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Biomedical subjects

J Macfarlane

Publications and source records attributed to J Macfarlane.

36 records · Page 2Linked to original sources

The functional integration of a polytopic membrane protein of Escherichia coli is dependent on the bacterial signal-recognition particle.

In eukaryotes, the cotranslational targeting of proteins to the endoplasmic reticular membrane is initially mediated by the signal-recognition particle (SRP), a ribonucleoprotein complex consisting of the 7SL RNA and six protein subunits. Since the discovery of sequence homology between (a) the Escherichia coli 4.5S RNA (Ffs) and 7SL RNA, and (b) the E. coli P48 (Ffh) and SRP 54-kDa subunit, more evidence has been obtained that E. coli also possesses an SRP-type pathway that acts in the translocation of secreted proteins. Such a pathway could possibly be involved in the cotranslational integration of hydrophobic membrane proteins that cannot be effectively targeted post-translationally due to folding and aggregation. In this study, we report that disruption of the E. coli SRP complex with a dominant lethal 4.5S RNA mutant in vivo prevents functional membrane integration of the E. coli lactose permease (LacY). Likewise, depletion of the P48 (Ffh) protein also results in a decrease in the amount of functional LacY inserted into the E. coli plasma membrane. In direct contrast, inhibition of SecA function does not affect LacY integration. These results suggest a major function of the bacterial SRP in the targeting and subsequent integration of hydrophobic membrane proteins as opposed to SecA mediating the post-translational targeting of secretory proteins.

Escherichia coli↗

An overview of community acquired pneumonia with lessons learned from the British Thoracic Society Study.

There are many factors resulting in a changing pattern of pneumonia. This varies from the impact of an aging population, patients surviving longer with underlying chronic disease, severe illness, and various causes of immunosuppression and the effect of new investigations, new antibiotics, and the recognition of new pathogens. Numerous studies have been performed over the last few years regarding the cause and outcome of community-acquired pneumonia (CAP). Marked variation in results has been seen related to the criteria used for defining and diagnosing pneumonia, the population studied, and the use of differing investigations and diagnostic criteria. This is particularly apparent when comparing the different incidence of pneumococcal infection as a cause of CAP in studies from different parts of the world. Extrapolation of the findings from the multicenter British Thoracic Society (BTS) study of pneumonia suggests that pneumococcal infection is more common than several studies suggest. Having said that, it is clear from examination of the many studies that CAP is a diverse disease and that different part of the world will have to develop individual management strategies based on a critical analysis of the best available study data appropriate to their local or national situation.

Bacteria↗

The unique N terminus of the herpes simplex virus type 1 large subunit is not required for ribonucleotide reductase activity.

Using purified bacterially expressed herpes simplex virus type 1 ribonucleotide reductase large subunit (R1) and the proteolytic enzymes chymotrypsin and trypsin, we have generated stable N-terminal truncations. Chymotrypsin removes 246 amino acids from the amino terminus to produce a fragment (dN246R1) which retains full enzymic activity and affinity for the small subunit (R2). Treatment of R1 with trypsin produces a 120K protein and a cleavage at amino acid residue 305 to produce a fragment (dN305R1) which remains associated with a 33K N-terminal polypeptide. Although this 33K-dN305R1 complex retains full binding affinity for R2 its reductase activity is reduced by approximately 50%. Increasing the concentration of trypsin removes the 33K N-terminal polypeptide resulting in dN305R1 which, when bound to R2, has full ribonucleotide reductase activity. Like R1, dN246R1 and dN305R1 each exist as dimers showing that the first 305 amino acids of R1 are not necessary for dimer formation. These results indicate that, in structural studies of subunit interaction, dN246R1 or dN305R1 can be considered as suitable replacements for intact R1.

Amino Acid Sequence↗

Antibiotic therapy, clinical features and outcome of 36 adults presenting to hospital with proven influenza: do we follow guidelines?

The impact of the 1989/1990 influenza epidemic on the Nottingham hospitals was assessed in a retrospective survey. Thirty-six cases of proven influenza were identified, 14 of whom died. Non-survivors were more likely to be confused, uraemic and to lack focal chest signs and symptoms. Antibiotic therapy both prior to admission and following hospitalization was not optimal and, in many cases, failed to follow previously published guidelines. Such guidelines need emphasis during influenza epidemics.

Adult↗

Interstitial deletion of (17)(p11.2p11.2) in nine patients.

We describe a new and distinct syndrome involving an interstitial deletion of short arm of chromosome 17 in nine unrelated patients (six males; three females) ranging in age from 3 months to 65 years. In eight patients, a deletion of a portion of band 17p11.2 was associated with a striking similar phenotype including brachycephaly, midface hypoplasia, prognathism, hoarse voice, and speech delay with or without hearing loss, psychomotor and growth retardation, and behavior problems. The one patient with a complete deletion of band 17p11.2 was more severely affected with facial malformations, cleft palate, and major anomalies of cardiac, skeletal, and genitourinary systems; the patient died at age 6 months. Careful cytogenetic analysis including high-resolution techniques will be important for the further identification of patients with this previously unrecognized deletion syndrome.

Abnormalities, Multiple↗

Lung biopsy.

Explore the source record for details and available documents.

Adult↗

Home nebulizers in severe chronic asthma.

Twenty-four outpatients who continued to have severe chronic asthma despite attending a chest clinic were studied. All were already using inhaled beta-agonists from a pressurized aerosol and regular inhaled corticosteroids. Nineteen were on long-term oral corticosteroids. Comparison was made between their symptoms and peak expiratory flow rate (PEFR) during 4 weeks on their usual treatment and the following month when they were also given 5 mg terbutaline night and morning by nebulizer. During the second month the symptom score for nocturnal asthma improved by 30% (P less than 0.01), for daytime wheeze by 23% (P less than 0.025) and shortness of breath by 15% (P less than 0.01). The prebronchodilator morning and evening PEFR increased by 8% (P less than 0.025) and 10% (P less than 0.01) respectively. A dose-response study with inhaled terbutaline in six patients before and after 4 weeks of nebulizer treatment showed no evidence of a decline in response. Home nebulizers produced considerable overall improvement. Because of variations in individual responses a monitored trial of the type which we have used is desirable before a decision is made on long-term treatment.

Adult↗

Mycoplasma pneumoniae infection, antibiotics and exanthema.

A retrospective survey of 81 patients with serologically proven Mycoplasma pneumoniae infection revealed that 72% received two or more different antibiotics during their illness, ampicillin and other penicillins being most frequently used. Fifteen (18.5%) patients had a skin rash, most commonly an erythematous maculopapular rash. It is suggested that such rashes may be due to antibiotics and, unlike mucocutaneous vesicular rashes, are probably not a useful indication of mycoplasmal pneumonia.

Adult↗

Use of the phenolsulphonphthalein dye test for fallopian tube patency in cattle.

Results of preliminary investigations of fallopian tube patency in cattle using a method based on intrauterine instillation of PSP dye, and detection of the dye in the urine, suggest that this test can provide a useful diagnostic aid in cases of bilateral occlusion. In such cases PSP dye is not evident in the urine two hours later. In normal animals dye is present within 30 minutes. In two animals with unilateral blockage dye appeared at an intermediate time between the normal and bilaterally occluded cases. Repetition of the test and the use of adequate volumes of dye to cause uterine distension may be necessary to eliminate false negatives.

Adnexal Diseases↗

Parental origin of a ring 13 chromosome in a female with multiple anomalies.

A ring chromosome No. 13 was found in a 21-year-old female with multiple anomalies suggestive of 13q--syndrome. Chromosomes of the girl and her parents, studied by quinacrine staining, revealed the ring to be of paternal origin. Detailed study of the quinacrine banding pattern of the ring indicated loss of the most distal band of the long arm (13q34) and possible partial loss of the next adjacent long arm band (13q33). The short arm (13q11) was present but the stalk (13p12) and satellite (13p13) regions appeared to be missing.

Abnormalities, Multiple↗