Expression profile of mucins (MUC2, MUC5AC and MUC6) in Helicobacter pylori infected pre-neoplastic and neoplastic human gastric epithelium

Background  

Helicobacter pylori (H. pylori) causes gastritis and intestinal metaplasia (IM) that may evolve to gastric carcinoma. The objective of this study was to compare the profile of mucins in the progressive stages of H. pylori infected pre-neoplastic and neoplastic human gastric epithelium. We used a panel of monoclonal antibodies with well-defined specificities of MUC2, MUC5AC and MUC6 to characterize the expression pattern of mucins by immunohistochemistry.     

Ullrich-Turner syndrome with a small ring X chromosome and presence of mental retardation.

Since some patients with Ullrich-Turner syndrome (UTS) have mental retardation, we reviewed our experience to look for a high-risk subgroup. Among 190 UTS and gonadal dysgenesis patients with X chromosome abnormalities, 12 had mental retardation. All of the six (100%) with a small ring X were educable (EMI) or trainable mentally impaired (TMI) with more severe delay than expected in UTS. Among the 184 with other X abnormalities, only 6 had similar delays (2 from postnatal catastrophes), for a frequency of 3.3% mental retardation among those without a small ring X; only 2.2% of these had unexplained mental retardation. Polymerase chain reaction studies showed no Y-derived material in the 2 patients who were evaluated, and in situ hybridization confirmed X origin of the ring in the 6 subjects who were evaluated. We describe the phenotype of the 6 individuals with a small ring X, and an additional 2 patients with a small ring X who were identified outside the survey. The subjects with a small ring X comprised a clinically distinct subgroup which had EMI/TMI and shorter stature than expected in UTS. Seizures and a head circumference less than 10th centile were observed in half of the patients with a small ring X, and strabismus, epicanthus, and single palmar creases were present in more than half. A "triangular" face in childhood, pigmentary dysplasia, sacral dimple, and heart defects were also common. Neck webbing appeared to be less frequent than in 45,X. We hypothesize that the high risk of mental retardation in this form of the UTS results from lack of lyonization of the ring X due to loss of the X inactivation center. Excluding those with a small ring X, mental retardation is not significantly increased in patients with UTS.     

The Smooth Muscle Myosin Seven Amino Acid Heavy Chain Insert's Kinetic Role in the Crossbridge Cycle for Mouse Bladder

The seven amino acid insert in the smooth muscle myosin heavy chain is thought to regulate the kinetics of contraction, contributing to the differences between fast and slow smooth muscle. The effects of this insert on force and stiffness were determined in bladder tissue of a transgenic mouse line expressing the insert SMB at one of three levels: an SMB wild type (+/+), an SMA homozygous type (−/−) and a heterozygous type (+/−). For skinned muscle, an increase in MgADP or inorganic phosphate (P_i) should shift the distribution of crossbridges in the actomyosin ATPase (AMATPase) to increase the relative population of the crossbridge state prior to ADP release and P_i release, respectively. Exogenous ADP increased force and stiffness in a manner consistent with increasing the Ca²⁺ concentration in both the +/+ and +/− mouse types. However, the −/− type showed a significantly greater increase in force than in stiffness suggesting that immediately prior to ADP release, the AMATPase either has an additional force producing isomerization state or a slower ADP dissociation rate for the −/− type compared to the +/+ or +/− types. Exogenous P_i led to a significantly greater decrease in stiffness than in force for all three mouse types suggesting that there is a force producing state prior to P_i release. In addition, the increase in P_i showed similar changes in the +/+ and −/− types whereas in the +/− type the decreases in both force and stiffness were greater than the other two mouse types indicating that the insert can affect the cooperativity between myosin heads. In conclusion, the seven amino acid insert modulates the kinetics and/or states of the AMATPase, which could lead to differences in the kinetics of contraction between fast and slow smooth muscle.     

Clinically important differences in health-related quality of life for patients with asthma: an expert consensus panel report.

BACKGROUND: Standards for change in health-related quality of life (HRQoL) measures used among asthmatic patients have been established by considering only patient preferences to determine important differences and may not reflect an informed clinical evaluation of change. OBJECTIVE: To establish clinically important difference (CID) standards through the consensus of an expert physician panel for the Juniper Asthma Quality of Life Questionnaire (AQLQ) and Medical Outcomes Study Short-Form 36-Item Health Survey (SF-36, version 2) when used to measure HRQoL among asthmatic patients. METHODS: We organized an 8-person panel of physicians familiar with measuring HRQoL among asthmatic patients with the AQLQ and the SF-36. This expert panel participated in 2 rounds of a modified Delphi process before attending an in-person consensus meeting to establish the CID standards for small, moderate, and large changes in the AQLQ and the SF-36. After the consensus meeting, the panel used an iterative improvement process to cooperatively complete their final report. RESULTS: The expert panel's thresholds for detecting CIDs in the domains of the AQLQ were much higher than previously established levels using patient-perceived changes. CIDs for asthma were also ascertained on the scales of the SF-36, version 2, which were markedly greater than previously cited cross-sectional differences between patient groups. CONCLUSIONS: The CID standards established by this expert panel elucidate a potential distinction between patient and physician perspectives of important HRQoL changes. The many stakeholders of HRQoL difference standards should consider this distinction when adopting standards to evaluate patient change.     

Single versus double insemination: a retrospective audit of pregnancy rates with two treatment protocols in donor insemination

Our objective was to evaluate the effect of a change in treatment protocols, suggested following an inspection visit by the regulatory authority, from single to double inseminations during donor insemination treatment cycles. We therefore conducted a retrospective audit of pregnancy rates in the reproductive medicine clinic of a major teaching hospital. All patients were treated for male factor infertility by donor insemination, without ovulation induction with gonadotrophins between October 1992 and December 1995. The main outcome measures were cumulative conception and live birth rates. During the study period 250 patients underwent treatment and 650 single insemination and 277 double insemination treatment cycles were undertaken. The pregnancy rate per cycle was 0.054 and 0.119 for single and double insemination respectively. After six cycles the cumulative pregnancy rates were 0.28 and 0.47 and the take-home baby rates were 0.25 and 0.37 for single and double inseminations respectively. The change in practice from single to double insemination resulted in a doubling of the pregnancy rate per treatment cycle. Cumulative pregnancy rates after two treatment cycles of double insemination were comparable with those achieved after six cycles of single insemination. These results have significant implications for both patients and purchasers.      

The clinical utility of carotid duplex scanning

We retrospectively compared the results of duplex scanning (DS) with contrast angiography (CAN) in the evaluation of 119 patients whose 238 carotid arteries were evaluated by both methods within a four-week period. The results of all patients were then categorized by two different definitions of severity of stenosis. Category A classified 1-29% stenosis as mild, 30-69% stenosis as moderate, and 70-99% diameter reduction as severe stenosis. Category B defined mild stenosis as 1-19% lumen diameter reduction, moderate as 20-49% stenosis, and severe as 50-99% stenosis. The findings by each classification were compared in 60 patients with hemispheric symptoms and in 59 patients with nonspecific symptoms. CAN was our "gold standard", and exhibited greater sensitivity, specificity, accuracy, and predictive values than DS. Carotid arteries with 70% stenosis were identified by DS with greater specificity, accuracy, and predictive values than were arteries with 50% stenoses. Only the sensitivity was comparable in categorizations A and B (80% and 83%). All parameters of measurement were superior in patients with hemispheric symptoms. DS alone cannot substitute for CAN in selecting patients for carotid endarterectomy because its error rate exceeded acceptable rates of complications for carotid artery surgery. The false positive rate of DS was 4%. DS failed to diagnose 7 of 19 carotid artery occlusions, 9 of 11 ulcerated plaques, 7 of 119 instances of aortic arch disease, and 13 cases of severe intracranial artery stenosis.     

Submicroscopic deletions in the Y chromosome of infertile men

Recent investigations have suggested a high prevalence of Y chromosome submicroscopic deletions in men with severely impaired spermatogenesis. We evaluated the frequency of Y chromosome deletions in 160 infertile men using a series of 36 sequence-tagged-sites, emphasizing intervals 5 and 6 of the long arm of the Y chromosome. Peripheral leukocyte DNA was extracted and amplified with two parallel techniques to minimize potential overestimation of the frequency of deletions. The presence of deletions was evaluated relative to patient's sperm concentration, testis volume, and hormonal parameters. Men with sperm concentration <5 x 10(6)/ml had a 7% prevalence of submicroscopic Y chromosome deletions. Deletions were detected in 7% of azoospermic men, 10% of men with <1 x 10(6) spermatozoa/ml, and 8% of men with >1 x 10(6) but <5 x 10(6) spermatozoa/ml. Other clinical parameters did not identify men with Y chromosome deletions prior to polymerase chain reaction (PCR)- based testing for the presence of sequence-tagged-sites. Two distinct regions of Y chromosome deletions were detected, approximately 3.6 Mb and 1.4 Mb in length respectively. These deleted regions are present in AZFb and AZFc respectively. No deletions were detected in AZFa. The loss of these two distinct areas is supported by the finding of highly repetitive sequences along the Y chromosome, predisposing to deletion of specific intervals on the Y chromosome during meiosis. Men with severe male infertility are at high risk for Y chromosome deletions. Testing of men for these genetic abnormalities is indicated prior to treatment with assisted reproduction.      

Genomic screening for beta-sarcoglycan gene mutations: missense mutations may cause severe limb-girdle muscular dystrophy type 2E (LGMD 2E)

Autosomal recessive limb-girdle muscular dystrophies (LGMDs) are genetically heterogeneous. A subgroup of these disorders is caused by mutations in the dystrophin-associated sarcoglycan complex. Truncating mutations in the 43 kDa beta-sarcoglycan gene (LGMD 2E) were originally identified in a sporadic case of Duchenne-like muscular dystrophy, and a common missense mutation (T151R) was identified independently in Indiana Amish pedigrees with a milder form of LGMD. To facilitate mutational analysis of larger numbers of patients directly from genomic DNA, as opposed to reverse transcribed RNA from muscle biopsies, we have determined the genomic structure of the beta-sarcoglycan gene. The open reading frame of the beta-sarcoglycan coding region extends over six exons. Primers were designed for PCR amplification of single exons from genomic DNA and subsequent single strand conformation polymorphism (SSCP) analysis. We screened 15 patients from the Brazilian LGMD patient population, 13 of whom followed a severe course. Most of the patients had been assessed previously for deficiency of alpha- sarcoglycan immunofluorescence on muscle biopsy sections as a marker for disease of the sarcoglycan complex. Novel mutations in two familial and two sporadic cases of severe childhood-onset LGMD were identified. Only one of these patients carried a truncating mutation (homozygous 2 bp deletion, FS164TER), while the other three carried missense mutations (homozygous R91P, homozygous M100K, heterozygous recessive L108R; only one allele could be identified in this family). All three missense mutations occurred in exon 3, coding for the immediate extracellular domain. Complete absence for all three of the known sarcoglycans was noted by immunohistochemistry on muscle biopsy sections of the patients.      

Isolation of salmonellae from dried rattlesnake preparations.

Salmonella arizonae and other Salmonella serovars were isolated from four different rattlesnake preparations which were used for self-treatment of various diseases. A case of disseminated S. arizonae infection is reported in a patient who had acquired immunodeficiency syndrome and ingested dried rattlesnake.