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Biomedical subjects

F Peters

Publications and source records attributed to F Peters.

At least 19 recordsLinked to original sources
PubMed1992

A site-directed mutagenesis study to identify amino acid residues involved in the catalytic function of the restriction endonuclease EcoRV.

We have used site-directed mutagenesis of the EcoRV restriction endonuclease to change amino acid side chains that have been shown crystallographically to be in close proximity to the scissile phosphodiester bond of the DNA substrate. DNA cleavage assays of the resulting mutant proteins indicate that the largest effects on nucleolytic activity result from substitution of Asp74, Asp90, and Lys92. We suggest on the basis of structural information, mutagenesis data, and analogies with other nucleases that Asp74 and Asp90 might be involved in Mg2+ binding and/or catalysis and that Lys92 probably stabilizes the pentacovalent phosphorus in the transition state. These amino acids are part of a sequence motif, Pro-Asp...Asp/Glu-X-Lys, which is also present in EcoRI. In both enzymes, it is located in a structurally similar context near the scissile phosphodiester bond. A preliminary mutational analysis with EcoRI indicates that this sequence motif is of similar functional importance for EcoRI and EcoRV. On the basis of these results, a proposal is made for the mechanism of DNA cleavage by EcoRV and EcoRI.

Amino Acid Sequence↗
PubMed1992

Multicentre study of gestrinone in cyclical breast pain.

Although the aetiology of cyclical mastalgia is poorly understood, the consistent finding of an increased prolactin stimulation response probably due to oestrogen dominance has led to the use of treatment with prolactin-lowering drugs and antioestrogens. The efficacy and safety in cyclical mastalgia of gestrinone, which has androgenic, anti-oestrogenic, and antiprogestagenic properties, were investigated in a multicentre study. In a double-blind randomisation procedure, 72 patients were allocated placebo and 73 treatment with gestrinone (2.5 mg twice a week) for 3 months. The patients recorded the severity of breast pain on a visual analogue scale before and during treatment and scored other breast symptoms as not present (0), mild (1), moderate (2), or severe (3). The gestrinone group had significantly greater reductions than the placebo group in breast pain score at months 1, 2, and 3 of treatment (mean reduction 59.5 [SD 22.6] to 11.7 [17.0] vs 58.2 [17.6] to 36.7 [23.0] at month 3; p less than 0.0001). All six breast symptoms had lower scores in the gestrinone than in the placebo group by the end of treatment. In a subset of 30 participants (15 from each group), serum concentrations of oestradiol, progesterone, and tri-iodothyronine were significantly lower than baseline after 3 months of gestrinone, but concentrations of luteinising hormone, follicle-stimulating hormone, prolactin, thyroid-stimulating hormone, and thyroxine did not change. 41% of gestrinone-treated and 14% of placebo-treated patients reported at least one side-effect; most of these were androgen-mediated. 11 placebo-treated patients and 4 on gestrinone discontinued treatment. Thus, gestrinone was very effective in the treatment of cyclical mastalgia and was well tolerated.

Adolescent↗
PubMed1992

[Hand disinfection as the central factor in prevention of puerperal mastitis. Clinical study and results of a survey].

The incidence of puerperal mastitis was evaluated in the course of two 12-month periods with and without additional hand disinfection at the bedside. Disinfection was available throughout both periods for all patients, mounted at the door of each room. Without additional disinfection at the bedside, 32 patients developed mastitis. With reference to the birth rate of 1095 during this period, the incidence of mastitis was 2.9%. When additional bedside disinfection was available, mastitis dropped to 8 cases per 12 months (1212 births = 0.66%) (p less than 0.001). A telephone survey, at 55 obstetrical units revealed that 41.8% of maternity clinics do not provide hand disinfectants at the bedside. These results indicate to the breast-feeding mother, that in the pathogenesis of puerperal mastitis, the essential recommendation emphasises, that puerperal women practise strict hygiene in maternity.

Breast Feeding↗
PubMed1991

[Drainage of large breast abscesses with reference to esthetic and functional aspects].

In 11 puerperal women, a breast abscess was treated by drainage from the inframammary fold. Eight patients wished to continue breast feeding. During the healing period, the babies were not breast fed on the operated side. In 3 patients, the skin over the abscess necrotised, resulting in a defect of 1 to 2 cm. In 2 patients, a small seroma had to be punctured after removing the drainage tube. Aesthetic results were judged by the patients as good. Resumation of suckling on the operated side revealed only 15 to 20% milk yield compared to that of the other breast. This treatment meets aesthetic and function-preserving criteria.

Abscess↗
PubMed1991

Thyrotrophin-releasing hormone--a lactation-promoting agent?

OBJECTIVE: To study the lactational and hormonal responses to nasal administration of thyrotrophin-releasing hormone (TRH) in puerperal women with inadequate lactation. DESIGN: Prospective randomized double-blind placebo-controlled study. SUBJECTS: 19 puerperal women with inadequate lactation (less than 50% of normal milk yield) on the 5th day postpartum. INTERVENTIONS: 10 women were allocated to receive TRH administered by a nasal spray of 1 mg, four times daily, between suckling episodes, for 10 consecutive days starting on day 6 postpartum. Nine women were allocated to receive placebo sprays. MAIN OUTCOME MEASURES: Daily milk yield, serum levels of prolactin and thyroid hormones. RESULTS: Before treatment all the women had significant prolactin responses to TRH and suckling stimuli. At the end of 10 days of treatment, milk yield increased significantly in the TRH group from a mean of 142.0 (SD 33.9) to 253.0 (SD 105.3) g/day (P = 0.014). There was no significant change in the placebo group. Basal prolactin levels increased from a mean of 117.4 micrograms/l (SD 45.2) to 173.3 micrograms/l (SD 55.5) (P less than 0.001) in the TRH group whereas in the placebo group prolactin levels decreased from 137.2 (SD 69.5) to 82.0 (SD 37.7) micrograms/l. A further rise in prolactin levels and milk yield was seen in seven women in the TRH group who received a second 10-day course of TRH treatment at their own request. There was no significant change in levels of thyroid stimulating hormone, thyroxine and triiodothyronine during treatment in either of the two treatment groups and no signs of hyperthyroidism. CONCLUSION: Repeated nasal TRH administration between suckling episodes may improve defective lactation.

Administration, Intranasal↗
PubMed1990

The influence of the concentrations of elongation factors and tRNAs on the dynamics and accuracy of protein biosynthesis.

Computer simulations of the elongation cycle of bacterial protein biosynthesis demonstrate that the accuracy of protein biosynthesis cannot be explained by a mechanism which involves only an initial selection and a proofreading reaction. It is suggested that only a combination of initial selection, proofreading and a retardation of non-cognate flows at the level of the EF-Tu-catalyzed GTPase reaction and the peptidyl transfer can guarantee sufficient accuracy at reasonable costs. According to this view the ribosome functions as an allosteric enzyme which, in both its affinity and enzymatic activity, responds optimally only to the cognate substrate. Detailed calculations show, furthermore, that increasing the concentration of EF-G and EF-Ts above the level prevailing in vivo only slightly increases the rate of elongation. In contrast, increasing the concentration of EF-Tu over aminoacyl-tRNA (aa-tRNA) leads to a sharp decline in the rate of elongation. While varying the concentration of EF-G has no effect on the accuracy of protein synthesis, excess of EF-Tu over aminoacyl-tRNA leads to a large increase in accuracy. These results suggest a mechanism by which the accuracy of protein biosynthesis is preserved during amino acid starvation.

Computer Simulation↗
PubMed1989

Hyperprolactinemia and nonpuerperal mastitis (duct ectasia).

In 108 patients with nonpuerperal mastitis (inflammatory symptoms of duct ectasia), serum prolactin levels were determined before, during, and after treatment. Twenty-nine patients (26.8%) exhibited transiently elevated prolactin levels during the period of inflammation (mean +/- SD level, 42 +/- 22 micrograms/L) that returned to normal within 4 weeks. Twenty-two patients (20.4%) presented with more severe hyperprolactinemia (78 +/- 56 micrograms/L), and 15 were found to have pituitary microadenomas. In 11 cases, mastitis was the first symptom of hyperprolactinemia. A second group of 83 patients with known hyperprolactinemia and 83 normoprolactinemic controls were interviewed with regard to recent symptoms or past treatment of nonpuerperal mastitis. Sixteen hyperprolactinemic women (19.3%) and none of the controls reported that they had experienced mastitis. We conclude that duct ectasia is due in part to increased prolactin secretion. Thus, nonpuerperal mastitis may be a symptom of hyperprolactinemia. On the other hand, nonpuerperal mastitis may induce transient hyperprolactinemia (neurogenic hyperprolactinemia) of about 3 weeks' duration that is less pronounced than central hyperprolactinemia.

Adenoma↗
PubMed1988

[Self-inflicted necroses (mastitis factitia) as an unusual course of non-puerperal mastitis].

The present paper reports of a long lasting necrotising mastitis which, regarding the psychiatric aspect of the patient as well, has to be interpreted as artefactual mastitis. The uncommon localisation, the unusual history and histology as well as the hardly accessible personality may be indicative of a self inflicted injury with subsequent inflammation. Additional to the local therapy, these patients need a psychological guidance, avoiding direct confrontation with the suspected pathogenesis.

Abscess↗
PubMed1988

[Gonadotropin resistance in Rothmund-Thomson syndrome].

A case of Rothmund-Thomson syndrome of a 24-year old woman with primary amenorrhoea is presented. This autosomal recessive disorder is characterised by atrophy, hyperpigmentation and teleangiectasiae of the skin, furthermore by juvenile cataracts and congenital bone defects as saddle nose. Endocrinologic and morphologic parameters suggest a resistant ovary syndrome as cause of this hypergonadotropic hypogonadism.

Adult↗
PubMed1987

The role of translocation in ribosomal accuracy. Translocation rates for cognate and noncognate aminoacyl- and peptidyl-tRNAs on Escherichia coli ribosomes.

The ribosomal translocation, as measured in vitro by peptide formation on poly(U)-programmed Escherichia coli ribosomes in the presence of ternary complex, deacylated tRNA or N-acetyl-Phe-tRNA, and elongation factor G, is the rate-limiting step of protein synthesis. Elongation factor G stimulates the spontaneous translocation by a factor of about 500. N-Acetyl-Phe-Phe-tRNA(Phe E. coli) is translocated with a rate constant of 1-2 s-1 at 25 degrees C. Translocation of N-acetyl-Phe-Phe-tRNA(Phe yeast) and N-acetyl-Phe-Leu-tRNA(Leu E. coli) under identical conditions proceeds with a rate by about a factor of 2 and 10, respectively, more slowly. The translocation rate, therefore, is influenced by the nature of the tRNAs in the A-site. We can show, furthermore, that also the tRNA in the P-site, and presumably in the E-site as well, influences the rate of translocation. Reduced rates of translocation of noncognate peptidyl-tRNAs are accompanied by preferential dissociation of these tRNAs at the beginning of the translation of a mRNA.

Escherichia coli↗
PubMed1986

Inhibition of lactation by a long-acting bromocriptine.

A long-acting form of bromocriptine, a prolactin (PRL) secretion inhibitor, was administered to 122 postpartum women in single intramuscular injections of 20 (N = 24), 30 (N = 22), 40 (N = 46), and 50 mg (N = 30). In 91 women the substance was administered immediately after delivery to prevent galactopoiesis and in the remaining 31 women to inhibit established lactation. Effectiveness was estimated by the absence of breast engorgement and of milk secretion. Successful prevention or inhibition of lactation was highest among women receiving 50 mg bromocriptine (97%), and comparison between dosages revealed a close linear dose-response relationship (r = 0.98). Persistent and significant (P less than .001) PRL inhibition could be recorded for up to 22 days in successfully treated puerperas in comparison with 12 normally breast-feeding women who served as control subjects. No significant side effects or local reactions were recorded. Eleven of 46 postpartum women receiving 20 or 30 mg bromocriptine experienced onset of milk secretion or lactation rebound, and responded to oral administration of the drug. The presence of milk was associated with plasma PRL concentrations persistently above 25 ng/mL in all of them, whereas nine women in the same dosage range in whom lactation suppression was effective exhibited values below this limit. Dose-response data allow the establishment of a putative PRL threshold for induction of milk secretion of about 25 ng/mL. Maintenance of plasma PRL values below this limit prevents lactogenesis and inhibits lactopoiesis.

Bromocriptine↗
PubMed1985

Thyroid hormones in benign breast disease. Normalization of exaggerated prolactin responsiveness to thyrotropin-releasing hormone.

To investigate the exaggerated prolactin (PRL) responsiveness to thyrotropin-releasing hormone (TRH) in patients with benign breast disease (BBD), 18 patients and 13 healthy controls underwent an 8-week-long thyroid hormone treatment. The clinical effect of thyroid hormones on cyclical mastodynia and concomitant galactorrhea was evaluated. TRH-stimulated PRL and thyroid-stimulating hormone (TSH) responses and thyroxine, triiodothyronine, thyroxine-binding globulin, as well as serum estradiol and progesterone levels, were measured before and during hormone treatment. Thirteen of the patients and one of the controls had euthyroid diffuse goiter. Patients and controls had normal thyroid function parameters. During thyroid hormone treatment, significantly elevated TRH-induced PRL responses of the patients decreased by 50% and reached levels of the controls, whereas responses of the controls decreased insignificantly. Patients exhibited significantly lower serum progesterone levels than the controls; the estradiol levels were not different. Thyroid hormone treatment had no significant influence on luteal function of patients or controls. In 16 of 18 patients thyroid hormones were of benefit to mastodynia, whereas galactorrhea remained unaffected.

Adolescent↗
PubMed1985

[Non-puerperal mastitis. Etiology, clinical aspects and therapy].

Non-puerperal mastitis was diagnosed in 79 patients (aged 12-77 years) over the years 1974-1984. Malignant neoplasm was not present. Bacterial infection in the region of the areola was the most frequent finding (40%), followed by abacterial inflammation without involvement of the nipples (29%). The other cases, bacterial or nonbacterial, occurred at different sites. The histological picture or clinical features of an increased secretory activity of the mammary gland (galactorrhoea, mastodynia) in addition to the mastitis was noted in 54 women. Causative organisms were proven in 53% of cases: Staph. aureus (41%) and coagulase-negative staphylococcus (41%), or anaerobic organisms (11%). Physical measures, antibiotics and bromocriptine were used as treatment. At the onset of treatment abscesses were already present or developed in 34 instances. In 28 cases one to six recurrences set in after the end of the treatment period. In 22 patients treated with bromocriptine prophylactically there were only two recurrences. In the majority of patients an increased alveolar secretion was important in the pathogenesis of the bacterial or abacterial inflammation. Prolactin-lowering treatment seems reasonable by itself in cases of abacterial mastitis, or in combination with antibiotics in bacterial mastitis. Recurrences can be prevented by long-term lowering of the peripheral prolactin level.

Adolescent↗