PubMed Health⌕ Search

Biomedical subjects

L K Lam

Publications and source records attributed to L K Lam.

At least 73 records · Page 4Linked to original sources
PubMed1979

Synthesis and chemical carcinogen inhibitory activity of 2-tert-butyl-4-hydroxyanisole.

The title compound 1 was selectively synthesized in its pure isomeric form by means of the hydroxyl-protecting reagent dimethyl-tert-butylchlorosilane. Exclusive silylation occurred at the less hindered hydroxyl group of 3. Dimethyl sulfate methylation of 4 gave 5 in excellent yield. Compound 1 was then obtained by acid hydrolysis of 5. The two BHA isomers, 1 and 2, were tested on their inhibitory effects toward benzo[alpha]pyrene-induced neoplasia in the forestomach of the ICR/Ha mouse. Both isomers, when added to the diet, reduced the number of mice with tumors and the number of tumors per mouse. Isomer 1, which has the less hindered free hydroxyl group, showed higher inhibitory effect in the present experimental model.

Animals↗
PubMed1979

Neoplastic effects of oral administration of (+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene and their inhibition by butylated hydroxyanisole.

The neoplastic effects of administration of benzo[a]pyrene (BP) and (+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (BP 7,8-dihydrodiol) by oral intubation to noninbred female Ha:ICR mice have been determined. Under the experimental conditions, BP induced papillomas of the forestomach. BP 7,8-dihydrodiol also induced papillomas of the forestomach and was more potent than BP. In addition, administration of BP 7,8-dihydrodiol caused a large number of pulmonary adenomas and lymphomas. Butylated hydroxyanisole (BHA) added to the diet at a concentration of 5 mg/g inhibited BP-induced neoplasia of the forestomach. BHA also inhibited neoplasia of the forestomach, lungs, and lymphoid tissues that was caused by administration of BP 7,8-dihydrodiol. These data suggest that the inhibitory effect of BHA on BP carcinogenesis may entail events that occur subsequent to the formation of BP 7,8-dihydrodiol.

Adenoma↗
PubMed1978

Effects of administration to mice of butylated hydroxyanisole by oral intubation on benzo[a]pyrene-induced pulmonary adenoma formation and metabolism of benzo[a]pyrene.

Administration of butylated hydroxyanisole (BHA) by oral intubation 4 hours before challenge with benzo[a]pyrene (BP) inhibited the formation of pulmonary adenomas in A/HeJ mice. Incubation of BP with liver microsomes from mice that received BHA 2,4, or 8 hours before being killed resulted in less binding of BP metabolites to added DNA than occurred with control microsomes. High-pressure liquid chromatography studies of the BP metabolite pattern produced by the incubation of BP with liver microsomes from mice given BHA by oral intubation showed a decrease in formation of BP-4,5-oxide and 9-hydroxybenzo[a]pyrene. In contrast, the formation of 3-hydroxybenzo[a]-pyrene was increased. The was increased. The short interval between the administration of BHA by oral intubation and the observed biochemical changes indicated that BHA could exert a direct effect on the microsomal metabolism of BP. These changes in metabolism of BP occurred under conditions of BHA administration that produced a decreased neoplastic response to this carcinogen.

Adenoma↗
PubMed1977

Inhibits of of colon carcinogenesis.

Disulfiram (tetraethylthiuram disulfide, Antabuse) and sodium diethyldithiocarbamate, when added to the diet, inhibit 1,2-dimethylhydrazine (DMH)-induced neoplasia of the large bowel in female CF1 mice. Ethylene bis(dithiocarbamato)manganese (Maneb) and bis(ethylxanthogen), two pesticides with structural similarities to disulfiram, produce comparable inhibition of DHM. In other work, disulfiram was found to inhibit the carcinogenic effect of azoxymethane (AOM) on the large bowel. Under comparable conditions the inhibition of AOM was considerably less than that obtained with DMH as the carcinogen. The data suggest that disulfiram inhibits DMH metabolism at more than one oxidative step.

Animals↗
PubMed1977

Effects of butylated hydroxyanisole on the metabolism of benzo[a]pyrene by mouse liver microsomes.

The metabolites of tritium-labeled benzo[a[pyrene (BP) extracted from liver microsomes prepared by butylated hydroxyanisole (BHA)-fed and control female A/HeJ mice were analyzed by high-pressure liquid chromatography. There was an overall decrease in diol formation as well as an increase in the phenol formation in microsomal incubations from the BHA-fed mice compared to the controls. The dione region, when analyzed together with the BP-4,5-oxide peak, showed an overall decrease with BHA feeding. The BP-4,5-oxide was isolated and identified. It was present in both the BHA-fed and control microsomal incubations but was substantially reduced in the former. BP-9,10-oxide and BP-7,8-oxide were not directly demonstrated. Data based on summation of diols and phenols resulting from the breakdown of these oxides indicated that they were present in reduced amounts in the microsomal incubation from BHA-fed mice. The 3-hydroxybenzo[a]pyrene (3-HOBP) was the major metabolite in both microsomal incubations and was present in a significantly higher percentage in the incubations from the BHA-fed mice when compared to control mice. Thus BHA resulted in two metabolic alterations which could result in its exerting an inhibitory effect on BP-induced carcinogenesis. The first was an increase in 3-HOBP, a metabolite of detoxification, and the second was a decrease in epoxidation, which is an activation process.

Animals↗
PubMed1977

Bumetanide in heart failure in infancy.

The effect of bumetanide in infants with congenital heart disease presenting with cardiac failure was studied. The study was divided into acute (3 days) and long-term (mean 10.5 weeks) cases. A total of 12 male infants was included in the acute study and 13 cases were evaluated in the long-term study. The dose used in the acute study (0.015 mg/kg) was suboptimal; notwithstanding it was found to cause significant natriuresis and chloruresis. Bumetanide in doses varying in different infants from as little as 0.015 mg/kg on alternate days to as much as 0.10 mg/kg daily was shown to be an effective diuretic for long-term use. No side effects were observed in either study.

Acute Disease↗
PubMed1976

Dietary constituents altering the responses to chemical carcinogens.

This paper deals with two categories of compounds having the capacity to inhibit the neoplastic effects of chemical carcinogens on the host. The first are inducers of increased microsomal mixed function oxidase activity. An increasing number of these inducers are being found in natural products. Cruciferous vegetables including brussels sprouts, cabbage, and cauliflower contain such compounds. Recently indole-3-acetonitrile, indole-3-carbinol and 3,3'-diindolylmethane have been identified as inducers in these three plants. Other naturally occurring inducers include flavones, safrole, isosafrole, beta-ionone, and oxidized sterols. Since previous work has shown that synthetic inducers may protect against chemical carcinogens, the composition of the diet could play a role in inhibiting the neoplastic response to these carcinogenic agents. The second category of inhibitors comprises the antioxidants. Several of these compounds have been found to inhibit the carcinogenic effects of a variety of chemical carcinogens. Considerable work of this nature has been done with butylated hydroxyanisole and butylated hydroxytoluene two antioxidants extensively used as food additives. Other antioxidants having carcinogen inhibiting capacities include ethoxyquin, disulfiram, and dimethyldithiocarbamate.

Animals↗
PubMed1975

Photooxidation of dinitrophenylhistidine-200 human carbonic anhydrase B.

Partial inactivation of tau-dinitrophenylhistidine-200 human carbonic anhydrase B, induced by visible light, followed first order kinetics (k(app) = 6.05 times 10-2 min-1). After 50 min the tau-dinitrophenylhistidine (tau-DNP-histidine) content decreased to a negligible level, but the illuminated enzyme retained, at pH 7.6, approximately 9.2 percent of the esterase activity of the native enzyme. The following lines of evidence suggest that the loss of activity results from the destruction of tau-DNP-histidine-200. (1) No significant loss of amino acid other than tau-DNP-histidine was detected after illumination. (2) The rate of loss of activity correlated well with the loss of tau-DNP-histidine. (3) In the photooxidized enzyme the DNP moiety was retained but had lost the characteristic sensitivity of tau-DNP-histidine to nucleophilic attack. Titration of the illuminated enzyme with acetazolamide indicated that the residual activity is an intrinsic property of the modified enzyme. The chromatographically purified photooxidized enzyme migrated as a single band on isoelectrofocusing in polyacylamide gel, and at pH 7.6 possessed 7.5 percent esterase activity relative to the native enzyme. By establishing effective destruction of histidine-200, it can be concluded that neither the pi N nor, as previously shown, the tau N of histidine-200 is critical for the catalysis.

Acetazolamide↗
PubMedDate not supplied

Occult lymph node metastasis in small oral tongue cancers.

The need to treat the neck in patients with a small primary cancer in the tongue remains controversial. Twenty-eight patients with stage I or II oral tongue squamous carcinomas were retrospectively reviewed. They had not received previous treatment. The tongue primary was excised via the transoral route and the neck was observed closely during follow-up. Thirteen patients developed ipsilateral nodal metastases during follow-up, three of whom also had simultaneous recurrence at the primary site. An additional patient had recurrence at the primary site alone. The incidence of occult neck metastasis was 42% (10 of 24). No tumor-related death occurred in the group without nodal metastasis. The salvage rate after appearance of nodal metastasis was 30%. In oral tongue cancers, elective neck treatment should be considered regardless of a small primary and negative neck examination because of the high incidence of occult nodal metastasis and the poor outcome after salvage treatment.

Adult↗
PubMedDate not supplied

Squamous cell carcinoma of the hypopharynx--analysis of treatment results.

The results of surgical treatment and causes of failure in 109 patients with squamous cell carcinoma of the hypopharynx were analyzed. The 5-year survival was significantly related to the stage of the disease (stage I, 74%; stage II, 63%; stage III, 32%; and stage IV, 14%) and the preoperative nodal staging (N0, 57%; N1, 28%; N2, 6%; and N3, 0%), but not related to the extent of tumor resection. The local control rate was 86% and the majority of the local recurrences occurred at the upper resection margin. There was no significant difference in the local recurrence rate between those patients who had pharyngolaryngoesophagectomy and those who had pharyngolaryngectomy. However, the resection-associated complications (bleeding, cardiac arrhythmia, pulmonary complications) were more frequent when total esophagectomy was performed. Reconstruction-associated complications such as wound infection and anastomotic leakage occurred less often after gastric pull-up reconstruction as compared with the use of myocutaneous flap, but was associated with more serious outcome after pharyngo-gastric anastomosis. Thirty-seven patients (34%) had neck node recurrences and these were significantly related to the preoperative nodal staging (N0, 20%; N1, 37%; N2, 48%; and N3, 83%). Additional primary cancers occurred in 17% of the patients and was a significant cause of death in those patients who survived more than 2 years.

Adult↗