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Biomedical subjects

M J Kramer

Publications and source records attributed to M J Kramer.

At least 19 recordsLinked to original sources
PubMed1998

Anhydrolide macrolides. 2. Synthesis and antibacterial activity of 2,3-anhydro-6-O-methyl 11,12-carbazate erythromycin A analogues.

A series of 3-descladinosyl-2,3-anhydro-6-O-methylerythromycin A 11, 12-cyclic carbazate analogues was prepared and evaluated for antibacterial activity. These 2,3-anhydro macrolides were found to be potent antibacterial agents in vitro against macrolide-susceptible organisms including Staphylococcus aureus 6538P, Streptococcus pyogenes EES61, and Streptococcuspneumoniae ATCC6303. These compounds were also very active against some organisms that show macrolide resistance (S. aureus A5177, S. pyogenes PIU2584, and S. pneumoniae 5649). The compounds generally showed poor activity against organisms with constitutive MLS resistance. Selected compounds were evaluated in vivo in mouse protection studies. Although most of the compounds tested in vivo showed poor efficacy, two compounds, 38 and 57, were more active than clarithromycin against S. pneumoniae ATCC6303.

Animals↗
PubMed1987

Damage and repair of lung connective tissue in rats exposed to toxic levels of oxygen.

We studied damage and repair of lung connective tissue in rats exposed to toxic amounts of oxygen by measuring lung content of collagen and elastin and the number of collagen fragments in lung lavage fluid after exposure to 98% O2 for 60 h. Lung collagen was decreased 17%, and collagen fragments in lavage fluid were increased 4- to 5-fold in O2-exposed rats compared with those in control rats. No biochemical evidence of elastin degradation was found. Mild emphysematous changes and a leftward shift of fluid-filled, pressure-volume curves were induced within 2 wk after recovery from exposure to O2. Administration of the lathyrogen beta-aminopropionitrile worsened the emphysematous lesion produced by hyperoxia, suggesting that replacement of connective tissue during repair limits the extent of emphysema. We conclude that lung collagen is degraded and an emphysematous lesion is produced by relatively short exposure to toxic amounts of oxygen.

Aging↗
PubMed1984

Pulmonary deposition and clearance of aerosolized interferon.

Small particle aerosols of a hybrid DNA recombinant human alpha interferon, A/D bgl, and a related DNA recombinant leukocyte interferon, A, were generated and delivered to mice for 23.5 h a day for 4 consecutive days. The antiviral activity of these interferons in delivery reservoirs, in the aerosols generated, and in the lungs of test mice was monitored during and after aerosol administration in cytopathic effect inhibition assays, using vesicular stomatitis virus as the indicator virus. In addition, the activity of these interferons in primary mouse embryo cells against influenza A/HK/68 (H3N2) virus was determined. The results obtained indicated that the interferon particles generated in the continuous aerosol therapy system used in these studies remained biologically active and could be readily detected in both aerosol mists and lungs of test mice; levels of exogenous interferon in the lungs equalled or exceeded levels of interferons produced endogenously during experimentally induced influenza virus infection. Titers of the exogenously administered interferons decreased gradually and disappeared from the lungs between 24 and 48 h after cessation of aerosolization. Recombinant human alpha interferon A/D, but not recombinant leukocyte alpha interferon A, significantly inhibited replication of A/HK/68 virus in primary mouse embryo cells in the in vitro studies.

Aerosols↗
PubMed1983

Morphologic changes produced by amdinocillin alone and in combination with beta-lactam antibiotics: in vitro and in vivo.

Scanning electron microscopy was used to study the morphologic effects of amdinocillin (mecillinam) when combined with several beta-lactam antibiotics in vitro (Escherichia coli, three isolates; Klebsiella pneumoniae, one isolate) and also in vivo (E. coli, one isolate). Ovoid forms were found in the cultures of E. coli and K. pneumoniae following in vitro exposure to amdinocillin. This characteristic in vitro effect was also produced in the amdinocillin-treated E. coli-infected mouse. Varying degrees of filament formation were seen both in vitro and in vivo with the other beta-lactam antibiotics tested. The in vitro combination of amdinocillin with the beta-lactam antibiotics produced morphologic effects on E. coli and K. pneumoniae (enhanced cell distortion and lysis) not seen with the individual agents at the doses tested. Amdinocillin was synergistic with ampicillin, carbenicillin, and cephalothin in mice challenged with E. coli 736; scanning electron microscopy of bacteria from peritoneal lavages of mice treated with these synergistic combinations indicated that the organisms were more enlarged and distorted than those from animals receiving the individual agents. The enhanced morphologic effect observed in vivo was in agreement with the in vitro effect. Viable counts of bacteria recovered from mice treated with ampicillin plus amdinocillin were appreciably less than those from mice treated with each agent alone. The morphologic results from the scanning electron microscopy study point to a synergistic or enhanced effect of amdinocillin in combination with beta-lactam antibiotics and are in accord with prior reports of the synergistic effects of amdinocillin.

Amdinocillin↗
PubMed1983

Antibodies to human leucocyte interferons in cancer patients.

During the course of clinical investigation of partly purified human leucocyte interferon (IFN) prepared at the Finnish Red Cross (PIF), neutralising IgG antibodies to human leucocyte IFN were detected in the sera of 3 patients with cancer. In 2 of these patients, the antibodies were detected in serum before treatment with PIF. In the third patient antibodies developed during the course of treatment. Antibody titres against six recombinant human leucocyte IFN sub-types and one recombinant hybrid human leucocyte IFN were different in the 3 patients.

Antibodies↗
PubMed1983

Cell and virus sensitivity studies with recombinant human alpha interferons.

The cell sensitivity of recombinant human alpha interferons (rIFN-alpha) of greater than 95% purity (A,D and the hybrid A/D) and crude nature (B and F) was studied in human (WISH, HeLa, AG1732), bovine (MDBK, BT), monkey (Vero), mouse (L), rabbit (RK-13), and hamster (BHK-21) cells. Based on an activity of 100% in WISH cells, the other cells responded to rIFN-alpha A as follows: AG1732 (90%), HeLa (94%), and MDBK and BT cells (170-190%). Rabbit, mouse, and hamster cells had a relative sensitivity of less than 1%. rIFN-alpha B and F were essentially equivalent to rIFN-alpha A in terms of cell sensitivity, but MDBK and BT cells were about 20 times more sensitive to rIFN-alpha D than were WISH cells and rIFN-alpha D was 1/5 to 1/10 as active on L cells as on WISH cells. The activity of the hybrid IFN A/D on bovine, mouse, and human cells was similar. The inhibitory dose50 (U/ml) of rIFN-alpha A, B, D, and F against virus infections in WISH cells were: vesicular stomatitis virus (1-4), rhinovirus types 1 and 42 (2-18), and herpes simplex virus (HSV) type 2 (45-70). Type 1 HSV, Semliki Forest (SFV) and encephalomyocarditis (EMC) viruses were tested against only rIFN-alpha A and D where SFV and EMC were the most sensitive to both IFNs (ID50-SFV, 0.2 U/ml, EMC, 1.2 U/ml) while 13 U/ml of rIFN-alpha A and D inhibited Type 1 HSV. The various rIFN-alpha s did not exhibit different antiviral spectra in vitro. When tested in mice rIFN-alpha A did not protect against infections with SFV, EMC, HSV, or influenza viruses. rIFN-alpha D and A/D protected mice infected with EMC, SFV, or HSV.

Animals↗
PubMed1983

In vivo antiviral activity of recombinant type alpha interferon A in monkeys with infections due to simian varicella virus.

Recombinant type alpha interferon A (rIFN-alpha-A) administered to African green monkeys (Cercopithecus aethiops) intramuscularly in a dose of 3 X 10(6) units/kg of body weight resulted in substantial blood levels of interferon. Peak levels of greater than 1,000 units/ml of serum appeared at 1 and 2 hr after inoculation and interferon was detectable for as long as 12 hr after inoculation. Injection of rIFN-alpha-A at a dose of 10(6) units/kg twice daily for eight days effectively inhibited simian varicella virus infection of the African green monkey. Antiviral activity was demonstrated in monkeys with prophylactic treatment begun 4 hr prior to virus inoculation or with therapeutic treatment deferred until 44 hr after virus inoculation. No adverse effects of treatment were observed.

Animals↗
PubMed1980

Fluorinated pyrimidine nucleosides. 4. Synthesis and antitumor testing of a series of 2',5'-dideoxy- and 2',3',5'-trideoxynucleosides of 5-fluorouracil.

Dideoxy- and trideoxynucleosides of 5-fluorouracil have been synthesized for antitumor evaluation. 2',5'-Dideoxy-5-fluorouridine (3) was prepared from 2'-deoxy-5-fluorouridine (1) by iodination using methyltriphenoxyphosponium iodide, followed by catalytic reduction. 1-(2',5'-Dideoxy-beta-D-threo-pentofuranosyl)5-fluorouracil (4) was prepared from 3 by mesylation, followed by alkaline hydrolysis. 2',3',5'-Trideoxy-5-fluorouridine (13), a methyl homologue of Ftorafur (17), was synthesized by two routes: Treatment of the 3'-mesylate 8 with potassium tert-butoxide yielded the 2',3'-unsaturated derivative 12, which on hydrogenation yielded 13. Alternatively, treatment of 1 with a large excess of methyltriphenoxyphosphonium iodide produced several products, including two 3'-epimeric diiodo compounds (14 and 15), each of which could be hydrogenated to 13. The major product from this iodination reaction was characterized 3-(2',3'-anhydro-2',5'-dideoxy-5'-iodo-beta-D-threo-pentofuranosyl)-5-fluorouracil (5), presumably produced by rearrangement of the corresponding 1-isomer 9. The dideoxy compounds 3 and 4, as well as the trideoxy compound 13, were tested against sarcoma 180 in mice in comparison with 5-flourouracil, FUDR (1), and Ftorafur (17).

Animals↗
PubMed1979

Synthesis of arabinofuranosyl derivatives of 3-deazaguanine.

Synthesis of four arabinofuranosyl derivatives of the antitumor agent 3-deazaguanine is described. By the use of 13C and 1H nuclear magnetic resonance spectroscopy, the structures of these nucleosides were established to be alpha and beta pairs of N-7 and N-9 arabinosides of 3-deazaguanine. In contrast to 3-deazaguanine and its ribosyl derivative, the nucleosides described in this paper were found to be inactive against Sarcoma 180 in mice at 100 mg/kg.

Animals↗
PubMed1979

Adamantylthiourea derivatives as antiviral agents.

A series of nine 3-substituted 1-adamantylthioureas was prepared and tested for antiviral activity against influenza A2/Asian/J305 virus in vivo and in vitro. Protective dose 50 values were calculated for three of the compounds. One of these compounds, 7, has antiviral activity which compares favorably with that of amantadine.

Adamantane↗
PubMed1979

Activity of oral amoxicillin, ampicillin, and oxytetracycline against infection with chlamydia trachomatis in mice.

The effects in mice of oral treatment with amoxicillin, ampicillin, and oxytetracycline against an otherwise lethal intranasal infection with Chlamydia trachomatis (mouse pneumonitis) were studied. When treatment was started 30 min after infection and continued once daily thereafter for a total of seven treatments, the mean protective doses of amoxicillin, ampicillin, and oxytetracycline were 9.5, greater than 50, and 31.3 mg/kg, respectively. If 14 oral treatments were given, these values were 1.6 mg/kg for amoxicillin, 12.7 mg/kg for ampicillin, and 12.3 mg/kg for oxytetracycline.

Administration, Oral↗
PubMed1979

Correlation by scanning electron microscopy of in vitro and in vivo effects of amoxicillin and ampicillin on the morphology of Escherichia coli.

The effect of in vitro incubation with subinhibitory and inhibitory doses of amoxicillin or ampicillin on the morphology of E. coli 257 was evaluated by scanning electron microscopy (SEM). No effect, with either penicillin was seen at 1/16 X MIC (0.39 microgram/ml). Filament formation was the major effect seen with both agents at 1/8, 1/4 and 1/2 X MIC but only with ampicillin at the MIC (6.25 microgram/ml). Cells incubated with amoxicillin at the MIC were primarily short rods with bulbous swellings. This morphological difference between the two antibiotics was dose-related since ampicillin, at 2 X MIC, also caused the formation of short rods with bulbous swellings. SEM examination of omentum from amoxicillin and ampicillin treated mice 2 h after infection with E. coli 257 indicated a correlation of morphological effects seen in vitro and in vivo with the respective antibiotics. For example, following a single subcutaneous treatment with amoxicillin and ampicillin at 250 mg/kg, the plasma concentrations 2 h later (the time of infection) were 8.2 and 7.7 microgram/ml respectively but short rods with bulbous swellings were seen in amoxicillin-treated mice whereas filaments were found in the ampicillin-treated mice.

Amoxicillin↗