplasia with Eosinophilia↗
PubMed2003

Formant interaction as a cue to vowel perception: a case report.

Accumulating evidence indicates that cerebral processing of consonants and vowels is separable. It has been shown that disordered temporal acuity leads to disturbed consonant perception in cases with pure word deafness. In contrast, there has been no clear explanation of how vowel perception is impaired. We examined a patient with auditory agnosia, who showed a differential ability to identify the five Japanese vowels after bilateral cerebral lesions. He correctly identified the vowel [a] in more than 70% of auditory presentations, whereas he identified [i] in only about 30% of presentations. The difference between the first and second formant frequencies "F2-F1" and an artificially defined value "F1-(F2-F1)" for each vowel correlated significantly with the percentage of correct identifications. These findings support the hypothesis that vowel perception is based on formant interactions.

Adult↗
PubMed2003

Immunomolecular mapping of adherens junction and desmosomal components in normal human epidermis.

Adherens junctions (AJs) are cell-cell and cell-matrix junctions that are known to comprise the transmembrane and cytoplasmic components linked to the f-actin cytoskeleton. Although the presence of AJs han been confirmed in normal human epidermis, previous studies immunolocalizing AJ-related antigens have been controversial. The purpose of this study was to produce a more precise molecular mapping of AJs and their constituents in relation to desmosomes in normal human epidermal keratinocytes. Using an electron microscope (EM) method to optimally fix plasma membranes. AJ structures were typically seen as a narrowing of the intercellular space between two keratinocytes that was distinct from desmosomes and gap junctions. Such structures were consistently found more frequently in the upper epidermis than in the basal layer. Immunogold electron microscopy showed an absence of the AJ components (E-cadherin and beta-catenin) from desmosomal areas but they were present at interdesmosomal areas at sites of close membrane association. Conversely, the desmosomal components plakoglobin and plakophilin 1 were restricted only to the outer attachment plaque of the desmosome. These results further confirm that AJs have a distinct molecular composition and distribution from desmosomes and that they regularly occur between desmosomes along the keratinocyte plasma membrane to provide alternative cell-cell adhesion mechanisms.

Actins↗
PubMed2003

The clinical significance of sialyl Lewis antigen expression in the spread of gastric cancer. Flow cytometric DNA analysis.

We previously reported significant relationships between sialyl Lewis antigen expression on gastric cancer cells and both hepatic metastasis and clinical prognosis. The purpose of this study was to compare the expression of sialyl Lewis antigens on gastric cancer cells to elucidate the possible role of sialyl Lewis antigens in predicting the spread of a tumor with regard to histological findings. Subjects consisted of 38 patients with gastric cancer. For comparison we measured the values for sialyl Lewisa (sLea) and sialyl Lewisx (sLex) expression on the surface of about 10,000-30,000 cancer cells. Monoclonal antibodies CA19-9 and KM-93 were used to determine the frequency (%) and quantity (channel) of the expression by flow cytometry. We assessed the correlation of sLea and sLex expression with histological findings (depth of tumor invasion (pT), lymphatic invasion (ly), venous invasion (v), and lymph node metastasis (pN)), by comparing sLea and sLex expression in relation to the grade of histological findings. A significant relationship was found between lymphatic invasion and the frequency of sLea expression (r = 0.40, p<0.05). The mean values of sLea frequency in cases categorized as ly 2 (36.30) and ly 3 (31.81) were statistically higher than those in ly 1 cases (12.74) (p<0.05). A significant relationship was also observed between lymph node metastasis and the frequency of sLea expression (r = 0.46, p<0.01). The mean value of sLea frequency in pN 3 cases (44.14) was statistically higher than those in pN 0 (17.11) and pN 1 (19.03) cases (p<0.05). Neither the depth of tumor invasion nor venous invasion showed any correlation with the expression of sialyl Lewis antigens. In conclusion the frequency of sLea expression on the surface of gastric cancer cells was greater in those patients who developed lymphatic invasion and lymph node metastasis. However, the mechanism by which sialyl Lewisa expression is upregulated remains unclear.

Adult↗
PubMed2002

A prospective cohort study of soy product intake and stomach cancer death.

The relationship between intake of soy products and death from stomach cancer was examined in a community-based prospective study of Japanese men and women in Takayama, Japan. Over 7 years of follow-up, 121 deaths from stomach cancer (81 men and 40 women) occurred among 30,304 (13,880 men and 16,424 women) participants who were at least 35 years of age. Diet including the intake of soy products and isoflavones was assessed by a validated semiquantitative food-frequency questionnaire at the beginning of the study. In men, the highest compared to the lowest tertile of total soy product intake was significantly inversely associated with death from stomach cancer after controlling for covariates (hazard ratios=0.50; 95% confidence intervals (CIs) 0.26-0.93, P for trend=0.03). Decreased hazard ratios for the highest compared to the lowest tertiles of total soy product intake (hazard ratios=0.49; 95% CI 0.22-1.13) was observed in women, although this association was of marginal significance. These data suggest that soy intake may reduce the risk of death from stomach cancer.

Chemoprevention↗