Genetics of club foot in Maori and Pacific people

The role of major gene and multifactorial inheritance in the aetiology of club foot in the New Zealand Polynesian population was studied using 287 New Zealand Maori and Pacific club foot families. The club foot family data were analysed by complex segregation analysis under the mixed model using the computer program POINTER. This analysis shows that the best genetic model for club foot in this population is a single dominant gene with a penetrance of 33% and a predicted gene frequency of 0.9%. These data provide a scientific foundation for molecular studies in the Maori and Polynesian population to identify putative club foot genes.


Keywords: club foot; New Zealand Maori; complex segregation analysis     

In vitro controllability of the MagScrew total artificial heart system

The purpose of this study was to evaluate the in vitro responses to preload and afterload of our total artificial heart (TAH), the MagScrew TAH. The TAH consists of two blood pumps and a control logic, developed at the Cleveland Clinic, OH, and the MagScrew actuator and its electronic control system, developed by Foster-Miller Technologies, Inc., Albany, NY. Tests were performed on a mock circulatory loop, using water as a test fluid. Preload sensitivity of the Mag-Screw TAH demonstrated a Frank-Starling response to preload in automatic mode. A peak flow of 10 L/min was obtained, with a left atrial pressure of 13 mm Hg. The relationship between right atrial pressure and left atrial pressure was well balanced when tested with a left bronchial shunt flow of 5% and a range of pulmonary artery and aortic pressures. With respect to afterload response, the left pump showed a relatively low sensitivity, which allowed the pump to maintain perfusion over a wide range of aortic pressures. The right pump, on the other hand, was much more sensitive to pulmonary artery pressure, which provided a measure of protection against pulmonary congestion. The very effective physiologic response of the MagScrew TAH is believed to result from employment of a left master, alternating ejection control logic, high inherent sensitivity of the blood pumps to atrial pressure, a lower effective stroke volume for the right pump, and a scaling of right side motor ejection voltage to 80% of that used for the left side ejection.     

Single nucleotide polymorphisms in TNFSF15 confer susceptibility to Crohn's disease

The inflammatory bowel diseases (IBDs), Crohn's disease (CD) and ulcerative colitis, are chronic inflammatory disorders of the digestive tract. The pathogenesis of IBD is complicated, and it is widely accepted that immunologic, environmental and genetic components contribute to its etiology. To identify genetic susceptibility factors in CD, we performed a genome-wide association study in Japanese patients and controls using nearly 80,000 gene-based single nucleotide polymorphism (SNP) markers and investigated the haplotype structure of the candidate locus in Japanese and European patients. We identified highly significant associations (P = 1.71 x 10(-14) with odds ratio of 2.17) of SNPs and haplotypes within the TNFSF15 (the gene encoding tumor necrosis factor superfamily, member 15) genes in Japanese CD patients. The association was confirmed in the study of two European IBD cohorts. Interestingly, a core TNFSF15 haplotype showing association with increased risk to the disease was common in the two ethnic groups. Our results suggest that the genetic variations in the TNFSF15 gene contribute to the susceptibility to IBD in the Japanese and European populations.     

Transmission electron microscope study of bacterial morphotypes on the anterior dorsal surface of human tongues

The human tongue has been the subject of many cytological and histological studies. When a literature search disclosed no reports of the ultrastructure of the morphotypes of bacteria residing on the tongue's surface, a transmission electron microscope study of ultrathin sections of bacteria obtained by scraping eight human tongues was undertaken. The scrapings from the anterior dorsal tongue surfaces, processed conventionally for electron microscope study, revealed 33-35 different bacterial morphotypes. Several of the morphotypes were unique to a tongue. Morphotype differences were also related to donor characteristics such as smoking, tongue site, location in centrifuge pellet, diet, and medications. The predominant morphotypes were Gram-positive cocci. These preliminary findings suggest that the microbiota of the human tongue and variations in that microbiota, related to physical condition, lifestyle, medications, and dietary preferences, merit more attention from anatomists.     

Effect of a short course of prednisone in the prevention of early relapse after the emergency room treatment of acute asthma

BACKGROUND. Relapse after the treatment of acute asthma in the emergency room is common (occurring in 25 to 30 percent of cases) and is not accurately predicted by any available measurements. We studied the usefulness of prednisone in reducing this high rate of relapse. METHODS. One hundred twenty-two patients treated in the emergency room for acute exacerbations of asthma were assigned in a randomized, double-blind fashion to receive at discharge either prednisone for eight days (the dose being tapered from 40 to 0 mg per day) or matching placebo. Ninety-three were subsequently discharged from the emergency room and participated in the trial. On days 1, 7, and 14 after discharge, the patients were assessed during home visits with spirometry and diary-card review; they were contacted by telephone on day 21. Relapse was defined as an unscheduled medical visit occasioned by the patient's perceived need for further asthma treatment. RESULTS. The overall risk of relapse was significantly lower in the prednisone group (P less than 0.05), with a significantly reduced rate of relapse during the first 10 days of follow-up (3 of 48, as compared with 11 of 45 in the placebo group; P less than 0.05). Thereafter (days 11 through 21), there was no further significant difference in relapse rates between treatment groups (five in the prednisone group and six in the placebo group). During the first week after discharge, patients receiving prednisone reported significantly lower mean (+/- SD) daily symptom scores for shortness of breath (1.4 +/- 0.4 vs. 2.5 +/- 0.4, P less than 0.01) and less frequent use of an inhaled bronchodilator (5.2 +/- 0.5 vs. 6.9 +/- 0.2 puffs per day, P less than 0.05) than patients receiving placebo. Subsequently, symptom scores and bronchodilator use were similar in the two groups. CONCLUSIONS. A short course of prednisone reduced early relapse rates after the treatment of acute asthma in the emergency room, an effect limited to the period of steroid administration.     

Raphe magnus inhibition of feline T1-T4 spinoreticular tract cell responses to visceral and somatic inputs

Background activity of spinoreticular tract neurons in the T1-T4 segments was on average inhibited 80% by electrical stimulation of nucleus raphe magnus. Nucleus raphe magnus stimulation inhibited responses of spinoreticular tract neurons to somatic input produced by touching the skin and hair (innocuous stimulus) or pinching the skin and muscle (noxious stimulus). Inhibition of responses to noxious and innocuous somatic inputs was not significantly different. Inhibition produced during nucleus raphe magnus stimulation was less effective when the activity of spinoreticular tract cells increased. This relationship was consistent for both background activity and responses to somatic noxious or innocuous input. Nucleus raphe magnus stimulation inhibited responses of spinoreticular tract neurons to visceral input produced by electrical stimulation of cardiopulmonary sympathetic afferent fibers. Responses to C-fiber sympathetic afferent fibers were more effectively inhibited than were responses to A-delta sympathetic afferent fibers. In conclusion, stimulation of the nucleus raphe magnus inhibits T1-T4 spinoreticular tract neuronal responses to visceral and somatic inputs. Since spinoreticular neurons project to the medullary reticular formation, activation of the nucleus raphe magnus could modulate affective-motivational behavior and cardiovascular adjustments that often occur during angina pectoris.     

The mouse Mid1 gene: implications for the pathogenesis of Opitz syndrome and the evolution of the mammalian pseudoautosomal region

We have recently reported isolation of the gene responsible for X- linked Opitz G/BBB syndrome, a defect of midline development. MID1 is located on the distal short arm of the human X chromosome (Xp22. 3) and encodes a novel member of the B box family of zinc finger proteins. We have now cloned the murine homolog of MID1 and performed preliminary expression studies during development. Mid1 expression in undifferentiated cells in the central nervous, gastrointestinal and urogenital systems suggests that abnormal cell proliferation may underlie the defect in midline development characteristic of Opitz syndrome. We have also found that Mid1 is located within the mouse pseudoautosomal region (PAR) in Mus musculus , while it seems to be X- specific in Mus spretus. Therefore, Mid1 is likely to be a recent acquisition of the M. musculus PAR. Genetic and FISH analyses also demonstrated a high frequency of unequal crossovers in the murine PAR, creating spontaneous deletion/duplication events involving Mid1. These data provide evidence for the first time that genetic instability of the PAR may affect functionally important genes. In addition, we show that MID1 is the first example of a gene subject to X-inactivation in man while escaping it in mouse. These data contribute to a better understanding of the molecular content and evolution of the rodent PAR.      

Risk factors for wheezing in a subtropical environment: role of respiratory viruses and allergen sensitization

BACKGROUND: Risk factors for acute wheezing among children in subtropical areas are largely unknown. OBJECTIVE: To investigate the role of viral infections, allergen sensitization, and exposure to indoor allergens as risk factors for acute wheezing in children 0 to 12 years old. METHODS: One hundred thirty-two children 0 to 12 years of age who sought emergency department care for wheezing and 65 children with no history of wheezing were enrolled in this case-control study. Detection of respiratory syncytial virus antigen, rhinovirus and coronavirus RNA, adenovirus, influenza, and parainfluenza antigens was performed in nasal washes. Total IgE and specific IgE to mites, cockroach, cat, and dog were measured with the CAP system. Major allergens from mites, cockroach, cat, and dog were quantified in dust samples by ELISA. Univariate and multivariate analyses were performed by logistic regression. RESULTS: In children under 2 years of age, infection with respiratory viruses and family history of allergy were independently associated with wheezing (odds ratio, 15.5 and 4.2; P = .0001 and P = .008, respectively). Among children 2 to 12 years old, sensitization to inhalant allergens was the major risk factor for wheezing (odds ratio, 2.7; P = .03). High-level allergen exposure, exposure to tobacco smoke, and lack of breast-feeding showed no association with wheezing. CONCLUSIONS: Some risk factors for wheezing previously identified in temperate climates were present in a subtropical area, including respiratory syncytial virus infection in infants and allergy in children older than 2 years. Rhinovirus was not associated with wheezing and did not appear to be a trigger for asthma exacerbations.     

Biochemical characterization of atherosclerotic plaque constituents using FTIR spectroscopy and histology

The behavior of vulnerable atherosclerotic plaques is believed to be closely related to plaque composition. There is a need for an effective in vivo technique for examining plaque constituent properties. In this study, Fourier transform infrared spectroscopy using attenuated total reflectance (FTIR-ATR) was used to assess and analyze the biochemical properties of human atherosclerotic plaques. FTIR spectra clearly revealed prominent spectral features corresponding to plaque constituents of interest: the 2930 cm(-1) and 2850 cm(-1) peaks (indicating the presence of lipids), the 1730 cm(-1) peak (lipid esters), the 1550 cm(-1) and 1650 cm(-1) peaks (fibrous tissues), and the 1100-1000 cm(-1) broad phosphate peak (calcification). Spectral data examined on a qualitative basis correlated well with both gross tissue anatomy and histologic features. Gross spatial mappings of tissue sections of both lipidic and calcified plaques were performed. Spectra from various regions of the plaques demonstrated the evolution of lipid peaks, fibrous tissue peaks, and the phosphate calcification band within the plaques. Histologic analysis corroborated the spectral findings in this study.