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Biomedical subjects

A M Suikkari

Publications and source records attributed to A M Suikkari.

46 records · Page 3Linked to original sources

Insulin regulates the serum levels of low molecular weight insulin-like growth factor-binding protein.

The serum levels of 34K insulin-like growth factor (IGF)-binding protein were measured by RIA in 88 type 1 diabetic patients, 9 patients with type 2 diabetes, 7 patients with insulinoma, 19 normal subjects (all after an overnight fast), and 82 normal subjects after a breakfast meal. In addition, the effect of 2- to 3-h euglycemic steady state hyperinsulinemia on serum IGF-binding protein and IGF-1 levels was studied in some subjects in each of the fasted groups. Compared with normal subjects, the mean serum IGF-binding protein levels were 4-fold (P less than 0.001) higher in type I diabetic patients treated with conventional insulin injections, 2.5-fold (P less than 0.001) higher in those treated with continuous sc insulin infusion, and 2-fold (P less than 0.05) higher in patients with type 2 diabetes. In the patients with insulinoma, the mean IGF-binding protein level was 63% below normal (P less than 0.001), and it normalized after removal of the tumor. There was a slight negative correlation between the IGF-binding protein level and insulin dose in the diabetic patients (r = -0.22; P less than 0.05). In normal subjects, serum insulin concentrations were 2-fold higher (P less than 0.001) and the IGF-binding protein level was 29% lower after a meal (P less than 0.05) than in the fasting state. Serum IGF-I concentrations were virtually identical in the type 1 and 2 diabetic patients, insulinoma patients, and normal subjects. During steady state euglycemic hyperinsulinemia, the IGF-binding protein level fell by 40-70% in each group (P less than 0.001), whereas the IGF-I level declined (P less than 0.05) in the type 2 diabetic patients only. The decline of binding protein was closely related to the baseline level (r = 0.94; P less than 0.001). No correlation was found between serum IGF-I and binding protein levels in any group. In conclusion, 1) serum 34K IGF-binding protein levels are elevated in type 1 and 2 diabetic patients and decreased in patients with insulinoma; 2) the serum binding protein, but not IGF-I concentration is decreased by acute hyperinsulinemia; and 3) these data suggest that the serum insulin concentration plays a role in regulation of the serum 34K IGF-binding protein concentration.

Adult↗

Different insulin-like growth factor binding species in human placenta and decidua.

Previous studies demonstrated that human decidua secretes a 34K insulin-like growth factor binding protein (34K IGF-BP) earlier designated placental protein 12, whereas placenta contains IGF receptors and IGF mRNA. We studied binding of [125I]IGF-I to paired placental and decidual tissues using competitive binding, gel filtration, RIA, and cross-linking techniques, and compared the binding characteristics of these two tissues which are located in close proximity in vivo. The effect of decidual cytosols on [125I]IGF-I binding to placental membranes also was studied. Consistent with previous data the dominating binding species in placental membranes were IGF receptors. In contrast, the binding of [125I]IGF-I to decidual membranes was mainly due to binding species with mol wts of 34K and 39K. The 34K IGF-BP was more readily detected in decidual cytosols than in decidual membranes and little was detected in placental cytosols. Purified 34K IGF-BP as well as decidual cytosols inhibited [125I]IGF-I binding to placental receptors. The inhibitory effect of decidual cytosol on IGF receptor binding was linearly correlated to the decidual content of 34K IGF-BP. The results suggest that the decidual 34K IGF-BP might act as a local modulator of the IGF action at the interface between the decidua and the placenta.

Autoradiography↗

Immunofluorometric demonstration and quantification of placental protein 5 in the absence of pregnancy.

This time-resolved immunofluorometric assay (IFMA) developed for measurement of placental protein 5 (PP5) involves two antibodies: a monoclonal anti-PP5 antibody attached to a solid phase and an europium(III) chelate-labeled polyclonal anti-PP5 antibody as a tracer. The measuring range is 0.05-100 micrograms/L and the detection limit is 20 times lower than that of a PP5 radioimmunoassay (RIA) performed with the same polyclonal antiserum. By IFMA, PP5 could be detected and quantified in all plasma and serum samples of nonpregnant and pregnant individuals, whereas PP5 was undetectable by RIA in serum of healthy men and nonpregnant women. The mean concentration of PP5 in sera from men was 0.43 micrograms/L (SD 0.13, range 0.19-0.75, n = 47) and in sera from nonpregnant women 0.49 micrograms/L (SD 0.19, range 0.20-0.90, n = 41). PP5 concentrations in serum showed no systematic variation during the menstrual cycle. In serum samples from 60 pregnant women the results obtained by IFMA and RIA correlated well (r = 0.97).

Female↗

Progesterone-associated proteins PP12 and PP14 in the human endometrium.

Two proteins, designated as PP12 and PP14 were originally isolated from soluble extracts of the human placenta and its adjacent membranes. We have shown that they are synthesized by decidualized/secretory endometrium and not by placenta. Both proteins occur at high concentrations in human amniotic fluid, which is therefore an excellent source for purification. PP12 is a 34-kDa glycoprotein, which has an N-terminal amino acid sequence of Ala-Pro-Trp-Gln-Cys-Ala-Pro-Cys-Ser-Ala. This is identical with that of somatomedin-binding protein purified from the amniotic fluid. PP12 too binds somatomedin-C, or IGF-I (insulin-like growth factor-I). Human secretory endometrium synthesizes and secretes PP12, and progesterone stimulates its secretion. PP14 is a 28-kDa glycoprotein. Its N-terminal sequence shows homology to that of beta-lactoglobulins from various species. We have found PP14 in the human endometrium, serum and milk. Immunologically, PP14 is related to progestagen-associated endometrial protein (PEP), alpha-2 pregnancy-associated endometrial protein (alpha-2, PEG), endometrial protein 15 (EP15), alpha-uterine protein (AUP) and chorionic alpha-2 microglobulin (CAG-2). In ovulatory menstrual cycles, the concentration of PP14 increases in endometrial tissue as the secretory changes advance. In serum, the PP14 concentration begins to rise later than the progesterone levels, and high serum PP14 levels are maintained for the first days of the next cycle. By contrast, no elevation of serum PP14 level is seen in anovulatory cycles. Our results show that progesterone-associated proteins are synthesized by the human endometrium and appear in the peripheral circulation, where they can be quantitatively measured using immunochemical techniques.

Amniotic Fluid↗

The effect of hysterectomy on serum CA 125 levels in patients with adenomyosis and uterine fibroids.

The human endometrium has been reported to release CA 125 in tissue culture, and elevated levels have been found in patients with endometriosis and adenomyosis. The serum levels of CA 125 were measured in 22 women undergoing hysterectomy for adenomyosis (n = 11) or fibroids (n = 11) of the uterus. In 20 patients (91%) the pre-operative CA 125 level was normal (less than 35 U/ml). All patients with adenomyosis had a normal pre-operative serum CA 125 concentration. Five weeks after the operation the CA 125 levels did not differ from the pre-operative levels. Our results show that the uterine contribution to the serum CA 125 level is minimal, and do not confirm the initial enthusiasm concerning the possible use of levels as an aid in the diagnosis of adenomyosis.

Antigens, Neoplasm↗

Circulating levels of immunoreactive insulin-like growth factor-binding protein in non-pregnant women.

Recent studies have shown that the human endometrium is capable of synthesizing a 34 kd insulin-like growth factor-binding protein (IGF-bp). Serum levels of immunoreactive IGF-bp were measured in non-pregnant women in order to find out whether the uterus contributes to the circulating level of 34 kd IGF-bp and whether these values would reflect the endometrial function. Serum samples were collected from 21 women of presumably fertile age before and after hysterectomy, from eight apparently healthy women at various phases of the menstrual cycle, and from 23 post-menopausal women. The serum concentrations of IGF-bp were estimated by radioimmunoassay (RIA), which measured both the unsaturated and the IGF-bound 34 kd IGF-bp. After hysterectomy, a significant decrease in serum IGF-bp levels was observed in samples taken one week post-operatively suggesting a uterine contribution to the circulating IGF-bp concentration. Five weeks after hysterectomy the serum IGF-bp level had returned to the pre-operative level indicating that other tissues can compensate for uterine IGF-bp. In healthy women of fertile age the serum IGF-bp level (94 samples from eight subjects) was 39 +/- 1.8 ng/ml (mean +/- SE) and, in post-menopausal women (23 subjects), it was 36 +/- 6.0 ng/ml. During the menstrual cycle, the average day-to-day variation of serum IGF-bp concentrations was 31%. No correlation was found between the levels of serum IGF-bp and oestradiol, progesterone, LH or FSH. These results indicate that, while the uterus is probably one of the sources of circulating 34 kd IGF-bp, other tissues must also contribute.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Prophylaxis and treatment of anaerobic infections following caesarean section with tinidazole.

The purpose of this prospective, double-blind, placebo-controlled study was to clarify the effect of a single intravenous infusion of 500 mg of tinidazole on infections that followed a caesarean section. 80 consecutive caesarean-section patients and thereafter 72 women undergoing non-elective caesarean section were randomly assigned to two groups, each receiving intravenous infusions at cord clamping. In the entire sample the incidence of endometritis/wound infection in the placebo group was 27.3% (21/77) versus 10.7% (8/75) in the tinidazole group (p less than 0.01). In the non-elective caesarean-section group the incidence of endometritis/wound infection was 39.6% (21/53) in the placebo group versus 14.3% (7/49) in the tinidazole group (p less than 0.01). 27 positive bacterial cultures yielded a pure anaerobic growth in 59% (16/27) of cases, of which 87.5% (14/16) were treated successfully with oral tinidazole.

Adult↗

Concentrations of metronidazole and tinidazole in female reproductive organs after a single intravenous infusion and after repeated oral administration.

Concentrations of metronidazole and tinidazole in serum and gynecological organs were analyzed after a single 500 mg intravenous infusion and after three days of treatment with 400 mg t.i.d. of metronidazole or 500 mg b.i.d. of tinidazole. The studies were performed in 67 patients subjected to hysterectomy and/or oophorectomy because of myomatosis uteri, carcinoma uteri or endometriosis. At the time of organ removal (about 30 min after infusion), metronidazole and tinidazole levels in serum were 14.5 +/- 0.45 mg/l and 12.3 +/- 0.38 mg/l, respectively. Concentrations of both drugs in the uterus and Fallopian tube were about the same as the simultaneous serum levels and concentrations in the ovaries about 55% thereof. At steady-state, the concentrations of tinidazole in serum (23.5 +/- 1.0 mg/l) were remarkably higher than those of metronidazole (13.5 +/- 0.84 mg/l) about three hours after the last oral dose. Drug concentrations in organs of the female reproductive tract were 70 to 100% those of the simultaneous serum levels.

Administration, Oral↗