Search PubMed⌕ Search

Biomedical subjects

A Kauppila

Publications and source records attributed to A Kauppila.

At least 55 records · Page 3Linked to original sources
PubMed1995

Insulin-like growth factor-binding protein-1: a biochemical marker of endometrial response to progestin during hormone replacement therapy.

OBJECTIVES: To compare immunohistochemical localization of insulin-like growth factor binding protein-1 (IGFBP-1) in endometrial stromal cells with endometrial morphology during three regimens of continuous combined hormone replacement therapy. METHODS: Endometrial samples for morphological examination and immunohistochemical staining with monoclonal antibody against IGFBP-1 were obtained from 30 menopausal women before treatment and after 12 and 24 months of continuous combined hormone replacement therapy. All women received percutaneous estradiolgel releasing 1.5 mg estradiol daily. Regarding progestins, patients were divided into three groups: one group (n = 15) had a 20 micrograms/24 h levonorgestrel-releasing intrauterine device (LNG-IUD); the women in the other two groups received micronised natural progesterone either 100 mg orally (n = 7) or 100-200 mg vaginally (n = 8) daily, 25 days per calendar month. RESULTS: Before treatment the endometrium of all women was atrophic or subatrophic and no IGFBP-1 could be detected in any of the samples which contained enough stromal cells for evaluation. After 12 and 24 months of treatment, epithelial atrophy with decidual transformation in stroma was detected in all specimens in the LNG-IUD group, and IGFBP-1 was localized in decidualized stromal cells in all samples. In the other two groups, no signs of progestin effect were detected by microscopic examination in any of the endometrial samples and IGFBP-1 staining was completely negative in all of them. CONCLUSION: A striking difference occurred in both morphological and biochemical response in the endometrium of women treated with LNG-IUD compared with those receiving oral or vaginal micronised progesterone during continuous combined HRT. Micronised progesterone at doses used in this study turned out to be ineffective to prevent the proliferative effect of estrogen. Immunohistochemical localization of IGFBP-1 in endometrial stromal cells strongly correlated with decidual reaction in all endometrial specimens exposed to LNG-IUD, suggesting that the immunostaining of IGFBP-1 can be used as a means of assessing the strength of progestin effect in the endometrium during HRT.

Administration, Cutaneous↗
PubMed1995

Intrafollicular insemination for the treatment of infertility.

The effectiveness of intrafollicular insemination (IFI) for the treatment of non-tubal infertility was investigated in a pilot study. A total of 50 infertility patients with normal tubal function verified by laparoscopy or hysterosalpingography were stimulated with clomiphene citrate/human menopausal gonadotrophin. Washed spermatozoa were injected into one to three pre-ovulatory follicles via vaginal puncture 12 or 30 h after human chorionic gonadotrophin administration. Natural progesterone was given for luteal support. The IFI procedure was technically very simple and convenient for the patient and no complications were recorded. One normal intra-uterine pregnancy resulted. The results indicate that by comparsion with other assisted reproductive technologies IFI is very inefficacious for treating non-tubal infertility. Our data suggest that the intrafollicular environment in the preovulatory period is not favourable for fertilization.

Adult↗
PubMed1995

Elevated serum ICTP concentrations reflect poor prognosis in patients with ovarian carcinoma.

The effect of ovarian carcinoma on the circulating concentration of the cross-linked carboxyterminal telopeptide of type I collagen (ICTP) was studied in 17 patients before and during treatment. ICTP is a complex peptide released from type I collagen, which is the main organic component of bone matrix but also induced in ovarian carcinoma tissue and the peritoneal cavity by the tumour. CA 125 and the aminoterminal propeptide of type III procollagen (PIIINP) were also measured. The preoperative CA 125, PIIINP and ICTP concentrations were pathological in 16 (94%), nine (53%) and seven (41%) patients, respectively. There was a positive correlation between the PIIINP and ICTP levels in serum. After surgery and one course of cytotoxic chemotherapy, the median CA 125 concentration decreased whereas those of PIIINP and ICTP increased. During monitoring of the treatment response, patients with regressive disease showed lower CA 125 concentrations than those with stable or progressive disease. For PIIINP and ICTP there was no clear difference between these response categories, but altogether, simultaneously increasing serum CA 125, PIIINP and ICTP concentrations were consistently associated with poor prognosis.

Adult↗
PubMed1995

Extracellular matrix interactions in early human embryos: implications for normal implantation events.

OBJECTIVE: To study the role of the extracellular matrix (ECM) proteins in supporting the development and implantation competence of human embryos. DESIGN: Expression of an implantation site adhesive glycoprotein, oncofetal fibronectin, and basement membrane collagen-degrading matrix metalloproteinase-2 and -9 were studied in cultured human embryos. The ability of exogenously added laminin and fibronectin to enhance hatching and matrix metalloproteinase-2 expression was quantitated also. PATIENTS: Fifty-four women with tubal factor infertility enrolled in the IVF program at the University Hospital of Oulu agreed to participate by providing 20 residual oocytes and 227 residual early embryos for this study. MAIN OUTCOME MEASURES: The presence of oncofetal fibronectin immunoreactive protein was assayed by immunocytochemical staining with two specific monoclonal antibodies, FDC-6 and X18A4. These antibodies bind to specific and distinct epitopes within tumor and trophoblast-derived oncofetal fibronectin. Changes in embryo matrix metalloproteinase-2 production were measured by zymography and confirmed by immunocytochemical staining. RESULTS: Intracellular oncofetal fibronectin was identified within blastomeres of early stage embryos. The immunoreactivity of oncofetal fibronectin in the zona pellucida was associated with fragmentation and dissolution of the zona. Exogenously added laminin or adult-type fibronectin significantly increased the hatching rate of the cultured embryos. Embryos cultured with added adult-type fibronectin or trophoblast-derived oncofetal fibronectin stimulated the matrix metalloproteinase-2 production (72-kd type IV collagenase) by 2.25 +/- 0.16-fold when compared with control embryos (mean +/- SD). CONCLUSIONS: Embryonic production of specific ECM proteins, such as oncofetal fibronectin, appears to be important for the morphological and biochemical development of human preimplantation embryos. Moreover, ECM proteins promote acquisition of the adhesive and degradative properties required by human embryos for successful implantation.

Adult↗
PubMed1995

Regulation of 72-kd type IV collagenase-matrix metalloproteinase-2 by estradiol and gonadotropin-releasing hormone agonist in human granulosa-lutein cells.

OBJECTIVE: To examine the hormonal regulation of 72-kd type IV collagenase-gelatinase-matrix metalloproteinase-2 in human granulosa-lutein cells. DESIGN: The effect of E2 and GnRH agonist (GnRH-a) on matrix metalloproteinase-2 amount was examined on a long-term granulosa-lutein cell cultures. PATIENTS: The preovulatory follicles from women participating in our IVF program were aspirated through the vaginal wall. Follicular fluids were centrifuged and the granulosa cells were separated and pooled for culturing. MAIN OUTCOME MEASURES: Matrix metalloproteinase-2 enzyme activity was assayed with type IV collagen degradation assay and zymography. The matrix metalloproteinase-2 immunoreactive protein was studied by using specific antibodies. RESULTS: Matrix metalloproteinase-2 was the predominant form of gelatinase in cultured granulosa-lutein cells. The enzyme activity as well as the immunoreactive protein increased in the culture medium of the granulosa-lutein cells in the presence of E2. The effect of E2 was abolished by GnRH-a. CONCLUSIONS: Estradiol regulates the matrix metalloproteinase-2 enzyme amount in granulosa-lutein cells; the effect may be antagonized by GnRH-a.

Cells, Cultured↗
PubMed1994

Maturation of vaginal and endometrial epithelium in postmenopausal breast cancer patients receiving long-term tamoxifen.

To assess the estrogenic effects of tamoxifen on vaginal and endometrial epithelium and to investigate whether these changes are associated with any pathological findings in the endometrium, 53 postmenopausal breast cancer patients receiving long-term tamoxifen and 52 control breast cancer patients without any hormonal treatment were examined. Pathological findings in the endometrium were evaluated by hysteroscopy and curettage. The main outcome measures were the maturation index in Papanicolaou (Pap) smears, estrogen-like epithelial changes in the endometrium, serum concentrations of gonadotropins, sex hormone-binding globulin (SHBG), estradiol (E2), and testosterone (T). Informative Pap smears showed estrogenic effects in 89% (41/46) of the tamoxifen group and in 49% (22/45) of the control group, and in endometrial aspiration samples in 71% (32/45) and in 41% (19/46), respectively. These changes were associated with increased concentrations of serum E2 in the control group but not in the tamoxifen group. All five patients (11%) with endometrial polyps in the control group showed estrogenic endometrial changes, whereas among 14 women with polyps in the tamoxifen group, 9 showed estrogenic changes and 5 endometrial atrophy. Endometrial adenocarcinoma was found in 3 patients in the tamoxifen group and in 2 in the control group. Pap smears showed atrophy in 2 patients in the former and in one in the latter group. These findings confirmed estrogen-like effects of tamoxifen on the vaginal and endometrial epithelium in postmenopausal breast cancer patients, but these were not closely associated with benign or malignant endometrial lesions.

Adenocarcinoma↗
PubMed1994

Differential processing of type I and type III procollagens in the tumour cysts and peritoneal ascitic fluid of patients with benign and malignant ovarian tumours.

Progressive ovarian carcinoma induces the synthesis of type I and type III procollagens both in the tumour tissue and in the peritoneal cavity. We studied the processing of these proteins by determining the different antigen forms related to their propeptide parts by gel filtration and subsequent immunological assays. Samples of ovarian cyst fluid and peritoneal ascitic fluid were obtained from patients with benign and malignant ovarian tumours. In both benign and malignant ovarian cysts, the predominant procollagen antigens were the free propeptides, with few or no larger components, indicating efficient processing of types I and III procollagens in the tumour tissue. In ascitic fluid the processing was more variable. The aminoterminus of type III procollagen was partially unprocessed in all samples studied, whereas that of type I procollagen was nearly always completely processed. There was a clear difference between malignant and benign tumours in the processing of the carboxyterminus of type I procollagen: a significant part of the carboxyterminal propeptide antigen was invariably associated with a collagenous domain in malignant tumours, whereas in benign tumours the free propeptide predominanted. The results indicate that interstitial procollagens are effectively processed in the tumour tissue during the fibroproliferative reaction typical of malignant ovarian tumours, whereas the processing of the procollagens released into peritoneal ascitic fluid is incomplete.

Ascitic Fluid↗
PubMed1994

Natural interpregnancy intervals of fertile couples: a longitudinal survey of grand grand multiparous women.

OBJECTIVE: To characterize the natural fecundity of grand grand multiparous women (> or = 10 deliveries) in relation to age, number of pregnancies, body mass index, and chronic diseases. DESIGN: A retrospective longitudinal analysis of interpregnancy intervals of married couples who had never used any kind of contraception. PATIENTS, PARTICIPANTS: The interpregnancy intervals (months from delivery or spontaneous abortion to the next conception) of 96 grand grand multiparous women with a total of 1,327 pregnancies were evaluated from the first to the latest pregnancy (14 +/- 1.7; mean +/- SD). Because of the lack of reliable data on conception times, 109 pregnancies had to be excluded. The number of interpregnancy intervals remaining for evaluation was thus 1,218. RESULTS: The mean interpregnancy intervals in the material of 1,218 pregnancies was 8.5 +/- 4.9 months, being significantly shorter after an abortion (5.3 +/- 4.8 months) or stillbirth (6.0 +/- 4.7 months) than after a delivery (8.9 +/- 5.6 months). The interpregnancy interval was significantly longer in women over 30 years of age than in the younger women, approximately 7 months in the latter and exceeding 10 months around the age of 40 years. Body mass index and chronic medical illness did not influence the interpregnancy intervals. The incidence of spontaneous abortions increased after the age of 30 years. It was 6% until 30 years, 10% between 31 and 35 years, and 25% after 40 years. CONCLUSIONS: In this retrospective longitudinal review, the reproductive capacity of fertile couples remains rather sound until premenopausal age. The data suggest that a woman's delivery capacity could be 25 births between 16 and 45 years of age.

Abortion, Induced↗
PubMed1993

Progressive ovarian carcinoma induces synthesis of type I and type III procollagens in the tumor tissue and peritoneal cavity.

Increased serum concentrations of aminoterminal propeptide of type III procollagen occur in advanced ovarian cancer. To study their origin, we compared the expressions of type I and type III procollagens in ovarian tumor tissue and the peritoneal cavity with immunoassays for the propeptide domains of these procollagens. Samples of tumor cyst fluid, peritoneal ascitic fluid, tumor vein blood, and peripheral blood were obtained at operation from 50 women with malignant ovarian neoplasms and 61 women with benign neoplasms. The ascitic fluid concentrations of both type I and type III procollagen antigens were significantly higher in the malignant tumors than in the benign ones, but this difference was evident only for type I procollagen in the tumor cysts. The aminoterminal propeptide of type III procollagen concentration in the peripheral blood was higher in the patients with malignant tumors, whereas the concentrations were similar in the tumor veins. The enhanced type I procollagen synthesis in the malignant tumors did not affect the corresponding antigen in the blood. The findings suggest that progressive ovarian carcinoma invariably induces a fibroproliferative response, characterized by active expression of type I and type III procollagens. The increased circulating aminoterminal propeptide of type III procollagen is derived from the peritoneal cavity rather than from the tumor tissue via the ovarian vein.

Adult↗
PubMed1993

Organization of type III collagen in benign and malignant ovarian tumors. An immunohistochemical study.

BACKGROUND: Abnormal interaction with the extracellular matrix is a basic property of malignant cells. Type III collagen is a major constituent of the extracellular matrix of soft tissues. METHODS: Deposition of the aminoterminal propeptide of type III procollagen (PIIINP) was studied in benign (n = 41), borderline (n = 4), and malignant (n = 32) human ovarian tumors using the avidin-biotin-immunoperoxidase technique and affinity-purified antibodies to human PIIINP: It was then compared with the serum PIIINP concentrations of the patients at the time of operation. RESULTS: In malignant tumors, the distribution of PIIINP was irregular both close to the epithelial cancer cells and further away, in the stroma. Another feature typical of malignant tumors was the varying staining intensity of the PIIINP-positive fibers. The benign tumors were characterized by a regular organization and an intensive staining of PIIINP: Borderline tumors showed a slightly decreased staining intensity and altered PIIINP distribution. A significant positive correlation was found between the PIIINP concentration in serum and the degree of irregularity in the distribution of PIIINP: CONCLUSIONS: These preliminary results indicate that malignant transformation in ovarian tumors is associated with disintegration of adjacent collagenous structures and with alterations in type III procollagen metabolism, which also leads to increased serum PIIINP levels. They suggest that biochemical or immunohistochemical detection of the PIIINP antigen could be clinically useful in ovarian tumors.

Adult↗
PubMed1993

Detection and typing of human papillomavirus infection affecting the cervix, vagina and vulva. Comparison of DNA hybridization with cytological, colposcopic and histological examinations.

The sensitivity of human papillomavirus (HPV) detection was compared by colposcopy, histology and DNA hybridization among 304 women with abnormal Papanicolaou (Pap) smear. Colposcopically directed biopsies revealed HPV infection in 71% of cases, DNA hybridization in 35%, and both together in 78%. DNA hybridization detected HPV in 24% of the 84 benign cases with no histological signs of HPV, in 32% of the 133 condylomas verified by biopsies and in 51% of the 85 cases with intraepithelial neoplasia, 95% of which presented histological signs of HPV. The pattern of occurrence of different HPV-types resembled findings in earlier reports. HPV infection is common with abnormal Pap smears and it can be identified relatively reliably by means of cytology, colposcopy and histology. DNA hybridization serves as a complementary technique which may reveal the oncological potential of the virus.

Adolescent↗
PubMed1993

Markers of type I and type III collagen synthesis in serum as indicators of tissue growth during pregnancy.

The concentrations of the carboxy-terminal propeptide of type I procollagen (PICP) and the amino-terminal propeptide of type III procollagen (PIIINP) in serum were followed prospectively as indicators of synthesis of the respective collagens in 266 healthy primiparas during the second and third trimesters of pregnancy. The PIIINP concentration increased 2-fold during the third trimester; the median value was 10.0 micrograms/L at gestational week 40, with a range from 4.6-32.7 micrograms/L (reference interval for nonpregnant women, 1.7-4.2 micrograms/L). A significant increase also took place in the PICP concentration. The frequency distributions of the two parameters were near normal at week 26. They started to broaden out at week 32 and were wide at week 38. In severe preeclampsia, PIIINP tended to increase more than in normal pregnancies of the same duration. The increase in PIIINP correlated significantly with maternal weight gain and the birth weight of the infant, but not with other parameters related to pregnancy or delivery. At gestational week 38, there was a significant correlation between the circulating concentrations of insulin-like growth factor-I and PIIINP or PICP, but not between human placental lactogen and PICP, and only a weak association between human placental lactogen and PIIINP. This suggests that insulin-like growth factor-I is involved in the regulation of type I and type III collagen synthesis during pregnancy.

Adolescent↗
PubMed1993

Changing concepts of medical treatment of endometriosis.

Studies on the natural history of endometriosis have demonstrated that the majority of endometriosis implants tend to progress, a finding that indicates eradication of the lesions by medical and/or surgical approaches. Infertility and dysmenorrhea are other indications for medical therapy in this disease. In recent prospective and controlled studies, progestin (at high doses), gestrinone and GnRH agonist analogues have been equally effective as regards elimination of endometriosis and relief of endometriosis-associated symptoms, compared to danazol, a standard treatment in endometriosis. These four classes of drugs differ, however, in their adverse effects and as regards compliance. Danazol is a steroid with androgenic and anabolic effects and it adversely affects lipid metabolism. Gestrinone and 17-OH progestins are weaker, and GnRH agonist analogues and some progestins neutral in these respects. GnRH agonist analogues induce a hypo-estrogenic state with associated climacteric symptoms and mineral loss from the bones. The clinical value of combinations of GnRH analogue and steroid(s), used to prevent these side-effects, is so far unclear. Laparoscopic microsurgery has revolutionized the treatment of endometriosis lesions. Hence, hormone treatment as a supplement to microsurgical approaches may become a dominant form of medical therapy in endometriosis. The definitive value of pre- or post-operative hormonal treatment in this disease should, however, be tested in controlled trials. Such studies have proved antiprostaglandins to be useful in the treatment of dysmenorrhea secondary to endometriosis. Because each of the four drugs was ineffective in the treatment of infertility associated with endometriosis it is a waste of time to expose patients desiring pregnancy to long-term hormonal therapy. Ovarian hyperstimulation with IVF and other methods of assisted fertilisation are promising alternatives, but their definitive value is so far unproven in this disease. Conclusively, the significance of medical therapy in endometriosis is only partly resolved, and therefore, many therapeutic problems await prospective randomised trials and new innovations.

Combined Modality Therapy↗
PubMed1993

Effect of gynecological operations on the serum concentration of the aminoterminal propeptide of type III procollagen.

Serum concentration of PIIINP (aminoterminal propeptide of type III procollagen), an indicator of connective tissue metabolism, is often increased in advanced gynecological carcinoma and correlates with the tumor growth. Because the healing wound also affects collagen metabolism we measured the serum PIIINP concentration in 15 patients operated on for endometrial carcinoma and in 28 patients operated on for benign gynecological diseases. Serial serum samples were collected for 35-51 days after surgery. In endometrial carcinoma, serum PIIINP level was increased in 53% of the patients before the operation. Postoperatively, the mean PIIINP concentration increased further, remaining at a pathological level throughout the study and with a peak at one week after the operation. In relative terms an abdominal operation for benign disease increased the serum PIIINP concentration as much as in endometrial carcinoma, but the mean level remained within the reference interval. After vaginal operation the increase in PIIINP concentration was not significant. The initially increased PIIINP concentration in endometrial carcinoma is probably caused by the effects of the malignancy on collagen metabolism. Because the relative response of PIIINP to abdominal operation was similar in both groups, the PIIINP response to surgical trauma in patients with malignant disease seems to depend only on the extent of the operation. In this group the transient increase in serum PIIINP concentration does not prevent the use of PIIINP as a tumor marker, since the follow-up examinations for malignancy do not start earlier than two months after operation.

Adenocarcinoma↗
PubMed1993

Expression of 72 kilodalton type IV collagenase (gelatinase A) in benign and malignant ovarian tumors.

BACKGROUND: 72 Kilodalton (kd) type IV collagenase is a matrix metalloproteinase that specifically cleaves type IV collagen molecules. The enzyme has been postulated to have an important role in the invasion and spread of malignant tumors. EXPERIMENTAL DESIGN: In situ hybridization was used to study the expression of the 72 kd type IV collagenase mRNA in 24 benign, 2 semimalignant, and 15 malignant ovarian tumors and in 5 metastases of ovarian serous adenocarcinomas. The results were correlated with the expression of the mRNA for the alpha 1(IV) chain of type IV collagen and with the corresponding immunohistochemical distribution of the enzyme. RESULTS: The results showed that the more malignant an ovarian tumor was, the more clearly mRNA expressions for both 72 kd type IV collagenase and the alpha 1(IV) chain could be detected in tumor cells. The expression of both types of mRNAs was localized within the cells of tumor stroma and occurred mainly in fibroblasts and vascular endothelial cells. Epithelial tumor cells only rarely expressed these mRNAs. Immunohistochemical stainings localized the 72 kd collagenase as well to the stromal cells as to the epithelial cells of both benign and malignant tumors. CONCLUSIONS: The findings indicate that genes for the 72 kd type IV collagenase and for its substrate are simultaneously active in the same cells of the tumor stroma. The difference in the in situ hybridization and immunohistochemical findings could be explained by a possible variation in the metabolic balance between synthesis and accumulation of the protein in different cell types. It can also be proposed that the activity of the 72 kd type IV collagenase would be mediated through a receptor-like mechanism present on epithelial cells which could bind the 72 kd type IV collagenase synthesized elsewhere. There is also a possibility that the gelatinolytic activity of the mesenchymally synthesized 72 kd type IV collagenase would be consumed to degrade extracellular matrix proteins other than basement membranes.

Adenocarcinoma↗