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Biomedical subjects

P Jakobs

Publications and source records attributed to P Jakobs.

13 recordsLinked to original sources
PubMed2006

Blockade of chemokine signaling in patients with multiple sclerosis.

We assessed the safety and efficacy of orally administered CC chemokine receptor 1 (CCR1) antagonist in 105 patients with relapsing/remitting MS (RRMS) in a 16-week, randomized, double-blind, placebo-controlled trial. The primary endpoint was the cumulative number of newly active lesions on serial MRI scans. Other MRI, immunologic, and clinical outcomes were also explored. No significant treatment difference was observed for any tested MRI variable. CCR1 does not contribute to initial leukocyte infiltration in RRMS.

Central Nervous System↗
PubMed2006

Treatment with interferon beta-1b delays conversion to clinically definite and McDonald MS in patients with clinically isolated syndromes.

OBJECTIVE: To assess efficacy, safety, and tolerability of every-other-day interferon beta-1b treatment in patients with a first clinical event suggestive of multiple sclerosis (MS) (clinically isolated syndrome). METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled trial. Patients with a first clinical demyelinating event and at least two clinically silent brain MRI lesions were randomized to interferon beta-1b (IFNB-1b) 250 mug subcutaneously (SC) every other day (EOD) (n = 292) or placebo (n = 176), until clinically definite MS (CDMS) was diagnosed or they had been followed for 24 months. RESULTS: After 2 years, 45% of placebo patients had converted to CDMS (Kaplan-Meier estimate; primary outcome measure) and 85% fulfilled the McDonald criteria (co-primary outcome measure). Overall interferon beta-1b delayed the time to diagnosis of CDMS (p < 0.0001) and McDonald MS (p < 0.00001). Hazard ratios (95% CI) were 0.50 (0.36 to 0.70) for CDMS and 0.54 (0.43 to 0.67) for McDonald MS favoring treatment with IFNB-1b. Treatment was well tolerated, as indicated by the low rate of patients dropping out of the study before CDMS was reached (6.6% overall, 7.2% in the IFNB-1b group). CONCLUSIONS: Interferon beta-1b 250 mug subcutaneously every other day delayed conversion to clinically definite multiple sclerosis, and should be considered as a therapeutic option in patients presenting with a first clinical event suggestive of multiple sclerosis.

Adult↗
PubMed2003

Oral interferon beta-1a in relapsing-remitting multiple sclerosis: a double-blind randomized study.

BACKGROUND: Interferon beta (IFNB) is available in parenteral formulations for treatment of multiple sclerosis (MS). The purpose of this study was to evaluate safety, tolerability and effects on MRI lesions of three different doses of oral IFNB-1a compared with placebo over six months in relapsing-remitting (RR) MS patients. METHODS: In this multicenter; double-blind randomized trial, RR-MS patients received 0.06, 0.6 or 6 million international units (MIU) IFNB-1a or placebo every other day for up to six months. Gadolinium DTPA-enhanced brain MRI scans were performed at screening and monthly during treatment. The primary variable was the cumulative number of newly active lesions. Secondary variables included volume of enhancing lesions on T1-weighted images each month and lesion volume on T2-weighted images at months three and six. Safety measures included adverse events, laboratory variables, vital signs, ECG, physical examination, EDSS and number of relapses. Neopterin was measured in 21 patients and neutralizing antibodies in 24 patients. RESULTS: Of 194 screened patients, 173 were randomized (42-44 patients per group) in 15 centers. Median cumulative numbers of newly active lesions over six months were 4.0 in the placebo and 0.6 MIU groups, compared with 7.5 and 9.0 in the 0.06 and 6 MIU groups (no significant differences). Secondary efficacy endpoints showed small and inconsistent differences between groups. Adverse events showed no notable group differences. Approximately two-thirds of patients in each group remained relapse free. No patients showed neutralizing antibodies. Neopterin levels were comparable between groups. CONCLUSION: Oral IFNB-1a showed neither beneficial effects in RRMS nor any systemic biological effects. Treatment was safe and well tolerated.

Adjuvants, Immunologic↗
PubMed1998

Subtyping analysis of Fanconi anemia by immunoblotting and retroviral gene transfer.

Fanconi anemia (FA) is an autosomal recessive cancer susceptibility syndrome with at least eight complementation groups (A-H). Two of the FA genes (FAA and FAC) have been cloned, and mutations in these genes account for approximately 80% of FA patients. Subtyping of FA patients is an important first step toward identifying candidates for FA gene therapy. In the current study, we analyzed a reference group of 26 FA patients of known subtype. Most of the patients (18/26) were confirmed as either type A or type C by immunoblot analysis with anti-FAA and anti-FAC antisera. In order to resolve the subtype of the remaining patients, we generated retroviral constructs expressing FAA and FAC for transduction of FA cell lines (pMMP-FAA and pMMP-FAC). The pMMP-FAA construct specifically complemented the abnormal phenotype of cell lines from FA-A patients, while pMMP-FAC complemented FA-C cells. In summary, the combination of immunoblot analysis and retroviral-mediated phenotypic correction of FA cells allows a rapid method of FA subtyping.

Amino Acid Sequence↗
PubMed1996

[Analysis of regional differences in hospitalization rate and length of stay costs].

PROBLEM: Performance of an analysis of hospitalised cases based on processed statutory health insurance data on inpatient treatments. Object of the examination were regional differences in the frequency of hospitalisation and in the volume of payable (invoised) days and the relevant determining parameters. MATERIAL AND METHODS: The analysis is based on a total of 152,854 cases of hospitalisation recorded in 1994 by the Magdeburg Statutory Health Insurance Body. These include data (rendered anonymous) on each insured person and on the specialist branch of the referring physician, case characteristics as well as characterising features of the hospital. Additionally, 249,471 diagnosis recordings are available from the total of the recorded cases. RESULTS: There is considerable regional variation in the number of hospital care days within the area of the Magdeburg Statutory Health Insurance Body. These regional differences are noticeable both in the frequency of referrals (broken down according to the regional statutory health insurance offices) and in the average duration of stay (in the hospitals of the region). Reasons for this heterogeneity are evident from the structural conditions of medical care by the physicians under contact with the statutory health insurance body (greater frequency of referral to hospital in areas where there are fewer doctors per 10.000 inhabitants and with less voluminous practices) and from different management strategies of hospitals even if medical care services are well standardised. DISCUSSION: The results prompt more detailed analyses of inpatient care activities including structural parameters of the outpatient sector. Actually we can recognise certain limitations preventing a uniform patient care by statutory health insurance physicians and uniform inpatient care, in the sense imposed by the official policy to ensure such uniformity.

Costs and Cost Analysis↗
PubMed1994

The Ashkenazi Jewish Fanconi anemia mutation: incidence among patients and carrier frequency in the at-risk population.

Fanconi anemia (FA) is an autosomal recessive disease for which at least four complementation groups exist. Recently the gene that corrects the defect in Fanconi anemia complementation group C cells (FACC) has been cloned. We have previously identified a common mutation in the FACC gene, which accounts for a majority of FA cases in Ashkenazi Jewish individuals. We here describe the use of allele-specific oligonucleotide (ASO) hybridization to determine the frequency of this mutation among additional Jewish FA patients and to determine the carrier frequency in the Jewish population. The common IVS4 + 4A-->T allele was found on 19/23 (83%) Jewish FA chromosomes, indicating that it is indeed responsible for most cases of FA among Ashkenazi Jews. The carrier frequency was 2/314 for Jewish individuals and the mutant allele was not detected in 130 non-Jewish controls.

Fanconi Anemia↗
PubMed1993

Sarcoplasmic reticulum calcium ATPase. Labeling of a putative Mg2+ site by reaction with a carbodiimide and a spin-label.

The sarcoplasmic reticulum Ca(2+)-ATPase loses hydrolytic activity and the ability to be phosphorylated by Pi following incubation with EDC [1-ethyl-3-(3-dimethylaminopropyl)carbodiimide]. 4 nmol of tempamine per mg SR protein can be coupled to either a glu or an asp side chain through the EDC reaction. Mg2+ protects against loss of activity and tempamine labeling with a mid-point of about 3 mM in the absence of Ca2+. This is similar to the Kd for a Mg2+ that serves as a cofactor in enzyme phosphorylation. The Mg2+ protection constant is lowered by an order of magnitude when Ca2+ is bound to the transport sites. It is suggested that control of the Mg2+ binding site affinity may be part of the mechanism of enzyme activation by Ca2+.

Animals↗
PubMed1991

Binding of ATP to uncoupling protein of brown fat mitochondria as studied by means of spin-labeled ATP derivatives.

ATP derivatives spin-labeled (SL) at C8, N6, C2' or C3' were employed in binding studies with the uncoupling protein of brown fat mitochondria. Substitution of the ribose strongly impaired binding, whereas labeling of the adenine moiety allowed for tight and functional complex formation. Detailed binding studies with C8-SL-ATP confirmed the known pH and Mg2+ dependence with a stoichiometry of one C8-SL-ATP bound per 66 kDa dimer. Corresponding studies of the uncoupling protein after modification with N-ethylmaleimide or diazobenzene-4-sulfonic acid revealed distinct differences in their effects on nucleotide binding and gating.

Adenosine Triphosphate↗
PubMed1989

Synthesis of spin-labeled 2-azido-ATP: evidence for distinct nucleotide-binding sites in calcium pump protein from sarcoplasmic reticulum.

A spin-labeled and photoreactive derivative of ATP was synthesized with the spin label attached to the 2'- or 3'-position of the ribose moiety and an azido group to C2 of the adenine ring (SL-2N3-ATP). Irradiation of this compound at 350 nm generates a nitrene, which then reacts with nucleophiles in its vicinty. SL-2N3-ATP, in the presence of Ca2+, was hydrolyzed by the calcium pump protein (Ca2+-ATPase) of fast twitch skeletal muscle sarcoplasmic reticulum. The SL-2N3-ATP-enzyme complex in the absence of Ca2+ exhibited strongly immobilized ESR spectra. ESR spectra obtained after covalent incorporation of SL-2N3-ATP into Ca2+-ATPase and removal of freely tumbling SL-2N3-ATP exhibited motionally constrained species indicative of distinct and possibly adjacent ATP-binding sites. By contrast, with SL-ATP devoid of the azido group or with the corresponding 'non-cleavable' beta, gamma-methylene triphosphate analogue (SL-AMP-PCP), two distinct sites were not as well resolved in the ESR spectra due to spectral overlap with the signal from the freely tumbling fraction even with the enhanced spectral resolution provided by perdeuteration of the spin label. Thus, SL-2N3-ATP may have general application for ESR studies of ATP-dependent proteins under conditions in which non-covalent interactions are too weak for motionally restricted species to be resolved.

Adenosine Triphosphate↗
PubMed1978

[The therapy of tinnitus resulting from blast injury (author's transl)].

In a prospective study aimed at the cure of tinnitus due to blast injury, oral treatment of 172 patients with the mono-substances Betahistine, Pentoxifyllin and Xantinol-nicotinate were compared with those of control patients who received no medications. Patients treated with Pentoxifyllin and Xantinol-nicotinate improved better than the comparative group without therapy although the differences were not considerable. Betahistine as compared with the other groups produced significantly better therapeutic results.

Adolescent↗
PubMed1977

[The treatment of acute acoustic trauma (blast injury) with dextran 40 (author's transl)].

In a prospective study the results of treatment of 72 patients with deafness due to blast injury were assessed. All patients received infusions of Dextran 40. When treatment started within 3 days of the injury 74% showed complete recovery of hearing and the remaining 26% showed some improvement. When treatment started within 3 weeks of the injury 26.5% showed complete recovery, 61.8% had some improvement and 11.8% had no improvement. In 87.5% of those patients who attended after a longer interval no change in the audiograms occurred and only 12.5% had any significant improvement. The disappearance of tinnitus was effectively more common with early treatment. On account of these results the use of Dextran 40 is strongly advised.

Blast Injuries↗