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Biomedical subjects

A K Chan

Publications and source records attributed to A K Chan.

13 recordsLinked to original sources
PubMed1992

Normocalcemic hyperparathyroidism. Biochemical and symptom profiles before and after surgery.

Patients with normocalcemic hyperparathyroidism represent a diagnostic and therapeutic challenge. It is unclear to what extent these patients benefit from surgery in terms of correction of their serum chemistry abnormalities and their symptoms. We studied 142 patients: 23 with normocalcemic hyperparathyroidism (serum calcium levels below 2.62 mmol/L), 35 with intermittent hypercalcemia, and 84 with hypercalcemic hyperparathyroidism. Serum chemistry analyses and a standardized questionnaire of symptoms were completed before and after surgery. Overall, patients in the normocalcemic group reported a similar frequency of preoperative symptoms; had a similar reduction in postoperative symptoms; and had a similar normalization of serum calcium, parathormone, and phosphate levels as those in the two control groups. This study indicates that factors other than elevated serum calcium levels are in large part responsible for the symptoms of hyperparathyroidism and that these patients benefit from operation.

Adenoma↗
PubMed1992

Segmental colonic dilatation in a neonate.

Segmental dilatation of the colon is rare, usually affecting older children, and may mimic Hirschsprung's disease. A neonate with Down's syndrome and malrotation presented with this condition and was cured by segmental resection.

Colon↗
PubMed1992

Cardioplegic arrest of the myocardium with calcium blocking agents.

This study was designed to compare the effects of the calcium slow channel blocking agents verapamil (0.15 mg/kg), diltiazem (0.15 mg/kg), and nifedipine (50 micrograms/kg) on the myocardium after global ischemia and reperfusion in the in situ canine model. Animals were subjected to 120-min normothermic global ischemia, followed by 45-min reperfusion. Cardioplegic arrest of the myocardium was achieved by administering one of the three calcium antagonists in a multidose fashion. Superior preservation (p less than 0.01) of left ventricular (LV) systolic function was achieved in group I (verapamil cardioplegia). dP/dt, at an intraventricular balloon volume of 25 cc, was 83% of control after reperfusion in group I. Group II (diltiazem) and group III (nifedipine) achieved only 55 and 63% of their preischemic dP/dt values. LV chamber stiffness was increased in hearts protected with nifedipine. The exponential constant m was increased from 0.04 +/- 0.01 to 0.08 +/- 0.01. Coronary blood flow after reperfusion increased from 120 to 184 cc/100 gr/min in group I (p less than 0.01). The hyperemic response in group III was negligible. The O2 consumption of the reperfused myocardium was not significantly altered in any of the treatment groups. Lactate metabolism during ischemia and after reperfusion was similar in all groups. ATP values were markedly reduced in all groups (p less than 0.05). Immediately after ischemia, ATP was 50, 28, and 44% of control in group I, II, and III, respectively. The excellent preservation of systolic function and a physiologic hyperemic response by verapamil could not be correlated with improved preservation of high-energy compounds or with significant changes in myocardial O2 consumption.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1992

Inhibition of mammalian ribonucleotide reductase by cis-diamminedichloroplatinum(II).

Ribonucleotide reductase is a highly regulated, rate-limiting activity in the synthesis of DNA. A previous study has shown that the Escherichia coli enzyme is inhibited by the clinically important antitumor agent cis-diamminedichloroplatinum(II) (DDP), and this has led to the hypothesis that ribonucleotide reductase is an important site of action for this chemotherapeutic agent. This hypothesis has been directly tested in this investigation. We observed that DDP inhibits the mammalian ribonucleotide reductase, with 50% inhibition occurring at 0.3 mM. Unlike the E. coli enzyme where only one of the two protein components is targeted by DDP, we observed that both of the mammalian proteins (R1 and R2) were sites for the inhibitory activity of the drug. Colony-forming experiments, enzyme activity studies, and analyses of R1 and R2 message levels in mutant cell lines containing either high levels of ribonucleotide reductase activity or exhibiting resistance to the cytotoxic effects of DDP were used to further investigate the potential role of ribonucleotide reductase in DDP cytotoxic action and drug resistance. These studies did not support a hypothesis formulated in the earlier investigation that inhibition of ribonucleotide reductase is an important component of DDP cytotoxic activity or that it is a major participant in DDP resistance mechanisms. From a biological point of view, DDP is a very active drug, and in addition to its cytotoxic effects it is capable of inducing a variety of cellular changes. Whether or not the inhibition of mammalian ribonucleotide reductase activity that we have described in this study plays a role in mediating any of these other effects remains to be determined.

Animals↗
PubMed1992

CD4 lymphocyte count as an indicator of delay in seeking human immunodeficiency virus-related treatment.

BACKGROUND: As many as half of patients infected with the human immunodeficiency virus who are medically eligible for Pneumocystis prophylaxis and zidovudine treatment have not received these treatments. We used the CD4 lymphocyte count as an indicator of delay in seeking treatment among patients infected with human immunodeficiency virus and assessed whether insurance status was associated with the stage of illness when care is initiated. METHODS: Data from 96 patients who initiated medical care at a university acquired immunodeficiency syndrome clinic from August 1989 to January 1991 were retrospectively reviewed. RESULTS: Patients initiated care at a relatively late stage of illness (mean CD4 lymphocyte count, 0.37 x 10(9)/L [369/mm3]), and 29% were below the threshold for Pneumocystis prophylaxis. Patients with private insurance had significantly lower CD4 counts (mean, 0.27 x 10(9)/L) than did individuals with public insurance (mean, 0.46 x 10(9)/L). CD4 counts did not increase during the 18-month study period. CONCLUSIONS: The majority of patients infected with human immunodeficiency virus are eligible for medical therapy and could benefit by initiating care sooner. Private insurance was not associated with initiating early care, supporting anecdotal reports that some privately insured individuals may be reluctant to seek care for a human immunodeficiency virus-related condition.

Adult↗
PubMed1992

Antimycobacterial therapy for disseminated Mycobacterium avium complex infection in patients with acquired immunodeficiency syndrome.

BACKGROUND--Antimycobacterial therapy for disseminated Mycobacterium avium complex (DMAC) in patients with acquired immunodeficiency syndrome (AIDS) may ameliorate symptoms and decrease bacteremia. However, no studies have demonstrated improved survival in patients with AIDS treated for DMAC. We assessed the effects of treatment of DMAC on the survival of patients with AIDS. METHODS--We retrospectively reviewed records of patients with AIDS and DMAC seen at two San Francisco, Calif, hospitals between January 1, 1988, and January 1, 1990. The treatment group (N = 76) consisted of patients who received 2 weeks or more of antimycobacterial therapy with at least three agents. The untreated group (N = 74) received either no therapy or isoniazid alone. Patients in both groups lived a minimum of 2 weeks after the diagnosis of DMAC. RESULTS--The median survival in the treatment group was 191 days, compared with 80 days in the untreated group. In a multivariate proportional hazards model (N = 145), both treatment of DMAC (relative hazard = 0.34; 95% confidence interval, 0.23 to 0.51) and treatment with zidovudine (relative hazard = 0.54; 95% confidence interval, 0.36 to 0.82) were associated with improved survival. CONCLUSION--Patients with AIDS and DMAC who are treated with antimycobacterial drugs may survive longer than untreated patients. We recommend that a randomized trial be conducted to evaluate the optimal treatment of DMAC.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Increasing sympathetic nerve terminal-dependent plasma extravasation correlates with decreased arthritic joint injury in rats.

This study compared the pharmacology of adrenergic agents that influence plasma extravasation in normal animals with those agents that influence tissue injury in an inflammatory disease model. Specifically we studied the effects of beta 2- and alpha 2-adrenergic receptor agonists and antagonists on bradykinin-induced plasma extravasation in normal Sprague-Dawley rats and on joint injury in rats with experimental arthritis. Plasma extravasation induced by infusion of bradykinin in the rat knee joint was attenuated by the beta 2-agonist salbutamol or by the alpha 2-antagonist yohimbine, and was enhanced by the beta 2-antagonist, ICI-118,551, or by the alpha 2-agonist, clonidine. In rats that had undergone chemical symphathectomy, bradykinin-induced plasma extravasation was markedly reduced, and there was no enhancement of bradykinin-induced plasma extravasation by either ICI-118,551 or clonidine. Although ICI-118,551 and clonidine enhanced bradykinin-induced plasma extravasation, these drugs significantly reduced joint injury in rats with adjuvant-induced arthritis. Neither salbutamol nor yohimbine, however, significantly increased joint injury in the arthritic rats, presumably because arthritis severity is already high in these animals. Consistent with this hypothesis, both salbutamol and yohimbine did significantly increase the joint injury associated with experimental arthritis in Wistar-Kyoto rats, a strain which develops a mild adjuvant arthritis. The fact that increased plasma extravasation is associated with decreased arthritis severity suggests that plasma extravasation, a major sign of acute inflammation, contributes to tissue reparative processes.

Animals↗
PubMed1990

Increased ferritin gene expression is associated with increased ribonucleotide reductase gene expression and the establishment of hydroxyurea resistance in mammalian cells.

In the present study, we show that hydroxyurea-inactivated ribonucleotide reductase protein M2 has a destabilized iron center, which readily releases iron. In addition, evidence is presented which indicates that single or multistep selection for hydroxyurea resistance, in a variety of mammalian cell lines, leads to alterations in the expression of the gene for the iron storage protein, ferritin. In all hydroxyurea-resistant cell lines examined, including human, hamster, rat, and mouse, there was an elevation in ferritin heavy (H)- and/or light (L)-mRNA levels, but no change in the corresponding gene copy number. A detailed analysis of ferritin expression in a hydroxyurea-resistant mouse L cell line showed that when compared to its wild type counterpart, there was an increase in H subunit concentration but no significant change in L subunit levels. The increased H/L subunit ratio was not brought about by specific changes in the rates of ferritin subunit biosynthesis, but rather resulted from changes in the post-translational stability of H subunits relative to L subunits in the resistant cell line compared to its parental wild type. Also, we show that treatment of cells with hydroxyurea results in an increased rate of ferritin biosynthesis in the absence of changes in H- or L-mRNA levels. These results indicate that the development of even low level hydroxyurea resistance in mammalian cells may require alterations in ferritin gene expression, and they show an interesting relationship between the expressions of two highly regulated activities, ribonucleotide reductase and ferritin.

Animals↗
PubMed1990

Regulation and drug resistance mechanisms of mammalian ribonucleotide reductase, and the significance to DNA synthesis.

Mammalian ribonucleotide reductase, which occupies a key position in the synthesis of DNA, is a highly controlled enzyme activity, because it is solely responsible for the de novo reduction of ribonucleoside diphosphates to their corresponding deoxyribonucleoside diphosphate forms, required for DNA synthesis. Ribonucleotide reductase consists of two dissimilar protein components often called M1 and M2, which are independently regulated during cell proliferation. The M1 component contains multiple effector binding sites and is responsible for the complex allosteric regulation of the enzyme, whereas the M2 protein contains nonheme iron and a unique tyrosyl-free radical required for ribonucleotide reduction. Since the reaction is rate limiting for DNA synthesis, ribonucleotide reductase plays an important role in regulating cell division, and hence, cell proliferation. There are many inhibitors of ribonucleotide reductase and perhaps the most valuable one from a cell biology, biochemistry, and clinical point of view is the hydroxamic acid, hydroxyurea. This drug has also been very useful as a selective agent for isolating a variety of mammalian mutant cell lines altered in ribonucleotide reductase gene expression. Regulatory, structural, and biological characteristics of ribonucleotide reductase are reviewed, including evidence that ribonucleotide reductase, particularly the M2 protein, has an important early role to play in tumor promotion. In addition, modifications in the expressions of genes altered in hydroxyurea-resistant mutants and cultured in the absence or presence of hydroxyurea are discussed, with emphasis on changes in M2 protein, M1 protein, and the iron-storage protein ferritin.(ABSTRACT TRUNCATED AT 250 WORDS)

Allosteric Regulation↗
PubMed1978

Ipsilateral limb variation in cats during overground locomotion.

The timing interval between the onset of knee extensor EMG (vastus lateralis) and the onset of the ipsilateral elbow flexor EMG (brachialis) was studied in adult cats during overground walking, trotting and galloping. Concurrent finding of the animals in locomotion was used to relate the electrical activity of the muscles to the physical events in a step cycle. The observed variability in the interval between the onset of knee extensor EMG and the onset of elbow flexor EMG lead to the conclusion that it is not appropriate to postulate a rigid neural coupling mechanism for the control and coordination of ipsilateral limbs in locomotion.

Animals↗