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Biomedical subjects

S K Sengupta

Publications and source records attributed to S K Sengupta.

At least 55 records · Page 3Linked to original sources
PubMed1984

Donovanosis affecting cervix, uterus, and adnexae.

Donovanosis (granuloma inguinale), a disease often related to sexual contact, has been a clinical problem in Papua New Guinea for more than 9 decades. It is a common cause of anogenital lesions in females in this country. Lesions on the cervix or vaginal vault, and extension of the disease process from the external genitalia to the uterus, tubes and ovaries, are thought to be rare. In this study an attempt was made to discover the frequency of involvement of cervix, uterus and adnexae, with or without external genital involvement, by retrospectively analyzing the histological and clinical records of patients with anogenital donovanosis for a period of 8 years (1975-1982). In 35 of 351 patients (10%), donovanosis involved the cervix. The clinical profile of these cases, certain unusual features in a few cases, and the pathological findings are discussed.

Adnexal Diseases↗
PubMed1983

DNA binding studies of 7-bulky-substituted actinomycin analogues.

The DNA binding properties of several 7-substituted aralkylaminoactinomycin D analogues have been studied by spectrophotometry, DNA melting temperature studies, DNA-drug dissociation studies, and circular dichroism. Despite the presence of such bulky groups as 2-pyrrolylmethylamino or 3,4-dichlorobenzylamino at the 7 position, these analogues bind to DNA, inhibit RNA synthesis, and exhibit antitumor activity. A model is proposed for the interaction of the pyrrolyl analogue with phosphate groups of the DNA binding site, explaining the increased binding affinity for DNA of this actinomycin D analogue.

Animals↗
PubMed1983

Tetracyclic chromophoric analogues of actinomycin D: synthesis, structure elucidation and interconvertibility from one form to another, antitumor activity, and structure-activity relationships.

Two different tetracyclic chromophoric analogues of actinomycin D have been synthesized by engaging two chromophoric DNA-binding functions in actinomycin D, i.e., 2-amino and 3-oxo, into either a 1,4-oxazin-2-one or an oxazole ring system. A third analogue has an extra quinone function at C-8 of the oxazole analogue. In all the analogues the chemical integrity of the peptide lactones of the parent antibiotic is kept intact, but their sterochemistry is altered. The analogues are designed as transport-modified prodrug forms of either the tricyclic active analogues of actinomycin D or actinomycin D itself. All analogues exhibit cytotoxicity that is several-fold less potent than AMD; they also have no binding affinity toward extracellular DNA. Nonetheless, the analogues of the first and the third series show improved antitumor activities (P388 leukemia, CDF1 mice). In fact, two of these analogues having a phenyl substituent at the C-3 site of the oxazinone ring or the C-2 position of the 8-oxo-8H-oxazole ring exhibit the highest antitumor effects. Most of the analogues are active over a broader dose range than actinomycin D and are 6- to 16-fold less cytotoxic to human lymphoblastic leukemia (CCFR-CEM) cells in vitro. The analogues with the most pronounced antitumor activity are those that retain most elements in the peptide stereochemistry of actinomycin D and have a quinone function or demonstrate susceptibility of their chromophores to biotransformation.

Animals↗
PubMed1983

Primary endometrial and endocervical granuloma inguinale (donovanosis). Case report.

Primary endometrial and endocervical granuloma inguinale (donovanosis) was diagnosed in an 18-year-old Melanesian woman in Papua New Guinea. Granulomatous involvement of the parametrium, salpinges, ovaries, and ureters was associated with ureteric obstruction and bilateral hydronephrosis. Granuloma inguinale of the cervix, labia majora, and anus developed after diagnostic endometrial curettage. Treatment with tetracycline and later chloramphenicol had to be stopped because of poor patient compliance. Hysterectomy was performed, after which the patient made a good recovery. This appears to be the first case of primary endometrial and endocervical granuloma inguinale to be reported.

Adolescent↗
PubMed1982

DNA-binding specificity and RNA polymerase inhibitory activity of bis(aminoalkyl)anthraquinones and bis(methylthio)vinylquinolinium iodides.

The determination of DNA-binding specificities for a series of bis(methylthio)vinylquinolinium iodides and two bis (aminoalkyl)-anthraquinones was accomplished by spectral analysis, equilibrium dialysis, elevation of melting temperature, and inhibition of DNA function as a template for Escherichia coli RNA-polymerase transcription activity in vitro. Studies of complex formation were carried out by comparison of difference spectra of the compounds in the presence of native double-stranded DNA and separated-strand DNA. Base specificity of the interaction between DNA and the compounds was demonstrated for both series, particularly for the anthraquinones, for the guanine-cytosine base pair. Comparison of the difference spectra of the compounds in the presence of DNA with varied base-pair ratios showed a strong preference of the anthraquinones for the guanine-cytosine base pair, but the quinolinium compounds showed no preference. The linear-binding isotherm for the quinolinium compounds indicated one type of binding site, while two types of binding sites were apparent for the anthraquinones. Since only one anthraquinone was active in leukemia tests, factors other than DNA binding must account for the activity of the antileukemic derivative.

Animals↗
PubMed1982

Carbon-7 substituted actinomycin D analogues as improved antitumor agents: synthesis and DNA-binding and biological properties.

7-(2,3-Epoxypropoxy)actinomycin D has been synthesized along with its major companion product, 7-(2,3-dihydroxypropoxy)actinomycin D. They were characterized by UV-visible and CD spectra and by NMR studies. According to UV-visible absorptiometry, circular dichroism, and thermal denaturation studies, they bind to DNA in a manner that is comparable to actinomycin D. The analogues are, like actinomycin D, extremely cytotoxic to human lymphoblastic leukemic cells (CCRF-CEM) in vitro but are significantly less toxic than actinomycin D to normal CDF1 mice is vivo. Unlike actinomycin, these analogues are metabolized in rats, and the metabolites are excreted in rat urine at a rapid rate. Compared to actinomycin D, the antitumor activity of the 7-(2,3-epoxypropoxy)actinomycin analogue against P-388 leukemia in mice is decidedly superior, and the therapeutic index is improved several fold.

Animals↗
PubMed1981

N2- and C-7 substituted actinomycin D analogues: synthesis, DNA-binding affinity, and biochemical and biological properties. Structure-activity relationship.

N2-n-Alkyl- and omega-amino-n-alkylactinomycin D and 7-alkoxy-, 7-aralkoxy-, and 7-(acyloxy)actinomycin D were synthesized by modification of the parent actinomycin D molecule at the N2 and C-7 positions of the phenoxazinone moiety. The intermediate for N2 substitution was 2-deamino-2-chloroactinomycin D. For C-7 substitution, 7-hydroxyactinomycin D was used as the intermediate. Treatment of 2-deamino-2-chloroactinomycin D with an excess of the appropriate amine produced the N2-substituted derivatives. Condensation of the required alkyl or acyl halides with 7-hydroxyactinomycin D, aided by solid anhydrous potassium carbonate, yielded the C-7-substituted analogues. Calf thymus DNA-binding affinity was determined by equilibrium binding and also by thermal denaturation of DNA techniques, inhibitory activity of nucleic acid synthesis was examined using P388 cells in vitro, cytotoxicity measurements to tumor cells in vitro employed human lymphoblastic leukemic cells (CCRF-CEM), and antitumor activity was assayed against P388 mouse leukemia in CDF1 mice. Synthesis of a number of new analogues in each series and determination of the biophysical, biochemical, and biological properties established a more thorough structure-activity relationship in these analogues. These results establish that with the selection of omega-(n-alkylamino) groups at the N2 site or O-n-alkyl or O-acyl groups at the C-7 site a variety of modifications can be carried out on the actinomycin molecule while preserving biological activity. N2-3'-Amino-n-propyl- and N2-10'-amino-n-decylactinomycin D, 7-methoxy- and 7-ethoxyactinomycin D, and the 7-O-(1'-adamantoyl) ester of 7-hydroxyactinomycin D were found to be the most effective antitumor agents in vivo and in vitro. They also strongly inhibit cellular RNA and DNA synthesis and, with the exception of the ester, retain high DNA-binding affinity.

Animals↗
PubMed1981

A five year review of deaths following trauma.

At Port Moresby General Hospital a retrospective analysis of 305 deaths that occurred between 1976 and 1980 following trauma was conducted. As road traffic accident fatalities made up 56% of all fatalities a more detailed analysis of the different factors involved in such accidents was made. Results show that 82% of the victims of road traffic accidents fatalities were below 35 years of age and that 57% of fatal accidents occurred during the period Friday to Sunday. Evidence of recent alcohol consumption was found in 85% of drivers involved in accidents. Eighteen out of 20 pedestrians tested had also been drinking alcohol. The overall incidence of head injuries was 65.5%. Chest injury was seen in 51% of cases. Sixty-six per cent of the victims died either at the site of the accident or before any effective treatment could be offered. Among the non-road traffic accident fatalities 21% of subjects with blunt and sharp penetrating injuries had a blood alcohol level exceeding 80 mg per 100 ml. Several measures have been recommended to prevent or to reduce the incidence of traumatic deaths in this country.

Accidents, Traffic↗
PubMed1979

Actinomycin D oxazinones as improved antitumor agents.

1,4-Oxazinone derivatives of the phenoxazinone chromophore in actinomycin D (AMD) have been synthesized by condensation of AMD with alpha-keto acids. By varying the starting alpha-keto acid, the substitutions on the oxazinone ring and, consequently, the lipophilicity of the molecule could be altered. These oxazinone derivatives revert to AMD in physiological media and it appears that these oxazinones are "depot" forms of AMD and possess physicochemical and DNA-binding properties which are significantly different from those of AMD. The oxazinones, which have bulky and lipophilic substituents at position 3, demonstrate more pronounced antitumor activity against P388 mouse leukemia and are less toxic than AMD.

Animals↗
PubMed1978

The interaction of 7-substituted actinomycin D analogs with DNA.

The interaction of actinomycin D and three new 7-substituted analogs with calf thymus DNA has been studied by a number of physical techniques. The methods utilized in this investigation include visible absorption spectrometry and ultrafiltration methodology for the determination of equilibrium binding constants; viscometry; and circular dichroism. The studies show that the 7-substituted actinomycin D analogs retain the G . C base pair specific DNA binding demonstrated by actinomycin D. The mode of binding to native DNA, despite substitution at position 7, is practically unaltered. The retention of this binding specificity by these analogs seems to be unaffected by changes in the electon properties of the chromophore.

Animals↗
PubMed1978

N7-Substituted 7-aminoactinomycin D analogues. Synthesis and biological properties.

A series of N7-substituted 7-aminoactinomycin D analogues with alkyl, aralkyl, and heteroaralkyl substituents was synthesized and their biological properties were studied. All of these analogues proved to be 22- to 28-fold less toxic than actinomycin D when tested against human lymphoblastic leukemia cells (CCRF-CEM) in vitro. Against the P388 mouse leukemia in vivo, most of the analogues had activity comparable to actinomycin D and one was significantly more active. The results show that substitutions of this kind do not interfere with the antitumor activity of actinomycin D and may be useful for the design of modified actinomycin D analogues with greater selectivity.

Animals↗
PubMed1977

Gene mapping by fluorescent in situ hybridization.

We describe a new method for the mapping of mammalian genes, utilizing in situ hybridization of mRNA to DNA of chromosomes. It involves the hydrogen bonding of the polyadenylic acid at the 3' end of hybridized mRNA to the polyuridylic acid tail of a highly fluorescent latex microsphere. The resultant double hybrid can be visualized by fluorescence microscopy. The chromosomal localization of human alpha + beta globin genes has been explored by this method. Our data point ot the long arms of chromosomes 4 and 5 as the loci for the human globin genes.

Chromosome Mapping↗