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Biomedical subjects

K Folkers

Publications and source records attributed to K Folkers.

At least 145 records · Page 8Linked to original sources
PubMed1982

Design and synthesis of effective antagonists of substance P.

The agonist/antagonist activities of four background analogs of substance P (SP) facilitated design and synthesis of 12 new analogs to achieve effective antagonists. (D-Pro2, D-Phe7, D-Trp9)-SP, (D-Pro2, D-Trp7,9)-SP and (D-Arg1, D-Phe7, D-Trp9)-SP showed no agonist activity; 9 analogs showed weak agonist activity of SP. (D-Pro2, D-Trp7,9)-SP was the most potent antagonist which at a concentration of 10(-5) required a 3-fold increase in SP to allow a 50% response by SP. (D-Pro2, Lys6, D-Phe7)-SP and (D-Pro2, D-pClPhe7, D-Trp9)-SP were also potent, and the antagonism was competitive. For specific pairs of peptides, Lys6 is a promising substituent. D-Trp7,9 was as effective as Lys6, D-Phe7. D-pClPhe7 was three times as effective as D-Phe7. D-Dln6 was 1.33-fold better than D-Gln5. D-Pro2 and D-Pro4 were equally effective. D-Pro2 was 1.5 times as effective as D-Lys3. D-Pro2 may not be important. D-pClPhe9 and D-Trp9 were equally effective.

Animals↗
PubMed1982

Peripheral and central nervous actions of substance P antagonists.

Studies with the SP-analogues (D-Pro2, D-Phe7, D-Trp9)-SP and (D-Pro2, D-Trp7,9)-SP show that they inhibit the action of SP in a variety of organs both in vitro and in vivo. They also block several non-cholinergic, non-adrenergic effects of nerve activation. Experimental evidence suggest that (D-Pro2, D-Phe7, D-Trp9)-SP and (D-Pro2, D-Trp7,9)-SP are specific SP-antagonists of the competitive type with little or no agonist activity. The present data show that SP-antagonists will be of great importance in clarifying functions of SP.

Animals↗
PubMed1982

Stimulation of lymphocyte proliferation to monitor fractionation of thymus extracts.

Multi-step fractionations by solvent extractions, gel filtrations, ion-exchange chromatography, etc., of bovine thymus extracts were monitored by a standardized assay, in vitro, which led to the described peptides, thymones A, B and C. The assay uses spleen cells from neonatally thymectomized mice as tissue relevant to immunoregulation. Assay of incorporation of [3H]-thymidine into DNA located peaks of activities. Calf thymus outer fraction ("CTO") showed activity, but Fraction 5, synthetic thymosin alpha 1, [G1n1]-FTS, and glutathione, were inactive in this assay.

Animals↗
PubMed1981

Sensory and motor functions of spinal cord substance P.

Low doses of D-Pro2-D-Phe7-D-Trp9-substance P, as specific substance P antagonist, depressed the scratching and biting behaviors elicited by intrathecal injections of substance P, and cutaneous application of algesic substances. Higher antagonist doses caused hindlimb paralysis. This suggests that substance P is a neurotransmitter for primary nociceptor afferents and may also have an important function in motor control.

Animals↗
PubMed1981

A substance P antagonist, [D-Pro2, D-Trp7,9]SP, inhibits inflammatory responses in the rabbit eye.

Neurogenic factors released by antidromic nerve stimulation are thought to be in part responsible for the vasodilation and breakdown of the blood-aqueous barrier that follows trauma to the eye. Substance P is one candidate for the mediation of the inflammatory response since it is thought to be a neurotransmitter in sensory afferents and since exogenous substance P is capable of eliciting a response characteristic of inflammation. In rabbits, intravitreal or topical application onto the eye of a specific substance P antagonist, [d-Pro2, D-Trp7,9]SP, inhibited not only the irritant effects of exogenous substance P but also the inflammatory response to a standardized trauma (infrared irradiation of the iris). These observations suggest that substance P, or a related peptide, is a neurogenic mediator of the inflammatory response in the eye.

Animals↗
PubMed1981

Distribution of vitamin B6 deficiency in university students.

The basal specific activities (S.A.; mumol of pyruvate/hr/10(8) erythrocytes) and the % deficiencies of activity of the glutamic oxaloacetic transaminase of the erythrocytes (EGOT) of 174 university students was 0.28 +/- 0.05 and 33 +/- 9%, respectively. There was a negative correlation, r = -0.65 (p less than 0.001), between the mean basal S.A. and the mean % def. (i.e., the lower the S.A., the higher the % def.). There were students with low basal S.A.'s who showed symptoms of carpal tunnel syndrome. On the basis of these data, 93% of 174 students had deficiencies of 20% and higher which was potentially correctable by oral pyridoxine; these students had B6-deficient diets. On the basis that a normal basal S.A. may be 0.7, and that the maximum S. A. (0.45) for all 174 students is about 65% of 0.7, all 174 students had varying vitamin B6 deficiency, and their diets provided inadequate amounts of this vitamin.

Aspartate Aminotransferases↗
PubMed1981

A synthetic peptide capable of eliciting antibodies that neutralize human chorionic gonadotropin.

Antisera generated to the human chorionic gonadotropin beta-subunit (hCGbeta) have been shown not only to neutralize the biologic activity of hCG but also to cross-react with human luteinizing hormone (hLH). In an attempt to reduce such cross-reactivity, a peptide fragment analogous to the amino acid sequence of the carboxylterminal 45 residues (101-145) of the hCGbeta-subunit with alpha-aminobutyric acid substituting for cysteine at position 110 was synthesized and tested for ability to produce antibodies interacting with hCG. Antisera were generated in rabbits to a conjugate of this peptide with tetanus toxoid emulsified with Freund's complete adjuvant. Antibody titers and specificity were assessed by the double-antibody technique. The results show that the antisera to the synthetic hCGbeta fragment bound 125I-labeled hCG and did not cross-react with hLH in the radioimmunoassay system. Most importantly, the antisera effectively neutralized the biologic activity of hCG as determined by the rat uterine weight assay.

Amino Acid Sequence↗
PubMed1981

Bioenergetics in clinical medicine. XVI. Reduction of hypertension in patients by therapy with coenzyme Q10.

Six untreated hypertensive patients and ten on therapy, but having elevated blood pressures, were treated with coenzyme Q10(CoQ10); 14/16 patients showed reductions (p less than 0.05-less than 0.001) in systolic pressures; 11/16 showed reductions (p less than 0.05-less than 0.001) in diastolic pressure; 9/10 showed reductions of elevated pressures to a normal range. By impedance cardiography and electrocardiography, there were no changes in cardiac outputs, stroke volumes and Heather Indices except for a few patients with changes of doubtful biological significance. 3/16 patients had exceptionally low basal specific activities of the succinate dehydrogenase-coenzyme Q10 reductase in blood which increased to a normal range on treatment. A greater deficiency of CoQ10 in the vascular system than in blood is likely. We consider that (1) the mechanism of reduction of elevated blood pressures by CoQ10 is based upon normalization or autoregulation of peripheral resistance rather than cardiac regulation, and (2) that the therapeutic activity of CoQ10 is not pharmacodynamic, but results from a translational increase in levels of CoQ10-enzymes in vascular tissue during ca. 4-12 weeks.

Blood Pressure↗
PubMed1981

Therapy with vitamin B6 with and without surgery for treatment of patients having the idiopathic carpal tunnel syndrome.

Blood samples from four patients at the time of surgery to relieve the compression of the carpal tunnel syndrome, which was diagnosed by clinical and electromyographic evaluation, were differentially assayed to determine the specific activities and the % deficiencies of the erythrocyte glutamic oxaloacetic transaminase (EGOT). The data from these assays revealed that these four patients had a severe deficiency of vitamin B6. These data, in conjunction with previous biochemical and clinical results over five years, underscore the desirability, and even necessity, of testing by the EGOT analysis for the presence of a severe deficiency of vitamin B6 in all such patients before surgery. Treatment with vitamin B6 (pyridoxine) for a minimum period of 12 weeks, depending upon the duration and severity of the symptoms, has been effective without exception. Surgery may relieve compression, but does not correct a deficiency of vitamin B6. Surgery in addition to therapy with vitamin B6 should be reserved for those patients who have had the deficiency for so many years that much tissue damage is irreversible by pyridoxine, and additional relief from pain can be achieved through the surgery.

Adult↗