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Biomedical subjects

S C Holmes

Publications and source records attributed to S C Holmes.

At least 19 recordsLinked to original sources
PubMed2004

Does solitary morphoea profunda progress?

Solitary morphoea profunda (SMP) is an unusual form of scleroderma and is rarely mentioned in the literature. The back of the trunk is described as the commonest site of involvement by SMP. This disease has been recognized as a nonprogressive condition. We report three cases of SMP seen at our department within a 1-year period. Interestingly, all three patients were females and the lesions were situated on the right upper buttock. In one patient the lesion extended despite using topical tacrolimus but subsequently the lesion was kept under control with topical clobetasol propionate.

Adult↗
PubMed2003

Post-menopausal frontal fibrosing alopecia.

Post-menopausal frontal fibrosing alopecia (PFFA) has become an increasingly recognized distinct clinical entity in recent years. Most cases have been reported from Australia; however, it seems likely that the condition is under-recognized. PFFA has similarities to lichen planopilaris but is differentiated by a distinctive symmetrical fronto-temporal distribution and progressive course. We report two cases from the UK and review the literature.

Aged↗
PubMed2001

Novel spermine-amino acid conjugates and basic tripeptides enhance cleavage of the hairpin ribozyme at low magnesium ion concentration.

Combinations of the polyamine spermine and magnesium ions synergize to dramatically enhance cleavage of the hairpin ribozyme. Certain synthetic basic tripeptides stimulate hairpin cleavage significantly at limiting magnesium ion concentration, notably the tripeptide of L-diaminobutyric acid (Dab). Of a range of novel synthetic spermine-amino acid conjugates, L-Dab-spermine (but not D-Dab nor other amino acid conjugates) was more effective than spermine itself.

Amino Acids↗
PubMed2001

Tinea capitis in two elderly women: transmission at the hairdresser.

Tinea capitis is rare in the elderly. We report cases of two elderly women who presented to our dermatology clinic within 8 weeks of each other, with scalp scaling and alopecia. In both cases, Microsporum canis grew on fungal culture of their hair, and required prolonged treatment with terbinafine. Neither of them gave a history of contact with young children or any animals. Both were fairly fit and not systemically immunocompromised. However, both had been regularly visiting the same hairdresser, during the presumed period of infectivity, making this the most likely source of infection.

Aged↗
PubMed2000

Capillaritis associated with interferon-alfa treatment of chronic hepatitis C infection.

We report the case of a 36-year-old man who was referred with an asymptomatic eruption that started on both lower legs. This started shortly after being commenced on interferon-alfa for chronic hepatitis secondary to hepatitis C. Clinically, the eruption was consistent with a capillaritis (pigmented purpuric dermatosis). Histology confirmed this to be lymphocytic vasculitis. Lymphocytic vasculitis is frequently identified in the salivary glands of patients who are hepatitis C positive. Although leukocytoclastic vasculitis confined to the skin is frequently reported with hepatitis C, lymphocytic vasculitis is rarely reported. We consider that the lymphocytic vasculitis in our patient occurred as a result of interferon-alfa treatment because of the strong temporal relationship between the onset of the skin eruption and drug therapy.

Adult↗
PubMed1999

The role of essential pyrimidines in the hairpin ribozyme-catalysed reaction.

The hairpin ribozyme is an example of a small catalytic RNA that catalyses the endonucleolytic transesterification of RNA in a highly sequence-specific manner. We have utilised chemical synthesis of RNA to create mutants of the hairpin ribozyme in which a nucleoside analogue replaces one of the essential pyrimidines in the ribozyme. Individual pyrimidine nucleosides were substituted by 4-thiouridine, O4-methyluridine, O2-methyluridine or 2-pyrimidinone-1-beta-d-riboside. To facilitate the synthesis of oligoribonucleotides containing 4-thiouridine, we have devised a new synthetic route to the key intermediate 5'-O-(4, 4'-dimethoxytrityl)-2'-O-tert-butyldimethylsilyl-S-cyanoethyl-4-thiou ridine. The ability of the modified ribozymes to support catalysis was studied and the steady-state kinetic parameters were determined for each mutant. The range of analogues used in this study allows the important functional groups of the essential pyrimidines to be identified. The results demonstrate that each pyrimidine (U41, U42 and C25) plays an important role in hairpin ribozyme catalysis. The findings are discussed in terms of the various models that have been proposed for loop B of the hairpin ribozyme.

Kinetics↗
PubMed1999

Identification of novel mutations in basic hair keratins hHb1 and hHb6 in monilethrix: implications for protein structure and clinical phenotype.

Monilethrix is an hereditary hair dystrophy recently shown to be due to mutations in the helix termination motif of two type II (basic) human hair keratin genes, hHb1 and hHb6. It has been suggested that mutation in hHb1 produces a less severe phenotype. We have studied hair keratin genes and clinical features in 18 unrelated pedigrees of monilethrix from Germany, Scotland, Northern Ireland, and Portugal, in 13 of which mutations have not previously been identified. By examining the rod domains of hHb1, hHb3 and hHb6, we have identified mutations in nine of the new pedigrees. We again found the glutamine-lysine substitution (E413K) in the helix termination motif of hHb6 in two families, and in another, the corresponding E413K substitution in the hHb1 gene. In four families a similar substitution E402K was present in a nearby residue. In addition two novel mutations within the helix initiation motif of hHb6 were found in Scottish and Portuguese cases, in whom the same highly conserved asparagine residue N114 was mutated to histidine (N114H) or aspartic acid (N114D) residues, respectively. In four other monilethrix pedigrees mutations in these domains of hHb1, hHb3, and hHb6 were not found. The mutations identified predict a variety of possible structural consequences for the keratin molecule. A comparison of clinical features and severity between cases with hHb1 and hHb6 mutations does not suggest distinct effects on phenotype, with the possible exception of nail dystrophy, commoner with hHb1 defects. Other factors are required to explain the marked variation in clinical severity within and between cases.

Amino Acid Sequence↗
PubMed1998

The prescription of isotretinoin to women: is every precaution taken?

A questionnaire survey of dermatologists practising in Scotland was carried out to assess strategies for the management of women prescribed isotretinoin for acne. The results of the study suggested that the prevention of pregnancy during treatment is of considerable concern to dermatologists: over 90% routinely asked women about sexual activity and 97% routinely gave both verbal and written advice on the need to avoid pregnancy during treatment. However, clinical practices which might place women at risk of pregnancy were identified: only 30% of trainees and 51% of consultants routinely carried out pregnancy tests before treatment, and when tests were carried out, there was a tendency to rely on potentially insensitive urine assays. Additionally, there was an apparent lack of recognition of the possibility of sexual activity in girls aged under 16 years. Suggestions for the management of women prescribed isotretinoin include taking a sexual history from all women; providing clear information on the need to avoid pregnancy during treatment; obtaining informed consent prior to treatment; recommending the use of effective contraceptive measures; and exclusion of pregnancy prior to treatment by means of a suitably timed blood or urine sample and sensitive assay technique.

Abortion, Therapeutic↗
PubMed1998

Lichen sclerosus and lichen planus: a spectrum of disease? Report of two cases and review of the literature.

There has long been controversy concerning the relationship between lichen planus and lichen sclerosus. Whilst these two conditions are now considered distinct, there are shared clinical and pathological features. We now describe two patients with the cutaneous involvement of both lichen planus and lichen sclerosus, presenting a review of similar reported cases and discussing the implications for pathogenesis of these two diseases. Neither lichen planus (LP) nor lichen sclerosus (LS) are uncommon yet they have only infrequently been reported as coexisting. In his original description of LS, however, Hallopeau considered it to be a variant of LP and Gougerot has also commented on a possible common pathogenesis for the two conditions. Features which tend to support such as association include the distribution of the cutaneous lesions, histopathological features such as hydropic basal cell degeneration and a band-like lymphohistiocytic infiltrate in the dermis, and the reported association with autoimmune disease. We now report two patients in whom coexistent cutaneous LS and LP was confirmed histologically.

Adult↗
PubMed1998

A mutational hotspot in the 2B domain of human hair basic keratin 6 (hHb6) in monilethrix patients.

Monilethrix is an inherited hair dystrophy in which affected, fragile, hairs have an unique beaded morphology. Ultrastructural studies suggest a defect in filament structure in the cortex of the hair, and the hard keratins of hair and nail are thus candidate genes. In several families with autosomal dominant monilethrix, the disorder has been linked to the type II keratin gene cluster at chromosome 12q13. Recently, causative mutations in the critical helix termination motif in the 2B domain of the human hair basic keratin 6 (hHb6) have been identified. We now report the results of sequencing this domain in 13 unrelated families or cases with monilethrix. Five of the 13 had the same mutation as previously found, a G to A transversion leading to a lysine for glutamic acid substitution (E413K) in the 2B domain (residue 117 of the 2B helix) of hHb6. The mutation was confirmed by a restriction fragment length polymorphism assay developed for this purpose, and, as this mutation is evidently a common cause of the syndrome, for use in screening other cases. In eight families or cases, however, including three in whom linkage data are consistent with a defect at the type II keratin locus, no mutation was found in this domain of hHb6.

Family Health↗
PubMed1997

24,25-(OH)2D3 regulation of matrix vesicle protein kinase C occurs both during biosynthesis and in the extracellular matrix.

Plasma membranes and matrix vesicles isolated from rat costochondral resting zone chondrocyte cultures contain predominantly protein kinase C alpha (PKCalpha) and PKCzeta, respectively, and the level of PKC specific activity in these membrane fractions is regulated by 24,25-(OH)2D3 [14]. In the present study, we examined whether the effect of 24,25-(OH)2D3 on membrane PKC is via genomic mechanisms during biogenesis and through a nongenomic mechanism after the matrix vesicles are resident in the matrix. There was a dose-dependent decrease in matrix vesicle PKC specific activity and a significant increase in plasma membrane enzyme activity in cultures treated for 90 minutes with 10(-9)-10(-7) M 24,25-(OH)2D3. However, at 12 hours, matrix vesicle PKC was stimulated, but no effect was seen in the plasma membranes, suggesting that the effect seen at 90 minutes was due to a direct action of the hormone on PKC activity in the membrane, and that the effect seen at 12 hours was due to new matrix vesicle production with altered PKC content. Neither actinomycin D nor cycloheximide inhibited matrix vesicle PKC at 30, 60, or 90 minutes, but by 12 hours, these inhibitors blocked the effect of the hormone. 24,25-(OH)2D3-dependent plasma membrane PKC was sensitive to both actinomycin D and cycloheximide at early time points, but by 12 hours, no effect of the inhibitors was seen. Monensin did not alter basal plasma membrane PKC activity or the 24, 25-(OH)2D3-dependent increase, suggesting that this increase was due to translocation of cytosolic PKC rather than new membrane synthesis. Monensin did not affect matrix vesicle PKC at early time points, but it decreased 24,25-(OH)2D3-dependent enzyme activity at later times, indicating that new matrix vesicle production was blocked. At least part of the effect of 24,25-(OH)2D3 on PKC involved phospholipase A2 (PA2). Quinacrine (a PA2 inhibitor) alone had no effect on matrix vesicle PKC, but in cultures treated for 12 hours with quinacrine and 24,25-(OH)2D3, a synergistic increase in matrix vesicle PKC was observed. Quinacrine caused a time-dependent decrease in matrix vesicle PKC and a dose- and time-dependent increase in plasma membrane PKC when incubated directly with the membranes, supporting the hypothesis that PA2 plays a role in the nongenomic regulation of PKC by 24,25-(OH)2D3. Experiments using anti-isoform specific antibodies showed that 24,25-(OH)2D3 modulated the distribution of PKCalpha, beta, and zeta between the plasma membrane and matrix vesicle compartments via translocation and new PKC synthesis. Thus, the data support the hypothesis that 24, 25-(OH)2D3 regulates matrix vesicles through two pathways: a genomic one at the stage of biosynthesis and packaging, and a second nongenomic mechanism acting directly upon matrix vesicles in the matrix. These data also indicate that matrix vesicle regulation consists of complex events with several different points of regulation.

24,25-Dihydroxyvitamin D 3↗
PubMed1996

The value of Nm23 expression as an independent prognostic indicator in primary thick melanoma.

Whilst tumour thickness is of great value in predicting prognosis for groups of patients in different categories, it is of less value for individual patients. It has been proposed that expression of the nm23 gene, a putative tumour suppressor gene, is associated with improved outcome in a number of human neoplasms including malignant melanoma. We assessed nm23 expression in 22 patients who had primary melanomas > 3mm thick. Ten have survived to date and 12 died of melanoma. Using immunohistochemical methods, we found no significant differences in gene expression between the two groups.

Adult↗
PubMed1995

A gene for monilethrix is closely linked to the type II keratin gene cluster at 12q13.

Monilethrix is an uncommon hereditary disorder of hair and nail which produces hair fragility and a variable alopecia. Many of the dystrophic hairs have a unique beaded morphology. Ultrastructural changes suggest a defect in the microfilament structure of the cortex of the hair shaft,and hence the cysteine-rich trichocyte keratins are candidate genes. Here, in two families with autosomal dominant monilethrix, we have excluded linkage to the type I keratin gene cluster on chromosome 17q, but show that the disorder is closely linked to the type II keratin cluster on 12q, where genes for basic trichocyte keratins are found. The combined maximum lod score for D12S96 was 12.27 at theta=0.0. This is the first mapping of a primary human hair disorder and the first evidence implicating a defect of the word 'hard' keratins of hair and nail disease.

Chromosomes, Human, Pair 12↗
PubMed1995

Recurrent chancriform pyoderma: report of a case with tongue lesions. Is Staphylococcus aureus implicated?

We report a case of recurrent chancriform pyoderma. Staphylococcus aureus was isolated from only one of seven lesions. Immunological responses to S. aureus, as measured by peripheral neutrophil function, were normal. We question the notion that chancriform pyoderma represents an abnormal immune response to a primary staphylococcal infection. To our knowledge, this is only the third reported patient with lesions affecting the tongue.

Adolescent↗