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Biomedical subjects

D S Martin

Publications and source records attributed to D S Martin.

At least 127 records · Page 7Linked to original sources
PubMed1991

Whole body vascular capacitance response to vasopressin is mediated by autonomic function.

Effects of intravenous infusions of arginine vasopressin (AVP) on whole body vascular capacitance were determined in anesthetized cats when autonomic nervous system function was intact and, in other cats, when reflexes were blocked by the ganglionic blocking agent pentolinium. With the use of the constant cardiac output-reservoir technique, changes in reservoir volume were assumed to reflect reciprocal changes in whole body vascular capacitance. Relationships between the dose of AVP and the plasma concentration of the peptide achieved during infusions were not significantly different in the two groups of animals. Blood pressure responses to AVP were greater, whereas heart rate responses to the peptide were abolished in ganglion-blocked cats. In cats with intact autonomic function, reservoir volume decreased by 1.6, 4.2, and 7.8 ml/kg at AVP doses of 1, 10, and 100 ng.kg-1.min-1, respectively. In contrast, in ganglion-blocked cats, reservoir volume did not change significantly at 1.0 and 10 ng.kg-1.min-1 of AVP, and the highest dose caused a much smaller change in volume (3 ml/kg) than that observed in cats with intact autonomic function (7.8 ml/kg). Systemic compliance was unchanged by AVP in both groups of animals, suggesting that the increases in whole body vascular capacitance were likely due to changes in unstressed volume. The results suggest that reflexively mediated changes in autonomic function increase whole body vascular capacitance during elevations in the circulating levels of AVP to plasma concentrations that are biologically relevant. These findings may explain how AVP decreases cardiac output in animals with an intact autonomic nervous system.

Animals↗
PubMed1991

Cardiovascular responses to bicuculline in the paraventricular nucleus of the rat.

The present study was undertaken to determine whether gamma-aminobutyric acid in the paraventricular nucleus contributes to the regulation of cardiovascular function. Blood pressure and heart rate were recorded and plasma catecholamines were measured in conscious rats receiving microinfusions of either artificial cerebrospinal fluid or a gamma-aminobutyric acid antagonist, bicuculline methiodide, bilaterally into the paraventricular nucleus. Artificial cerebrospinal fluid had no effect on any of the recorded variables. In contrast, infusion of bicuculline into the region of the paraventricular nucleus produced increases in blood pressure (20 +/- 2 mm Hg), heart rate (110 +/- 11 beats/min), and plasma concentrations of norepinephrine (640 +/- 107 pg/ml) and epinephrine (1,266 +/- 267 pg/ml). Pretreatment with a ganglionic blocking agent abolished both the blood pressure (-1 +/- 2 mm Hg) and heart rate (5 +/- 18 beats/min) effects. Bilateral adrenal medullectomy reduced the changes in plasma norepinephrine concentrations (81 +/- 14 pg/ml) significantly and abolished the changes in plasma epinephrine concentrations (5 +/- 4 pg/ml). Conversely, adrenal medullectomy reduced the pressor effects (18 +/- 2 mm Hg) only slightly while the heart rate responses were attenuated (42 +/- 9 beats/min) by approximately 50%. These results suggest that an endogenous gamma-aminobutyric acid system exerts a tonic inhibitory effect on the sympathetic nervous system at the level of the paraventricular nucleus of the hypothalamus.

Adrenal Medulla↗
PubMed1991

Asymptomatic versus symptomatic herniated thoracic discs: their frequency and characteristics as detected by computed tomography after myelography.

We retrospectively reviewed the myelograms of 433 patients and identified those who had no symptoms or signs referable to the thoracic cord, roots, or nerves. By post-myelography computed tomographic scan criteria, our frequency of asymptomatic thoracic herniated discs (ATHDs) was calculated. Post-myelography computed tomographic scans of 68 ATHDs were analyzed. Their imaging characteristics were compared with our own series of 5 symptomatic thoracic herniated discs and symptomatic thoracic herniated discs in the literature. We were unable to identify any imaging features that could reliably classify a disc as an ATHD or a symptomatic thoracic herniated disc. Our results call into question the propriety of prophylactic surgery for ATHDs, even when the lesions are radiographically impressive.

Adult↗
PubMed1991

Infectivity of cultured Trypanosoma fallisi (Kinetoplastida) to various anuran species and its evolutionary implications.

Trypanosoma fallisi, a hemoflagellate infecting Bufo americanus from Ontario, was grown in vitro, and metatrypanosomes from the primary culture were inoculated into 4 uninfected test groups from 3 anuran families: Bufonidae, Hylidae, and Ranidae. In vitro-cultured T. fallisi was found to infect B. americanus and to induce transient infections in Bufo valliceps and Hyla versicolor. The flagellate was not infective to Rana clamitans. Trypanosoma ranarum was uninfective to the bufonids and hylids tested. These data suggest that the potential for host-switching decreases with increased evolutionary distance of the potential anuran host.

Animals↗
PubMed1990

Hematologic effects of interleukin-1 beta, granulocyte colony-stimulating factor, and granulocyte-macrophage colony-stimulating factor in tumor-bearing mice treated with fluorouracil.

Myelosuppression following intensive chemotherapy in cancer patients is associated with increased morbidity and mortality. Hematopoietic growth factors such as granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF), alone or in combination with interleukin-1 (IL-1), have been shown to counteract myelosuppression resulting from some, but not all, chemotherapeutic regimens. In an attempt to apply these findings to intensive therapy with proliferation-dependent chemotherapeutic drugs such as fluorouracil (5-FU), we investigated combination biochemotherapy in a murine model. Female CD8F1 [(BALB/c X DBA/8)F1] mice bearing first-passage transplants of spontaneous CD8F1 breast tumors were treated intraperitoneally once a week for 3 successive weeks with a course of 5-FU alone or with a course of 5-FU in combination with recombinant human interleukin-1 beta (rHuIL-1 beta) alone or in combination with CSFs. rHuIL-1 beta alone or in combination with rHuG-CSF or recombinant murine GM-CSF significantly improved tumor growth inhibition (60% vs. 90%) and survival (20% vs. 90%-100%), increased the maximally tolerated dose of 5-FU, accelerated recovery of neutrophil counts in peripheral blood, and reduced duration of significant neutropenia and loss of body weight (29% vs. 10% loss). Clinical trials of IL-1 have been initiated in patients with advanced cancer receiving multiple courses of high-dose 5-FU.

Animals↗
PubMed1990

In vitro and in vivo growth and casein gene expression of mouse mammary tumor epithelial cells in response to hormones.

Cells from autochthonous mouse mammary carcinomas which display estrogen-independent growth in vivo were studied for their hormonal responses in primary culture. A culture system employing insulin-supplemented, serum-free medium and basement membrane Matrigel as a substratum was used to cultivate tumor cells. The cells did not exhibit in vitro estrogen- or prolactin-dependent growth. Primary tumors still displayed a constitutional expression of alpha-, beta-, and gamma-casein mRNAs. These messages were dramatically reduced during the culture period. However, seven to eightfold increases in alpha- and beta-casein mRNAs were inducible in the 5-day cultures by treatment with prolactin and hydrocortisone. If the hormones were present through a 2-week culture period, the levels of alpha-, beta-, and gamma-casein mRNAs in the cells were maintained and displayed in a time-dependent increase with a peak at 10-14 days. The accumulation of beta-casein mRNA in vitro did not require DNA synthesis. Administration of prolactin directly into the growing tumors in vivo could also enhance beta-casein mRNA levels in the tumor cells. Morphological studies of the cells cultured in the presence of prolactin and hydrocortisone did not reveal visible changes compared with those without hormonal treatment. Transplantation of tumor cells cultured in the presence or absence of hormones resulted in the development of tumors in mice at approximately the same time. The current studies suggest that the autochthonous mammary tumor cells, independent of estrogen for cell growth, were still inducible for casein gene expression in vitro and in vivo by appropriate hormones. The induction and maintenance of casein messages by a single hormonal treatment did not appear to correlate with morphology and DNA synthesis of cells in vitro or with tumor-producing capacities in vivo.

Adenocarcinoma↗
PubMed1990

Physical dependence and attributions of addiction among cigarette smokers.

Examination of the attitudes and attributions of cigarette smokers has differentiated smokers who believe their behavior is a "sickness" from those who believe they are "hooked." Among other things, the hooked smoker, more than the sick one, believes they are addicted and their chances of stopping smoking are poor. If there is a causal association between the attribution of addiction and perceived prospects of change, as this suggests, it could mean treatment and preventative programs stressing the addictive nature of cigarettes may be counterproductive. However, the present study, using a survey of 105 male and female smokers from the general population, suggests the attribution of addiction is related to a smoker's estimate of their chances of stopping only through a common association that each of these measures has with actual (not necessarily perceived) physical dependence. Caution is needed in the application of cognitive research when related physical measures have not been included in the research design.

Adult↗
PubMed1990

Occult thoracic intradural extramedullary spinal canal lesions discovered by extending cervical and lumbar myelography.

We retrospectively reviewed the extended myelograms of 388 patients and identified two clinically occult intradural extramedullary lesions of the thoracic region of the spinal canal. Quality evaluation of the adjacent thoracic region can be quickly and simply performed at the time of lumbar or cervical myelography with the high volumes of relatively nontoxic water soluble intrathecal contrast agents allowed today. We recommend this screen to detect otherwise occult thoracic lesions.

Female↗
PubMed1990

Arginine vasopressin increases apparent whole body capacity in anesthetized cats.

The effects of arginine vasopressin (AVP) on capacitance function were assessed in anesthetized cats by draining blood from the superior and inferior venae cavae into an external reservoir and then returning blood to the right atrium at a constant rate. Under these conditions, changes in reservoir volume were assumed to reflect reciprocal changes in whole body capacity. Intravenous infusions of AVP (1, 10, and 100 ng.kg-1.min-1) that elevated plasma AVP concentrations by approximately 30, 400, and 4,000 fmol/ml were associated with concentration-dependent increases in whole body capacity that ranged between 1.6 and 8 ml/kg. In contrast to AVP, intravenous infusions of angiotensin II (5, 10, and 50 ng.kg-1.min-1) had relatively little influence on capacity, whereas norepinephrine administration (300, 1,000, and 3,000 ng.kg-1.min-1) was associated with dose-dependent decreases in capacity of 4.5-10.3 ml/kg. Virtually the entire increase in whole body capacity to AVP can be accounted for by summation of the predicted contributions of an active reflex venodilatatory component and those of a passive component (arterial and cardiopulmonary compartments). Because systemic compliance (delta reservoir volume/delta venous pressure) was not changed by AVP administration, the contribution of a reflex venodilatatory component must be the result of increases in unstressed vascular volume (contained volume at 0 transmural pressure) as opposed to changes in compliance. These results may explain why AVP decreases cardiac output to a greater extent than either angiotensin II or sympathomimetics and, thus, why AVP is a weaker pressor agent in animals with intact autonomic function.

Anesthesia↗
PubMed1990

Chemotherapeutic activity of L-histidinol against spontaneous, autochthonous murine breast tumors.

In experiments designed to investigate the biochemical basis for the diminution of the antitumor activity of 5-fluorouracil (FUra) by L-histidinol in CD8FI breast tumors, it was discovered that L-histidinol inhibits RNA and DNA synthesis in these tumors. This finding suggested the possibility that L-histidinol might have antiproliferative activity in the CD8FI breast tumor, and on that basis we evaluated different administration schedules of L-histidinol for antitumor activity in vivo. The present report describes a schedule of L-histidinol administration which yielded significant activity against spontaneous, autochthonous CD8FI breast tumors consistently at tolerable doses. To our knowledge, there are no previous reports of in vivo antitumor activity associated with the administration of L-histidinol as a single agent.

Animals↗
PubMed1989

Effects of extracellular matrix on the growth and casein gene expression of primary mouse mammary tumor cells in vitro.

This study describes a serum-free culture system and provides a tumor model to investigate the effects of extracellular matrices on the growth and beta-casein gene expression of mouse mammary tumor epithelial cells (MMTCs) in vitro. Primary cultures of MMTCs derived from autochthonous mammary tumors in BALB/cfC3H x DBA/8 F1 mice, FUKU cells, an established MMTC line, and COMMA-1D cells established from mouse mammary tissues were studied. A reconstituted basement membrane from the Englbreth-Holm-Swarm tumor (Matrigel) allowed a 2.7-fold increase in cell number of 5-day primary MMTC cultures in serum-free, insulin-supplemented medium. FUKU and COMMA-1D cells in serum-free medium displayed a 13.6- and 11.5-fold increase in cell number, respectively, after 5 and 6 days in culture on Matrigel. In semisolid agar cultures, Matrigel or laminin was shown to promote colony-forming efficiency of FUKU cells when either of the matrices was mixed in the top agar layer. An increase of 4.4 or 2.1 times in colony-forming efficiency was detected when 20% (v/v) Matrigel or 112 micrograms/ml of laminin were mixed in the agar layer compared with FUKU cells plated in plain agar. beta-Casein mRNA was detectable by Northern blot assays in the primary mammary tumors. MMTCs in primary cultures grown on Matrigel in serum-free, insulin-supplemented medium for 4 days were inducible for beta-casein mRNA following the treatment with prolactin and hydrocortisone (FPRL) for 24 h. No beta-casein mRNA was detectable in the absence of FPRL. MMTCs in the primary cultures could also be induced for beta-casein mRNA when they were cultivated on type I collagen gels for 4 days but not on laminin, type IV collagen, or plastic. However, the capacity to respond to FPRL was not lost in MMTCs cultured on laminin. When MMTCs were initially cultured on laminin for 4 days and then subcultured on Matrigel for another 4 days, they were inducible for beta-casein mRNA upon exposure to FPRL for 24 h. In contrast, no beta-casein mRNA upon exposure to FPRL for 24 h. In contrast, no beta-casein mRNA was found in MMTCs from the same tumors cultured on laminin for 8 days with the same treatment of hormones. These data demonstrate that cells from autochthonous mammary tumors, which are not dependent on estrogen for growth in vivo, are inducible in vitro for beta-casein mRNA by FPRL; and this hormonal response of MMCTs requires appropriate extracellular matrix.

Animals↗
PubMed1989

Phase I trial of N-(phosphonacetyl)-L-aspartate, methotrexate, and 5-fluorouracil with leucovorin rescue in patients with advanced cancer.

Based on an animal model to improve the antitumor activity of 5-fluorouracil (FUra), a Phase I study of N-(phosphonacetyl)-L-aspartate, methotrexate, FUra, and leucovorin was conducted on 44 patients. Methotrexate was given in an intermediate dose (250 mg/m2) to overcome potential drug resistance, and N-(phosphonacetyl)-L-aspartate was given at a low dose (250 mg/m2) in order to allow escalation of FUra to toxicity. These two drugs were given 24 h before FUra to enhance maximal incorporation of FUra into RNA. Two schedules of administration were used; one every other week and one weekly for 2 weeks. The every other week schedule was well tolerated, with minimal gastrointestinal and hematological toxicity. However, the weekly for 2 weeks schedule was more toxic with increased mucositis, diarrhea requiring therapy, and decreased performance status of 20% in 4 of 6 patients. There were no responders in the every other week schedule. There was one partial response and three patients with stable disease in four evaluable patients on the weekly for 2 weeks schedule. At 24 h post-N-(phosphonacetyl)-L-aspartate-methotrexate treatment, PRPP levels were doubled in bone marrow biopsies, and increased 2.5- to 25-fold in tumor biopsies. We have currently added uridine rescue to this combination with the hope of further escalating the dose of FUra.

Adenocarcinoma↗