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Biomedical subjects

O Castrén

Publications and source records attributed to O Castrén.

At least 19 recordsLinked to original sources

Lymphocyte beta-2-adrenoceptors and plasma catecholamines in fetal hypoxia.

Conclusive evidence has been furnished that the beta 2-adrenoceptor density in circulating lymphocytes is related to that of beta 2-adrenoceptors in tissues from the same subjects. This study was designed to evaluate the effect of fetal hypoxia on lymphocyte beta 2-adrenoceptor density. The material consisted of 8 hypoxic newborns, 4 delivered by vacuum extraction and 4 by Caesarean section, after approximately 10 h parturition. The control group consisted of 8 vaginally delivered newborns without hypoxia. Umbilical plasma adrenaline and noradrenaline were significantly elevated in the hypoxic newborns. Their lymphocyte beta 2-adrenoceptor density was lower (p less than 0.01) than that in the controls. A plausible explanation for this finding might be downregulation of beta 2-adrenoceptors because of elevated plasma catecholamine level.

Down-Regulation

Decreased numbers of lymphocyte beta 2-adrenoceptors in pregnant women receiving beta 2-adrenergic agonist therapy.

Intravenous infusion of buphenine hydrochloride was administered on 4 successive days to 8 pregnant women with imminent preterm labor. Serial blood samples taken before and throughout the study were assayed for lymphocyte beta 2-adrenoceptor density and cyclic adenosine-3',5'-monophosphate (cAMP). The lymphocyte beta 2-adrenoceptor density declined significantly (p less than 0.01) during the treatment. The plasma cAMP concentration was highest 4 h after commencement of infusion and decreased thereafter. Despite the decrease in lymphocyte beta 2-adrenoceptor density, the clinical response remained good and the parturients did not go into labor until several days after infusion was started.

Adrenergic beta-Agonists

Cryotherapy and CO2-laser vaporization in the treatment of cervical and vaginal human papillomavirus (HPV) infections.

A series of 119 women with Human papillomavirus (HPV) infections of the uterine cervix and/or vagina were included in the present study, where the efficacy of cryotherapy and CO2-laser vaporization was assessed after a mean follow-up of 14 months (SD 6 months) after treatment, as related to the natural history of the disease. Routine Papanicolaou (PAP) smears with HPV-induced changes were the basis for patient recruitment. Patients with cervical HPV lesions (HPV-NCIN, HPV-CIN I or II) were randomly allocated into laser (55 women) and cryotherapy (42 women) groups. Women with combined lesions (HPV-CIN & HPV-VAIN) were treated by laser (22 patients). The cure rate after laser vaporization was practically identical to that of cryotherapy, 64% and 54%, respectively (difference not statistically significant). The success rate was significantly lower (40%) for the combined lesions (HPV-CIN & HPV-VAIN) (p less than 0.05). The residual disease encountered in patients after the first treatment with cryotherapy and laser was classified as HPV-NCIN in 78.9% and 37.0%, respectively. The number of patients is still too small to draw reliable conclusions on the effects of these therapy modes, as related to HPV type of lesion (HPV 6, 11, 16, 18, 31 and 33). The cure rates for both cryotherapy and laser in our treatment groups were significantly higher than the spontaneous regression rate (p less than 0.001), suggesting that treatment by either cryotherapy or CO2-laser vaporization significantly changes the natural history of genital HPV infections. More patients and longer follow-up are still needed, however, to fully establish the efficacy of the current treatment modalities in gynecological HPV infections.

Adolescent

Effect of freezing and ultrasonication on the density of human lymphocyte beta 2-adrenoceptors.

In this study 21 pregnant volunteers were divided into three equal groups; blood samples were taken from each, and after isolation of the lymphocytes the cell suspensions were divided into two equal samples. The density of beta 2-adrenoceptor in intact lymphocytes was compared with the receptor density for lymphocytes stored 7 days or 19 days at -70 degrees C and with cells disrupted by ultrasonication. Storage by lymphocytes at -70 degrees C for 7 days to 19 days decreased the beta 2-adrenoceptor density by 20% and 37%, respectively; ultrasonication decreased the density by 65%.

Adult

Plasma renin activity and cAMP in termination of pregnancy induced by sulprostone.

Plasma renin activity (PRA), plasma concentrations of cyclic adenosine-3',5'-monophosphate (cAMP) and the serum levels of oestradiol, progesterone, chorionic gonadotrophin, potassium, sodium and calcium were estimated in connection with termination of pregnancy induced in 23 women by sulprostone, a derivative of prostaglandin E2. A rapid decrease in PRA was observed during and after infusion of 1000 micrograms or 1500 micrograms sulprostone. PRA returned to the initial values at 24 h after drug administration. The lowest levels of PRA were 36% and 51% of the initial values (P less than 0.001) in the two drug concentration groups. No significant changes were observed in the control group. The value for plasma cAMP did not correspond completely to the changes in PRA. Serum concentrations of oestradiol, progesterone and chorionic gonadotrophin showed a gradual decrease during drug administration. The changes in serum potassium, sodium and calcium were minimal. The decrease in PRA associated with sulprostone is very surprising. Our finding elucidates in part the still rather poorly known mechanisms and function of renin-angiotensin system in pregnancy.

Abortifacient Agents

Evolution of human papillomavirus infections in the uterine cervix during a long-term prospective follow-up.

A series of 513 women presented with cervical human papillomavirus (HPV) infections (with or without cervical intraepithelial neoplasia; CIN) have been prospectively followed up since 1981 (mean 25.6 months), at 6-month intervals, by colposcopy with PAP smears and/or punch biopsies. The latter were analyzed by light microscopy, as well as immunohistochemically for HPV structural proteins. HPV DNA typing was accomplished by Southern blot, spot, and in situ hybridization techniques using the DNA probes for HPV 6, 11, 16, 18 and 31. Of the 513 lesions, 24.8% regressed, 59.8% persisted, and 14.1% progressed, 11.9% having been coned due to progression to carcinoma in situ (CIS). So far, 1.1% of lesions have recurred after such a treatment. The natural history was significantly associated with the grade of CIN (HPV-NCIN versus HPV-CIN, p less than 0.01). The progression rate was highest (33.3%) and regression lowest (5.6%) in HPV 16 lesions. All the recurrent lesions disclosed HPV 16 DNA, this type being found most frequently in the severest lesions (CIN III). Depending on the hybridization technique used, changes in HPV type were found in 11-17% of the lesions during the follow-up. Noteworthy is the discovery of all the HPV types also in biopsies with no signs of HPV infection on light microscopy, suggesting a latent HPV infection in these 'regressor' lesions. The results confirm that cervical HPV infections show a natural history comparable to that of classical CIN. Although the high-risk character of HPV 16 (and HPV 18) was clearly established, the inherent potential for progression (25.6%) of the HPV 6/11 lesions should not be neglected in therapeutic considerations.

Adolescent

Human papillomavirus (HPV) infections involved in the neoplastic process of the uterine cervix as established by prospective follow-up of 513 women for two years.

A total of 513 women with cervical HPV infections have been followed-up since 1981 (mean 25.6 months) to establish the biological potential of HPV in cervical carcinogenesis. On each attendance, the patients were subjected to colposcopy accompanied by Papanicolaou (PAP) smears and/or punch biopsies. The latter were analysed for HPV particles on TEM, for the cytopathic changes of HPV, as well as for HPV structural proteins. The local immunocompetent cell (ICC) infiltrates are enumerated using ANAE-technique to define B-, MPS- and T cells, and monoclonal antibodies for T cell subsets, NK and K cells and Langerhans cells. HPV DNA typing was accomplished by Southern blot and spot hybridization using the DNA probes for HPV 6, 11, 16 and 18. Antibody titres for HSV were measured, and Chlamydia trachomatis isolations completed in cervical swabs. No correlation with the clinical course, e.g. regression (RE), persistence (PE), progression (PR) or recurrence (RC) of the HPV lesions could be established for the following factors; expression of HPV antigens, presence of HPV particles on TEM, Chlamydia in cervical swabs, the levels of HSV antibodies, and the levels of the ICCs. The OKT4+/OKT8+ cell ratio, however, was inversely correlated with PR, being most markedly reduced in recurrent lesions. Of the 513 lesions, 24.8% regressed, 59.8% remained persistent, and 14.1% progressed, 11.9% having been coned due to progression into CIS. So far, 1.1% of lesions have recurred after such a treatment. The progression rate was highest (45.5%) in HPV 16 lesions, followed by that (27.3%) in HPV 18 lesions, as contrasted to 0% and 13.3% for HPV 6 and 11, respectively. The results clearly confirm that cervical HPV infections are capable of progressing into CIS and thus show a natural history equivalent to that of classical CIN. The inherent potential of HPV 16 and HPV 18 lesions for clinical progression was clearly established, supporting the concept on HPV 16 and HPV 18 as the high risk HPV types in cervical carcinogenesis.

Adolescent

Coexistent chlamydial infections related to natural history of human papillomavirus lesions in uterine cervix.

To assess the role of Chlamydia trachomatis in the development of cervical intraepithelial neoplasia (CIN) and to evaluate possible synergism between chlamydiae and human papillomavirus (HPV) in this process, 418 women who had been prospectively followed up for cervical HPV infections at our clinic since 1981 were tested for chlamydiae. At each visit the patients were examined by colposcopy, and other investigations, such as Papanicolaou (Pap) smears, punch biopsies, urethral, and cervical swabs, were undertaken as indicated. In biopsy specimens the cytopathic changes of HPV, concomitant CIN, and the local immunocompetent cell infiltrates were analysed. The latter were measured and further identified using an alpha naphthyl acetate esterase (ANAE) technique to define B cells, macrophages, and T cells and using monoclonal antibodies to define T cell subsets, NK (natural killer cells), and Langerhans cells. Chlamydial isolation (4.1% in the cervix, and 3.6% in the urethra) did not positively correlate with the degree of cytological atypia in PAP smears or with the degree of CIN lesions associated with HPV. Chlamydial cervicitis did not affect the ANAE definable cell composition of the immunocompetent cell infiltrates in HPV lesions, or that of the immunocompetent cell subsets, including the ratios of T helper to T suppressor cells and the numbers of NK cells. Chlamydial infection did not alter the natural history of HPV lesions, of which 30% regressed, 53% persisted, and 17% progressed during follow up. The present results do not provide evidence to substantiate the hypothesis that chlamydiae and HPV might act synergistically in cervical carcinogenesis, or the view that C trachomatis may be a major aetiological agent of CIN lesions. Chlamydiae and HPV are covariables of sexual behaviour, and their concomitant appearance in sexually promiscuous women is best explained by this fact. As we do not have more direct evidence for the oncogenic potential of C trachomatis (as we have of HPV), it seems reasonable to consider that this agent is not a major cause of CIN, but rather a sexually transmitted agent commonly found in women with CIN because of their promiscuous sexual behaviour.

Adolescent

Electron microscopy in assessment of the biological behavior of human papillomavirus infections in the uterine cervix.

To asses the natural history of human papillomavirus (HPV) infections in uterine cervix, currently implicated in etiology of cervical cancer, a prospective follow-up study has been conducted for 418 women at our clinic since 1981. The present communication summarized the current follow-up data of these patients, with special emphasis on detection of the virus in cervical punch biopsies, as correlated with other characteristics pertinent to the clinical behavior of cervical HPV infections. On each attendance, the patients are subjected to colposcopy accompanied either by Papanicolaou (PAP) smears or punch biopsies. The latter are analyzed for the cytopathic changes of HPV, for concomitant cervical intraepithelial neoplasia (CIN), for HPV structural proteins with IP-PAP technique as well as on transmission electron microscopy (TEM) for the presence of HPV particles. The local immunocompetent cell (ICC) infiltrates are analyzed using ANAE technique to define B cells, MPS cells and T cells and monoclonal antibodies (McAb) for T cell subsets, NK (natural killer) cells and Langerhans cells. HPV particles were disclosed with equal frequency (approx. 65%) in all three types of HPV lesions. Surprisingly, HPV particles were present in 70% of the biopsies derived from the regressed lesions (e. g. in those without histological evidence of HPV lesions), suggesting a possibility of a latent HPV infection. Presence of viral particles did not bear any direct correlations with the expression of HPV antigens, intensity or cellular composition of the ICC infiltrate, defined by ANAE or using McAb. Presence of HPV particles was not a major prognostic determinant, whereas the clinical course was most significantly influenced by the grade of HPV-associated CIN, to which regression was inversely and progression directly related. The results clearly confirm that cervical HPV infections are capable of progressing into carcinoma in situ and thus present with a natural history equivalent to that of classical CIN.

Female

Immunophenotypes of lymphocytes in prospectively followed up human papillomavirus lesions of the cervix.

From 1981 286 women were prospectively followed up for a mean (SD) of 16 (14) months for established infection with human papillomavirus (HPV) with or without coexistent cervical intraepithelial neoplasia (CIN). The in situ immunocompetent cell infiltrates in 263 cervical punch biopsy specimens from these women were phenotypically identified by the avidinbiotin peroxidase complex (ABC) technique using monoclonal antibodies Leu-10, OKT-3, OKT-4, and OKT-8. Leu-10+ B lymphocytes far outnumbered the OKT-3+ T lymphocytes in all types of HPV lesions (flat, inverted, and papillomatous condylomas of the cervix). The ratio of OKT-4+ to OKT-8+ (T helper to T suppressor cells) was slightly reduced in HPV lesions with more severe CIN and correlated positively with the intensity of the immunocompetent cell infiltrate. The ratio of OKT-4+ to OKT-8+ cells was highest in the 47 (28.8%) patients with HPV lesions that regressed during follow up, somewhat lower in the 85 (52.1%) with persistent lesions, and lowest in the 31 (19.1%) with lesions showing clinical progression. The results are discussed in terms of the proposed immune surveillance functions attributed to immunocompetent cells in situ according to the mucosal associated lymphatic tissue (MALT) concept. The conclusion drawn is that a dynamic balance between the immunoregulatory cells and their subtypes is a prerequisite for the proper handling of intracellular infections of the mucosa, including that with HPV.

Adolescent

Chlamydial cervicitis in women followed-up for human papillomavirus (HPV) lesions of the uterine cervix.

To assess the concomitant appearance of Chlamydia trachomatis and Human papilloma virus (HPV) (currently linked with the development of cervical cancer) in uterine cervix, a series of 250 women under continuous observation for cervical HPV lesions (with or without concomitant cervical intra-epithelial neoplasia (CIN)) were the subject of cervical culturing for C. trachomatis, as well as for IP-PAP (indirect immunoperoxidase) staining of the cervical biopsies with monoclonal antibody to C. trachomatis. Chlamydia-positive staining was found in only 2/204 biopsies (0.98%), whereas Chlamydia could be isolated from the cervix of as many as 26/250 (10.4%) women. In repeat cultures, Chlamydia was isolated in 39/936 specimens (4.2%), reflecting the effect of the treatment instituted. The results are discussed in terms of the suggested association of Chlamydia with CIN, as well as of the possible synergism between Chlamydia and HPV in cervical oncogenesis. The conclusion is drawn that Chlamydia and HPV are covariables of sexual behavior, their concomitant appearance in the uterine cervix most probably being ascribable to sexual promiscuity.

Chlamydia Infections

Colposcopy in women with papillomavirus lesions of the uterine cervix.

Colposcopic examinations for human papillomavirus lesions were performed in 271 women, some of whom had developed concomitant cervical intraepithelial neoplasia since 1981. The colposcopic appearance was classified into one of the following categories: normal, punctate, mosaic, warty, leukoplakial, or combination, and was related to findings in Papanicolaou smears and punch biopsy specimens. There was a good correlation between the colposcopic appearance and the findings in the Papanicolaou smears and punch biopsy specimens, facilitating the diagnosis of the lesions. The accuracy of colposcopy in disclosing the atypias varied according to the growth pattern of the papillomavirus lesions, with the most accurate (100%) in cases of papillomatous condylomas, and the least accurate (50%) in the inverted lesions. White epithelium and combination patterns were most frequently associated with the papillomavirus lesions and cervical intraepithelial neoplasia, as evidenced by both cytology and biopsy. During the follow-up, normal colposcopic appearance increased from 32 to 50%, reflecting the established spontaneous regression of a certain percentage of the cervical lesions, or their regression as a result of biopsy. The results are discussed in terms of the mutually complementary roles of colposcopy, cytology, and biopsy, and in view of the clinical behavior of cervical papillomavirus lesions. Colposcopy is mandatory for adequate prospective follow-up of these patients but should not replace cytology and punch biopsy.

Adult

The in situ immunological reactivity and its significance in the clinical behavior of the cervical human papillomavirus lesions.

The in situ immunocompetent cell (ICC) infiltrates in 286 cervical punch biopsies derived from the women prospectively followed-up since 1981 (16 +/- 14 months, M +/- SD) for an established human papillomavirus (HPV) infection with or without coexistent cervical intraepithelial neoplasia (CIN) were characterized using the histochemical ANAE (acid alpha-naphthyl acetate esterase) staining. Only minor fluctuations in the relative proportions of ANAE T+, ANAE M+, and ANAE- cells were found between the three types of HPV lesions (flat, inverted and papillomatous condylomas), as well as between the lesions with varying degree of HPV-CIN. The percentage of ANAE- cells (mediators of humoral immune response) increases in parallel with the increasing density of the ICC infiltrate. The intensity of the local infiltrate was inversely correlated with the progression, but not with regression or persistence of the HPV lesions. The percentage of ANAE T+ cells was highest in the 32 (18.7%) HPV lesions progressed during the follow up, almost identical in the 88 (51.5%) persistent lesions and lowest in those 51 (29.8%) lesions showing clinical regression. The results are discussed in terms of the proposed immune surveillance functions attributed to the local ICCs according to the MALT (mucosal-associated lymphatic tissue) concept. Conclusion is drawn that no major imbalance in the ANAE- definable main populations of ICCs exist in the cervical HPV lesions, which readily could explain their divergent clinical behavior. Other factors (like HPV type, synergistic action of cocarcinogens or a deranged balance between the ICC subsets) should be searched for to elucidate this issue.

Animals

Electron microscopic assessment of cervical punch biopsies in women followed-up for human papillomavirus (HPV) lesions.

Cervical punch biopsies from 102 women prospectively followed-up for HPV (Human papillomavirus) lesions (flat, inverted and papillomatous condylomas) were assessed on transmission electron microscopy (TEM) for the presence of HPV particles. The virus discovery rate was correlated with the other characteristics of significance to the clinical behaviour (natural history) of these lesions, i.e. the colposcopic pattern, expression of papillomavirus genus specific structural antigens (demonstrated by an indirect immunoperoxidase, IP-PAP technique), as well as the degree of HPV-associated cervical intraepithelial neoplasia (CIN). Virus particles were disclosed with equal frequency in all three types of HPV lesions. Noteworthy, and so far unreported, was the discovery of HPV particles in 56 and 64% of the biopsies derived from the epithelium without colposcopic or histological evidence (cytopathic effects) of HPV lesions, respectively. The degree of CIN was without influence on the virus discovery rates. Viral particles were present with equal frequency (57 and 60%, respectively) in the lesions expressing HPV antigens and in those which did not. The highest frequency (89%) of viral particles was found in lesions presented with warty or mosaicism pattern in colposcopy. The implications of these findings to understanding the biology of HPV infections in the uterine cervix is discussed, and the importance of TEM in the follow-up of these lesions is emphasized.

Animals

Factors influencing the biological behaviour of cervical human papillomavirus (HPV) infections in prospectively followed-up women.

To assess the natural history of Human papillomavirus (HPV) infections in uterine cervix, recently linked with cervical intraepithelial neoplasia (CIN), a long-term prospective follow-up study was started at our clinic in 1981. At this writing, a total of 418 women have been followed-up for a mean of 20 +/- 15 (M SD) months. On each attendance (at six-month intervals), the patient is subjected to colposcopy accompanied either by Papanicolaou (PAP) smears or punch biopsies. The latter are analysed for the cytopathic changes of HPV, for concomitant CIN, as well as for HPV structural proteins with IP-PAP technique. The local immunocompetent cell (ICC) infiltrates are analysed using ANAE technique to define B cells, MPS cells and T cells and monoclonal antibodies (McAb) for T cells subsets, NK (natural killer) cells and Langerhans cells. The relative levels of B- and T lymphocytes and MPS cells did not correlate with the clinical course, i.e. regression (RE), persistence (PE) or progression (PR) of the HPV lesions. The same was true with the expression of HPV antigens, intensity of the ICC infiltrate, as well as with the relative levels of NK (HNK-1+) cells and Langerhans (OKT-6+) cells. The T helper/T suppressor cell ratio was subject to minor fluctuations only as determined in three subsequent biopsies, and did not bear any meaningful relationship to the natural history of the HPV lesions. During the follow-up, 24.0% of the HPV lesions regressed, 54.9% remained persistent, and 21.1% progressed, 26 (6.2%) having been coned due to progression into CIS. The clinical course was most significantly influenced by the grade of HPV-associated CIN, to which RE was inversely and PR directly related. The results clearly confirm that cervical HPV infections are capable of progressing into CIS and thus show a natural history equivalent to that of classical CIN. Therefore, cervical HPV infections should be regarded as truly precancerous lesions, which should be examined, treated and followed-up with the same concern as the classical CIN.

Adult

The relation between the type of immunoreactive cells found in human papillomavirus (HPV) lesions of the uterine cervix and the subsequent behaviour of these lesions.

Human papillomavirus (HPV) lesions in the skin are rejected by immunological mechanisms, but very little is known about such mechanisms in HPV lesions of the uterine cervix. We studied the mononuclear cell infiltrates in cervical biopsies from 65 women with an HPV lesion (flat, inverted or papillomatous condyloma) who were followed for at least twelve months. We examined cryostat sections using the ANAE (acid alpha-naphthylacetate esterase) technique to demonstrate B cell, T cells, and mononuclear phagocytes (MPs), and monoclonal antibodies (OKT3, OKT4, OKT6, and OKT8) for the T cell subsets. The percentages of B-, T-, and MPs in HPV lesions with concomitant cervical intraepithelial neoplasia (CIN) were similar to those lesions without CIN. Similarly, no significant differences in cell type percentages were found in HPV lesions which regressed (n = 24), remained stationary (n = 24) or progressed (n = 3) during the follow-up period. The ratio OKT4+/OKT8+ (T helper/T suppressor, cytotoxic) cells was 1.44 and 0.81 in HPV lesions with CIN and those without CIN respectively (p less than 0.025). No statistically significant differences in that ratio were found between the lesions which remained stationary, regressed or progressed. The tendency to progress was directly related to the degree of CIN associated with HPV.

Antibodies, Monoclonal

Langerhans cells in human papillomavirus (HPV) lesions of the uterine cervix identified by the monoclonal antibody OKT-6.

The local inflammatory cell infiltrates in 263 cervical punch biopsies of the women followed-up since 1981 (16 +/- 14 months, mean +/- S.D.) for an established human papillomavirus (HPV) lesion with or without concomitant cervical intraepithelial neoplasia (CIN) were analysed for occurrence of Langerhans cells, defined by the monoclonal antibody OKT-6 using the avidin-biotin peroxidase complex (ABC) technique. OKT-6+ cells remained at the constant low level (1.5-1.9% of the inflammatory cells) in the different types of HPV lesions (flat, inverted or papillomatous condylomas), their percentages (range 0.8-2.1% of the cells) being slightly affected by the grade of HPV-associated CIN, however, (P less than 0.05 between HPV-CIN I and HPV-CIS). Although cervical HPV lesions characteristically are a disease of young females, the relative levels of in situ Langerhans cells did not show any age-dependence. Furthermore, the intensity of the inflammatory cell infiltrate did not correlate with the relative levels of OKT-6+ cells in the biopsies. Practically identical (1.6%) levels of OKT-6+ cells were found in the first biopsies of the HPV lesions shown to regress during the follow-up period (28.8% of cases), when compared with those (1.7%) in the lesions persisted (52.1% of cases) or progressed (19.1% of lesions). The results are discussed in terms of the proposed immune surveillance function against viral infections, attributed to Langerhans cells in the SALT/MALT concept.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent