Allele frequencies for 15 autosomal STR loci and admixture estimates in Puerto Rican Americans.

Allelic frequencies of 15 short tandem repeats (STR) markers (CSF1PO, FGA, THO1, TPOX, VWA, D3S11358, D5S818, D7S820, D8S1179, D13S317, D16S539, D18S51, D21S11, D19S433 and D2S1338) were determined using the AmpFl STR Identifiler PCR Amplification Kit in Puerto Rican American individuals (N=205) from Massachusetts. The FGA, D18S51 and D2S1338 loci had a high power of discrimination (PD) with values of 0.967, 0.965 and 0.961, respectively. Significant deviations from the Hardy-Weinberg (HW) equilibrium were not detected. An important genetic contribution of Caucasian European (76.4%) was detected in Puerto Rican Americans. However, comparative analysis between Puerto Rican American and other neighboring populations from United States mainly with African and Caucasian Americans, revealed significant differences in the distribution of STR markers. Our results are important for future comparative genetic studies of different American ethnic groups, in particular a cultural group called Hispanic-Americans and should be helpful for forensic and paternity testing.

Genetic relationship of the Guambino, Paez, and Ingano Amerindians of southwest Colombia using major histocompatibility complex class II haplotypes and blood groups.

We analyzed the Amerindian tribes, Guambiano, Ingano, and Paez of the southwest section of Colombia by major histocompatibility complex class II typing and blood group analysis in order to establish their genetic relationship. In addition, genetic admixture with Caucasian and African ancestry were determined based on blood group typing. The Paez showed admixture with Caucasian populations (22.4%), while the Ingano and Guambiano showed some admixture with Black populations (9.2 and 4.6%, respectively). The Ingano had MHC class II haplotypes found mainly in Amerindian and Asian populations with no evidence of class II haplotypes of African origin. MHC class II haplotypes of Amerindian and Asian populations and some haplotypes frequently found in European Caucasians and Asians and haplotypes of European Caucasians were found in Guambiano and Paez tribes. We compared our results with those previously reported for four Amerindian tribes on Northern Colombia. The presence of some MHC class II haplotypes in the Guambiano, Paez, and Ingano tribes and their absence in the Chibcha speaking groups of Northern Colombia suggest that these tribes originated, together with other Amerindians, from a separate migration or by genetic drift from an ancestral population. Therefore they are genetically distant from Chibcha speaking tribes of Colombia.

Association of HLA-DRB1*1602 and DRB1*1001 with Takayasu arteritis in Colombian mestizos as markers of Amerindian ancestry.

We performed HLA Class I and Class II typing in 16 patients (15 women, one man) with a confirmed diagnosis of Takayasu arteritis. We did not find any of the previously described associations with HLA-B52, and/or HLA-DRB1*1301 alleles. However, in our patients, HLA-DRB1*1602 and HLA-DRB1*1001 were significantly increased. The association of Takayasu arteritis with Amerindian and Asian HLA-DRB1 alleles (DRB1*1602 and DRB1*1001) in the Colombian mestizo patients reported here, and with HLA-B*3906 previously reported in Mexicans, suggest the possibility that some HLA and disease associations are markers for ethnicity of a population carrying a disease gene which is present in an admixed population with the disease.

Population data on 6 short tandem repeat loci in a sample of Caucasian-Mestizos from Colombia.

Blood samples from 409-452 unrelated Colombian Caucasian-Mestizo individuals were amplified and typed for six short tandem repeat (STR) markers (HUMF13A01, HUMFES/FPS, HUMVWA, HUMCSF1PO, HUMTPOX, HUMTH01). The allele frequencies, genotype frequencies, heterozygosity, mean paternity exclusion chance, polymorphism information content, discrimination power, assumption of independence within and between loci and Hardy Weinberg equilibrium were determined. The results demonstrate that all markers conform to Hardy-Weinberg equilibrium expectations. In addition, the results demonstrate the assumption of independence within and between the loci analysed. The mean exclusion chance (MEC) was 0.9851 for all six STR loci analysed and the discrimination power (DP) was 0.9999973. Therefore, this Colombian population database can be used in identity testing to estimate the frequency of a multiple PCR-based locus DNA profile in forensic cases as well as in paternity testing.

Rapidly progressive cholestasis: An unusual reaction to amoxicillin/clavulanic acid therapy in a child.

Hepatotoxity associated with amoxicillin/clavulanic acid is usually a self-limited disease with complete recovery. We report a rapidly progressing liver disease with ductopenia and portal fibrosis in a 3-year-old boy treated with Augmentin.

Excess admixture proportion of extended major histocompatability complex haplotypes of Caucasian origin among rheumatoid arthritis associated haplotypes in African Americans and Afro-Caribbeans.

Several extended major histocompatability complex (MHC) haplotypes are associated with susceptibility to autoimmune disease in Caucasian populations. It is known that African Americans and Afro-Caribbeans are ethnic groups descended from west, central and southern black African populations which are admixed with Caucasians. To examine the possible association of some marker of Caucasian MHC genes and susceptibility to rheumatoid arthritis (RA) in African Americans, we studied extended MHC haplotypes (HLA-B, complement and DR) in a sample of 18 African American and Afro-Caribbean probands with RA, their first degree relatives and in 15 non-RA families. We defined 36 disease-associated RA haplotypes among the probands and 96 normal haplotypes in normal individuals. To obtain the most conservative estimate, we excluded recognized Caucasian, DR4-bearing, extended MHC haplotypes from the analysis. Admixture proportions for non-HLA-DR4 extended MHC haplotypes of known Caucasian origin among RA-associated and normal haplotypes were computed (0.40 versus 0.163 respectively). When we compared the difference in proportions between RA and normal haplotypes, the proportion of extended MHC haplotypes of known Caucasian origin was significantly increased among RA-associated haplotypes (Z = 3.16, p (one sided) < 0.001, p (adjusted) < 0.008). Our results suggest that racial admixture with Caucasian MHC genes may augment RA susceptibility and thus may be one mechanism to explain the higher prevalence of RA in African Americans and Afro-Caribbeans than in black African populations.

Major histocompatibility complex class II alleles and haplotypes and blood groups of four Amerindian tribes of northern Colombia.

MHC class II alleles and haplotypes were determined from unrelated individuals and families of the Arhuaco (n = 107), Kogi (n = 42), Arsario (n = 18), and Wayú (n = 88) tribes located in the northern part of Colombia. Class II DRB, DQA1, and DQB1 alleles were determined by PCR-SSO and PCR-RFLP based methods. Four haplotypes, [DRB1*0407, DRB4*0101, DQA1*03, DQB1*0302]; [DRB1*0403, DRB4*0101, DQA1*03, DQB1*0302]; [DRB1*1402/1406, DRB3*0101, DQA1*0501, DQB1*0301]; and [DRB1*0802, DQA1*0401, DQB1*0402], were observed among these four tribes. In addition to these haplotypes, the Wayú Indians showed a frequency of 21.3% for the [DRB1*1602, DRB5*02, DQA1*0501, DQB1*0301] haplotype, 13.1% for the [DRB1*0411, DRB4*0101, DQA1*03, DQB1*0302] haplotype, and 8.1% for the [DRB1*0411, DRB4*0101, DQA1*03, DQB1*0402] haplotype. Red cell antigen typing was used to calculate genetic admixture. The Kogi and Arsario showed no genetic admixture while the Arhuaco tribe showed admixture with genes of African origin and the Wayú showed admixture with Caucasians as well as genes of African origin. These findings were confirmed by the MHC class II allele and haplotype data obtained, as alleles and haplotypes of Caucasian and African origin were detected in the Wayú and Arhuaco and not in the Kogi or Arsario. These studies will be important in disease association and transplantation studies for Amerindian and colombian populations and for correlating genetic traits with the anthropologic and linguistic data available in order to better understand the Amerindian populations.

Failure of tumor necrosis factor to produce hypotensive shock in the absence of endotoxin.

Tumor necrosis factor (TNF) is reported to cause a shock syndrome similar to that produced by endotoxin (LPS). The purpose of this study was to determine the relationship between TNF and LPS in causing shock. Eighty rats received infusions of either TNF, LPS, or TNF plus LPS, as compared with saline solution. Temperature, blood, and tissue specimens were obtained at 2 hours. Blood pressure was measured over 4 hours in a separate group of awake rats. Mortality was assessed over 24 hours. Neither TNF (1 mg/kg) nor LPS (1 mg/kg) altered hematocrit, blood gases, temperature, or caused hypotension or mortality. If the same dose of TNF was combined with LPS, however, there was significant (p less than 0.05) hemoconcentration and metabolic acidosis associated with hypotension and 100% mortality by 4 hours. Pathologic changes were restricted to the small intestine and occurred in this group only. It was concluded that TNF does not cause hypotension or shock in the rat. TNF will cause lethal shock, however, if combined with a sublethal dose of endotoxin. This suggests that synergy between TNF and endotoxin is important in septic shock.

Sharing of MHC haplotypes among apparently unrelated patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

From the study of HLA, complement, and glyoxalase I alleles in 82 Venezuelan individuals belonging to 19 families of mixed ethnic origin having 20 affected newborns with salt-wasting congenital adrenal hyperplasia due to 21-hydroxylase (21-OH) deficiency, a total of 38 disease haplotypes and 53 nondisease haplotypes were found. Of the pathological haplotypes 47% were found to share the HLA-B39 or -Bw62 specificities, 55% of them in combination with the BFS, C2C, C4A4, C4B2 (SC42) complotype. The frequencies of HLA-B39 and -Bw62 among the affected haplotypes were 29 and 18% as compared with 6 and 0% among the nondisease haplotypes of the same families. Statistical associations (P less than 0.01) with salt-wasting adrenal hyperplasia were found with the SC42 complotype and with the combination SC42, HLA-B39. These results are markedly different from those reported in the literature which show an "association" at the population level among many Caucasoid samples of HLA-Bw47 and the extended haplotype (HLA-Bw47, DR7,FC91,0) with the salt-wasting form of the disease. Furthermore, four of the unrelated patients reported here were homozygous for all the major histocompatibility complex loci tested, while three others were homozygous for at least two HLA loci. Analysis of the geographical origin of the grandparents indicated clustering of the deficiency carrier HLA haplotypes. This observation, together with the fact that there is an excess of homozygotes among the patients in Venezuela, strongly suggests that salt-wasting 21-OH deficiency congenital adrenal hyperplasia is mostly the result of a founder effect of relatively hyperplasia is mostly the result of a founder effect identity by descent of a few abnormal alleles at the 21-OHB locus in most cases. The mutation marked by HLA-Bw47 was not observed in this population.

Focal glomerulosclerosis in children: correlation of histology with prognosis.

The clinical and pathologic data of 32 nephrotic children diagnosed as having focal glomerulosclerosis were retrospectively analyzed to determine what factors were responsible for progression to renal failure in 12 of these children. The patients were classified into three groups based on the histologic findings in their initial renal biopsies: Group I (n = 19) had a combination of global and segmental lesions; Group II (n = 8) had only globally sclerotic or obsolescent glomeruli; and Group III (n = 5) had only segmentally sclerosed glomeruli. Ten of the 12 patients with end-stage renal failure came from Group I and two from Group II. The median period from recognition of symptoms to renal failure was four years. Clinical features were of little prognostic value. However, comparison of the histopathologic data of the ten patients in Group I with renal failure (Group Ia) and Groups Ib, II, and III revealed that the risk of progressing to renal failure was significantly higher in patients having greater than 20% of their glomeruli involved by both global and segmental lesions (P = 0.005). Furthermore, patients in Group I and III had a lower probability of responding to treatment as compared to patients in Group II (P less than 0.025).

The distribution of HLA antigens in the Motilones Indians of Venezuela.

The HLA antigen profile of the Bari and Yupa Indians who live in the Motilones Valley on the border between Venezuela and Colombia was studied. Both groups showed very limited polymorphism. HLA--A1, A3, A11, Aw23, A25, A26, A29, Aw30, Aw32, and Aw33, and HLA--B7, B8, B12, B13, B14, B17, B18, Bw22, and B27 were not observed in either population.

Encephalopathy following measles infection in children with chronic illness.

Five patients with an unusual encephalopathy, possible secondary to measles virus infection, are described. Features common to these patients are: an existing chronic disease, neurologic deterioration 2 1/2 to 6 months after a measles infection, and death several weeks later. These events occurred when the chronic disease (e.g. leukemia or neuroblastoma) was in remission. That the measles virus was the causative agent is suggested only by finding in brain and extracranial tissues intracytoplasmic and intranuclear inclusions which contained measleslike particles. Additional clinical features seen in each of the five patients were: seizures, hypertension, and the inappropriate secretion of antidiuretic hormone.