Ancient, highly polymorphic human major histocompatibility complex DQA1 intron sequences.

A 438 basepair intron 1 sequence adjacent to exon 2 in the human major histocompatibility complex DQA1 gene defined 16 allelic variants in 69 individuals from wide ethnic backgrounds. In contrast, the most variable coding region spanned by the 247 basepair exon 2 defined 11 allelic variants. Our phylogenetic human intron 1 tree derived by the Bootstrap algorithm reflects the same relative allelic relationships as the reported DQA1 exon 2 tree [Gyllensten and Erlich, Hum Immunol 36:1-10, 1989]. Thus 3' DQA1 intron 1 and exon 2 have cosegregated since divergence of the human races. Comparison of human alleles to a Rhesus monkey DQA1 first intron sequence found only 10 nucleotide substitutions unique to Rhesus, with the other 428 positions (98%) found in at least one human allele. This high degree of homology reflects the evolutionary stability of intron sequences since these two species diverged over 20 million years ago. Because more intron 1 alleles exist than exon 2 alleles, these polymorphic introns can be used to improve tissue typing for transplantation, paternity testing, and forensics and to derive more complete phylogenetic trees. These results suggest that introns represent a previously underutilized polymorphic resource.

Strategy for definition of DR/DQ haplotypes in the 4AOHW cell panel using noncoding sequence polymorphisms.

Our previously described intron-based DQA1-typing method provides 11 allelic and suballelic groups, including the eight alleles encoded at the second exon. Concurrent testing for the presence of the DRB3, DRB4, and DRB5 loci and the Rsa I pattern of the DRw52 group simplifies the typing requirements for allele assignment at the highly polymorphic DRB1 locus. The DRB1-allele-shortlisting process relies on known DR/DQ haplotypes. In addition to reducing the testing requirements for definitive DRB1 allele assignment, this strategy allows inference of the DR/DQ haplotype and assists in recognition of novel and/or unusual associations.

Occupational risk factors for infection with parvovirus B19 among pregnant women.

To identify exposures associated with parvovirus B19 infection during pregnancy, two groups of pregnant women were studied during an outbreak of erythema infectiosum (EI). Of 796 pregnant women from Connecticut who were tested serologically because of perceived exposure to B19, 53% (419/796) had serologic evidence of previous B19 infection, and 6% (23/376) of the rest had evidence of recent infection. Of 121 pregnant women who had not requested testing but who lived in a community where a large outbreak of EI had occurred among schoolchildren, 36% (43/121) had serologic evidence of previous infection, and only 3% (2/78) of the rest had had a recent infection. In the exposed group, 479 women returned a supplemental exposure questionnaire. The highest infection rates among susceptible women were for schoolteachers (16%, 10/64), followed by day care workers (9%, 2/22) and homemakers (9%, 4/46). Women working outside the home but not in school or day care settings had the lowest risk (4%, 3/80). This study suggests that there is risk for B19 infection in selected occupational settings and in households.

Management and outcomes of pregnancies complicated by human B19 parvovirus infection: a prospective study.

During a large statewide outbreak of fifth disease in Connecticut in 1988, 39 pregnant women were identified who had serologic evidence of recent human B19 parvovirus infection. The patients were followed up prospectively with targeted fetal ultrasonographic examinations to detect signs of fetal hydrops. Of these 39 pregnant women, 37 had healthy infants and two patients had miscarriages. None of the fetuses developed hydrops. We propose that pregnant women exposed to B19 parvovirus be tested for evidence of IgG and IgM B19-specific antibodies and that targeted fetal ultrasonography be considered when IgM antibodies are found. Percutaneous umbilical blood sampling and intrauterine transfusion can be considered in cases of B19 parvovirus-associated hydrops and anemia. The overall fetal loss rate in this prospective follow-up group was 5%.

Human parvovirus infection in pregnancy.

During an outbreak of fifth disease in the Hartford, Connecticut area in the winter of 1986, nine pregnant women were exposed to the parvovirus. Five of these nine had serologic evidence of previous exposure and immunity; all five had uneventful pregnancies. Three of the four women who exhibited serologic evidence of recent exposure to the parvovirus had hydropic fetuses who died, one of whom was anencephalic. Histologic and DNA hybridization studies suggest parvovirus infection as a cause for nonimmune hydrops and fetal death. A review of the literature suggests that of 37 women who were exposed and infected by human B19 parvovirus during pregnancy, 14 (38%) had adverse outcomes, including spontaneous abortions, intrauterine fetal death, and congenital anomalies. Women at high risk for exposure (school teachers) should have screening for immunoglobulin G parvovirus-specific antibodies; if these are absent, they should avoid close contact with schoolchildren. Pregnant women with evidence of recent infection should have a level II ultrasound. Because no vaccine is currently available, routine screening cannot be recommended.

The trans-most cisternae of the Golgi complex: a compartment for sorting of secretory and plasma membrane proteins.

The intracellular site for the sorting of proteins destined for regulated or constitutive pathways is presently unknown for any one cell. By immunoelectron microscopy, we directly followed the routes taken by a regulated hormone, insulin, and a constitutive protein, hemagglutinin. Both proteins are present in individual Golgi stacks where they appear randomly distributed throughout the cisternae. In contrast, the two proteins do not colocalize outside the Golgi area:insulin is concentrated in dense-core secretory granules, while hemagglutinin is found predominantly in clear 100-300 nm vesicles. These vesicles do not label significantly with an endocytic tracer, indicating that they are exocytic carriers for hemagglutinin. The site at which the two proteins diverge is the clathrin-coated, trans-most cisterna of the Golgi, where the packaging of proinsulin takes place.

Staging of non-small cell bronchogenic carcinoma. Relationship of the clinical evaluation to organ scans.

Organ scans are generally performed on patients with bronchogenic carcinoma only when clinical evaluation is suspicious for metastases. However, it is not clear whether the clinical abnormalities will direct attention to the single organ which should be scanned, or if all three organs (bone, brain, liver) should be evaluated if any clinical abnormality is present. We investigated the use of triple organ radionuclide scanning and computerized tomography (CT) of the brain in the initial staging of patients with non-small cell bronchogenic carcinoma with no obvious metastases. Of 122 patients with newly diagnosed lung cancer, 53 met our criteria for further study. Thirty-three (62 percent) of these had at least one clinical abnormality suggestive of metastasis. Bone scanning detected metastases in seven (21 percent) and head CT in two additional patients (6 percent). Brain and liver scanning had no yield. In only five of these nine patients did the clinical abnormality direct attention to the organ with detectable metastases. Twenty of the 53 (38 percent) patients had a negative routine clinical evaluation, yet bone scanning showed metastases in three (15 percent). We concluded that clinical abnormalities are not specific for the organ in which metastases may be detected, so three scans (bone, liver, CT of the brain) should be obtained if there is any suspicion of metastasis based on history, physical examination, and laboratory tests. The value of bone scanning in clinically normal patients deserves further study.

Role of fiberoptic bronchoscopy in patients with hemoptysis and a normal chest roentgenogram.

We reviewed the charts of 48 consecutive patients who had fiberoptic bronchoscopy performed in the evaluation of hemoptysis with a normal chest roentgenogram. Fiberoptic bronchoscopy provided a diagnosis other than endobronchial inflammation in only four patients--benign fibromuscular polyp in one patient, Mycobacterium tuberculosis in 1 patient, and carcinoma in two others. A literature review revealed an overall 3 percent incidence of bronchogenic carcinoma in patients with hemoptysis and normal findings on chest roentgenogram. Other than abnormal findings on chest roentgenogram, risk factors for carcinoma in patients with hemoptysis include: (1) age greater than 40; (2) significant smoking history; and (3) duration of hemoptysis for longer than one week. We concluded that in patients with hemoptysis and normal chest x-ray film findings, routine fiberoptic bronchoscopy may not always be indicated to rule out malignancy.

Lipoid pneumonia caused by an Oriental folk medicine.

With recognition of the problem of aspiration, mineral oil has been removed from nose drops. We have described a Thai woman who had lipoid pneumonia after instillation of a common Oriental folk medicine. At 2 1/2-year follow-up, she had persistent cough, interstitial disease, air trapping, and widened A-aDO2.

Comparative effectiveness of preoptic and tuberal stimulation for luteinizing hormone release and ovulation in two strains of rats.

Proestrous rats under pentobarbital anesthesia during the 'critical period' were electrically stimulated in either the medial preoptic area (mPOA) or the anterior basal tuber. In Osborne-Mendel (O-M) and Charles River CD rats, comparisons were made of the ovulatory responses to trains of matched biphasic pulse pairs of different microamperage, 30 sec on and 30 sec off for 45 min. In CD rats, comparisons were made of the relative efficiencies of stimulation through a coaxial platinum electrode near the midline and a pair of platinum electrodes spaced bilaterally 2 mm apart across either the mPOA or the tuber. Other comparisons, with either type of electrode in the basal tuber, were made between 4-day and 5-day cyclic CD rats with respect both to the ovulatory responses and to the serum concentrations of LH 90 min after the start of the 45-min stimulus. In both O-M and CD rats, tuberal stimulation was more effective for ovulation than mPOA stimulation. CD rats were much less responsive to mPOA stimulation (spaced electrodes) than O-M rats, but the responses of both strains to tuberal stimulation were essentially alike. In 4-day cyclic CD rats, the ovulatory responses to mPOA stimulation with the coaxial electrode were much superior to those from spaced-electrode stimulation. In contrast, tuberal stimulation with either type of electrode gave equivalent ovulation frequencies and equivalent tubal ovum numbers in both 4-day and 5-day cyclic rats. However, the serum LH concentrations disclosed somewhat better responses to stimulation with the coaxial electrode (coaxial/spaced=1.57). The advantage of stimulation with the coaxial electrode may be due to high current density or, at least in part, to its more medial location. The results are compatible with the concept of preoptic-tuberal neuronal system, diffuse rostrally and convergent upon the medial basal tuber, controlling the ovulatory surge of LH.