Many human endogenous retrovirus K (HERV-K) proviruses are unique to humans.

BACKGROUND: Endogenous retroviruses contribute to the evolution of the host genome and can be associated with disease. Human endogenous retrovirus K (HERV-K) is related to the mouse mammary tumor virus and is present in the genomes of humans, apes and cercopithecoids (Old World monkeys). It is unknown how long ago in primate evolution the full-length HERV-K proviruses that are in the human genome today were formed. RESULTS: Ten full-length HERV-K proviruses were cloned from the human genome. Using provirus-specific probes, eight of the ten were found to be present in a genetically diverse set of humans but not in other extant hominoids. Intact preintegration sites for each of these eight proviruses were present in the apes. A ninth provirus was detected in the human, chimpanzee, bonobo and gorilla genomes, but not in the orang-utan genome. The tenth was found only in humans, chimpanzees and bonobos. Complete sequencing of six of the human-specific proviruses showed that full-length open reading frames for the retroviral protein precursors Gag-Pro-Pol or Env were each present in multiple proviruses. CONCLUSIONS: At least eight full-length HERV-K genomes that are in the human germline today integrated after humans diverged from chimpanzees. All of the viral open reading frames and cis-acting sequences necessary for HERV-K replication must have been intact during the recent time when these proviruses formed. Multiple full-length open reading frames for all HERV-K proteins are present in the human genome today.

A HERV-K provirus in chimpanzees, bonobos and gorillas, but not humans.

Evidence from DNA sequencing studies strongly indicated that humans and chimpanzees are more closely related to each other than either is to gorillas [1-4]. However, precise details of the nature of the evolutionary separation of the lineage leading to humans from those leading to the African great apes have remained uncertain. The unique insertion sites of endogenous retroviruses, like those of other transposable genetic elements, should be useful for resolving phylogenetic relationships among closely related species. We identified a human endogenous retrovirus K (HERV-K) provirus that is present at the orthologous position in the gorilla and chimpanzee genomes, but not in the human genome. Humans contain an intact preintegration site at this locus. These observations provide very strong evidence that, for some fraction of the genome, chimpanzees, bonobos, and gorillas are more closely related to each other than they are to humans. They also show that HERV-K replicated as a virus and reinfected the germline of the common ancestor of the four modern species during the period of time when the lineages were separating and demonstrate the utility of using HERV-K to trace human evolution.

Developmental changes in serum ferritin and erythrocyte protoporphyrin in normal (nonanemic) children.

We studied 4039 children who were 6 months to 12 yr of age to characterize developmental variations of serum ferritin and erythrocyte protoporphyrin. Age-related descriptive statistics were derived. The -2 SD value for serum ferritin was found to increase progressively from 12 to 21 micrograms/1 with increasing age, while the +2 SD value for erythrocyte protoporphyrin was found to decrease progressively from 65 to 42 micrograms/dl whole blood with increasing age. While the mean serum ferritin value was found to continue to rise throughout the first 12 yr of life, erythrocyte protoporphyrin values were highest at 1 to 2 yr of age, then fell to essentially constant levels after 4 to 6 yr of age. These relationships, as well as the linear relationship of increasing hematocrit and serum ferritin with increasing age, suggest that the rise of hematocrit with age, as previously observed, is associated with improving storage and availability of iron for heme synthesis.

Screening for iron deficiency with the erythrocyte protoporphyrin test.

Elevation of erythrocyte protoporphyrin (EP) level is one of the consequences of iron deficiency. As the EP test has been established to be a screening test for lead poisoning, the screening capability of the EP test for iron deficiency was investigated. A total of 4,160 children between ages 6 months to 12 years had EP determined together with serum ferritin and hematocrit. Comparing the relationship of EP to serum ferritin and using a serum ferritin value less than or equal to 15 micrograms/L as the criterion of iron deficiency, the optimal cutoff limit for the EP test appears to be 35 micrograms/dL of whole blood. At this level, 88% of the subjects with low levels of serum ferritin can be detected (sensitivity), in contrast to the 53% detected at a higher cutoff value (greater than or equal to 50 micrograms/dL) used to screen for lead toxicity, or to the 59% detected by age-related hematocrit value. At an EP screening level of 35 micrograms/dL of whole blood, 90% of the subjects with normal serum ferritin level are correctly determined to be screen negative (specificity). The predictive value of low levels of serum ferritin for all subjects above screening level is 38%. In general, an elevated EP level, by itself, represents inadequate iron supply for hematopoiesis and signals iron deficiency regardless of whether the serum ferritin value is below the diagnostic level or not. A trial course of orally administered iron is suggested for children who are found to have an elevated EP value, with an increase in hemoglobin or hematocrit value serving, retrospectively, as confirmation of prior iron deficiency.

Evolution of a D2 dopamine receptor intron within the great apes and humans.

Although direct DNA sequencing may allow rapid and high quality comparative phylogenetic analyses among species, such an approach may not be the most efficient method by which to make a large number of cross-species comparisons. We illustrate the use of Denaturing Gradient Gel Electrophoresis (DGGE) to screen a D2 Dopamine Receptor intron for DNA sequence variation, both within and between closely related species, in order to infer their evolutionary relationships. Our results suggest that: a) humans have less genetic variation than the great apes; b) pygmy chimpanzees have less genetic variation than common chimpanzees; and c) DNA sequence comparative analyses of primates require adequate sampling, both in number and in geographical range.

Analyses of cross species polymerase chain reaction products to infer the ancestral state of human polymorphisms.

In numerous population genetic and disease association studies decisions about the ancestry of polymorphic alleles are often made based on the relative frequency of the alleles in the extant populations with the most frequent allele being deemed as ancestral. However, the frequency of an allele in a population is generally not a perfect indicator of its ancestral status. A more accurate method to assess ancestral/derived status of polymorphic alleles involves identification of shared alleles between species. We used this strategy to examine genomic regions homologous to several human polymorphisms in four species of non-human primates. Cross species polymerase chain reaction (CS-PCR), with primers designed from human sequence, was used to investigate regions of interest. Nineteen polymorphisms at six loci (DRD2, HOXB@, PAH, D4S10, RBP3, and RET) were examined either by restriction fragment length analysis of PCR products (PCR-RFLP) or by direct sequencing. At seventeen of the eighteen PCR-RFLPs, non-human primates were monomorphic and identical to each other for either lack of restriction enzyme site or presence of the site. Thus, at these seventeen polymorphic sites the shared alleles are most likely to be the ancestral ones in humans. In several cases we have used sequence data to further demonstrate that the nucleotide at the site of the polymorphism is conserved between species confirming the hypothesis of a single ancestral allele. However, not all human alleles can be simply resolved into ancestral and derived; sequence data from one PCR-RFLP (in an intron of the PAH locus) and a single strand conformational polymorphism (SSCP) in the 3' untranslated region (UTR) of the DRD2 gene illustrate this point.

Pediatric emergency care in a metropolitan area.

Regional emergency medical services (EMS) system planning requires a data base describing the population to be served. No such regional data base exists for childhood emergencies. This study was undertaken for two reasons: (1) to establish, in a metropolitan region, the demographics of the population and the type of clinical problems for which pediatric emergency care is sought, and (2) to determine if the critical care categories used for EMS planning accurately reflect the emergency care needs of pediatric patients in the region. All pediatric visits (6,190) to 13 area hospitals during 1 month were reviewed. The most common diagnostic categories seen were trauma (48%) and infectious illness (29%). Six hundred and six visits satisfied criteria for inclusion in one of the following critical care categories: trauma, poisonings, burns, spinal cord injuries, behavioral disorders, cardiovascular illness, and a general category designated "medical." The last group was the largest of the categories (185 visits) and contained the greatest number of seriously or critically ill children. Of the total visits, 9.5% were by children 1 year or under, and 19.1% were by children 13 to 16 years old. For visits of a serious or critical nature, these age groups comprised 16% and 29%, respectively, of the total for such visits. This study documents that the emergency care needs of children differ from those of adults and deserve special attention in the planning of emergency care systems.

Lead levels among pregnant women in Hennepin County.

The purpose of this study was to determine the blood lead levels (Pb-B) of urban pregnant women with low incomes and/or living in areas with heavily traveled roads, dilapidated housing, and industrial plants. We measured blood lead in 1,055 pregnant Minneapolis-area women at entry to prenatal care and in one-third of the sample during the second half of pregnancy. The mean Pb-B level of the first sample (n = 1,055) was 1.83 +/- 1.83 micrograms/dL; of the second sample (n = 375), 1.99 +/- 1.92 micrograms/dL. Only one woman had a Pb-B level greater than 12.0 micrograms/dL, which was the result of occupational exposure. The low lead levels found in this study indicate that it is not necessary to routinely screen pregnant women for elevated Pb-B levels in our geographic area. Rather, women should be screened via an environmental questionnaire to ascertain the risk of lead exposure.

Great expectations: the retraining of refugee health care personnel.

PIP: The refugee population's basic unfamiliarity with Western health care concepts and the equal unfamiliarity of Western health care providers with the refugee's perceptions of health care, disease, and treatment, have presented a major problem for all involved. Although interpreters were occasionally asked about patient preferences, Western health care was promoted according to the principle that what was best for native born Americans was best for Southeast Asian refugees. 105 individuals who responded to a general community announcement about this project were contacted and interviewed. 48 students who remained in the program underwent a 4 week pre-vocational course designed to assist them in their preparation for the health training program. After the 30 day pre-vocational course, students were interviewed again to go over their test results and also to offer program options. Because of this program, 9 students were placed in new careers in health occupations; 6 of these had been receiving public assistance. Besides the benefit of providing employment and educational opportunities for the students in the program, refugee students serve as role models, draw other Southeast Asian patients to the clinics where they are employed, and act as liasons when communication problems arise between patient and doctor. The most frustrating obstacle that stood between the students and licensure was the actual licensing examination. Not only was the vocabulary foreign to the students, but the exam has a distinctly Western flavor that did not always test basic nursing concepts.^ieng

A/NJ/8/76 influenza vaccination program: effects on maternal health and pregnancy outcome.

One hundred eighty-nine women who were immunized with Influenza A/New Jersey/8/76 virus vaccine (InfA/NJ) just prior to or during their pregnancy were compared with a control group of 517 pregnant women who did not receive the vaccine. This longitudinal, prospective study demonstrated no association between immunization with InfA/NJ and maternal, perinatal, or infant complications. No teratogenicity was demonstrated, and the two groups of infants did not differ in physical or neurological assessments at birth and at 8 weeks of life.

Identifying conservation units within captive chimpanzee populations.

One of the primary objectives in the captive management of any endangered primate is to preserve as much as possible the genetic diversity that has evolved and still exists in wild gene pools. The rationale for this is based on the theoretical understanding of the relationship between genetic diversity and fitness in response to selection. There remains little consensus, however, as to the type of genetic data that should be used to monitor captive populations. In order to develop a deeper understanding of the degree and nature of genetic diversity among "wild" chimpanzee gene pools, as well as to determine if one type of genetic data is more useful than others, DNA sequence data were generated at three unlinked, nonrepetitive nuclear loci, one polymorphic microsatellite, and the mitochondrial D-loop for 59 unrelated common and pygmy chimpanzees. The results suggest that: 1) data from nuclear loci can be used to differentiate common chimpanzee subspecies; 2) pygmy chimpanzees may have less genetic diversity than common chimpanzees; 3) shared microsatellite alleles do not always indicate identity by descent; and 4) nonrepetitive loci provide unique insights into evolutionary relationships and provide useful information for captive management programs.

Hematocrit values in white, black, and American Indian children with comparable iron status. Evidence to support uniform diagnostic criteria for anemia among all races.

We compared the hematocrit values of 425 black and 164 American Indian children with an equal number of white children who were matched for sex, age, and iron nutrition status based on serum ferritin level. Black children were found to have a mean hematocrit value 0.7% lower than that of white, matched controls. No hematocrit difference was found between American Indian children and their white controls. This finding in blacks is consistent with those of previous series, except the magnitude of the hematocrit difference is smaller. The lower value in blacks may be accounted for by mild thalassemias, which are associated with lower hematocrit values. The use of the same diagnostic criteria for anemia among all races will permit uniform detection of nutritional anemia as well as a greater rate of diagnosis of certain hereditary hemoglobinopathies.

Function studies of monocytes from patients with cyclic neutropenia.

In vitro studies of peripheral blood monocytes from patients with cyclic neutropenia have shown them to be able to phagocytize and kill bacteria as efficiently as PMN's, but not monocytes, from normal controls at both low and high ratios of bacteria to leukocytes. Monocytes from these patients, as well as from normal controls, are able to respond to chemotactic stimuli in vitro. In vivo Rebuck skin-window studies revealed the mononuclear cell response to be normal in these patients, even in the complete absence of circulating and inflammatory exudate neutrophils. These findings suggest that peripheral blood monocytes from patients with cyclic neutropenia are as phagocytically and bactericidally competent as normal peripheral blood neutrophils. As "stimulated" cells, they may serve as an effective line of defense against bacterial infections during periods of neutropenia in these patients.

Sociocultural factors in the use of prenatal care by Hmong women, Minneapolis.

Understanding the sociocultural context of prenatal care underuse by an immigrant population can suggest programmatic changes that result in more effective health care delivery. Ethnographic survey interviews of female Hmong clinic patients conducted in 1987/88 revealed that they objected to biomedical procedures and to being attended by several doctors; the women also reported poor communication with staff as a problem. Clinic reforms implemented in 1989/90 included hiring a nurse-midwife, reducing the number of pelvic examinations, expanding hours of operation, creating a direct telephone line to Hmong interpreters, and producing a Hmong-language prenatal health care education videotape. Women interviewed in 1993 reported a more positive clinic experience.

1% permethrin cream rinse vs 1% lindane shampoo in treating pediculosis capitis.

The therapeutic efficacy and tolerance of a single application of 1% permethrin cream rinse, applied for ten minutes, and a single application of 1% lindane shampoo applied, as recommended by the manufacturer, for four minutes, against the head louse Pediculus humanus var capitis were compared in a single-blinded, randomized, controlled clinical trial. Of 573 patients enrolled at eight centers, 559 were assessable for tolerance and 508 for efficacy. Of the 257 patients treated with 1% permethrin cream rinse, 99% were lice free at 14 days; of the 251 patients treated with 1% lindane shampoo, 85% were lice free at 14 days. The difference is statistically significant. For both treatments, adverse experiences were infrequent, mild, and usually difficult to distinguish from the symptoms of head lice infestation. A single ten-minute application of 1% permethrin cream rinse was well tolerated, highly effective, and therapeutically superior to a single four-minute application of 1% lindane shampoo.