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Biomedical subjects

M Klein

Publications and source records attributed to M Klein.

At least 469 records · Page 26Linked to original sources

Identification of a potent synthetic HIV1 immunogen compromising gag-P24 tandem T- and B-cell epitopes.

Recent studies indicate that the gag gene products may play a crucial role in the immune response against HIV infection since clinical progression to AIDS is associated with a reduction in the level of circulating antibodies to gag p24 and antibodies raised against p17 peptide can inhibit HIV1 infection in vitro. Using conventional structure prediction algorithms for T-cell and B-cell epitopes, we have selected and chemically synthesized several gag peptides. In particular, an unconjugated HIV1-p24 peptide containing both B- and T-cell epitopes in tandem plus Freund's adjuvant induced a strong antibody response in both mice and rabbits against p24 and its precursor p55 as judged by immunoblotting. In addition, the peptide presented in the appropriate MHC context was shown to be highly stimulatory for p24 specific murine T-cell clones.

Acquired Immunodeficiency Syndrome↗

[Transmetatarsal border zone amputation in arterial blood supply disorders].

Transmetatarsal amputations (TA) were performed in 32 patients (22 men, 10 women; mean age 64 [40-91] years) with occlusive arterial disease. Previous revascularization procedures (bypass, thrombendarterectomy, embolectomy) had been performed in 26 patients. Surgical results of TA after one year were good in 16, satisfactory in seven, and unsatisfactory in nine. Further amputations became necessary after a mean of 52 (4-221) days in four of the six patients without and five of 26 with previous revascularization. Follow-up examination 1-6 years after discharge found that six had died, 16 were able to walk and fully rehabilitated, while in ten walking was limited and they required help in walking.

Adult↗

A CA125 score as a prognostic index in patients with ovarian cancer.

Due to its high specificity (90%) and sensitivity (86%) measurement of CA125 has become well-established in patients with epithelial ovarian cancer. We have formulated a CA125 prognostic score and examined its validity as an additional prognosis index. This score is composed of two CA125 values (one determined preoperatively and one 1 month after operation). CA125 serum levels of 0-64 IU/ml received 1 point, levels of 65-299 IU/ml were given 2 points, and those greater than 300 IU/ml were given 3 points. These points are added to produce the CA125 prognostic score. Statistical comparison demonstrated that patients with scores of 2 or 3 had a significantly (P = 0.0005) better prognosis than patients with scores of 4, 5 or 6. The classical prognostics features such as the FIGO stage, residual tumor mass and ascites were found to correlate with the CA125 prognostic score.

Adult↗

Bacillus thuringiensis potency bioassays against Heliothis armigera, Earias insulana, and Spodoptera littoralis larvae based on standardized diets.

Bacillus thuringiensis screening programs based on the official potency bioassay using third-instar larvae and on a neonate bioassay were developed for Heliothis armigera, Earias insulana, and Spondoptera littoralis. In these bioassays, the diets were standardized to be suitable, with minor modifications, for feeding of the three lepidopterans. The bioassay protocol was based on determination of the LC50 of the microbial standard HD-1-S-80 in the insects susceptible to B. thuringiensis var. kurstaki strains. This was followed by preliminary screening of B. thuringiensis strains at the LC50 of the B. thuringiensis standard. The B. thuringiensis strains causing 100% mortality at this LC50 in the larvae were selected for potency determinations. The neonate bioassay was suitable for accurate determinations of potencies also in S. littoralis--a representative of insects weakly susceptible to the HD-1 standard. The role of the official and the neonate bioassays in developing microbial control programs is discussed.

Animals↗

Computer-assisted analysis of dextromethorphan and (+)-3-(-3-hydroxyphenyl)-N-(1-propyl)piperidine binding sites in rat brain. Allosteric effects of ropizine.

Computer-assisted analysis of self- and cross-displacement studies between dextromethorphan (DM) and (+)-3-(3-hydroxyphenyl)-N-(1-propyl) piperidine ((+)-3-PPP) demonstrated in the rat brain the existence of two high-affinity and one low-affinity binding site for each ligand. One high-affinity site is the common DM1/sigma 1 site, the affinity of which is allosterically increased 4 to 5-fold by 10 microM ropizine. The Kd values of the DM1/sigma 1 for DM and (+)-3-PPP are 17 and 11 nM respectively. DM binds to the second high-affinity site (R2) with a Kd of 15 nM; this site has low affinity for (+)-3-PPP. Conversely, (+)-3-PPP binds with high affinity (Kd 53 nM) to another site (R3), that has low-affinity for DM. The Bmax of the common DM1/sigma 1 site in the rat is about ten times smaller than that in the guinea pig. Thus, extreme caution should be exercised in extrapolating from one species to another. Since DM and most sigma ligands bind to more than one site, not all of which are shared, it is important not to attribute the complex pharmacological effects of these ligands to a single hypothetical receptor.

Allosteric Site↗

Second messengers involved in the two processes of presynaptic facilitation that contribute to sensitization and dishabituation in Aplysia sensory neurons.

Presynaptic facilitation of transmitter release contributes to behavioral sensitization and dishabituation, two simple forms of learning in Aplysia. This enhancement of transmitter release can be simulated by the facilitatory transmitter serotonin and has been shown to result from two types of mechanisms. The first facilitating process involves broadening of the presynaptic action potential in the sensory neurons of the reflex and is maximally effective when the synapse has not been depressed by repeated stimulation, as during sensitization. The second process is independent of changes in spike duration and can enhance release even when the synapse is quite depressed, as during dishabituation. Earlier work suggests that the first process is mediated by an increase in the intracellular level of cyclic AMP in the sensory neurons. We show here that release of free cyclic AMP from a photolyzable analogue introduced into sensory neurons can enhance release even at depressed synapses, indicating that cyclic AMP can activate the second as well as the first process. In addition, we find that phorbol esters, activators of protein kinase C, enhance release at depressed synapses. This is consistent with the report in the accompanying paper [Sacktor, T. C. and Schwartz, J. H. (1990) Proc. Natl. Acad. Sci. USA 87, 2036-2039] that serotonin and sensitizing stimuli translocate protein kinase C from cytoplasm to membrane. Our findings suggest that the cyclic AMP-dependent phosphorylation system can mediate more than one facilitatory process and that both cyclic AMP-dependent kinase and protein kinase C may be involved in facilitation of depressed synapses.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

[The effect of the protein level of feed on the energy maintenance requirement of rats during the course of growth and after the conclusion of the intensive growth phase using different feeding regimens].

In two experiments with male Wistar rats energy metabolism was measured on the feeding level of maintenance in the course of growth and in various adult periods after the application of feed mixtures with various protein-carbohydrate quotas (10, 40 and 70% crude protein) according to two different feeding regimes. While there was a change of protein levels between the animal groups in periods 1 to 3 and 8 to 10 from one period to the other, the protein levels in periods 4 to 7 and 11 to 13 remained the same for each animal group. Irrespective of the feeding regime, a dependence of the energy maintenance requirement on the nutrients according to the expected values was measured, which result from the different efficiency of ATP synthesis in the oxidative degradation of the nutrients. On an average of the periods maintenance requirement amounted to 357 +/- 21, 399 +/- 16 and 443 +/- 28 kJ/kg LW0.75.d (experiment 1) and 350 +/- 29, 383 +/- 34 and 442 +/- 30 kJ/kg LW0.75.d (experiment 2) for 10, 40 and 70% crude protein in the feed. The relation between the maintenance requirement values was 100:112:124 and 100:109:126. This contrasts with the relative expected values of 100:108:115 and 100:109:116.

Adenosine Triphosphate↗

[Effect of the nutrition level and sex on the energy maintenance requirement of broilers and rats].

In 3 experiments young broiler chickens were supplied on various feeding levels in the growth range between 200 and 2500 g live weight (2.8 and 2.0 in experiment 1, 2.8, 2.3 and 1.8 in experiments 2 and 4, maintenance = feeding level 1.0). In experiments 1 and 2 short-time measurings (30 min) of heat production by means of gas exchange were made at 500, 1000, 1500 and 2000 g live weight in the post-absorptive state and on the maintenance level of feeding. In experiment 1 the heat production of the restrictively fed chickens was in 3 out of the 4 stages of development studied significantly lower by 10-14% than that of the intensively fed ones. In experiment 2 such an effect could not be observed. Fed on the level of energy maintenance, broilers weighing approximately 2000 g (experiment 3) did not show a significant influence of the sex on heat production as a result of 30-minute gas exchange measurings in the post-absorptive state. In experiment 4 24-hour measurings of the energy metabolism were carried out in the growth development in periods of feeding on the maintenance level by means of indirect calorimetry. In the live weight range between 0.9 and 1.3 kg there was only a low, non-significant decrease of the energy maintenance requirement of 4-6% of the highly restrictively fed chickens in comparison to the intensively fed ones. After continued feed restriction (live weight range 1.7-2.2 kg) an energy maintenance requirement reduced by 17% was measured. In an analogously arranged experiment with 24-hour energy metabolism measurings (experiment 5) male Wistar rats in the growth range between 70 and 280 g were supplied on the feeding levels 1.8 and 1.4 resp. In all three periods studied on the feeding level maintenance--beginning at 140-150 g live weight--the highly restrictively fed animals showed a slightly reduced energy maintenance requirement by 8%, 3% (non-significant) and 6% in comparison with the intensively fed animals.

Animal Feed↗

Biochemical characterization and worldwide distribution of serologically distinct lipopolysaccharides of Haemophilus influenzae type b.

The sugar composition and the electrophoretic mobility in SDS-polyacrylamide gel electrophoresis of the various lipopolysaccharides (LPS) from clinical isolates of Haemophilus influenzae type b (Hib) were determined to correlate epidemiologic data with compositional data. Rabbit sera specific in Ouchterlony immunodiffusion for 10 different LPS (LPS 1-10) reacted with 647 or 690 Hib strains isolated from patients with invasive disease in various continents. Serotype 1 was predominant and was found in 550 isolates (80%). None of the Hib isolates reacted with antisera specific for LPS of two nonencapsulated isolates (LPS 5 and 6). Sugar analysis by gas-liquid chromatography of trimethylsilylated methyl glycosides revealed that the LPS of the 10 serotypes contained glucose, galactose, L-glycero-D-mannoheptose, and glucosamine in various proportions. LPS 1, 2, 8, and 9 contained the highest amounts of glucose and galactose relative to L-glycero-D-mannoheptose, which is considered present in constant amounts in H. influenzae LPS. LPS 1, 2, and 9 were most frequently found in invasive disease isolates.

Carbohydrates↗

Serum gastrin levels during long-term omeprazole treatment.

Serum gastrin was determined in 33 patients during treatment with the proton pump inhibitor omeprazole. After 4 weeks of therapy, gastrin levels increased to a median of 55 pg/ml compared to 15 pg/ml prior to omeprazole (P less than 0.001). There was a close correlation (r = 0.939; P less than 0.001) between pre-treatment gastrin and levels at 4 weeks. Comparison of serum gastrin concentrations at 1 month of omeprazole with levels at 6 (n = 21) and 12 months (n = 12) continuous therapy revealed a close correlation (r = 0.961 and r = 0.882, respectively; P less than 0.001) despite dose adjustment. In marked hypochlorhydria documented by continuous pH monitoring, serum gastrin varied from normal up to profound hypergastrinaemia. These results demonstrate that the serum gastrin increase under powerful acid-inhibitory drug therapy depends upon a number of variables. (a) Only in patients with elevated gastrin levels, prior to omeprazole treatment, can moderate to marked hypergastrinaemia during omeprazole be expected. (b) Gastrin increases reached during the initial period of omeprazole treatment remain constant during long-term therapy. (c) Acid inhibition itself is not necessarily associated with an increase in serum gastrin in every patient, which suggests that the individual sensitivity of the gastrin cell to acid inhibition is more important for serum gastrin changes than the degree of acid inhibition itself.

Esophagitis, Peptic↗

Prospective evaluation of omeprazole treatment in reflux oesophagitis refractory to H2-receptor antagonists.

The efficacy of omeprazole therapy (40 mg daily) in H2-blocker refractory severe reflux oesophagitis (Grade II-IV; Savary and Miller classification) was investigated in 61 patients. Mean duration of reflux disease and preceding H2-antagonist treatment were 4.3 years and 15 months, respectively. Healing rates at 4, 8 and 12 weeks were 48%, 80% and 92%, respectively. There was a correlation between severity of oesophagitis and duration of omeprazole therapy necessary for healing. Three patients (5%) required higher dosages than 40 mg for healing. Symptomatic responses paralleled healing. It is concluded that omeprazole is a highly effective drug for severe reflux oesophagitis not responding to H2-blocker treatment and that 40 mg daily is the optimal dose.

Adolescent↗

Hyperandrogenemia as a cause of primary infertility.

A total of 205 female infertility patients were investigated for hormonal causes of infertility after other factors such as tubal dysfunction or andrologic disorders had been ruled out. Increased androgen serum levels were found in 72/205 (35.1%) of females. In 28/205 (13.7%), elevated prolactin serum levels were noted. 119/205 (58%) of patients suffered from primary infertility versus 86/205 (42%) with secondary infertility. The incidence of hyperandrogenemia was higher in the primary infertility group (p less than 0.0015). No differences relative to hyperprolactinemia were noted between the two groups. Computerized tomography and sonographic methods did not reveal tumors in any of the subjects where serum concentrations of testosterone and dehydroepiandrosterone sulfate were greater than 2 ng/ml and 7 micrograms/ml, respectively. Present data combine to suggest that the determination of androgen serum levels is of major importance when investigating infertile patients.

Adolescent↗

Intraocular pressures during high-flux hemodialysis.

The intraocular pressures of 16 patients with end stage renal failure treated with high-flux dialysis were measured before and during a high-flux dialysis treatment. The patients were selected so as not to have glaucoma or history of glaucoma. Intraocular pressures did not change significantly in any patients during or following a high-flux hemodialysis treatment. These data suggest that high-flux hemodialysis does not result in increases in intraocular pressure nor does it precipitate acute glaucoma in well-dialyzed patients undergoing intermittent in-center hemodialysis.

Adult↗