Blood pressure in adults with short stature skeletal dysplasias

Hypertension, compounded by obesity, contributes to cardiovascular disease and mortality. Data describing hypertension prevalence in adults with short stature skeletal dysplasias are lacking, perhaps due to poor fit of typical adult blood pressure cuffs on rhizomelic or contracted upper extremities. Through health screening research, blood pressure was measured in short stature adults attending support group meetings and skeletal dysplasia clinics. Blood pressure was measured with a commercially available, narrower adult cuff on the upper and/or lower segment of the arm. Height, weight, age, gender, diagnosis, exercise, and medications were collected. Subjects were classified as normotensive, prehypertensive, or hypertensive for group analysis; no individual clinical diagnoses were made. In 403 short stature adults, 42% were hypertensive (systolic >140, diastolic >90 OR taking antihypertensive medications). For every BMI unit and 1 kg weight increase in males, there was a 9% and an 8% increase, respectively, in the odds of hypertension versus normotension. In females, the increase was 10% and 6%, respectively. In those with achondroplasia, the most common short stature dysplasia, males (n = 106) had 10% greater odds of hypertension versus normotension for every BMI unit and kilogram increase. In females with achondroplasia (n = 128), the odds of hypertension versus normotension was 8% greater for each BMI unit and 7% for each additional kilogram. These data suggest a high population prevalence of hypertension among short stature adults. Blood pressure must be monitored as part of routine medical care, and measuring at the forearm may be the only viable clinical option in rhizomelic short stature adults with elbow contractures.     

Assessing treatment progress of individual patients using expected treatment response models

The dosage model provides a normative estimate of the overall pattern of patient improvement in psychotherapy. The phase model further specifies patterns of change in the domains of subjective well-being, symptom remediation, and functioning. The expected treatment response (ETR) approach uses patient characteristics to predict an expected path of progress for each patient. With repeated measures of mental health status, the treatment progress of an individual patient can be assessed against the patient's ETR to support decisions that would enhance the quality of a clinical service while it is being delivered.     

An advanced culture method for generating large quantities of highly pure dendritic cells from mouse bone marrow

As dendritic cells (DC) are rare populations in all organs, their generation from hematopoietic precursors in large quantities has proven critical to study their biology. From murine bone marrow about 5 x 10(6) cells at 70% purity are obtained per mouse after 8 days of culture with GM-CSF. We have improved this standard method and routinely achieve a 50-fold higher yield, i.e., 1-3 x 10(8) immature and mature DC per mouse at 90-95% purity. The major modifications were: (i) the avoidance of any active depletion of bone marrow cell subpopulations to circumvent loss of precursors, (ii) a lower plating density of bone marrow cells, (iii) a prolonged culture period of 10-12 days, (iv) the reduction of the GM-CSF dose from day 8 or 10 onwards to reduce granulocyte contaminations. The final non-adherent population at day 10-12 constitutes a mixture of immature and mature DC. Further maturation of DC could be induced by high doses of LPS or TNF-alpha for the last 24 h, where 50-70% of the non-adherent fraction represented mature DC with high levels of NLDC-145, CD86 and CD40. This method allows by simple means the generation of high numbers of murine DC with very low B cell or granulocyte contaminations. It will be valuable to study DC biology notably at the molecular level.     

Quantitative analysis of muscle fibre type and myosin heavy chain Distribution in the frog hindlimb: implications for locomotory design

To investigate the design of the frog muscular system for jumping, fibre type distribution and myosin heavy chain (MHC) isoform composition were quantified in the hindlimb muscles of Rana pipiens. Muscles were divided into two groups: five large extensor muscles which were predicted to shorten and produce mechanical power during jumping (JP), and four much smaller muscles commonly used in muscle physiology studies, but that do not shorten or produce power during jumping (NJP). Fibres were classified as one of four different types (type 1, 2, 3 or tonic) or an intermediate type (type 1–2) based ontheir relative myosin-ATPase reactivity and MHC immunoreactivity in muscle cross-sections according to previous nomenclature established for amphibian skeletal muscle. Type 1 fibres correspond to the fastest and most powerful of the twitch fibres, and type 3 fibres are the slowest and least powerful. Myosin-ATPase histochemistry revealed that the JP muscles were co mposed primarily of type 1 fibres (89%) with a small percentage of type 2 (7%) and intermediate type 1–2 fibres (4%). The fibre type composition of NJP muscles was more evenly distributed between type 1 (29%), type 2 (46%) and type 1–2 (24%) fibres. Tonic fibres comprised less than 2% of the muscle cross-section in both JP and NJP groups. Similarly, MHC composition determined by quantitative SDS–PAGE revealed that JP muscles were composed predominantly of type 1 MHC (86%), with a balance of type 2 MHC (14%). The opposite pattern was found for MHC composition in the NJP muscles: type 1 (28%), type 2 (66%) and type 3 (6%). These results demonstrate that the large extensor muscles that produce the power required for jumping have a fibre type distribution that enables them to generate high levels of mechanical power, with the type 1 isoform accounting for 85–90% of the total M HC content.     

Effect of increasing dosage of an inhaled beta-2 specific agonist on pulmonary function, tremor, and cardiovascular indices.

In this investigation we evaluated the effect of increasing dosage, using an inhaled beta-2 specific agonist, pirbuterol, administered by a metered dose inhaler on pulmonary function, tremor, and cardiovascular parameters in nonacute adult asthmatic patients. This study was conducted with a randomized crossover study design in which each individual was administered a single dose of pirbuterol (0.4, 0.8 and 1.2 mg) [corrected] on separate days. Measurements of pulmonary function, tremor (by accelerometer readings), electrocardiogram, blood pressure and pulse were obtained at 0, 15, 30, 60, 90, 120, and 180 minutes following test drug administration where appropriate. These measurements were performed until there had been no change from baseline in tremor by 60 minutes or return of tremor measurements to within 15% of baseline for up to six hours. The data demonstrated that the onset of bronchodilator effectiveness had occurred by 15 minutes after test drug administration (the first testing time). The peak percent change from baseline for the FEV1 occurred at 60 minutes after administration for all three test doses. The duration of activity was never truly established as there was no significant difference between any of the potential side effects for any of the three test drugs at any testing time period. This study demonstrated that with the beta-2 specific agent pirbuterol, administered as a metered dose inhaler, there is little risk of development of skeletal muscle or cardiovascular toxicity when as much as three times the recommended dose is used in a single usage, and that there is no direct correlation between the onset, peak, and/or duration of tremor with the onset and peak of bronchodilator efficacy with this agent.     

Rapid trafficking of membrane type 1-matrix metalloproteinase to the cell surface regulates progelatinase a activation

Pericellular matrix degradation during cancer invasion and inflammation is dependent on activation of progelatinase A by membrane type 1-matrix metalloproteinase (MT1-MMP); a stoichiometric concentration of tissue inhibitor of metalloproteinase-2 (TIMP-2) is required. Activation of progelatinase A has generally been considered to be a slow process occurring as a result of enhanced expression of MT1-MMP. We herein report that ConA treatment of HT1080 fibrosarcoma cells is followed by MT1-MMP-induced activation of progelatinase A on the cell surface within 1 hour. Cell surface biotinylation, immunohistochemistry, and (125)I-labeled TIMP-2 binding to cell surface MT1-MMP were used to characterize the appearance and function of MT1-MMP on the plasma membrane. Treatment of HT1080 cells with ConA resulted in increased specific binding of (125)I-labeled TIMP-2 to cell surface receptors within 5 minutes. TIMP-2 binds almost exclusively to activated MT1-MMP on the surface of HT1080 cells. MT1-MMP function at the cell surface was also accelerated by treatment of cells with cytochalasin D, an inhibitor of actin filaments, PMA, a stimulator of protein kinase C, and bafilomycin A(1), an inhibitor of lysosome/endosome function. A functional pool of intracellular MT1-MMP available for trafficking to the cell surface was demonstrated by repetitive ConA stimulation. ConA-induced expression of MT1-MMP mRNA (Northern blot analysis) in HT1080 cells was a delayed event (>6 hours). These data suggest that presynthesized MT1-MMP is sorted to a transient storage compartment (trans-Golgi network/endosomes), where it is available for rapid trafficking to the plasma membrane and cell surface proteolytic activity.     

Distinct immunological signatures discriminate severe COVID-19 from non-SARS-CoV-2-driven critical pneumonia

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Hypo- and hypertetraploidy in a case of erythroleukemia analyzed by fluorochrome banding techniques

Chromosome studies of a case of erythroleukemia in a 57-year-old female patient were made from bone marrow aspirates using the fluorescent primary stain/counterstain methodology. The chromosome number ranged from 42 to 110. There was a high proportion of hypotetraploid cells and a few hypertetraploid and hypooctaploid ones. Structurally normal chromosomes varied in number from cell to cell, ranging from one to seven in the polyploid cells. A number of marker chromosomes were observed, some of which occurred repeatedly in two copies per hypotetraploid cell. The chromosomes involved in aberrations were tentatively identified as #3, #5, #7, #12, #13, #15, #16, #18, #19, and #21. In the abnormal chromosome #16, which was missing a normal short arm, a new kind of heterochromatin was demonstrated by sequential staining with DA-DAPI and DAPI-AMD, suggesting de novo amplification of an A-T-rich satellite DNA sequence.     

Feline coronavirus serotypes 1 and 2: seroprevalence and association with disease in Switzerland

To determine the prevalence of antibodies to feline coronavirus (FCoV) serotypes 1 and 2 in Switzerland and their association with different disease manifestations, a serological study based on immunofluorescence tests was conducted with Swiss field cats using transmissible gastroenteritis virus (TGEV), FCoV type 1 and FCoV type 2 as antigens. A total of 639 serum samples collected in the context of different studies from naturally infected cats were tested. The current study revealed that, with an apparent prevalence of 83%, FCoV serotype 1 is the most prevalent serotype in Switzerland. FCoV type 1 viruses induced higher antibody titers than FCoV type 2, and were more frequently associated with clinical signs and/or feline infectious peritonitis. The antibody development in seven cats experimentally infected with FCoV type 1 revealed that, with progressing duration of infection, antibodies to FCoV type 1 significantly increased over those to FCoV type 2. There was a significant relationship between antibody titers against TGEV, FCoV 1, and FCoV 2 and TGEV antigen detected the highest proportion of seropositive cats. We conclude that a vaccine against FCoV should be based on FCoV type 1-related antigens and that for serodiagnosis of FCoV infection TGEV should be used to attain the highest diagnostic efficiency. When serology is used in addition to clinical signs, hematology, and clinical chemistry results as an aid to diagnose clinical FIP, TGEV shows a diagnostic efficiency equal to that of a FCoV antigen.     

Concurrent infections with vector-borne pathogens associated with fatal anaemia in cattle: haematology and blood chemistry

An outbreak of a fatal haemolytic anaemia in a dairy herd of cattle in Switzerland was shown to be associated with infections with five vector-borne pathogens, namely Anaplasma marginale, A. phagocytophilum, Babesia bigemina, a Theileria spp belonging to the buffeli/sergenti/orientalis complex and haemotrophic Mycoplasma spp. The latter three had not been documented before this outbreak in Switzerland. To characterise the haematological and blood chemical changes in these unique cows, packed cell volume was determined in all 286 blood samples, blood smears, and complete haematology were performed from 285 and 173 blood samples, respectively, and biochemical parameters were assayed in 105 serum samples. Regenerative anaemia was the key sign of illness. Red blood cells of anaemic cattle were hypochromic and macrocytic. Anaemic animals had reduced platelet cell counts and increased total white cell counts. In addition, increased serum bilirubin, blood aspartate aminotransferase, gamma glutamyltransferase, glutamic dehydrogenase and blood urea nitrogen and decreased magnesium, calcium and albumin levels were found in anaemic cattle when compared to animals with normal packed cell volume. Most changes could not be attributed to a single infection. A. marginale seemed to be important in causing the outbreak, but co-infections may have aggravated the disease development and clinical signs. Thus, when encountering cattle with haemolytic anaemia, all of the mentioned pathogens should be included as differential diagnosis.