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Biomedical subjects

H Kunz

Publications and source records attributed to H Kunz.

At least 37 records · Page 2Linked to original sources

Synthesis of beta-D-mannosides from beta-D-glucosides via an intramolecular SN2 reaction at C-2.

The selective synthesis of beta-D-mannosides was achieved by first synthesizing beta-D-glucosides that carry a N-phenylcarbamoyl protecting group at O-3. These derivatives were transformed into the corresponding beta-D-mannosides by intramolecular nucleophilic substitution with inversion of configuration at C-2, the O-trifyl group being the leaving group. Subsequent intramolecular attack of the neighboring carbamoyl group resulted in the formation of the 2,3-carbonate of the desired beta-D-mannoside.

Carbohydrate Sequence↗

Evidence that the fate of class II-disparate corneal grafts is determined by the timing of class II expression.

While the immune privilege nature of the eye affords significant protection to corneal grafts, immunologic rejection is the leading cause of graft failure. Class II antigens are normally absent or expressed at very low levels in normal cornea. The role that class II antigens play in causing graft rejection is particularly interesting. Class II molecules are present on many cells of the immune system, and therefore are important in modulating and mediating immune reactions. The absence of class II bearing cells in the cornea leads to the interesting issue of whether or not those antigens can induce immune rejection of a corneal graft. In the current study we have made use of a pair of congenic rat strains that differ only at class II loci to determine the impact of these antigens on corneal graft survival. Central corneal grafts were not rejected. Recipients preimmunized with skin grafts rejected 100% of the class II disparate corneas with a median survival time (MST) of 15.5 days. When class II disparate Langerhans-cell-containing (LC+) corneas were grafted, the corneas were not rejected, but they immunized the recipients as evidenced by the rejection of a second corneal graft on the contralateral eye. Immunofluorescent stains demonstrated transient expression of class II antigens on graft epithelium after transplantation. This temporary appearance of class II provides a target for rejection in the preimmunized animals but is of insufficient duration to both prime naive animals and provide a target for antigraft effectors.

Animals↗

New enzymatic protecting group techniques for the construction of peptides and glycopeptides.

The use of non-proteases for the selective removal of protecting groups from peptides and glycopeptides is described. The N-terminal deprotection of peptides can be achieved by the hydrolysis of the phenylacetyl (PhAc) amide blocking group catalyzed by penicillin G acylase. On the other hand, the lipase-mediated hydrolysis of n-heptyl (Hep) and 2-bromoethyl esters allows for the liberation of the C-terminal carboxy group. The selective C-terminal deprotection can be applied advantageously for the construction of acid- and base-sensitive polyfunctional O-glycopeptides. In all cases the enzymatic reactions are completely selective and proceed under mildest conditions (pH 7-8, r.t. to 37 degrees C) without damaging the various other functionalities present in the complex substrates.

Amino Acid Sequence↗

Synthesis of glycopeptides with the TN and T antigen structures, and their coupling to bovine serum albumin.

Glycopeptides with TN and T antigen structures that represent the N-terminal tripeptide of asialoglycophorin with blood-group M specificity have been synthesized using fluorenylmethoxycarbonyl (Fmoc) and 2-pyridylethoxycarbonyl (Pyoc) groups for amino protection and the benzyl ester as the carboxyl-blocking function. The Fmoc and the Pyoc groups could be removed by treatment with the weak base morpholine under conditions where the base-sensitive O-glycosyl-serine and -threonine linkages were stable. Ester groups were removed from the carbohydrate moieties with methanolic hydrazine, to give the TN and T antigen glycopeptides which were coupled to bovine serum albumin (BSA) via a carbodi-imide procedure and without any spacer groups. The resulting conjugates contained an average of greater than 20 glycopeptides per protein molecule. They are not microheterogeneous in the carbohydrate part as is commonly found for glycoproteins isolated from biological sources.

Antigens, Neoplasm↗

Synthesis of 2-acetamido-2-deoxyglucosylasparagine glyco-tripeptides and -pentapeptides by selective C- and N-terminal elongation of the peptide chain.

The synthesis of protected 2-acetamido-2-deoxyglucosylasparagine glycopeptides, using the allyl ester as the C-terminal protecting group, their deprotection, and some possible applications of these glycopeptides for the synthesis of modified silica gels and the construction of liposomes are described. The selective carboxyl deblocking is achieved under neutral conditions by rhodium(I)-catalyzed isomerization of the allyl group followed by hydrolysis of the resulting propenyl ester. The tert-butoxycarbonyl group can be cleaved selectively in the presence of the allyl ester with hydrogen chloride in ether. The allyl ester and the acetates can be removed simultaneously with ammonia in methanol. This method opens up a preparative route to glycopeptide model structures of biological interest.

Amides↗

Synthetic tumor-associated glycopeptide antigens.

Glycopeptides with TN antigen (GalNAc)Ser/Thr and T-antigen structures (beta Gall-3GalNAc)Ser/Thr, described as tumor-associated antigens, were synthesized and coupled to bovine serum albumin. Alternatively, synthetic methods for the construction of beta-anomeric analogues of the TN and T-antigen glycopeptides were developed, aiming at antigenic structures having a varied stereochemistry of the linkage between the carbohydrate and the peptide moiety. As a further type of potential tumor-associated antigen, fucosyl-chitobiose asparagine glycopeptides were synthesized, deprotected, and coupled to bovine serum albumin. The chemical methods developed now make the complex sensitive glycoprotein partial structures accessible in analytically pure form and in preparative amounts.

Amino Acid Sequence↗

Prophylactic treatment of acute gastroduodenal stress ulceration. Low-dose antacid treatment without and with additional ranitidine.

Low-dose antacid treatment without and with additional ranitidine in the prevention of acute gastroduodenal stress ulceration in high-risk patients was compared in a randomized, double-blind clinical trial with endoscopic examination of the upper gastrointestinal tract before entry and after the 7-day study period. Of 67 patients who entered the study, 56 could be evaluated. Only one patient, allocated to antacid and placebo, had massive acute upper gastrointestinal bleeding, arising from a gastric ulcer. Although gastric intraluminal pH was better controlled with additional ranitidine treatment, the occurrence of mucosal lesions did not depend on the assigned treatment. We conclude that there is no significant difference between the two regimens in terms of endoscopically visible lesions and clinical outcome.

Acute Disease↗

Assessment of leukocyte alkaline phosphatase by image analysis.

We have shown that it is possible to automate the assessment of leukocyte alkaline phosphatase by using an azo dye cytochemical staining procedure and a commercial, highly sophisticated image analysis instrument originally designed specifically as a differential white cell counter. The data to date indicate that values obtained by this approach are at least as precise and accurate as current manual techniques. Instrumental analysis avoids the subjectivity associated with manual interpretation of staining intensity and should permit meaningful interlaboratory comparisons. The stability of the stained smears upon exposure to immersion oil or Polymount mounting medium proved to be an unexpected bonus. In addition to such functional data on leukocytes as illustrated by this report, these instruments, with appropriate staining methods and software, can also provide clinically useful quantitative data on red cells, as have been described for reticulocytes. We hope to see more clinical applications in the future for these expensive and target-oriented image analysis instruments. They are capable of automatically providing objective quantitative information on a cell by cell basis--providing feature data that cannot be obtained by other means.

Alkaline Phosphatase↗

Cinematographical analysis of javelin throwing techniques of decathletes.

Th purpose of this study was to analyse by correlational methods the biomechanical factors involved in achieving the maximal distance thrown in the javelin event. Twelve Swiss decathletes and two world class javelin specialists were filmed by a high speed (102 fps) 16 mm camera throwing a total of 20 trials. The co-ordinates of the resulting cyclograms were processed by a computer programme and the results submitted to correlational analysis. The highest correlation was 0.76 between velocity at release and distance thrown. Other negative correlations were found between distance thrown and angle of the javelin with the horizontal (0.52) and distance thrown and throwing hand to contralateral foot distance during the last strides (0.67). Javelin specialists, who had longer throws than decathletes (mean = 79.03 m versus 54.29 m), had a smaller difference between the angle of attack and angle of release. The results suggest that in order to attain maximal distance thrown the javelin thrower should achieve positive acceleration during the running approach, effective thrusting with th right leg on the penultimate stride and carry the javelin during the last strides at the optimal angle of release (32 to 36 degrees).

Adult↗

Genetics of natural resistance to thermal injury.

The possible influence of genetic factors in conditioning the host's natural resistance to the lethal effects of severe thermal injury has been studied in 908 rats of comparable age and weight, originating from two outbred, eight inbred, and two congenic strains of animals of defined genetic background. Each animal was exposed to a standard, full-thickness, 40% body surface area skin burn by controlled contact with a heated metal plate. The 21-day postburn mortality was 100% in 217 Fisher (F-344) and 97 ACI male and female rats. The mortality was reduced to 49-63% in an intermediate group of 84 Lewis, 98 Wistar, 48 Sprague-Dawley, 96 Wistar-Furth (WF), and 48 Osborne-Mendel (OM) male rats; 48 female OM rats had a mortality of 86% at 21 days after injury. The same injury produced a mortality in 4% in 90 Buffalo (BUF) and 22% in 41 Brown-Norwegian (BN) males, while females of the same strains exhibited a 21-day mortality of 23% and 54%, respectively. Further studies of the effects of similar injury in two congenic strains of rats derived from some of the inbred lines of animals listed above yielded a 21-day mortality of 50% in 18 BN.1B(BUF) and 20% in 15 BN.1U(WF) male rats, and 65% and 36%, respectively, in females of the same lines. These data point to the importance of genetic factors as a key determinant of host resistance or susceptibility to the effects of severe thermal injury. The segregation of responses to thermal injury in inbred rats into susceptible, intermediate, and resistant groups on the basis of strain origin indicates that such natural resistance may be a quantitative trait. One of the genetic components affecting host resistance is sex-linked. The existence of genetically controlled variations in natural resistance to trauma may be an important determinant of survival and may be a source of guidelines for the triage and clinical care of injured patients. It may also be an important selective factor in evolution.

Animals↗

Biomechanical analysis of sprinting: decathletes versus champions.

The purpose of this study was to compare some biomechanical variables of decathletes and world class sprinters while running the 100 metre race. Sixteen Swiss national decathletes and three world class American sprinters were filmed by a 16 mm Locam (100 fps) camera at the 70 m mark of the race. The co-ordinates for a 26-point stick figure were digitised and then submitted to analysis by a computer programme which produced quantitative data for 12 biomechanical variables. The data indicated that world-class sprinters differed from decathletes in running the 100 m dash by having (1) an optimal combination of a larger stride length and higher stride frequency (2) a smaller thigh angle at contact which shortens the contact time (3) a larger stride landing angle (4) a greater average acceleration of the thigh angle was (5) a larger trunk angle which contributes to a larger trunk/thigh angle. Although other factors such as culture, training, physique and racial differences may influence differences in performance between American world-class sprinters and Swiss decathletes, these data do indicate that biomechanical variables may contribute to differences in 100 m dash performance.

Biomechanical Phenomena↗

[Frequent cases of agranulocytosis due to clozapin (leponex) in eastern Switzerland].

Two personally observed cases of severe agranulocytosis within 3 months, one of them fatal, could be attributed to the new dibenzodiazepine derivative Clozapine (Leponex). Clozapine, a very effective neuroleptic for the treatment of acute and chronic schizophrenia, has been found before to induce agranulocytosis of the metabolic type, as phenothiazines are known to do. An inquiry in al Swiss medical departments and mental hospitals revealed a total of 20 cases of Clozapine induced agranulocytosis in some 50% of institutions responding. 9 of these were observed in Eastern Switzerland. This time-space clustering recalls the "finnish epidemic" of 1975 in Southern Finland. Possible explanations for this phenomenon are discussed. Calculations of the incidence suggest a higher rate of agranulocytosis induced by Clozapine than has been assumed for the phenothiazines. Clozapine should therefore be restricted to schizophrenic patients and initially (6 weeks) be given only on a stationary basis under regular blood controls.

Adult↗