Inheritance of phenotypic traits in the progeny of a Ceratocystis interspecific cross.

Ceratocystis fimbriata is a fungal plant pathogen that causes black rot on Ipomoea batatas. Based on inoculation studies on numerous tree species, the pathogen is known to be host specific. The closely related species, Ceratocystis manginecans, causes severe wilt on a broad range of tree hosts, including Mangifera indica, Acacia mangium and other leguminous tree species. The genetic factors underlying the pathogenicity and host specificity of Ceratocystis species have rarely been investigated. In this study, an F1 population of 70 recombinant progeny from a cross between C. fimbriata and C. manginecans was generated and the inheritance of various phenotypic traits was investigated. Results showed that colony colour, growth rate, asexual spore production and aggressiveness to I. batatas and A. mangium are all quantitative traits with high levels of heritability. However, conidia production and aggressiveness appeared to be regulated by a small number of genes. No correlation could be found between aggressiveness and other phenotypic traits, suggesting that these are inherited independently. This is the first study to consider genetic inheritance of pathogenicity and host specificity in Ceratocystis species and the results will contribute, in future, to the identification of quantitative trait loci and candidate genes associated with the traits investigated.

Life expectancy of the 20th century Venda: a compilation of skeletal and cemetery data.

Little information is available on the 20th century mortality rates of rural black South African groups, such as the Venda. The purpose of this study was to apply abridged life tables in order to estimate life expectancy from both skeletal remains and death registry information of modern South African communities. Comparisons were also made with prehistoric and contemporary groups as a means to better evaluate life expectancy for this time period. The sample consisted of 160 skeletons of known Venda origin and burial registry information for 1364 black South Africans from the Rebecca Street and Mamelodi Cemeteries in Pretoria, South Africa. Standard anthropological techniques were applied to determine sex and estimate age from the skeletal remains. The stationary and non-stationary life table models were used to analyse the data. A high rate of child mortality, low juvenile and adult mortality with a steady increase in mortality after the age of 30 years was observed for both the Venda and the cemetery samples. Throughout the 20th century, life expectancy was shown to increase for black South Africans. However, due to the widespread HIV infection/AIDS of the 21st century, infant and young adult mortality rates continue to rise at such a speed that the decline in mortality seen for South Africans in the last 50 years will most likely to be lost in the next decade due to this disease.

Transilluminated powered phlebectomy accomplished by local tumescent anaesthesia in the treatment of tributary varicose veins: preliminary clinical results.

BACKGROUND: Transilluminated powered phlebectomy (TIPP) is a minimal invasive method of varicose vein surgery that is often performed with spinal or general anaesthesia following the removal of the greater saphenous vein (GSV). The use of exclusively local tumescent anaesthesia (TA) during TIPP has never been reported in the literature. OBJECTIVE: To introduce and evaluate the use of TIPP under TA in the treatment of tributary varicose veins. METHODS: Twenty patients with tributary varicose veins were treated with TIPP using the TriVex System. According to duplex scanning, patients had a competent or previous ligated saphenofemoral junction. All patients were clinically classified atleast as C2 according to the clinical, aetiological anatomical, pathological elements (CEAP) classification. The postoperative follow-up was at one week, one month and three months. RESULTS: The mean operative time was 40.5 (+/- 10.8) min, associated with an average number of 3.6 (+/- 0.7) incisions. The mean pain score (10-point visual analog scale) during the procedure, at one and three months after treatment were 2.0 (+/- 1.1), 1.6 (+/- 0.9) and 1.2 (+/- 0.5), respectively. Thigh haematoma and complications such as discolouration, indurations and paraesthesia were reported. Fifteen (75%) patients were satisfied with the cosmetic result (based on a 4-point visual analog scale) after three months and 13 (65%) patients were satisfied with the performed treatment. The mean venous clinical severity (VCS) scores among the patients before treatment, one week, four weeks and three months after treatment was 2.7 (+/- 1.5), 3.9 (+/- 1.6), 2.4 (+/- 2.0) and 1.7 (+/- 1.9), respectively. CONCLUSIONS: The use of TA resulted in adequate anaesthesia during TIPP. The pain, during and post-treatment, was minimal and acceptable for the patients. TIPP was associated with a high incidence of haematoma and reduction of the number of incisions. Patients were satisfied with the cosmetic result.

The Pretoria Bone Collection: a modern South African skeletal sample.

The Pretoria Bone Collection began with the inception of the Department of Anatomy and the Medical School at the University of Pretoria in August 1942. Since then the collection has grown from a student aid to a resource for research. In the year 2000, the Pretoria Bone Collection was reorganised. The research material was divided into skulls, complete postcranial and incomplete postcranial remains. The collection presently contains 290 complete skeletons, 704 complete skulls and 541 complete postcranial remains. This paper presents information on the composition of this collection and hopes to heighten both national and international awareness of the collection and research opportunities in South Africa.

Causes, investigation and treatment of leg ulceration.

Chronic ulceration of the lower leg is a frequent condition, with a prevalence of 3-5% in the population over 65 years of age. The incidence of ulceration is rising as a result of the ageing population and increased risk factors for atherosclerotic occlusion such as smoking, obesity and diabetes. Ulcers can be defined as wounds with a 'full thickness depth' and a 'slow healing tendency'. In general, the slow healing tendency is not simply explained by depth and size, but caused by an underlying pathogenetic factor that needs to be removed to induce healing. The main causes are venous valve insufficiency, lower extremity arterial disease and diabetes. Less frequent conditions are infection, vasculitis, skin malignancies and ulcerating skin diseases such as pyoderma gangrenosum. But even rarer conditions exist, such as the recently discovered combination of vasculitis and hypercoagulability. For a proper treatment of patients with leg ulcers, it is important to be aware of the large differential diagnosis of leg ulceration.

Cultured fibroblasts from chronic diabetic wounds on the lower extremity (non-insulin-dependent diabetes mellitus) show disturbed proliferation.

Patients with diabetes mellitus experience impaired wound healing often resulting in chronic foot ulcers. Hospital discharge data indicate that 6-20% of all diabetic individuals hospitalized (mostly with type 2 diabetes) have a lower extremity ulcer. Maintaining glucose levels at acceptable levels (below 10 mmol/l) is considered to be an important part of the clinical treatment, but the exact mechanism by which diabetes delays wound repair is not yet known. We studied this phenomenon by determining the potential of fibroblasts isolated from the ulcer sites of four patients with non-insulin-dependent diabetes mellitus to proliferate in vitro. Controls were fibroblasts isolated from normal skin of the upper leg of five healthy age-matched volunteers and of six non-insulin-dependent diabetes patients. Proliferative capacity was analysed by evaluation of plates after trypsinization and [3H]thymidine incorporation. Fibroblast morphology was studied by light and transmission electron microscopy. Diabetic ulcer fibroblasts, measured by [3H]thymidine incorporation, proliferated significantly more slowly than the nonlesional control fibroblasts (P < 0.00047) and age-matched control fibroblasts (P < 0.00003). After culturing the fibroblasts for a prolonged period in high-glucose (27.5 mM) and low-glucose (5.5 mM, i.e. physiological) medium, this difference in proliferation rate between diabetic ulcer fibroblasts and nonlesional diabetic fibroblasts remained (P < 0.0001 for high-glucose and P < 0.0009 for low-glucose on day 7). Fibroblast proliferation in all three groups was slightly lower in high-glucose than in low-glucose medium, although not significantly at any time-point. Light microscopy showed diabetic ulcer fibroblasts to be large and widely spread. Transmission electron microscopy of cultured diabetic ulcer fibroblasts and nonlesional diabetic skin fibroblasts revealed a large dilated endoplasmic reticulum, a lack of microtubular structures and multiple lamellar and vesicular bodies. These results show a diminished proliferative capacity and abnormal morphology of fibroblasts derived from diabetic ulcers of non-insulin-dependent diabetes patients.

Differences in cellular infiltrate and extracellular matrix of chronic diabetic and venous ulcers versus acute wounds.

In diabetic patients, wound healing is impaired. We studied the pathogenesis behind this clinical observation by characterizing the pattern of deposition of extracellular matrix (ECM) molecules and the cellular infiltrate in chronic (>8 wk) diabetic wounds, compared with chronic venous ulcers and an acute wound healing model. Punch biopsies were obtained from the chronic ulcer margins and control samples were collected from upper leg skin 5, 19, 28 d and 12 and 18 mo postwounding (p.w.). T cells, B cells, plasma cells, granulocytes and macrophages, and the ECM molecules fibronectin (FN), chondroitin sulfate (CS), and tenascin (TN) were visualized using immunohistochemical techniques. Expression of FN, CS, and TN was detected in dermal tissue early in normal wound healing (5-19 d p.w.). Abundant staining was seen 3 mo p.w., returning to prewounding levels after 12-18 mo p.w. In the dermis of chronic diabetic and venous ulcers with a duration of 12 mo or more, a prolonged presence of these ECM molecules was noted. Compared with normal wound healing: (i) the CD4/CD8 ratio in chronic wounds was significantly lower (p < 0.0027) due to a relatively lower number of CD4+ T cells; (ii) a significantly higher number of macrophages was present in the edge of both type of chronic ulcers (p < 0.001 versus day 29 p.w.); and (iii) more B cells and plasma cells were detected in both type of chronic wounds compared with any day in the acute wound healing model (p < 0.04 for CD20+ and p < 0.01 for CD79a+ cells). These data indicate that important differences exist in the cellular infiltrate and ECM expression patterns of acute, healing versus chronic wounds, which may be related to the nonhealing status of chronic wounds.

(Phosphinyloxy)acyl amino acid inhibitors of angiotensin converting enzyme. 2. Terminal amino acid analogues of (S)-1-[6-amino-2 [[hydroxy(4-phenylbutyl)phosphinyl]oxy]-1-oxohexyl]-L-proline.

Analogues of (S)-1-[6-amino-2[[hydroxy(4-phenylbutyl)phosphinyl] oxy]-1-oxohexyl]-L-proline (1, SQ 29,852) in which the terminal proline residue has been replaced by a variety of substituted and heteroatom-substituted prolines, N-arylglycines, N-cycloalkylglycines, and bicyclic amino acids have been synthesized and evaluated as inhibitors of angiotensin converting enzyme in vitro and in vivo. In general, the addition of lipophilic substituents to the 4-position of proline of the parent phosphonate 1 resulted in substantial increases in in vitro activity. The largest improvements were observed in the case of cis-benzyl (36-fold) and dithioketal (24-fold) analogues 2r and 2x, respectively. These enhancements of in vitro activity were accompanied by modest increases (2-3.5-fold) in in vivo (iv) activity. Among the various terminal amino acid replacements examined in this study, the indoline-based analogue 2i was by far the most potent compound on iv administration in the normotensive rat.

(Phosphinyloxy)acyl amino acid inhibitors of angiotensin converting enzyme (ACE). 1. Discovery of (S)-1-[6-amino-2-[[hydroxy(4-phenylbutyl)phosphinyl]oxy]-1-oxohexyl]-L -proline a novel orally active inhibitor of ACE.

The synthesis of a series of orally active, phosphinyloxyacyl proline inhibitors of angiotensin converting enzyme (ACE) is described. The in vitro and in vivo ACE inhibitory activities are reported for each compound. The structure-activity relationship for this series of compounds in relation to the carboxyalkyl dipeptide ACE inhibitors as well as other types of hydroxyphosphinyl-containing ACE inhibitors (e.g., the corresponding nitrogen and carbon isosteres) is discussed. Within an isosteric series of phosphorus-containing inhibitors based on the lysylproline terminal dipeptide sequence, only the phosphonates (oxygen isosteres) show a high level of oral activity. Optimum potency and oral activity in the phosphonate series occurs with the (phenylbutyl)- and n-hexylphosphonate side chains. An aminobutyl side chain in the P1' residue is an absolute requirement for full expression of oral activity. The most potent of these compounds, 8b (SQ 29,852), has intravenous and oral activities superior in potency to those of captopril in the normotensive rat.