Biomedical subjects

N Tamura

Publications and source records attributed to N Tamura.

At least 91 records · Page 5Linked to original sources

PubMed1999

Intrathoracic esophageal replacement in the dog with the use of an artificial esophagus composed of a collagen sponge with a double-layered silicone tube.

OBJECTIVES: Intrathoracic esophageal replacement with an artificial esophagus is considered difficult. We attempted to replace the intrathoracic esophagus with an artificial esophagus composed of a collagen sponge with a double-layered silicone tube and examined the state of host tissue regeneration. METHODS: A 5-cm long gap was created in the intrathoracic esophagus in 9 dogs and repaired by interposition of our prosthesis. The dogs were fed only by intravenous hyperalimentation for 28 days. The silicone tube was removed at 29 days after the operation, and oral feeding was reintroduced. RESULTS: One dog was put to death at each of the following times: 1, 2, 3, 3, 6, 12, and 24 months after the operation. One dog is still surviving without problems after more than 26 months. One dog died of malnutrition at 10 months. In all dogs, the host regenerated tissue had replaced the resulting gap at the time of silicone tube removal. The mucosa had fully regenerated within 3 months and the glands within 12 months. The process of stenosis and shrinkage was complete within 3 months and did not advance thereafter. The lamina muscularis mucosae were observed as islets of smooth muscle within 12 months. Although the skeletal muscle regenerated close to the anastomoses, it did not extend to the middle of the regenerated esophagus even after 24 months. CONCLUSIONS: Use of a collagen sponge with a double-layered silicone tube was shown to be feasible even in the thorax and to allow the regenerated host tissue, consisting of the mucosa, glands, and lamina muscularis mucosae, to replace the esophageal gap.

Anastomosis, Surgical↗

PubMed1999

Platelet adhesion and complement activation studies on poly(N-alkyl mono and disubstituted) acrylamide derivatives.

Poly(N-alkyl mono and disubstituted) acrylamide derivatives were synthesized from poly(acryloyl chloride) by monomer analogous reaction. The polymers were characterized by FTIR-ATR and GPC. The contact angle measurements were performed to evaluate hydrophobic/hydrophilic characters of these polymers. The N-alkyl substituents changed contact angle between 55 and 75 degrees. In vitro platelet adhesion studies showed that surfaces of poly(N-alkyl substituted) acrylamides are prone to adhere platelets. Platelet spreading was more on poly(N-benzyl-N-ethyl acrylamide) surfaces in comparison to that on poly(N-benzyl-N-propionic acid ethyl ester acrylamide) and poly(N-benzyl acrylamide) surfaces. As a result of modification of amino group with N-alkyl substituents, the activations of C3a and C5a complements were suppressed 9-20% and 5-6% of native poly(acrylamides), respectively.

Acrylates↗

PubMed1999

Determinant of microvolt-level T-wave alternans in patients with dilated cardiomyopathy.

OBJECTIVES: The aim of this study was to clarify the clinical significance and the determinant of microvolt-level T-wave alternans (TWA) in patients with dilated cardiomyopathy (DCM). BACKGROUND: The prevention of sudden death in patients with DCM remains the therapeutic target. T-wave alternans has been proposed as a powerful tool for identification of patients at high risk for ventricular arrhythmias and sudden death in coronary artery disease. METHODS: In 58 DCM patients, TWA was measured during bicycle exercise testing using a CH 2000 system (Cambridge Heart, Bedford, Massachusetts). The New York Heart Association class, signal-averaged electrocardiogram, QT dispersion, left ventricular end-diastolic diameter (LVDd) and percent fractional shortening detected by echocardiogram and the grade of the ventricular arrhythmia were obtained in all patients. RESULTS: T-wave alternans was positive in 23 patients (TWA+ group), negative in 25 (TWA- group) and indeterminate in 10. Univariate analysis showed that the percentage of patients with ventricular tachycardia (VT) and the LVDd in the TWA+ group was significantly higher than those in the TWA- group (61% vs. 8%, p < 0.001 and 65 +/- 11 mm vs. 58 +/- 8 mm, p < 0.05, respectively). The sensitivity, specificity and predictive accuracy of TWA for VT were 88%, 72% and 77%, respectively. Multivariate analysis showed that the presence of VT was a major independent determinant of TWA in patients with DCM (p = 0.003). CONCLUSIONS: T-wave alternans was closely related to VT in patients with DCM. T-wave alternans is a useful noninvasive test for identifying high risk patients with DCM who have VT.

Adult↗

PubMed1999

Potentiation of anticoagulant effect of warfarin caused by enantioselective metabolic inhibition by the uricosuric agent benzbromarone.

OBJECTIVE: To clarify the mechanism(s) for the interaction between warfarin and benzbromarone, a uricosuric agent, and to predict changes in the in vivo pharmacokinetics of (S)-warfarin from in vitro data. METHODS: Warfarin enantiomers and benzbromarone in serum, 7-hydroxywarfarin in urine, and serum unbound fractions of warfarin enantiomers were measured in patients with heart disease given warfarin with (n = 13) or without (n = 18) oral benzbromarone (50 mg/d). In vitro inhibition constants (K(i)) of benzbromarone for (S)-warfarin 7-hydroxylation were determined with use of human CYP2C9 and liver microsomes. The magnitude of changes in the formation clearance for 7-hydroxylation (CLf), the unbound oral clearance (CL(oral,u)), and the oral clearance (CL(oral)) for (S)-warfarin were predicted by equations incorporating the in vitro Ki, the theoretical maximum unbound hepatic benzbromarone concentration, and the fractions of warfarin eliminated through metabolism and of CYP2C9-mediated metabolic reaction susceptible to inhibition by benzbromarone. RESULTS: The patients given warfarin with benzbromarone required a 36% less (P < .01) warfarin dose than those given warfarin alone (2.5 versus 3.9 mg/d) to attain similar international normalized ratios (2.1 and 2.2, respectively), and the former had 65%, 53%, and 54% lower (P < .05 or P < .01) CLf, CL(oral),u, and CL(oral) for (S)-warfarin than the latter, respectively. In contrast, no significant differences were observed for (R)-warfarin kinetics between the groups. Benzbromarone was found to be a potent competitive inhibitor (Ki < 0.01 micromol/L) for (S)-warfarin 7-hydroxylation mediated by CYP2C9. The average changes in the in vivo CLf, CL(oral),u, and CL(oral)values for (S)-warfarin induced by benzbromarone were largely predictable by the proposed equations. CONCLUSION: Benzbromarone would intensify anticoagulant response of warfarin through an enantioselective inhibition of CYP2C9-mediated metabolism of pharmacologically more potent (S)-warfarin. The magnitude of changes in the in vivo warfarin kinetics may be predicted by in vitro data.

Aged↗

PubMed1999

Renin-angiotensin system and fibronectin gene expression in Dahl Iwai salt-sensitive and salt-resistant rats.

OBJECTIVE: The tissue renin-angiotensin system and extracellular matrix are involved in the cardiovascular hypertrophy and remodeling induced by hypertension. In this study, we examined the gene expression of the tissue renin-angiotensin system and fibronectin in inbred Dahl Iwai salt-sensitive and salt-resistant rats. MATERIALS AND METHODS: Eight pairs of 6-week-old male Dahl Iwai salt-sensitive and salt-resistant rats were fed either a low- or high-salt diet (0.3% or 8% NaCl, respectively) for 4 weeks. Activities of the circulating renin-angiotensin system were measured by radioimmunoassay and the gene expression of tissue angiotensinogen, the angiotensin II type 1 receptor (AT1) and fibronectin were analyzed by Northern blot analysis. RESULTS: Salt loading significantly increased blood pressure and produced cardiovascular hypertrophy and nephrosclerosis in the salt-sensitive rats. Activities of the circulating renin-angiotensin system were lower in salt-sensitive rats than in salt-resistant rats fed the low-salt diet, and salt loading lowered these activities in salt-resistant rats but not in salt-sensitive rats. In salt-resistant rats, salt loading increased renal, cardiac and aortic angiotensinogen, AT1 and fibronectin messenger (m)RNA expression except for aortic fibronectin mRNA expression. In contrast, in the salt-sensitive rats, salt loading stimulated the expression of cardiac fibronectin and aortic angiotensinogen, AT1 and fibronectin mRNAs. Furthermore, the cardiac and aortic fibronectin mRNA levels in salt-sensitive rats were higher than those in salt-resistant rats when both strains were fed the high-salt diet. CONCLUSIONS: These results demonstrate that the expression of tissue angiotensinogen, AT1 and fibronectin mRNAs is regulated differently in Dahl Iwai salt-sensitive and salt-resistant rats, and indicate that salt-mediated hypertension activates the cardiac fibronectin gene independently of the tissue renin-angiotensin system and stimulates the aortic fibronectin gene with activation of the tissue renin-angiotensin system.

Angiotensin I↗

PubMed1999

The soluble CD40 ligand sCD154 in systemic lupus erythematosus.

We found that the plasma of patients with active systemic lupus erythematosus (SLE) could induce a human B-cell line (Ramos) to express high levels of immune accessory molecules that are commonly found on blood B cells of patients with active SLE. The ability of SLE plasma to induce such phenotypic changes could be abrogated by neutralizing antibodies specific for the CD40 ligand (CD154) but not by antibodies to TNF-alpha. Immunoprecipitation studies with anti-CD154 identified a 20-kDa protein in the plasma of SLE patients with active disease, but not in plasma of normal donors, indicating that such plasma contained soluble CD154 (sCD154). Using a quantitative ELISA method, we found that the plasma of patients with active disease had levels of sCD154 that were significantly higher than those found in plasma of normal donors. Levels of CD154 transcripts in SLE blood lymphocytes correlated with the relative concentrations of sCD154 found in SLE plasma. Furthermore, plasma levels of sCD154 correlated with the titers of anti-double-stranded DNA autoantibody and with clinical disease activity. These studies indicate that sCD154 of patients with SLE may act as a functional ligand for CD40 that is associated with SLE disease activity.

Adult↗

PubMed1999

Optically active antifungal azoles. VIII. Synthesis and antifungal activity of 1-[(1R,2R)-2-(2,4-difluoro- and 2-fluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]- 3-(4-substituted phenyl)-2(1H,3H)-imidazolones and 2-imidazolidinones.

New optically active antifungal azoles, 1-[(1R,2R)-2-(2,4-difluoro- and 2-fluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl ]-3-(4- substituted phenyl)-2(1H,3H)-imidazolones (1,2) and 2-imidazolidinones (3,4), were prepared in a stereocontrolled manner from (1S)-1-[(2R)-2-(2,4- difluoro- and 2-fluorophenyl)-2-oxiranyl]ethanols (15, 16). Compounds 1-4 showed potent antifungal activity against Candida albicans in vitro and in vivo, as well as a broad antifungal spectrum for various fungi in vitro. Furthermore, the imidazolidinones, 3b--e and 4d, e, were found to exert extremely strong growth-inhibitory activity against Aspergillus fumigatus.

Animals↗

PubMed1999

Tissue-specific changes of type 1 angiotensin II receptor and angiotensin-converting enzyme mRNA in angiotensinogen gene-knockout mice.

This study examined whether type 1 angiotensin II receptor (AT1) and angiotensin-converting enzyme (ACE) mRNAs are regulated during dietary salt loading in angiotensinogen gene-knockout (Atg-/-) mice which are genetically deficient in endogenous production of angiotensin II. Wild-type (Atg+/+) and Atg-/- mice were fed a normal-salt (0.3% NaCl) or a high-salt (4% NaCl) diet for 2 weeks. The mRNA levels were measured by Northern blot analysis. In Atg+/+ mice, concentrations of plasma angiotensin peptides were decreased by salt loading, whereas the treatment increased the brainstem, cardiac, pulmonary, renal cortex, gastric and intestinal AT1 mRNA levels. Salt loading also enhanced renal cortex ACE mRNA levels in Atg+/+ mice. Although plasma angiotensin peptides and urinary aldosterone excretion were not detected in Atg-/- mice, salt loading increased blood pressure in Atg-/- mice. In Atg-/- mice, pulmonary, renal cortex, gastric and intestinal AT1, and renal cortex and intestinal ACE mRNA levels were higher than those in Atg+/+ mice. However, salt loading upregulated AT1 mRNA expression only in the liver of Atg-/- mice, and the treatment did not affect ACE mRNA levels in Atg-/- mice. Furthermore, although the levels of ACE enzymatic activity showed the same trend with the ACE mRNA levels in the lung, renal cortex and intestine of both Atg-/- and Atg+/+ mice, the results of radioligand binding assay showed that cardiac expression of AT1 protein was regulated differently from AT1 mRNA expression both in Atg-/- and Atg+/+ mice. Thus, expression of AT1 and ACE is regulated by salt loading in a tissue-specific manner that appears to be mediated, at least partly, by a mechanism other than changes in the circulating or tissue levels of angiotensin peptides.

Angiotensin II↗

PubMed1999

Production of menaquinones by lactic acid bacteria.

Lactic acid bacteria were examined for their ability to produce quinone compounds, which may include dietary sources of menaquinones. Isoprenyl quinones in bacterial cells grown in a synthetic medium were extracted and analyzed by thin layer chromatography. Lactococcus lactis ssp. cremoris (three strains), Lactococcus lactis ssp. lactis (two strains), and Leuconostoc lactis were selected as high producers of quinone that synthesized more than 230 nmol of quinones/g of dried cells. The quinones were presumed to be menaquinone-7 to -10 by high performance liquid chromatography. Precise molecular weights were determined by mass spectrometry for Lactococcus lactis ssp. cremoris YIT 2011 and Leuconostoc lactis YIT 3001 and identified as menaquinone-8 and -9 for the former and menaquinone-9 and -10 for the latter. Those strains, when grown either in reconstituted nonfat dry milk or a soymilk medium, produced a beneficial quantity for dietary supplement (i.e., 29 to 123 micrograms of menaquinones/L of the fermented medium).

Benzoquinones↗

PubMed1999

[Chlamydia-induced reactive arthritis--HLA-B 27 negative two patients].

Two cases with HLA-B 27 negative, Chlamydia-induced reactive arthritis (ReA) were described. Case 1: A 30 y.o. male developed balanitis, urethritis, arthritis of both knees, elbows, shoulders and hip joints on May in 1997. Laboratory findings revealed CRP 2.7 mg/dl (normal range < 0.3), ESR 33 mm/h and negative rheumatoid factor (RF) test. Anti-Chlamydia trachomatis antibodies, IgG 2.22, IgA 3.33 were positive. HLA-typing revealed A 2, A 24 (9), B 39 (16), B 52 (5). He was diagnosed as ReA and arthritis subsided with treatment of minocycline and nonsteroidal antiinflammatory drugs (NSAIDs). Case 2: A 40 y.o. Iranian American male developed balanitis, urethritis, lumbago, arthritis of both elbows, knees and foot joints, iridocyclitis on August in 1995. Chlamydia trachomatis was detected in the urethral swab culture. He was diagnosed as ReA and treated with minocycline and NSAIDs. He was referred to our hospital on June in 1996. Arthritis at both knees and feet was detected. Laboratory findings revealed CRP 0.8 mg/dl, negative RF test was revealed. Antibodies to Chlamydia were positive (IgG 1.49, IgA 1.53) positive. HLA typing revealed A 1, A 2, B 37, B 55 (22). He was again treated with minocycline and NSAIDs and ReA ameliorated. Since HLA-B 22, B 37 and B 39 have been reported to cross-react or to have homology with B 27, B 22, B 37 and B 39 are likely to related to inducing ReA.

Adult↗

PubMed1999

[Oral and dental health and oral and dental support of home patients--role of dental hygienist in the home service nursing station].

Home patients have few chances for going out, so communication with their family means a lot. Talking and eating are particular pleasures. Therefore, oral and dental health and oral and dental support are very important for home patients. A dental hygienist from our clinic visits and offers oral and dental health (oral care) and oral and dental support (oral rehabilitation) to home patients as part of a care plan with home care nurses. Moreover, as general conditions are closely related with oral function, maintaining oral and dental health and regular oral and dental support are very important in order to improve the quality of life (QOL) of home patients.

Aged↗

PubMed1998

The role of tricorn protease and its aminopeptidase-interacting factors in cellular protein degradation.

Tricorn protease was previously described as the core enzyme of a modular proteolytic system displaying multicatalytic activity. Here we elucidate the mode of cooperation between Tricorn and its interacting factors, and we identify two additional factors, F2 and F3, closely related aminopeptidases of 89 kDa. In conjunction with these three factors, Tricorn degrades oligopeptides in a sequential manner, yielding free amino acids. We have been able to reconstitute a proteolytic pathway comprising the proteasome, Tricorn, and its interacting factors, F1, F2, and F3, which converts proteins efficiently into amino acids. Therefore, it is quite likely that Tricorn also acts in vivo downstream of the proteasome and, in cooperation with its interacting factors, completes protein catabolic pathways.

Amino Acid Sequence↗

PubMed1998

Vascular endothelial growth factor (VEGF) expression in human coronary atherosclerotic lesions: possible pathophysiological significance of VEGF in progression of atherosclerosis.

BACKGROUND: Vascular endothelial growth factor (VEGF) is an important angiogenic factor reported to induce migration and proliferation of endothelial cells, enhance vascular permeability, and modulate thrombogenicity. VEGF expression in cultured cells (smooth muscle cells, macrophages, endothelial cells) is controlled by growth factors and cytokines. Hence, the question arises of whether VEGF could play a role in atherogenesis. METHODS AND RESULTS: Frozen sections from 38 coronary artery segments were studied. The specimens were characterized as normal with diffuse intimal thickening, early atherosclerosis with hypercellularity, and advanced atherosclerosis (atheromatous plaques, fibrous plaques, and totally occlusive lesions). VEGF expression as well as the expression of 2 VEGF receptors, flt-1 and Flk-1, were studied with immunohistochemical techniques in these samples at the different stages of human coronary atherosclerosis progression. The expression of VEGF mRNA was also studied with reverse transcription-polymerase chain reaction. Normal arterial segments showed no substantial VEGF expression. Hypercellular and atheromatous lesions showed distinct VEGF positivity of activated endothelial cells, macrophages, and partially differentiated smooth muscle cells. VEGF positivity was also detected in endothelial cells of intraplaque microvessels within advanced lesions. In totally occlusive lesions with extensive neovascularization, intense immunostaining for VEGF was observed in accumulated macrophages and endothelial cells of the microvessels. Furthermore, VEGF mRNA expression was detected in atherosclerotic coronary segments but not in normal coronary segments. The immunostainings for flt-1 and Flk-1 were detected in aggregating macrophages in atherosclerotic lesions and also in endothelial cells of the microvessels in totally occlusive lesions. CONCLUSIONS: These results demonstrate distinct expression of VEGF and its receptors (flt-1 and Flk-1) in atherosclerotic lesions in human coronary arteries. Considering the multipotent actions of VEGF documented experimentally in vivo and in vitro, our findings suggest that VEGF may have some role in the progression of human coronary atherosclerosis, as well as in recanalization processes in obstructive coronary diseases.

Adult↗

PubMed1998

Mechanism of angiotensin II-mediated regulation of fibronectin gene in rat vascular smooth muscle cells.

This study was performed to investigate a mechanism of angiotensin II (Ang II)-mediated activation of the fibronectin (FN) gene in rat vascular smooth muscle cells. Actinomycin D and CV11974 completely inhibited Ang II-mediated increase in FN mRNA levels. Inhibitors of protein kinase C (PKC), protein-tyrosine kinase (PTK), phosphatidylinositol-specific phospholipase C, Ras, phosphatidylinositol 3-kinase, p70 S6 kinase, and Ca2+/calmodulin kinase also decreased Ang II-induced activation of FN mRNA. In contrast, cycloheximide; PD123319; or inhibitors of Gi, protein kinase A, or mitogen-activated protein kinase kinase did not affect the induction. FN promoter contained a putative AP-1 binding site (rFN/AP-1; -463 to -437), and the results of a transient transfection and electrophoretic mobility shift assay showed that Ang II enhanced rFN/AP-1 activity. CV11974 and inhibitors of PKC or PTK suppressed Ang II-mediated increases in rFN/AP-1 activity, although neither PD123319 nor a protein kinase A inhibitor affected the induction. Furthermore, mutation of rFN/AP-1 that disrupted nuclear binding suppressed Ang II-induced transcription in the native FN promoter (-1908 to +136) context. Thus, Ang II activates transcription of the FN gene through the Ang II type 1 receptor in vascular smooth muscle cells, at least in part, via the activation of AP-1 by a signaling mechanism dependent on PKC and PTK.

Angiotensin II↗

PubMed1998

Natriuretic peptide regulation of endochondral ossification. Evidence for possible roles of the C-type natriuretic peptide/guanylyl cyclase-B pathway.

The natriuretic peptide family consists of three structurally related endogenous ligands: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). The biological actions of natriuretic peptides are thought to be mediated through the activation of two guanylyl cyclase (GC)-coupled receptor subtypes (GC-A and GC-B). In this study, we examined the effects of ANP and CNP, which are endogenous ligands for GC-A and GC-B, respectively, on bone growth using an organ culture of fetal mouse tibias, an in vitro model of endochondral ossification. CNP increased the cGMP production much more potently than ANP, thereby resulting in an increase in the total longitudinal bone length. Histological examination revealed an increase in the height of the proliferative and hypertrophic chondrocyte zones in fetal mouse tibias treated with CNP. The natriuretic peptide stimulation of bone growth, which was mimicked by 8-bromo-cGMP, was inhibited by HS-142-1, a non-peptide GC-coupled natriuretic peptide receptor antagonist. The spontaneous increase in the total longitudinal bone growth and cGMP production was also inhibited significantly by HS-142-1. CNP mRNA was expressed abundantly in fetal mouse tibias, where no significant amounts of ANP and BNP mRNAs were detected. A considerable amount of GC-B mRNA was present in fetal mouse tibias. This study suggests the physiologic significance of the CNP/GC-B pathway in the process of endochondral ossification.

Animals↗

PubMed1998

Skeletal overgrowth in transgenic mice that overexpress brain natriuretic peptide.

Longitudinal bone growth is determined by the process of endochondral ossification in the cartilaginous growth plate, which is located at both ends of vertebrae and long bones and involves many systemic hormones and local regulators. Natriuretic peptides organize a family of three structurally related peptides: atrial natriuretic peptide, brain natriuretic peptide (BNP), and C-type natriuretic peptide. Atrial natriuretic peptide and BNP are cardiac hormones that are produced predominantly by the atrium and ventricle, respectively. C-type natriuretic peptide occurs in a wide variety of tissues, where it acts as a local regulator. These peptides can influence body fluid homeostasis and blood pressure control through the activation of two guanylyl cyclase (GC)-coupled natriuretic peptide receptor subtypes-GC-A and GC-B. We report here marked skeletal overgrowth in transgenic mice that overexpress BNP. Transgenic mice with elevated plasma BNP concentrations exhibited deformed bony skeletons characterized by kyphosis, elongated limbs and paws, and crooked tails. Bone abnormalities resulted from a high turnover of endochondral ossification accompanied by overgrowth of the growth plate. Studies using an in vitro organ culture of embryonic mouse tibias revealed that BNP increases the height of cartilaginous primordium directly, thereby stimulating the total longitudinal bone growth. The present study demonstrates that natriuretic peptides can affect the process of endochondral ossification.

Aging↗

PubMed1998

Expression of arthritis-causing HLA-B27 on Hela cells promotes induction of c-fos in response to in vitro invasion by Salmonella typhimurium.

HLA-B27 confers a very strong genetic predisposition to development of a reactive arthritis after infection by bacteria such as Salmonella typhimurium. This study examines the role of HLA-B27 in the initiation of the earliest host activities after exposure to Salmonella, namely activation of the immediate early genes in the epithelial cells. Our major finding is that in Hela cells, the expression of c-fos was induced by Salmonella invasion only when the cells expressed the transfected HLA-B27 gene, but not the HLA-A1 gene or a truncated HLA-B27 gene lacking the exons encoding the cytoplasmic domain. C-fos is potentially capable of complexing with members of the c-jun family to become the AP-1 transcription complex. Parallel to c-fos expression, we found that only with the HLA-B27 transfectant was there expression of AP-1. AP-1 potentially controls the expression of a large number of genes. On screening a panel of proinflammatory molecules, we found that Salmonella invasion induced expression of monocyte chemoattractant protein-1 in the HLA-B27 cells. Since each of these separate positive findings belong to the same cascade of events after cell activation, together they reinforce the hypothesis that HLA-B27 plays a modulatory role in the early signal transduction events induced by Salmonella invasion. This hypothesis adds another item to the list of allele-specific activities carried out by HLA class I molecules. If similar activation also occurs in the joints, it may play a major role in arthritis.

Arthritis↗

PubMed1998

Mutation analysis of patients with Hermansky-Pudlak syndrome: a frameshift hot spot in the HPS gene and apparent locus heterogeneity.

Hermansky-Pudlak syndrome (HPS) is a rare, autosomal recessive disorder in which oculocutaneous albinism, bleeding, and lysosomal ceroid storage result from defects of multiple cytoplasmic organelles-melanosomes, platelet-dense granules, and lysosomes. As reported elsewhere, we mapped the human HPS gene to chromosome segment 10q23, positionally cloned the gene, and identified three pathologic mutations of the gene, in patients from Puerto Rico, Japan, and Europe. Here, we describe mutation analysis of 44 unrelated Puerto Rican and 24 unrelated non-Puerto Rican HPS patients. A 16-bp frameshift duplication, the result of an apparent founder effect, is nearly ubiquitous among Puerto Rican patients. A frameshift at codon 322 may be the most frequent HPS mutation in Europeans. We also describe six novel HPS mutations: a 5' splice-junction mutation of IVS5, three frameshifts, a nonsense mutation, and a one-codon in-frame deletion. These mutations define an apparent frameshift hot spot at codons 321-322. Overall, however, we detected mutations in the HPS gene in only about half of non-Puerto Rican patients, and we present evidence that suggests locus heterogeneity for HPS.

Albinism, Oculocutaneous↗