The role of single nucleotide variant rs3819817 of the Histidine Ammonia-Lyase gene and 25-Hydroxyvitamin D on bone mineral density, adiposity markers, and skin pigmentation, in Mexican population.

PURPOSE: Vitamin D (VD) deficiency and osteoporosis have become a global public health problem. A variant in the Histidine Ammonia-Lyase (HAL) gene has been associated with VD levels and bone mineral density (BMD). However, whether this variant has an influence on VD levels and BMD in Mexican adults remain unclear. METHODS: This cross-sectional analysis included 1,905 adults participating in the Health Worker Cohort Study and 164 indigenous postmenopausal women from the Metabolic Analysis in an Indigenous Sample (MAIS) cohort. The rs3819817 variant was genotyped by TaqMan probe assay. Total 25 hydroxyvitamin D levels were measured by DiaSorin Liaison. BMD at the different sites was assessed through dual-energy X-ray absorptiometry. Linear and logistic regression models were performed to evaluate the associations of interest. RESULTS: The prevalence of VD deficiency was 41%, showing differences between sexes. Obesity and skin pigmentation were associated with lower levels of VD in males and females. rs3819817-T allele was associated with low levels of 25-hydroxyvitamin D, VD deficiency, and hip and femoral neck BMD values (g/cm2). We found two interactions with VD levels, one between adiposity and rs3819817-T allele (P = 0.017) and another between skin pigmentation and rs3819817-T allele (P = 0.019). In indigenous postmenopausal women, we observed higher VD levels in the southern region compared to the northern region (P < 0.001); however, we did not observe differences by genotype. CONCLUSION: Our findings confirm that the genetic variant rs3819817 has an essential function in VD levels and BMD and suggests a role in skin pigmentation in the Mexican population.

Anal trauma caused by bull-horn injury.

BACKGROUND: Bullfighting festivals are commonly performed at Spain. Perineal trauma due to bull-horn injury is associated with high morbidity due to sphincteric associated lesions METHODS: We report a case of 37-year-old male patient with anal trauma due to a bull-horn injury involving the sphincter complex, treated in our Emergency department RESULTS: Urgent surgery was performed with primary sphincteroplasty, without performing a colostomy. The associated complication was a partial dehiscence of the surgical wound (Clavien-Dindo I). No transfusions, re-interventions or readmissions were registered. The degree of incontinence at discharge and after 12 month follow-up, according to the Wexner scale was 8 points and 2 points, respectively. CONCLUSIONS: The main treatment of bull-horn injuries is extensive surgical debridement, antibiotic therapy, and lavage of the area. In cases involving the anal sphincter, primary sphincteroplasty is recommended. The modern trend does not include the systematic performance of a colostomy however, it has been described in cases with catastrophic wounds and urological lesions associated.

Association between vitamin D deficiency and common variants of Vitamin D binding protein gene among Mexican Mestizo and indigenous postmenopausal women.

PURPOSE: Vitamin D deficiency (VDD) and polymorphisms in the group-specific component (GC) gene are known to be associated in different populations. However, the effects of such genetic variants may vary across different populations. Thus, the objective of this study was to estimate the association between Vitamin D-Binding Protein (VDBP) haplotypes and VDD in mestizo postmenopausal women and Mexican Amerindian ethnic groups. METHODS: This was a cross-sectional study of 726 postmenopausal Mexican women from the Health Workers Cohort Study (HWCS) and 166 postmenopausal women from the Metabolic Analysis in an Indigenous Sample (MAIS) cohort in Mexico. GC polymorphisms (rs7045 and rs4588) were analyzed by TaqMan probes. Serum 25-hydroxyvitamin D [25(OH)D] levels were measured by Chemiluminescent Microparticle Immuno Assay. RESULTS: The prevalence of VDD serum 25(OH)D < 20 ng/mL was 43.7% in mestizo women and 44.6% in indigenous women. In HWCS, the single nucleotide polymorphisms (SNPs) rs7041 and rs4588 were associated with VDD. In addition, women from the HWCS, carrying the haplotypes GC2/2 and GC1f/2 had higher odds of VDD (OR = 2.83, 95% CI 1.14, 7.02; and OR = 2.30, 95% CI 1.40, 3.78, respectively) compared to women with haplotype 1f/1 s. These associations were not statistically significant in the MAIS cohort. CONCLUSIONS: Our results show genetic association of the analyzed SNPs and related haplotypes, on the GC gene, with VDD in mestizo Mexican postmenopausal women. Moreover, a high prevalence of VDD with high genetic variability within the country was observed. Our results support the need for national policies for preventing VDD.

Approach and management of patients injured by bullfighting trauma. / Abordaje y manejo médico-quirúrgico del paciente herido por traumatismo taurino.

INTRODUCTION: Bullfighting festivals are attributed to the cultural idiosyncrasies of the Ibero-American people, posing an extreme risk to the physical integrity of the participants. Spain is considered the country with the highest number of bull-related celebrations worldwide and, therefore, with the highest number of patients injured by bullfighting trauma treated, thus justifying a public health problem. The generalities associated with this type of trauma define the people injured as polytraumatised patients. In addition, it is important to know the kinematics of the injuries and their specific characteristics, in order to implement quality medical-surgical care. METHODS: scientific review of the literature to promote a comprehensive guide for the medical-surgical management of patients injured by bullfighting trauma. RESULTS: We described the guidelines to standardise protocols for in-hospital approach of patients injured by bullfighting trauma. CONCLUSIONS: Bullfighting trauma is considered a real health problem in the emergency departments of the ibero-Americans countries, especially in Spain, where bullfighting is part of the national culture. The inherent characteristics of these animals cause injuries with special aspects, so it is important to know the generalities of bullfighting trauma. Because of the multidisciplinary approach, this guidelines are adressed to all healthcare providers involved in the management of these patients. It is essential to establish particular initial care for this type of injury, specific therapeutic action and follow-up based on the medical-surgical management of the trauma patient in order to reduce the associated morbidity and mortality.

Treatment of esophageal perforation: A review of our experience at a tertiary referral hospital spanning the past 19 years.

INTRODUCTION AND AIMS: Esophageal perforation is an uncommon event that is a medical/surgical emergency, with a 15-30% mortality rate. The aim of the present study was to communicate our experience in the management of esophageal perforation, evaluating the different strategies utilized, in an effort to establish measures to guide decision-making in selecting treatment. MATERIALS AND METHODS: A retrospective descriptive study was conducted on patients diagnosed with esophageal perforation at our hospital center, within the time frame of 2000 and 2019. RESULTS: Over the past 19 years, 15 patients were diagnosed with esophageal perforation. Surgical treatment was carried out in 80% of the cases. Primary closure, reinforced with plasty, was performed in 67% of the patients, of whom 62.5% had early diagnosis and a 100% survival rate. Diagnosis was late in 37.5% of the cases, with a 33.3% survival rate. Esophagectomy and gastric pull-up were performed on 25% of the patients, 66.6% of whom had early diagnosis and a 100% survival rate. In the 33.3% that had late diagnosis, the mortality rate was 100%. Esophagectomy, with cervical esophagostomy and feeding jejunostomy, was performed on one of the patients (8.3%) that had early diagnosis and a 100% survival rate. CONCLUSIONS: The main survival predictor in esophageal perforation is the interval of time between the injury and its diagnosis, and in turn, the resulting treatment. Each patient with esophageal perforation should have individualized treatment to adequately manage the condition.

Pigmentary mosaicism as a recurrent clinical manifestation in three new patients with mosaic trisomy 12 diagnosed postnatally: cases report and literature review.

BACKGROUND: To date, only twenty-one cases diagnosed postnatally with mosaic trisomy 12 have been reported. The most frequent phenotypic manifestations are developmental delay, dysmorphic facial features, congenital heart defects, digital alterations, and pigmentary disorders. In the present report, detailed clinical and genetic profiles of three unrelated new patients with mosaic trisomy 12 are described and compared with previously reported cases. CASE PRESENTATION: In the present report, we include the clinical, cytogenetic, and molecular description of three Mexican patients diagnosed postnatally with mosaic trisomy 12. At phenotypic level, the three patients present with developmental delay, dysmorphic facial features, congenital heart defects and skin pigmentary anomalies. Particularly, patient 1 showed unique eye alterations as bilateral distichiasis, triple rows of upper lashes, and digital abnormalities. In patient 2 redundant skin, severe hearing loss, and hypotonia were observed, and patient 3 presented with hypertelorism and telecanthus. Hyperpigmentation with disseminated pigmentary anomalies is a common trait in all of them. The cytogenetic study was carried out under the strict criteria of analysis, screening 50-100 metaphases from three different tissues, showing trisomy 12 mosaicism in at least one of the three different tissues analyzed. With SNParray, the presence of low-level mosaic copy number variants not previously detected by cytogenetics, and uniparental disomy of chromosome 12, was excluded. STR markers allowed to confirm the absence of uniparental disomy as well as to know the parental origin of supernumerary chromosome 12. CONCLUSIONS: The detailed clinical, cytogenetic, and molecular description of these three new patients, contributes with relevant information to delineate more accurately a group of patients that show a heterogeneous phenotype, although sharing the same chromosomal alteration. The possibility of detecting mosaic trisomy 12 is directly associated with the sensitivity of the methodology applied to reveal the low-level chromosomal mosaicism, as well as with the possibility to perform the analysis in a suitable tissue.

Polymorphisms CYP2R1 rs10766197 and CYP27B1 rs10877012 in Multiple Sclerosis: A Case-Control Study.

BACKGROUND: Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease. Low vitamin D levels have been reported to be a risk factor for MS, and genetic variances could be implicated. The aim of this study was to evaluate the association of MS with rs10766197 polymorphism of CYP2R1 gene and rs10877012 polymorphism of CYP27B1 gene. The second aim was to analyse whether these polymorphisms are associated with the severity of the progression of MS. Material and Methods. In a case-control study, we included 116 MS patients and 226 controls, all of whom were Mexican Mestizo. MS was diagnosed by McDonald criteria (2017). A complete neurological evaluation was performed to evaluate the severity of disease progression. Serum 25-hydroxyvitamin D [25(OH) vitamin D] levels were measured by ELISA. Single nucleotide polymorphisms rs10766197 of CYP2R1 gene and rs10877012 SNP of CYP27B1 gene were genotyped by real-time PCR. RESULTS: Serum 25(OH) vitamin D levels were lower in MS patients than in controls (p = 0.009). No differences were observed between serum 25(OH) vitamin D levels of MS patients with severe progression compared to low progression (p = 0.88). A higher frequency of the A allele of CYP2R1 rs10766197 was observed between MS patients and controls (p = 0.05). No differences were observed in the frequency of T allele of CYP27B1 rs10877012 (p = 0.65). In subanalysis, patients with GA + AA genotypes of CYP2R1 rs10766197 had an increased risk of MS compared to controls (p = 0.03). No increased risk was observed in GT + TT genotypes of CYP27B1 rs10877012 (p = 0.63). No differences were observed in allele frequencies of either polymorphism between patients with severe vs. low disease progression. CONCLUSION: Lower serum 25(OH) vitamin D levels were observed in MS patients than in controls, although these levels were not associated with disease progression. Carriers of GA + AA genotypes of CYP2R1 rs10766197 had an increased risk of MS. None of these polymorphisms was associated with severe progression of MS.

Localization of the membrane attack complex (MAC) in experimental immune complex glomerulonephritis.

The role of the membrane attack complex (MAC) as a mediator of renal tissue injury was evaluated in rats affected by bovine serum albumin (BSA)-induced immune complex glomerulonephritis. Immunofluorescence studies revealed concurrent deposits of IgG, BSA, C3, and the MAC along glomerular capillary walls, although the MAC manifested a more restricted distribution than that observed for immune complexes. Immunoelectron microscopic techniques were utilized to demonstrate immune complexes, C3, and the MAC within dense deposits in the subepithelial aspect of the basement membrane. Visceral epithelial foot processes were fused in areas overlying large dense deposits and exhibited intense staining for the MAC, lesser reactivity for C3 but IgG was absent from the foot process membranes. Smaller granular deposits of immune complexes, C3, and the MAC were observed in the subendothelial region of the lamina rara interna and the lamina densa. Immune complexes may activate the classical complement pathway causing diffuse injury to the glomerular basement membrane (GBM), allowing subepithelial accumulation of complexes. These observations implicate the MAC as a mediator of GBM and juxtaposed podocyte membrane injury, thereby contributing to disruption of the glomerular filtration barrier. IgG and C3 were demonstrated within tubulointerstitial regions on the surface of collagen fibers in close proximity to the tubular basement membrane (TBM) of proximal convoluted tubules. Within the TBM, C3 localization was prominent with diminished reactivity for the MAC, but IgG was not detectable. The demonstration of C3 and scant MAC deposits in the TBM of nonimmunized control rats without evidence of interstitial IgG and C3 deposits suggests that both nonimmune and immune processes play a role in the pathogenesis of extraglomerular lesions. Evidence derived from these morphologic studies indicates that the MAC is associated with injury to the GBM, foot process membranes of visceral epithelium, and the TBM. Further experiments designed to selectively enhance or inhibit the deposition of MAC and assess consequent renal dysfunction are required to substantiate hypotheses concerning the in vivo membranolytic potential of the MAC in experimental immune complex glomerulonephritis.

Isolation and characterization of the nephritogenic antigen producing anti-tubular basement membrane disease.

Using monoclonal antibody affinity chromatography, we isolated a 48,000 mol wt, glucose-rich glycoprotein (3M-1) from collagenase-solubilized rabbit renal tubular basement membrane (SRTA). The purified 3M-1 protein is noncollagenous, and is capable of inducing anti-TBM (tubular basement membrane) antibodies and interstitial nephritis in susceptible hosts. Further, when SRTA, at a normally nephritogenic dose, was selectively depleted of 3M-1, it lost its ability to induce disease. As shown by immunofluorescent techniques, 3M-1 appears to be localized on rodent TBM to the exclusion of the glomerular basement membrane, but was lacking in the TBM of the LEW rat, a strain devoid of the relevant antigen of anti-TBM disease. Immunoelectron microscopy revealed that 3M-1 was associated with the most lateral aspect of the TBM, which borders, and lies in the interstitium. These results indicate that 3M-1 is the nephritogenic antigen producing experimental anti-TBM disease.

[Functional results of floating shoulder treatment]. / Resultados funcionales del tratamiento del hombro flotante.

INTRODUCTION: The floating shoulder has an incidence of 0.1% of all fractures, the result of high-energy trauma. There is still no consensus in the literature on the best treatment: surgical versus conservative. MATERIAL AND METHODS: Patients with floating shoulder diagnosis were evaluated from January 2013 to December 2018, collecting initial data from the electronic file. The morphological types of fractures were described using the Allman and AO classifications. Patients were evaluated using the UCLA scale for shoulder functionality. RESULTS: From 14 patients, 4 were excluded due to lack of follow-up. Of the remaining 10, 9 were men, 1 woman. The average age was 29 years (range 15-42 years). Three patients had left injury, and 7 patients, right; 6 patients hurt the dominant limb. The most common morphological pattern was glenoid neck fracture + clavicle fracture in 7 patients. Surgical treatment was indicated in 7 patients; and in 3, conservative. Of the 7 patients treated surgically, 6 were with clavicle and scapula osteosynthesis; 1 just the clavicle. Patients with conservative management used a universal shoulder immobilizer for 4-8 weeks. There were no cases of consolidation delay, pseudoarthrosis, or vicious consolidation. Rehabilitation began in the first 4 weeks, and lasted up to 8 weeks. CONCLUSION: Surgical treatment was predominant due to instability. Conservative treatment was used when injuries are minimally displaced. Both treatments generate a favorable functional result.

INTRODUCCIÓN: El hombro flotante tiene una incidencia de 0.1% de todas las fracturas, resultado de traumatismos de alta energía. Aún no existe consenso en la literatura sobre el mejor tratamiento: quirúrgico versus conservador. MATERIAL Y MÉTODOS: Se evaluaron individuos con diagnóstico de hombro flotante, de Enero 2013 a Diciembre 2018, recabando datos iniciales del archivo electrónico. Los tipos morfológicos de fracturas se describieron utilizando las clasificaciones de Allman y AO. Se valoraron los pacientes mediante la escala de la UCLA para la funcionalidad del hombro. RESULTADOS: De 14 pacientes, se excluyeron cuatro por falta de seguimiento. De los 10 restantes, nueve fueron hombres, una mujer. La edad promedio fue de 29 años (rango 15-42 años). Tres pacientes con lesión izquierda y los otros siete, derecha; seis de ellos se lesionaron la extremidad dominante. El patrón morfológico más común fue fractura de cuello de glenoides + fractura de clavícula en siete pacientes. En siete pacientes se indicó tratamiento quirúrgico; y en tres, conservador. De los siete individuos tratados quirúrgicamente, en seis se fijaron clavícula y escápula; en uno, solamente clavícula. Los pacientes con manejo conservador utilizaron inmovilizador universal de hombro por 4-8 semanas. No hubo casos de retardo en la consolidación, pseudoartrosis, ni consolidación viciosa. La rehabilitación inició en las primeras cuatro semanas y se prolongó hasta ocho semanas. CONCLUSIÓN: El tratamiento quirúrgico fue el predominante por inestabilidad. El tratamiento conservador se usó cuando las lesiones están poco desplazadas. Ambos tratamientos generan un resultado funcional favorable.

Ultrastructural localization of type V collagen in rat kidney.

Antibodies specific for the alpha 1 (V) chain and native collagen molecules containing the alpha 1 (V) chain have been used in electron immunohistochemical studies of rat kidney to determine the ultrastructural distribution of this class of collagen molecules. In addition, antibodies against type I collagen and whole basement membrane were used as markers for interstitial collagen and authentic basement membranes. Our results indicate that type V collagen is present in the renal interstitium in different forms: in close apposition to interstitial collagen fibers; in the stromal aspect of vascular basement membranes; and as particulate material not bound to other structures. On the basis of these findings, we postulate a binding or connecting function for this collagen type.

Location and identification of the collagen found in the 14.5-d rat embryo visceral yolk sac.

The collagens associated with 14.5-d rat visceral yolk sacs were localized and identified by a variety of procedures. Morphological examination showed that both the visceral epithelium and mesothelium rested upon thin basement membranes, whereas the majority of the extracellular matrix consisted of a stroma containing occasional cells and abundant banded fibrils. Immunohistochemistry at the electron microscope level showed that the basement membranes specifically cross-reacted with antibodies directed against mouse basement membrane components, whereas the stroma specifically cross-reacted with antibodies directed against rat type I collagen. Extractions of acellular visceral yolk sacs and subsequent analyses showed that type I collagen components were prevalent. Furthermore, in vitro biosynthetic studies showed only the presence of type I procollagen components (or their conversion products) and alpha-fetoprotein. These findings, taken together with our previous studies on the 14.5-d rat parietal yolk sac, provide us with protein markers for studying the origin of cells in rat parietovisceral yolk sac carcinomas.

Deposition of fibronectin and laminin in the basement membrane of the rat parietal yolk sac: immunohistochemical and biosynthetic studies.

Rat parietal yolk sacs (PYS) at gestational ages 7.5, 9.5, 11.5, 13.5, 14.5, and 16.5 d were reacted with antibodies against laminin or plasma fibronectin. At all times studied, laminin consistently gave a positive reaction with Reichert's membrane and with the cytoplasm of PYS cells. In contrast, fibronectin gave a negative reaction with Reichert's membrane at day 7.5, was weakly positive at day 9.5, and from then on was increasingly positive with maximum reactivity at 14.5 d. By electron microscopic immunohistochemistry, antilaminin reacted strongly with 14.5-d Reichert's membrane and with the contents of the rough endoplasmic reticulum RER cisternae of the PYS cells. Antifibronectin had some spotty reactivity with Reichert's membrane, but the cytoplasm of the PYS cells was negative. The contents of the vitelline vessels and the interface between trophoblast and Reichert's membrane were strongly positive. Metabolic labeling of PYS cells in organ culture clearly demonstrated the presence of laminin, type IV procollagen, and entactin both in the medium and in tissues, but fibronectin was absent. No component in the medium bound to gelatin-Sepharose columns. These studies demonstrate that PYS cells, which actively synthesize and secrete basement membrane components, do not synthesize any detectable fibronectin. Furthermore, the anti-fibronectin staining pattern in the vitelline vessels and trophoblast-Reichert's membrane interface strongly suggests that the fibronectin present in Reichert's membrane is derived from the maternal circulation and is merely "trapped" in the membrane.

Glutamine synthetase: glial localization in brain.

Light microscopy immunohistochemical techniques were used to examine the distribution of glutamine synthetase in rat brain. Glutamine synthetase was found to be localized in the glial cells. Neuronal cell bodies, endothelial cells, and choroid epithelium contained no enzyme. The findings indicate that glia have a crucial role in glutamic acid, gamma-aminobutyric acid, and ammonia metabolism in brain.

[Femoral neck fracture management in patient with bilateral femoral supracondylar amputation and literature review]. / Manejo de fractura de cuello femoral en paciente con amputación supracondílea femoral bilateral y revisión de la literatura.

The treatment of a patient with amputation above the knee who has suffered a femoral neck fracture is a challenge for both the orthopedic surgeon and the rehabilitation team. We present a case, in which different difficulties are discussed in their treatment, choice of implant and return to their daily activities. The clinical case of a young man diagnosed with supracondylar bilateral traumatic amputation, with fracture of the femoral neck, treated by total non-cemented hip arthroplasty is presented. The functionality of the total hip prosthesis with Houghton scale after 12 months, obtaining a final score of 9 points which are the result of a satisfactory rehabilitation.

El tratamiento de un paciente con amputación supracondílea femoral bilateral, y que ha sufrido una fractura de cuello femoral, es un evento poco común tanto para el cirujano ortopédico como para el equipo de rehabilitación. Presentamos un caso, en el cual se discuten diferentes dificultades en su tratamiento, elección de implante y regreso a sus actividades diarias. Se trata de un joven con diagnóstico de amputación traumática bilateral supracondílea, con fractura de cuello femoral, tratado mediante artroplastía total de cadera primaria no cementada. La evaluación de la funcionalidad de la prótesis total de cadera con escala de Houghton fue al cabo de 12 meses, se obtuvo una puntuación final de 9 puntos, los cuales son el resultado de una rehabilitación satisfactoria.

Molecular composition of the paralyzing venom of three solitary wasps (Hymenoptera: Pompilidae) collected in southeast Mexico.

The chemical and biological characterization of peptide and protein components of the paralyzing venom from three Pompilidae solitary spider wasps (Pepsis mexicana, Pepsis terminata, and Anoplius nigritus) is described for the first time. The molecular masses of the most abundant peptides were determined. The N-terminal sequences of two cysteine-rich peptides were obtained from Pepsis. Metalloproteinase and hyaluronidase activities were identified in the venom of P. mexicana. A novel non-lethal method to collect venom is described.

Identification of up-regulated genes from the metal-hyperaccumulator aquatic fern Salvinia minima Baker, in response to lead exposure.

Lead (Pb) is one of the most serious environmental pollutants. The aquatic fern Salvinia minima Baker is capable to hyper-accumulate Pb in their tissues. However, the molecular mechanisms involved in its Pb accumulation and tolerance capacity are not fully understood. In order to investigate the molecular mechanisms that are activated by S. minima in response to Pb, we constructed a suppression subtractive hybridization library (SSH) in response to an exposure to 40µM of Pb(NO3)2 for 12h. 365 lead-related differentially expressed sequences tags (ESTs) were isolated and sequenced. Among these ESTs, 143 unique cDNA (97 were registered at the GenBank and 46 ESTs were not registered, because they did not meet the GenBank conditions). Those ESTs were identified and classified into 3 groups according to Blast2GO. In terms of metabolic pathways, they were grouped into 29 KEGG pathways. Among the ESTs, we identified some that might be part of the mechanism that this fern may have to deal with this metal, including abiotic-stress-related transcription factors, some that might be involved in tolerance mechanisms such as ROS scavenging, membrane protection, and those of cell homeostasis recovery. To validate the SSH library, 4 genes were randomly selected from the library and analyzed by qRT-PCR. These 4 genes were transcriptionally up-regulated in response to lead in at least one of the two tested tissues (roots and leaves). The present library is one of the few genomics approaches to study the response to metal stress in an aquatic fern, representing novel molecular information and tools to understand the molecular physiology of its Pb tolerance and hyperaccumulation capacity. Further research is required to elucidate the functions of the lead-induced genes that remain classified as unknown, to perhaps reveal novel molecular mechanisms of Pb tolerance and accumulation capacity in aquatic plants.

Ultrastructural comparison of differentiation of stem cells of murine adenocarcinomas of colon and breast with their normal counterparts.

Two rats with chemically induced transplantable adenocarcinomas of the colon were given pulses of [3H]thymidine, and autoradiography with electron microscopes was used to compare the degrees of differentiation of the stem cells of the tumor and colon. The best differentiated portions of the tumor had acini composed of vacuolated, mucous, and argentaffin cells in various stages of differentiation. Vacuolated and mucous cells incorporated [3H]thymidine and corresponded in degree of differentiation to that of their labeled normal counterparts in the normal colon. An exceedingly undifferentiated labeled cell, hitherto undescribed, was identified in the tumor and crypts of the colon; this may be an undifferentiated colon stem cell that differentiates into vacuolated and mucous stem cells and/or into argentaffin cells. Normal stem cells of the breast and malignant stem cells of spontaneous adenocarcinomas of the breast of C3H mice had comparable degrees of differentiation. Since normal stem cells in these tissues were as undifferentiated as the least differentiated stem cells of the tumors, there is now no need to postulate dedifferentiation as a mechanism to explain the undifferentiated appearance of tumors.

Human chorionic gonadotropin in human neoplastic cells.

Peroxidase-labeled antibody against the beta chain of human chorionic gonadotropin was used to demonstrate that 25 human malignant tumors contained this antigen. The antigen was localized both in the cytoplasm and on the surface of the malignant cells. Human chorionic gonadotropin may be responsible for both selective maternal immuno-suppression by fetal tissue and host immunosuppression by tumors.

In vitro plasminogen activator activity in human brain tumors.

Cell cultures were prepared from nine human brain tumors. Fibrin plate assays showed plasminogen-dependent fibrinolytic activity in lysates and in material released by these neoplastic cells but not in those from normal adult human white matter. Antibodies against human urokinase caused catalytic inhibition of the urokinase and of the plasminogen activator from WI-38 cells, simian virus 40-transformed WI-38 cells, human prostatic cells, and human ovarian carcinoma cells. However, the anti-urokinase immunoglobulin G did not inhibit the plasminogen activator activity of any of the human brain tumor preparations. These studies indicate that the plasminogen activator produced by human brain tumor cells is antigenically different from the plasminogen activator of other human normal and neoplastic cells.