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Biomedical subjects

V K Havu

Publications and source records attributed to V K Havu.

At least 19 recordsLinked to original sources

Expression of cell-cycle proteins p53, p21 (WAF-1), PCNA and Ki-67 in benign, premalignant and malignant skin lesions with implicated HPV involvement.

A series of 120 biopsies from benign (verruca vulgaris and keratoacanthoma), premalignant (actinic keratosis and extragenital Bowen's disease) and malignant (squamous cell carcinoma) skin lesions were studied immunohistochemically for the expression of cell-cycle proteins p53, p21 (WAF-1), PCNA and Ki-67. The presence of human papillomavirus (HPV) DNA in these samples had been analysed previously using in situ hybridization (ISH) and PCR. Moderate to intense expression of both PCNA and Ki-67 was present in most of the lesions studied. PCNA staining was extensive in the epidermis underneath the layers where abundant HPV DNA staining was shown in HPV DNA-positive verrucas. In keratoacanthomas, p21 and PCNA expression remained low, despite intense p53 expression. In actinic keratosis, only half of the specimens showed overexpression of p53 associated with moderate or intense expression of PCNA. In extragenital Bowen's lesions, all these cell-cycle markers were overexpressed, but in squamous cell carcinomas, they were heterogeneously expressed and showed no correlation with tumour differentiation. Our results suggest a mechanism by which HPV can reactivate the host genes (leading to cell proliferation) to support its own DNA replication. Also p21 might start keratinocyte differentiation in areas where HPV DNA replication starts. Cell proliferation remained active in actinic keratosis and Bowen's lesions, emphasizing the precancer character of these lesions in contrast with the benign nature of keratoacanthoma and verruca vulgaris.

Bowen's Disease↗

The role of low resistance blood flow pathways in the pathogenesis and healing of venous leg ulcers.

In an attempt to clarify the pathophysiology of haemodynamics in legs with venous ulcer we investigated the effect of a single intermittent pneumatic compression treatment on the peripheral resistance of leg arteries and the cutaneous laser Doppler flux in the leg. Eight patients with venous leg ulcers and 10 subjects with healthy legs were investigated. Doppler waveforms of the leg arteries and laser Doppler flux of the leg skin were recorded before and after a single intermittent pneumatic compression treatment with the subjects in a recumbent position. In the legs with venous ulcer, the peripheral resistance of the arteries was lower and the laser Doppler flux was greater, compared with healthy legs (p = 0.003 and p = 0.002, respectively). A single intermittent pneumatic compression treatment raised the peripheral resistance in the arteries of legs with ulcer and laser Doppler flux of the skin more in ulcer legs than in healthy legs (p = 0.046 and p = 0.034, respectively). These findings suggest that removal of oedema causes redistribution of skin blood flow in the legs with venous ulcer favouring the superficial capillary perfusion. This could explain why compression treatment promotes the healing of venous leg ulcers.

Adult↗

The peripheral resistance in arteries of legs is inversely proportional to the severity of chronic venous insufficiency.

There are conflicting reports in the literature about the existence of arteriovenous shunting in legs with chronic venous insufficiency. Using duplex scanning, we have earlier shown that there is lowered peripheral resistance in the arteries of legs with venous ulcer together with premature venous filling in angiography. In the present study we investigated the peripheral resistance in the arteries of 16 legs with chronic venous insufficiency without present ulcer. We compared the results with those obtained from 12 healthy legs and from 18 legs with venous ulcer. There was a highly significant inverse correlation between the severity of chronic venous insufficiency and the peripheral resistance in the popliteal, the dorsal pedal and the posterior tibial arteries (p < 0.001). These results suggest that there is arteriovenous shunting in legs with chronic venous insufficiency and that this phenomenon correlates with the degree of chronic venous insufficiency.

Arteries↗

Known HPV types have no association with keratoacanthomas.

Certain HPV types have been linked to the genesis and development of premalignant and malignant skin diseases. There have been several contradictory reports on the role of HPV infections in the development of keratoacanthomas (KAs). To further study the involvement of HPVs in the aetiology of KAs, we investigated paraffin-embedded specimens of 80 biopsies of KAs for the presence of HPV 1, 2, 3, 4, 5, 7, 26, 37, 38, 47 and 59 DNA by in situ hybridization (ISH) with biotinylated probes under high stringency conditions (Tm-10 degrees C). Every fourth biopsy specimens was also examined by polymerase chain reaction (PCR) with consensus primers targeting the HPV E1 and L1 regions. The positive cases were further studied by direct DNA sequencing. All specimens proved to be negative for all HPV DNAs studied by ISH. Three out of 20 cases produced in positive PCR amplifications when consensus primers targeting the L1 region were used. However, the same samples remained negative with general primers targeting the E1 region. The DNA sequence analysis of the PCR-positive products showed a 76% homology with HPV type 17. Our results suggest that the known HPV types are unlikely to have any role in the aetiology of KAs.

Base Sequence↗

Expression of PCNA is associated with the presence of HPV DNA in skin warts.

A series of 90 excised cutaneous warts (verrucae vulgaris) were studied for the presence of HPV (human papillomavirus) DNA using in situ hybridization (ISH) with biotinylated full genomic DNA probes of HPV types 1, 2, 3, and 4. The expression of PCNA (proliferating cell nuclear antigen) was examined using conventional immunohistochemistry. The aim was to test the hypothesis that HPV can reactivate PCNA, including in the host replication machinery. HPV DNA of the above types was detected in 60 of 90 verruca biopsies studied (66.7%): HPV 2 in 56 cases, HPV 1 in 2 cases, and HPV 3 in 2 cases. PCNA was expressed in all samples except two. The signal distribution of HPV DNA markedly differed from that of PCNA expression. ISH revealed strong HPV DNA signals in both the granular and the upper spinous cell layers, the most intense signals being detected in the upper epidermis. On the other hand, nuclear PCNA staining was present in the majority of parabasal and basal cells. Although strong PCNA signals within the wart lesions were found in the areas where HPV DNA was present, the PCNA positivity was almost invariably localized in the differentiated cells of the spinous cell layers, just below the HPV DNA-expressing cells. At the margins of the lesions, PCNA expression was still strong but disappeared abruptly towards the normal epidermis. HPV DNA-positive warts showed more intense expression of PCNA than did the HPV DNA-negative ones in this study. Our results indicate that PCNA induction is associated with the presence of HPV DNA, suggesting that HPV can reactivate PCNA, thus interfering with the host cell DNA replication machinery.

Cell Differentiation↗

Failure to demonstrate human papillomavirus (HPV) involvement in Bowen's disease of the skin.

To assess the role of human papillomavirus (HPV) in the aetiology of extragenital Bowen's disease (EBD), a series of 91 cases were analysed using in situ hybridization (ISH) with whole genomic DNA probes of HPV types 1, 2, 4, 6, 7, 11, 12, 15, 16, 18, 26, 36, 37, 39, 42, 55 and 59. No HPV DNA was found in any of the samples tested. A polymerase chain reaction (PCR) was also used to analyse 37 of the 91 samples, using both the consensus primers MY09/MY11 which amplify a large number of HPV types from the L1 region and the degenerate primers CP65/CP70, which amplify the complete set of epidermodysplasia verruciformis (EV) HPV types. All the cases were also negative in the PCR. The results suggest that EBD is not HPV-related, at least in immunocompetent patients.

Aged↗

No evidence of human papillomavirus DNA in actinic keratosis.

Human papillomaviruses (HPVs) are involved in premalignant and malignant skin diseases as well as in a variety of benign cutaneous and mucosal lesion disease. Its association with HPV infection has recently been evaluated in a few studies, but the results are contradictory. For further assessment of the role of HPVs in AK, a series of 100 paraffin-embedded biopsy specimens taken from subjects with AK were studied for the presence of HPV types 1, 2, 3, 4, 5, 7, 12, 15, 26, 36, 37 and 59 DNA using in situ hybridization (ISH) under high stringency conditions (Tm -10 degrees C). All specimens were definitely negative for all bion specimens were definitely negative for all biotinylated HPV DNA probes tested. One fifth of the specimens were studied using the polymerase chain reaction (PCR) with general primers to confirm the negative results. All cases were also in the PCR. Our results suggest that HPVs are not directly involved in the aetiology of AK.

Adult↗

Serum IgE in non-atopic adults and in dermatitis patients.

Total serum IgE was determined with the PRIST technique, and specific reaginic antibodies against 10 allergens were measured in 163 healthy adults with no personal or family history of symptoms indicative of atopy (Group A). 103 non-atopic adults with a family history of atopic diseases were similarly investigated (Group B). When all subjects who at the second interview presented with a history of atopic symptoms and those with positive RAST results were excluded, the geometric mean serum IgE value for Group A was 14.5 (SD = 2) - 94.4 U/ml and for Group B 14.4 (SD = 2) - 130.2 U/ml. There was no significant difference in the IgE values between men and women. Subjects under 40 years of age had significantly higher IgE values than subjects over 40 years. In the series of 276 dermatitis patients the geometric mean IgE value for the men was significantly higher (46.8) than for the women (28.8 U/ml). There was a highly significant difference in the mean serum IgE levels between the patients with a personal history of atopic diseases and the other patients. Patients with present atopic disease had significantly higher mean IgE values than those with past atopic disease while no significant difference was discernible in the mean IgE levels between the non-atopic patients from atopic families and those with no personal and family atopy. Three years later, total serum IgE was controlled in subjects with initial IgE levels greater than 100 U/ml. During this time, eight subjects had developed an atopic disease. In most cases, there were only slight variations in the IgE values.

Adolescent↗

Cell-mediated immunity against herpes simplex virus envelope, capsid, excreted, and crude antigens.

Cell-mediated immunity to herpes simplex virus envelope, capsid, excreted, and crude antigens was studied by in vitro lymphocyte stimulation tests during 198 recurrent attacks in 69 patients. Excreted antigen caused no blast transformation. Envelope and capsid antigen-induced lymphocyte stimulation was at the maximum 7 to 14 days postinfection, declining thereafter to a rather constant level in 1 to 2 months. The lowest levels were measured just a few days before a new attack. In persons with frequent relapses, the fluctuation was more rapid and stimulation index levels stayed higher, although no protective level seemed to exist. Cultures stimulated with the crude antigen in autologous serum showed rapid increases and declines in the stimulation index values, contrary to those grown in agamma serum, in which the stimulation level stayed rather constant up to 1 year postinfection.

Adult↗

Failure of oral inosiplex treatment of recurrent herpes simplex virus infections.

A compound, a mixture of acedoben, dimepranol, and inosine (inosiplex) was used to treat recurrent local herpes simplex virus (HSV) infections in a double-blind placebo-controlled crossover study. Altogether, 58 patients with a history of frequently recurrent HSV infections were examined. Eighteen selected patients participated in the drug trial. Ten patients received both inosiplex and placebo, three received only inosiplex, and five received only the placebo. Three patients received both placebo and inosiplex twice. No substantial differences between the treatments with inosiplex or placebo could be seen in the frequency of occurrence or healing of the local lesions, nor in the results of these patients' immunologic studies. An evident placebo effect was observed, since only 15 (26%) of the 58 subjects examined continued to have an often relapsing form of the disease when followed up regularly.

Administration, Oral↗

Occurrence of contact allergy and hand eczemas in hospital wet work.

The occurrence of contact sensitivity and hand dermatitis was studied in hospital employees. The incidence of contact allergy was 21%. Nickel (9%) was the most common allergen followed by perfumes (6%). Present of previous hand dermatitis was detected in 46%. Of those with positive reactions, 53% had suffered from hand dermatitis as compared to 44% of those without positive reactions. 70% of those with sensitivity to fragrances had suffered from hand dermatitis. The occurrence of hand dermatitis was more frequent in persons, who had developed contact allergy to rubber chemicals or to both nickel and cobalt simultaneously.

Allergens↗

Contact allergy in atopics, who perform wet work in hospital.

The relation of atopy, i.e. previous or present atopic dermatitis, allergic rhinitis/conjunctivitis and asthma, to contact allergy in hospital employees, who perform wet work, was studied. Patch tests were carried out with the ICDRG standard series. Among these workers the frequency of contact allergy was similar in nonatopics (21%) as in atopics (22%), who represented 33% from the whole group. Atopics were sensitized more often to balsam of Peru (5.1%) as well as to fragrances in total (8,5%) than nonatopics, (1.7% and 4.1%, respectively) (p less than 0.05). Same kind of tendency was found in the amount of rubber reactions, though the difference was not statistically significant. Nickel was the most common allergen in all workers.

Allergens↗