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Biomedical subjects

M L Lim

Publications and source records attributed to M L Lim.

At least 19 recordsLinked to original sources
PubMed2001

The protonophore CCCP induces mitochondrial permeability transition without cytochrome c release in human osteosarcoma cells.

Mitochondrial permeability transition (MPT) and cytochrome c redistribution from mitochondria are two events associated with apoptosis. We investigated whether an MPT event obligatorily leads to cytochrome c release in vivo. We have previously shown that treatment of human osteosarcoma cells with the protonophore m-chlorophenylhydrazone (CCCP) for 6 h induces MPT and mitochondrial swelling without significant cell death. Here we demonstrate that release of cytochrome c does not occur and the cells remain viable even after 72 h of treatment with CCCP. Bax is not mobilized to mitochondria under these conditions. However, subsequent exposure of CCCP-treated cells to etoposide or staurosporine for 48 h results in rapid cell death and cytochrome c release that is accompanied by Bax association with mitochondria, demonstrating competency of these mitochondria to release cytochrome c with additional triggers. Our findings suggest that MPT is not a sufficient condition, in itself, to effect cytochrome c release.

Bone Neoplasms↗
PubMed2001

A perspective on tropical sprue.

A diagnosis of tropical sprue, an infrequent affliction of inhabitants and travelers in tropical regions, should be considered in patients with a compatible history, malabsorption, and chronic diarrhea. It can occur in either endemic or epidemic form and can be preceded by acute gastroenteritis. The cause of tropical sprue is still unknown, although most data support an infectious etiology. Therapeutic experience is greatest with folic acid and tetracycline. Most patients can be expected to recover with proper nutritional support, although relapses and slow responses occur.

Folic Acid↗
PubMed2001

DPC-083. DuPont Pharmaceuticals.

DPC-083 and DPC-961 are non-nucleoside reverse transcriptase inhibitors (NNRTIs) under development by DuPont Pharmaceuticals for the potential treatment of HIV infection [312865]. Phase I trials were completed by September 2000 [383661], and by April 2001, DPC-083 was in phase II trials as a once-daily oral dose in combination therapy, with phase III studies expected to begin in the third quarter of 2001 [392761]. NDA filing is anticipated for 2003, for which the company would expect an FDA expedited review [405548]. DPC-083 and DPC-961 possess antiviral activity against mutant variants of HIV-1, including the K103N mutant, and have the same potency as efavirenz against wild-type virus in rhesus monkeys [312865]. DuPont has also described a series of novel tricyclic quinazolinones which were found to possess noteworthy biological activity during investigation of DPC-083 and DPC-961.

Anti-HIV Agents↗
PubMed1999

Concurrent increase of oxidative DNA damage and lipid peroxidation together with mitochondrial DNA mutation in human lung tissues during aging--smoking enhances oxidative stress on the aged tissues.

Although mutation of mitochondrial DNA (mtDNA) in human tissues has been established to associate with intrinsic aging, the impact of environmental factors on the formation and accumulation of mtDNA mutations and oxidative DNA damage in human tissues is poorly understood. We have investigated the levels of mtDNA with the 4977-bp deletion and A3243G point mutation, oxidative DNA damage (indicated by the formation of 8-hydroxy-2'-deoxyguanosine, 8-OH-dG), and lipid peroxides in lung tissues from smokers and nonsmokers of subjects of different ages. The results showed concurrent age-dependent increase of the 4977-bp deleted mtDNA (P < 0.001), 8-OH-dG (P < 0.05), and lipid peroxides (P < 0.05) in the human lung. In the group of subjects above 60 years old, smokers had more extensive DNA damage and lipid peroxidation than did the nonsmokers. However, the levels of mtDNA with the 4977-bp deletion and A3243G point mutation in the lung of smokers were not significantly different from those of the age-matched nonsmokers. Taken together, these results suggest that accumulation of mtDNA with the 4977-bp deletion together with oxidative DNA damage and lipid peroxides is associated with aging and that smoking enhances oxidative damage in human lung tissues.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1993

Estimate of perinatal mortality risk.

Perinatal mortality is usually calculated according to the World Health Organisation as stillbirth and first week mortality at a specified week of gestation divided by all births at that same gestational week. This is not a meaningful indicator of the risk of future perinatal death for a living fetus. We have developed an approach to estimate the prospective risk of perinatal mortality. Data were derived from the Perinatal Database of the Netherlands. We calculated the prospective risk of perinatal mortality by dividing all future perinatal deaths from a certain week of gestation by all fetuses that remained undelivered. Using this statistic there is a decline in risk from 16 to 39 gestational weeks and an increase from 39 weeks onwards.

Databases, Factual↗
PubMed1989

Nipple aspirate fluids in adult nonlactating women--lactose content, cationic Na+, K+, Na+/K+ ratio, and coloration.

The presence of lactose in nipple secretions is considered biochemical evidence of breast secretory activity, and has been reported to occur more frequently in white compared to brownish or green colored breast fluid. We studied lactose, Na+, and K+ concentrations, the Na+/K+ ratio, and the coloration of nipple aspirate fluid (NAF) from 49 nonpregnant women. A significant relationship was found between the concentrations of lactose, Na+, and K+, and age and the coloration of NAF. Lactose was present in 22/49 (44.8%) of the NAF samples and declined with age from 100% positivity in women less than or equal to 29 years to 29% in those less than or equal to 35 years. In NAF of deep yellow, brown and green colorations, only traces of lactose were found. Na+ and K+ increased with age and with darker colorations compared to white, pale yellow, or colorless NAF. Lactose was present in NAF samples from both parous and nulliparous younger women, indicating that the breasts of many nonpregnant women respond to prolactin stimulation; hence, lactose may provide a simple marker indicating active physiologic secretory activity of the breast. As reported previously, NAF of darker coloration, containing elevated levels of cholesterol, cholesterol oxidation products, and other substances, suggests retention and impaired reabsorption of these and other products of secretion. Because of the secretion and temporary retention by the breast glands of chemical substances of exogenous and endogenous origin, including mutagens and carcinogens, lactose concentration and coloration of NAF may be useful as markers of secretion and reabsorption in future physiologically based clinical and epidemiologic studies of the pathogenesis of breast disease.

Adult↗
PubMed1989

Beta-thalassemia mutations in Indonesia and their linkage to beta haplotypes.

A total of 72 chromosomes from 36 Indonesian patients, 23 with beta-thalassemia major and 13 with Hb E-beta-thalassemia, were analyzed by specific oligonucleotide hybridization after DNA amplification. Thirteen had the beta E mutation (codon 26 GAG----AAG). Of the 59-beta-thalassemic chromosomes, 32 were of the variant IVS-1 nt5 (G----C). Seven had the mutation IVS-2 nt654 (C----T), one had the mutation codon 41/42 (deletion CTTT), and one had the mutation codon 17 (AAG----TAG). Another six with the mutation IVS-1 nt1 (G----T), one with the mutation IVS-1 nt1 (G----A), four with the mutation codon 15 (TGG----TAG), one with a mutation codon 30 (AGG----ACG), and one with a mutation codon 35 (deletion C) were first identified by direct sequencing of a patient's genomic DNA followed by further hybridizing other patients' DNA with the appropriate oligonucleotide probes. Five did not carry the common mutations previously described in Asian populations. The four most prevalent mutations encountered made up 83% of the total number of beta-thalassemic chromosomes studied. The most common mutation, IVS-1 nt5 (G----C), was mostly associated with two different haplotypes.

Blotting, Southern↗
PubMed1987

Elevated G gamma gene expression with specific beta S gene haplotype, normal gamma gene maps and presence of the Xmn I site -158 5' to the G gamma gene in Indian sickle cell anemia.

In nine Indian patients ranging in age between four and 61 years, with mild Hb SS disease and very high Hb F levels, the G gamma globin chain levels of their fetal hemoglobin ranged between 64.0% and 70.0%, with a mean of 68.1% (S.D. +/- 2.6) of the total amount of gamma-globin chains. Eight of the nine patients were homozygous for a specific beta S gene haplotype #31. The other one was doubly heterozygous for the same specific haplotype and another haplotype, which differed from haplotype #31 by the presence of Bam HI site 3' to the beta gene and absence of Pvu II site 5' to the psi beta gene. The gamma gene organization studied by Pst I restriction enzyme analysis was found to be normal and the Xmn I site -158 5' to G gamma gene was present in all patients examined.

Anemia, Sickle Cell↗
PubMed1987

Quantitation of hepatitis B virus DNA in serum of patients with hepatoma.

Hepatitis B virus (HBV) DNA in the serum of 31 patients with histologically confirmed primary hepatocellular carcinoma (PHC) from Malaysia and Indonesia was quantitated by densitometric scanning of autoradiograms obtained by Southern blot DNA hybridization, after electrophoresis using a 32P DNA cloned into plasmid pBR325 as a probe. This quantitation after electrophoresis is more informative than the usual spot hybridization technique. Five of the 31 sera were positive for HBV DNA. Levels ranged between 1.36 pq and 143.18 pq per ml of serum, and the levels of HBsAg, anti-HBs, anti-HBc, HBeAg and anti-HBe in the serum were serologically determined. All five sera positive for HBV DNA were also positive for HBsAg. Three of the five positive for HBV DNA were positive for HBeAg and negative for anti-HBe. Two of the sera positive for HBV DNA were negative for HBeAg but positive for anti-HBe. All sera negative for HBV DNA were also negative for HBeAg. Many sera which were negative for HBV DNA and HBeAg were positive for HBsAg. Of the 31 sera from PHC patients, 23 had at least one HBV marker positive (74.2%).

Carcinoma, Hepatocellular↗
PubMed1986

Sickle cell anemia associated with alpha-thalassemia in Malaysian Indians.

The Indian rubber estate workers in Negri Sembilan, Malaysia, who originated from Orissa in India were found to have a high frequency of Hb S (Joishy SK, Hassan K: Clin Res 28:280, 1980). Unlike the usually severe clinical picture of sickle cell anemia seen in African and American blacks, the clinical picture of the disease in this population was mild and many have reached old age. We studied the leukocyte DNA of 12 patients with sickle cell anemia, ranging in age from 4 to 61 years and 30 sickle cell trait carriers, ranging in age from 7 to 63 years, for the presence of alpha-globin gene deletions by gene mapping according to Southern (Southern EM: J Mol Biol 98:503, 1975), using alpha- and zeta-globin gene probes obtained by nick translation of the alpha- and zeta-globin genes cloned into plasmid. All 12 sickle cell anemia patients were found to have alpha-thalassemia2 (alpha-thal2), either in the homozygous or heterozygous condition. Of the Hb S trait carriers, six did not have alpha-thal2 or alpha-thal1 and 24 had alpha-thal2 (15 heterozygous, 9 homozygous). Seven of these Hb S trait carriers with alpha-thal2 had an additional gene abnormality. Five of them had a fast-moving Eco RI fragment 5.6 kb long that hybridized with zeta-specific probe but not with alpha-specific probe. An unusual DNA pattern of a different type was further found in the other two. Bgl II restriction analysis showed that the alpha-thal2 was mostly of the rightward deletion alpha-thal1 genotype. None of the sickle cell anemia patients and Hb S trait carriers had deletion type alpha-thal1. The sickle cell anemia patients had very high levels of Hb F and low levels of Hb A2. The Hb S trait carriers with alpha-thal2 had relatively low levels of Hb S.

Adolescent↗
PubMed1983

Depression after stroke: a hospital treatment survey.

Treatment with anti-depressant drugs of 61 inpatients admitted on account of stroke was studied. Eighteen patients (30%) were being so treated. Only 5 patients (17%) with dysphasia were being treated with anti-depressant drugs compared with 13 patients (41%) without dysphasia (P less than 0.05). Dosage levels used were generally low and only one patient had been referred for a psychiatric opinion. We suggest that the difference in anti-depressant usage is because dysphasic patients are more difficult to assess and therefore less likely to have depressive symptoms recognized and treatment given. We also think that psychiatric referral should be used more often for assessment of stroke patients and for advice about treatment.

Aged↗
PubMed1982

The influence of warfarin of levamisole on the incidence of metastases following local irradiation of a solid tumor.

KHT sarcomas were implanted in the right rear legs of C3H mice. An x-ray dose of 6000 rad, delivered in ten equal fractions over 12 days, resulted in 60% local tumor control, but 83% of these mice developed metastases. Three strategies to use the tumoricidal effect of x-radiation and reduce the incidence of metastases were compared. A modification of the fractionation scheme to deliver an initial large fraction of 1800 rad followed by seven 600-rad fractions resulted in a decreased incidence of metastases compared with the same dose delivered in ten equal fractions. The use of warfarin anticoagulation during the ten-fraction course of radiation resulted in a small decrease in the incidence of metastases. Immune stimulation with levamisole, injected subcutaneously every second day during the irradiation, also resulted in a decrease in the incidence of metastases. However, when warfarin or levamisole were combined with the eight-fraction radiation scheme there were fewer metastases than following the ten-fraction scheme. The combination of the eight-fraction radiation course with levamisole also produced a significant increase in primary tumor control. In this treatment regimen, therefore, levamisole appears to act as a radiation sensitizer. An hypothesis to explain this action is proposed.

Animals↗
PubMed1981

Dose local x-irradiation of a tumor increase the incidence of metastases?

KHT sarcomas were implanted into the right rear legs of C3H mice. Animals receiving no treatment died at 32 days with a 67% incidence of metastatic tumors. A dose of 6000 rads in ten fractions over 12 days, starting ten days after implant, delivered to the primary tumor (with the remainder of the body shielded) produced 55% local tumor control. However, 83% of the mice with local tumor control, subsequently developed metastatic lesions. Amputation of the tumor-bearing leg either prior to the start of radiation treatment, at the end of treatment or at intervals during treatment or sham treatment, indicated that 1) metastases occurred predominantly during the initial three radiation fractions and 2) the increased incidence of metastases following irradiation was a result of the manipulations associated with the irradiation and not the irradiation per se. Irradiation did not change the distribution of organ sites involved with metastatic tumors compared to untreated or sham-treated tumors.

Animals↗
PubMed1979

Esthesioneuroblastoma.

Esthesioneuroblastoma is an uncommon tumor of neural crest origin arising in the nasal cavity. Since 1966, 97 cases have been reported in the world literature. In this report an analysis is presented of the following aspects of these 97 patients: age and sex distribution, disease staging, treatment results, interval to recurrence, and survival. Staging was according to a system proposed by Kadish et al. There is a bimodal age distribution with peaks in age groups 11-20 years and 51-60 years. Prognosis is favorable in early stage disease (A and B) with 3-year crude survivals of 88.9% and 83.3%, respectively. Stage C patients have a poor prognosis, with 52.9% surviving 3 years. Treatment consisted of radiotherapy, surgery, or a combination of radiotherapy and surgery. In stage A, prognosis is favorable in all three treatment groups with one 1 of 24 patients dying of recurrent disease. In stage B, recurrence rates and 3-year survivals are also similar in the three treatment groups. Thus, single modality treatment is as effective as combined treatment for early stage disease. Local recurrence is the predominant site of failure occurring in 68% of recurrences. The overall crude survival for the 97 patients was 95.4%, while the determinate survival (corrected for intercurrent disease) was 70.8%.

Adolescent↗