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Biomedical subjects

D Hardy

Publications and source records attributed to D Hardy.

At least 91 records · Page 5Linked to original sources
PubMed1986

In vitro and in vivo evaluation of A-56268 (TE-031), a new macrolide.

The in vitro and in vivo antibacterial activity of A-56268 (TE-031), the 6-O-methyl derivative of erythromycin, was compared with those of erythromycin and other reference drugs. A-56268 had the same spectrum of antibacterial activity as erythromycin. A-56268 was generally 1 log2 dilution more potent or equal to erythromycin against all organisms except haemophilus influenzae and Propionibacterium acnes, for which A-56268 was 1 log2 dilution and 3 log2 dilutions, respectively, less potent. The MBC of A-56268 and erythromycin was not significantly different from the MIC against Streptococcus pyogenes, Streptococcus pneumoniae, Staphylococcus epidermidis, and H. influenzae but was more than 2 log2 dilutions higher than the MICs for some Staphylococcus aureus strains. Human serum at a concentration of 50% did not change the in vitro potency of A-56268 or erythromycin. A-56268 was similar to erythromycin in being more active at pH 8.0 than at the physiologic pH of 7.3. The activity of A-56268 was synergistic with sulfamethoxazole against 4 of 12 strains of H. influenzae. In mouse protection tests, when administered orally A-56268 was more potent than erythromycin against H. influenzae, S. pyogenes, S. pneumoniae, and S. aureus. After subcutaneous administration the potencies of A-56268 and erythromycin were not statistically different from each other. A-56268 was more potent than erythromycin against Legionella infection in guinea pigs. The concentration of A-56268 in the serum and lung was higher than that of erythromycin after intraperitoneal administration. In A-56268 in the serum and lung was higher than that of erythromycin after intraperitoneal administration. In mice, the peak levels in serum of A-56268 and erythromycin were similar after subcutaneous administration and seven times higher for A-56268 after oral administration. The serum half-life of A-56268 was approximately twice that of erythromycin after administration by both routes.

Administration, Oral↗
PubMed1985

pH and protease control of acrosomal content stasis and release during the guinea pig sperm acrosome reaction.

The purpose of this study was to examine how trypsin inhibitors affect the guinea pig sperm acrosome reaction in vitro. Using spermatozoa pretreated with lysophosphatidyl choline, we found that both naturally occurring high molecular weight and the smaller synthetic trypsin inhibitor p-aminobenzamidine (PAB) delayed the onset of the acrosome reaction as monitored by light microscopy. Examination with electron microscopy revealed that acrosomal matrix dispersal rather than membrane fusion was affected. Despite the morphologic delay in acrosomal content release, PAB unexpectedly permitted 96% of soluble acrosomal antigen to be released into the supernatant. In addition, total acrosin release in the presence of PAB was 74% of control, with the vast majority as latent rather than active enzyme. A morphologically intact but membrane-free target of acrosomal matrix (AM), which is sensitive to trypsin inhibitor, was partially purified using Triton-x-100 at pH 5.2. AM remained morphologically stable at pH 5.2; however, shift up to pH 7 resulted in rapid dissolution within several minutes as monitored by light and electron microscopy and light scattering. Trypsin inhibitor prevented dispersion of AM at pH 7. The results suggest that, during the acrosome reaction, one distinct region of the acrosomal contents disperses after membrane vesiculation in a pH and trypsin inhibitor-insensitive fashion while a pH sensitive trypsin-like activity (acrosin?) disperses another discrete region of acrosomal matrix.

Acrosin↗
PubMed1982

Bullous pemphigoid and ulcerative colitis.

A 21-year-old white woman, who had ulcerative colitis for 14 years, developed generalized severe bullous pemphigoid. Following the resection of her colon, her skin showed marked clinical improvement, but this was only temporary. Direct immunofluorescence was performed on the surgical specimen and no antibodies (BMZ) to colonic mucosal cells were evident. Anti-basement membrane zone antibodies were found on direct and indirect immunofluorescent studies and have persisted. Sera from 15 patients with ulcerative colitis and 11 patients with Crohn's disease, evaluated for the presence of an anti-basement membrane zone antibody did not contain any demonstrable levels of anti-BMZ antibodies. The co-existence of ulcerative colitis and bullous pemphigoid is more likely incidental rather than etiopathologic.

Adult↗
PubMed1977

Pterin-6-aldehyde, a cancer cell catabolite: identification and application in diagnosis and treatment of human cancer.

Active folic acid degradation with the formation pterin-6-aldehyde is a previously undescribed characteristic of cancer cells in tissue culture. Neither normal adult epithelial and fibroblastic cells nor human amniotic cells nor mouse embryonic fibroblasts degrade folic acid to a measurable degree. Twenty-nine patients whose diagnoses were not revealed until after the test of their first morning urine for pterin-6-aldehyde was completed were studied for the presence or absence of pterin-6-aldehyde by thin-layer chromatography. Pterin-6-aldehyde was found in the urine at about 300 nmol/ml or greater only in those 13 patients with a tissue diagnosis of cancer. When the cancer was totally resected, the pterin-6-aldehyde was no longer found in the urine postoperatively. Pterin-6-aldehyde is not found in the urine of healthy patients at this level of detection unless their diets are supplemented with folic acid.

Adolescent↗
PubMed1977

Rapid detection of microbial contamination in frozen vegetables by automated impedance measurements.

Automated impedance measurements can be used to rapidly assess whether a sample of frozen vegetables contains greater or less than 10(5) organisms per g. Microorganisms growing pureed food samples cause a change in the impedance of the medium when the organisms reach a threshold concentration of between 10(6) and 10(7) organisms per ml. Estimates of the concentration of microorganisms initially present in the food sample can be made by recording the time required for the organisms in the sample to replicate to threshold levels. In this study, the detection times for 357 samples of frozen vegetables were compared with standard plate counts for each sample. The agreement between the two methods in distinguishing samples containing more than 10(5) organisms per g was 92.6% for 257 assorted frozen vegetables and somewhat higher (93 to 96%) when separate cutoff times were used for each type of vegetable. The time required for analysis was about 5 h, compared to the 48 to 72 h required for standard plate counts.

Bacteria↗
PubMed1977

Involvement of T cells in the recall of Salmonella-induced resistance to tumour.

Immunization of mice with Salmonella enteritidis 11RX (11RX) induces resistance to tumour growth in these animals. The degree and duration of resistance is dependent on the routes used for immunization and tumour challenge. When resistance to tumour growth has declined, it can be recalled using various 11RX antigen preparations. In the present study we have shown that the ability to recall resistance to i.p. challenge with 131I-labelled Ehrlich ascites tumour cells could be transferred to normal mice by i.p. injection of an antigen preparation of 11RX mixed with spleen cells from 11RX-immunized mice. The active cells in this test were apparently sensitized T cells, since spleen cells from normal mice were not effective and the activity of immune spleen cells could be markedly reduced by removing theta antigen-bearing cells but not by removing glass-adherent cells. The induction of in vivo cytotoxicity appeared to depend on the involvement of radiation-sensitive cells derived from the non-immunized recipients, since recall of resistance to tumour challenge was reduced when irradiated mice were used as recipients of spleen cells from immunized mice.

Animals↗
PubMed1976

Resistance of mice to Krebs ascites tumour, sarcoma S180 and PC6 plasmacytoma after immunisation with Salmonella enteritidis 11RX.

Resistance to Krebs ascites tumour, sarcoma S180 (ascitic form) and PC6 plasmacytoma can be induced with prior immunisation with live Salmonella enteritidis 11RX. One thousand to ten thousand more tumour cells are needed to give an LD50 after immunisation. Resistance to PC6 could be recalled 137 days after intravenous immunisation with 11RX protein antigen intraperitoneally as measured by prolonged survival or monitoring the death of 5[131I]-iodo-2'-deoxyuridine labelled tumour cells in vivo. The range of tumours to which resistance can be produced by 11RX immunisation suggests that the mechanism of resistance does not involve antigens common to the tumours and Salmonella enteritidis 11RX.

Animals↗
PubMed1976

Local and systemic effects in the non-specific tumour resistance induced by attenuated Salmonella enteritidis 11RX in mice.

Suppression of growth of a number of different murine tumours, injected subcutaneously or into the foot pad, was induced by prior intraperitoneal or intravenous immunisation with Salmonella enteritidis 11RX. The effect of immunisation on tumour growth was relatively minor, but could be enhanced by addition of 11RX antigen preparations to the suspensions of tumour cells used for challenge. The significance of these findings is discussed.

Animals↗