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K Fukai

Publications and source records attributed to K Fukai.

At least 19 recordsLinked to original sources
PubMed1996

Positional cloning of a gene for Hermansky-Pudlak syndrome, a disorder of cytoplasmic organelles.

Hermansky-Pudlak syndrome (HPS) is an often-fatal autosomal recessive disease in which albinism, bleeding, and lysosomal storage result from defects of diverse cytoplasmic organelles: melanosomes, platelet dense bodies, and lysosomes. HPS is the most common single-gene disorder in Puerto Rico, with an incidence of 1 in 1,800. We have identified the HPS gene by positional cloning, and found homozygous frameshifts in this gene in Puerto Rican, Swiss, Irish and Japanese HPS patients. The HPS polypeptide is a novel transmembrane protein that is likely to be a component of multiple cytoplasmic organelles and that is apparently crucial for their normal development and function. The different clinical phenotypes associated with the different HPS frameshifts we observed suggests that differentially truncated HPS polypeptides may have somewhat different consequences for subcellular function.

Albinism, Oculocutaneous↗
PubMed1996

Homozygosity mapping of the gene for Chediak-Higashi syndrome to chromosome 1q42-q44 in a segment of conserved synteny that includes the mouse beige locus (bg).

Chediak-Higashi syndrome (CHS) is an autosomal recessive disorder characterized by hypopigmentation or oculocutaneous albinism and severe immunologic deficiency with neutropenia and lack of natural killer (NK) cell function. Most patients die in childhood from pyogenic infections or an unusual lymphoma-like condition. A hallmark of the disorder is giant inclusion bodies seen in all granule-containing cells, including granulocytes, lymphocytes, melanocytes, mast cells, and neurons. Similar ultrastructural abnormalities occur in the beige mouse, which thus has been suggested to be homologous to human CHS. High-resolution genetic mapping has indicated that the bg gene region of mouse chromosome 13 is likely homologous to the distal portion of human chromosome 1q. Accordingly, we carried out homozygosity mapping using markers derived from distal human chromosome 1q in four inbred families or probands with CHS. Our results indicate that the human CHS gene maps to an 18.8-cM interval in chromosome segment 1q42-q44 and that human CHS therefore is very likely homologous to mouse bg.

Adult↗
PubMed1995

Organization and sequence of the human P gene and identification of a new family of transport proteins.

We have determined the structure, nucleotide sequence, and polymorphisms of the human P gene. Mutations of the P gene result in type II oculocutaneous albinism (OCA2) in humans and pink-eyed dilution (p) in mice. We find that the human P gene is quite large, consisting of 25 exons spanning 250 to 600 kb in chromosome segment 15q11-q13. The P polypeptide appears to define a novel family of small molecule transporters and may be involved in transport of tyrosine, the precursor to melanin synthesis, within the melanocyte. These results provide the basis for analyses of patients with OCA2 and may point toward eventual pharmacologic treatment of this and related disorders of pigmentation.

Albinism, Oculocutaneous↗
PubMed1995

Autosomal recessive ocular albinism associated with a functionally significant tyrosinase gene polymorphism.

Autosomal recessive ocular albinism (AROA) is a disorder characterized by reduced pigmentation of the retina and iris, hypoplastic fovea, variably reduced visual acuity and nystagmus. Pigmentation of the skin and hair is normal, but is usually slightly lighter than in unaffected sibs. We analysed 12 unrelated patients with AROA, and found that two had abnormalities of the tyrosinase (TYR) gene. These two patients were each a compound heterozygote for a different pathologic mutant allele and an allele containing a 'normal' polymorphism, Arg402Gln, which results in a tyrosinase polypeptide with reduced thermal stability. In these patients, AROA thus appears to represent a clinically mild form of OCA1, with a fixed visual deficit resulting from low tyrosinase activity during fetal development but with normal pigmentation of the skin and hair postnatally.

Albinism, Ocular↗
PubMed1995

Pertussis immunization with acellular vaccines in Ghanaian children.

In the present study, the persistence of antibodies to pertussis antigens was assessed in 51 Ghanaian children immunized with one of two acellular vaccines and one whole cell vaccine in early infancy. The effect of a booster dose 1 year after primary immunization was also examined. Antibody titres to pertussis toxin (PT) and filamentous haemagglutinin (FHA) were measured 1 month and 1 year after primary immunization and 1 month after the booster dose. Although geometric titres (GMTs) to FHA were significantly higher in the two types of acellular vaccinees in the whole cell vaccinees 1 month after primary immunization, GMTs to FHA and PT after 1 year were not significantly different in the three groups. Geometric mean titres to PT and FHA following the booster dose were significantly higher in the acellular vaccinees than in the whole cell vaccinees. Seropositivity rates to PT and FHA in the acellular vaccinees, which were more than 93.3% 1 month after primary immunization, ranged from 50.0 to 77.8% after 1 year. In conclusion, the acellular vaccines did not produce higher antibody levels than the whole cell vaccine 1 year after primary immunization. The booster dose was essential to maintaining sufficient seropositivity to pertussis antigens.

Antibodies, Bacterial↗
PubMed1995

Linkage disequilibrium mapping of the gene for Hermansky-Pudlak syndrome to chromosome 10q23.1-q23.3.

Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by the triad of tyrosinase-positive oculocutaneous albinism, bleeding diathesis due to storage-pool deficiency of platelets, and a lysosomal ceroid storage disease. The disorder is particularly frequent in Puerto Rico and in an isolated village in the Swiss Alps. We have used a linkage disequilibrium mapping approach to localize the HPS gene in both of these groups to a 0.6 centiMorgan interval in chromosome segment 10q23.1-q23.3. These results indicate that the Puerto Rican and Swiss forms of HPS are either allelic or that they result from mutations in very closely linked genes in this region. This region of distal chromosome 10q is syntenic to the region of mouse chromosome 19 that includes 'pale ear' (ep) and 'ruby-eye' (ru), which must be considered as potential murine homologues to human HPS.

Albinism, Oculocutaneous↗
PubMed1995

Frequent intragenic deletion of the P gene in Tanzanian patients with type II oculocutaneous albinism (OCA2).

Type II oculocutaneous albinism (OCA2) is an autosomal recessive disorder in which the biosynthesis of melanin pigment is reduced in the skin, hair, and eyes. OCA2, which results from mutations of the P gene, is the most frequent type of albinism in African and African-American patients. OCA2 is especially frequent in Tanzania, where it occurs with an incidence of approximately 1/1,400. We have identified abnormalities of the P gene in each of 13 unrelated patients with OCA2 from Tanzania. One of these, a deletion of exon 7, is strongly predominant, accounting for approximately 77% of mutant alleles in this group of patients.

Albinism, Oculocutaneous↗
PubMed1994

A randomized controlled trial of two acellular pertussis-diphtheria-tetanus vaccines in primary immunization in Ghana: antibody responses and adverse reactions.

Two acellular pertussis vaccines combined with diphtheria and tetanus toxoids (APDT vaccines) were compared with a whole cell PDT (WCPDT) vaccine in primary immunization in Ghana. One is a liquid vaccine which is used for general immunization in Japan and the other is a freeze-dried vaccine newly developed as a heat-stable vaccine. Eighty-nine infants were recruited in the study. Sixty-eight who completed three doses of the immunization were assessed for immunological responses. Twenty-one dropped out because of sickness or moving from the study area. A total of 242 vaccinations in 89 infants were followed up for adverse reactions. Geometric mean titres (GMTs) to filamentous haemagglutinin in the two APDT vaccinees were significantly higher than in the WCPDT recipients. GMTs to pertussis toxin, diphtheria and tetanus toxoids were not significantly different among the three groups. Seropositive rates to pertussis antigens, tetanus and diphtheria toxoids were 94.4 to 100% in the two APDT vaccines. Systemic reactions within 7 days of inoculation were similarly low in the three groups, but significantly fewer infants had local reactions after either of the two APDT vaccines than after the WCPDT vaccine.

Antibodies, Bacterial↗
PubMed1994

Immunohistochemical localization of lysyl oxidase in normal human skin.

Lysyl oxidase (EC 1.4.3.13), a copper-dependent enzyme which catalyses the formation of aldehyde cross-links, and acts primarily on collagen and elastin, is known to be increased during wound healing and in fibrotic disorders including liver cirrhosis and atherosclerosis, and to be decreased in some hereditary connective tissue diseases and in malignant cell lines. A recent study showed that lysyl oxidase might possess tumour suppressor activity as an antioncogene for ras. Little is known about the localization of this enzyme in human skin. In this study, we determined immunohistochemically the localization of lysyl oxidase in normal skin of young and elderly subjects obtained from sun-exposed and unexposed regions of the body. All skin samples tested had similar distributions of lysyl oxidase. The enzyme was present both extracellularly and intracellularly. Extracellularly, a few granular aggregates of immunoreactants were observed along collagen and elastic fibres. These granules were more common in the adventitial portion of the dermis than in the reticular portion. Of all sun-exposed and unexposed regions studied, the skin of the face displayed the greatest amount of extracellular immunoreactants. Immunopositive granules were observed intracellularly in fibroblasts, vascular endothelial cells, sweat glands, sebaceous glands, arrector pili muscles and some keratinocytes. These findings provide evidence that, as suggested in recent reports, lysyl oxidase may have a variety of intracellular functions.

Adolescent↗
PubMed1994

Selective decrease of eumelanin in hypopigmented epidermis of hypomelanosis of Ito.

A Japanese infant had bilateral hypopigmented macules in a whorled or marble-cakelike configuration on her trunk and extremities. Her irides were bluish gray and her hair was dark brown. She had photophobia and macrocephaly with developmental delay. Analysis of peripheral lymphocytes and dermal fibroblasts disclosed a normal chromosomal pattern. A new finding was that the eumelanin content of the hypopigmented epidermis was decreased. We suggest that at least a portion of patients with this disorder have a defect in eumelanogenesis in hypopigmented skin.

Epidermis↗
PubMed1993

Chédiak-Higashi syndrome: report of a case and review of the Japanese literature.

We report the case of a Japanese female infant with Chédiak-Higashi syndrome born to consanguineous parents. At birth she had fair skin but, when she was three months old, marked hyperpigmentation of the sun-exposed skin areas developed. Microscopic examination of blood and electron microscopic examination confirmed the diagnosis. She enjoyed good health until she was two years old when she had pneumonia with marked hepatosplenomegaly. It is important for dermatologists and pediatricians to be aware of the skin manifestations of this disease because hyperpigmentation after sun exposure may be a characteristic, initial feature of this condition.

Chediak-Higashi Syndrome↗
PubMed1993

Nevus depigmentosus systematicus with partial yellow scalp hair due to selective suppression of eumelanogenesis.

We report a Japanese patient with congenital hypomelanosis with a segmental pattern on the left abdomen, whorl-like pattern on the back; mosaic pattern on the chest, right abdomen, and proximal extremities; and with yellow hair on a portion of the scalp. Chemical analysis of the yellow hair revealed decreased eumelanin content, whereas the pheomelanin content was normal.

Hair Color↗
PubMed1993

Cytolytic activity of natural killer cells and lymphokine activated killer cells against hepatitis A virus infected fibroblasts.

The role of Natural Killer (NK) cells, Lymphokine Activated Killer (LAK) cells and the induction of cytokines in the hepatocellular injury of hepatitis A were studied in vitro using a 51Cr release assay in hepatitis A virus (HAV) infected MRC-5 cells (MRC-HAV). When fresh peripheral mononuclear cells (PBMC) from healthy, anti-HAV antibody (-) and (+) human donors, or patients with acute hepatitis A were used as effector cells, MRC-HAV were lysed more extensively than uninfected cells. Similarly, in models using recombinant interleukin-2 (rIL-2) pretreated PBMC from HAV antibody (-) and (+) donors or patients with hepatitis A as effector cells, MRC-HAV were lysed more extensively than uninfected MRC. Both fresh PBMC and rIL-2 pretreated PBMC from anti-HAV antibody (+) donor lysed MRC-HAV cells more effectively than PBMC collected from anti-HAV antibody (-) patients. PBMC from patients with hepatitis A during the acute phase demonstrated more severe lysis of both uninfected MRC and MRC-HAV target cells. However, MRC-HAV lysis was enhanced to a greater degree. In an attempt to identify which cells were involved in cell lysis, cytotoxicity assays were performed by separating PBMC by cell sorter using monoclonal antibodies against all T cells, NK and B-cell fractions and culturing each with supplemental rIL-2. The NK cell fraction selectively destroyed MRC-HAV, but the lytic activity of both the pan T-cell and B-cell fractions was too weak to demonstrate any significant difference. Therefore, NK-LAK cells appeared to play a more significant role in cytolysis than did T-LAK cells. Morphologic observations of cellular damage were accomplished with PBMC obtained from healthy anti-HAV antibody (+) donors. PBMC were suspended in media containing rIL-2 and incubated for 4 days on monolayers of uninfected MRC and MRC-HAV. IFN-alpha and IFN-gamma in the supernatant of the cultured media were simultaneously assayed. Severe damage to HAV-infected cells was observed. Moreover, strong induction of IFN-alpha and IFN-gamma was found with high levels measured in the supernatant. Therefore, it is likely that non-specific immune mechanisms involving NK and LAK cells play a central role in hepatocellular damage prior to the initiation of damage due to Cytotoxic T Lymphocytes (CTL).

B-Lymphocytes↗
PubMed1992

Seroepidemiological survey for antibody to Borrelia burgdorferi in cows.

Antibody to Borrelia burgdorferi was examined in 380 healthy and 38 clinical cases of cows from Hokkaido and Shizuoka in Japan. In healthy animals, IgG and IgM antibody to B. burgdorferi HO14 strain were found in 44 cows (14.6%) and 24 cows (8.0%) from Hokkaido. In contrast, antibody-positive case was not observed except for only 1 case which was IgM positive (1/79: 1.3%) in cows from Shizuoka. Mean antibody levels of healthy animals in Hokkaido and Shizuoka were 0.651 and 0.263 (IgG antibody to HO14 strain), 0.642 and 0.169 (IgG to HP3 strain), 0.613 and 0.367 (IgM to HO14 strain) and 0.582 and 0.286 (IgM to HP3 strain). The differences of the antibody levels between cows from Hokkaido and Shizuoka were significant. Seasonal difference was found in seropositive cows from Hokkaido. The rate of seropositive cows was high in summer (23.4% in June and 11.8% in July) but low in winter (0% in January and February). The pattern was discussed to be associated with activation of ticks. One of 4 cows with arthritis showed significantly higher IgG antibody level than that of healthy cows and cows with some disease, although the serum was collected from Shizuoka where antibody-positive animals for B. burgdorferi were rare among healthy cows. This high IgG antibody may suggest that the arthritis of such cows was caused by infection with B. burgdorferi. Two of 7 cows with unclassified abortion showed positive antibody reaction in Hokkaido. These cases, however, may not be related to the B. burgdorferi infection because the positive rate was similar to those of healthy cows in the same season.

Animals↗
PubMed1992

The role of natural killer cells and lymphokine activated killer cells in the pathogenesis of hepatic injury in hepatitis A [corrected].

In order to clarify the mechanism of liver damage in hepatitis A, we studied the role of Natural Killer (NK) cells and Lymphokine Activated Killer (LAK) cells in non-specific immunological reactions using hepatitis A (HAV) infected cells (JTC-12.P3 cell) using the 51Cr release assay. No significant difference in specific cytotoxicity was observed between uninfected cells (JTC) and HAV-infected cells (JTC-HAV) to fresh and Poly I:Cor rIL-2 pretreated peripheral blood mononuclear cells (PBMC) from healthy donors or patients with acute hepatitis A. But in an experiment employing fresh and rIL-2 pretreated PBMC from cynomolgus monkey as effectors, a significant difference in NK and LAK sensitivity between JTC and JTC-HAV was noticed. Cytotoxicity assay was then carried out using as effectors fresh or rIL-2 pretreated cells of B, NK and T cell fractions obtained after separation of PBMC from monkey by the E-rosette formation method. Both fresh and rIL-2 pretreated B/NK cells showed significantly higher cytotoxicity for JTC-HAV than JTC, but neither fresh or rIL-2 pretreated T cells showed cytotoxicity for JTC-HAV or JTC. These results imply that both NK and LAK cells may play a part in the mechanism of hepatocellular injury.

Acute Disease↗
PubMed1991

Immunohistochemical localization of type I, III, IV, V, and VI collagens and laminin in neurofibroma and neurofibrosarcoma.

By using antibodies to type I, III, IV, V, and VI collagens and laminin, we examined the localization of interstitial collagens and basement membrane components with indirect immunofluorescence and immunoelectron microscopy (IEM). Furthermore, the morphological changes of these collagens in malignant transformation were investigated. In neurofibroma, IEM showed type I, III, and V collagens to be present diffusely on cross-striated collagen fibrils, whereas type VI collagen was present between the fibrils. Type IV collagen and laminin were observed to surround tumor cells. In neurofibrosarcoma, tumor collagen bundles that reacted with antibodies to type I, III, V, and VI collagens were irregularly arranged. Immunofluorescent deposits that reacted with anti-type IV collagen and anti-laminin antibodies were decreased in number, showing a thin and sparse arrangement.

Collagen↗