Search PubMed⌕ Search

Biomedical subjects

K Peters

Publications and source records attributed to K Peters.

At least 199 records · Page 11Linked to original sources
PubMed1993

Structure of the complex of proteinase K with a substrate analogue hexapeptide inhibitor at 2.2-A resolution.

The crystal structure of a transition state/product complex formed by the interaction between proteinase K and the substrate analogue N-Ac-L-Pro-L-Ala-L-Pro-L-Phe-D-Ala-L-Ala-NH2 has been determined at a resolution of 2.2 A and refined to an R-factor of 0.165 for 12,725 reflections. The inhibitor forms a stable complex through a series of hydrogen bonds with protein atoms and water molecules. The inhibitor is hydrolyzed between Phe 4I and D-Ala5I (I indicates inhibitor). The two fragments are separated by a distance of 3.07 A between the carbonyl carbon and the main chain nitrogen. Both fragments remain bound to the protein. The N-terminal fragment occupies subsites S5 to S1, whereas the C-terminal part is bound in S1' and S2', the first time that electron density for a substrate analogue has been observed in the P1' and P2' sites of a subtilisin-like enzyme. The flexible segments of the substrate recognition sites Gly100-Tyr104 and Ser132-Gly136 move appreciably to accommodate the inhibitor. Biochemical results indicate an inhibition by this specifically designed peptide of 95%.

Amino Acid Sequence↗
PubMed1993

Unique expression pattern of the FGF receptor 3 gene during mouse organogenesis.

The actions of fibroblast growth factors (FGFs) are mediated via a family of four closely related FGF receptor genes (FGFRs 1-4). FGFR1, FGFR2, and FGFR4 have unique patterns of expression during embryogenesis suggesting that these receptors mediate different functions of FGFs during development. In the present study, we used in situ hybridization analysis to show that FGFR3 also has a unique pattern of expression during organogenesis. Like FGFR1 and FGFR2, FGFR3 was expressed in the germinal epithelium of the neural tube (9.5-16.5 days pc). However, at 1 day postpartum and in the adult brain, FGFR3 was expressed diffusely and localized in cells with morphologic characteristics of glia, a pattern distinctly different from the discrete neuronal expression of FGFR1. FGFR3 was also expressed at high levels in differentiating hair cells of the cochlear duct, but was not detected in other sensory epithelia. Outside the nervous system, the highest level of FGFR3 expression was found in the cartilage rudiments of developing bone. During endochondral ossification, FGFR3 was expressed exclusively in resting cartilage, a pattern distinct from FGFR1 and FGFR2 which are also expressed during this process. Unlike FGFR1 and FGFR2, FGFR3 was not detected in most other epithelial or mesenchymal tissues during these stages of organogenesis. The unique expression pattern of FGFR3 compared with the other FGF receptors strongly suggests that FGFR3 performs specific functions during organogenesis.

Animals↗
PubMed1993

Evaluation of two enzyme immunoassays for rapid detection of group B streptococci in pregnant women.

The performance of two enzyme immunoassays for rapid detection of group B streptococci (GBS) was evaluated in comparison to culture using cervical swabs from 191 pregnant women. Ten percent of the women harboured GBS. There were two positive results in the Icon assay (Hybritech), both in women with heavy growth in the culture, and four positive results in the Quidel assay (Quidel), two in the women with heavy colonization and one each in women with moderate and light growth of GBS respectively. The sensitivity of both assays was low, being 11% (2/18) for the Icon assay and 24% (4/17) for the Quidel assay. The specificity of both assays was 100%. Both assays could detect > or = 10(6) group B streptococci per swab. A positive result justifies ampicillin prophylaxis due to the high risk for the newborn. A negative result should be confirmed by rapid culture techniques.

Carrier State↗
PubMed1993

Two types of sites required for meiotic chromosome pairing in Caenorhabditis elegans.

Previous studies have shown that isolated portions of Caenorhabditis elegans chromosomes are not equally capable of meiotic exchange. These results led to the proposal that a homolog recognition region (HRR), defined as the region containing those sequences enabling homologous chromosomes to pair and recombine, is localized near one end of each chromosome. Using translocations and duplications we have localized the chromosome I HRR to the right end. Whereas the other half of chromosome I did not confer any ability for homologs to pair and recombine, deficiencies in this region dominantly suppressed recombination to the middle of the chromosome. These deletions may have disrupted pairing mechanisms that are secondary to and require an HRR. Thus, the processes of pairing and recombination appear to utilize at least two chromosomal elements, the HRR and other pairing sites. For example, terminal sequences from other chromosomes increase the ability of free duplications to recombine with their normal homologs, suggesting that telomere-associated sequences, homologous or nonhomologous, play a role in facilitating meiotic exchange. Recombination can also initiate at internal sites separated from the HRR by chromosome rearrangement, such as deletions of the unc-54 region of chromosome I. When crossing over was suppressed in a region of chromosome I, compensatory increases were observed in other regions. Thus, the presence of the HRR enabled recombination to occur but did not determine the distribution of the crossover events. It seems most likely that there are multiple initiation sites for recombination once homolog recognition has been achieved.

Animals↗
PubMed1993

Prognosis of depression in the elderly. A comparison with younger patients.

The prognosis of depression in the elderly was investigated in a mixed-age sample of 242 consecutive referrals, with DSM-III defined unipolar major depressive episode, to a specialist unit for mood disorders. Subjects were followed up at about 1 and 3.8 years. There was no significant difference in outcome between younger (under 40 years), middle aged (40-59 years) and older (60 years or more) depressed patients. For the 61 elderly subjects with depression, prognosis improved with time, with 25% having a lasting recovery at the first and 41% at the second follow-up. Early onset, recurrence, and poor premorbid personality were associated with a worse prognosis. Three (5%) elderly depressives had committed suicide and seven (11%) had died from natural causes by the second follow-up. Despite some methodological limitations, our findings suggest a more optimistic outlook and the need for longer, more assertive treatment for elderly, depressed patients.

Adolescent↗
PubMed1993

Interferon alpha-2b treatment of symptomatic chronic vulvodynia associated with koilocytosis.

In an open study with identical criteria for diagnosis, 16 female patients with typical symptoms of chronic vulvodynia associated with acetowhitening of the vestibular epithelium and koilocytosis in biopsy specimens received recombinant interferon alpha-2b 5 MIU intralesionally 3 times weekly for 3 weeks or subcutaneously 3 times weekly for 8 weeks. Three months after end of therapy, clinical symptoms had disappeared in 7 (70%) of the 10 patients treated intralesionally, compared with only one (16%) of the 6 patients treated subcutaneously. In addition, the last 3 (30%) patients in the first group had a partial response to therapy. The acetowhitening persisted in all patients. The koilocytosis remained unchanged in 13 (81%) of the 16 patients. Our results indicate that recombinant interferon alpha-2b administered intralesionally seems to be efficacious in reducing clinical symptoms in vulvodynia with suspected human papillomavirus infection but does not eliminate the infection. Subcutaneous administration had neither symptomatic nor antiviral effect. A placebo-controlled study is needed, but with our present knowledge we recommend intralesionally administered interferon as a symptomatic treatment of vulvodynia.

Adult↗
PubMed1993

Kinetic characterization of alkaline mesentericopeptidase. Comparison with serine proteinases from different origins.

Comparative studies of the hydrolysis of succinyl-Ala2-Phe-methylcoumarylamide with mesentericopeptidase, a mesophilic extracellular serine proteinase from Bacillus mesentericus, and proteinases produced by organisms representing different levels of evolutionary development, were performed. Drastic differences in the proteolytic coefficient kcat/Km were found. As regards their catalytic efficiency, the proteinases studied can be placed in the following order: mesentericopeptidase < subtilisin Novo << subtilisin DY < proteinase K < subtilisin Carlsberg < thermitase < alpha-chymotrypsin. The size of the substrate-binding site of mesentericopeptidase for synthetic peptides was studied by using chloromethyl ketones with the general formula benzyloxycarbonyl-Alan-Phe-CH2Cl (n = 1, 2, 3). The presence of at least five binding subsites (S1 ... S5) on the S-side of the hydrolysed bond was suggested. Studies of the primary specificity of mesentericopeptidase with a series of dipeptide chloromethyl ketones having the general formula benzyloxycarbonyl-Ala-Aa-CH2Cl (Aa = Ala, Val, Leu, Phe) revealed the following order of reactivity toward these inhibitors: Aa = Leu >> Ala > Phe > Val. Kinetically, mesentericopeptidase is similar to subtilisin BPN'/Novo.

Dipeptides↗
PubMed1992

The impact of abdominal computerized tomography on the pretreatment staging and prognosis of small cell lung cancer.

One hundred six patients with small cell lung cancer (SCLC) were prospectively evaluated with regard to the prognostic impact of abdominal CT-scan in the pretreatment staging when compared to ultrasonography of the abdomen. Staging based on abdominal ultrasonography (US) plus bilateral bone marrow examinations gave as a result that 47 patients had extensive disease (ED) (44%). Seventeen patients with proven ED at time of referral were not included in this study. Abdominal CT-scan was performed in 76 of the 106 patients. Thirty patients of these 76 patients (39%) were classified as having ED after staging including US, but abdominal metastases were disclosed in another ten patients at the subsequent CT-scan. Liver metastases seen in two patients at ultrasonography were overlooked on the CT-scans. Median survival of the 36 patients classified as having limited disease (LD) after both procedures was 458 days, which was significantly better compared to 330 days for the ten patients with stage migration from LD to ED based on CT-scan, (p less than 0.05) and compared to 242 days in the 30 patients with ED demonstrated by both US and CT-scans (p less than 0.05). The prognostic impact of the CT-scan was further investigated in a multivariate analysis (Cox). Stage disease, performance status, LDH and alkaline phosphatase were significant prognostic factors in a proportional hazards model based on the original 106 patients. Patients in the best prognostic group were characterized by LD, good performance status (0-1) and normal LDH and alkaline phosphatase serum values. This group consisted of 22 patients (21%).(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Neoplasms↗
PubMed1992

Collagen types I and III propeptides as markers of healing in chronic leg ulcers. A noninvasive method for the determination of procollagen propeptides in wound fluid--influence of growth hormone.

A noninvasive method allowing measurements of the propeptides of collagen type III (PIIINP) and type I (PICP) in ulcer washings was developed. The response to topical human growth hormone was examined. Fourteen patients with venous ulcers were treated sequentially with human growth hormone (0.1, 0.25, and 1 IU/cm2/day), each dose for 1 week, followed by 1 week washout. On alternate days, three and two times during treatment and washout periods, respectively, the ulcers were washed and incubated for 30 minutes with sterile water. No changes in healing rates in relation to growth hormone application were observed. In contrast, PIIINP increased significantly to 168% (154% to 184%) (mean, 95% confidence interval) and 195% (179% to 218%) 5 and 9 days, respectively, after start of treatment, (p < 0.01). Propeptides of collagen type I reached a significant increase, to 196% (172% to 232%), in the fourth week, (p < 0.01). The areas under the curves of PICP and PIIINP correlated significantly with the healing rates (r = 0.57, p = 0.04; and r = 0.64, p = 0.01, respectively). The authors conclude that propeptide measurements may be useful markers of healing in clinical studies.

Administration, Topical↗
PubMed1992

Basal cell and squamous cell carcinoma and Kaposi's sarcoma.

The mortality rate of nonmelanoma skin cancer is higher than generally considered. An actual nonmelanoma skin cancer is a risk factor not only for other skin cancers but also for cancers in other organs. The recurrence rate can, according to the method of calculation, yield surprisingly diverging results. Statistical mapping of subclinical tumor growth in basal cell carcinoma supplies the margins for tumor-free excision. An even better but more expensive tool for therapy planning is tumor imaging with magnetic resonance imaging. Psoralen plus ultraviolet light of the A wavelength-treated patients run a dose-dependent risk of developing squamous cell carcinoma of the skin but also cancers in other organs. Human papilloma virus-16 seems not to be associated with squamous cell carcinoma of the skin except for the anogenital region and possibly the finger. The finding of retroviruslike particles in endemic non-acquired immunodeficiency syndrome Kaposi's sarcoma strongly suggests that a virus other than human immunodeficiency virus may play a role in the pathogenesis of this disease.

Basal Cell Carcinoma↗
PubMed1992

Cytotoxicity of a selected series of substituted phenols towards cultured melanoma cells.

Substituted phenolic compounds were previously shown to exhibit cytotoxicity towards epithelial cells in the presence of the enzyme tyrosinase as a result of the formation of their quinone products. Seventeen of these compounds were tested for cytotoxic properties towards three different melanoma cell lines. The compounds were split into four groups of phenol derivatives, A; alkoxyethers, including 4-hydroxyanisole (4HA), B; oxyethers derivatized at the acyl side chain, C; oxyethers derivatized at the phenol, and D; acyl thioethers. Toxicity was determined by total cell counts after 3 days exposure to the compounds. Large reductions in cell numbers were observed with 4HA (the methoxy-), ethoxy-, propoxy and iso-butoxyethers of group A and the methyl- and propyl thioethers of phenol of group D. Derivatization of the ethoxy- and propoxy side chains (group B) did not seem to increase the cytotoxic effects, as determined by cell counts. Compounds of group C, which need intracellular esterase activity to release the phenols, showed moderate toxicities. Toxicity of certain compounds was confirmed by LDH release into the culture medium and by increased trypan blue uptake of cells exposed to the compounds. Flow cytometric investigations of cells after exposure for 24 h revealed that most compounds caused an increase in the proportion of cells in G1 phase. A complete accumulation of cells in S-phase was observed after exposure to 4-ethoxyphenol. Inhibition of DNA synthesis was also shown by inhibition of bromodeoxyuridine incorporation. The results presented show that phenolic compounds exhibit cytotoxic properties towards melanoma cells some of which may be mediated by tyrosinase activity. Toxicity of the compounds was shown to be exerted during DNA replication but their toxic action may also be due to membrane damage and inhibition of cell metabolism.

Antineoplastic Agents↗
PubMed1992

Anterior third ventricle meningioma in an adolescent: a case report.

A case of an anterior third ventricular meningioma in a 17-year-old girl is presented. Gross total resection of this tumor with minimal morbidity was accomplished by transcallosal exposure through a frontal craniotomy. A review of the literature implies that surgical morbidity and mortality for the removal of third ventricular meningiomas markedly improved with the use of the operating microscope. Despite advanced imaging capabilities, radiographic analysis of a solid third ventricular mass may not always determine tissue diagnosis. In addition, preoperative placement of a ventriculoperitoneal shunt will treat hydrocephalus, but may limit the surgical options for tumor exposure. The differential diagnosis for this solid anterior third ventricular mass is presented, and the method of treatment for this case is discussed.

Adolescent↗
PubMed1992

Exercise tolerance and working capacity after valve replacement.

Between 1978 and 1987, 1270 patients who survived single aortic or mitral valve replacement at the Rehabilitation Center in Bad Krozingen, Germany, underwent a comprehensive rehabilitation program. The preoperative diagnosis was isolated aortic stenosis in 425, isolated aortic regurgitation in 159, mixed aortic lesion in 211, isolated mitral stenosis in 208, isolated mitral insufficiency in 137 and mixed mitral lesion in 130 cases. Follow up examinations were carried out one and six months after surgery, and at yearly intervals thereafter. Exercise testing was performed with an electrically braked bicycle ergometer in the supine position, and the load was increased by 25 or 50 watts every two minutes until fatigue, severe angina, more than 0.3 mV ST-segment depression, or 80% of the age predicted maximum heart rate was achieved. Patients after aortic valve replacement had a better exercise performance one month after operation than did those after mitral valve replacement. Those with mitral stenosis showed more severe impairment of exercise tolerance than did the mitral insufficiency group. There was a steady increase in exercise tolerance between one and six months postoperatively, both in patients with aortic and those with mitral valve replacement, but the difference in performance between the two groups was still present (72% versus 57% of normal). The results of univariate and multivariate analyses showed that the preoperative employment status was the most important factor for postoperative return to work, followed by gender (male > female), exercise tolerance and valualar lesion (aortic > mitral).(ABSTRACT TRUNCATED AT 250 WORDS)

Aortic Valve↗
PubMed1991

Age and depression.

The interaction of age and depression was investigated by comparing differences between elderly (greater than or equal to 60 years old) and younger consecutive in- and out-patient referrals to a tertiary referral mood disorders unit. Older patients with unipolar major depressive episode were more likely to be psychotic and agitated regardless of depressive subtype and less likely to have personality inadequacies or a family history of affective disorder. In this sample, elderly depressives' rating of diagnosis, severity, endogeneity and social impairment were similar, irrespective of age of first onset of depression, but a positive family history and personality abnormalities were less likely in late-onset depressives.

Adjustment Disorders↗
PubMed1991

Mutations in the bli-4 (I) locus of Caenorhabditis elegans disrupt both adult cuticle and early larval development.

The bli-4 (I) gene of Caenorhabditis elegans had been previously defined by a single recessive mutation, e937, which disrupts the structure of adult-stage cuticle causing the formation of fluid-filled separations of the cuticle layers, or blisters. We report the identification of 11 new alleles of bli-4, all early larval lethals, including an allele induced by transposon mutagenesis. Nine of the lethal alleles failed to complement the blistered phenotype of e937; two alleles, s90 and h754, complement e937. The complementing alleles arrested development somewhat later than the noncomplementing alleles, which blocked just prior to hatching. We conclude that bli-4 is a complex locus with an essential function late in embryogenesis. We investigated the blistered phenotype of e937 through interactions with other mutations that alter worm morphology or cuticle structure. Recessive and dominant epistasis of several dumpy mutations over the blistered phenotype was observed. Using two heterochronic mutations that alter the developmental stage at which adult cuticle is expressed, we observed that adult worms that lack an adult-stage cuticle could not express blisters. However, late larval worms that expressed the adult cuticle did not express blisters either. It seems likely that the presence of the adult cuticle is necessary, but not sufficient, for blister expression. Blistering resulting from e937 is more severe in trans to null alleles, indicating that e937 is hypomorphic. We postulate that the adult-specific blistering is due to an altered or reduced function of bli-4 gene product in the adult cuticle.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗
PubMed1991

Lower leg subcutaneous blood flow during walking and passive dependency in chronic venous insufficiency.

The blood flow in the subcutaneous adipose tissue of the lower leg of eight normal subjects and 19 patients with chronic venous insufficiency was measured. The 133Xe-washout technique was used with portable CdT1(C1) detectors and a data storage unit. Only those patients with ulcers and a systolic blood pressure at the toe of greater than or equal to 60 mm were investigated. In the controls the relative blood flow during sitting was 0.61 (range 0.35-0.80). In the patients it was 0.46 (range 0.22-0.87). This difference was not significant. During walking the blood flow increased in controls as well as in the patients compared to the value determined in the sitting position (P = 0.0078 and P = 0.0028, respectively, Wilcoxon matched-pairs test). The relative blood-flow rate during walking was 0.96 (range 0.60-1.58) in the controls, and 1.04 (range 0.49-1.46) in the patients. The difference between the normal subjects and the patients was not significant (P = 0.79). We conclude from our studies that patients with venous insufficiency are able to increase their blood flow during walking to the same extent as normal controls.

Adipose Tissue↗