Showing papers by "University of Texas Health Science Center at Houston published in 1985"

A new method for estimating synonymous and nonsynonymous rates of nucleotide substitution considering the relative likelihood of nucleotide and codon changes.

Abstract: A new method is proposed for estimating the number of synonymous and nonsynonymous nucleotide substitutions between homologous genes. In this method, a nucleotide site is classified as nondegenerate, twofold degenerate, or fourfold degenerate, depending on how often nucleotide substitutions will result in amino acid replacement; nucleotide changes are classified as either transitional or transversional, and changes between codons are assumed to occur with different probabilities, which are determined by their relative frequencies among more than 3,000 changes in mammalian genes. The method is applied to a large number of mammalian genes. The rate of nonsynonymous substitution is extremely variable among genes; it ranges from 0.004 X 10(-9) (histone H4) to 2.80 X 10(-9) (interferon gamma), with a mean of 0.88 X 10(-9) substitutions per nonsynonymous site per year. The rate of synonymous substitution is also variable among genes; the highest rate is three to four times higher than the lowest one, with a mean of 4.7 X 10(-9) substitutions per synonymous site per year. The rate of nucleotide substitution is lowest at nondegenerate sites (the average being 0.94 X 10(-9), intermediate at twofold degenerate sites (2.26 X 10(-9)). and highest at fourfold degenerate sites (4.2 X 10(-9)). The implication of our results for the mechanisms of DNA evolution and that of the relative likelihood of codon interchanges in parsimonious phylogenetic reconstruction are discussed.

Memory processing of serial lists by pigeons, monkeys and people

Abstract: List memory of pigeons, monkeys, and humans was tested with lists of four visual items (travel slides for animals and kaleidoscope patterns for humans). Retention interval increases for list-item memory revealed a consistent modification of the serial-position function shape: a monotonically increasing function at the shortest interval, a U-shaped function at intermediate intervals, and a monotonically decreasing function at the longest interval. The time course of these changes was fastest for pigeons, intermediate for monkeys, and slowest for humans.

Gene genealogy and variance of interpopulational nucleotide differences.

Abstract: A mathematical theory is developed for computing the probability that m genes sampled from one population (species) and n genes sampled from another are derived from l genes that existed at the time of population splitting. The expected time of divergence between the two most closely related genes sampled from two different populations and the time of divergence (coalescence) of all genes sampled are studied by using this theory. It is shown that the time of divergence between the two most closely related genes can be used as an approximate estimate of the time of population splitting (T) only when T identical to t/(2N) is small, where t and N are the number of generations and the effective population size, respectively. The variance of Nei and Li's estimate (d) of the number of net nucleotide differences between two populations is also studied. It is shown that the standard error (Sd) of d is larger than the mean when T is small (T much less than 1). In this case, Sd is reduced considerably by increasing sample size. When T is large (T greater than 1), however, a large proportion of the variance of d is caused by stochastic factors, and increase in the sample size does not help to reduce Sd. To reduce the stochastic variance of d, one must use data from many independent unlinked gene loci.

The MRFIT behavior pattern study. II. Type A behavior and incidence of coronary heart disease.

Abstract: Behavior pattern was assessed by interview for 3,110 men at eight centers in the Multiple Risk Factor Intervention Trial (1973-1976). The Type A pattern was not significantly associated with risk of first major coronary events (coronary death and definite nonfatal myocardial infarction) after a mean follow-up of 7.1 years. Crude relative risks for Types A1-A2 versus X-B were 1.08 in usual care, 0.82 in special intervention, and 0.92 overall. Adjustment for age, blood pressure, cigarette smoking, serum cholesterol, consumption of alcohol, and educational attainment yielded relative risks of 0.99 in usual care, 0.81 in special intervention, and 0.87 overall (95% confidence interval = 0.59-1.28). The Jenkins Activity Survey Type A score, obtained for 12,772 men at all 22 centers, was also not significantly associated with risk of first major coronary events. Overall, crude risks in the lowest (Type B) through highest (Type A) quintiles of the score's distribution were 5.0%, 4.4%, 4.0%, 4.3%, and 4.1%, respectively. The proportional hazards regression coefficient, adjusted for the variables listed above, was -0.006 (95% confidence interval = -0.015-0.003). These results raise questions regarding the robustness of the Type A hypothesis in its present form. Further studies are needed to investigate these questions and to evaluate the validity of procedures used to assess behavior patterns.

Methods for computing the standard errors of branching points in an evolutionary tree and their application to molecular data from humans and apes.

Abstract: Statistical methods for computing the standard errors of the branching points of an evolutionary tree are developed. These methods are for the unweighted pair-group method-determined (UPGMA) trees reconstructed from molecular data such as amino acid sequences, nucleotide sequences, restriction-sites data, and electrophoretic distances. They were applied to data for the human, chimpanzee, gorilla, orangutan, and gibbon species. Among the four different sets of data used, DNA sequences for an 895-nucleotide segment of mitochondrial DNA (Brown et al. 1982) gave the most reliable tree, whereas electrophoretic data (Bruce and Ayala 1979) gave the least reliable one. The DNA sequence data suggested that the chimpanzee is the closest and that the gorilla is the next closest to the human species. The orangutan and gibbon are more distantly related to man than is the gorilla. This topology of the tree is in agreement with that for the tree obtained from chromosomal studies and DNA-hybridization experiments. However, the difference between the branching point for the human and the chimpanzee species and that for the gorilla species and the human-chimpanzee group is not statistically significant. In addition to this analysis, various factors that affect the accuracy of an estimated tree are discussed.

Inactivation of Norwalk virus in drinking water by chlorine.

Abstract: Norwalk virus in water was found to be more resistant to chlorine inactivation than poliovirus type 1 (LSc2Ab), human rotavirus (Wa), simian rotavirus (SA11), or f2 bacteriophage. A 3.75 mg/liter dose of chlorine was found to be effective against other viruses but failed to inactivate Norwalk virus. The Norwalk virus inoculum remained infectious for five of eight volunteers, despite the initial presence of free residual chlorine. Infectivity in volunteers was demonstrated by seroconversion to Norwalk virus. Fourteen of 16 subjects receiving untreated inoculum seroconverted to Norwalk virus. Illness was produced in four of the eight volunteers and in 11 of 16 control subjects. A similar Norwalk virus inoculum treated with a 10 mg/liter dose of chlorine produced illness in only one and failed to induce seroconversion in any of eight volunteers. Free chlorine (5 to 6 mg/liter) was measured in the reaction vessel after a 30-minute contact period. Norwalk virus appears to be very resistant to chlorine which may explain its importance in outbreaks of waterborne disease.

Transpulmonary passage of venous air emboli

Abstract: Twenty-seven paralyzed anesthetized dogs were embolized with venous air to determine the effectiveness of the pulmonary vasculature for bubble filtration or trapping. Air doses ranged from 0.05 to 0.40 ml X kg-1 X min-1 in 0.05-ml increments with ultrasonic Doppler monitors placed over arterial vessels to detect any microbubbles that crossed the lungs. Pulmonary vascular filtration of the venous air infusions was complete for the lower air doses ranging from 0.05 to 0.30 ml X kg-1 X min-1. When the air doses were increased to 0.35 ml X kg-1 X min-1, the filtration threshold was exceeded with arterial spillover of bubbles occurring in 50% of the animals and reaching 71% for 0.40 ml X kg-1 X min-1. Significant elevations were observed in pulmonary arterial pressure and pulmonary vascular resistance. Systemic blood pressure and cardiac output decreased, whereas left ventricular end-diastolic pressure remained unchanged. The results indicate that the filtration of venous bubbles by the pulmonary vasculature was complete when the air infusion rates were kept below a threshold value of 0.30 ml X kg-1 X min-1.

Gene diversity in hymenoptera.

Abstract: Hymenopteran species display levels of electrophoretic variation significantly lower than most other insects, and a few of them lack variation altogether. These observations are variably explained by reduced heterozygote advantage, inbreeding, eusociality, environmental stability conferred by the nest microhabitat, facilitation of exposure of deleterious genes in the haploid sex, reproduction by arrhenotokous parthenogenesis with balancing selection, and small effective population size resulting in a reduction in the amount of neutral polymorphism (Suomalainen, 1962; Crozier, 1970; Hartl, 1971, 1972; Snyder, 1974; Metcalf et aI., 1975; Pamilo et aI., 1978a, 1978b; Pamilo and Crozier, 1981; Wagner and Briscoe, 1983). Recently, Berkelhamer (1983) tested several hypotheses concerning the low levels of intraspecific genetic variability in Hymenoptera. Her conclusions were: (I) Hymenopterans have significantly lower variability than other insects due to their haplodiploidy. (2) Primitively eusocial insects are less variable than either solitary or advanced social species, implying that eusociality arises as a consequence of inbreeding. (3) Polygynous and monogynous species have similar levels of variability, challenging the expectations derived from both the neutral theory ofevolution (Kimura, 1968) and Hamilton's (1964) hypothesis. Hamilton's hypothesis is later rescued by assuming that the increased effective population size provided by polygyny is balanced by a more severe regime of inbreeding than in monogynous species. Unfortunately, three major errors and several minor ones in the analysis raise doubts as to the validity of these conclusions. The first error concerns the interchangeable use of observed heterozygosity, Hob, (the average proportion of heterozygous loci per individual) and expected heterozygosity or average gene diversity, Hexp, defined as the mean of h over all loci, where h = I :!: xl, and Xi is the frequency of the ith allele at a locus (Nei, 1975). In her Procedures section, Berkelhamer (1983) claims to have used Hobn but her data contain both Hob' and Hew For example, in the case of Opius juglandis and other species from Lester and Selander (1979), she uses Hexp, whereas, when given a choice between ,Hexp and Hobn as in the case of Rhytidoponera impressa (Ward, 1980), she chooses Hob,.. Hob, is very sensitive to the mating structure of a population and the amount of inbreeding. When inbreeding is strong, Hob, can be very low, while Hexp is not affected. In extreme cases such as selfing species (e.g., Selander and Hudson, 1976) Hob, is effectively 0, yet Hexp can be large. We also note that haploid organisms, which, by definition, have Hob' = 0, are among the species with the highest gene diversity (Spieth, 1975; Krzakowa and Szweykowski, 1979; Selander and Levin, 1980; Gaur et al., 1981; Yamazaki, 1981). For comparative purposes, Hexp rather than HOb' should be used as a measure of genetic variability (for further details see Nei, 1975; Nei and Graur, 1984). In Hymenoptera, where mating structure can assume diverse forms, the distinction between HOb' and Hexpis particularly important. While it may be difficult to ascertain which species are inbred, the fact is that, in almost all cases, Hob, is less than Hexp, such that using HOb' will introduce a unidirectional bias. In Heliothis zea, for instance, the difference is 21%. It should be noted that other compilations of protein polymorphism (e.g., Soule, 1976; Nevo, 1978) often include a mixture of Hob' and Hexp. The second problem concerns the number ofloci used to determine gene diversity. In Table 2 of Berkelhamer (1983), 51 hymenopteran species are listed, but the number of loci in the majority of them is very low. Presumably, the same is true for non-hymenopterans. Since genetic diversity is known to have a huge standard error (Nei and Roychoudhury, I974b), it is advisable to use estimates based on at least 20 loci. This is especially true when genetic variability is low. When different groups of species are compared by pooling many species within each group, fewer than 20 loci may be used, provided that we examine the same set ofloci. This stipulation derives from the fact that different loci have different levels of heterozygosity (for reasons see Zouros, 1976; Harris et al., 1977; Koehn and Eanes, 1977, 1978; Ward, 1977; Nei et al., 1978; Turner et aI., 1979). Moreover, since students of genetic diversity tend to study the more polymorphic loci first, using a small number of loci tends to introduce an additional bias in Hexp. This sometimes has dramatic effects on estimates of gene diversity. For example, in humans, estimates of Hexp for blood groups are 0.264, 0.197,0.130, and 0.114 when calculated in chronological order, on the basis of 21, 34, 57, and 67 loci respectively (Nei and Roychoudhury, 1974a, 1982). In the case of Drosophila pseudoobscura, Hexp was estimated to be 0.136 based on 46 loci (Fuerst et aI., 1977), while

Statistical methods of DNA sequence analysis: detection of intragenic recombination or gene conversion.

Abstract: Simple but exact statistical tests for detecting a cluster of associated nucleotide changes in DNA are presented. The tests are based on the linear distribution of a set of s sites among a total of n sites, where the s sites may be the variable sites, sites of insertion/deletion, or categorized in some other way. These tests are especially useful for detecting gene conversion and intragenic recombination in a sample of DNA sequences. In this case, the sites of interest are those that correspond to particular ways of splitting the sequences into two groups (e.g., sequences A and D vs. sequences B, C, and E-J). Each such split is termed a phylogenetic partition. Application of these methods to a well-documented case of gene conversion in human gamma-globin genes shows that sites corresponding to two of the three observed partitions are significantly clustered, whereas application to hominoid mitochondrial DNA sequences--among which no recombination is expected to occur--shows no evidence of such clustering. This indicates that clustering of partition-specific sites is largely due to intragenic recombination or gene conversion. Alternative hypotheses explaining the observed clustering of sites, such as biased selection or mutation, are discussed.

Associative conditioning analog selectively increases cAMP levels of tail sensory neurons in Aplysia.

Abstract: Bilateral clusters of sensory neurons in the pleural ganglia of Aplysia contain cells involved in a defensive tail withdrawal reflex. These cells exhibit heterosynaptic facilitation in response to noxious skin stimulation that can be mimicked by the application of serotonin. Recently it has been shown that this facilitation can be selectively amplified by the application of a classical conditioning procedure to individual sensory neurons. We now report that an analog of this classical conditioning paradigm produces a selective amplification of the cAMP content of isolated sensory neuron clusters. The enhancement is achieved within a single trial and appears to be localized to the sensory neurons. These results indicate that a pairing-specific enhancement of cAMP levels may be a biochemical mechanism for associative neuronal modifications and perhaps learning.

Lack of correlation between known virulence properties of Aeromonas hydrophila and enteropathogenicity for humans.

Abstract: Five strains of Aeromonas hydrophila were selected for use in volunteer challenge trials. All five strains produced cytotoxin, hemolysin enterotoxin, lysine decarboxylase, acetylmethylcarbinol, and DNase. Two strains hydrolyzed esculin. All strains produced purulent hemorrhagic fluid accumulation in rabbit ileal loops, but failed to induce keratoconjunctivitis in guinea pigs. None of the strains produced mannose-resistant hemagglutinins. In challenge studies, diarrhea was demonstrated in only 2 of 57 human volunteers with doses ranging from 10(4) to 10(10) CFU. One person experienced mild diarrhea with 10(9) CFU of strain 6Y. A second person developed moderate diarrhea with 10(7) CFU of strain 3647. At higher doses, no diarrhea was seen in any of the volunteers. The other three strains (B158, SSU, 3284) failed to cause diarrhea and were not recovered from stools of volunteers. Additional virulence properties of A. hydrophila need to be sought before enteropathogenicity for humans can be established.

Ethnicity, survival, and delay in seeking treatment for symptoms of breast cancer.

Abstract: This study examined differences in 10-year survival rates from breast cancer among white, black, and Hispanic women controlling for the effects of age, socioeconomic status (SES), stage of disease, and delay in seeking treatment for symptoms. Breast cancer patients (n = 1983) treated at M. D. Anderson Hospital and Tumor Institute in Houston, Texas between 1949 and 1968, were followed for 10 years. Ethnicity, SES, stage of disease, and delay were all found to affect survival when considered separately. Black patients were less likely to survive than either white or Hispanic patients whose survival experience appeared to be similar. Multivariate analysis that used a Cox regression technique showed that ethnic differences remained when age, SES, stage, and delay were included in the model. In contrast, the authors could not detect an effect of delay on survival when ethnicity and all other variables were included. These data suggest that ethnic differences in breast cancer survival are not mediated by differences in delay in seeking treatment for breast cancer symptoms.

The significance of scapular fractures.

Abstract: Scapular fractures in the multiply injured patient have received little attention. Fifty-six patients with 58 scapular fractures secondary to blunt trauma were reviewed. The patients averaged 3.9 major injuries excluding their scapular fractures. The injury pattern associated with blunt scapular fracture is unique. Patients with scapular fracture have a high incidence of injury to the ipsilateral lung and chest wall and to the ipsilateral shoulder girdle and its contained structures: rib fractures, 53.6%; pulmonary contusions, 53.6%; clavicular fracture, 26.8%; brachial plexus injury, 12.5%; subclavian, brachial, or axillary artery injury, 10.7%. Eight patients died (14.3%). Although no patient died from the scapular fracture, half of the deaths in this series were the result of pulmonary sepsis arising in an associated ipsilateral pulmonary contusion. Scapular fractures provide the trauma surgeon with a reliable clinical clue that the patient is at inordinate risk to have associated injuries of major consequence to the ipsilateral lung and chest wall, the ipsilateral shoulder girdle, and the ipsilateral subclavian, axillary, or brachial artery.

Type A score (Jenkins activity Survey) and risk of recurrent coronary heart disease in the aspirin myocardial infarction study

Abstract: The Jenkins Activity Survey (JAS), a questionnaire developed to assess the type A behavior pattern, was administered to 2,314 participants in the Aspirin Myocardial Infarction Study. All had a myocardial infarction (MI) before entering the study and were followed for at least 3 years. The JAS type A score was not significantly related to risk of recurrent major coronary events (definite nonfatal MI and coronary death) in the group of 244 women, the group of 2,070 men, or the subgroup of 671 men who were employed full-time in professional, technical or managerial positions. These results indicate that the JAS type A score is not useful in assessing prognosis after MI. By inference, traits measured by the JAS type A score, such as competitiveness, orientation toward achievement and preference for a rapid pace of life, appear not to be associated with increased risk of recurrent major coronary events.

Synergistic activation by recombinant mouse interferon-γ and muramyl dipeptide of tumoricidal properties in mouse macrophages

Abstract: Mouse peritoneal macrophages were activated to become cytotoxic against B16-BL6 melanoma cells by the combination of subthreshold amounts of murine interferon-gamma (IFN-gamma; 01 to 10 U/ml) and N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP; 0001 to 10 micrograms/ml), but not by the combination of pH 2-treated IFN-gamma and MDP, heat-treated IFN-gamma and MDP, or IFN-gamma and the inactive stereoisomer of MDP, N-acetyl-muramyl-D-alanyl-D-isoglutamine (MDP-D) The encapsulation of intact IFN-gamma and MDP within the same liposome preparation was synergistic for macrophage activation In contrast, the presentation of identical concentrations of IFN-gamma and MDP in separate liposome preparations did not activate macrophages These data allow us to conclude that the encapsulation of genetically engineered IFN-gamma and synthetically produced MDP within the same liposome is highly efficient in producing synergistic activation of tumoricidal properties in mouse macrophages

Increasing resistance to trimethoprim-sulfamethoxazole among isolates of Escherichia coli in developing countries.

Abstract: Resistance of Escherichia coli to trimethoprim (TMP)-sulfamethoxazole remains at 3%-8% at many medical centers within the United States. In this study a 44% resistance rate was observed among E. coli isolated at a pediatric hospital in Santiago, Chile, and a 40% resistance rate at a general teaching hospital in Bangkok, Thailand. Most isolates were from urinary tract infections and showed high-level resistance (minimal inhibitory concentration of TMP greater than 1,000 micrograms/ml). Nineteen of 35 isolates tested transferred resistance to TMP; most cotransferred resistance to streptomycin and sulfonamides. Dihydrofolate reductase type I was detected by gene probing in 14 of 35 strains. Subsequent investigations in Brazil, Honduras, and Costa Rica revealed that this high rate of resistance was not an isolated phenomenon.

Studies on vitiligo I. Epidemiological profile in Calcutta, India

Abstract: An epidemiological profile of vitiligo in Calcutta is presented. Prevalence data were gathered from 15,685 individuals drawn from the general population; pedigree data were collected through 293 vitiligo patients. The overall prevalence of vitiligo is about 5 per 1,000 individuals. There are no significant sex or age differences in prevalence rates. About a 4.5-fold increase in prevalence is observed among close biological relatives of affected individuals. There is, however, no clearcut correspondence between relative risks and kinship coefficients. There are no significant differences in the frequencies of various types of vitiligo between probands with and without positive family history. The overall mean and modal ages of onset are about 22 years and 15 years, respectively. The mean ages among males (24.8 years) and females (19.3 years) are significantly different.

Dietary nucleotides, a requirement for helper/inducer T lymphocytes.

Abstract: Previous investigations have revealed that dietary nucleotide restriction delays the onset of primary murine cardiac allograft rejection and acute graft-versus-host disease followed H-2-incompatible bone marrow transplantation, suppresses sensitization to intradermally injected antigens and suppresses in vivo and in vitro lymphocyte proliferation to alloantigen or lectin stimulation. To determine the mechanisms responsible for these phenomena, BALB/c mice were placed on chow (F), nucleotide free (NF) diet, or NF diet supplemented with 0.25% RNA (NFR), with 0.6% adenine (NFA), or with 0.06% uracil (NFU). Following four weeks of dietary equilibrium, splenic lymphocytes harvested from naive or immunostimulated mice in the various dietary groups were stained with monoclonal antibodies directed Lyt 1, Lyt 2, 3, or surface mouse immunoglobulin (IgG) surface markers. While naive animals demonstrated no differences in lymphocyte subpopulations between groups, following complete Freund's adjuvant (CFA) stimulation, splenic lymphocytes for NF mice demonstrated 27.3 +/- 1.7% Lyt 1+ cells compared with F (32.6 +/- .04%) and NFR mice (33.2 +/- 1.2%) (P less than 0.02). Restriction of dietary nucleotides affected not only phenotypes of T lymphocytes, but also T cell function. Following conconavalin A stimulation of irradiated splenic lymphocytes, IL-2 production was decreased in NF mice compared with the F control group (P less than 0.01). The RNA-repleted diet maintained normal IL-2 production, while addition of adenine or uracil alone did not. Finally, NF diets adversely affected host resistance to the opportunistic pathogen Candida albicans. Following inoculation with 0.25 X 10(6) organisms NF or NFA-fed hosts succumbed more rapidly than F, NFR, or NFU fed hosts (P less than 0.001). These data suggest that helper/inducer T lymphocytes require exogenous nucleotides to respond normally following immune stimulation. Uracil may be the critical substrate, based upon the studies of Candida resistance. By understanding the metabolic basis of NFD-induced immunosuppression, the role of dietary nucleotides in combatting infection and alloantigen rejection can be more clearly defined.

Mineralocorticoid regulation of apical cell membrane Na+ and K+ transport of the cortical collecting duct.

Abstract: The effects of mineralocorticoid (DOCA) treatment of rabbits on the Na+ and K+ transport properties of the cortical collecting duct apical cell membrane were assessed using microelectrode technique...

Parathyroid hormone and dibutyryl cAMP inhibit Na+/H+ exchange in renal brush border vesicles.

Abstract: Parathyroid hormone (PTH) and cAMP inhibit sodium, water, and bicarbonate reabsorption in the proximal tubule. We wished to determine whether these agents directly inhibit proximal tubular Na+/H+ exchange. A suspension of rabbit proximal tubules was prepared by enzymatic digestion and Ficoll gradient centrifugation. Oxygen consumption at 37 degrees C was stable over 60 min, averaged 20 nmol X mg protein-1 X min-1, and was inhibited 60% by ouabain. Over 96% of cells excluded trypan blue. From this suspension, brush border membrane vesicles were isolated. The vesicles were enriched 12.7 times in alkaline phosphatase relative to a cortical homogenate and demonstrated pH gradient-stimulated, amiloride-sensitive Na+/H+ countertransport and sodium-phosphate and sodium-D-glucose cotransport. When the tubule suspension was exposed to PTH or dibutyryl cAMP, the activity of Na+/H+ countertransport in the resultant brush border vesicles was inhibited. Neither PTH nor dibutyryl cAMP affected the amiloride-insensitive component of sodium transport or sodium-phosphate or sodium-D-glucose cotransport. The effect of PTH on Na+/H+ counter-transport could not be explained by an alteration in fluidity of the brush border membrane. These experiments demonstrate that PTH and dibutyryl cAMP directly inhibit Na+/H+ countertransport in the brush border membrane of the rabbit proximal tubule.

Treatment of acquired immunodeficiency syndrome--related Kaposi's sarcoma with lymphoblastoid interferon.

Abstract: Twelve homosexual patients with Kaposi's sarcoma associated with the acquired immune deficiency syndrome (AIDS) were treated with a preparation of purified human lymphoblastoid interferon (Wellferon [Burroughs Wellcome, Research Triangle Park, NC]). They were given a dose of 20 X 10(6) U/m2 intramuscularly daily for approximately two months. Responders continued their treatment on a maintenance schedule of 20 X 10(6) U/m2 three times a week. Four patients experienced complete remissions, and four experienced partial remissions that resulted in a total response rate of 67%. The median duration of treatment was 14 weeks (7 to 28+ weeks), and the median response duration was 28+ weeks (19 to 29+ weeks). Of the four patients in complete remission, one relapsed at 25 weeks and one at 26 weeks; the other two remained in complete remission at 28 and 29+ weeks. The clinical toxicity consisted of chills, fever, fatigue, and asthenia. Hematologic toxicity was similar to that previously described for other preparations of alpha-interferon and consisted of moderate leukopenia and thrombocytopenia. Asthenia, a condition present in all 12 patients, was severe in 50%. A minimal tumor burden, the absence of circulating interferon before treatment, and a performance status of greater than or equal to 90% on the Karnofsky scale were related to an improved response rate. Measurement of immunologic parameters showed significant declines in the already impaired T cell levels, lymphocyte blastogenic response to concanavalin A, monocyte-mediated antibody-dependent cellular cytotoxicity, and monocyte-adherence. Activation of natural killer cells was not noted, and no life-threatening infections occurred during treatment. These data suggest that human lymphoblastoid interferon is an active agent in the treatment of Kaposi's sarcoma, and its use warrants further study in a larger number of patients.