Search PubMed⌕ Search

Biomedical subjects

S M Singh

Publications and source records attributed to S M Singh.

At least 19 recordsLinked to original sources
PubMed1995

Effect of Dalton's lymphoma on the antigen presentation of murine peritoneal macrophages.

The antigen presenting ability of the murine peritoneal macrophages in response to coincubation, in vitro, with Dalton's lymphoma (DL) cells was investigated. The antigen presenting ability of the macrophages was observed to increase on in vitro treatment with lipopolysaccharide (LPS) (10 micrograms/ml) and cisplatin (5 micrograms/ml). Coincubation of the macrophages with DL cells or DL-conditioned medium (DLCM) decreased the antigen presenting ability of the cisplatin or LPS treated macrophages. However, the DL-associated macrophages (DLAM) showed increased antigen presenting ability as compared with the normal peritoneal macrophages which was further increased on in vivo administration of the cisplatin (8 mg/kg body weight). The effect of the in vitro treatment of the macrophages with DLCM and/or LPS on the synthesis of DNA, RNA and proteins was also studied. The DLCM was found to inhibit the RNA as well as the protein synthesis of the LPS-treated macrophages. This study shows that DL differentially modulates the antigen presenting ability of the macrophages depending on the local conditions of cellular interactions involved in the in vitro or the in vivo systems.

Animals↗
PubMed1995

Synthesis and in vitro evaluation of 4-substituted N-(1,1-dimethylethyl)-3-oxo-4-androstene-17 beta-carboxamides as 5 alpha-reductase inhibitors and antiandrogens.

4-Substituted N-(1,1-dimethylethyl)-3-oxo-4-androstene-17 beta-carboxamides with the hydroxy (OH) 3d, mercapto (SH) 3e, chloro (Cl) 3f, and bromo (Br) 3g substituents at the 4-position were prepared in a two-step sequence with overall yields of 21%, 27%, 41%, and 37%, respectively. Compounds 3d-g showed weak inhibitory activity on human type I 5 alpha-reductase (IC50 > or = 700 nM) while they had intermediate inhibitory activity on human type II 5 alpha-reductase at IC50S of 172, 437, 192, and 387 nM, respectively. In androgen-sensitive Shionogi cells, the inhibition of dihydrotestosterone (DHT) stimulatory action on the proliferation of the androgen-sensitive cancer cells by all four compounds was high at IC50S of 170-279 nM compared with 117 nM for hydroxyflutamide. The present data show compounds having both moderate inhibition of human type II 5 alpha-reductase activity and relatively potent antiandrogenic action, two beneficial characteristics in the therapy of androgenic-sensitive diseases.

5-alpha Reductase Inhibitors↗
PubMed1995

Synthesis and in vitro activity of 17 beta-(N-alkyl/arylformamido)- and 17 beta-[(N-alkyl/aryl)alkyl/arylamido]-4-methyl-4-aza-3-oxo-5 alpha-androstan-3-ones as inhibitors of human 5 alpha-reductases and antagonists of the androgen receptor.

A number of 17 beta-(N-alkyl/arylformamido)- and 17 beta-[(N-alkyl/aryl)alkyl/arylamido]-3-oxo-4-aza-5 alpha-steroids were prepared from 17 beta-hydroxy-4-azasteroids and evaluated as inhibitors of human 5 alpha-reductase and antagonists of the androgen receptor. Jones' oxidation of 17 beta-hydroxy compounds gave the 17-keto-4-azasteroids, which were treated with amines and NaBH(OAc)3/NaBH3CN to give 17 beta-(N-alkyl/arylamino)-4-azasteroids 10-27. Alternatively, the above-indicated compounds were prepared from amines and 17-keto-4-azasteroids to form imines, which were then reduced with NaBH4. Formylation of amines 10-27 gave 17 beta-(N-alkylformamides) 28-41; however, acylation afforded 17 beta-[(N-alkyl/aryl)alkyl/arylamides] 42-53. In comparison to N,N-diethyl-4-methyl-3-oxo-4-aza-5 alpha-androstane-17 beta-carboxamide (4-MA; IC50 = 4.15 nM), 17 beta-(N-alkylformamido)-4-azasteroids were potent inhibitors of human type I 5 alpha-reductase, IC50 values of compounds 29, 30, 36, and 37 being measured as 3.05, 0.91, 2.19, and 2.35 nM, respectively. The structure-activity relationships suggest that the type I enzyme has preference for N-substituted straight alkyl side chains of four to five carbon atoms. On the other hand, formamides 32 (N-heptyl) and 33 (N-octyl), in addition to inhibiting the type I enzyme (IC50s = 9.57 and 16.9 nM, respectively), showed also strong inhibitory activity (IC50s = 14.0 and 18.4 nM, respectively) for human type II 5 alpha-reductase, in comparison to N-(1',1'-dimethylethyl)-3-oxo-4-aza-5 alpha-androst-1-ene-17 beta-carboxamide (MK-906; IC50 = 4.53 nM). Other compounds in this series showed moderate activities (IC50 > 100 nM) on the type II enzyme. 17 beta-[(N-Alkyl/aryl)alkyl/arylamides] 45, 46, 48, and 51 exhibited highly potent inhibitory activity for human type I 5 alpha-reductase with IC50s of 1.77, 2.42, 2.93, and 5.44 nM, respectively, while moderate to no effect was observed on the type II enzyme (100 < IC50s < 1000 nM), except for compound 48 (IC50 = 3.75 nM). In another substitution pattern, N-aryl/alkylamides were studied; an electron-donating group increased the potency of compound 51, whereas an electron-withdrawing group decreased the potency of compounds 52 and 53 compared to parent compound 50. In addition to their 5 alpha-reductase activities, 17 beta-(N-alkylformamides) were also studied for their inhibitory activities on dihydrotestosterone (DHT)-stimulated proliferation of androgen-sensitive Shionogi mouse mammary carcinoma cells (clone SEM-107).(ABSTRACT TRUNCATED AT 400 WORDS)

Androgen Receptor Antagonists↗
PubMed1995

The enzyme and inhibitors of 4-ene-3-oxosteroid 5 alpha-oxidoreductase.

Since evidence of 5 alpha-reductase activity in rabbit liver homogenate was discovered in 1954, the presence of this enzyme has been demonstrated in many other organs and tissues of mammalian species. 5 alpha-Reductase selectively transforms a 4-ene-3-oxosteroid (e.g., testosterone) irreversibly to the corresponding 5 alpha-3-oxosteroid (e.g., 5 alpha-dihydrotestosterone) in the presence of NADPH as an essential coenzyme at an optimal pH. However, excessive production of 5 alpha-dihydrotestosterone is the major cause of many androgen-related disorders, such as prostate cancer, benign prostatic hyperplasia, acne, female hirsutism, and male pattern baldness; therefore, inhibition of androgenic action by 5 alpha-reductase inhibitors is a logical treatment. During the past two decades, research has focused on understanding the biological functions and effects of 5 alpha-reductase and its 5 alpha-reduced metabolites: purification of the enzyme, substrates, and metabolites; characterization of their physical, chemical, and biochemical properties; analysis of the amino acid sequence of the enzyme; synthesis of various classes of molecules as potential inhibitors; and examination of the biological activity of the inhibitors in vitro and/or in vivo. This review summarizes the biochemical studies on this enzyme, suggests the mechanisms of action of the enzyme or inhibitors, and discusses the chemistry necessary for the preparation, structure-activity relationships, and in vitro and/or in vivo data obtained from the evaluation of nonsteroidal and steroidal compounds that have been tested as inhibitors of 5 alpha-reductase. In particular, IC50 and Ki values for relevant compounds will be compared according to molecular class. This review could function as a comprehensive working reference of what research has been accomplished so far and what problems remain to be solved in the future for those engaged in this interesting field.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1995

Effect of cisplatin and FK565 on the activation of tumor-associated and bone marrow-derived macrophages by Dalton's lymphoma.

The present investigations were undertaken to study the effect of Dalton's lymphoma (DL) in situ on the functions of DL-associated macrophages (DL-AM) and bone marrow-derived macrophages (BMDM) in C3H/He mice. DL-AM showed enhanced production of reactive nitrogen intermediates (RNI) and tumor necrosis factor (TNF) compared with normal peritoneal macrophages (NMO). BMDM of DL mice also showed enhanced production of RNI compared with BMDM of normal mice. These observations suggest that the presence of DL in situ creates an environment which favours the activation of both DL-AM and macrophage progenitors located at a distant site. The effect of in vivo administration of chemotherapeutic drugs cisplatin and FK565 on the activation of DL-AM by DL cells was also investigated. Both cisplatin and FK565 augmented RNI production of NMO but differed in their effect on DL-AM. The production of RNI by DL-AM of cisplatin-treated mice was inhibited, whereas in the FK565 group it was up-regulated.

Animals↗
PubMed1995

Effect of cisplatin administration on the proliferation and differentiation of bone marrow cells of tumour-bearing mice.

In the present study the effect of tumour growth with respect to two tumour systems (Dalton's lymphoma [DL] and P815) on the in vitro, colony-forming ability (CFA) and proliferation of the bone marrow cells (BMC) of C3H/He mice was investigated. The P815-bearing mice showed an enhanced bone marrow colony forming ability in vitro, in response to L929 conditioned medium (L929 CM) used as a source of CSF. On the other hand, DL-bearing mice did not have any significant alteration in this process compared to normal mice. In vivo, administration of cisplatin resulted in a significant rise in the CFA of normal as well as DL- or P815-bearing mice. The tumour-conditioned medium (TCM) and ascitic fluid (AF) of P815 but not of DL, was found to support the in vitro colony formation of BMC obtained from cisplatin-treated or untreated mice. The number of CFU-granulocyte-macrophage was predominantly high in the cultures of BMC incubated with TCM or AF of P815. The TCM and AF of P815 also enhanced the in vitro proliferation of BMC obtained from cisplatin-treated or untreated mice. In vivo, administration of cisplatin in normal mice resulted in enhanced numbers of peritoneal exudate macrophages (PEM) and PBL. Similarly, the number of PEM and PBL was augmented in both the P815- and DL-bearing mice. However, cisplatin administration in the tumour-bearing mice decreased the count of PEM, while the number of leucocytes remain unaffected. This study indicates that the cancer chemotherapeutic drug cisplatin can influence the differentiation of the bone marrow progenitor cells in response to tumour growth in situ.

Animals↗
PubMed1995

Local and systemic reduction by topical finasteride or flutamide of hamster flank organ size and enzyme activity.

The hamster flank organ is a widely used model of the control of sebaceous gland activity by androgens and anti-androgens. Finasteride, a 5 alpha-reductase inhibitor, was administered locally on the surface of the right flank organ and right ear twice daily for 4 weeks. The treatment caused similar 12% to 30% reductions in the size of the sebaceous glands in both flank organs. Moreover, relative mRNA levels of the androgen-regulated FAR-17a gene measured by in situ hybridization as well as [3H]-thymidine incorporation and 5 alpha-reductase activity were similarly decreased in the two flank organs after topical application. The pure anti-androgen flutamide, at the same doses, exerted a more potent effect on all the same parameters, and the effect was also comparable on both the treated and untreated sides of flank organs. Finasteride and flutamide significantly decreased ventral and dorsal prostatic weights after topical application. The present data show that the topical administration of finasteride, in analogy with flutamide, causes local inhibition of sebaceous gland growth in both the costovertebral organs and ears. However, as demonstrated by the similar inhibitory effect in the contralateral untreated side and the reduced weight of the dorsal and ventral lobes of the prostate and seminal vesicles, finasteride and flutamide both exert significant systemic effects.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1992

Chaos game representation of coding regions of human globin genes and alcohol dehydrogenase genes of phylogenetically divergent species.

Chaos game representation (CGR) is a novel holistic approach that provides a visual image of a DNA sequence quite different from the traditional linear arrangement of nucleotides. Although it is known that CGR patterns depict base composition and sequentiality, the biological significance of the specific features of each pattern is not understood. To systematically examine these features, we have examined the coding sequences of 7 human globin genes and 29 relatively conserved alcohol dehydrogenase (Adh) genes from phylogenetically divergent species. The CGRs of human globin cDNAs were similar to one another and to the entire human globin gene complex. Interestingly, human globin CGRs were also strikingly similar to human Adh CGRs. Adh CGRs were similar for genes of the same or closely related species but were different for relatively conserved Adh genes from distantly related species. Dinucleotide frequencies may account for the self-similar pattern that is characteristic of vertebrate CGRs and the genome-specific features of CGR patterns. Mutational frequencies of dinucleotides may vary among genome types. The special features of CG dinucleotides of vertebrates represent such an example. The CGR patterns examined thus far suggest that the evolution of a gene and its coding sequence should not be examined in isolation. Consideration should be given to genome-specific differential mutation rates for different dinucleotides or specific oligonucleotides.

Alcohol Dehydrogenase↗
PubMed1992

Pathogenicity of Sporotrichum pruninosum and Cladosporium oxysporum, isolated from the bronchial secretions of a patient, for laboratory mice.

In this study we have demonstrated the occurrence of Sporotrichum pruinosum and Cladosporium oxysporum in the bronchial secretions of a patient with a presumptive diagnosis of tuberculosis. This observation coupled with the ability of both fungi to cause infection and elicit tissue responses in experimentally infected mice supported a probable etiologic relationship with the patient which could not be confirmed in the absence of histologic evidence. In vitro some antimycotics were tested against S. pruinosum and C. oxysporum by the agar dilution method. Oxiconazole with a minimum inhibitory concentration of 0.1 micrograms/ml-1 after 72 h and amorolfine at a concentration of 0.001 micrograms/ml-1 after 72 h were the most active ones against S. pruinosum and C. oxysporum respectively. It is suggested that the isolation of S. pruinosum and C. oxysporum from patients with bronchopulmonary disorders should be viewed with caution. Clinical and laboratory evaluation of such patients should be done critically before arriving at a firm diagnosis.

Animals↗
PubMed1992

Hyalohyphomycosis caused by Paecilomyces variotii: a case report, animal pathogenicity and 'in vitro' sensitivity.

A case of cutaneous infection in a 25-year-old male caused by Paecilomyces variotii is described. Animal pathogenicity studies with normal and cortisone-treated mice revealed the predeliction of P. variotii for skin and liver in both normal and cortisone-treated mice and for lungs and heart only in immunosuppressed mice. 5-fluorocytosine gave the best MIC value for P. variotii in vitro. This report documents for the first time that P. variotii causes cutaneous infection.

Adult↗
PubMed1992

Pancreatic ductal and interstitial pressures in cats with chronic pancreatitis.

We investigated the etiology of interstitial hypertension in chronic pancreatitis by examining the relationship between pancreatic ductal and interstitial pressures in cats. The main pancreatic duct was cannulated in the tail of the gland and perfused at 1, 2, or 5 ml/hr, to simulate pancreatic secretion. Intraductal and interstitial pressures were measured in four groups of animals: (1) normal cats; (2) normal cats after acutely narrowing the main duct to 25% of its original diameter; (3) normal cats after encasing the body and tail in a rigid latex capsule; and (4) cats with chronic pancreatitis created by narrowing the main duct five weeks earlier. Duct perfusion increased intraductal pressure in all of the cats, but significantly more in groups 2, 3, and 4 compared to group 1. Pancreatic interstitial pressure was unchanged by duct perfusion in groups 1 and 2, but increased in groups 3 and 4. We concluded that the compliant tissue of the normal pancreas expanded to effectively dissipate the increase in duct pressure associated with duct perfusion. In chronic pancreatitis, the inelastic parenchyma and capsule limited the distensibility of the gland, which resulted in elevated interstitial pressures during duct perfusion.

Animals↗
PubMed1992

Effect of interferon-gamma priming on the activation of murine peritoneal macrophages to tumouricidal state by cisplatin, IL-1, and tumour necrosis factor (TNF): production of IL-1 and TNF.

The effect of interferon-gamma (IFN-gamma) priming of murine peritoneal macrophages on the activation to tumouricidal state by cisplatin, lipopolysaccharide (LPS)-IL-1 and TNF was investigated. Cisplatin-, LPS-, IL-1- or TNF-treated IFN-gamma-primed macrophages showed significantly enhanced tumouricidal activity and binding to tumour cells, compared with unprimed treated or untreated macrophages. Macrophages treated with cisplatin, LPS, IL-1 and TNF produced released and membrane-associated IL-1 and TNF activity which was significantly enhanced after priming with IFN-gamma. These observations suggest the use of IFN-gamma along with these biological response modifiers in designing immunotherapeutic protocols for treatment of malignancy.

Animals↗
PubMed1992

Clinical studies regarding the plaque removal efficacy of manual toothbrushes.

Two independent cross-over design studies were performed to compare two toothbrushes for their ability to remove plaque. In Study I, the Colgate Precision toothbrush was compared to the Oral-B 40 toothbrush; in Study II, the Colgate Precision toothbrush was compared to the Reach Full-Head soft toothbrush. A total of 54 and 72 adult male and female subjects who met the inclusion/exclusion criteria completed Study I and Study II, respectively. In each study, subjects refrained from brushing for 24 hours, and were screened for dental plaque on the facial and lingual surfaces of all natural teeth, using the Rustogi, et al. index. Based on mean scores and number of teeth, qualifying subjects were randomly assigned to one of two groups. Subjects were then scheduled to return one week later, having again abstained from all oral hygiene procedures for a 24-hour period. At this visit, each subject was evaluated for plaque, then brushed with his/her assigned toothbrush for sixty seconds, and was again scored for plaque after brushing. Subjects were instructed to resume their normal routine and return to the clinical site one week later. At this visit, a different test toothbrush was assigned to each group in a cross-over design. Plaque evaluations and toothbrushing procedures were again performed. In both studies, the Colgate Precision toothbrush was significantly more effective (p < 0.01) than either the Oral-B 40 toothbrush or the Reach Full-Head soft toothbrush in reducing whole mouth plaque scores, plaque scores at the gumline, and plaque scores at interproximal areas.

Adult↗
PubMed1992

HLA-D-region genomic DNA restriction fragments in DRw15 (DR2) familial narcolepsy.

Restriction fragment length polymorphism (RFLP) associated with the three human lenkocyte antigen (HLA)-D-region gene-specific cDNA probes (gene-specific DQ alpha, DQ beta and DP beta) was evaluated in two Caucasian families from southwestern Ontario, each with two confirmed narcoleptic siblings. The special feature of the two families is that the affected members are not necessarily DRw15 (previously DR2) positive. In family 1, of the two affected sibs one is DRw15 positive, whereas in family 2 all members including the two affected sibs are DRw15 negative. There is no association between narcolepsy and HLA haplotype in the two families. Further, the polymorphic DNA band patterns generated by a number of restriction enzymes do not show a relationship with the presence or absence of narcolepsy. The probe-specific DNA and patterns however do follow the HLA haplotypes associated with the DQ and DR loci. These results suggest that in DRw15-negative narcolepsy, the DNA patterns are not informative with respect to diagnosing or predicting the presence of narcolepsy. Further, such results argue for genetic heterogeneity in narcolepsy, and the role of DRw15 in the development of the disease could at best be viewed as contributory and not essential.

DNA↗
PubMed1992

Clinical efficacy of a triclosan/copolymer pre-brush rinse.

A five-day, double-blind parallel clinical study was conducted to determine the effect on plaque removal of a pre-brush rinse containing 0.03 triclosan (Irgacare MP, Ciba-Geigy Corp.) and 0.125% of a copolymer of methoxyethylene and maleic acid (Gantrez, GAF Corp.), as compared to a matching placebo pre-brush rinse. One hundred eleven subjects were stratified into two balanced groups according to baseline Quigley-Hein Plaque Index scores. Each group was randomly assigned to use either the triclosan/copolymer pre-brush rinse or the matching placebo pre-brush rinse. In order to determine plaque removal efficacy of the pre-brush rinses, subjects rinsed their mouths twice daily (mornings and evenings) for one minute with 15 ml of their assigned pre-brush rinse. Immediately after rinsing, subjects brushed their teeth for 30 seconds with a commercially available dentifrice containing 0.76% sodium monofluorophosphate and a soft-bristled toothbrush. The morning rinsing/brushing procedure was done under supervision at the clinical facility. The evening rinsing/brushing procedure was done at home. After five days' use of their assigned pre-brush rinse and toothbrushing, subjects were evaluated by the dental examiner for residual plaque using the modified Quigley-Hein Plaque Index scoring procedure. When mean five-day Quigley-Hein Plaque Index scores were compared for both groups, the triclosan/copolymer pre-brush rinse removed 22.54% more plaque from all surfaces of the teeth than the matching placebo pre-brush rinse. When mean Quigley-Hein Plaque Index decrements (the difference between baseline and five-day Quigley-Hein Plaque Index scores) were compared for both groups, the triclosan/copolymer pre-brush rinse removed more than twice as much plaque from all surfaces of the teeth than the matching placebo pre-brush rinse (33.99% efficacy versus 15.19% efficacy). When mean five-day Plaque Severity Index scores were compared for both groups, the triclosan/copolymer pre-brush rinse removed 46.15% more plaque from the "more difficult to brush" surfaces of the teeth than the matching placebo pre-brush rinse. rinse.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Effect of cisplatin treatment of human monocyte cell line U937 on the induction of tumoricidal activity.

U937, a human monocyte-like, cell line was checked for cytotoxic activity against tumor target cells. Untreated U937 cells showed little cytotoxicity against tumor cells. Granulocyte-macrophage colony stimulating factor (GM-CSF) and LPS significantly activated the U937 cells to tumoricidal state. Treatment of U937 cells with cisplatin did not enhance the tumoricidal activity. Similarly, interferon gamma (IFN-Y) and macrophage colony stimulating factor (M-CSF) could also not activate either the tumoricidal activity of U937 cells. Pretreatment of U937 cells with GM-CSF for 24 h and then the treatment with cisplatin significantly augmented the tumoricidal activity as compared to that of GM-CSF alone.

Cisplatin↗