Identification of genetic variants associated with anterior cruciate ligament rupture and AKC standard coat color in the Labrador Retriever.

Canine anterior cruciate ligament (ACL) rupture is a common complex disease. Prevalence of ACL rupture is breed dependent. In an epidemiological study, yellow coat color was associated with increased risk of ACL rupture in the Labrador Retriever. ACL rupture risk variants may be linked to coat color through genetic selection or through linkage with coat color genes. To investigate these associations, Labrador Retrievers were phenotyped as ACL rupture case or controls and for coat color and were single nucleotide polymorphism (SNP) genotyped. After filtering, ~ 697 K SNPs were analyzed using GEMMA and mvBIMBAM for multivariate association. Functional annotation clustering analysis with DAVID was performed on candidate genes. A large 8 Mb region on chromosome 5 that included ACSF3, as well as 32 additional SNPs, met genome-wide significance at P < 6.07E-7 or Log10(BF) = 3.0 for GEMMA and mvBIMBAM, respectively. On chromosome 23, SNPs were located within or near PCCB and MSL2. On chromosome 30, a SNP was located within IGDCC3. SNPs associated with coat color were also located within ADAM9, FAM109B, SULT1C4, RTDR1, BCR, and RGS7. DZIP1L was associated with ACL rupture. Several significant SNPs on chromosomes 2, 3, 7, 24, and 26 were located within uncharacterized regions or long non-coding RNA sequences. This study validates associations with the previous ACL rupture candidate genes ACSF3 and DZIP1L and identifies novel candidate genes. These variants could act as targets for treatment or as factors in disease prediction modeling. The study highlighted the importance of regulatory SNPs in the disease, as several significant SNPs were located within non-coding regions.

Psychopathic personality in children: genetic and environmental contributions.

BACKGROUND: The current study investigates whether the underlying factor structure of psychopathic personality traits found in adults is similar to that in children and what the extent of the genetic and environmental influences are on these psychopathic traits. METHOD: Psychopathic personality traits were assessed in a community sample of 1219 twins and triplets (age 9-10 years) through caregiver reports of each child's behavior using the Child Psychopathy Scale (CPS). RESULTS: Confirmatory factor analyses revealed an optimal two-factor solution (callous/disinhibited and manipulative/deceitful) to the CPS subscales. Bivariate genetic modeling of the two computed factor scores revealed significant genetic as well as unique environmental influences on psychopathic personality traits in both boys and girls, with heritability estimates of 0.64 and 0.46, respectively, in boys and 0.49 and 0.58, respectively, in girls. No shared environmental influences on psychopathic personality traits were found. CONCLUSIONS: The relationship between the two factors was mediated by both genetic and unique environmental factors common to both traits.

Carbon, nitrogen, and phosphorus fluxes in household ecosystems in the Minneapolis-Saint Paul, Minnesota, urban region.

Rapid worldwide urbanization calls for a better understanding of the biogeochemical cycling of those macroelements that have large environmental impacts in cities. This study, part of the Twin Cities Household Ecosystem Project, quantified fluxes of carbon (C), nitrogen (N), and phosphorus (P) at the scale of individual households in the Minneapolis-Saint Paul metropolitan area in Minnesota, USA. We estimated input and output fluxes associated with several components of household activities including air and motor vehicle travel, food consumption, home energy use, landscape, pets, and paper and plastic use for 360 owner-occupied, stand-alone households. A few component fluxes dominated total input fluxes of elements. For instance, air and motor vehicle transportation, together with home energy use, accounted for 85% of total C consumption and emissions. All total and component fluxes were skewed to varying degrees, suggesting that policies targeting disproportionately high fluxes could be an effective and efficient way to reduce pollution. For example, 20% of households contributed 75% of air travel emissions and 40% of motor vehicle emissions. Home energy use was more nearly normally distributed. Nitrogen fluxes were dominated by human diet and lawn fertilizer applications, which together accounted for 65% of total household N inputs. The majority of P inputs were associated with human diet, use of detergents, and pet food. A large portion of the variation among household fluxes of C, N, and P was related to a few biophysical variables. A better understanding of the biophysical, demographic, and behavioral drivers of household activities that contribute to C, N, and P fluxes is pivotal for developing accurate urban biogeochemical models and for informing policies aimed at reducing sources of pollution in urban ecosystems.

Utility of retrograde ureterocelogram in management of complex ureterocele.

INTRODUCTION: Symptomatic pediatric ureterocele has diverse manifestations, making evidence-based management impractical. Thus, detailed visualization of ureterocele anatomy prior to first surgical incision is invaluable. Retrograde ureterocelogram (RUC) is a simple, underutilized radiologic technique that can be performed during cystoscopy. This study sought to determine whether RUC changes surgical management by more accurately depicting the complex ureteral and ureterocele anatomy, compared with renal ultrasound (US) and voiding cystourethrography (VCUG). METHODS: Patients who underwent surgical management of ureterocele from 2003 to 2015 were identified; those who received concomitant fluoroscopic RUC were selected for the case series. Data collected included: demographics, pre-operative evaluation, surgical interventions, and outcomes. The RUC images were individually examined, and the anatomic impression compared with previous renal US and VCUG. Novel RUC findings not previously appreciated by the pre-operative evaluation were noted. The RUC was performed by cystoscopically inserting a needle into the ureterocele and injecting contrast retrograde. If indicated, simultaneous PIC (Positioning the Instillation of Contrast) cystography was performed. RESULTS: Of the 43 patients that underwent surgery for suspected ureterocele, 28 underwent cystoscopy + RUC (10 M: 18 F) at a median age of 4.6 months and median follow-up of 37.0 months. All patients had prior US, 25 had prior VCUG, and 20 had prior radionuclide studies. Ureteroceles were either duplex system (n = 21) or single system (n = 7); 17 were ectopic into the bladder neck or urethra; seven were intravesical; and four were pseudoureteroceles. Fourteen patients underwent concomitant transurethral incision of the ureterocele (TUIU); two were deferred for surgery; and 11 received concomitant definitive surgery (e.g., nephrectomy). The RUC illuminated novel aspects of the anatomy in 20 of the 28 patients. No adverse events occurred. Notably, in nine of the 28 children, significant observations from RUC prompted change to the pre-operative surgical plan. DISCUSSION: Retrograde ureterocelogram clearly revealed ureterocele ectopy, pseudoureterocele, ureterocele disproportion, and unsuspected duplex systems, making it a useful adjunct to standard US and VCUG studies. Retrograde ureterocelogram can also be used to fluoroscopically verify decompression of the ureterocele post incision, document severity of ureteral dilation, and teach residents about the great damage generated by ureterocele variations. Limitations of RUC included increasing radiation dose and overall cost. The study design was limited by its small size, retrospective approach, selection bias, and availability of RUC images. CONCLUSIONS: While not indicated in routine ureterocele management, intraoperative RUC further defined ureterocele anatomy in nearly all cases and yielded changes to the original surgical plan frequently enough to merit greater use in complex patients.

Clitoral hoodplasty in females with disorders of sex development.

INTRODUCTION: The surgical management of girls with masculinized genitalia is gradually changing towards a more conservative approach. Reports on loss of clitoral sensitivity and related impairment of sexual function in women after feminizing genital surgery in childhood have been pivotal in this evolution. An exposed clitoral glans is occasionally seen at follow-up, and while patients may complain of aesthetics, no clitoral discomfort secondary to glans exposure has been reported. A technique has been developed to reconstruct the clitoral hood and the present study reports the preliminary results. OBJECTIVES: To report the novel technique and preliminary results of clitoral hood reconstruction to cover an exposed glans after previous clitoroplasty in patients with congenital adrenal hyperplasia (CAH). PATIENTS AND METHODS: Six female patients (mean age 13, range 4-21 years) with CAH sought medical help for clitoral concerns after previous reduction clitoroplasty. In two of the six patients, the main complaint was clitoral hypersensitivity or even pain. The clitoral glans was completely exposed in all patients, who were subsequently treated with a bi-laminar V-Y clitoral hoodplasty to create a mobile and natural-looking clitoral hood composed of an inner and outer preputial skin layer. RESULTS: Postoperative covering of the glans was complete in five patients, and partial in one. The two patients with pre-operative pain became asymptomatic; all six patients were pleased with the cosmetic postoperative results. CONCLUSION: Clitoral hoodplasty provides simple, yet effective, relief for women with cosmetic concerns or clitoral discomfort after previous feminizing surgery.

Subsyndromal symptoms in bipolar disorder. A comparison of standard and low serum levels of lithium.

Ninety-four patients with bipolar disorder participating in a random-assignment, double-blind, prospective maintenance trial of standard- (0.8 to 1.0 mmol/L) vs low-range (0.4 to 0.6 mmol/L) serum lithium levels were assessed to determine the presence and significance of subsyndromal symptoms during periods of remission and recovery. A significant relationship was found between prescribed serum lithium level and the probability of major affective relapse and the occurrence of subsyndromal symptoms. Patients given lithium carbonate to achieve low-range levels had 2.6 times the risk of major affective relapse as those given lithium for standard-range levels and nearly twice the risk of developing subsyndromal symptoms. Patients given the low-range therapy showed a greater variance in weekly Psychiatric Status Rating measures, and their symptoms were more likely to worsen at any time than were symptoms in their standard-level group counterparts. The first occurrence of subsyndromal symptoms increased the risk of major affective relapse fourfold. Following the onset of subsyndromal symptoms, the patients originally randomized to receive standard-range lithium therapy were still better protected from relapse than were patients randomized to receive low-range lithium treatment. Patients were two times more likely to develop depressive than hypomanic symptoms between acute episodes of illness. However, onset of hypomanic symptoms predicted subsequent major affective relapse twice as strongly as did depressive symptoms. Seventy-six percent of patients who became hypomanic had a major affective relapse, compared with 39% of patients who were subclinically depressed.

Impact and frequency of extra-genitourinary manifestations of prune belly syndrome.

INTRODUCTION: Prune belly syndrome (PBS) extra-genitourinary (extra-GU) manifestations are serious comorbidities beyond the genitourinary (GU) anomalies of this disease. We hypothesized an underestimation of the reported frequency and understated impact on quality of life (QOL) of extra-GU comorbidities in PBS survivors beyond the newborn period. To assess this, the frequencies of extra-GU manifestations of PBS in a contemporary cohort of living patients were compared to compiled frequencies from published literature. Second, the impact of extra-GU PBS manifestations on patient/family QOL was assessed via a non-validated open-ended survey. MATERIAL AND METHODS: From 2010 to 2013, PBS survivors were prospectively recruited locally or at three PBS Network National Conventions. The family/subject was asked to complete a detailed PBS questionnaire, non-validated QOL survey, and provide medical records for review. Clinical data were extracted from medical records for local patients. The frequencies of extra-GU manifestations were compared between the contemporary, living cohort and a published literature cohort derived from PubMed. RESULTS AND DISCUSSION: Seven of 706 published studies met criteria for frequencies tabulation of extra-GU PBS manifestations. This largest reported living PBS patient cohort (n = 65) was 99% male with mean age 10 years (1 month-45 years). The living PBS cohort had a statistically significantly higher incidence of gastrointestinal (63%), orthopedic (65%), and cardiopulmonary (49%) diagnoses compared to the compiled published cohort (n = 204). Eleven PBS males and 32 family members completed the QOL survey. Of these, 47% listed at least one non-GU problem (i.e. lung disease, skeletal problems, constipation) as negatively affecting their QOL; 42% listed at least one GU problem (i.e. self-catheterization, recurrent UTIs) as negatively affecting their QOL; 56% reported musculoskeletal surgery and 21% reported gastrointestinal surgery/medication as positively impacting their QOL. CONCLUSIONS: In this large contemporary series, surviving individuals with PBS had a significantly higher incidence of orthopedic, gastrointestinal, and cardiopulmonary diagnoses than previously reported in PBS publications. From the patient/family QOL perspective, non-GU PBS manifestations negatively impact their QOL and treatment of these non-GU conditions improves their lives. As urologic surgeons for these medically complex patients, it is extremely important to be aware of and prepare for the high incidence of non-GU PBS comorbidities directly impacting the medical and surgical treatment and QOL of PBS patients and their families.

An analysis of clinical outcomes using color doppler testicular ultrasound for testicular torsion.

OBJECTIVES: To delineate the clinical outcomes of color Doppler ultrasound (US) in the equivocal torsion patient. METHODS: From 1992 to 1997, 130 patients (<23 years old) from 2 institutions underwent US imaging using a 7.5-mHz linear transducer to evaluate an acute scrotum equivocal, or of low suspicion, for torsion. The US reports and hospital charts of these patients were retrospectively reviewed. RESULTS: After clinical and radiologic evaluation, torsion was excluded in 110 patients without surgical exploration. In 3 patients, intermittent testicular torsion was diagnosed and in 17 patients, emergent exploration was performed for US diagnosis of testicular torsion. Twenty-five patients (22.7%) were subsequently lost to follow-up. Follow-up of 85 patients with US negative for torsion (mean length of follow-up = 466.9 days) revealed no testicular atrophy in 83. Two patients underwent delayed orchiectomy/contralateral orchiopexy for missed testicular torsion. Of 17 patients with US positive for torsion, 9 underwent orchiectomy for a necrotic torsed testis, 7 viable torsed testes were found, and 1 torsed appendix testis was found. Therefore, color Doppler US for the equivocal acute scrotum yielded a 1% false-positive rate, sensitivity of 88.9%, and specificity of 98.8%. CONCLUSION: When faced with ruling out testicular torsion, it is necessary to integrate the multiple pieces of patient data, knowing that each piece of data may have inaccuracies. With this in mind, this analysis of outcomes verifies that color Doppler US is an excellent adjunctive study in the clinically real situation in which the clinical evaluation is equivocal or low suspicion.

Embryonic development of the ureter.

During human embryonic development, the ureteric bud, a simple epithelial tube that arises from the Wolffian duct, initiates a cascade of events which results in the formation of the metanephros and its collecting system. In this review, the anatomic and molecular basis of ureteric development are discussed. Although it is difficult to separate metanephrogenesis from ureterogenesis of the proximal segment, the data presented are biased toward the latter. Some of the factors involved in the budding and branching of the embryonic ureter and the maturation of the fetal ureter into a peristaltic conduit are discussed as presently understood. Finally, a brief description of congenital abnormalities in ureteral development is presented with some putative mechanisms.

The clinical course of panic disorder and depression.

The evidence obtained in the past decade that depression is both chronic and recurrent in many patients has started to change the way the disorder is diagnosed and treated. The authors review findings from the Clinical Studies of the National Institute of Mental Health Collaborative Program on the Psychobiology of Depression that support the existence of high rates of chronicity and relapse in depression. They then review naturalistic studies conducted before the development of efficacious treatments for panic disorder and follow-up studies conducted in the past 10 years, both of which revealed high levels of chronicity in panic disorder patients. The implications of those findings for the diagnosis and treatment of panic disorder are discussed, and directions for future work in both depression and panic disorder are suggested.

Antisperm autoantibody responses to vasectomy and vasovasostomy in Fischer and Lewis rats.

Antisperm autoantibodies were studied in Fischer and Lewis strains of rats after either vasectomy, vasectomy followed one month later by vasovasostomy, or sham operations. The time course of antibody response to sperm protein autoantigens was assayed by Western blot analysis of sera obtained at intervals up to 3 months. Rats of both strains responded to immunization with isologous spermatozoa with production of high titer hyperimmune sera. Sera from vasectomized Fischer rats showed antisperm antibodies on Western blots, but bands were stained with less intensity and frequency than for Lewis rats. In both Fischer and Lewis strains, major protein autoantigens were observed at 75-83, 68-71, 63, 57, 51, 41, and 21-23 kDa, lending support to the hypothesis that there is a set of dominant sperm autoantigens recognized by a consensus of postvasectomy rat sera. The lesser response of Fischer rats to vasectomy was not due to absence of dominant postvasectomy sperm autoantigens in Fischer sperm extracts, nor was it attributable to inability of Fischer rats to mount an immune response to these antigens, since immunization with isologous sperm was successful in raising antibodies to the dominant autoantigens. Vasovasostomy did not result in a general decrease in antisperm antibodies, and reactions to some antigens actually increased.

Temporal recognition of sperm autoantigens by IgM and IgG autoantibodies after vasectomy and vasovasostomy.

Temporal patterns of IgM and IgG autoantibodies to sperm proteins were studied by western blot analysis at intervals after bilateral vasectomy, vasectomy followed one month later by vasovasostomy, or sham operations. Responses were detected to eight major autoantigens at 21-23, 36, 41, 51, 57, 63, 68-71 and 75-83 kDa, by study of staining patterns of sequential serum samples from individual animals and by analysis of the incidence of reaction to each protein. The four lower molecular weight antigens (21-23, 36, 41 and 51 kDa) provoked mainly IgG responses. The strongly stained set of higher molecular weight antigens (57, 63, 68-71 and 75-83 kDa) tended to show more clearly defined temporal patterns of IgM followed by IgG response, including a high incidence of IgM antibody at the 2-week interval. Three of the larger peptides (57, 63 and 68-71 kDa) appeared highly immunogenic, since some reactions were detected even in sham-operated rats. The classical patterns of IgM and IgG antibody responses to the majority of the dominant sperm autoantigens are in accord with the hypothesis that vasectomy mimics immunization with spermatozoa. The high incidence of IgM antibodies in the earliest sample, taken 2 weeks after vasectomy, suggests that the initial immunizing event takes place within about a week after the operation. Vasovasostomy did not bring about a decrease in antisperm antibodies. Instead, some animals demonstrated an increased reaction to certain antigens after reversal of vasectomy, even though the vasovasostomies were anatomically successful.

PIP: The production of antisperm antibodies is common subsequent to vasectomy and antisperm antibodies frequently persist following the reversal of vasectomy. The number of such antibodies may even increase after vasovasostomy. Using adult male Lewis rats, the authors analyzed the dominant autoantigens which evoke IgM and/or IgG autoantibodies after vasectomy by western blotting (WB) methods, the temporal patterns of IgM and IgG autoantibodies to specific sperm proteins, and the influence of vasovasostomy upon IgM and IgG antisperm autoantibodies. The temporal patterns were studied by WB at intervals after bilateral vasectomy, vasectomy followed 1 month later by vasovasostomy, and fake operations. Responses were detected to 8 major autoantigens of 21-23, 36, 41, 51, 57, 63, 68-71, and 75-83 kDa through the study of staining patterns of sequential serum samples from individual animals and by analysis of the incidence of reaction to each protein. The 4 lower-molecular-weight antigens provoked mainly IgG responses, while the strongly stained higher-molecular-weight antigens showed more clearly defined temporal patterns of IgM followed by IgG response, including a high incidence of IgM antibody at the 2-week interval. The peptides of 57, 63, and 68-71 kDa seemed to be highly immunogenic, since some reactions were detected even in rats which received only a fake operation. Results support the hypothesis that vasectomy mimics immunization with spermatozoa, while the high incidence of IgM antibodies in the earliest sample, taken 2 weeks after vasectomy, suggests that the initial immunizing event occurs within approximately 1 week after the operation. Vasovasostomy caused no decrease in antisperm antibodies.

Obesity and decreased femoral anteversion in adolescence.

The degree of femoral anteversion in a group of obese adolescent children and a group of adolescent children of normal weight was determined by either magnetic resonance imaging or computerized axial tomography. Compared with the children of normal weight, the obese children showed a significantly reduced angle of femoral anteversion. Increased biomechanical forces generated across the hip joint of obese children leads to increased remodeling of the femoral neck. This may account for the association of slipped capital femoral epiphysis, reduced femoral anteversion, and obesity in the adolescent population.

Leydig cell function after experimental testicular torsion despite loss of spermatogenesis.

Little is known about specific testicular cell responses to periods of testicular torsion. In particular, the steroidogenic capacity of Leydig cells in the post-torsion testis is unknown. Male Sprague-Dawley rats (450-550 g) underwent no torsion (control) or a 720 degrees unilateral testicular torsion for either 0 (sham), or 1 or 2 Such torsions have previously been shown to cause progressive damage to the rat testis. One, 15, or 30 days after torsion repair all animals (n = 5-10/group) were prepared for testicular venipuncture and intravenous infusion of ovine luteinizing hormone (LH) via the femoral vein. Testicular venous blood was collected directly from the surface of the testis both 5 minutes prior to and 90 minutes after infusion of predetermined ED50 (0.1 microgram) or ED100 (0.5 microgram) doses of LH. Testicular venous serum (TVS) was assayed for testosterone (T) by radioimmunoassay. Control animal TVS T concentrations before LH infusion and 90 minutes after ED50 and ED100 LH stimulation were 103 +/- 25, 621 +/- 103, and 1,055 +/- 140 ng/ml, respectively. Testes having experienced a 1-hour torsion did not have a significantly (P < 0.05) reduced capacity to respond to ED50 and ED100 stimulation at either 15 and 30 days after the torsion. Testes having experienced a 2-hour torsion did have significantly reduced (P < 0.05) ED50 responses at both 1 hour and 30 days after torsion repair. More remarkably, significant steroidogenic reserve was still present in testes after torsion, which in previous studies had been shown to have permanent loss of spermatogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunoscintigraphy of colorectal cancer using a monoclonal antibody 77-1.

The monoclonal antibody (mAb) 77-1 recognizes epithelial membrane antigen (EMA) expressed by the majority of colorectal cancers. Following administration of indium-111 labelled 77-1, gamma camera imaging was carried out on 16 patients with known or suspected colorectal cancer prior to surgery or endoscopic laser therapy. Fourteen of the patients were found to have cancer, with one patient having two primary lesions. Two patients suspected of tumour recurrence were not found to have a lesion at laparotomy. Imaging before operation or laser therapy detected 10 out of 15 lesions (67%). Tumours which produced positive images were found to express the target antigen on immunocytochemical staining of the excised tumours. A mean tumour to normal colon ratio of 1.63 +/- S.D. 0.46 and a mean tumour to blood ratio of 3.60 +/- 1.48 were found at day 6 after antibody administration. A high uptake of radiolabel by the liver prevented the detection of hepatic metastases, present in three patients. Of the two patients with suspected recurrence a false positive scan was found in one owing to the presence of inflammatory tissue. Indium-111 labelled 77-1 may have a role in the imaging or targeting of colorectal cancer.

Influence of depression on the treatment of panic disorder with imipramine, alprazolam and placebo.

This paper presents findings from a multisite study of 126 subjects meeting DSM-III-R criteria for Panic Disorder who also met criteria for a concurrent Major Depressive Episode, Dysthymia, or Depressive Disorder NOS. The study's primary aim was to discern the influence of varying degrees of depression on the comparative efficacy of alprazolam, imipramine and placebo on anxiety outcomes. A placebo-controlled, double-blind, parallel random assignment design was utilized over a total of 16 weeks. There was no medication effect on panic outcomes. At endpoint, percent of anticipatory anxiety (i.e., time spent worrying about having an anxiety attack) was significantly lower in the patients taking active medications vs. placebo. Phobic measures were significantly improved by alprazolam, vs. both imipramine and placebo early in the study; however, by week 8 both active medications were equally superior to placebo in the reduction of phobic symptoms. In addition, both active medications were significantly more effective than placebo in reducing depression. The same efficacy pattern (i.e., active medications superior to placebo) was observed on measures of general functioning. Importantly, there were no significant interactions observed between medication and presence of major depression on the depression measures, indicating that both alprazolam and imipramine were equally efficacious in treating the depression in patients with panic disorder and major depression. Since the patients enrolled in this study suffered from major depressive disorder in the mild to moderate severity range, these results may not be transferrable to patients with panic disorder and severe major depression.

Nonshared environmental influences and personality differences in adult twins.

The twin design was used to examine the importance of different experiences of siblings within the family and to identify relations between twins' personality differences and their differential experiences. A sample of 161 monozygotic and 74 dizygotic twin individuals between the ages of 18 and 75 years retrospectively reported on their different experiences when growing up. The Sibling Inventory of Differential Experience (SIDE) was used for the first time with a sample of twin siblings. In addition, the twins provided self-report measures of affect and personality. In contrast to results from a sibling adoption design, this study of twins showed greater evidence for genetic variance in the SIDE scales. Nevertheless, the SIDE showed significant associations with differences in personality and affect for monozygotic twins, which reflect pure environment-behavior relations.

Immunolocalisation of an anti-EMA monoclonal antibody to a renal carcinoma xenograft.

The monoclonal antibody 77-1 originally raised to a membrane extract of human bladder cancer reacted with a human renal carcinoma xenograft XK1 on immunoperoxidase staining. This suggested a potential role for its immunolocalisation to renal carcinoma, and prompted a localisation study of the I-125 and In-111 labelled 77-1 to the xenograft. The uptake of the radiolabelled antibody by the xenograft was measured as a tumour to blood ratio taken at 24 hour intervals for up to 72 hours. Four animals were used for each time point and the mean tumour to blood ratio obtained. A monoclonal antibody 48-1, non reactive with XK1, was similarly radiolabelled and administered to another group of animals bearing the xenografts to act as a control. Statistical analysis using the unpaired Student't' test showed that the uptake of the 1-125 and In-111 labelled 77-1 by the xenografts was significantly higher than the non-specific antibody 48-1 at all time points (p less than 0.002-0.018), demonstrating that a specific localisation to the xenograft XK1 by the radiolabelled 77-1 had occurred.