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Biomedical subjects

C M Lang

Publications and source records attributed to C M Lang.

At least 37 records · Page 2Linked to original sources
PubMed1996

Identification and characterization of zeta-opioid receptor in human colon cancer.

Opioid growth factor (OGF, [Met5]enkephalin) inhibits the growth of human colon cancer in nude mice in a receptor-mediated fashion. Ligand binding assays using HT-29 human colon cancer tissue and [3H][Met5]enkephalin were performed to characterize the receptor responsible for the growth-regulatory effects of OGF in colon cancer. Specific and saturable binding was detected, and Scatchard analysis revealed that the data were consistent for a single binding site with a binding affinity of 15.4 +/- 2.0 nM and a binding capacity of 364.8 +/- 25.7 fmol/mg protein. Subcellular fractionation studies revealed that binding was restricted to the nuclear fraction. Competition experiments showed that cold [Met5]enkephalin was the most effective ligand at displacing [3H][Met5]enkephalin. Binding to radiolabeled [Met5]enkephalin also was detected in colon cancers obtained from surgical resections. The function, pharmacological and biochemical characteristics, distribution, and subcellular location of this OGF receptor in human colon cancer are consistent with the zeta-opioid receptor.

Animals↗
PubMed1996

Opioid growth factor ([Met5]enkephalin) prevents the incidence and retards the growth of human colon cancer.

Endogenous opioid peptides serve as growth factors in normal and neoplastic cells and tissues, and both opioids and their receptors have been identified in human colon cancer. This study examined the hypothesis that opioids serve to modulate the growth of human colon cancer. Daily administration of the native opioid growth factor (OGF), [Met5]enkephalin, at dosages of 0.5, 5, or 25 mg/kg prevented the occurrence of human colon cancer HT-29 xenografts in nude mice. More than 80% of the mice receiving OGF beginning at the time of tumor cell inoculation did not exhibit neoplasias within 3 wk, in comparison with a tumor incidence of 93% in control subjects. Even 7 wk after cancer cell inoculation, 57% of the mice given OGF did not display a tumor. OGF delayed tumor appearance and growth in animals developing colon cancer with respect to the control group. The suppressive effects of OGF on oncogenicity were opioid receptor mediated. OGF and its receptor, zeta (zeta), were detected in transplanted human HT-29 colon tumors. Surgical specimens of human colon cancers also contained OGF. These results show that a naturally occurring opioid peptide acts as a potent negative regulator of human gastrointestinal cancer and may suggest pathways for tumor etiology, progression, treatment, and prophylaxis.

Adenocarcinoma↗
PubMed1996

Bladder dysfunction in the spontaneously diabetic male Abyssinian-Hartley guinea pig.

The spontaneously diabetic adult male Abyssinian-Hartley guinea pig develops bladder hypertrophy and voiding dysfunction. In contrast to animals with chemically induced diabetes, this animal demonstrates changes in bladder function in the absence of diuresis. The diabetic guinea pigs void a total daily volume similar to that of control animals, but have a greater mean volume per void and a longer interval between voiding. Cystometry demonstrates that the diabetic guinea pig produces greater intraluminal bladder pressure, but maintains voiding pressure for a shorter interval. A significantly decreased contractile response of the diabetic bladder base may be responsible for the bladder hypertrophy and voiding dysfunction.

Analysis of Variance↗
PubMed1995

N-acetyl-beta-D-glucosaminidase activity within BAL from macaques exposed to generic coal dusts.

N-acetyl-beta(beta)-D-glucosaminidase is a lysosomal enzyme secreted by alveolar macrophages in response to phagocytosis of particulate material. Alveolar macrophages participate in the degradation and fibrosis of pulmonary tissue that results in pneumoconiosis. Known quantities of four characterized respirable dusts were bronchoscopically placed into the right caudal lung lobe of macaque monkeys. Bronchoalveolar lavage (BAL) samples were collected from dust-exposed right lung and unexposed left lung of the same individuals at 2-week intervals for 12 weeks after dust instillation. The samples were tested for N-acetyl-beta-D-glucosaminidase activity to determine if the enzyme levels could serve as an indicator of pulmonary injury induced by generic coal dusts when compared to known fibrogenic and nuisance dusts. Installation of generic quartz, anthracite, or TiO2 dusts produced significant elevations of enzyme activity and increased numbers of macrophages in the dust-exposed lobes. Elevations in enzymatic activity and macrophage numbers were greatest in response to generic quartz dust. These results suggest that quantitative levels of N-acetyl-beta-D-glucosaminidase activity may be a useful indicator of acute and chronic lung injury following exposure to fibrogenic and nonfibrogenic dusts.

Acetylglucosaminidase↗
PubMed1995

Methylation of cottontail rabbit papillomavirus DNA and tissue-specific expression in transgenic rabbits.

Transgenic rabbits carrying multiple copies of CRPV genomic DNA were described previously (Peng et al. (1993) J. Virol. 67, 1698-1701). CRPV DNA was detectable in all tissues of the transgenic rabbits, however, the transcripts of CRPV genes only were found in skin and skin tumors. Tumor development was also restricted to skin. To study the mechanism involving tissue-specific expression of CRPV genes in rabbits, cellular DNAs, isolated from different normal tissues and skin tumors, were digested with the two isoschizomeric restriction endonucleases MspI (methylation resistant) and HpaII (methylation sensitive), respectively, and analyzed by Southern blot. CRPV DNA, especially its upstream regulatory region (URR), was extensively methylated in all normal tissues, but methylation was remarkably reduced in skin tumors. These data suggest that extensive methylation of CRPV genome, especially in the URR, might be a factor in controlling its tissue-specific expression.

5-Methylcytosine↗
PubMed1995

Comparison of the effects of five adjuvants on the antibody response to influenza virus antigen in guinea pigs.

Five adjuvants were tested for their effect on the immune response in guinea pigs to the hemagglutinin antigen of influenza virus strain B/Panama. Vaccines containing 924 micrograms of hemagglutinin antigen/ml were prepared at high and low doses of Freund's complete and incomplete adjuvants, Syntex adjuvant, RIBI's adjuvant, TiterMax adjuvant, and aluminum phosphate adjuvant. Responses to these vaccines were compared with those to a control vaccine containing influenza virus B/Panama hemagglutinin antigen and saline. On day 28, vaccines containing the following adjuvant doses had significantly higher titers than the titer for the control: Freund adjuvants at high and low doses, RIBI at high dose, TiterMax at high and low doses, and aluminum phosphate at high dose. On day 42, vaccines containing the following adjuvant doses had significantly higher titers than that for the control: Freund adjuvants at high and low doses, RIBI at high dose, TiterMax at high dose, and aluminum phosphate at high dose. Freund adjuvants at high and low doses, RIBI adjuvant at high dose, and aluminum phosphate at high dose caused significantly greater swelling at the inoculation site than did the control vaccine. TiterMax adjuvant at high and low doses, and aluminum phosphate at low dose caused minor swelling at the inoculation site, but it was not significantly different from the swelling caused by the control vaccine. Syntex adjuvant at high and low doses, RIBI at low dose, and control (saline/antigen) at high and low doses caused no swelling after inoculation. Overall, the high dose of adjuvants caused greater tissue swelling than did the low dose of adjuvants.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1995

Comparison of anesthesia induced by ketamine-fentanyl combination and maintained by propofol or etomidate in New Zealand white rabbits.

Ketamine-fentanyl-propofol and ketamine-fentanyl-etomidate combinations were administered intravenously to four groups of rabbits. Each group received ketamine (30 mg/kg of body weight) and fentanyl (0.025 mg/kg) for anesthesia induction. Either propofol or etomidate was administered by an infusion pump to maintain anesthesia. The rabbit's responses to noxious stimuli were determined before anesthesia was induced and at 10-min intervals thereafter until the rabbit recovered. The effects of the anesthetic combinations on the cardiopulmonary system were measured by monitoring respiratory and heart rates, blood pressure, and arterial blood gas tensions. Etomidate infused at the rate of 0.2 or 0.1 mg/kg/min could maintain surgical anesthesia with fewer effects on the cardiopulmonary system for 40 and 30 min respectively. However, the high mortality and side effects such as hemolysis in these two groups preclude the clinical use of etomidate for anesthesia maintenance. Propofol administered intravenously at rates of 0.8 and 0.4 mg/kg/min could maintain surgical anesthesia for 40 and 30 min respectively. However, relatively severe hypotension, hypercapnia, and respiratory acidosis were associated with this drug. Recovery from the propofol infusion was very rapid. Ketamine-fentanyl-etomidate combination is not recommended for clinical anesthesia in rabbits. Ketamine-fentanyl-propofol combination at a dosage of 30-0.025-0.4 mg/kg/min can be safely used for short-term surgery.

Anesthesia, Intravenous↗
PubMed1994

Use of capillary electrophoresis-isoelectric focusing for the determination of bovine hemoglobin variants.

A capillary electrophoretic technique was developed to monitor patterns of hemoglobin production in young calves subjected to multiple phlebotomies. The method is similar to one previously described for the determination of human hemoglobin variants in whole blood using isoelectric focusing. After a single collection of one-half the circulating blood volume, there were obvious alterations in hemoglobin chain variants. HbA levels diminished as blood loss increased with minimum values corresponding to maximum blood loss. HbF levels did not appear to be affected. Also visible during the regenerative process were atypical overlapping peaks preceding the normal hemoglobin peaks. At the conclusion of the 18-day study, most of the electropherograms had returned to initial states. These changes were found to be a sensitive indicator of accelerated erythropoiesis in contrast to the standard technique of total hemoglobin determination by colorimetric means.

Animals↗
PubMed1994

An animal model of visual loss from orbital hemorrhage.

Intraorbital hemorrhage may arise spontaneously or following orbital or periorbital surgery or trauma and may be associated with visual loss or impairment. This project was designed to evaluate the ophthalmic effects and underlying mechanism(s) associated with visual impairment secondary to intraorbital hemorrhage. An experimental surgical procedure was developed to simulate intraorbital hemorrhage. A reversible state of unilateral visual loss secondary to acutely increased intraorbital volume was induced and maintained under general anesthesia for either 90, 120, or 180 min duration in nine adult nonhuman primates (NHPs) (Macaca arctoides). Color funduscopic photography, i.v. fluorescein angiography, electrophysiological testing, and tonometry were obtained during baseline, experimental, and follow-up procedures. The globes and optic nerves were obtained for histopathologic evaluation. One of three animals in the 180 min experimental group exhibited clinical and histopathological changes of optic neuropathy 6 weeks after the experimental procedure. Optic neuropathy is one of several proposed etiologies for producing visual loss secondary to intraorbital hemorrhage. This study offers a reliable, safe, and reversible technique to study the effects of acutely increased intraorbital volume in nonhuman primates. The animal model described may be useful for evaluating mechanism(s) involved with visual impairment in other acquired optic neuropathies.

Animals↗
PubMed1993

Cardiovascular and respiratory effects of tiletamine-zolazepam.

The combination of tiletamine and zolazepam is an important dissociative anesthetic-tranquilizer. However, little is known about the effects of this combination on the heart and respiration in rats. Adult, male rats anesthetized with tiletamine-zolazepam alone or tiletamine-zolazepam combined with xylazine or butorphanol were evaluated for changes in heart rate, mean arterial blood pressure, arterial blood pH, and blood gases during a 75-min period of anesthesia. Rats anesthetized with tiletamine-zolazepam had increased mean arterial blood pressure and less respiratory depression than did rats anesthetized with sodium pentobarbital. Tiletamine-zolazepam combined with xylazine at either dose produced bradycardia and a marked hypotension that persisted throughout the 75-min period. This combination produced respiratory depression comparable to tiletamine-zolazepam alone. The addition of butorphanol to tiletamine-zolazepam caused a transient hypotension and bradycardia. Tiletamine-zolazepam plus butorphanol produced a mild to severe respiratory depression that was dose and time dependent. These results demonstrate that: a) Tiletamine-zolazepam is cardiostimulatory, a property consistent with the known cardiovascular effects of other dissociative anesthetics; b) xylazine plus tiletamine-zolazepam is a potent cardiovascular depressant combination; and c) tiletamine-zolazepam plus butorphanol at specific doses is an anesthetic-analgesic combination with minimal effects on cardiovascular and respiratory function.

Anesthetics, Dissociative↗
PubMed1993

Papillomas and carcinomas in transgenic rabbits carrying EJ-ras DNA and cottontail rabbit papillomavirus DNA.

Two transgenic rabbits (TRI and TRIII) that carried cottontail rabbit papillomavirus (CRPV) DNA alone were identified; another (TRII) carried both CRPV DNA and EJ-ras. TRI and TRIII developed extensive skin papillomas at about 1 month of age, and transcripts of CRPV DNA were detectable only in skin and/or papillomas. TRII developed extensive squamous carcinomas of the skin at a very early age. Transcription of both CRPV DNA and EJ-ras was found in the skin cancers. Thus, the tissue specificity of CRPV DNA expression in transgenic rabbits was the same as in virion-infected animals. The expression of EJ-ras could be dependent on the expression of certain CRPV genes and may be a critical cofactor of CRPV DNA in the progression of carcinomas.

Animals↗
PubMed1993

Anaesthetic effects of chloral hydrate, pentobarbitone and urethane in adult male rats.

Chloral hydrate, pentobarbitone and urethane were evaluated and compared for onset, duration and depth of anaesthesia, cardiovascular and respiratory effects, nociception and mortality in adult male rats. Chloral hydrate (300 and 400 mg/kg) severely depressed the cardiovascular and respiratory systems. Duration of anaesthesia was linearly related to dose, and anaesthetic depth and analgesia were excellent. Pentobarbital (40 mg/kg) produced a short period of light surgical anaesthesia. Moderate to severe respiratory and cardiovascular depression occurred. Duration of anaesthesia was not related to dose. Urethane (1.2 and 1.5 g/kg) caused moderate cardiovascular depression. In addition, mortality was high at the 1.5 g/kg dose. Duration of anaesthesia was greater than 24 h for most animals. Anaesthesia depth and analgesia were excellent.

Anesthesia↗
PubMed1992

Antinociceptive properties of tiletamine-zolazepam improved by addition of xylazine or butorphanol.

A combination of tiletamine HCl and zolazepam HCl is frequently used as an anesthetic, but little is known about the antinociceptive properties of tiletamine-zolazepam. The antinociceptive properties of tiletamine-zolazepam alone or combined with xylazine or butorphanol were determined in the adult male rate using the tail-flick test. Changes in tail-flick latency were determined at 15, 45, and 75 min after IP drug administration of sterile water, sodium pentobarbital, morphine, tiletamine-zolazepam, xylazine, butorphanol, and tiletamine-zolazepam plus xylazine or butorphanol. Tail-flick latency approximated 100% maximum possible effect (MPE) at 15-75 min postinjection in morphine-treated rats. Tiletamine-zolazepam, xylazine, and butorphanol alone, at any dose utilized, produced less than 50% MPE. However, the combination of tiletamine-zolazepam with butorphanol or xylazine increased tail-flick latency approximately three times greater than tiletamine-zolazepam alone. These results demonstrate that: a) consonant with earlier findings, analgesia and anesthesia are independent states; b) tiletamine-zolazepam is not an effective combination with respect to analgesia; but c) in concert with appropriate drugs, it can exhibit potent antinociceptive properties.

Analgesics↗
PubMed1990

Cystitis, urolithiasis and cystic calculi in ageing guineapigs.

Nineteen cases of cystitis were diagnosed at necropsy and/or by histology in a group of 170 (96 females, 74 males) guineapigs (11.2%). Seventeen of the 19 cases (89.4%) were females. The mean age of guineapigs with cystitis was 34.7 months, which was higher than the mean age of 24 months of the 170 members of the study group. In addition, 6 cases of urolithiasis and cystic calculi in 5 females and one male were also found in the 170 guineapigs (3.5%). The mean age of the 6 cases was 30 months, which was also higher than the mean age of the 170 animals. The study suggests that aged female guineapigs were much more predisposed to cystitis and urolithiasis or cystic calculi than male and young guineapigs. The cause may be related to infection with Escherichia coli and Staphylococcus sp, cystic calculi, diabetes mellitus and female guineapig urogenital anatomy and function.

Aging↗
PubMed1990

An evaluation of three intravenous anesthetic regimens in New Zealand rabbits.

Intravenous anesthetics can be readily administered to rabbits through the marginal ear vein. In this study, three intravenous anesthetic protocols were evaluated in New Zealand White rabbits. The three anesthetic regimens were: (a) pentobarbital (40 mg/kg); (b) ketamine-xylazine (25-5 mg/kg); (c) midazolam-xylazine-alfentanil (1-1-0.1 mg/kg). The anesthetics were injected slowly over defined time intervals. Reactions to noxious stimuli were determined before and after administration of the anesthetics. Additionally, the effects of the anesthetic agents on the rabbit's cardiopulmonary system were evaluated. Rabbits anesthetized with midazolam-xylazine-alfentanil did not have a pedal withdrawal or ear pinch reflex throughout the testing period. The ketamine-xylazine combination produced a shorter duration of non-responsiveness to noxious stimuli. Rabbits anesthetized with pentobarbital had the greatest variability in response to noxious stimuli. Apnea occurred in at least one rabbit in each group. A side effect unique to the midazolam-xylazine-alfentanil group was the occurrence of opisthotonus or seizure activity during or shortly after the administration of alfentanil. Hypotension, hypercapnia and respiratory acidosis were characteristic of the cardiopulmonary effects of the anesthetics. When choosing an anesthetic regimen for rabbits, intravenous infusion should be considered as an option. Advantages include ease of administration, possibility of redosing as required, and minimal requirements for equipment. Disadvantages of intravenous anesthetic infusion in rabbits include potential for lethal overdose and metabolic alterations after administration.

Alfentanil↗
PubMed1990

Effect of in-house transport on murine plasma corticosterone concentration and blood lymphocyte populations.

The effect of in-house transport on plasma corticosterone concentration and blood lymphocyte populations of laboratory mice was investigated. Mice were transported within a research facility at 0900 hours in a pattern designed to simulate that commonly used by investigators prior to experimental manipulation. Plasma corticosterone concentration and WBC count were determined at 0.25, 2, 4, 8, 12, and 24 hours after transport. A significant (P less than 0.05) increase in plasma corticosterone concentration was seen in mice immediately after transport. The normal circadian rhythm of plasma corticosterone concentration was altered for the subsequent 24-hour period. Corresponding significant (P less than 0.05) decreases in total WBC numbers, lymphocyte count, and thymus gland weight were observed. The decrease in total blood lymphocyte numbers at 4 hours was reflected in B- and T-lymphocyte populations. The subsequent acute increase in plasma corticosterone concentration was associated with alterations in the cellular components of the immune system. Results of the study indicated that routine in-house transport of laboratory mice should be considered a stressful stimulus.

Animals↗