Corrigendum to "Single-chain fragment variable antibody targeting cholecystokinin-B receptor for pain reduction" [Neurobiol. Pain 10 (2021) 100067].

[This corrects the article DOI: 10.1016/j.ynpai.2021.100067.].

Single-chain Fragment variable antibody targeting cholecystokinin-B receptor for pain reduction.

The cholecystokinin B receptor and its neuropeptide ligand are upregulated in chronic neuropathic pain models. Single-chain Fragment variable antibodies were generated as preferred non-opioid targeting therapy blocking the cholecystokinin B receptor to inhibit chronic neuropathic pain models in vivo and in vitro. Engineered antibodies of this type feature binding activity similar to monoclonal antibodies but with stronger affinity and increased tissue penetrability due to their smaller size. More importantly, single-chain Fragment variable antibodies have promising biotherapeutic applications for both nervous and immune systems, now recognized as interactive in chronic pain. A mouse single-chain Fragment variable antibody library recognizing a fifteen amino acid extracellular peptide fragment of the cholecystokinin B receptor was generated from immunized spleens. Ribosome display, a powerful cell-free technology, was applied for recombinant antibody selection. Antibodies with higher affinity, stability, solubility, and binding specificity for cholecystokinin B not A receptor were selected and optimized for in vivo and in vitro efficacy. A single dose of the lead candidate reduced mechanical and cold hypersensitivity in two rodent models of neuropathic pain for at least seven weeks. Continuing efficacy was evident with either intraperitoneal or intranasal dosing. Likewise, the lead single-chain Fragment variable antibody totally prevented development of anxiety- and depression-like behaviors and cognitive deficits typical in the models. Reduction of neuronal firing frequency was evident in trigeminal ganglia primary neuronal cultures treated in vitro with the cholecystokinin B receptor antibody. Immunofluorescent staining intensity in the trigeminal neuron primary cultures was significantly reduced incrementally after overnight binding with increasingly higher dilutions of the single-chain Fragment variable antibody. While it is reported that single-chain Fragment variable antibodies are removed systemically within 2-6 h, Western blot evidence indicates the His-tag marker remained after 7 weeks in the trigeminal ganglia and in the dorsolateral medulla, providing evidence of brain and ganglia penetrance known to be compromised in overactivated states. This project showcases the in vivo efficacy of our lead single-chain Fragment variable antibody indicating its potential for development as a non-opioid, non-addictive therapeutic intervention for chronic pain. Importantly, studies by others have indicated treatments with cholecystokinin B receptor antagonists suppress maintenance and reactivation of morphine dependence in place preference tests while lowering tolerance and dose requirements. Our future studies remain to address these potential benefits that may accompany the cholecystokinin B receptor biological therapy. Both chronic sciatic and orofacial pain can be unrelenting and excruciating, reducing quality of life as well as diminishing physical and mental function. An effective non-opiate, non-addictive therapy with potential to significantly reduce chronic neuropathic pain long term is greatly needed.

Detecting the Hidden Properties of Immunological Data and Predicting the Mortality Risks of Infectious Syndromes.

BACKGROUND: To extract more information, the properties of infectious disease data, including hidden relationships, could be considered. Here, blood leukocyte data were explored to elucidate whether hidden information, if uncovered, could forecast mortality. METHODS: Three sets of individuals (n = 132) were investigated, from whom blood leukocyte profiles and microbial tests were conducted (i) cross-sectional analyses performed at admission (before bacteriological tests were completed) from two groups of hospital patients, randomly selected at different time periods, who met septic criteria [confirmed infection and at least three systemic inflammatory response syndrome (SIRS) criteria] but lacked chronic conditions (study I, n = 36; and study II, n = 69); (ii) a similar group, tested over 3 days (n = 7); and (iii) non-infected, SIRS-negative individuals, tested once (n = 20). The data were analyzed by (i) a method that creates complex data combinations, which, based on graphic patterns, partitions the data into subsets and (ii) an approach that does not partition the data. Admission data from SIRS+/infection+ patients were related to 30-day, in-hospital mortality. RESULTS: The non-partitioning approach was not informative: in both study I and study II, the leukocyte data intervals of non-survivors and survivors overlapped. In contrast, the combinatorial method distinguished two subsets that, later, showed twofold (or larger) differences in mortality. While the two subsets did not differ in gender, age, microbial species, or antimicrobial resistance, they revealed different immune profiles. Non-infected, SIRS-negative individuals did not express the high-mortality profile. Longitudinal data from septic patients displayed the pattern associated with the highest mortality within the first 24 h post-admission. Suggesting inflammation coexisted with immunosuppression, one high-mortality sub-subset displayed high neutrophil/lymphocyte ratio values and low lymphocyte percents. A second high-mortality subset showed monocyte-mediated deficiencies. Numerous within- and between-subset comparisons revealed statistically significantly different immune profiles. CONCLUSION: While the analysis of non-partitioned data can result in information loss, complex (combinatorial) data structures can uncover hidden patterns, which guide data partitioning into subsets that differ in mortality rates and immune profiles. Such information can facilitate diagnostics, monitoring of disease dynamics, and evaluation of subset-specific, patient-specific therapies.

Prolixicin: a novel antimicrobial peptide isolated from Rhodnius prolixus with differential activity against bacteria and Trypanosoma cruzi.

We identified and characterized the activity of prolixicin, a novel antimicrobial peptide (AMP) isolated from the hemipteran insect, Rhodnius prolixus. Sequence analysis reveals one region of prolixicin that may be related to the diptericin/attacin family of AMPs. Prolixicin is an 11-kDa peptide containing a putative 21 amino acid signal peptide, two putative phosphorylation sites and no glycosylation sites. It is produced by both adult fat body and midgut tissues in response to bacterial infection of the haemolymph or the midgut. Unlike most insect antibacterial peptides, the prolixicin gene does not seem to be regulated by NF-κB binding sites, but its promoter region contains several GATA sites. Recombinant prolixicin has strong activity against the Gram-negative bacterium Escherichia coli and differential activity against several Gram-negative and Gram-positive bacteria. No significant toxicity was demonstrated against Trypanosoma cruzi, the human parasite transmitted by R. prolixus.

Development of paratransgenic Artemia as a platform for control of infectious diseases in shrimp mariculture.

AIM: To study the accumulation and retention of recombinant proteins in Artemia gut for optimizing paratransgenic disease control in shrimp aquaculture. METHODS AND RESULTS: Transgenic Escherichia coli expressing fluorescent marker proteins and the transgenic cyanobacterium Synechococcus bacillarus expressing a functional murine single chain antibody, DB3, were fed to Artemia franciscana. Stable expression and retention of several marker molecules (e.g. GFP, DS Red and DB3) up to 10 h after of feeding with E. coli were evident within the gut of Artemia. Engineered strains of S. bacillarus expressing DB3 accumulated within the gut of Artemia with detectable antibody activity for 8-10 h of feeding via ELISA, coincident with the time period of the highest density of transgenic S. bacillarus in the Artemia gut. CONCLUSIONS: Artemia fed transgenic bacteria or algae accumulated recombinant proteins for up to 10 h that retained biological activity. Co-delivery of multiple recombinant proteins simultaneously in the gut of Artemia was also demonstrated. SIGNIFICANCE AND IMPACT OF THE STUDY: Expression of molecules that target infectious agents of mariculture in shrimp via commonly deployed feed organisms such as Artemia could potentially offer powerful new tools in the ongoing global effort to increase food supply.

Expression of a functional single-chain antibody via Corynebacterium pseudodiphtheriticum.

Antibody-based therapeutics are effective against conditions ranging from acute infections to malignancy. They may prove crucial in combating bioterrorism and responding to drug-resistant and emerging pathogens. At present the cost of producing therapeutic monoclonal antibodies is between $1,000 to $6,000 per gram. The need to administer antibodies parenterally at frequent intervals further drives the cost of this treatment. Here we present an antibody delivery system, termed paratransgenesis, with the potential to overcome these limitations. The paratransgenic approach involves genetically transforming a commensal or symbiont bacterium to express foreign molecules that target pathogens. We describe transformation of Corynebacterium pseudodiptheriticum, a commensal bacterium found in the human respiratory tract, to express a murine single-chain antibody binding progesterone. The antibody was functional and bound specifically to progesterone in a concentration-dependent manner. This marker antibody system is the precursor to development of expression systems producing recombinant humanized single-chain antibodies. Studies are in progress evaluating fitness, transgene stablility, and pathogenecity of the genetically engineered C. pseudodiptheriticum. We anticipate developing a repertoire of expressed molecules targeting infectious agents and surface epitopes of pulmonary mass lesions. If expression systems for anti-pathogen molecules in C. pseudodiptheriticum and other respiratory commensal bacteria can be optimized, these bacteria have the potential for a range of therapeutic and prophylactic applications.

Discrepancies between self-report and objective measures for stimulant drug use in HIV: cognitive, medication adherence and psychological correlates.

While it has long been recognized that self-reported drug use may be at variance with objectively obtained evidence such as urine toxicology assays, few studies have explored the behavioral correlates of such discrepancies. Here we compared self-reported and objective measures of stimulant drug use for 162 HIV infected individuals and identified a sub-group with discrepancies between data obtained via the two methods. Results showed poorer neurocognitive performance (attention, learning/memory) and lower medication adherence rates for the discrepant group as compared to those who either acknowledged their drug use or accurately denied recent stimulant use. Using the Millon Clinical Multiaxial Inventory-III, it was also found that those in the discrepant group were more hesitant to reveal psychopathology. Comparisons of self-reported and objectively measured medication adherence data are also discussed.

Medication adherence among HIV+ adults: effects of cognitive dysfunction and regimen complexity.

BACKGROUND: Although the use of highly active antiretroviral therapy in the treatment of HIV infection has led to considerable improvement in morbidity and mortality, unless patients are adherent to their drug regimen (i.e., at least 90 to 95% of doses taken), viral replication may ensue and drug-resistant strains of the virus may emerge. METHODS: The authors studied the extent to which neuropsychological compromise and medication regimen complexity are predictive of poor adherence in a convenience sample of 137 HIV-infected adults. Medication adherence was tracked through the use of electronic monitoring technology (MEMS caps). RESULTS: Two-way analysis of variance revealed that neurocognitive compromise as well as complex medication regimens were associated with significantly lower adherence rates. Cognitively compromised participants on more complex regimens had the greatest difficulty with adherence. Deficits in executive function, memory, and attention were associated with poor adherence. Logistic regression analysis demonstrated that neuropsychological compromise was associated with a 2.3 times greater risk of adherence failure. Older age (>50 years) was also found to be associated with significantly better adherence. CONCLUSIONS: HIV-infected adults with significant neurocognitive compromise are at risk for poor medication adherence, particularly if they have been prescribed a complex dosing regimen. As such, simpler dosing schedules for more cognitively impaired patients might improve adherence.

Hormone replacement therapy and malignant melanoma: to prescribe or not to prescribe?

The mean age of presentation of malignant melanoma in women is the early fifties, a time that may be concomitant with the onset of the menopause. As the lesion can often be successfully surgically excised, many women will enter the menopause disease-free but in need of treatment for their menopausal symptoms. Melanoma has traditionally been considered to be an estrogen receptor-positive tumor, whose prognosis is adversely affected by estrogen, whether during pregnancy or in association with the oral contraceptive pill or hormone replacement therapy (HRT). Recent evidence now refutes this. As most recurrences occur in the first 2 years following treatment, it may be prudent to defer HRT until this time. There is a particular paucity of information pertaining to HRT and melanoma, such that, at present, there appears to be no justification for withholding this potentially beneficial therapy from menopausal women who have undergone treatment for melanoma.

Podocyte expression of the CDK-inhibitor p57 during development and disease.

BACKGROUND: The mature podocyte is a terminally differentiated cell with a limited proliferative capacity. The precise cell cycle proteins necessary for establishing podocyte quiescence during development or permitting podocyte cell cycle re-entry in disease states have not been fully defined. Accordingly, we studied the role of the cyclin dependent kinase (CDK)-inhibitor p57Kip2 (p57) in modulating these processes. METHODS: The expression of p57 protein in relation to markers of DNA synthesis was examined in developing mouse kidneys, and in the passive Heymann nephritis (PHN) and anti-glomerular antibody models of glomerular disease by immunohistochemistry. The role of p57 in glomerulogenesis was explored by examining renal tissue from embryonic p57-/- mice, and the expression of p21, p27 and p57 protein and mRNA was examined in podocytes in vitro. RESULTS: The de novo expression of p57 during glomerulogenesis coincides with the cessation of podocyte proliferation, and the establishment of a mature phenotype, and p57 is expressed exclusively in podocytes in mature glomeruli. However, p57 knockout mice have normal glomerular podocyte development. In addition, mRNA but not protein levels of p57 increased upon differentiation of podocytes in vitro. There was a marked decrease in p57 expression in both animal models of podocyte injury. This was diffuse in PHN, whereas in the murine model, loss of expression of p57 occurred predominantly in proliferating podocytes, expressing proliferating cell nuclear antigen (PCNA). CONCLUSION: Despite the de novo expression of p57 protein coinciding with the cessation of primitive podocyte proliferation during glomerulogenesis, embryonic p57-/- mice glomeruli were histologically normal. Cultured podocytes did not require changes in p57 protein levels to undergo differentiation. These data suggest that p57 alone is not required for podocyte differentiation, and that other cell cycle regulators may play a role. Furthermore, although injury to mature podocytes in experimental glomerular disease is associated with a decrease in p57, the levels of all three members of the Cip/Kip family of CDK inhibitors appear to determine the capability of podocytes to proliferate.

Bacterial symbiosis and paratransgenic control of vector-borne Chagas disease.

The triatomine vectors of Chagas disease are obligate haematophagous insects, feeding on vertebrate blood throughout their entire developmental cycle. As a result of obtaining their nutrition from a single food source, their diet is devoid of certain vitamins and nutrients. Consequently, these insects harbour populations of bacterial symbionts within their intestinal tract, which provide the required nutrients that are lacking from their diet. We have isolated and characterised symbiont cultures from various triatomine species and developed a method for genetically transforming them. We can then reintroduce them into their original host species, thereby producing stable paratransgenic insects in which we are able to express heterologous gene products. Using this methodology, we have generated paratransgenic Rhodnius prolixus that are refractory for infection with Trypanosoma cruzi. Two examples of potentially refractory genes are currently being expressed in paratransgenic insects. These include the insect immune peptide cecropin A and active single chain antibody fragments. We have also developed an approach that would allow introduction of genetically modified bacterial symbionts into natural populations of Chagas disease vectors. This approach utilises the coprophagic behaviour of these insects, which is the way in which the symbionts are transmitted among bug populations in nature. The production and ultimate release of transgenic or paratransgenic insects for public health applications is potentially very promising but also worthy of much careful consideration with respect to environmental, political, and human safety concerns.

Predictors of neuropsychological performance in HIV positive women.

This study examines predictors of neuropsychological (NP) performance in a community sample of 237 HIV seropositive and seronegative women. Consistent with literature describing the NP sequelae of HIV infection in men, we expected that HIV status would predict poorer NP performance on tests assessing verbal memory, psychomotor speed and motor speed. Multiple regression analyses testing the association between HIV serostatus and NP performance and controlling for predictors including age, ethnicity, education, psychological distress, and drug and alcohol use indicated that HIV serostatus was associated with slowed psychomotor speed. Specifically, AIDS diagnosis and HIV seropositivity predicted poorer performance on tests of psychomotor speed relative to HIV seronegatives. Contrary to expectations, no relationship between HIV serostatus and either motor speed or verbal memory performance emerged. Education, ethnicity, depressive distress, recent exposure to drugs as indexed by toxicology, and alcohol use were also associated with NP performance. Given that the HIV seropositive and seronegative samples differed on a number of demographic and drug use variables, a second series of analyses examining a subset of participants (matched on all key demographic factors) and with no illicit drug use during the past year was also conducted. Results of these analyses were similar to those obtained for the full sample, with AIDS diagnosis and HIV seropositivity predicting psychomotor slowing. To date, little work describing the NP sequelae of HIV infection in women has been conducted. This study provides one of the first descriptions of the NP effects of HIV/AIDS in a largely non-injection drug using community sample of women.

HIV-1, cocaine, and neuropsychological performance in African American men.

The purpose of this study was to examine the independent and interactive effects of HIV-1 serostatus and cocaine on neuropsychological (NP) performance in a sample of 237 gay and bisexual urban-dwelling African American men. Consistent with current evidence, it was expected that the greatest neuropsychological performance deficits would be evident (1) in the symptomatic seropositives (SSPs), especially in domains affected by HIV (i.e., memory and psychomotor speed), and on tests that are sensitive to subtle slowing; (2) in those who are recent and frequent cocaine abusers; and (3) in those who are both HIV seropositive and cocaine abusers. Multivariate analyses controlling for age and alcohol use confirmed expectations, with symptomatic seropositives (SSPs) evidencing significantly poorer psychomotor speed than the seronegatives (SNs), and slower reaction time and poorer nonverbal memory than the asymptomatic seropositives (ASPs). Moderate to heavy recent cocaine use was associated with slower psychomotor speed. However, contrary to expectations, no interaction of serostatus and cocaine was noted for any NP domain, and the expected serostatus and cocaine effects on verbal memory and frontal systems were not obtained. Level of alcohol consumption exacerbated the detrimental effects of HIV-1 on a computerized reaction time test which is especially sensitive to subtle slowing. This study provides one of the first descriptions of the neuropsychological effects of HIV-AIDS in a non-injection drug-using community sample of gay and bisexual African American men.

Correlates of first intercourse among women in Jamaica.

This study examines retrospective reports of factors anticipated to impact first intercourse in a random sample of 897 Jamaican women, and contributes to our understanding of the relationship between sexual risk, knowledge, and economic and demographic correlates of first intercourse. A relationship between initiation of intercourse prior to the age of consent (16 years) and factors occurring at or around the time of first intercourse was found. Early initiators were more likely to have had less early family stability and to have experienced menarche at a younger age than late initiators. Although early initiators of intercourse were more likely to report lower socioeconomic status, less STD knowledge, and greater numbers of pregnancies, they were no more likely to report more sexual partners than women who engaged in first intercourse after the age of consent, and had a greater number of long-term relationships. Regardless of age of first intercourse, women need to be made aware of the risks of sexual contact so that they can make informed decisions about the consequences of sexual activity. Overall, results are consistent with work conducted in other parts of the Caribbean and America regarding the age at which young women engage in first intercourse. Findings suggest the need for further work exploring expectations at first intercourse such as marriage, economic support, or relationship stability. Implications of these findings are discussed within the context of economic and structural factors that both increase and decrease risks.

PIP: This study examines retrospective reports of factors anticipated to impact first intercourse among 897 women selected randomly in Jamaica. Three groups of factors were associated with early vs. late initiation of intercourse. A significant association was noted between family structure in childhood and age of first intercourse. Women growing up in one-parent families were more likely to engage in intercourse before the age of 16. The age of menarche was also significantly associated with age of intercourse. The characteristics of the first sexual partner and the characteristics of the relationship were significantly associated with the age of intercourse. On the other hand, there are four sets of variables assessing current demographic characteristics, current relationship status, and factors such as religiosity and knowledge on sexually transmitted diseases (STDs). It was observed that early initiators of intercourse were more likely to report lower socioeconomic status, less STD knowledge, and a greater number of pregnancies. This study identifies some of the circumstances of first intercourse, which highlight the need to develop health and educational intervention programs that offer more options to young adolescents who may consider early childbearing to stabilize relationships.

Expression of a functional antibody fragment in the gut of Rhodnius prolixus via transgenic bacterial symbiont Rhodococcus rhodnii.

Expression within insects of foreign antiparasitic gene products via microbial symbionts could be used to prevent transmission of vector-borne pathogens to vertebrate hosts. Genetically transformed symbiotic bacteria Rhodococcus rhodnii expressed functional antibody fragments (rDB3 encoding murine V(H)/K which binds progesterone) that were exported into the gut lumen of the triatomine bug Rhodnius prolixus (Hemiptera: Reduviidae), a vector of Chagas disease. Transgenic symbionts were maintained in successive nymphal instars and adults of Rhodnius prolixus despite competition with native untransformed Rhodococcus rhodnii. This is the first description of a functional mammalian antibody fragment expressed in an insect. Our system is a model for constructing paratransgenic insects (insects carrying transformed symbionts) with compromised ability to transmit pathogens.

Hydrocarbon chain packing and the effect of ethanol on the thermotropic phase behavior of mixed-chain phosphatidylglycerols.

Previous studies in this laboratory have delineated the relationship between the acyl chain asymmetry of mixed-chain phosphatidylcholines and the effect of ethanol concentration ([EtOH]) on their melting behavior (Li et al., Biophys J., 70 (1996) 2784-2794). This present investigation extends these findings to another phospholipid family by using high-resolution differential scanning calorimetry (DSC) to characterize the effect of ethanol concentration on the main phase transition temperature (Tm) of five molecular species of mixed-chain phosphatidylglycerol (PG). For C(14):C(18)PG, C(15):C(17)PG, C(16):C(16)PG, and C(17):C(15)PG, a biphasic profile in the Tm versus [EtOH] plot was observed, and the minimum in the plot for each PG occurred at 33, 15, 19, and 36 mg/ml, respectively. This biphasic behavior is typical of phospholipids whose acyl chain asymmetry is fairly small. For C(18):C(14)PG, only a linear decrease in the Tm was observed as a function of ethanol concentration; this effect is characteristic of highly asymmetric phospholipids. Our DSC results obtained with mixed-chain PG in the presence of ethanol demonstrate that the acyl chain asymmetry of the five lipids studied can be ranked as follows: C(15):C(17)PG

Thermotropic phase behavior of mixed-chain phosphatidylglycerols: implications for acyl chain packing in fully hydrated bilayers.

In this communication we report the first systematic investigation of the thermodynamic properties of fully hydrated mixed-chain phosphatidylglycerols (PG) using high-resolution differential scanning calorimetry (DSC). The crystal structure of dimyristoylphosphatidylglycerol shows an acyl chain conformation that is nearly opposite to that of phosphatidylcholine (PC). In PC, the sn-1 chain is straight while the sn-2 chain contains a bend; for PG, the sn-1 contains a bend while the sn-2 chain is in the all-trans conformation (R.H. Pearson, I. Pascher, The molecular structure of lecithin dihydrate, Nature, 281 (1978) 499-501; I. Pascher, S. Sundell, K. Harlos, H. Eibl, Conformational and packing properties of membrane lipids: the crystal structure of sodium dimyristoylphosphatidylglycerol, Biochim. Biophys. Acta, 896 (1987) 77-88). If the structure of PG found in the single crystal can be extrapolated to that in the fully hydrated gel-state bilayer, the observed difference in acyl chain conformations implies that modulation of the acyl chain asymmetry will have an opposite effect on the thermotropic phase behavior of PG and PC. For example, it is expected, based on the crystal structures, that C(15):C(13)PG should have a higher main phase transition temperature (Tm) than C(14):C(14)PG, and C(13):C(15)PG should have a lower Tm than C(14):C(14)PG. However, our DSC studies show clearly that the expectation is not borne out by experimental data. Rather, the Tm values of C(15):C(13)PG, C(14):C(14)PG, and C(13):C(15)PG are 18.2 degrees C, 23.1 degrees C, and 24.4 degrees C, respectively. Several other PGs, each with a unique acyl chain composition, have also been studied in this laboratory using high-resolution DSC. It is shown that the acyl chain conformation of fully hydrated PG in general is nearly opposite to that seen in the PG crystal structure.

Bacterial symbiosis in arthropods and the control of disease transmission.

Bacterial symbionts may be used as vehicles for expressing foreign genes in arthropods. Expression of selected genes can render an arthropod incapable of transmitting a second microorganism that is pathogenic for humans and is an alternative approach to the control of arthropod-borne diseases. We discuss the rationale for this alternative approach, its potential applications and limitations, and the regulatory concerns that may arise from its use in interrupting disease transmission in humans and animals.

Prevention of insect-borne disease: an approach using transgenic symbiotic bacteria.

Expression of molecules with antiparasitic activity by genetically transformed symbiotic bacteria of disease-transmitting insects may serve as a powerful approach to control certain arthropod-borne diseases. The endosymbiont of the Chagas disease vector, Rhodnius prolixus, has been transformed to express cecropin A, a peptide lethal to the parasite, Trypanosoma cruzi. In insects carrying the transformed bacteria, cecropin A expression results in elimination or reduction in number of T. cruzi. A method has been devised to spread the transgenic bacteria to populations of R. prolixus, in a manner that mimics their natural coprophagous route of symbiont acquisition.

Impact of breast cancer on Asian American and Anglo American women.

This pilot study constitutes the first exploration of the impact of breast cancer on Asian American women. Three hypotheses guided this study: (1) Asian American women would choose breast conserving therapy and breast reconstruction at a lower rate than the Anglo American women due to cultural differences in body image, (2) Asian American women with breast cancer would express psychological distress somatically and Anglo American women would express distress emotionally, and acculturation levels of the Asian American women would modify the expressions of distress such that women with high acculturation will express distress more emotionally and less acculturated women would express distress more somatically, and (3) Asian American women would seek assistance for psychosocial problems at a significantly lower rate than Anglo women. Ethnicity, age, and levels of acculturation were found to be significant variables that had to be considered simultaneously. The three hypotheses were only partially supported: (1) Asian American women chose breast conserving therapy and adjuvant therapy at a significantly lower rate than the Anglo American women, (2) Contrary to the hypothesis, somatization did not appear to be a dominant form of symptom presentation for Asian American women regardless of level of acculturation, and (3) Asian American women sought professional assistance for psychosocial problems at a significantly lower rate than Anglo women. Asian American women reported using different modes of help-seeking behavior for emotional concerns and receiving different sources of social support than the Anglo American women. Cultural interpretations of the findings are offered to explain the differences in the physical, emotional, and social responses to the breast cancer experience of Asian American women compared with the Anglo Americans, and notably between the Chinese- and Japanese Americans as well. The findings of this study warrant more refined exploration in order to improve the medical, psychological and social outcomes for Asian American women with breast cancer.