Biomedical subjects
Publications and source records attributed to J Holder.
Arthritis is a well-recognized but uncommon accompaniment to several chronic cutaneous inflammatory conditions in which severe acne is one component. We report the case of a man with dissecting cellulitis of the scalp who developed severe peripheral and axial arthritis.
We present a child on long-term treatment with levamisole, and heterozygous for factor V Leiden, who developed cutaneous necrosis associated with formation of p-ANCA and lupus anticoagulant. Symptoms resolved when the levamisole treatment was stopped.
The adenosine subtype 1 (A1) receptor, which may influence cardiac function and modulate renal function, may have particular relevance in congestive heart failure (CHF). However, the effects of A1 receptor inhibition in the setting of CHF are poorly defined. Systemic hemodynamics and indices of renal function were measured in pigs with pacing-induced CHF at 240 bpm for 3 weeks (n = 10) before and after A1 receptor blockade with 100 microg of BG9719 (1,3-dipropyl-8-[2-(5,6-epoxynorbornyl)]xanthene) or in CHF pigs after infusion of vehicle only (n = 10). Heart rate, mean aortic pressure, and left ventricular peak pressure increased following A1 blockade in the CHF group, consistent with an adenosine inhibitory effect. However, cardiac output and global measures of vascular resistance did not significantly change following A1 blockade. Urine output increased twofold and sodium clearance increased threefold following A1 blockade (p < 0.05). Creatinine clearance increased following A1 blockade (127 +/- 17 vs. 62 +/- 7 ml/min, p < 0.05). Selective A1 receptor blockade improved glomerular filtration rate and induced a natriuresis and diuresis in a model of CHF without adverse effects on cardiac function. These unique results suggest that renal A1 receptor activation may contribute to the reduced renal function associated with CHF.
Tim23p (translocase of the inner membrane) is an essential import component located in the mitochondrial inner membrane. To determine how the Tim23 protein itself is transported into mitochondria, we used chemical cross-linking to identify proteins adjacent to Tim23p during its biogenesis. In the absence of an inner membrane potential, Tim23p is translocated across the mitochondrial outer membrane, but not inserted into the inner membrane. At this intermediate stage, we find that Tim23p forms cross-linked products with two distinct protein complexes of the intermembrane space, Tim8p-Tim13p and Tim9p-Tim10p. Tim9p and Tim10p cross-link to the COOH-terminal domain of the Tim23 protein, which carries all of the targeting signals for Tim23p. Therefore, our results suggest that the Tim9p-Tim10p complex plays a key role in Tim23p import. In contrast, Tim8p and Tim13p cross-link to the hydrophilic NH(2)-terminal segment of Tim23p, which does not carry essential import information and, thus, the role of Tim8p-Tim13p is unclear. Tim23p contains two matrix-facing, positively charged loops that are essential for its insertion into the inner membrane. The positive charges are not required for interaction with the Tim9p-Tim10p complex, but are essential for cross-linking of Tim23p to components of the inner membrane insertion machinery, including Tim54p, Tim22p, and Tim12p.
Biochemical profiles, restriction endonuclease analysis (REA) and ribotyping were used to investigate a total of 38 Pasteurella multocida isolates from four separate outbreaks of pasteurellosis in Australian piggeries. Six isolates were obtained from Outbreak 1, 16 from Outbreak 2 and eight each from outbreaks 3 and 4. Outbreaks 1 and 2 were cases of pneumonic pasteurellosis while outbreaks 3 and 4 involved systemic pasteurellosis. Biochemical characterisation established that a number of different types of P. multocida were present in outbreaks 1 and 3 while outbreaks 2 and 4 were associated with a single type of P. multocida. Outbreaks 1 and 3 yielded isolates of P. multocida that belonged to the subspecies multocida and gallicida, with the subspecies multocida isolates being identified as biovar 3 (6 in total) or 12 (1 in total) and the subspecies gallicida isolates (7 in total) being identified as biovar 8. All 24 isolates from outbreaks 2 and 4 belonged to the subspecies multocida and were all biovar 3. REA and ribotyping showed that, in outbreaks 1 and 3, there were three different types of P. multocida in each outbreak with no common strains between the outbreaks. The molecular methods showed that only a single strain of P. multocida was associated with outbreaks 2 and 4, although the outbreaks were associated with strains that differed in REA profiles but shared a ribotype profile. This study has shown that both, systemic and pneumonic pasteurellosis can be associated with either a single strain or multiple strains of P. multocida. The results also indicate that the molecular typing methods of REA and ribotyping are superior to biochemical characterisation for epidemiological investigation of porcine pasteurellosis.
OBJECTIVE: The rarer allele of a polymorphism within the promoter region at position -308 of the gene for tumor necrosis factor alpha is associated with increased gene transcription. In this study we tested the hypothesis that this rarer allele is associated with spontaneous preterm birth. STUDY DESIGN: We conducted a case-control study of women admitted to our labor and delivery unit. To assess data from a single racial group with a high incidence of preterm birth we restricted our analysis to African American women, who contributed 73.6% of the samples collected during the study period. Case patients (n = 55) were defined as women who were delivered before 37 weeks' gestation after idiopathic preterm labor or preterm premature rupture of membranes. Control subjects (n = 110) included women who were delivered after 37 weeks' gestation and had no history of preterm delivery. We also performed subgroup analyses of women with idiopathic preterm labor and delivery (n = 29) and women who were delivered preterm after preterm premature rupture of the fetal membranes (n = 26). RESULTS: Although carriers (homozygotes plus heterozygotes) of the rarer allele of the polymorphism at position -308 in the gene for tumor necrosis factor alpha were not significantly more common among women who were delivered preterm (n = 24/55, 44%) than among control subjects (n = 33/110, 30%, P =.08, odds ratio 1.81, 95% confidence interval 0.92-3.54), carriers of the rarer allele were more common among women who were delivered preterm after preterm premature rupture of membranes (n = 15/26, 58%) than among control subjects (P =.008, odds ratio 3.18, 95% confidence interval 1.33-7.83). CONCLUSIONS: Our results demonstrate an association between allelic variants of the polymorphism at position -308 in the gene for tumor necrosis factor alpha and preterm birth after preterm premature rupture of the fetal membranes. We hypothesize that host susceptibility to environmental factors, such as hyperresponsiveness of the gene for tumor necrosis factor alpha to genital tract infection, may promote preterm premature rupture of the fetal membranes and subsequent preterm delivery.
In order to audit United Kingdom laboratory diagnostic and reference services including novel molecular methods for tuberculosis, a questionnaire was sent to laboratories submitting specimens to the PHLS Mycobacterium Reference Unit (MRU) and regional centres and to the Scottish Mycobacteria Reference Laboratory (SMRL) in 1996-7. Nationally, 67.2% of laboratories responded. Most UK laboratories were fully or conditionally CPA accredited and take part in the NEQAS proficiency scheme. On average only 3.3% of primary samples submitted for mycobacterial diagnosis in 1995 produced a mycobacterial culture from approximately half as many patients (that is, a mean of 1488 specimens producing 49 isolates from 23 patients). Potentially over 380,000 specimens are processed for mycobacteria in the UK each year. The majority of laboratories use 4% NaOH +/- NALC for specimen decontamination. Culture on solid media was used by most laboratories and 62.9% also use liquid media. Most laboratories incubated cultures for eight weeks. Few laboratories use molecular diagnostic methods. Laboratories were most likely to use molecular methods for diagnosing tuberculous meningitis and for specimens from immunocompromised patients, although usage was strongly influenced by cost. Within England and Wales 43.9% (47/107) and 56% (61/109) of laboratories wanted a rapid service for rifampicin resistance detection in M tuberculosis from immunocompetent and immunocompromised patients, respectively. In regard to a tuberculous meningitis service, 80.5% (43/112) and 84.3% (102/121) of laboratories wanted this service for immunocompetent and immunocompromised patients, respectively. The quality of reference services was rated as "very good"/"good" by 85.6% of respondents nationally. Rapid molecular amplification diagnostic services were established at the PHLS MRU for rifampicin drug resistance detection nationally and for tuberculous meningitis at the MRU.
The value of pigmented lesion clinics (PLCs) for the early detection and treatment of malignant melanoma has been questioned. We have examined the effect of the introduction of a PLC on the referral interval between patients with melanoma presenting to their general practitioner (GP) and their attendance at hospital. The case notes of all patients presenting with melanoma in Leicestershire between 1984 and 1994 were reviewed. There was a significant initial reduction in the mean referral interval following the introduction of the PLC from 27.9 days (SEM = 6.6) in 1984 to 11.3 (2.3) days in 1987 (P < 0.01). However, the referral interval gradually rose over the following 7 years to a mean of 20.4 (4.4) days in 1994, which was not significantly better than the 1985/86 level. The increase in the referral interval was due to a greater percentage of melanomas being referred to clinics other than the PLC. Only 48% of melanomas were referred to the PLC in 1994 compared with 70% in 1987. We also reviewed the referral letters for those patients presenting in 1991 and 1994, and decided, on the basis of the content of the letter, whether the GP had suspected the diagnosis of melanoma. More than 50% of the melanomas were correctly diagnosed by the GP, but only half of these were then appropriately referred to the PLC. We believe that PLCs are of value in the early diagnosis and treatment of melanoma, but only if they are appropriately utilized by GPs.
The authors examined the prevalence of Alzheimer's disease and apolipoprotein E allele frequencies in the Old Order Amish. A lower frequency of dementia in the Amish does not appear to be due to a reduced E4 frequency.
We investigated the transfer of the lacZ reporter gene into human trophoblastic cells using herpes simplex virus and adeno-associated virus vectors. We used an established choriocarcinoma cell line (BeWo cells) that can be induced to terminally differentiate after treatment with cyclic-AMP. Our results demonstrate that transduction of trophoblastic cells by the herpes simplex virus vector, HSV.CMVlac, and the adeno-associated virus vector, AAV.CMVlac, is affected by cellular differentiation. Treatment of BeWo cells with cyclic-AMP reduced transduction by HSV.CMVlac but increased transduction by the AAV vector. In contrast, when BeWo cells were transfected with herpes simplex virus and adeno-associated virus plasmids, lacZ expression was not affected by treatment with cyclic-AMP. Southern blot analysis demonstrated 2.75 times less herpes simplex virus DNA in cyclic-AMP treated BeWo cells, but 2.0 to 7.4 times more adeno-associated virus DNA in treated cells. We conclude that inefficient transduction of differentiated trophoblastic cells with HSV.CMVlac is because of diminished viral entry, whereas cellular differentiation is associated with increased entry of AAV.CMVlac. These observations suggest that adeno-associated virus vectors may be used to modify trophoblast function and study placental physiology. Additionally, trophoblast differentiation leads to alterations in the mechanisms of virus uptake that may affect maternal-to-fetus transmission.
We have identified a new protein, Tim54p, located in the yeast mitochondrial inner membrane. Tim54p is an essential import component, required for the insertion of at least two polytopic proteins into the inner membrane, but not for the translocation of precursors into the matrix. Several observations suggest that Tim54p and Tim22p are part of a protein complex in the inner membrane distinct from the previously characterized Tim23p-Tim17p complex. First, multiple copies of the TIM22 gene, but not TIM23 or TIM17, suppress the growth defect of a tim54-1 temperature-sensitive mutant. Second, Tim22p can be coprecipitated with Tim54p from detergent-solubilized mitochondria, but Tim54p and Tim22p do not interact with either Tim23p or Tim17p. Finally, the tim54-1 mutation destabilizes the Tim22 protein, but not Tim23p or Tim17p. Our results support the idea that the mitochondrial inner membrane carries two independent import complexes: one required for the translocation of proteins across the inner membrane (Tim23p-Tim17p), and the other required for the insertion of proteins into the inner membrane (Tim54p-Tim22p).
The human placenta serves as a barrier to the transmission of some viruses, but allows others to reach the fetal circulation. The resistance and permissiveness of the placenta to viral transmission appears to be determined in large part by the placental trophoblast. In order to define the mechanisms by which human trophoblast cells influence vertical transmission of viruses, we have studied the interaction of replication-deficient recombinant viral vectors with transformed human choriocarcinoma (BeWo) cells and primary trophoblast cell cultures. Recombinant adenovirus vectors efficiently transduce BeWo cells and primary trophoblast cells. However, as BeWo cells differentiate after treatment with cAMP analogs, they become relatively resistant to adenovirus-mediated transduction due to diminished uptake of the virus particles. This differentiation-dependent loss of adenovirus transduction may be related to the down-regulation of the coxsackie adenovirus receptor, which we have detected in undifferentiated trophoblast cells. Recombinant herpes simplex virus vectors also transduce undifferentiated BeWo cells and isolated cytotrophoblast cells, but transduction by herpes simplex virus vectors declines with cAMP-induced trophoblast differentiation, apparently due to reduced viral uptake. In contrast, cAMP treatment augments trophoblast transduction by recombinant adeno-associated virus, a member of the parvovirus family. This augmentation appears to be due to increased virus uptake by a yet to be determined mechanism. The understanding of the molecular basis of these interactions between recombinant viral vectors and trophoblast cells may yield strategies to prevent vertical transmission of viruses as well as to create opportunities to modify trophoblast function through gene transfer using viral vectors.
A 47-year-old man presented with diarrhoea, acquired hypogammaglobulinaemia and a cutaneous graft-versus-host-like reaction in association with a spindle cell thymoma. Graft-versus-host reactions usually occur following allogeneic transplantation or transfusion of immunocompetent lymphoid cells but have been described rarely in the context of a thymoma.
Standard radiography of the cervical spine is still the first imaging procedure applied in degenerative disease of the cervical spine. Spondylosis deformans, osteochondrosis and uncovertebral arthrosis are well depicted by such images. Whether or not additional imaging is needed depends on the clinical symptoms. Special projections (anteroposterior oblique radiographs, lateral radiographs in flexion and extension) may be the next step. For many abnormalities, mainly of the intervertebral discs and the myelon, MR imaging has become the standard procedure, largely because of its multiplanar capabilities and its excellent contrast resolution. CT can be used instead of MR imaging if the latter method is not available, and its strength lies in the depiction of bone abnormalities. Scintigraphy is suitable for early detection of abnormalities with unclear clinical symptoms and may then indicate the correct level of the cervical spine for MR imaging or CT. Myelograms and myelo-CT can no longer be considered routine imaging methods. A number of imaging abnormalities are not strictly related to clinical findings and should therefore always be discussed in the clinical context.
Cyclosporin is a highly effective treatment for severe psoriasis and atopic dermatitis. However, both inter- and intrapatient gastrointestinal absorption of the conventional formulation of cyclosporin (Sandimmun) are very variable, ranging from 20 to 50%. Variations in bioavailability may explain isolated resistance to therapy. Neoral is a novel microemulsion formulation of cyclosporin which has been developed to enhance and standardize its absorption. We report the first experience with Neoral in patients with psoriasis and atopic dermatitis refractory to Sandimmun.
We report the case of a 57-year-old woman who developed bullous pemphigoid 3 weeks after electron beam radiotherapy. The bullae were confined to the area of the radiation field and responded to topical clobetasol propionate 0.05% cream (Dermovate). This is the second case of bullous pemphigoid confined to an area of previous radiotherapy. Radiotherapy may be a rare trigger for the development of bullous pemphigoid.
Volume 60, no. 12, p. 4553: a present address for S. J. Wells should be given, as follows: (dag) Present address: Cadbury Beverages North America, Trumbull, CT 06611. [This corrects the article on p. 4553 in vol. 60.].
Medical career choices and Machiavellianism of 36 junior and 37 senior medical students at one private midwestern medical school were studied. Machiavellianism was measured by the Mach V Scale. Students choosing psychiatry did not score significantly higher on Machiavellianism than those choosing medicine, surgery, or other clinical medical specialties. This is contrary to previous research which indicated those medical students choosing psychiatry scored higher on Machiavellianism. There were no significant differences in Machiavellianism scores from two different age groups (20-30 yr. and 31-40 yr.). No significant differences were reported in Machiavellianism scores of 45 male and 29 female medical students or between junior and senior medical students.