The role of sex in daily levels of high-risk alcohol and cannabis co-use.

Background: Co-use of alcohol and cannabis is highly prevalent and may be associated with negative outcomes. The intersection between alcohol and cannabis use remains poorly understood. The present study assessed this intersection and the moderating effects of sex on the daily levels of high-risk alcohol and cannabis co-use. Methods: A secondary analysis of an experimental pharmacology study specifically designed to recruit individuals using both alcohol and cannabis was conducted. Thirty-three non-treatment seeking subjects (19 M/14F) reporting high-risk levels of alcohol and cannabis use completed a 30-day Timeline Follow-back (TLFB) assessment for alcohol and cannabis use, resulting in a total of N = 990 observations. Logistic models tested the probability of same day cannabis use as predicted by alcohol use (any use, total drinking, and binge drinking), sex, and alcohol use by sex interactions. Results: Drinking any alcohol on a given day was associated with a significant increase in the likelihood of same-day cannabis use (b = 0.61, p = 0.001) as was amount of alcohol consumed on a given day (b = 0.083, p = 0.012). These relations were significantly moderated by sex (b = 1.58, p<0.001; b = 0.14, p = 0.044). Male-identifying individuals demonstrated an increased probability of concurrent cannabis use with any alcohol use on a given day, and this relationship increased linearly as the number of drinks consumed increased. Conclusions: The present study investigated the patterns associated with co-using alcohol and cannabis in individuals reporting high-risk levels of both alcohol and cannabis use. The sex-dependent findings suggest that males are at higher risk for co-using alcohol and cannabis compared with females.

Hepatitis C Within a Single Health System: Progression Along the Cascade to Cure Is Higher for Those With Substance Misuse When Linked to a Clinic With Embedded Support Services.

BACKGROUND: Hepatitis C is now curable for most individuals, and national goals for elimination have been established. Transmission persists, however, particularly in nonurban regions affected by the opioid epidemic. To reach goals of elimination, barriers to treatment must be identified. METHODS: In this open cohort of all individuals diagnosed with active hepatitis C from 2010 to 2016 at a large medical center, we identified patient and clinic characteristics associated with our primary outcome, sustained virologic response (SVR). We performed a subgroup analysis for those with documented substance misuse. RESULTS: SVR was achieved in 1544 (41%) of 3790 people with active hepatitis C. In a multivariable Poisson regression model, SVR was more likely in individuals diagnosed outpatient (incident rate ratio [IRR], 1.7; 95% confidence interval [CI], 1.5-2.0), living in close proximity to the medical center (IRR, 1.2; 95% CI, 1.1-1.3), with private insurance (IRR, 1.1; 95% CI, 1.0-1.3), and with cirrhosis (IRR, 1.4; 95% CI, 1.3-1.5). Achieving SVR was less likely in those qualifying as indigent (IRR, 0.8; 95% CI, 0.8-0.9) and those with substance misuse (IRR, 0.8; 95% CI, 0.7-0.9). In the subgroup analysis of those with substance misuse, SVR rates were higher in those linked to the infectious diseases clinic, which has embedded support services, than those linked to the gastroenterology clinic, which does not (IRR, 1.4; 95% CI, 1.1-1.9). CONCLUSIONS: Social determinants of health including proximity to care and poverty impacted achievement of SVR. Those with substance misuse, a high-priority population for treatment of hepatitis C, had better outcomes when receiving care in a clinic with embedded support services.

Terminalia ferdinandiana Exell. Extracts inhibit the growth of body odour-forming bacteria.

OBJECTIVE: Terminalia ferdinandiana extracts are potent growth inhibitors of many bacterial pathogens. They may also inhibit the growth of malodour-producing bacteria and thus be useful deodorant components, although this is yet to be tested. METHODS: Terminalia ferdinandiana fruit and leaf solvent extracts were investigated by disc diffusion and liquid dilution MIC assays against the most significant bacterial contributors to axillary and plantar malodour formation. Toxicity was determined using the Artemia franciscana nauplii bioassay. Non-targeted HPLC separation of the methanolic leaf extract coupled to high-resolution time-of-flight (TOF) mass spectroscopy was used for the identification and characterization of individual components in the extract. RESULTS: The T. ferdinandiana leaf extracts were the most potent bacterial growth inhibitors. The leaf methanolic extract was particularly potent, with low MIC values against C. jeikeium (233 µg mL-1 ), S. epidermidis (220 µg mL-1 ), P. acnes (625 µg mL-1 ) and B. linens (523 µg mL-1 ). The aqueous and ethyl acetate leaf extracts were also potent growth inhibitors of C. jeikeium and S. epidermidis (MICs < 1000 µg mL-1 ). In comparison, the fruit extracts were substantially less potent antibacterial agents, although still with MIC values indicative of moderate growth inhibitory activity. All T. ferdinandiana leaf extracts were non-toxic in the Artemia franciscana bioassay. Non-biased phytochemical analysis of the methanolic leaf extract revealed the presence of high levels of and high diversity of tannins and high levels of the flavone luteolin. CONCLUSION: The low toxicity of the T. ferdinandiana leaf extracts and their potent growth inhibition of axillary and plantar malodour-producing bacteria indicate their potential as deodorant components.

Characterizing the prevalence of chromosome instability in interval colorectal cancer.

A substantial proportion of colorectal cancers (CRCs) are interval CRCs (I-CRCs; i.e., CRCs diagnosed soon after a colonoscopy). Chromosomal instability (CIN) is defined as an increase in the rate of which whole chromosomes/large chromosomal fragments are gained or lost and is observed in 85% of non-hereditary CRCs. The contribution of CIN to the etiology of I-CRCs remains unknown. We established a fluorescence in situ hybridization (FISH) approach to characterize CIN by enumerating specific chromosomes and determined the prevalence of numerical CIN in a population-based cohort of I-CRCs and control (sporadic) CRCs. Using the population-based Manitoba Health administrative databases and Manitoba Cancer Registry, we identified an age, sex, and colonic site of CRC matched cohort of I-CRCs and controls and retrieved their archived paraffin-embedded tumor samples. FISH chromosome enumeration probes specifically recognizing the pericentric regions of chromosomes 8, 11, and 17 were first used on cell lines and then CRC tissue microarrays to detect aneusomy, which was then used to calculate a CIN score (CS). The 15th percentile CS for control CRC was used to define CIN phenotype. Mean CSs were similar in the control CRCs and I-CRCs; 82% of I-CRCs exhibited a CIN phenotype, which was similar to that in the control CRCs. This study suggests that CIN is the most prevalent contributor to genomic instability in I-CRCs. Further studies should evaluate CIN and microsatellite instability (MSI) in the same cohort of I-CRCs to corroborate our findings and to further assess concomitant contribution of CIN and MSI to I-CRCs.

Is the way to a man's heart through his stomach? Enteropericardial fistula: case series and literature review.

Fistula formation between the pericardium and the gastrointestinal tract is rare. Enteropericardial fistulae may present dramatically, many have prodromal symptoms even though they are not symptoms usually associated with esophageal disease. Prompt diagnosis and expedient surgery can result in survival. We describe three cases of enteropericardial fistulae diagnosed during emergency surgery for sepsis or hemorrhage. All had previous surgery though the details were not available to the operating surgeons because of the time that had passed since their original operation. All three patients survived, albeit with prolonged hospital stay and repeated surgery. A review of the English language literature revealed 95 cases (Table 1). Fifty-eight had a history of previous surgery, particularly fundoplication or esophagectomy. Ten had advanced malignancy and were treated conservatively. All eight patients with fistulae, which were iatrogenic or due to foreign bodies, survived without aggressive surgery. For more extensive pathology, a successful outcome was achieved in 32 of the 36 cases when the upper gastrointestinal (GI) tract was defunctioned because of the presence of major sepsis or because the healthy vascularized tissue was transposed into the area at risk for further fistula formation. Where less aggressive surgery was performed only 12 of 27 patients survived (P < 0.0001). Esophageal surgeons need to be aware of the late complications and associated atypical symptoms of historical procedures which are no longer in common usage. Where an enteropericardial fistula is present, defunctioning of the upper GI tract or repair with transposition of vascularized tissue gives a better chance of a successful outcome. [Table: see text].

Diet type and changes in food cravings following weight loss: findings from the POUNDS LOST Trial.

Few well-controlled trials have evaluated the effects that macronutrient composition has on changes in food cravings during weight loss treatment. The present study, which was part of the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial, investigated whether the fat and protein content of four different diets affected changes in specific food cravings in overweight and obese adults. A sample of 811 adults were recruited across two clinical sites, and each participant was randomly assigned to one of four macronutrient prescriptions: 1) low fat (20% of energy), average protein (15% of energy); 2) moderate fat (40%), average protein (15%); 3) low fat (20%), high protein (25%); 4) moderate fat (40%), high protein (25%). With few exceptions, the type of diet that participants were assigned did not differentially affect changes in specific food cravings. Participants assigned to the high-fat diets, however, had reduced cravings for carbohydrates at month 12 (p<0.05) and fruits and vegetables at month 24. Also, participants assigned to high-protein diets had increased cravings for sweets at month 6 and month 12 (ps<0.05). Participants in all four dietary conditions reported significant reductions in food cravings for specific types of foods (i.e., high fat foods, fast food fats, sweets, and carbohydrates/starches; all ps<0.05). Cravings for fruits and vegetables, however, were increased at month 24 (p<0.05). Calorically restricted diets (regardless of their macronutrient composition) yielded significant reductions in cravings for fats, sweets, and starches whereas cravings for fruits and vegetables were increased.

Portal hypertension and hypersplenism in a patient with a Bochdalek hernia: a case report.

BACKGROUND: A congenital diaphragmatic hernia (Bochdalek's hernia) rarely presents in adulthood. CASE PRESENTATION: We present the case of a 21-year-old woman with thrombocytopenia secondary to hypersplenism due to left-sided (sinistral) portal hypertension. This portal hypertension was caused by strangulation of the spleen within a Bochdalek's hernia. Subacute gastric volvulus compounded by portal hypertensive gastropathy resulted in her presentation with acute haematemesis. CONCLUSIONS: Congenital diaphragmatic hernias may present in the adult. Their presentation is variable, and they may produce life-threatening complications.

Descending necrotising mediastinitis: a safe treatment algorithm.

Descending necrotising mediastinitis can complicate oropharyngeal infection and has a high associated mortality. We present three cases treated in our department and propose a treatment algorithm based on our experience and literature review. The primary oropharyngeal infection was peritonsillar abscess in two cases and odontogenic abscess in one. Two patients underwent cervicotomy and later thoracotomy. The third underwent cervicotomy with transcervical mediastinal drainage and later required pericardial drainage via a subxiphoid incision. All recovered fully and were discharged within 6 weeks. To enable successful treatment, diagnosis needs to be prompt and surgical drainage adequate. Thoracic management of the chest is essential.

Treatment and outcomes of oesophageal perforation in a tertiary referral centre.

OBJECTIVE: The diagnosis and management of oesophageal perforation continues to challenge clinicians. We present our experience of perforated oesophagus in a Tertiary Referral Centre for Thoracic and Oesophageal Surgery. METHODS: Between 1985 and 2000, 75 patients (40 male) with oesophageal perforation were treated in out unit; age range 24-89, median 63. Retrospective review of these cases has been performed. RESULTS: There were 12 deaths (16%). With increases in time from perforation to diagnosis, there was a stepwise increase in the mortality rate. Immediate diagnosis 5%; early diagnosis (1-24h) 14%; late diagnosis (>24h) 44% (P>or=0.002). Site of perforation, aetiology, and treatment strategy had no influence on mortality. The only independent predictor of mortality identified was time to diagnosis from perforation (beta 0.429, P=0.001). Time to definitive management in those undergoing an operative procedure had no influence on outcome with multivariate analysis. CONCLUSIONS: Prompt recognition of the diagnosis of oesophageal perforation and rapid institution of supportive measures, followed by an appropriate, patient specific treatment option optimises the chance of a successful outcome. The wide range of presentation of oesophageal perforation necessitates individualisation of treatment.

Increased nm23 immunoreactivity is associated with selective inhibition of systemic tumour cell dissemination.

AIMS: In vitro transfection experiments show that the nm23 gene suppresses metastasis, although the evidence from clinical studies is contradictory. The purpose of this study was to investigate whether nm23 selectively influences systemic, pleural, and lymphatic metastasis in non-small cell lung cancer (NSCLC). METHODS: Forty two patients undergoing resection of NSCLC and lymph node sampling were enrolled prospectively. In each case, a bone marrow aspirate, pleural lavage, and lymph nodes were assessed using immunohistochemistry for epithelial antigens and morphology. The intensity of nm23-H1 immunoreactivity of the primary tumour was compared with the internal control of normal bronchial epithelium in 32 cases where available. The microvessel count (MVC) of each tumour was determined using immunohistochemistry for the endothelial cell marker CD34. RESULTS: Tumour cell dissemination was detected in the bone marrow in 18 patients, in the pleura in seven, and in the lymph nodes in 21. Increased immunoreactivity for nm23 was found in the primary tumour in six patients, with none having tumour cells in the bone marrow, compared with 12 of 26 patients who showed nm23 immunoreactivity equal to or less than the control (Fisher's exact test: p = 0.043). This effect was confirmed to be independent of the MVC on multivariate analysis. There was no significant difference in the incidence of pleural or lymphatic tumour cell dissemination between the two groups. CONCLUSION: nm23 appears to be a suppressor of systemic, but not lymphatic, metastasis in primary NSCLC.

Effect of ethinyl estradiol on the panic response to the panicogenic agent pentagastrin.

BACKGROUND: Panic disorder (PD) symptomatology has been reported to be altered by hormonal events or treatments which affect estrogen levels. Coryell et al. [Arch. Gen. Psychiatry, 39 (1982) 701-703; Am. J. Psychiatry, 143 (1986) 508-510] have suggested that the increased cardiovascular risk associated with PD is significantly greater in males, alluding to a potential cardioprotective effect of female hormones in the context of panic attacks. In the present study, we were, therefore, interested in elucidating the role of estrogen in modulating the behavioural and cardiovascular responses induced by the panicogenic agent pentagastrin, a cholecystokinin-B (CCK(B)) receptor agonist. METHODS: A double-blind cross-over placebo-controlled design with randomization of the order of a 3-day pretreatment of ethinyl estradiol (EE) (50 microg/day) or placebo was used to assess the effect of a 30-microg i.v. bolus injection of pentagastrin on panic symptom intensity and on increases in heart rate (DeltaHR), systolic (DeltaSBP) and diastolic (DeltaDBP) blood pressure following each pretreatment. Subjects were 9 male healthy controls and 11 male PD patients. RESULTS: EE pretreatment did not significantly reduce the pentagastrin-induced panic symptom scale (PSS) scores and had no effect on DeltaDBP or DeltaSBP. EE did, however, attenuate the pentagastrin-induced increase in HR in both PD patients and healthy controls. LIMITATIONS: Only male subjects were included in the present study; however, we are currently investigating the influence of female gonadal hormones on the panic response to pentagastrin in female PD patients and healthy controls. CONCLUSION: Our results suggest that estrogens may display cardioprotective effects in the context of panic attacks.

A randomized controlled trial of a moderate-fat, low-energy diet compared with a low fat, low-energy diet for weight loss in overweight adults.

CONTEXT: Long-term success in weight loss with dietary treatment has been elusive. OBJECTIVE: To evaluate a diet moderate in fat based on the Mediterranean diet compared to a standard low-fat diet for weight loss when both were controlled for energy. DESIGN: A randomized, prospective 18 month trial in a free-living population. PATIENTS: A total of 101 overweight men and women (26.5-46 kg/m(2)). INTERVENTION: (1) Moderate-fat diet (35% of energy); (2) low-fat diet (20% of energy). MAIN OUTCOME MEASUREMENTS: Change in body weight. RESULTS: After 18 months, 31/50 subjects in the moderate-fat group, and 30/51 in the low fat group were available for measurements. In the moderate-fat group, there were mean decreases in body weight of 4.1 kg, body mass index of 1.6 kg/m(2), and waist circumference of 6.9 cm, compared to increases in the low-fat group of 2.9 kg, 1.4 kg/m(2) and 2.6 cm, respectively; P < or = 0.001 between the groups. The difference in weight change between the groups was 7.0 kg. (95% CI 5.3, 8.7). Only 20% (10/51) of those in the low-fat group were actively participating in the weight loss program after 18 months compared to 54% (27/50) in the moderate-fat group, (P<0.002). The moderate-fat diet group was continued for an additional year. The mean weight loss after 30 months compared to baseline was 3.5 kg (n = 19, P = 0.03). CONCLUSIONS: A moderate-fat, Mediterranean-style diet, controlled in energy, offers an alternative to a low-fat diet with superior long-term participation and adherence, with consequent improvements in weight loss.

Self-expanding oesophageal stents: strategies for re-intervention.

BACKGROUND AND STUDY AIMS: Self-expanding metal stents have become accepted palliation for inoperable malignant oesophageal obstruction, the cost of the devices being offset against the ease of insertion and the reduced complication rate. However, re-intervention is often required for obstruction, malposition, migration and tumour progression. The marginal cost of re-stenting is generally higher than other modalities. This study aims to determine the rate of re-intervention and the effectiveness of the various intervention modalities. PATIENTS AND METHODS: A population of 165 patients, treated in a tertiary referral oesophageal centre, (132 with oesophageal cancer, 31 with mediastinal metastases from other tumours, two with benign conditions) whose initial stent placement was performed between January 1994 and December 1998 was followed-up through July 1999 or till death. RESULTS: A total of 75 re-interventions were required in 44 patients and were successful in 51 (68%). Rigid oesophagoscopy and removal of food bolus was successful in three out of three, dilation in one of 11, rigid oesophagoscopy and physical debridement in 12 of 17 and laser debridement in 12 of 20. Re-stenting was the primary re-intervention in 10 cases and was ultimately necessary in 14 patients (with 11 self-expanding metal stents, three Celestin) who had previously undergone other forms of re-intervention. It was not successful in one case. The median survival following first re-intervention was 9.8 weeks (compared with 14.3 weeks for initial stenting) and was longer in those receiving radiotherapy (23.6 weeks) or chemotherapy (14.4 weeks). CONCLUSIONS: While repeated stenting is usually successful, debridement and laser vaporization are viable alternatives for proximal tumour overgrowth or ingrowth in the upper or middle third of the oesophagus. Distal tumour growth or ingrowth at the oesophagogastric junction are best treated with a second stent. Repeated treatment is justified, as survival following first re-intervention is comparable to that after initial stenting, particularly in those patients who are able to undergo chemotherapy or radiotherapy.

CBP, a transcriptional coactivator and acetyltransferase.

The CREB binding protein (CBP) was first identified as a protein that specifically binds to the active phosphorylated form of the cyclic-AMP response element binding protein (CREB). CBP was initially defined as a transcriptional coactivator that, as a result of its large size and multiple protein binding domain modules, may function as a molecular scaffold. More recently, an acetyltransferase activity, both of histones and nonhistones, has been found to be essential for transactivation. In this review, we will discuss the current understanding of the acetyltransferase specificity and activity of the CBP protein and how it may function to coactivate transcription. We will also examine the regulation of the CBP histone acetyltransferase activity in the cell cycle, by signal-transduction pathways and throughout development.

Effect of medroxyprogesterone pretreatment on pentagastrin-induced panic symptoms in females with panic disorder.

Clinical observation, as well as epidemiological and research data, suggest that female gonadal hormones influence the course of panic disorder (PD). Panicogenic agents such as pentagastrin are useful tools with which to study the pathophysiology of panic attacks. Nine women with PD were randomly assigned to receive, in a crossover design, a 3-day pretreatment with medroxyprogesterone acetate (MP) prior to an injection of pentagastrin, and a 3-day pretreatment with a placebo prior to another injection of pentagastrin. The panic response and the anxiety response to pentagastrin were decreased after MP pretreatment. These preliminary results support the use of laboratory models for investigations of the interactions between progestins and anxiety.

Muscle sparing thoracotomy: a biomechanical analysis confirms preservation of muscle strength but no improvement in wound discomfort.

OBJECTIVES: This study compares the posterior auscultatory triangle thoracotomy incision (muscle sparing) with full posterolateral thoracotomy (where latissimus dorsi muscle is always cut across its full width), with particular attention to the difference between latissimus dorsi muscle strength, post operative pain and chronic wound related symptoms. METHODS: Ten patients who had undergone auscultatory triangle thoracotomy (ATT) at least 1 year previously were matched with ten patients who had undergone posterolateral thoracotomy (PLT). Each pair was matched for age, sex, dominant hand, side of the operation, time since operation and presence or absence of history of previous muscle training. Latissimus dorsi muscle strength was assessed by testing the shoulder adduction strength through an arc of 90-0 degrees using isokinetic technique. Early post-operative pain was assessed indirectly by calculating the analgesic requirement in the first 5 post-operative days. A subjective assessment of chronic post-thoracotomy pain was made using a questionnaire presented to the patients at the time of muscle testing. Variability of the torque curves, recorded as coefficient of variance at the time of muscle strength testing, provided objective measurements of chronic pain. Data were analysed using two sample t-tests. RESULTS: All patients reported at least one chronic post-thoracotomy symptom. There was no significant difference between the two groups in terms of acute or chronic wound pain and other long term wound related symptoms. Shoulder adduction strength was 24% greater in ATT than PLT (95% confidence limits=1-43%, P=0.04). CONCLUSIONS: All thoracotomy patients have long term wound related symptoms. This situation is not improved by performing a muscle sparing incision. However thoracotomy through the triangle of auscultation can preserve latissimus dorsi strength which is compromised in a posterolateral thoracotomy incision. We therefore recommend that a muscle sparing thoracotomy be considered for patients where preservation of muscle strength is deemed important, providing the operation is not compromised due to inadequate access.

An amino acid substitution in the putative second extracellular loop of RBC band 3 accounts for the Froese blood group polymorphism.

BACKGROUND: The low incidence RBC antigen Fr(a) has been excluded from 17 of the 25 established blood group systems. Previous genetic analysis assigned the gene controlling Fr(a) expression to the same chromosomal region as the solute carrier family 4, anion exchanger member 1 gene (SLC4A1). Because SLC4A1 encodes RBC band 3 and controls the expression of Diego blood group system antigens, the possible relationship of Fr(a) to the Diego blood group system was investigated by molecular analysis of SLC4A1. STUDY DESIGN AND METHODS: Blood samples were obtained from the members of two unrelated Mennonite kindreds segregating for Fr(a). DNA was extracted, amplified by PCR using intronic primer sets flanking exons 11-20 of SLC4A1, and screened by single-strand conformation polymorphism (SSCP) analysis. Those exons displaying SSCPs were subjected to DNA sequence analysis. RESULTS: An exon 13 SSCP mobility shift was observed in the DNA from all Fr(a+) persons that was not seen in the DNA from Fr(a-) family members or control subjects. Linkage between the exon 13 SSCP and FR:(a) was established, with peak lods = 3.62 at theta = 0.00 for combined paternal and maternal meioses. DNA sequencing revealed a GAG --> AAG mutation that underlies a Glu480Lys substitution in RBC band 3. CONCLUSIONS: A point mutation in exon 13 of SLC4A1 accounting for a Glu480Lys substitution in band 3 controls Fr(a) expression. On the basis of these our results, the International Society of Blood Transfusion Working Party on Terminology for Red Cell Surface Antigens has assigned Fr(a) to the Diego blood group system, with the designation DI20.

Amino acid substitutions in human erythroid protein band 3 account for the low-incidence antigens NFLD and BOW.

BACKGROUND: The low-incidence red cell antigens NFLD (700.37) and BOW (700.46) were first described in 1984 and 1988, respectively. Recent investigations showed that antigens of the Diego blood group system (including a number of low-incidence antigens) are coded by SLC4A1 (solute carrier family 4, anion exchanger member 1 gene). Among these newly characterized Diego system antigens is Wu (designated DI9). Because a serologic relationship among Wu, NFLD, and BOW has been established, a series of genetic and molecular investigations of SLC4A1 in relation to NFLD and BOW were undertaken. STUDY DESIGN AND METHODS: By the use of exon-specific primers, single-strand conformational polymorphism (SSCP) analysis of SLC4A1 was performed on DNA isolated from an NFLD+ person from Japan, from the members of a Canadian kindred segregating for NFLD, and from two unrelated BOW+ persons. Exons displaying SSCPs were subjected to genetic linkage analysis (for NFLD only) and DNA sequencing. RESULTS: SSCPs in DNA amplified from exons 12 and 14 of SLC4A1 were observed for all NFLD+ subjects. Linkage between each of these polymorphisms and NFLD was established with peak lods = 4.82 at theta = 0.00 for combined paternal and maternal meiosis. DNA sequencing of exons 12 and 14 of SLC4A1 from NFLD+ persons identified A-->T and C-->G mutations that underlie Glu429Asp and Pro561Ala substitutions in human erythroid band 3 protein (band 3). DNA from the two unrelated BOW+ persons only exhibited an SSCP in exon 14 of SLC4A1. Subsequent DNA sequencing revealed a C-->T mutation that accounts for a Pro561Ser substitution in band 3. CONCLUSION: SLC4A1 codes for the low-incidence red cell antigens NFLD and BOW. In light of these findings, both antigens have been assigned to the Diego blood group system.