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Biomedical subjects

S Hudson

Publications and source records attributed to S Hudson.

At least 73 records · Page 4Linked to original sources
PubMed1991

Response of dairy cows to high doses of a sustained-release bovine somatotropin administered during two lactations. 1. Production response.

This study evaluated the effect of sometribove (zinc methionyl bST) in a sustained-release formulation administered to lactating cows at concentrations up to 3.0 g every 14 d over two lactations. Eighty-two lactating Holstein cows in their first, second, or third lactation were assigned to the study. Cows received .6, 1.8, or 3.0 g of bST in one, three, or five intramuscular injections of a unit dose (.6 g) every 2 wk. Controls received five injections of the vehicle (equivalent volume to the 3.0-g treatment) every 2 wk. Injections were administered from 60 +/- 3 d postpartum until dry-off or necropsy. Thirty-eight animals were continued on treatment for a second consecutive lactation. During the 1st yr of treatment, bST increased mean 3.5% FCM by 7.2, 9.4, and 8.4 kg/d over control production (21.1 kg/d). During the 2nd yr, milk response to .6, 1.8, and 3.0 g of bST averaged 10.6, 3.6, and 4.9 kg/d over controls (24.8 kg/d). The incidence of clinical mastitis increased in the 3.0-g group relative to controls during the 2nd yr. Thus, salable FCM averaged 8.1, 9.1, and 6.2 kg/d above controls (yr 1) and 12.1, 4.7, and -2.8 kg/d (yr 2) for the .6-, 1.8-, and 3.0-g groups. Salable FCM was unaffected by mastitis at a proposed commercial dose (.6 g). Milk fat, protein, lactose, calcium, phosphorus, zinc, magnesium, and ash concentrations were unaffected by bST treatment. Calculated energy, calcium, phosphorus, and protein balances also were unaffected except for early decreases of up to 5 Mcal/d, and 40, 20, and 600 g/d, respectively, until feed intake increased. Milk serum bST concentrations greater than the assay limit of sensitivity (1 ng/ml) were routinely measurable only at doses of 1.8 and 3.0 g. Results confirmed that bST concentrations in milk serum are exceedingly small. Overall, supraphysiological doses of sometribove increased milk production with little effect on composition. No toxic effects of bST were observed.

Animals↗
PubMed1990

Human astrocytes proliferate in response to tumor necrosis factor alpha.

Two different human astrocytic cell lines derived from adult epilepsy surgical specimens were exposed in vitro to concentrations of 1-100 ng/ml recombinant tumor necrosis factor alpha (TNF alpha). Results indicated dose-dependent stimulation of DNA synthesis and proliferation. Both of these effects were abrogated by treatment with monoclonal antibody specific for TNF alpha but not by irrelevant murine IgG. Immunocytochemical characterization of TNF alpha-treated and control cultures indicated that greater than 98% of proliferating cells contained cytoplasmic glial fibrillary acidic protein (GFAP), and were therefore astrocytic in nature. These studies demonstrate that growth of adult human non-neoplastic astrocytes is stimulated by TNF alpha, an inflammatory cytokine produced primarily by macrophages but also by astrocytes.

Astrocytes↗
PubMed1990

Effect of acute challenge with an extreme dose of somatotropin in a prolonged-release formulation on milk production and health of dairy cattle.

Eight pregnant Holstein cows were given weekly injections of 15 g of recombinant bST over a 2-wk period for a total dose of 30 g to determine signs of acute toxicity. Cows were monitored intensively throughout the study, and samples were taken for analyses of hormones, metabolites, chemistries, hematology, and urine analytes. Animal health throughout the study was generally excellent. Mean rectal temperatures were significantly higher in treated cows (38.7 vs. 39.2 degrees C). Least squares means for 3.5% FCM production were 15.9 and 23.0 kg/d, and net energy intakes were 29.4 and 26.9 Mcal/d for control and treated cows, respectively. Somatotropin concentrations reached more than 250 ng/ml on d 10 and remained above 200 ng/ml. Insulin and glucose concentrations were also increased but returned toward baseline values. Free fatty acid concentrations were higher in treated cows, but beta-hydroxybutyrate was not affected. Most hematological measurements were unaffected except for a reduction in erythrocyte number in treated cows and decreases in hematocrit and hemoglobin, but values were within clinically normal ranges. Although cows received in 2 wk a dose that was equivalent to the amount administered during more than 2 yr of continuous use, no signs of acute toxicity to bST were observed.

Animals↗
PubMed1990

Exposure to high pressure may produce the 5-HT behavioral syndrome in rats.

In addition to the motor events associated with high pressure neurologic syndrome (HPNS), we have observed behavioral changes that resemble the 5-hydroxytryptamine (5-HT) syndrome in free-moving rats exposed to pressures up to 70 ATA. These include a flat body posture, head weaving, reciprocal forepaw treading, and hyperlocomotion. Such changes occur when brain 5-HT levels are raised or when 5-HT receptors are activated. We have therefore studied the behavior of rats at pressure treated either with saline or with one of the following drugs: p-chlorophenylalanine (pCPA) which depletes brain 5-HT by 85-90%, Wy 27587 which inhibits 5-HT reuptake, 5-hydroxytryptophan (5-HTP) and carbidopa which increase brain 5-HT synthesis, and quipazine which is a 5-HT receptor-agonist. After treatment, rats were individually exposed to pressure, and behavioral scores were made for 5 min every 10 ATA up to 70 ATA by an unbiased observer who was not aware of the treatment given. Analysis of all control rats indicated that only a flat body posture, forepaw treading, and hyperlocomotion were positively correlated with pressure, and these events were used in all subsequent analysis. Rats treated with pCPA with whole brain 5-HT levels reduced by 90% had scores significantly less than controls. Rats treated with Wy 27587 showed significantly increased scores. Rats treated with 5-HTP and quipazine failed to show a significant increase in scores. These results suggest that a modified form of the 5-HT syndrome occurs when rats are exposed to increased pressure, and the behavioral events seen are consistent with some activation of the 5-HT1A receptor subtype.

5-Hydroxytryptophan↗
PubMed1989

Detection of minimal disease in hematopoietic malignancies of the B-cell lineage by using third-complementarity-determining region (CDR-III)-specific probes.

Approximately 80% of hematopoietic malignancies of the B-cell lineage carry only one or two immunoglobulin heavy chain gene rearrangements indicating their clonal origin. These rearrangements due to the recombination of various variable, diversity, and joining regions of the heavy-chain gene segments during B-cell commitment result in a region called complementarity-determining region III (CDR-III). This region, which encompasses the diversity region of the heavy-chain segment, because of extensive somatic mutations, provides a DNA-encoded signature specific for each B-cell clone. CDR-III sequences were obtained from DNA of pre-B-cell acute lymphoblastic leukemia by using suitable primers and the polymerase chain reaction. The sequences were used to generate diagnostic probes that hybridized only to the amplified CDR-III of leukemic cells from which the sequences were derived. With these probes, leukemic cells could be detected when diluted 1:10,000 with other cells. By cloning the amplified CDR-III into recombinant libraries residual leukemic cells were accurately quantitated in bone-marrow samples from repeated relapses and remissions in one case of acute lymphoblastic leukemia. During a clinical remission lasting greater than 7 mo, malignant cells were present in marrow at greater than 1 per 1000 cells. These findings indicate that custom-made diagnostic probes will be useful in accurate quantitation of malignant cells in acute lymphoblastic leukemia patients in clinical remission and will allow investigation of the biological significance of low or high numbers of residual leukemic cells in evolution of that disease.

Alleles↗
PubMed1989

Point mutations in both transforming and non-transforming codons of the N-ras proto-oncogene of Ph+ leukemias.

The distribution and frequency of point mutations in the first and second coding exons of the N-ras proto-oncogene was examined in 6 cases of Philadelphia positive (Ph+) hemopoietic malignancies. To increase the detection sensitivity of the mutations and to estimate more accurately the frequency of abnormal alleles in the hemopoietic cell population, a polymerase chain reaction (PCR)/shotgun cloning/double stranded DNA sequencing method was used. Mutations activating the ras oncogenes involving codon 61 were observed in 5 out of 6 cases; in one of these cases (CML3), mutation at codon 61 involved a two base transition. Mutations involving codon 59 were also observed in one case (CML1). In longitudinal studies of 3 cases of chronic myelogenous leukemia samples obtained at the time of initial diagnosis and 5 to 7 years later, a multiplicity of mutations were detected at the time of initial diagnosis prior to any therapy. In one case (CML3), a mutation in codon 61 detected at diagnosis was still present 5 years later, in a second case (CML1) a mutation in codon 61 appeared during the course of the disease and persisted for at least one year, and in the third case (CML2) a mutation in codon 61 was present at diagnosis but absent 5 years later. In one instance (CML1) a mutation in codon 59 was present at the time of initial diagnosis but was not detectable in later samples. Several other point mutations leading to aminoacid changes were scattered predominately through the second exon but were not consistently detected in longitudinal studies on cells from the same patient. The data suggest that there is considerable genetic instability in the 2nd exon of N-ras in the myeloid leukemias but in every case a small subset of cells contains the mutations and these cells do not have a proliferative advantage.

Adult↗
PubMed1988

A comparison of OKT3 monoclonal antibody and corticosteroids in the treatment of acute renal allograft rejection.

The monoclonal antibody OKT3 (Ortho Pharmaceutical, Raritan, NJ) was utilized in two separate protocols for treatment of acute renal allograft rejection in patients receiving cyclosporine, azathioprine, and prednisone for maintenance immunosuppression. In Group I, 54 patients received steroids for primary treatment of acute rejection with OKT3 used for resistant rejections and second rejection episodes. In Group II, 34 patients received OKT3 as primary treatment of acute rejection while steroids were used for rescue and second rejection episodes. OKT3 successfully reversed 82% of initial acute rejection episodes in Group II as compared with a 63% reversal with steroids in Group I. Rescue treatment was required in only 15% of Group II patients compared with 33% of Group I patients. Overall patient survival was 96% and 94%, respectively, for steroid primary and OKT3 primary treatments. Allograft survival at 3 months was identical, 74% in both groups. Based on allograft survival data, OKT3 is equally effective either as primary treatment for allograft rejection, or for rescue therapy if initial corticosteroid treatment fails.

Acute Disease↗
PubMed1987

Characterization of cDNA clones for human myeloperoxidase: predicted amino acid sequence and evidence for multiple mRNA species.

Myeloperoxidase is a component of the microbicidal network of polymorphonuclear leukocytes. The enzyme is a tetramer consisting of two heavy and two light subunits. A large proportion of humans demonstrate genetic deficiencies in the production of myeloperoxidase. As a first step in analyzing these deficiencies in more detail, we have isolated cDNA clones for myeloperoxidase from an expression library of the HL-60 human promyelocytic leukemia cell line. Two overlapping plasmids (pMP02 and pMP062) were identified as myeloperoxidase cDNA clones based on the detection with myeloperoxidase antiserum of 70 kDa protein expressed in pMP02-containing bacteria and a 75 kDa polypeptide produced by hybridization selection and translation using pMP062 and HL-60 RNA. Formal identification of the clones was made by matching the predicted amino acid sequences with the amino terminal sequences of the heavy and light subunits. Both subunits are encoded by one mRNA in the following order: pre-pro-sequences--light subunit--heavy subunit. The molecular weight of the predicted primary translation product is 83.7 kDa. Northern blots reveal two size classes of hybridizing RNAs (approximately 3.0-3.3 and 3.5-4.0 kilobases) whose expression is restricted to cells of the granulocytic lineage and parallels the changes in enzymatic activity observed during differentiation.

Amino Acid Sequence↗
PubMed1987

Time-resolved fluorescence anisotropy for systems with lifetime and dynamic heterogeneity.

The time dependence of the fluorescence anisotropy expected when a fluorophore exists in distinct environments having different fluorescence decay and motional behavior is illustrated by simulation calculations. A wide range of behavior is observed. The analysis of such decays in terms of the underlying physical parameters is also illustrated and discussed. In particular, the analysis of 'associated' heterogeneous behavior using a homogeneous environment model with complex motional behavior is evaluated. It is argued that anisotropy decays that exhibit a high initial anisotropy and that rise at long times must be due to a heterogeneous environment. Anisotropic rotor diffusion cannot give rise to behavior of this type. A similar conclusion is reached for anisotropies that exhibit downward curvature. On the other hand, anisotropy decays that are monotonically decreasing and have a positive second derivative at all times cannot be analyzed in a unique fashion and therefore an ambiguity exists in the interpretation of such data in terms of motional behavior.

Fluorescence Polarization↗
PubMed1982

Carcinoembryonic antigen in carcinoma of the uterine cervix: antigen distribution in primary and metastatic tumors.

Immunohistochemical staining for carcinoembryonic antigen (CEA) was performed on primary tumors and regional lymph nodes from 100 patients undergoing radical hysterectomies and pelvic lymphadenectomies for invasive carcinoma of the uterine cervix. Antigen staining was present in 82% of keratinizing squamous carcinomas as compared with 50% in nonkeratinizing tumors. Seventeen patients with CEA-producing cervical cancer had regional lymph nodes metastases, all of which stained positively for CEA. Conversely, antigen could not be detected in lymph nodal metastases from primary tumors devoid of CEA. The pattern and intensity of CEA staining in primary tumors and their metastases were similar in all cases. Antigen was present in highest concentrations in the cytoplasm and tumor cell membrane of all tissues examined and isolated nuclear staining was absent. The clinical implications of these findings are discussed.

Adenocarcinoma↗