Hermansky-Pudlak syndrome: models for intracellular vesicle formation

Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by pigment dilution, nystagmus, decreased visual acuity, a bleeding diathesis, and lysosomal accumulation of ceroid lipofuscin. Electron microscopic evidence demonstrating lack of platelet-dense bodies provides the sine qua non for diagnosing HPS. Ceroid lipofuscinosis is considered to cause several serious complications, including progressive pulmonary fibrosis leading to death in the fourth or fifth decades. Currently, only symptomatic treatment can be offered. Although rare in the general population, HPS occurs in northwest Puerto Rico with a prevalence of 1 in 1800. HPS1, the first gene found to be responsible for HPS, was mapped to chromosome 10q23 and subsequently isolated and sequenced. It consists of 20 exons encoding a 700-amino acid, 79.3-kDa peptide with no homology to any known protein. All 10 HPS1 mutations reported to date, including the 16-bp duplication found in all northwest Puerto Rican patients, result in truncated proteins. The two mutations in the mouse pale ear gene (ep), which is the murine homology of HPS1, cause similarly truncated proteins. The pathologic nature of these truncation mutations may result from unstable mRNA. However, in combination with the absence of any disease-causing missense mutations, it may indicate that the C-terminus of the HPS1 peptide is functionally important. The disorder HPS displays locus heterogeneity, consistent with the existence of 14 mouse strains manifesting both hypopigmentation and a platelet storage pool deficiency. Two mouse models, pearl and mocha, have mutations in the beta3A and delta subunits of the adaptor-3 complex, respectively. This suggests that defective vesicular trafficking, specifically cargo packaging, vesicle formation, vesicle docking, or membrane fusion, may comprise the basic defect in HPS. Studies of the proteins involved in intercompartmental transport for melanosomes, platelet-dense bodies, and lysosomes should lead to a better understanding of the mechanisms of organellogenesis and to more effective therapies for HPS.     

OA1 mutations and deletions in X-linked ocular albinism

X-linked ocular albinism (OA1), Nettleship-Falls type, is characterized by decreased ocular pigmentation, foveal hypoplasia, nystagmus, photodysphoria, and reduced visual acuity. Affected males usually demonstrate melanin macroglobules on skin biopsy. We now report results of deletion and mutation screening of the full-length OA1 gene in 29 unrelated North American and Australian X-linked ocular albinism (OA) probands, including five with additional, nonocular phenotypic abnormalities (Schnur et al. 1994). We detected 13 intragenic gene deletions, including 3 of exon 1, 2 of exon 2, 2 of exon 4, and 6 others, which span exons 2-8. Eight new missense mutations were identified, which cluster within exons 1, 2, 3, and 6 in conserved and/or putative transmembrane domains of the protein. There was also a splice acceptor-site mutation, a nonsense mutation, a single base deletion, and a previously reported 17-bp exon 1 deletion. All patients with nonocular phenotypic abnormalities had detectable mutations. In summary, 26 (approximately 90%) of 29 probands had detectable alterations of OA1, thus confirming that OA1 is the major locus for X-linked OA.     

Puerto Rican patients travel to Puerto Rico: assessing the effect on clinical care

OBJECTIVE: To examine travel habits of Puerto Rican patients and assess the potential effect of this travel on their health care. DESIGN: Interview and survey of patients. SETTING: Urban medical clinic. PATIENTS: Two hundred consecutive, self-identified Puerto Rican patients presenting for follow-up care. INTERVENTION: Immediately prior to a follow-up office visit, patients were interviewed in either Spanish or English. MEASUREMENTS: The patients' age, sex, education level, employment status, and place of birth were recorded. The patients were asked questions concerning the principle place of residence of their family members, their ability to speak English, and their preferences in television and radio programs. Patients who had visited Puerto Rico were asked about the duration and purpose of their most recent trip and about the health care they received in Puerto Rico. Chi-square testing was applied to categorical data and t tests for continuous data; P values were calculated using the SPSS statistical analysis program. RESULTS: Of the 200 subjects, 110 (55%) had traveled to Puerto Rico in the last five years and 90 (45%) had not. The patients who traveled were more likely to have been born in Puerto Rico, less likely to speak English, and less likely to listen to English-language programs. A majority of the patients who traveled to Puerto Rico visited for a month or less (80%) and did not experience a change in health care (78%). In comparison, however, a majority (59%) of the patients who visited for longer than a month did experience a major change in their health care status (P < .00001). CONCLUSIONS: Puerto Rican patients, particularly those born in Puerto Rico with stronger cultural "ties" to the island, frequently return to Puerto Rico. Patients who visit for longer than a month often experience changes in care which are likely to have significant effect on their health. Clinicians caring for Puerto Rican patients should ask about upcoming visits to Puerto Rico and take steps to assure continuous and coordinated medical care.     

Carbonic anhydrase II deficiency: single-base deletion in exon 7 is the predominant mutation in Caribbean Hispanic patients

To date, three different structural gene mutations have been identified in patients with carbonic anhydrase II deficiency (osteopetrosis with renal tubular acidosis and cerebral calcification). These include a missense mutation (H107Y) in two families, a splice junction mutation in intron 5 in one of these families, and a splice junction mutation in intron 2 for which many Arabic patients are homozygous. We report here a novel mutation for which carbonic anhydrase II-deficient patients from seven unrelated Hispanic families were found to be homozygous. The proband was a 2 1/2-year-old Hispanic girl of Puerto Rican ancestry who was unique clinically, in that she had no evidence of renal tubular acidosis, even though she did have osteopetrosis, developmental delay, and cerebral calcification. She proved to be homozygous for a single-base deletion in the coding region of exon 7 that produces a frameshift that changes the next 12 amino acids before leading to chain termination and that also introduces a new MaeIII restriction site. The 27-kD truncated enzyme produced when the mutant cDNA was expressed in COS cells was enzymatically inactive, present mainly in insoluble aggregates, and detectable immunologically at only 5% the level of the 29-kD normal carbonic anhydrase II expressed from the wild-type cDNA. Metabolic labeling revealed that this 27-kD mutant protein has an accelerated rate of degradation. Six subsequent Hispanic patients of Caribbean ancestry, all of whom had osteopetrosis and renal tubular acidosis but who varied widely in clinical severity, were found to be homozygous for the same mutation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Puerto Rican intellectuals in New York: Some intragroup and intergroup contrasts.

A factor analysis of coded interview data on 20 Puerto Rican intellectuals in the New York City area yielded 5 item-factors (R) and 2 person-factors (Q). The R factors dealt with Spanish language dominance, ideological language maintenance, Puerto Rican cultural emphases, American awareness, and sociolinguistic sophistication. The Q groups differed meaningfully and consistently on these 5 factors and on demographic background variables, particularly with respect to ideological vs. behavioral Puerto Rican culture and language maintenance. Intellectuals as a group were found to differ greatly and systematically from ordinary Puerto Rican males in having more ideological positions with respect to Puerto Rican culture and Spanish language maintenance in New York. (French summary) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Carlos Albizu-Miranda (1920-1984): Obituary.

Carlos Albizu-Miranda died in Houston, Texas on October 6, 1984, several weeks after heart surgery. Albizu-Miranda was one of the early and continuing leaders of Puerto Rican psychology, and his death was a significant loss to Puerto Rican and American psychology. Puerto Rican psychology, as well as all of psychology, was enriched by his work and life. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Alterations of CDKN2 gene structure in childhood acute lymphoblastic leukemia: mutations of CDKN2 are observed preferentially in T lineage

We analyzed homozygous deletions and mutations of the CDKN2(p16(INK4A)/MTS1) gene, using polymerase chain reaction and Southern blot analysis, in 120 children with acute lymphoblastic leukemia (ALL). Homozygous deletion was found in 17 of 89 (19%) precursor B-ALL patients, in 11 of 24 (46%) T-ALL patients, and in 0 of 7 other phenotype ALL patients. After excluding 28 (23%) patients who showed a homozygous deletion of CDKN2, we found that three patients (3%) had mutation at exon 2 of CDKN2 using PCR-SSCP and sequencing strategy. One had a CGA to TGA nonsense mutation (Arg to stop) at codon 72, one had a 1-bp deletion at codon 117, and the third had a 2-bp deletion at codon 70, resulting in frameshifts in the two latter patients. All three of these patients were T phenotype ALL, and the incidence of mutation in the 24 T-ALL patients examined was 13%. In contrast, no mutation was detected in the remaining patients with precursor-B or other type ALL (0/96). Our results suggest that mutational inactivation of the CDKN2 gene may contribute to the leukemogenic growth, especially in some patients with T-ALL.     

Hero/heroine modeling for Puerto Rican adolescents: A preventive mental health intervention.

Culturally sensitive treatments of the special mental health needs of high-risk Puerto Rican adolescents are lacking. The hero/heroine intervention was based on adult Puerto Rican role models to foster ethnic identity, self-concept, and adaptive coping behavior. 90 nonclinical Puerto Rican 8th and 9th graders were screened for presenting behavior problems in school and randomly assigned to an intervention and a control group. After 19 sessions, the intervention significantly increased adolescents' ethnic identity and self-concept and reduced anxiety. Treatment outcomes varied as a function of grade level, sex, and household composition. Self-concept was negatively affected among girls from intact families. The study supports the effectiveness of the culturally sensitive modality as a preventive mental health intervention for high-risk Puerto Rican adolescents, especially from single-parent families. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Further data on key influencers of occupational expectation among minority youth.

Reports the relative frequency with which each of 9 specific "key figures" was reported by 73 Puerto Rican, 211 black, and 200 white high school females from "working-class" families to have exercised the principal influence over their selection of occupations they expected to hold as adults. Rank-order coefficients reveal the least similarity in citation of key figures between white and Puerto Rican Ss and virtually no difference between black and Puerto Rican Ss or between black and white Ss. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A critical analysis of Puerto Rican machismo: Implications for clinical practice.

Reviews the 2 prevalent theories of the Puerto Rican machismo concept found in the Puerto Rican and mental health literature, including the traditional and the culturalist perspectives. A new paradigm that integrates historical and sociopolitical interpretations of the male role configuration is proposed. This model examines machismo more as a result of the socioeconomic status (SES) of Puerto Rican males rather than an intrapsychic, ethnic cultural, or national characteristic issue and aims to educate the client as to how machismo functions for society and for his ethnic group. Recommendations for the use of this dialectical perspective in counseling approaches to Puerto Rican males are offered. It is suggested that a recognition of the class-related nature of machismo provides the possibility of approaching therapy or service delivery goals from a similarly based socioclinical model, with a focus on engagement and education. A group therapy case example is presented to illustrate the application of this approach to clinical practice, and its general applicability to individual, couple, and family work is noted. (33 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Polymorphism of the tumour necrosis factor-alpha and lymphotoxin-alpha genes in hairy cell leukaemia

Erythrocytosis arises from a variety of pathogenic mechanisms. We sequenced a 256-bp region 3' to the erythropoietin (Epo) gene which included a 24- to 50-bp minimal hypoxia-responsive element spanning HIF-1- and HNF-4-binding sites in 12 patients with erythrocytosis and 4 normal subjects. Four polymorphisms were found, none of which affected the HIF-1-binding site, although one polymorphism was present in the HNF-4 consensus region. The data indicate that none of these polymorphisms cause erythrocytosis.     

Deletion analysis of the p16 tumor suppressor gene in gastrointestinal mucosa-associated lymphoid tissue lymphomas

BACKGROUND & AIMS: The molecular mechanisms responsible for initiation and progression of gastrointestinal mucosa-associated lymphoid tissue (MALT) lymphomas are largely unknown. The aim of this study was to analyze the p16 tumor suppressor gene in MALT lymphomas of the stomach and colon. METHODS: Tumor samples were obtained from 28 patients with low-grade (n = 12) and high-grade (n = 14) gastric MALT lymphomas and from 2 patients with colonic MALT lymphomas. DNA was extracted from microdissected areas with at least 80% tumor cells. To detect homozygous p16 deletions, a semiquantitative polymerase chain reaction assay was used, whereby either p16 exon 1 or exon 2 was coamplified with an unrelated sequence as internal control. RESULTS: Homozygous p16 deletions were found in 2 of 14 (14%) cases with high-grade gastric MALT lymphomas. Both patients had Helicobacter pylori-associated gastritis; however, DNA extracted from areas of gastritis showed a normal p16 complement. No deletion was found in any of the low-grade gastric or the colonic MALT lymphoma specimens. CONCLUSIONS: In a subset of gastric MALT lymphomas, homozygous p16 deletions are acquired and may contribute to the transformation from a low-grade to a high-grade malignancy.     

Demonstration of a new pathogenic mutation in human complex I deficiency: a 5-bp duplication in the nuclear gene encoding the 18-kD (AQDQ) subunit

We report the cDNA cloning, chromosomal localization, and a mutation in the human nuclear gene encoding the 18-kD (AQDQ) subunit of the mitochondrial respiratory chain complex I. The cDNA has an open reading frame of 175 amino acids and codes for a protein with a molecular mass of 23.2 kD. Its gene was mapped to chromosome 5. A homozygous 5-bp duplication, destroying a consensus phosphorylation site, in the 18-kD cDNA was found in a complex I-deficient patient. The patient showed normal muscle morphology and a remarkably nonspecific fatal progressive phenotype without increased lactate concentrations in body fluids. The child's parents were heterozygous for the mutation. In 19 other complex I-deficient patients, no mutations were found in the 18-kD gene.     

Acute dissection of the thoracic aorta: experience at the Puerto Rico Medical Center (1991 through 1995)

BACKGROUND: Acute dissection of the thoracic aorta has a very poor prognosis unless promptly diagnosed and treated. The clinical presentation, diagnosis and management of 16 patients was reviewed. METHODS: We identified 12 patients from the Puerto Rico Medical Center and 4 patients from the "Centro Cardiovascular de Puerto Rico y del Caribe" whose diagnosis was made from January 1991 to December 1995. Medical records and autopsy reports were reviewed. RESULTS: Of the 16 patients, 10 [62%] were males, 10 [62%] were 60 years old or older [range 25 to 85 years], and 15 [93%] had a past history of hypertension although only 6 [38%] were found with an initial blood pressure of 140/90 or higher. Chest pain was the initial symptom in 13 [81%]. Of these 46% [6/13] described it as oppressive, with radiation to back or neck in 38% [5/13]. In none a neurological abnormality was the initial presentation. No physical sign was present in more than 40% of patients. One patient had a diastolic murmur suggestive of aortic regurgitation but none had a pericardial rub or a neurologic deficit. The electrocardiogram showed left ventricular hypertrophy in 35% but none had changes compatible with an acute Q wave infarction. The chest radiography was compatible with dissection in all in whom it was done [8/8]. Computerized tomography of the chest was diagnostic in 6 of 8 patients [sensitivity 75%]. Aortography had a sensitivity of 80% [4/5]. Trans-thoracic echocardiogram was diagnostic in 3 of 4 patients [75% sensitivity]. Transesophageal echocardiogram had a 100% sensitivity [2/2]. In 8 patients [50%] the correct diagnosis was made by postmortem examination, all of whom died within 24 hours of Emergency Room's evaluation. Of those properly diagnosed 5 died without being surgically intervened. Only one survived surgery [1/3] Overall mortality was 93%. The most common pathological finding was Type A dissection in 14 [88%]. Cardiac tamponade was found in 9 [56%]. Hemothorax was found in 6 [38%]. Aortic valve insufficiency was reported in 20% and coronary artery involvement in 28%. CONCLUSIONS: The dismal prognosis traditionally associated with acute dissection of the thoracic aorta remains unchanged. Prompt diagnosis based on high clinical suspicion. followed by expeditious medical and surgical treatment are fundamental to change the natural course of this condition.     

Cryptic T-cell epitopes and their role in the pathogenesis of autoimmune diseases

OBJECTIVE: To determine whether expectations about normal infant and child development are different among mothers from 4 ethnocultural groups. PARTICIPANTS: Two hundred fifty-five mothers (90 Puerto Rican, 59 African American, 69 European American, 37 West Indian-Caribbean) whose children received health care at hospital-based pediatric clinics and private pediatricians' and family practitioners' offices. DESIGN: Verbally administered questionnaire that included 25 questions in which mothers were asked to give their opinions about the age at which a normal child should begin to accomplish standard developmental milestones. ANALYSIS: Responses (mean ages at which mothers expected children to attain the milestones) from each group were compared after controlling for age of mother, number of children, level of education, and socioeconomic status. RESULTS: Significant differences among ethnic groups' responses were seen for 9 of 25 developmental milestones. Differences were mainly seen among personal and social milestones, and Puerto Rican mothers tended to expect children to attain these milestones at a later age than did other mothers. No differences in responses were seen between Spanish- and English-speaking Puerto Rican mothers. European-American mothers expected children to take first steps and become toilet trained at a later age. CONCLUSIONS: Developmental expectations differ among mothers from different ethnocultural groups. Many of these differences can be explained by underlying cultural beliefs and values and specific child-rearing practices. Clinicians should ask about maternal expectations during child health visits to interpret mothers' concerns and opinions about their children's development.     

Potthoff bias analyses of K-ABC MPC and Nonverbal Scale IQs among Anglo, Black, and Puerto Rican kindergarten children.

Bias analyses, via R. F. Potthoff's (1966) regression technique, were conducted to investigate the predictive utility of Kaufman Assessment Battery for Children (K-ABC) Mental Processing Composite (MPC) and Nonverbal scale IQs using 65 Anglo, 24 Black, 27 English-dominant Puerto Rican, and 30 Spanish-dominant Puerto Rican kindergarten children (aged 5 yrs through 5 yrs 11 mo) on 4 achievement criteria. Nonverbal scale IQs were poor predictors for English-dominant Puerto Rican Ss. MPC slope and intercept differences underestimated low-scoring Blacks on the teacher-assigned-grades criterion. When significant differences were found during other comparisons, results consistently showed that K-ABC IQs overestimated achievement for the minority Ss. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Patterns of high-grade prostatic intraepithelial neoplasia associated with clinically aggressive prostate cancer

BACKGROUND: The combination of low concentrations of sclerosing solution and the Nd:YAG, Q-switched laser with multiple (quadruple) frequency provides good results in the treatment of telangiectases and reticular varicose veins of the lower extremities, as well as pigmentation that may appear during sclerotherapy. OBJECTIVE: This paper is based on a series of patients with telangiectases and reticular veins who were treated with sclerotherapy and the Nd:YAG, Q-switched laser with quadruple frequency. METHODS: Patients with telangiectases and reticular veins received two or three treatment sessions with polydocanol and the Nd:YAG, Q-switched laser with quadruple frequency. Then, they were assessed a clinical score corresponding to the level of improvement achieved. Residual hematic pigmentation lesions were also eliminated with the laser. RESULTS: Excellent improvement was evident in 90% of the patients with minimal residual lesions. CONCLUSIONS: The combined technique of sclerosing solution and the Nd:YAG laser with multiple frequency is a valid alternative for the elimination of telangiectases and reticular veins of the lower limbs. This technique has several advantages, such as the use of low concentrations of sclerosing solution, high patient acceptance levels due to minimal disturbances, and the fact that local anesthesia is unnecessary. Good results are obtained without complications and minimal residual pigmentation. These mild pigmentation can be treated with the Nd:YAG laser.     

FH-Sydney 1 and 2: two novel frameshift mutations in exon 10 of the low-density lipoprotein receptor gene detected by heteroduplex formation

We report two novel frameshift mutations in exon 10 of the low-density lipoprotein receptor gene that lead to familial hypercholesterolemia in separate lineages. The lesions, FH-Sydney 1 and FH-Sydney 2, were detected by a modified heteroduplex analysis of exon-specific polymerase chain reaction (PCR) amplified DNA, and characterized at the molecular level by sequencing. Restriction enzyme digestion of PCR amplified DNA confirmed the presence of the mutant alleles in affected family members and their absence in nonaffected family members in both lineages. FH-Sydney 1 is a 4-bp duplication at position 1373, while FH-Sydney 2 is a 2-bp deletion at position 1478. The predicted result of both mutations is the premature truncation of the receptor at stop codons generated downstream of the mutations. Neither mutation was detected in a survey of 54 unrelated familial hypercholesterolemia patients.     

Surface treated large bore catheters with silver based coatings versus untreated catheters for extracorporeal detoxification methods

A population-based series of incident cases of malignant glioma were analyzed for mutations in the tumor suppressor gene p53. Exons 4-8 were screened using PCR-single-strand conformation analysis and confirmed through direct sequencing. Of 62 tumors analyzed, 12 (19%) contained mutations in p53: one 18-bp duplication in exon 5, five point mutations in exon 4, three point mutations in exon 7, two point mutations in exon 8, and a splice-site mutation at the exon 6/intron 7 boundary. In contrast to previous studies of malignant glioma, the prevalence of transversion mutations (56%) was higher than transition mutations (33%). A large proportion of transversion mutations occurred in exon 4, a region that is not routinely screened in gliomas. We present here an improved method for screening exon 4 (and other GC-rich regions) of p53 using PCR-single-strand conformation analysis. The high frequency of transversion mutations suggests a role for exogenous carcinogens in the etiology of malignant glioma.