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Acromegaly is associated with increased cardiovascular risk. Although conventional risk factors such as glucose intolerance, hypertension, and dyslipidemia probably contribute, there may also be direct effects of GH/IGF-I excess on the vasculature. To study the effects of GH excess on the vasculature, we have assessed arterial stiffness in acromegalic subjects with and without active disease and have investigated the effects of Sandostatin LAR (OCT-LAR) on vascular function. Sixteen normotensive subjects with acromegaly (10 males and 6 females) and 8 healthy controls were studied. Of the acromegalic subjects, eight had active disease (group A), and eight were cured (GH < 2.5 mU/liter; group B). The three groups were age, sex, and blood pressure matched. Group A subjects were restudied after 3 and 6 months of OCT-LAR therapy. Arterial stiffness was assessed by analyzing central arterial pressure waveforms derived from measured radial artery waveforms. This allowed determination of the augmentation of central pressure and the augmentation index. Lipids, glucose, and IGF-I were also measured. Comparing the three groups (ANOVA; mean +/- SD), the augmentation index was higher in group A (28 +/- 12 vs. 12 +/- 13%; P < 0.01) but not in group B (22 +/- 7 vs. 12 +/- 13%; P = 0.60), compared with controls. IGF-I was higher in group A (50.3 +/- 21.2 nmol/liter; P < 0.01), compared with group B (22.5 +/- 8.9 nmol/liter) and controls (19.5 +/- 5.3 nmol/liter). On regression analysis, IGF-I concentration was identified as a strong independent predictor of the augmentation index (beta = 0.50; P = 0.007). There were no significant differences in aortic systolic pressure, aortic diastolic pressure, lipids, or glucose. Compared with baseline, OCT-LAR treatment resulted in a lowering of augmentation index at 3 months (20 +/- 15 vs. 28 +/- 12%; P < 0.05), but at 6 months (24 +/- 16%; P = 0.21) there was no significant change. IGF-I was reduced from 50.3 +/- 21.2 nmol/liter at baseline to 31.4 +/- 13.2 nmol/liter at 3 months (P < 0.05) and 26.6 +/- 15.8 nmol/liter at 6 months (P < 0.05). In conclusion, acromegaly is associated with changes in the central arterial pressure waveform, suggesting large artery stiffening. This may have important implications for cardiac morphology and performance in acromegaly as well as increasing the susceptibility to atheromatous disease. Large artery stiffness is reduced in cured acromegaly and partially reversed after pharmacological treatment of active disease.

Although GH deficiency may underlie the increased cardiovascular risk in adult hypopituitarism, other coexisting hormonal deficiencies and/or unphysiological hormone replacement may contribute. L-Deamino-8-D-arginine (DDAVP), when administered parenterally, potentiates hemostasis by increasing plasma procoagulant factors. We investigated whether chronic intranasal DDAVP therapy influences clotting factors (plasma fibrinogen, factor VIII, and von Willebrand factor antigen) and endothelial function (flow-mediated dilation of the brachial artery) in 30 GH-treated hypopituitary subjects, including both DDAVP-treated subjects (group A) (mean age, 46 +/- 11 yr) and vasopressin-sufficient subjects (group B) (mean age, 47 +/- 16 yr). Fifteen healthy controls (group C) (mean age, 48 +/- 12 yr) were also studied. All hypopituitary patients were receiving stable GH replacement (median duration, 19 months). Comparing the three groups, concentrations of fibrinogen (mean +/- SD) (A, 3.3 +/- 1.0 g/liter vs. B, 3.5 +/- 0.9 vs. C, 2.6 +/- 0.8, P < 0.05), factor VIII (A, 130% +/- 30% vs. B, 128% +/- 30% vs. C, 104% +/- 35%, P < 0.05) and von Willebrand factor antigen (A, 124% +/- 35% vs. B, 134% +/- 45% vs. C, 93% +/- 36%, P < 0.05) were higher in hypopituitary subjects, compared with controls. However, there were no differences in clotting factors between groups A and B. Flow-mediated dilation did not differ significantly between the two hypopituitary groups (A, 5.9% +/- 2.0% vs. B, 4.7% +/- 1.6%) and was similar to that in the control group (C, 5.7% +/- 2.1%). In conclusion, although endothelium-dependent vasodilation is intact in GH-treated hypopituitary adults, elevated concentrations of hemostatic markers suggest the persistence of a prothrombotic tendency and endothelial dysfunction. Intranasal DDAVP does not appear to influence this proatherogenic profile in hypopituitary adults with vasopressin deficiency.

Sex hormones appear to play a pivotal role in determining cardiovascular risk. Androgen deprivation therapy for males with prostate cancer results in a hypogonadal state that may have important, but as yet undetermined, effects on the vasculature. We studied the effects of androgen deprivation therapy on large artery stiffness in 22 prostate cancer patients (mean age, 67 +/- 8 yr) over a 6-month period. Arterial stiffness was assessed using pulse-wave analysis, a technique that measures peripheral arterial pressure waveforms and generates corresponding central aortic waveforms. This allows determination of the augmentation of central pressure resulting from wave reflection and the augmentation index, a measure of large artery stiffness. Body compositional changes were assessed using bioelectrical impedance analysis. Fasting lipids, glucose, insulin, testosterone, and estradiol were measured. After a 3-month treatment period, the augmentation index increased from 24 +/- 6% (mean +/- SD) at baseline to 29 +/- 9% (P = 0.003) despite no change in peripheral blood pressure. Timing of wave reflection was reduced from 137 +/- 7 to 129 +/- 10 msec (P = 0.003). Fat mass increased from 20.2 +/- 9.4 to 21.9 +/- 9.6 kg (P = 0.008), whereas lean body mass decreased from 63.2 +/- 6.8 to 61.5 +/- 6.0 kg (P = 0.016). There were no changes in lipids or glucose during treatment. Median serum insulin rose from 11.8 (range, 5.6-49.1) to 15.1 (range, 7.3-83.2) mU/liter at 1 month (P = 0.021) and to 19.3 (range, 0-85.0 mU/liter by 3 months (P = 0.020). There was a correlation between the changes in fat mass and insulin concentration over the 3-month period (r = 0.56; P = 0.013). In a subgroup of patients whose treatment was discontinued after 3 months, the augmentation index decreased from 31 +/- 7% at 3 months to 29 +/- 5% by 6 months, in contrast to patients receiving continuing treatment in whom the augmentation index remained elevated at 6 months compared with baseline (P = 0.043). These data indicate that induced hypogonadism in males with prostate cancer results in a rise in the augmentation of central arterial pressure, suggesting large artery stiffening. Adverse body compositional changes associated with rising insulin concentrations suggest reduced insulin sensitivity. These adverse hemodynamic and metabolic effects may increase cardiovascular risk in this patient group.

Primary hyperparathyroidism (PHPT) is associated with increased cardiovascular risk, although the mechanisms involved remain unclear. Recent evidence has shown increased pulse pressure to be a powerful predictor of cardiovascular events. As increases in pulse pressure are due largely to arterial stiffening, we measured arterial stiffness in 21 subjects with PHPT (18 women and 3 men; 46-71 yr old) and 21 age- and sex-matched healthy controls using pulse wave analysis, a technique that measures peripheral arterial pressure waveforms and generates corresponding central aortic waveforms. This allows determination of the augmentation of central pressure resulting from wave reflection and augmentation index, a measure of vessel stiffness. Metabolic parameters were also measured. The serum calcium level among PHPT subjects was (mean +/- SD) 2.74+/-0.14 mmol/L. pulse wave analysis showed that both augmentation and the augmentation index were significantly higher in the PHPT group vs. controls [16+/-5 vs. 10+/-4 mm Hg (P < 0.001) and 36+/-9% vs. 25+/-6% (P < 0.001)] despite comparable brachial systolic pressures between groups (136+/-13 vs. 134+/-18 mm Hg). Patients with PHPT had higher fasting serum insulin levels [median (range), 15.8 (7.4-39.4) vs. 11.6 (5.1-23) mU/L; P < 0.05] and triglyceride (1.6+/-0.6 vs. 1.2+/-0.4 mmol/L; P < 0.05), but lower high density lipoprotein cholesterol (1.4+/-0.4 vs. 1.6+/-0.3 mmol/L; P < 0.05). These data indicate that subjects with mild PHPT (calcium, <3.0 mmol/L) have increased arterial stiffness, as evidenced by higher augmentation of central aortic pressures. Enhanced vessel stiffness may arise from a combination of structural and functional vascular changes due to hypercalcemia and/or metabolic abnormalities. Increased vascular stiffness in subjects with PHPT may account in part for the increased cardiovascular risk in this group.

Modelled structures of the acetylcholine receptor-mimicking antibody, Malpha2-3, both free and bound to its antigen, toxin alpha, are assessed in the light of new experimental mutational data from functional mapping of the paratopic region of Malpha2-3. The experimental results are consistent with the previously-predicted structure of the free antibody, and also demonstrate that structural particularities of the Malpha2-3 combining site that were identified in the models play a role in the protein association. The modelled conformations of the hypervariable loops are discussed in the context of recent new data and analyses. The new mutational data allow several previously-considered modelled structures of the complex to be rejected. Two quite similar models now remain.

The hormonal precursor pro-ocytocin-neurophysin is activated by selective cleavage at Arg2-Ala13, producing mature ocytocin and neurophysin. To understand the cleavage mechanism better, and in particular the recognition of the cleavage site, it is necessary to characterize the three-dimensional structure of the precursor molecule. Here we combine a variety of experimental data with molecular modeling and dynamics calculations to derive possible precursor conformations. In the models obtained, the N-terminus of the precursor, corresponding to the ocytocin segment, is hydrogen bonded in a pocket of the neurophysin moiety in a similar manner to a crystallographically obtained non-covalent complex between the two molecules. The calculations suggest that although the ocytocin segment is relatively flexible, it adopts a stable, broad loop structure in the vicinity of the cleavage region, which may constitute the structural element recognized by the cleaving enzyme. The calculations also suggest a possible widening of the distance between the two neurophysin domains in the precursor relative to that in the non-covalent neurophysin-ocytocin complex.

In the South-East Asia Region (SEAR) of WHO, paralytic poliomyelitis has decreased from 25,711 cases in 1988 to 3304 cases in 1995, representing an 87% reduction. By 1995, in 6 of 10 member countries--India, Bangladesh, Myanmar, Nepal, Indonesia, and Democratic People's Republic of Korea--polio remained endemic. Two countries, Sri Lanka and Thailand, appear close to polio eradication, and 2, Bhutan and Maldives, reported no cases during 1989-1995. Although reported rates of acute flaccid paralysis and the percentage of cases virologically investigated are low in some countries, no isolates of wild poliovirus type 2 have been reported outside India since 1993. By the end of 1996, all 8 countries in which polio is endemic will have conducted national immunization days for polio eradication. The major challenge for polio eradication in SEAR will be strengthening surveillance, because national immunization days alone cannot eradicate polio.

The decision to develop rotavirus vaccines was predicated on the extensive burden of rotavirus disease among children worldwide. US reports on nationwide hospitalizations (1979-1992) and deaths (1968-1991) due to diarrhea and weekly reports of rotavirus infection by 74 laboratories were reviewed to estimate the burden of rotavirus disease, identify epidemiologic trends, and consider methods for evaluating an immunization program when a vaccine becomes available. From 1968 to 1985, diarrhea-related deaths among US children <5 years old declined from 1100 to 300/year. This decline was associated with the disappearance of winter peaks for diarrhea-related deaths previously associated with rotavirus infection among children 4-23 months old. From 1979 to 1992, however, hospitalizations for diarrhea averaged 186,000/year and retained their winter peaks, which have been linked to rotavirus infections. Each year an estimated 54,000-55,000 US children are hospitalized for diarrhea, but <40 die with rotavirus. A rotavirus vaccine program will require improved surveillance, including the timely collection of data from sentinel hospitals, in which a diagnosis of rotavirus can be established or ruled out for all children hospitalized for diarrhea.

Photoperiodic regulation of the melatonin rhythm was studied in juvenile Djungarian hamsters to test the hypothesis that magnetic field (MF) exposures disrupt sexual maturation. Juveniles in long or short days postweaning were exposed each day to a 1-gauss 60-Hz MF (15 min, 2 h before lights-off). At age 25 days, nighttime duration of the melatonin rise in the pineal gland and circulation of sham-treated controls (adjacent coil system but without current) was < 8 h in long-day juveniles and nearly 13 h in short-day hamsters. This is the first study in juveniles to demonstrate that the melatonin rhythm duration is regulated by photoperiod and that reproductive development was not disrupted by daily or acute MF exposures; puberty was initiated in long days but arrested by short days, irrespective of MF treatment. In a replicate study, MF exposures had no effect on the duration of increased melatonin. In the initial and the replicate study, amplitude differences in the nighttime pineal or serum melatonin rise possibly reflected inherent variability in repetitive melatonin rhythms. In addition, effects of daily melatonin injections to arrest puberty were not blocked by daily MF exposures. The findings support the conclusion that MF exposures fail to disrupt photoperiodic time measurement or the neuroendocrine mechanism regulating reproductive maturation in the juvenile Djungarian hamster.

Data are presented showing that rats can discriminate among sucrose solution concentrations by some cue other than taste, possibly by olfaction. Non-taste factors need to be considered in taste discrimination studies.

Structural features associated with the ability of a monoclonal antibody (mAb) to discriminate between protein variants are identified and engineered. The variants are the curaremimetic toxin alpha from Naja nigricollis and erabutoxin a or b from Laticauda semifasciata, which differ from each other by 16 substitutions and one insertion. The neutralizing mAb M alpha 1 recognizes with high affinity a topographical epitope on the surface of toxin alpha, but fails to recognize the erabutoxins although they possess most of the residues forming the presumed epitope. Examinations of the toxin alpha and erabutoxin 3-D structures and molecular dynamics simulations reveal several differences between the variants. In particular, the region involving the beta-turn 17-24 is organized differently. Analysis of the differences found in this region suggest that the insertion (or deletion) at position 18 of the variant amino acid sequences is particularly important in determining the differential cross-reactivity. To test this proposal, residue 18 was deleted in one erabutoxin using site-directed mutagenesis, and the biological properties of the resulting mutant were examined. We found that full antigenicity was restored in the previously unrecognized variant. The implications of this finding are discussed.

A reliable short-term NaCl taste test was developed for rats which resulted in differential responding to a variety of concentrations. The rats were required to exist on a low sodium diet for 8-10 days prior to the initiation of testing. The peak response in this test was to isotonic NaCl with lesser responding to hyper- and hypotonic solutions. After stable responding was obtained, bilateral sections were made of the chorda tympani nerves. This surgery resulted in a loss of sensitivity to the lowest hypotonic solutions (0.03 and 0.06 M NaCl). Little, if any, effect was noted in the perception of sucrose following these nerve sections.

The recent development of yeast artificial chromosome (YAC) vectors has provided a system for cloning fragments that are over ten times larger than those that can be cloned in more established systems. We have developed a method for the rapid isolation of terminal sequences from YAC clones. The YAC clone is digested with a range of restriction enzymes, a common linker is ligated to the DNA fragments and terminal sequences are amplified using a vector specific primer and a linker specific primer. Sequence data derived from these terminal specific products can be used to design primers for a further round of screening to isolate overlapping clones. The method also provides a convenient method of generating Sequence Tagged Sites for the mapping of complex genomes.

The construction of a yeast artificial chromosome (YAC) primary gridded library of 35,000 clones from human lymphoblastoid (48,XXXX) cell line DNA is described. The average YAC size is approximately 350kb representing a greater than 3.5 times coverage of the genome. The library is stored at -70 degrees C as gridded clones on nylon filters impregnated with 20% glycerol and as glycerol suspensions of individual clones in microtitre plates providing a prolonged multi-user potential. To date we have used 14 single copy probes to screen this library by colony hybridisation as well as PCR and have isolated between 1 and 5 YAC clones for every probe.

Using synthetic oligodeoxyribonucleotides to prime the transcription of interferon mRNA and cDNA, we recently determined the mRNA sequence coding for the 47 amino-terminal amino acids of mature human fibroblast interferon (1). From this sequence, we have now synthesised an oligodeoxyribonucleotide that is homologous with the mRNA sequence coding for amino acids 42-45 and used it as a primer to selectively transcribe an interferon cDNA template. The sequence of the newly synthesised DNA predicted the sequence of amino acids 48-109 in the interferon polypeptide. By repeating this process with one more primer, we have determined the complete amino acid sequence of mature human fibroblast interferon, a polypeptide of 166 amino acids.

Field studies and epidemiological surveys may necessitate obtaining a blood sample from a nonfasted subject for nutritional assessments. We measured the effect of a standardized test meal, eaten after an overnight fast, on the concentrations of seven carotenoid fractions, retinol, and tocopherol in plasma of eight healthy adults. The 790-calorie test meal did not alter the measured concentrations. We conclude that blood sampled up to 4 h after breakfast can be validly used for these measurements.

A method is described for the preparation of p-aminophenyl oligo(dT)-Sepharose. This matrix has been used for the purification of polynucleotide phosphorylase from both E.coli and B.stearothermophilus. The effects of temperature and pH on the binding of the different enzymes to the matrix have been investigated. B.stearothermophilus isolated by affinity chromatography may be useful in selectively removing the polyA tract on the 3'-end of mRNA's.

The results of ribonuclease T1 oligonucleotide fingerprint analyses indicate that influenza virus messenger RNAs are incomplete transcripts of the corresponding genome RNAs and that in this respect they differ from the unpolyadenylated virus specific complementary RNAs obtained from infected cells. From the position of the untranscribed oligonucleotide in the virus RNA sequence and the ability or inability of the different transcripts to protect the 5' terminal nucleotide of virus RNAs against nuclease S1 digestion, it is concluded that whereas the unpolyadenylated cRNAs are complete transcripts, the polyadenylated messenger RNAs lack sequences complementary to the 5' end of the genome molecules.

A rare cDNA coding for most of the alpha subunit of the Torpedo nicotinic acetylcholine receptor has been cloned into bacteria. The use of a mismatched oligonucleotide primer of reverse transcriptase facilitated the design of an efficient, specific probe for recombinant bacteria. DNA sequence analysis has enabled the elucidation of a large part of the polypeptide primary sequence which is discussed in relation to its acetylcholine binding activity and the location of receptor within the plasma membrane. When used as a radioactive probe, the cloned cDNA binds specifically to a single Torpedo mRNA species of about 2350 nucleotides in length but fails to show significant cross-hybridisation with alpha subunit mRNA extracted from cat muscle.

We investigated the effects of storage and handling on measured values for carotenoids, retinol, and tocopherol in plasma. We found no significant differences in the concentrations of these analytes measured in plasma samples that were frozen immediately after separation as compared with replicate samples maintained at room temperature in the dark for 24 h. Analytes were stable in solvents for at least 18 h at 23 degrees C after extraction. Purging samples with nitrogen gas before freezing had no detectable beneficial effects. All analytes were stable in plasma stored at -70 degrees C for at least 28 months or at -20 degrees C for five months. By 15 months the concentrations of carotenoids were significantly less (P less than 0.05) in plasma stored at -20 degrees C than in plasma stored at -70 degrees C, while retinol and tocopherol concentrations were not significantly different. Concomitant with the decrease in carotenoids was the appearance of unidentified peaks in the ultraviolet. Adding ascorbic acid or butylated hydroxytoluene antioxidants to the precipitating solvent did not alter the losses of carotenoids or alter the appearance of unidentified peaks. Under appropriate conditions, plasma carotenoids, retinol, and tocopherol are stable for more than two years.

In the Micronesian island of Ponape blood pressures were found in 1947 and again in 1953 to be very low and to show no difference between age groups. As part of the US Trust Territory of the Pacific from 1945, the island had begun to change in the direction of modernity, the changes being most dramatic in the capital town of Kolonia, but no part of the island being unaffected. After a generation of modernization, a cross-sectional study was done to assess the impact of changing way of life on blood pressure. Communities were sampled at three levels of impact of modernization: the capital town of Kolonia, an intermediate area, and a remote area. No differences in salt intake were found for the three areas; but the population in the most modern area was younger and heavier. No consistent ecological differences were found in blood pressure level. Since there is considerable variation in modernity within each area, a Guttman-type scale of individual modernity was developed. No trends of variation of blood pressure with modernization were found to be consistent for both sexes and all areas. However, among males in the most modern area both systolic and diastolic pressures increased consistently with increasing modernity, controlling for age. For diastolic pressures, significant increases were found for all males, Kolonia males, and intermediate area males. When body mass as well as age were controlled, the strength of the trends decreased. But among Kolonia males the increase of diastolic pressure with increasing modernity remained highly significant; that of systolic pressure, marginally significant.

The content, chemical form, and distribution of mercury and selenium in edible tissue were determined for several samples of fish and other marine animal organisms (mollusks, crustaceans and pods). For most fish samples, except Pacific blue marlin, 53 to 94% of the total mercury content was present as methylmercury, being notably higher in freshwater species. Other marine organisms, except shrimp, contained only 29 to 47% methylmercury. For all samples, a significant part of the total selenium content (4 to 47%) was present as selenate (Se VI). Tissue selenium levels did not correlate with corresponding mercury levels. In freshwater and older processed (canned) marine fish, except marlin, 55 to 80% of the total mercury content was water-extractable. For non-processed (fresh) and newly-processed marine samples, only 22 to 47% was extractable. On a percentage basis, inorganic mercury was generally more extractable than methylmercury. For all fish samples, except marlin, 55 to 60% of the total selenium content was water-extractable, while only 35 to 45% was extractable for other marine species. On a percentage basis, Se VI was more extractable than selenite (Se IV) and selenide (Se II).

Frequently it is assumed that concentrations of biochemical analytes are similar for serum and plasma, without regard to the anticoagulant. Recently it has been hypothesized that use of certain anticoagulants results in an osmotic redistribution of fluid between blood cells and plasma, causing some dilution of the plasma. We sought to determine the effect of two commonly used anticoagulants, heparin and citrate, on the measured concentrations of 13 clinical-chemical analytes, including selected trace elements, vitamins, lipids, and proteins. The data demonstrate that hyperosmolar citrate causes a significant dilution of all indices measured. In contrast, heparin had no osmotic effect; concentrations of most of the analytes measured in the heparinized plasma were statistically no different from those measured in the corresponding serum. Therefore, anticoagulants must be chosen carefully, especially if concentrations in plasma and serum are to be compared.

We have improved the "polymerase chain reaction" (PCR) to permit rapid analysis of any known mutation in genomic DNA. We demonstrate a system, ARMS (Amplification Refractory Mutation System), that allows genotyping solely by inspection of reaction mixtures after agarose gel electrophoresis. The system is simple, reliable and non-isotopic. It will clearly distinguish heterozygotes at a locus from homozygotes for either allele. The system requires neither restriction enzyme digestion, allele-specific oligonucleotides as conventionally applied, nor the sequence analysis of PCR products. The basis of the invention is that unexpectedly, oligonucleotides with a mismatched 3'-residue will not function as primers in the PCR under appropriate conditions. We have analysed DNA from patients with alpha 1-antitrypsin (AAT) deficiency, from carriers of the disease and from normal individuals. Our findings are in complete agreement with allele assignments derived by direct sequencing of PCR products.

From recently published data on the amino-terminal structures of human and mouse interferons, we have predicted and synthesised an oligonucleotide capable of priming specifically the reverse transcription of human fibroblast interferon mRNA present within a total mRNA population. From these transcripts we determined the sequence of the 5'-terminus of the mRNA and identified a putative pre-peptide signal sequence. This enabled us to predict the sequence of another primer capable of directing the synthesis of interferon double-stranded cDNA corresponding to the entire coding region of the mRNA. Further sequencing studies also enabled us to establish the identity of 47 consecutive amino acids beginning with the methionine residue at the amino-terminus of the mature protein.

To assess the usefulness of vital statistics and surveillance for monitoring abortion mortality, the authors compared data from two systems of classification: 1) deaths classified according to the underlying cause by the National Center for Health Statistics (NCHS) under the International Classification of Disease, Adapted (ICDA) code numbers 640-645 (abortion) for 1972-1975; and 2) abortion-related deaths reported to the Center for Disease Control (CDC) through its epidemiologic surveillance of abortion mortality for the same years. Vital statistics classifications dealing with the underlying cause of death are based on criteria defined by ICDA guidelines applied to all available information listed on death certificates, and exclude some deaths classified as abortion-related by CDC. Surveillance classifications are based on broader criteria developed by CDC for expanded data gathered by individual case investigation. Results showed that the surveillance techniques had identified more deaths as abortion-related and had resolved more cases into the specific abortion categories of legal, illegal, and spontaneous than vital statistics tabulations based on death certificates. The authors estimate that the surveillance system alone reported 88% of all abortion-related deaths, the vital statistics system 52%, and the two systems combined a total of 94%. Inadequate physician documentation on the death certificate was the primary reason vital statistics data contained a smaller number of reported abortion deaths than surveillance data.

The content, chemical form, and distribution of mercury and selenium were determined for selected samples of human and animal tissue by gas chromatography. Methylmercury averaged 38.7% of the total mercury content in homogenized human brain. For human heart, spleen, liver, kidney and placenta, methylmercury comprised 40.2%, 57.0%, 39.6%, 6.0% and 57.1% respectively, of the total mercury content. Similar results were obtained for the heart and liver of a whitetail deer. Methylmercury represented 9.1%, 62.9% and 24.1% of the total mercury content in seal liver, seal meat and deer meat, respectively. For all samples, a significant portion of the total selenium content, averaging 27%, was present as selenate (Se VI). Tissue selenium content did not correlate with the corresponding mercury content. In brain, heart and placenta, and in seal liver and meat, 53% to 80% of the total mercury content was water-extractable. For human kidney, liver and spleen, and deer meat, only 15% to 45% of the total mercury was extractable. On a percentage basis, inorganic mercury was more extractable than methylmercury, except for human kidney and liver, and deer meat. For all samples, except kidney, liver and deer meat, 55% to 76% of the total selenium content was water-extractable, Se VI being more extractable on a percentage basis than selenite (Se IV) and selenide (Se-II).