Citrinin hydrate and radicinin: human rhinovirus 3C-protease inhibitors discovered in a target-directed microbial screen.
Explore the source record for details and available documents.
3C Viral Proteases↗
Biomedical subjects
M Jackson
Publications and source records attributed to M Jackson.
Dorrigocins: novel antifungal antibiotics that change the morphology of ras-transformed NIH/3T3 cells to that of normal cells. I. Taxonomy of the producing organism, fermentation and biological activity.
The dorrigocins are new secondary metabolites produced by submerged fermentation of a streptomycete which was isolated from a soil sample collected in Australia. The dorrigocins show moderate antifungal activity and reverse the morphology of ras-transformed NIH/3T3 cells from a transformed phenotype to a normal one. The producing culture was identified as Streptomyces platensis subsp. rosaceus strain AB1981F-75.
3T3 Cells↗
[Patterns of failed internal unicompartmental knee prostheses, allowing persistence of undercorrection].
THE PURPOSE OF THIS STUDY: was to investigate how deliberate slight undercorrection of varus deformities influenced the patterns of failure seen following medial unicompartmental knee replacements. METHODS: Between 1980 and 1989, 335 medial unicompartmental knee replacements were performed using the St George Sled prosthesis. The replacements were preformed so that the postoperative mechanical axis, as defined as the line joining the centre of the femoral head to the centre of the talus, passed medial to the centre of the knee joint and through the replaced medial compartment. The mean follow-up for these patients was 6.4 years (range of 2 to 12). By 1992, 33 of these cases had required revision. The radiographs and case notes of cases were available for study. RESULTS: There were no significant differences in the demographic details between those coming to revision and the successful group. Analysis of the post-operative alignments in the successful group revealed that the desired undercorrection was achieved in 73 per cent of cases. 2 per cent were left grossly undercorrected with their mechanical axis passing medially outside the medial compartment. In 20 per cent of cases the mechanical axis was almost fully restored passing through the centre of the knee. 4 per cent of cases had an overcorrection with the mechanical axis passing through the lateral compartment. Early failures (N = 11), classified as those cases in whom satisfactory result were never obtained, were primarily due to poor patient selection or to gross technical errors at surgery. Late failures (N = 22) were those that required revision for symptomatic failure after an initially successful primary arthroplasty and were due to progressive disease (N = 6), prosthetic failure (N = 22) were those that required revision for symptomatic failure after an initially successful primary arthroplasty and were due to progressive disease (N = 6), prosthetic failure (N = 10) and recurrent medial pain (N = 6). DISCUSSION: Patients who otherwise meet the criteria for medial unicompartmental replacement, usually have a mild degree of osteoarthritis in the lateral compartment. Suddenly loading the lateral compartment, by fully correcting a varus deformity, could accelerate the degenerative process in this compartment. Progressive disease in the lateral compartment was seen in only 4 cases in our series. In 6 patients failure was associated with recurrent medial medial joint pain with increasing varus deformity. In these cases the mechanism of failure was probably the result of an excessive medial load from a gross undercorrection of the mechanical axis which passed close to or outside the medial aspect of the knee. The crude revision rate for our series with an average follow-up of 6.4 years was 10 per cent. After excluding the early failures, which resulted largely from the potentially avoidable problems the revision rate was 6.7 per cent. CONCLUSIONS: The results from this series suggest that slight undercorrection of varus deformities does not produce any significant differences in the revision rates for unicompartmental replacements when compared to previous reports. Slight undercorrection would appear, nevertheless, to effect the relative importance of the modes of failure seen. Most notably there are fewer failures from disease in the lateral compartment. This potential advantage, however, is somewhat offset by failures from excessive loading of the medial compartment as technical errors at surgery may result in gross undercorrection of the mechanical axis.
Aged↗
Atrioventricular conduction system in hearts with muscular ventricular septal defects in the setting of complete transposition.
The detailed structure of a ventricular septal defect was compared in 90 hearts with complete transposition (concordant atrioventricular and discordant ventriculoarterial connections) and in 102 hearts with concordant connections at both junctions; the latter group was selected to include only cases with the septums aligned in the normal way. The interventricular communications observed in 13% of the group with complete transposition, which, in our material, had no counterpart in the hearts with concordant segmental connections, were of special interest. These defects, completely surrounded by muscle, were positioned around the midline on the right side of the septum but always lay under or partially under the septal leaflet of the tricuspid valve. The medial papillary muscle group was always to the "left hand margin" of the defect as seen by the surgeon. Because these defects lay within the boundaries set by the septal leaflet of the tricuspid valve, they would conform to the criteria for classification as inlet muscular defects but could equally be described as central or subtricuspid. It is significant that, in all those cases with histologic sectioning, the axis of atrioventricular conduction tissue ran to the surgeon's right hand margin. This position is markedly different from the pattern found in typical defects of the inlet septum, which are completely surrounded by muscle and extend to the posterior wall of the heart. In this more common situation, the conduction axis runs above the left hand margin of the defect. This finding has obvious implications for surgical treatment.
Heart Conduction System↗
The progression of mild congenital aortic valve stenosis from childhood into adult life.
UNLABELLED: We studied 187 patients who presented with mild congenital aortic valve stenosis or a bicuspid aortic valve without stenosis at presentation; 63% were males. Information on all clinical events was obtained, and patients were traced to assess current clinical status. RESULTS: The median age at presentation was 2 years (range, 0-15). Additional cardiac lesions occurred in 51 patients, more commonly in patients presenting under 1 year of age (P < 0.0001). The median duration of follow-up was 10 years (range, 1-28); seven patients were lost to follow-up. Thirty-two patients progressed to require intervention (28 surgical, five balloon valvuloplasty) at a median age of 10.5 years. No patient who presented with a bicuspid aortic valve required intervention. Two patients developed endocarditis. There were eight deaths; four after surgery for aortic stenosis and four due to other cardiac lesions. There were no sudden deaths. Actuarial and hazard analysis showed that progression beyond mild stenosis was closely related to duration of follow-up. CONCLUSIONS: Congenital aortic valve stenosis is most frequently mild at presentation. Progression is related to duration of follow-up. Fewer than 20% of patients are likely to still have mild stenosis after 30 years. Follow-up into adult life is essential.
Actuarial Analysis↗
Infrared spectroscopic characterisation of multiple sclerosis plaques in the human central nervous system.
Fourier transform infrared spectroscopy has been used for the characterisation of white matter, grey matter and multiple sclerosis plaques from human central nervous system tissue. We demonstrate significant differences in the infrared spectra of the three types of tissue, which show that an infrared spectroscopic discrimination of multiple sclerosis plaques from healthy brain tissue is possible in principle. The spectral changes reveal pronounced lipid loss in plaques, consistent with the demyelinating nature of the disease. The chronic plaques studied here can also be distinguished from other non-myelinated areas of the brain, based on differences in water content.
Amides↗
An erythromycin analog produced by reprogramming of polyketide synthesis.
The polyketide-derived macrolactone of the antibiotic erythromycin is made through successive condensation and processing of seven three-carbon units. The fourth cycle involves complete processing of the newly formed beta-keto group (beta-keto reduction, dehydration, and enoyl reduction) to yield the methylene that will appear at C-7 of the lactone ring. Synthesis of this molecule in Saccharopolyspora erythraea is determined by the three large eryA genes, organized in six modules, each governing one condensation cycle. Two amino acid substitutions were introduced in the putative NAD(P)H binding motif in the proposed enoyl reductase domain encoded by eryAII. The metabolite produced by the resulting strain was identified as delta 6,7-anhydroerythromycin C resulting from failure of enoyl reduction during the fourth cycle of synthesis of the macrolactone. This result demonstrates the involvement of at least the enoyl reductase from the fourth module in the fourth cycle and indicates that a virtually complete macrolide can be produced through reprogramming of polyketide synthesis.
Amino Acid Sequence↗
Cerebral arterial narrowing with nicotine patch.
Explore the source record for details and available documents.
Administration, Cutaneous↗
Spectral Doppler flow profiles in neonates with obstructive lesions of the aortic arch.
The aim was to assess the value of continuous and pulsed wave Doppler ultrasound in the detection and differentiation of obstructive lesions of the aortic arch in neonates. In 31 neonates with proven arch obstruction (pre- or juxtaductal coarctation in 19 patients; postductal coarctation in five patients; interrupted aortic arch in four patients; aortic arch atresia in three patients), continuous wave Doppler interrogation of the descending aorta from the suprasternal notch revealed a high velocity jet (greater than 2.2 m/s) directed away from the transducer in 12 patients. Of these, four neonates had preductal coarctation, and five postductal coarctation. The remaining three patients had arch interruption or atresia. Image guided pulsed Doppler ultrasound recordings were obtained from the arch upstream from the obstruction, the descending aorta distal to the obstruction, and from the arterial duct. Patients with coarctation had a prominent diastolic flow directed away from the transducer in the arch upstream from the obstruction, representing a diastolic coarctation gradient, or diastolic steal either by the patent arterial duct or by collateral vessels. In contrast, patients with arch interruption or atresia had only a systolic flow signal in the proximal arch. Ductal flow was either bidirectional (preductal coarctation, arch interruption, arch atresia), continuous right to left flow from pulmonary artery to aorta (one case each of juxtaductal coarctation and arch atresia), or continuous left to right flow from aorta to pulmonary artery (postductal coarctation). In neonates wide patency of the duct often precludes the development of a large pressure drop across a coarctation. Conversely, a high velocity signal may be recorded from a patent but restrictive duct. In conjunction with imaging, pulsed Doppler velocity profiles from the arch and patent duct permit a meaningful interpretation of the haemodynamics of arch obstruction.
Analysis of Variance↗
Epidermal cancer associated with expression of human papillomavirus type 16 E6 and E7 oncogenes in the skin of transgenic mice.
Certain "high-risk" anogenital human papillomaviruses (HPVs) have been associated with the majority of human cervical carcinomas. In these cancers, two papillomaviral genes, E6 and E7, are commonly expressed. In this study we provide evidence that expression of the E6 and E7 genes from the high-risk HPV-16 in the skin of transgenic mice potentiated the development of preneoplastic lesions, and a high percentage of these epidermal lesions subsequently developed into locally invasive cancers. High levels of E6/E7 expression were found in these tumors relative to the preneoplastic lesions, and expression was localized to the proliferating, poorly differentiated epidermal cells. Also, the p53 and Rb genes were found to be intact, not mutationally inactivated, in representative skin tumors. These findings demonstrate that the E6 and E7 genes from a papillomavirus etiologically associated with human cervical cancer can contribute to the development of epidermal cancers in an animal model.
Animals↗
Development of the collagen network of the human fetal myocardium: an immunohistochemical study.
We have studied the development of the collagen network within the ventricular myocardium of sixteen human fetuses of gestational age 12 weeks to 22 weeks. Using the technique of indirect immunohistochemistry with antibodies raised against collagen Types I and III, we have demonstrated that the 12 week old heart has a rudimentary endomysial collagen structure which coexpresses both collagen types. Perimysial structures evolve with the onset of the second trimester and are collagen III positive before expressing collagen Type I. No differences in collagen deposition were detected between the right and left ventricular free walls, but collagen content of the interventricular septum appeared relatively high and expressed in thick highly organised fibrils. Transventricular gradients of collagen distribution were seen for both collagen isoforms which persisted with increased age. Intraventricular differences in collagen deposition were marked due to the insertion of the atrioventricular valves and tension apparatus. These findings suggest that the collagen network of the fetal myocardium is composed of copolymer fibrils, possibly rich in collagen type III which evolve at a time when the mechanical efficiency of the fetal heart must improve to keep pace with the escalating demands of a rapidly growing body.
Collagen↗
Migraine angiitis precipitated by sex headache and leading to watershed infarction.
Vasospasm is a rare cause of cerebrovascular disease except following subarachnoid haemorrhage. We describe a woman who developed an explosive-type sex headache, followed by a series of severe migrainous headaches associated with fully reversible segmental cerebral arterial narrowing and dilatation, resulting in widespread infarction in cerebral arterial border zones. This led to transient loss of consciousness and multiple focal cortical deficits including blindness. She had a past history of migraine and a family history of both migraine and sex headaches. Similar cases have been reported in the literature under a variety of rubrics. We suggest that this newly recognized clinico-radiological syndrome is a migraine variant.
Adult↗
Evaluation of a gastric delivery system for iron supplementation in pregnancy.
The present investigation was undertaken to assess the efficacy of oral iron supplementation during pregnancy by using a gastric delivery system (GDS). Three hundred seventy-six pregnant women between 16 and 35 y of age and 14 and 22 wk gestation were selected if mild anemia was present (hemoglobin concentration 80-110 g/L). The participants were randomly assigned to one of three study groups given no iron, two FeSO4 tablets (100 mg Fe) daily, or one GDS capsule (50 mg Fe) daily. Blood was obtained initially and after 6 and 12 wk for measurement of red blood cell and iron indexes, including serum transferrin receptor. There was a significant and comparable improvement in hematologic and iron-status measurements in the two groups of women given iron whereas iron deficiency evolved in women given no iron supplement. We conclude that by eliminating gastrointestinal side effects and reducing the administration frequency of an iron supplement to once daily, a GDS offers significant advantages for iron supplementation of pregnant women.
Administration, Oral↗
Incidence and prognosis of congenital aortic valve stenosis in Liverpool (1960-1990).
OBJECTIVE: To determine the incidence and prognosis of congenital aortic valve stenosis in the five Health Districts of Liverpool that make up the Merseyside area. DESIGN: The records of the Liverpool Congenital Malformations Registry and the Royal Liverpool Children's Hospital identified 239 patients (155 male, 84 female) born with aortic valve stenosis between 1960 and 1990. Patients were traced to assess the severity of stenosis at follow up. Information on the severity at presentation and all subsequent events was obtained. RESULTS: Congenital aortic valve stenosis occurred in 5.7% of patients with congenital heart disease born in the Merseyside area. The median age at presentation was 16 months (range 0-20 years). Stenosis was mild at presentation in 145 patients, moderate in 33, severe in one and critical in 21 and 39 had a bicuspid valve without stenosis. Additional cardiac lesions were significantly more common in children presenting under one year of age and in those with critical stenosis. The median duration of follow up was 9.2 years (range 1-28 years) and seven patients were lost to follow up. 81 operations were performed in 60 patients. The reoperation rate was 28.3% after a median duration of 8.7 years (range 2.5-18 years). 15% of patients who presented with mild stenosis subsequently required operation compared with 67% of those with moderate stenosis. There were no sudden unexpected deaths and no deaths after aortic valvotomy, except in those presenting with critical stenosis. Mortality was 16.7% but patients presenting with critical aortic stenosis had a much worse prognosis. Actuarial and hazard analysis showed that the survival and absence of serious events (aortic valve surgery or balloon dilatation, endocarditis, or death) were significantly better in patients who presented with mild aortic stenosis than in those who presented with moderate aortic stenosis. 75% of patients presenting with mild stenosis had not progressed to moderate stenosis after 10 years of follow up. CONCLUSIONS: Congenital aortic valve stenosis may be progressive even when it is mild at presentation. Patients presenting with mild stenosis, however, have a significantly better prognosis than those presenting with moderate stenosis. An accurate clinical and echocardiographic assessment of the severity of aortic valve stenosis at presentation provides a good guide to prognosis into early adult life.
Actuarial Analysis↗
Alien hand sign in association with Alzheimer's histopathology.
A 68 year old man is described with an alien left hand, cortical myoclonus, bilateral parietal lobe dysfunction and memory impairment but preserved language skills. The clinical diagnosis was of corticobasal degeneration but at necropsy, four years after the onset of symptoms, the pathology was of Alzheimer's disease together with some scattered chromatolytic pale neurons in the cerebral cortex. The alien hand sign has not previously been described in Alzheimer's dementia and is an illustration of the clinical heterogeneity that may occur in association with Alzheimer histopathology.
Aged↗
Guillain-Barré syndrome in a patient with chronic lymphocytic leukaemia.
Explore the source record for details and available documents.
Aged↗
Treatment of symptomatic pulmonary aspergillomas with intracavitary instillation of amphotericin B through an indwelling catheter.
BACKGROUND: The treatment of symptomatic pulmonary aspergillomas can be difficult. One approach has been to deliver antifungal drugs directly into the lung cavity. The use of this method of treatment is described in which an indwelling percutaneous catheter is used which avoids repeated needlings of the cavity and may allow extended treatment on a domiciliary basis. METHODS: Amphotericin B was delivered through indwelling percutaneous intracavitary catheters to treat five symptomatic episodes in four patients with pulmonary aspergillomas. RESULTS: The treatment was well tolerated by all patients and their symptoms resolved in four of the five episodes. Two patients died, one from an unrelated bronchopneumonia and the other from advanced cachexia. Two patients remain symptom free after eight and 12 months. CONCLUSIONS: Intracavitary administration of amphotericin through an indwelling catheter should be considered for any patient who has troublesome sputum production, haemoptysis, or systemic symptoms attributable to an aspergilloma.
Adult↗