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J Risteli

Publications and source records attributed to J Risteli.

At least 163 records · Page 9Linked to original sources
PubMed1993

p53 immunohistochemistry in transitional cell carcinoma and dysplasia of the urinary bladder correlates with disease progression.

Immunohistochemically detectable p53 protein using a polyclonal antibody (CM-1) was studied in 42 carcinomas of which 11 were grade I, 22 grade II and nine grade III carcinomas. Additionally 14 urothelial dysplasias were studied. In 11 of these a diagnosis of transitional cell carcinoma was established before and in one after the dysplasia diagnosis. Twenty-one out of 42 (50%) cases of transitional cell carcinoma were positive for the p53 protein. Eleven out of 14 (78%) dysplasias and 10/12 (83%) related carcinomas were p53 positive. One out of 11 grade I (9%), 12/22 grade II (55%) and 8/9 grade III (89%) tumours showed positivity for p53. There were significantly more p53 positive cases in grade II-III tumours than in grade I tumours (P = 0.004). There were significantly more p53 positive cases in stage T2-T4 tumours than in stage T1 tumours (P = 0.035). In only one case among the 11 dysplastic lesions following the treatment of a carcinoma the dysplastic lesion was p53 negative while the preceding carcinoma was p53 positive. All dysplasias and 28 carcinomas were also immunostained for laminin and type IV collagen to evaluate the continuity of basement membranes (BMs). Clearly disrupted BMs were observed only in grade III carcinomas. These cases showed the most p53 immunopositivity. The results show a strong association of p53 staining between dysplasias and transitional cell carcinomas of the urinary bladder indicating that these lesions might share similar p53 changes. The correlation to grade, clinical stage and to disrupted BM suggests that p53 mutations may be associated with the evolution of aggressive growth characteristics in transitional cell carcinomas or, alternatively, that p53 positive tumours of a more aggressive type from the start. Whether p53 staining can be used as an adjunct in the assessment and follow-up of epithelial changes of patients treated for a p53 positive bladder carcinoma deserves to be studied.

Carcinoma, Transitional Cell↗
PubMed1993

Collagen synthesis in intact skin is suppressed during wound healing.

OBJECTIVE: Simultaneous monitoring of total collagen synthesis as well as synthesis in intact skin and in the wound to verify the higher priority of wound healing after surgery. SUMMARY BACKGROUND DATA: Synthesis of acute phase proteins is stimulated by surgical trauma. At the same time, production of albumin is inhibited and there is a net catabolism of skeletal muscle proteins. Similarly, the authors have found a transient inhibition of total collagen synthesis after surgery. The authors hypothesized a lower priority in synthesis of structural and peripheral collagen for the benefit of wound healing. METHODS: The concentrations of the carboxyterminal propeptide of type I procollagen (PICP) and the aminoterminal propeptide of type III procollagen (PIIINP) were measured in suction blister fluid of intact skin and in wound fluid in ten surgical patients. PICP and PIIINP concentrations in serum were also measured. Specific radioimmunoassays were used. RESULTS: In peripheral skin, the median preoperative concentrations of PICP and PIIINP were 228 and 140 micrograms/L, respectively. On postoperative days 1, 2, 4 and 7, the median concentration of PICP was 145 (p = 0.01, Wilcoxon signed rank sum test), 102 (0.02), 159 (0.03), and 152 (0.06) micrograms/L, respectively. The postoperative medians of PIIINP were 68 (p = 0.17), 76 (0.04), 66 (0.06), and 56 (0.03) micrograms/L, respectively. At the same time, collagen synthesis in the wound increased dramatically from the second day on. After an initial decrease, propeptide concentrations in serum gradually increased from the fourth day on. CONCLUSIONS: Collagen synthesis is regulated for the benefit of the wound during the acute phase response.

Acute-Phase Reaction↗
PubMed1993

Lymphatic clearance of synovial fluid in conscious pigs: the aminoterminal propeptide of type III procollagen.

The aminoterminal propeptide of type III procollagen (PIIINP) in serum is employed as a direct marker of fibrillogenesis. The balance between local fibrillogenesis and serum PIIINP is governed by the transport and possible degradation en route from tissue to circulation. In conscious pigs, we investigated the transport of PIIINP from the knee cavity into the circulation after intra-articular injection of radiolabelled PIIINP followed by sequential sampling of thoracic duct lymph, serum and urine. Clearance from the joint space was evaluated by external detection of 131I-HSA, used as co-tracer. Lymph samples were gel filtrated to assess possible lymphatic degradation of the intact PIIINP. 125I-PIIINP and 131I-HSA were found in thoracic duct lymph within 20 min of the intra-articular injection. Both isotopes had a biphasic appearance, with the first peak after 60 min and a larger peak after 150 min. During the 6 h observational period 18% of the injected PIIINP was found in the lymph. Gel chromatography of lymph showed the fast formation of a small fraction with a lower MW than that of PIIINP, which suggests that some degradation of PIIINP may occur through the lymphatics. The half-life of the joint clearance of HSA by bulk flow was assessed to be 8.3 h. The clearance of PIIINP from the joint was estimated to be equal to that of HSA, which indicates that PIIINP leaves the joint space by bulk flow as has been proposed for HSA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Increased type I collagen degradation correlates with disease severity in rheumatoid arthritis.

OBJECTIVES: To assess the extent and clinical significance of type I collagen degradation in rheumatoid arthritis (RA). METHODS: Serum samples from 90 consecutive patients with RA from a cross-sectional population based study and 90 age- and sex-matched controls were analysed with the new assay of cross-linked carboxyterminal telopeptide of type I collagen (ICTP). RESULTS: Patients with RA had significantly higher concentrations of ICTP than the controls. ICTP correlated strongly with measures of impairment in RA, such as the erosive state of joint disease (ES) (r = 0.57, p < 0.001) and Keitel function test (KFT) (r = 0.49, p < 0.001), and more weakly with various disease activity markers. When erythrocyte sedimentation rate (ESR), ES or KFT were used as indicators of disease severity among the patients with disease duration over five years, ICTP distinguished the more serious RA from milder cases. CONCLUSIONS: Elevated serum concentrations of ICTP are common in RA and are associated with signs of aggressive disease.

Adult↗
PubMed1993

Serum osteocalcin and carboxyterminal propeptide of type I procollagen in rheumatoid arthritis.

OBJECTIVES: Previous reports indicate that serum osteocalcin (serum bone GLA protein (S-BGP)) and carboxyterminal propeptide of type I procollagen (PICP) can be used as indicators of bone formation and turnover. The purpose of this study was to assess the activity of bone formation in patients with rheumatoid arthritis (RA) using S-BGP and S-PICP. The biochemical data were compared with data obtained from bone histomorphometry. METHODS: Concentrations of S-BGP and S-PICP were measured in 119 women with RA aged 30-66 years and 47 healthy female controls matched for age. Bone histomorphometry of iliac crest samples was performed in 107 patients with RA. RESULTS: Weak to moderate correlations between the serum markers and histological bone formation parameters were found. Concentrations of S-BGP and S-PICP were significantly decreased in patients with RA compared with the controls (S-BGP 7.2 (2.3) v 8.7 (2.1) micrograms/l; S-PICP 105 (32) v 117 (38) micrograms/l. The lowest values were found in patients with recent onset RA. CONCLUSIONS: These findings suggest that bone formation and bone remodelling are generally reduced in patients with RA.

Adult↗
PubMed1993

Fate of circulating amino-terminal propeptide of type III procollagen in conscious pigs.

The amino-terminal propeptide of type III procollagen (PIIINP, M(r) 42,000) is a promising marker for the formation of type III collagen of granulation tissue in experimental and clinical studies. The disposal kinetics of circulating PIIINP is, however, almost unknown. In conscious pigs with a thoracic duct-venous shunt, 125I-labeled PIIINP was injected intravenously. The initial distribution volume was 2.2 liters, which was 1.7 times the plasma volume (P < 0.01). The disappearance curve was three-phased, with an initial steep decline (t1/2 58 min), followed by two slower phases (t1/2 239 min and 289 h). Consecutive gel filtrations showed that the initial slope of the plasma disappearance curve corresponded to the plasma clearance of the intact PIIINP. The initial plasma clearance was 26.5 ml plasma/min, whereas the urinary clearance was 8.7 ml plasma/min (P < 0.01). The other components of the plasma disappearance curve originated from the formation and disappearance of a high and a low molecular weight (MW) fraction as part of the degradation of PIIINP. The high MW fraction (approximately M(r) 90,000) was similar to a previously described, but not further characterized, PIIINP immunoreactive component. The existence of the low MW fraction (approximately M(r) 20,000) has not been reported before. The lymphatic recirculation of intact PIIINP was rapid, and the lymph-serum ratio was almost constant within 1 h of injection. We conclude that the t1/2 of circulating PIIINP is 58 min, that PIIINP escapes the circulation very quickly, and that the degradation of PIIINP includes at least two intermediary steps.

Animals↗
PubMed1993

Clinical characteristics and circulating collagen and laminin metabolites in insulin-dependent diabetic children with joint and skin manifestations.

One hundred seventy-four children and adolescents with insulin-dependent diabetes mellitus were examined for joint contractures and skin manifestations in their hands. Joint contractures were found in 52 (29.8%) and skin manifestations in 29 (16.6%) patients. To eliminate the possible confounding effects of age and duration of diabetes on the variables to be studied, patients younger than 7 y and with a duration of diabetes shorter than 3 y were excluded from the subsequent analyses. Of the remaining 108 children, those with joint contractures had lower serum concentrations of the 7-S domain of type IV collagen and the P1 fragment of laminin than the other patients (p = 0.033) but higher mean glycated Hb levels (p = 0.048). A clear association was noted between the occurrence of joint contractures and skin changes (p = 0.007). Background retinopathy was found in six patients (5.6%), three of whom had stage II joint contractures (p = 0.064). The children with skin changes and those with combined joint and skin manifestations more often had insulin-dependent diabetes mellitus in their first-degree relatives (p = 0.038 and p = 0.043, respectively). No difference in relative height was found between the groups. No association could be seen between disease susceptibility antigens in the HLA-D locus and joint or skin manifestations. The lower levels of circulating collagen and laminin metabolites in the diabetic children with joint contractures suggest that these patients are characterized by a reduced turnover of basement membranes in tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

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

Possible variation in bone resorption during the normal menstrual cycle.

In order to determine whether bone turnover varies during the normal menstrual cycle, we measured biochemical markers of bone resorption (serum pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (sICTP), fasting urinary hydroxyproline/creatinine, fasting urinary pyridinoline/creatinine and fasting urinary deoxypyridinoline/creatinine) and bone formation (plasma osteocalcin, serum carboxy-terminal propeptide of type I procollagen and serum alkaline phosphatase) in ten healthy premenopausal women every two or three days for a complete menstrual cycle. A cyclic pattern was detected in sICTP, with its nadir during the follicular phase and its peak during the luteal phase, and an overall variation of 17% during the menstrual cycle (p = 0.004). No cyclic changes were observed in the urinary parameters of bone resorption or in the biochemical markers of bone formation. We conclude that sICTP, a new biochemical marker of bone resorption, undergoes small variations during a normal menstrual cycle in premenopausal women, whereas the biochemical markers of bone formation remain constant.

Adult↗
PubMed1993

Treatment of psoriasis vulgaris with topical calcipotriol has no short-term effect on calcium or bone metabolism. A randomized, double-blind, placebo-controlled study.

The purpose of this double-blind, placebo-controlled study was to examine whether the vitamin D analogue calcipotriol, topically applied to psoriatic skin lesions, had any effect on calcium or bone metabolism. Thirty-four outpatients with psoriasis vulgaris were randomized to treatment with either calcipotriol ointment (50 micrograms/g) or vehicle ointment twice daily for 3 weeks. The patients were put on a calcium energy fixed diet and examined once weekly. The mean amount of calcipotriol ointment used was 40.3 g/week (range 8.2-95.4 g/week). The results of biochemical markers on calcium and bone metabolism showed no significant differences between the two groups. No correlation was found between the amount of ointment used and changes in parameters on calcium and bone metabolism during the 3-week treatment. It is concluded that calcipotriol ointment (50 micrograms/g), applied in doses of 8.2-95.4 g/week for 3 weeks to psoriatic skin lesions, has no effect on calcium or bone metabolism.

Administration, Cutaneous↗
PubMed1993

Effects of systemic isotretinoin on serum markers of collagen synthesis and degradation.

In the present investigation, collagen synthesis and degradation were studied by measuring the carboxyterminal propeptide of type I procollagen (PICP), the aminoterminal propeptide of type III procollagen (PIIINP) and a type I collagen-specific degradation peptide (ICTP) in the sera of 43 male patients, treated for acne with isotretinoin or with tetracycline. The values were compared with those observed in 24 acne patients without treatment and in healthy controls. The treatment with isotretinoin did not seem to affect these parameters in a cross-sectional setting, whereas tetracycline treatment was associated with slightly decreased levels of ICTP. Since there were marked variations in the PICP, PIIINP and ICTP levels between individual subjects, a follow-up study, including male and female patients, others than in the first part of the study, was conducted. Two other biochemical markers of bone metabolism, osteocalcin, reflecting osteoblastic activity, and tartrate-resistant acid phosphatase (TRAP), reflecting osteoclastic activity, were also analyzed. In females, all these parameters were lower than in males. In addition, the changes in females were more pronounced; in particular, PIIINP and TRAP were significantly increased in females during retinoid treatment (p < 0.05 and p < 0.01, respectively). Importantly, no increase was found in the synthesis of type I collagen during retinoid treatment, suggesting that the commonly used retinoid dosages do not stimulate the synthesis of type I collagen in vivo.

Acne Vulgaris↗
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

Biochemical markers of bone metabolism.

In this article we review the biochemical basis for markers of bone metabolism and comment on their bone specificity and representativeness for bone tissue. Major developments have recently taken place particularly with respect to markers of bone collagen metabolism; accordingly, they are in the focus of this review. We also attempt to relate the various collagenous and non-collagenous markers to each other and to the phases of the osteoblast phenotype.

Acid Phosphatase↗
PubMed1993

Concurrent p53 expression in bronchial dysplasias and squamous cell lung carcinomas.

We analyzed the p53 protein immunohistochemically in bronchial dysplasias or squamous cell carcinomas in situ and in squamous cell lung carcinomas occurring in the same patients. The polyclonal antibody used (CM-1) is directed against the wild-type p53 protein, but also recognizes the mutated p53 in formalin-fixed and paraffin-embedded sections. To study the integrity of basement membranes (BMs) and the possible invasion of the dysplastic epithelium, immunostainings for the BM proteins laminin and type IV collagen were used. Nine of the 17 dysplasias showed p53 protein expression (53%); it was significantly more often seen in severe dysplasias and carcinomas in situ than in mild or moderate dysplasias (P = 0.04). The p53 antigenicity was generally located in the basal part of the epithelium. The BMs beneath mildly dysplastic epithelia were continuous. In contrast, those under moderately or severely dysplastic epithelia showed occasional disruptions. p53 protein expression was also found in dysplastic epithelium above a continuous BM suggesting an ominous process before signs of invasion. Twelve of the 17 squamous cell carcinomas showed p53 protein expression (71%). There was a significant concurrent p53 expression in bronchial dysplasias and their related squamous cell carcinomas (P = 0.009), so that all nine cases of p53 positive bronchial dysplasia also showed p53 positivity in the associated squamous cell carcinomas. These findings indicate that p53 protein expression is possible in premalignant bronchial lesions, and suggests that the p53 expression could, at least in some cases, be an early event in the development of a squamous cell carcinoma of the lung.

Aged↗
PubMed1993

Radioimmunoassay for the pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen: a new serum marker of bone collagen degradation.

We developed a radioimmunoassay (RIA) for the carboxy-terminal telopeptides of type I collagen (ICTP), cross-linked with the helical domain of another type I collagen molecule, after isolation from human femoral bone. The cross-linked peptide was liberated by digesting insoluble, denatured bone collagen either with bacterial collagenase or with trypsin, and purified by two successive reversed-phase separations on HPLC, with monitoring of pyridinoline-specific fluorescence. The purity of the peptide was verified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and its origin in the type I collagen fibers was determined by amino-terminal amino acid sequencing. Polyclonal antibodies and a separation reagent containing second antibody and polyethylene glycol are used in the RIA. An immunologically identical, somewhat larger antigen is present in human serum; its concentration increases in multiple myeloma and in rheumatoid arthritis. The ICTP antigen seems to be cleared from the circulation by the kidneys, because glomerular filtration rates that are two-thirds of normal or less are associated with increased circulating ICTP concentrations. The CVs of the method are between 3% and 8% for a wide range of concentrations. The analysis of 40 serum samples can be completed in 4 h.

Adult↗
PubMed1992

Serum procollagen peptides and collagen type VI for the assessment of activity and degree of hepatic fibrosis in schistosomiasis and alcoholic liver disease.

Schistosomiasis, in contrast to alcoholic liver disease, leads to presinusoidal hepatic fibrosis, which determines the prognosis of the disease. Because conventional liver function tests and liver biopsy specimens provide little information about the dynamics of the fibrotic process, we measured the serum concentrations of procollagen type III N-propeptide and procollagen type I C-propeptide, believed to mainly reflect collagen synthesis, and procollagen type IV C-propeptide and collagen type VI, two presumptive markers of collagen degradation. Determinations were performed in 15 healthy control subjects, 69 patients with various stages of infection with Schistosoma mansoni/Schistosoma haematobium (28 with an early active infection and no organ involvement, 27 with hepatosplenic involvement and 14 with complications of portal hypertension) and 16 patients with alcoholic cirrhosis. In addition, liver biopsy specimens were obtained from 30 schistosomal patients (18 with hepatosplenic involvement and 12 with complications of portal hypertension for histopathological grading and collagen histochemistry. Procollagen type III N-propeptide was significantly elevated in the three patient groups with schistosomiasis when compared with controls (p less than 0.01). Also, patients with higher histological grading showed significantly higher procollagen type III N-propeptide values (p less than 0.05). In alcoholic patients, procollagen type III N-propeptide was even higher and increased parallel to the severity of the disease, determined by using a combined clinical and laboratory index. Procollagen type I C-propeptide was only elevated in early infection (p less than 0.05) and steadily decreased with disease progression.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Diurnal variation in serum markers of type I collagen synthesis and degradation in healthy premenopausal women.

There are several indications that the functions of human osteoblasts and osteoclasts have circadian rhythms with peak activities occurring at night. It is not known, however, whether the principal function of these cells, namely synthesis and degradation of the organic matrix of bone, of which about 90% is type I collagen, also has a circadian rhythm. This was therefore investigated for both the formation of type I collagen and the degradation of type I collagen in bone using two newly developed serum markers: the serum concentration of the carboxy-terminal propeptide of type I procollagen (PICP) as a marker of formation and the serum concentration of the carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen (ICTP) as a marker of degradation. PICP and ICTP were measured by RIA in samples taken every 3 h over a 24 h period in 12 healthy premenopausal women (age 32 +/- 5 years, mean +/- SD). Both PICP (p = 0.003) and ICTP (p = 0.00003) showed a significant circadian rhythm, with about 20% higher values at night than in the afternoon. We conclude that serum markers of both the formation of new type I collagen and the degradation of old type I collagen in bone exhibit a clear circadian rhythm, with increased activity of both osteoblasts and osteoclasts at night. The etiology of this circadian rhythm is still unknown.

Adult↗