On the nature of transplantation immunity in the adenovirus tumor system.

The existence of a virus-induced, virus-specific transplantation, antigen in adenovirus 12-induced CBA mouse tumors was demonstrated. The antigen is virus-specific, but not related to structural virion or T antigens. It is a weak antigen, and required immunization with whole, infectious adenovirus 12 to produce considerable immunity. Comparable immunity could not be achieved with homologous cellular or subcellular materials, but some indication of enhancement was produced with low tumor dose. Immunization required at least 2 wk and was mediated by immune lymphoid cells. Serum of immunized animals showed no demonstrable cytotoxicity or enhancement. Animals immunized with virus and Freund's adjuvant showed diminished transplantation immunity, although these animals were actively immunized against adenovirus type 12 structural virion antigens.

[Association of the polymorphisms of the ERBB3 and SH2B3 genes with type 1 diabetes].

To study the association with diabetes mellitus type 1 we performed analysis of the distribution of frequencies of alleles and genotypes of polymorphic marker rs2292239 of ERBB3 gene, encoding epidermal growth factor receptor type 3 and polymorphic marker rs3184504 of SH2B3 gene, encoding adaptor protein LNK. The study included groups of T1DM patients and unrelated controls of Russian origin. Genotyping was performed using methods of RFLP and real-time amplification. For the polymorphic marker rs2292239 of ERBB3 gene was not found statistically significant associations with type 1 diabetes, while analysis of the distribution of frequencies of alleles and genotypes of the polymorphic marker rs3184504 of SH2B3 gene showed the presence of association with T1DM in Russian population.

Primary structure of the leukocyte function-associated molecule-1 alpha subunit: an integrin with an embedded domain defining a protein superfamily.

The leukocyte function-associated molecule 1 (LFA-1, CD11a/CD18) is a membrane glycoprotein which functions in cell-cell adhesion by heterophilic interaction with intercellular adhesion molecule 1 (ICAM-1). LFA-1 consists of an alpha subunit (Mr = 180,000) and a beta subunit (Mr = 95,000). We report the molecular biology and protein sequence of the alpha subunit. Overlapping cDNAs containing 5,139 nucleotides were isolated using an oligonucleotide specified by tryptic peptide sequence. The mRNA of 5.5 kb is expressed in lymphoid and myeloid cells but not in a bladder carcinoma cell line. The protein has a 1,063-amino acid extracellular domain, a 29-amino acid transmembrane region, and a 53-amino acid cytoplasmic tail. The extracellular domain contains seven repeats. Repeats V-VII are in tandem and contain putative divalent cation binding sites. LFA-1 has significant homology to the members of the integrin superfamily, having 36% identity with the Mac-1 and p150,95 alpha subunits and 28% identity with other integrin alpha subunits. An insertion of approximately 200 amino acids is present in the NH2-terminal region of LFA-1. This "inserted/interactive" or I domain is also present in the p150,95 and Mac-1 alpha subunits but is absent from other integrin alpha subunits sequenced to date. The I domain has striking homology to three repeats in human von Willebrand factor, two repeats in chicken cartilage matrix protein, and a region of complement factor B. These structural features indicate a bipartite evolution from the integrin family and from an I domain family. These features may also correspond to relevant functional domains.

Existence of a flat phase in red cell membrane skeletons.

Biomolecular membranes display rich statistical mechanical behavior. They are classified as liquid in the absence of shear elasticity in the plane of the membrane and tethered (solid) when the neighboring molecules or subunits are connected and the membranes exhibit solid-like elastic behavior in the plane of the membrane. The spectrin skeleton of red blood cells was studied as a model tethered membrane. The static structure factor of the skeletons, measured by small-angle x-ray and light scattering, was fitted with a structure factor predicted with a model calculation. The model describes tethered membrane sheets with free edges in a flat phase, which is a locally rough but globally flat membrane configuration. The fit was good for large scattering vectors. The membrane roughness exponent, zeta, defined through h alpha L zeta, where h is the average amplitude of out-of-plane fluctuations and L is the linear membrane dimension, was determined to be 0.65 +/- 0.10. Computer simulations of model red blood cell skeletons also showed this flat phase. The value for the roughness exponent, which was determined from the scaling properties of membranes of different sizes, was consistent with that from the experiments.

[Association of the C1858T polymorphism of the PTPN22 gene with type 1 diabetes].

To study the association with diabetes mellitus type 1 (T1DM) we performed TDT analysis and analysis of the distribution of frequencies of alleles and genotypes of polymorphic marker C1858T of the PTPN22 gene, encoding tyrosine phosphatase of non-receptor type (LYP). Groups of concordant (27 families) and discordant (62 families) sibpairs and groups of T1DM patients and unrelated controls of Russian origin were recruited in Endocrinology Research Center, Moscow and Center of Diabetes, Samara. For a given polymorphic marker was not found statistically significant associations with type 1 diabetes in the transmission disequilibrium test, while analysis of the distribution of frequencies of alleles and genotypes showed the association with T1DM. Thus, the polymorphic marker C1858T of the PTPN22 gene is associated with T1DM in Russian patients.

Feasibility of percutaneous organ biopsy as part of a minimally invasive perinatal autopsy.

To determine the feasibility of percutaneous fetal organ biopsies in the context of a 'minimally invasive' perinatal autopsy after stillbirth and termination for abnormality is the aim of this study. We assessed successful biopsy rate and the proportion adequate for histological examination in 30 fetuses undergoing organ sampling before autopsy. The relationship between gestational age, body weight, death-biopsy interval, operator experience and successful biopsy rate was investigated. Significant findings from conventional block histology were compared with corresponding percutaneous biopsies. Of 210 organ biopsies attempted from seven target organs, 107 were obtained, of which 94 were adequate for pathological comment. The median delivery-autopsy interval was 4 (range 2-11) days. Adequate samples were obtained from the lung in 86% cases (95% CI 68, 96%), liver 76% (95% CI 56, 90%) and less frequently for the myocardium, kidney, adrenal, thymus and spleen. There was no relationship between biopsy success and time to biopsy, gestational age, body weight and user experience. No histological abnormalities found at autopsy were diagnosed from needle biopsies. Although targeted percutaneous biopsies appear feasible for some organs, fewer than 50% of all biopsies are adequate for histological examination. This technique cannot be considered to provide useful clinical information as part of a 'minimally invasive' perinatal autopsy.

[Association of the chromosomal region 2q35 with type 1 diabetes mellitus in the Russian patients from Moscow].

To map human chromosome 2 region associated with type 1 diabetes mellitus, 89 families with concordant and discordant sib pairs were analyzed. Linkage and association with type 1 diabetes were examined using polymorphic microsatellite markers spanning the region of about 4 Mb. The linkage plot was constructed, and association of the five microsatellite markers within the chromosomal region 2q35 was examined. Polymorphic marker D2S137 (Z' = 3.225, p(c) = 0.0048) demonstrated maximum linkage and association with type 1 diabetes.

Anti-KJ: a new antibody associated with the syndrome of polymyositis and interstitial lung disease.

Antibodies to aminoacyl-tRNA synthetases (anti-Jo-1, anti-PL-7, anti-PL-12) have been found in the serum of some patients with polymyositis (PM). Patients with these antibodies have an unusually high rate of interstitial lung disease (ILD) in association with their PM. Two patients (K.J. and B.T.) with severe ILD and PM were found to have antibodies to a cytoplasmic antigen, but tests to determine whether the antigen was an aminoacyl-tRNA synthetase were negative, including tests of KJ serum for inhibitory effects on the 20 synthetases. KJ immunoprecipitates did not contain tRNA, in contrast to antisynthetase sera. When IgG samples were added to a reticulocyte in vitro translation system at a concentration of 0.3 mg/ml, KJ IgG inhibited globin mRNA translation by 98%, while anti-Jo-1 IgG inhibited 62% and normal IgG had little effect. Thus, both anti-KJ and the antisynthetases are directed at antigens that are involved in translation and protein synthesis, and both are associated with the syndrome of lung disease and PM. This syndrome may be associated with antibodies to translation-related proteins in general, which may have implications for the link of PM and enteroviruses, which are mRNA viruses.

Hereditary sideroblastic anemia and glucose-6-phosphate dehydrogenase deficiency in a Negro family.

Detailed clinical and genetic studies have been performed in a Negro family, which segregated for sex-linked sideroblastic anemia and glucose-6-phosphate dehydrogenase (G-6-DP) deficiency. This is the first such pedigree reported. Males affected with sideroblastic anemia had growth retardation, hypochromic microcytic anemia, elevated serum iron, decreased unsaturated iron-binding capacity, increased (59)Fe clearance, low (59)Fe incorporation into erythrocytes, normal erythrocyte survival ((51)Cr), normal hemoglobin electrophoretic pattern, erythroblastic hyperplasia of marrow with increased iron, and marked increase in marrow sideroblasts, particularly ringed sideroblasts. Perinuclear deposition of ferric aggregates was demonstrated to be intramitochondrial by electron microscopy. Female carriers of the sideroblastic gene were normal but exhibited a dimorphic population of erythrocytes including normocytic and microcytic cells. The bone marrow studies in the female (mother) showed ringed marrow sideroblasts. Studies of G-6-PD involved the methemoglobin elution test for G-6-PD activity of individual erythrocytes, quantitative G-6-PD assay, and electrophoresis. In the pedigree, linkage information was obtained from a doubly heterozygous woman, four of her sons, and five of her daughters. Three sons were doubly affected, and one was normal. One daughter appeared to be a recombinant. The genes appeared to be linked in the coupling phase in the mother. The maximum likelihood estimate of the recombination value was 0.14. By means of Price-Jones curves, the microcytic red cells in peripheral blood were quantitated in female carriers. The sideroblast count in the bone marrow in the mother corresponded closely to the percentage of microcytic cells in peripheral blood. This is the second example in which the cellular expression of a sex-linked trait has been documented in the human red cells, the first one being G-6-PD deficiency. The coexistence of the two genes in doubly heterozygous females has made it possible to study correlations in cell counts; our studies showed a strong positive correlation except in the probable recombinant in which a reciprocal relation held which indicated that X-inactivation was at least regional, rather than locus by locus.

Surgical site infections in neonates are independently associated with longer hospitalizations.

OBJECTIVE: There is limited data characterizing the risk and impact of surgical site infection (SSI) in neonates; this makes it difficult to identify factors that increase neonatal SSI risk and to determine how SSI affects outcomes in this special population. STUDY DESIGN: The American College of Surgeons National Surgical Improvement Program Pediatric (NSQIP-P) collected data on children undergoing surgery at children's hospitals from 2012 to 2014. Neonates undergoing general surgical procedures were characterized with regard to demographic characteristics and comorbidities. Perioperative variables such as wound class, type of surgery and length of operation were also evaluated. RESULTS: Seven thousand three hundred and seventy-nine neonates were identified in the NSQIP-P participant user file. The overall SSI rate was 2.6%. Only wound class and length of surgery were significantly associated with SSI. Furthermore, SSI was independently associated with longer length of stay, even after adjusting for covariates. CONCLUSIONS: This is the largest study to date analyzing SSI in neonates. We found that perioperative variables have a more significant impact on SSI than patient factors, suggesting that operation-related characteristics are influencing SSI. Furthermore, neonates with SSI are more likely to have prolonged hospitalizations even after adjusting for patient comorbidities.

Functional outcomes of conservatively managed acute ruptures of the Achilles tendon.

AIMS: This prospective cohort study aims to determine if the size of the tendon gap following acute rupture of the Achilles tendon shows an association with the functional outcome following non-operative treatment. PATIENTS AND METHODS: All patients presenting within two weeks of an acute unilateral rupture of the Achilles tendon between July 2012 and July 2015 were considered for the study. In total, 38 patients (nine female, 29 male, mean age 52 years; 29 to 78) completed the study. Dynamic ultrasound examination was performed to confirm the diagnosis and measure the gap between ruptured tendon ends. Outcome was assessed using dynamometric testing of plantarflexion and the Achilles tendon Total Rupture score (ATRS) six months after the completion of a rehabilitation programme. RESULTS: Patients with a gap ≥ 10 mm with the ankle in the neutral position had significantly greater peak torque deficit than those with gaps < 10 mm (mean 23.3%; 7% to 52% vs 14.3%; 0% to 47%, p = 0.023). However, there was no difference in ATRS between the two groups (mean score 87.2; 74 to 100 vs 87.4; 68 to 97, p = 0.467). There was no significant correlation between gap size and torque deficit (τ = 0.103), suggesting a non-linear relationship. There was also no significant correlation between ATRS and peak torque deficit (τ = -0.305). CONCLUSION: This is the first study to identify an association between tendon gap and functional outcome in acute rupture of the Achilles tendon. We have identified 10 mm as a gap size at which deficits in plantarflexion strength become significantly greater, however, the precise relationship between gap size and plantarflexion strength remains unclear. Large, multicentre studies will be needed to clarify this relationship and identify population subgroups in whom deficits in peak torque are reflected in patient-reported outcome measures. Cite this article: Bone Joint J 2017;99-B:87-93.

Molecular genetic analysis of the mldr mouse: a spontaneous revertant at the mld locus containing a recombinant myelin basic protein gene.

The mld mutation is a complex genetic lesion affecting the myelin basic protein (MBP) locus in the mouse. The mutation consists of a variety of DNA rearrangements including: tandem duplication of the MBP structural gene, partial inversion of the 3' end of the upstream gene copy, duplication of a region flanking the rearrangement junction in the upstream copy and insertion between the two gene copies of a segment of extraneous DNA not associated with the wild-type MBP locus. The net result of the mutation is a dysfunctional MBP locus. Homozygous mld/mld mice produce very little MBP and consequently very little myelin. They exhibit a clinical phenotype characteristic of hypomyelination (shaking, convulsions). We have discovered a revertant mld mouse which does not exhibit clinical symptoms of hypomyelination. Genetic analysis indicates that the reversion is allelic to mld. We have designated the revertant locus mldr. Restriction analysis of mldr genomic DNA indicates that there is a single intact MBP gene. Analysis of various junction regions using the polymerase chain reaction indicates that the single MBP gene in mldr is derived by recombination from the 5' end of the upstream gene and the 3' end of the downstream gene. Studies on MBP expression in mldr mice indicate that the developmental regulation, level of expression and pattern of post-transcriptional processing of MBP gene products in mldr are similar to wild type. These results indicate that the recombinant MBP gene in mldr is fully functional. From this we infer that the MBP-deficient phenotype of the original mld mutant is attributable to the complex rearrangements in the upstream gene copy which render the locus dysfunctional.(ABSTRACT TRUNCATED AT 250 WORDS)

3D reconstruction of the skeletal anatomy of the normal neonatal foot using 3D ultrasound.

Currently imaging plays a limited role in the assessment of the neonate with a foot deformity. The aim of this study was to establish a technique for examining the neonatal foot with three-dimensional ultrasound (3D US). 3D US was attempted on the normal feet of 20 infants (9 male, 11 female) under 6 weeks old (range 35-41 days). The data sets were obtained whilst the infants were feeding or asleep to minimize movement artefact. A high-resolution optically tracked freehand 3D US system (Diasus, 16 MHz transducer) was used with Stradx software to acquire and analyse the data sets. Manual segmentation of the non-ossified tarsi from the data sets was performed. Five infants were too restless to be examined. 107 data sets were recorded from 22 feet of the remaining 15 infants. 21 of the data sets were discarded due to movement artefact. 86 were suitable for manual segmentation. Surface interpolation of the segmented data sets produced surface rendered reconstructions illustrating the complex 3D anatomy of the foot. This new technique may offer a method of examining the deformed foot, e.g. congenital talipes equinovarus.

Spatial mapping of the brachial plexus using three-dimensional ultrasound.

Imaging of the brachial plexus with MRI and standard two-dimensional (2D) ultrasound has been reported, and 2D ultrasound-guided regional anaesthetic block is an established technique. The aim of this study was to map the orientation of the brachial plexus in relation to the first rib, carotid and subclavian arteries, using three-dimensional (3D) ultrasound. A free-hand optically tracked 3D ultrasound system was used with a 12 MHz transducer. 10 healthy volunteers underwent 3D ultrasound of the neck. From the 3D ultrasound data sets, the outlines of the brachial plexus, subclavian artery and first rib were manually segmented. A surface was interpolated from the series of outlines to produce a spatially orientated 3D reconstruction of the brachial plexus. The brachial plexus could be mapped in all volunteers, although a variation in image resolution between individuals existed. Anatomical variations were demonstrated between the 10 volunteers; the most notable and clinically relevant was the alignment of the plexus divisions. 3D reconstructions illustrated the plexus, changing its orientation from a vertical alignment in the interscalene region to a more horizontal alignment in the supraclavicular fossa. Spatial mapping of the brachial plexus is possible with 3D ultrasound using the subclavian artery and first rib as landmarks. There is a deviation from the conventionally described anatomy and this may have implications for the administration of regional anaesthesia.

Tracheal extubation of the neonate at 2 to 3 cm H2O continuous positive airway pressure.

To investigate the efficacy of extubation at higher levels of continuous positive airway pressure (CPAP), 49 newborns (0.95 to 4.0 kg) were extubated at 2 to 3 cm H2O following 1 to 47 days of CPAP therapy. Pre- and postextubation measurements of Po2, PCO2, pH, FiO2, and CPAP were made in all infants. No significant differences (P less than.05) were found between pre- and post-extubation arterial blood gas values for all patients. Comparison of pre- and post-extubation blood gas data with respect to birthweight (less than 2.0 kg vs greater than 2.0 kg) and intubation time (less than 8 days vs. greater than 8 days) also indicated no statistical differences. Mean alveolar-arterial oxygen differences and FiO2 for 41 infants showed progressive decreases following extubation. Six of the 49 infants required reintubation within 72 hours following extubation. The results of this study indicate that newborns with respiratory disease requiring CPAP may be extubated at 2 to 3 cm H2O with no significant changes in arterial blood gas values, thus preventing prolonged intubation associated with weaning to 0 cm H2O CPAP.

The therapeutic application of end-expiratory pressure in the meconium aspiration syndrome.

The effectiveness of end-expiratory pressure (EEP) in relieving hypoxemia in the meconium aspiration syndrome (MAS) was studied in 14 patients with the disorder. These infants demonstrated a direct, mean PO2 response of 12 torr/cm H2O EEP. A maximum PO2 response was observed in an EEP range of 4 to 7 cm H2O. EEP was equally effective whether patients were breathing spontaneously or were being mechanically ventilated. EEP is useful in the treatment of hypoxemia in the infants with meconium aspiration syndrome.

Novel approaches to female sexual dysfunction.

Female sexual dysfunction is age-related, progressive and highly prevalent, affecting 30 - 50% of American women. While there are emotional and relational elements to sexual function, it has become increasingly evident that female sexual dysfunction can occur secondary to medical problems and has an organic basis. A plethora of different female sexual dysfunctions exist and in order to obtain a greater understanding of the possible treatments for these problems, it is essential to have a strong knowledge base of female pelvic anatomy, the neurogenic mediators of female sexual response, the impact of hormones on female sexual function and the aetiologies of female sexual dysfunction. Currently, there are potential therapeutic options for the treatment of female sexual dysfunction and these options include both hormonal and pharmacological therapy. However, therapeutic agents may not prove to be enough and the ideal approach to female sexual dysfunction is thus a collaborative effort between therapists and physicians, which should include a complete medical and psychosocial evaluation, as well as inclusion of the partner or spouse in the evaluation and treatment process.

The optimal age for vaccination against measles in an Asiatic city, Taipei, Taiwan: reduction of vaccine induced titre by residual transplacental antibody.

Children vaccinated when aged between six and thirteen months against measles in Taipei showed a high frequency of response, similar to that reported from Nairobi, Kenya and contrasting with analogous data for the USA. The age for optimal protection against measles mortality by a single dose of vaccine in this group of children is nine months. Maternal antibody exerted a negative effect on measles antibody titre in vaccinees beyond the age at which it blocked the response so that the infants of mothers with the higher titres themselves had lower titres. A separate effect of immunological immaturity on titre of the response could not be demonstrated in children over six months of age.

Peliosis of the spleen.

Peliosis of the spleen is a rare condition that accompanies peliosis hepatis. Two cases are presented, and a detailed morphologic description is given. The lesions are confined to the red pulp and appear to arise by progressive distention of splenic sinuses, with eventual thrombosis and organization. Peliotic involvement of the spleen is probably more common than realized and can have serious clinical implications.

Peripheral T-cell lymphoma: a clinicopathologic study of nine cases.

The clinicopathologic features of nine cases of peripheral T-cell lymphoma were analyzed. Although the youngest patient was 18 years old, the median age was 59.8 years. They usually presented with widespread disease and had an aggressive course. Seven have died with a median survival of 10.9 months. Five cases were of mixed cell type, sharing certain histopathologic features that we believe are characteristic of peripheral T-cell lymphomas. Three cases were of large cell type; one was a small cell (PDL) type. This latter patient lived symptom-free without treatment for over 3 years, despite stage III disease. Another patient, whose tumor had nodular sclerosis-like fibrosis, is in complete remission two years after chemotherapy for stage III B disease. Because peripheral T-cell lymphoma is morphologically heterogeneous, it may be clinically heterogeneous as well. We believe that classification according to a modified Rappaport system may clarify possible variations in biologic behavior.