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Biomedical subjects

M Lee

Publications and source records attributed to M Lee.

At least 577 records · Page 32Linked to original sources
PubMed1995

Novel cytotoxic DNA sequence and minor groove targeted photosensitizers: conjugates of pyrene and netropsin analogues.

The design, syntheses, photochemical and biological properties of conjugates of pyrene with pyrrole- (1) and imidazole-containing (2) analogues of netropsin are reported. The results of an ethidium displacement assay and circular dichroism (CD) titration studies show both compounds bind with a higher affinity to poly(dA-dT) than to poly(dG-dC). In addition they bind as strongly to T4 coliphage DNA as to calf thymus DNA suggesting the binding occurs in the minor groove. The quenching rate constants of the singlet excited states of agents 1 and 2 by molecular oxygen were found to be 8.5 x 10(9) M-1S-1 and 7.7 x 10(9) M-1S-1, suggesting the involvement of singlet oxygen. Both compounds showed some cytotoxicity to human chronic myeloid leukemia K562 cells in the dark. Upon irradiation the activities were significantly enhanced resulting in photoinduced dose modifications of 8 and 14 for 1 and 2, respectively under the conditions employed. Both agents were markedly more phototoxic than 1-pyrenebutyric acid 8. To address the mechanism of action of compounds 1 and 2 their photoactivated abilities to produce DNA strand breaks were measured. Both agents caused increased single strand breakage with increasing UV exposure. The concentrations (EC50) of 1 and 2 needed to cause 50% single-strand cleavage of pBR322 DNA upon UV-A activation were found to be 40 microM and 45 microM, respectively. In contrast, no DNA strand breaks were observed in the dark with either conjugate or with 8 following irradiation. DNA strand breaks were measured in drug treated K562 cells using alkaline elution.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Agents↗
PubMed1995

Central neurocytoma. A clinicopathological, immunohistochemical and ultrastructural study of 7 cases.

Characterised by distinctive clinicopathological features, the central neurocytoma (CN) is an uncommon and possibly under-recognised primary cerebral neuronal neoplasm. We present clinical and pathological details of seven patients with CN. Histological examination revealed a greater diversity of morphological appearances than is typically described in CN. No anaplastic features were identified. Cellular areas resembling both oligodendroglioma and ependymoma were present in all cases, but each tumour also contained stroma rich areas with hyalinised or aneurysmal vessels. Synaptophysin was expressed by all tumours and probably represents the immunohistochemical marker of choice for identifying CN. Distinguishing ultrastructural features included rounded cell bodies separated by numerous cell processes containing microtubules, pleomorphic neurosecretory granules and occasional synapses. Ki-67 immunostaining revealed a low cell proliferation index in each case. The distinction of CN from other pathological mimics can be reliably made using this multiparametric approach to diagnosis. The generally benign behaviour of CN is confirmed, though there was one patient death in the follow-up period of 10-122 months. Aggressive behaviour in this case was not associated with anaplastic histological features.

Adult↗
PubMed1995

Spinal models.

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Biomechanical Phenomena↗
PubMed1995

Physical therapy to improve functioning of older people in residential care facilities.

BACKGROUND AND PURPOSE: The purpose of this study was to determine the effectiveness of an individualized physical therapy mobility training program on the gait, balance, and functional performance of elderly individuals living in residential care facilities. SUBJECTS: Twenty-seven elderly individuals with impaired balance and difficulty performing at least one functional activity participated in the study. The subjects ranged in age from 71 to 97 years (mean = 87.1, SD = 6.7). METHODS: Balance and gait speed were assessed at baseline and following physical therapy that consisted of exercises to improve specific functional limitations. Outcomes were reassessed 1 month following completion of the physical therapy. RESULTS: Gait and balance outcomes were analyzed using a one-way repeated-measures analysis of variance. Improvement was obtained in balance, which was maintained at 1 month follow-up. Gait speed did not improve to a level of statistical significance. CONCLUSION AND DISCUSSION: After physical therapy, subjects improved in balance and functional performance. An improvement in gait speed may require a longer duration of treatment.

Activities of Daily Living↗
PubMed1995

Angiotensin II receptor blockade in TGR(mREN2)27: effects of renin-angiotensin-system gene expression and cardiovascular functions.

OBJECTIVE: To study the effect of angiotensin II receptor AT1 blockade on blood pressure, gene expression and pathomorphology of transgenic rats harbouring the mouse Ren-2 gene [TGR(mREN2)27], that develop fulminant hypertension while exhibiting suppressed components of the circulating renin-angiotensin system. DESIGN: TGR(mREN2)27 were treated orally with the newly developed AT1-specific angiotensin receptor antagonist Telmisartan, 4'-[(1,4'-dimethyl-2'-propyl[2,6'-bi-1H-benzimidazol]-1'-yl) methyl]-[1,1'-biphenyl]-2-carboxylic acid, in three doses (0.1, 1 and 3 mg/kg body weight) for 9 weeks. METHODS: The concentrations of the renin-angiotensin system components were analysed in plasma and tissues by radioimmunoassay. Messenger RNA levels for the angiotensinogen and renin genes were quantified by RNAase protection assay in several tissues. Heart hypertrophy and kidney morphology and function were monitored at the end of the treatment. RESULTS: In contrast to 0.1 mg/kg, 1 and 3 mg/kg Telmisartan normalized tail blood pressure measured once a week. Plasma renin and angiotensin II concentration increases were dose-dependent. The renin-angiotensin system genes in various cardiovascular organs were differentially regulated by angiotensin II receptor blockade. Treatment with Telmisartan stimulated angiotensinogen gene expression in the liver, kidney and heart, whereas it remained unchanged in the hypothalamus, thymus and adrenal gland. In the kidney, the expression of the endogenous, but not of the mouse Ren-2 gene, was increased in parallel to the renin concentration. Telmisartan reduced the severe glomerulosclerosis and proteinuria as well as cardiac hypertrophy observed in untreated TGR(mREN2)27 even with the lowest dose of 0.1 mg/kg, at which the blood pressure of the rats still exceeded 225 mmHg and the plasma renin-angiotensin system parameters were unchanged. CONCLUSION: From these experiments using a specific antagonist we can conclude that high blood pressure in TGR(mREN2)27 is angiotensin II-dependent. Furthermore, the expression of the renin-angiotensin system genes seems to be regulated not only by blood pressure and the plasma renin-angiotensin system but also by other, tissue-specific mechanisms. Pathomorphological changes in the kidney and in the heart do not seem to be caused by the systemic hypertension exclusively, but are also influenced by angiotensin II directly.

Adrenal Glands↗
PubMed1995

Ethanolamine sclerotherapy of a renal cyst.

We report the effective use of 5% ethanolamine oleate to sclerose a large simple renal cyst. The comparative advantages of ethanolamine versus other sclerosants are discussed in terms of adverse effects, availability and convenience. Guidelines to optimize sclerotherapy with ethanolamine are provided.

Aged↗
PubMed1995

Comparison of a rapid nonisotopic polymerase chain reaction assay with four commonly used methods for the early diagnosis of human immunodeficiency virus type 1 infection in neonates and children.

To initiate antiretroviral therapy and prophylaxis for Pneumocystis carinii pneumonia, it is important to identify human immunodeficiency virus (HIV-1)-infected infants as soon after birth as possible. This study was undertaken to evaluate a novel 5-hour nonisotopic (NI) polymerase chain reaction (PCR) assay (Amplicor PCR; Roche Molecular Systems) and four other commonly used HIV-1 diagnostic tests including culture, oligonucleotide hybridization PCR, p24 antigen and immune complex-dissociated (ICD) p24 antigen tests and to determine the optimal age at which to perform these tests for the early and rapid diagnosis of HIV-1 in infants and children. We prospectively evaluated 225 infants and children, including 114 neonates, for HIV-1 infection. HIV-1 infection was defined as 2 positive HIV cultures. Of the 225 infants and children, 57 were infected, 138 were uninfected and 30 were of unknown (Centers for Disease Control and Prevention Classification P0) status. The sensitivity of NI PCR was 60% in cord blood, 40% at 0 to 2 days, 67 to 80% in the neonate (3 to 30 days) and 95 to 100% after 1 month of age. NI PCR was as sensitive as oligonucleotide hybridization PCR, culture, p24 antigen and ICD p24 antigen in the first 2 months of life and was more sensitive than p24 antigen or ICD p24 antigen thereafter. Specificity was 94% for cord blood and 99 to 100% for all age groups. The majority of HIV-1-infected newborns can be identified with NI PCR if testing is performed at birth and again between the third and fourth weeks of life. For older infants and children 2 NI PCR tests can correctly diagnose 98.5% of infected and uninfected infants and children. NI PCR of umbilical cord blood might also be useful as an initial screening test to identify infants who may be infected with HIV-1.

AIDS Serodiagnosis↗
PubMed1995

Prevention and treatment of nonsteroidal anti-inflammatory drug-induced gastropathy.

Numerous human studies have shown that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with various gastroduodenal mucosal lesions, collectively referred to as NSAID gastropathy. NSAIDs should not be prescribed unless there is a clear-cut indication for them. Acetaminophen should be used initially to treat most patients with osteoarthritis. If NSAID therapy is required, the lowest possible NSAID dose should be prescribed, and the patient should be advised to reduce any modifiable risk factors. In patients who take NSAIDs occasionally and are at low risk for NSAID gastropathy, no specific prophylactic measures seem justified. In high-risk NSAID users, risk reduction and prophylaxis with misoprostol would be appropriate. If an ulcer is documented during NSAID treatment, NSAID therapy should be discontinued if possible. However, NSAID therapy need not be discontinued if it is therapeutically justifiable and if appropriate antiulcer treatment is initiated.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1995

Aspirin, age, and proximity to lymphoid nodules influence cell proliferation parameters in rat colonic crypts.

Recent epidemiological studies have demonstrated a correlation between regular aspirin (acetylsalicylic acid) use and decrease risk for the development of fatal colorectal cancer. An increase in the size of the cell proliferation compartment in colorectal crypts has been correlated with an increased risk for the development of colon cancer in animals and in humans. To determine if acetylsalicylic acid acts to decrease the size of the cell proliferation compartment, young (3 month) and old (22 month) rats were treated intragastrically with: 1 the vehicle for acetylsalicylic acid delivery (0.25% wt/vol carboxymetylcellulose in 0.15 N (HCl), 2 a single dose of acetylsalicylic acid (100 mg/kg), or 3 acetylsalicylic acid (30 mg/kg) given daily for 30 days. One day after the last treatment, colons were resected, fixed, sectioned and mounted on slides for immunohistochemical staining with a monoclonal antibody to proliferating cell nuclear antigen to assess cell proliferation parameters in the colonic crypts. The results were subjected to three way analysis of variance to assess the effects of: 1 rat age, 2 acute or chronic acetylsalicylic acid treatment, and 3 location of crypts over and away from aggregates of lymphoid nodules on the crypt proliferative parameters. Results demonstrated that: 1 acetylsalicylic acid treatment caused on overall decrease in the proliferative zone height, as measured in number of cells in the crypt column, 2 that crypts located over aggregates of lymphoid nodules had significantly higher proliferative activity than crypts located away from aggregates of lymphoid nodules, and 3 after chronic acetylsalicylic acid treatment there was a greater suppression of proliferative zone height in the crypts of old rats than in the crypts of young rats. In conclusion, acute and chronic intragastric delivery of acetylsalicylic acid caused an overall downward shift in the cell proliferation compartment of colonic crypts of young and of old rats. Whether or not acetylsalicylic acid administration will cause the same proliferative zone height response in carcinogen-treated rats is not yet established.

Aging↗
PubMed1995

The Adelaide preschool language unit: results of follow-up.

OBJECTIVE: To determine educational, social and behavioural functioning of children who had been involved in a preschool language intervention programme between 1982 and 1990. METHODOLOGY: Fifty children who attended the Unit were available for follow-up. The children were divided into three groups: (i) language disorder; (ii) speech disorder; and (iii) mixed speech and language disorder. A psychologist administered educational, cognitive and social behavioural tests. Speech, language and articulation were assessed by a speech pathologist. RESULTS: Cognitively, the 'mixed' speech and language group obtained lower scores than the speech and language disorder children; results on educational tests were also generally lower. All three groups were significantly underachieving in areas of language, reading, spelling and arithmetic relative to their performance IQ. No socialization problems were found. CONCLUSIONS: Severe speech and language disorders in young children, even after periods of intensive intervention, have a significant effect on later educational achievement even when children appear to be 'coping' in their educational settings.

Child↗
PubMed1995

Mutations on the DNA-binding surface of TATA-binding protein can specifically impair the response to acidic activators in vivo.

The TATA-binding protein (TBP) contains a concave surface that interacts specifically with TATA promoter elements and a convex surface that mediates protein-protein interactions with general and gene-specific transcription factors. Biochemical experiments suggest that interactions between activator proteins and TBP are important in stimulating transcription by the RNA polymerase II machinery. To gain insight into the role of TBP in mediating transcriptional activation in vivo, we implemented a genetic strategy in Saccharomyces cerevisiae that involved the use of a TBP derivative with altered specificity for TATA elements. By genetically screening a set of TBP mutant libraries that were biased to the convex surface that mediates protein-protein interactions, we identified TBP derivatives that are impaired in the response to three acidic activators (Gcn4, Gal4, and Ace1) but appear normal for constitutive polymerase II transcription. A genetic complementation assay indicates that the activation-defective phenotypes reflect specific functional properties of the TBP derivatives rather than an indirect effect on transcription. Surprisingly, three of the four activation-defective mutants affect residues that directly contact DNA. Moreover, all four mutants are defective for TATA element binding, but they interact normally with an acidic activation domain and TFIIB. In addition, we show that a subset of TBP derivatives with mutations on the DNA-binding surface of TBP are also compromised in their responses to acidic activators in vivo. These observations suggest that interactions at the TBP-TATA element interface can specifically affect the response to acidic activator proteins in vivo.

Base Sequence↗