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Biomedical subjects

B Chaudhuri

Publications and source records attributed to B Chaudhuri.

At least 55 records · Page 3Linked to original sources
PubMed1992

Estrogen receptor in carcinoma in situ of the cervix.

The lining epithelium of the human cervix uteri is an estrogen dependent tissue containing specific intracellular receptors for this hormone. However, the influence of estrogen on an early neoplastic lesion arising from this epithelium, such as carcinoma in situ of the cervix, has not been determined. We evaluated 24 formalin fixed paraffin embedded tissue specimens of cervical carcinoma in situ for the presence of estrogen receptor by the immunoperoxidase technique. The antigenic sites of estrogen receptor were exposed by DNAse treatment followed by peroxidase-antiperoxidase (PAP) staining with monoclonal antibody against estrogen receptor. Parallel negative controls were run using negative control antibody and rat serum. Quality control for positive staining was performed using breast cancer tissue sections from specimens with known estrogen receptor detected by the radioreceptor method. Strongly positive staining was observed in all specimens in the nuclei of glandular epithelium, stromal cells, and basal and parabasal cells. However, nuclei within carcinoma in situ of the cervix showed no evidence of positive staining. Due to lack of specific intracellular receptor for estrogen, it appears that carcinoma in situ of the cervix will not be under direct influence of estrogen.

Adult↗
PubMed1992

Effect of CCK receptor antagonist on growth of pancreatic adenocarcinoma.

Cholecystokinin (CCK) exerts an influential effect on the growth of normal pancreas. It is postulated that carcinoma arising from the pancreas may retain some normal pancreatic properties as far as hormone dependency is concerned. In an effort to examine the effect of CCK on the growth of pancreatic cancer, we evaluated the effect of CCK receptor antagonist on the growth of a transplantable adenocarcinoma of the pancreas. For this study we utilized three groups of hamsters with adenocarcinoma of the pancreas transplanted subcutaneously on the right flank. Group I (n = 15) served as control. Group II (n = 15) received CCK receptor antagonist (L-364,718), 0.1 mg/100 g body wt subcutaneously BID. Group III received CCK receptor antagonist in the same dose but treatment was started after tumors became palpable. All animals were examined daily. Latency for tumor growth, tumor size, and body weight were recorded. Animals were sacrificed after 3 weeks and final tumor volume and weight were measured. CCK receptor antagonist (L-364,718) significantly reduced pancreatic carcinoma growth when given immediately after transplantation and also in animals with established tumor. However, this inhibitory effect of L-364,718 was only partial and effective only for a brief time. This finding suggests CCK may have only a minimal influence on the biologic behavior of exocrine pancreatic cancer.

Adenocarcinoma↗
PubMed1992

Ductal carcinoma in situ in rat mammary gland.

Antiestrogen therapy has been proposed as a treatment option for ductal carcinoma in situ (DCIS). However, its effectiveness has not been evaluated in the laboratory due to lack of an animal model. The present study was undertaken to evaluate the incidence, time span, and number of mammary glands involved with DCIS in a rat model treated with N-nitroso-N-methylurea (NMU). Sprague Dawley female rats 44 to 49 days old were treated with two iv doses of 5 mg NMU/100 g body wt given 7 days apart, initiated at diestrus. Animals were killed at intervals beginning 21 days following first injection. Breast tissues were evaluated following routine H&E stain. Standard histologic criteria were followed to establish the diagnosis of DCIS. The number of glands involved with DCIS increased from one to seven with time from first injection. This model demonstrates an incidence of 87% for DCIS and 0% for invasive Ca between 22 and 45 days following NMU injection. Nine rats were sacrificed between 50 to 60 days and five showed invasive carcinoma. This model appears suitable for studying the efficacy of hormone or chemoprevention in the progression of DCIS to invasive Ca.

Animals↗
PubMed1991

A Lys27-to-Glu27 mutation in the human insulin-like growth factor-1 prevents disulfide linked dimerization and allows secretion of BiP when expressed in yeast.

Recombinant human insulin-like growth factor-1 (IGF1) secreted from yeast contains only 10-15% of the active monomer. A majority of the IGF1-like molecules are disulfide bonded dimers. These dimers are not formed in an IGF1 mutant where Lys27 has been replaced by glutamic acid. However, increased levels of secreted BiP (the yeast KAR2 gene product) are seen in cells expressing the mutant. These results imply that by preventing ionic interactions between two IGF1 molecules, intermolecular disulfide bonds do not form in yeast, and that in the mutant there is a structural change which induces BiP, allowing its secretion.

Base Sequence↗
PubMed1991

Alpha-factor-leader-directed secretion of recombinant human-insulin-like growth factor I from Saccharomyces cerevisiae. Precursor formation and processing in the yeast secretory pathway.

A synthetic gene coding for human-insulin-like growth factor I (IGFI) was fused to the leader sequence of yeast prepro-alpha-factor and expressed in Saccharomyces cerevisiae under the control of a glyceraldehyde-3-phosphate dehydrogenase promoter fragment. Recombinant IGFI was found inside yeast cells and secreted into the medium. The secreted IGFI migrated on SDS gels with the same electrophoretic mobility as authentic IGFI, i.e. at about 7.5 kDa. HPLC analysis of secreted IGFI revealed the presence of the correctly folded, genuine molecule as well as an isomeric byproduct of equal molecular mass but with two of the three disulfide bonds interchanged. Inside exponentially growing cells the 7.5-kDa IGFI was also found, along with up to four additional IGFI-related polypeptides of higher molecular mass. By endoglycosidase F treatment the three polypeptides between 19-26 kDa were converted to a single peptide of 17 kDa. Since this peptide also reacted with an anti-alpha-factor antibody, it represents most likely the unglycosylated alpha-factor--IGFI fusion precursor. Pulse-chase experiments established the precursor nature of the intracellular higher-molecular-mass IGFI species. Conversion of the primary translation product to the differently glycosylated IGFI precursor proteins and into the mature form occurred very rapidly, within 2 min. Rapid maturation was, however, not followed by an equally rapid secretion of the mature form into the medium: only after 30-40 min did IGFI appear outside the cells. We therefore postulate the presence of an as yet undefined Golgi or post-Golgi bottleneck representing a major obstacle in secretion of recombinant IGFI from S. cerevisiae cells.

Chromatography, High Pressure Liquid↗
PubMed1991

Pharmacokinetics and toxicity of isolated perfusion of lung with doxorubicin.

The treatment of pulmonary metastases from soft tissue sarcomas with chemotherapy has an overall response rate of less than 30%, and the majority of these responses are short lived. It is postulated that increased drug delivery to the pulmonary metastases may improve the outcome of these patients. An isolated perfusion system would have the ability of delivering increased levels of drug to target tissue without the systemic toxic effect of the drug. The purpose of this study was to establish the pharmacokinetics of doxorubicin delivery, lung toxicity, and the ideal dose for clinical application in an in vivo isolated perfusion model. Our results suggest that normothermic isolated perfusion of the lung with doxorubicin using a dose level up to 6 micrograms/ml in the perfusate can be accomplished without histologic lung injury, systemic toxicity, or adverse clinical outcome. Perfusate concentration of greater than 7 micrograms/ml caused significant histologic injury and adverse clinical outcome without systemic toxicity. The technique may be utilized in selective settings to improve treatment in mesenchymal tumors metastatic to the lung.

Animals↗
PubMed1990

Isolated perfusion of pancreas with mitomycin C.

The current treatment of pancreatic cancer with resection and/or radiation is considered unsatisfactory because of a high incidence of failure and a moderate incidence of complications. A sizable number of these patients present with localized or regional disease. Regional high-dose chemotherapy, such as with isolated perfusion, may offer an alternative therapy with low treatment-related morbidity and mortality and better end results in this group of patients. In an effort to develop such a treatment modality, we evaluated the pharmacokinetics and toxicity of mitomycin C (MMC) during isolated perfusion of pancreas in a canine model. From this study, it appears that a dose of 0.25 mg MMC/kg body weight is most suitable for isolated perfusion of pancreas at 39 degrees C, maintaining flow rate and pressure within physiologic range. Isolated perfusion with a dose of 0.25 mg/kg body weight has very mild short- and long-term toxicities and markedly increases drug delivery to the pancreas, duodenum, and peripancreatic lymph nodes, making it the most suitable dose for possible clinical application.

Amylases↗
PubMed1990

Estrogen receptors in ductal carcinoma in situ of breast.

A number of investigators have suggested treatment of precursor lesions for invasive breast cancer such as ductal carcinoma in situ with antiestrogen. However, very little information is available on the incidence of estrogen receptor in such lesions and the probability of treatment success. Fourteen formalin-fixed tissue specimens of intraductal carcinoma in situ from 14 female patients aged 40 to 66 years were evaluated for the presence of estrogen receptor by immunoperoxidase technique using estrogen receptor antibody. Eight of the 14 lesions (57%) were positive for estrogen receptor. The incidence of estrogen receptor in intraductal carcinoma in situ is very similar to that of invasive carcinoma of breast, leading to the speculation that ER-positive invasive carcinoma originates from ER-positive precursor lesions. Since only 70 per cent of positive receptor lesions are expected to respond to antiestrogens, it appears that only 40 per cent of patients with ductal carcinoma in situ of breast will benefit from endocrine therapy.

Adult↗
PubMed1989

Pharmacokinetics and tissue uptake of mitomycin C in isolated perfusion of pancreas.

Isolated perfusion of organs or anatomic sites with chemotherapeutic agents offers a pharmacokinetic advantage of increasing drug bioavailability to target tissues which may result in a greater magnitude of biologic effect (pharmacologic or toxic) without systemic toxicity. Using a previously developed animal model, isolated perfusion (IP) of the canine pancreas-duodenum with incremental doses of mitomycin C (MMC) had shown a dose of 0.25 mg/kg body weight to be the maximum tolerable dose. The current study was designed to compare the pharmacologic advantage of drug delivery by IP by directly measuring tissue drug levels of radiolabeled MMC and comparing them with tissue levels attained by selective intraarterial (IA) and intravenous (IV) routes using identical doses of drug (n = 4 each). IP of pancreas-duodenum was performed for 45 min with a perfusate-to-systemic drug leak rate of less than 5%. IP was accomplished by using extracorporeal pump oxygenator at 39 degrees C and flow initiated at 110-120 ml/min, with a mean pressure of 90 mm Hg. Vascular inflow and outflow was isolated to the cannulated superior pancreaticoduodenal artery and vein. In the IA group drug was infused over 45 min through same artery as IP. IV group underwent identical dosing through the jugular vein. Direct measurement of drug in harvested pancreas and duodenum for each individual was done by tissue solubilization and scintillation assay. A 6-fold greater tissue level of drug in IP over IA and a 15-fold increase in IP over IV methods of delivery were found (P less than 0.01).

Animals↗
PubMed1986

Cloning and expression of cDNA encoding mouse tyrosinase.

We have isolated a pigment cell-specific cDNA clone from a B16 mouse melanoma cDNA library by differential hybridization. The mRNA of isolated cDNA is highly expressed in B16 melanoma cells and in black mouse (C57BL/6) skin, but is not detectable in mouse neuroblastoma cells nor in K1735 mouse amelanotic melanoma cells. The protein sequence deduced from the nucleotide sequence of the cloned cDNA shows significant similarity to the entire region of Neurospora tyrosinase. To know the identity of cDNA, we transfected K1735 amelanotic melanoma and COS-7 cells with the cDNA carried in a simian virus 40 vector (pKCRH2). We confirmed that the isolated cDNA encodes mouse tyrosinase by immunofluorescence staining of transfected cells using two different anti-T4-tyrosinase monoclonal antibodies. Tyrosinase is composed of 513 amino acids with a molecular weight of 57,872 excluding a hydrophobic signal peptide of 24 amino acids.

Amino Acid Sequence↗
PubMed1986

Modulation of estrogen receptor by insulin and its biologic significance.

It has been proposed that a nonsteroidal hormone such as insulin may directly exert an influence through estrogen receptors and alter the biologic behavior of steroid hormone target tissue. The implication of such a proposal is that diabetes may alter the outcome of estrogen receptor-positive tumors such as breast or endometrial carcinomas. To evaluate the effect of insulin on a receptor-positive tumor, we examined the direct effect of insulin on an estrogen receptor and its subsequent biologic effect on a receptor-positive endometrial carcinoma model in vitro and in vivo. An in vitro experiment demonstrated that when the estrogen receptor-positive cell line was grown in serum-free media with low insulin, there was a loss of intracellular receptors for estrogen. This loss of estrogen receptors was also associated with increased growth rate as reflected by increased thymidine uptake. Similarly, in vivo experiments demonstrated that a diabetic host with a high blood glucose level and a low insulin level exhibited development of growth of a receptor-negative tumor with accelerated growth rate in contrast to growth of a receptor-positive tumor with slower growth rate in a normal host with normal serum insulin and blood glucose levels. Data suggest that insulin may modulate the growth of estrogen receptor-positive tumors through its direct effect on estrogen receptors.

Animals↗
PubMed1986

Limitation of immunohistochemical localization of estrogen receptor.

Although the radioreceptor method is widely used for estrogen receptor assay in human tissue, it has several limitations and a number of alternative methods are being explored. An immunohistochemical method of estrogen receptor assay using a specific antibody to estradiol has been proposed as a suitable alternative. The present study was designed to evaluate the validity of this method in detecting true estrogen receptors in human tumor tissue. Using radioiodinated antibody to estrogen, we have demonstrated that the estrogen antibody can detect the estrogen when it is bound to 4S type receptor but is unable to bind to estrogen when the hormone is bound to 8S type receptor. Our observations suggest that the immunohistochemical method of detection of intracellular cytosolic receptor for estrogen is not a suitable alternative to the currently used radioreceptor method.

Breast Neoplasms↗
PubMed1983

Glycerokinase activity in human brown adipose tissue.

Brown adipose tissue (BAT) is known to be responsible for heat production in newborn and adult hibernating mammals. In rats and mice, BAT has been demonstrated to possess a much higher glycerokinase activity than white adipose tissue (WAT). It has been speculated that this high activity may cause the futile cycle of triglyceride breakdown and resynthesis to be activated, thus contributing to heat production. However, at present very little information is available regarding the location, function, and quantitative importance of BAT in adult human subjects. Our objective in this study was to locate BAT in human subjects and to characterize it biochemically, especially with respect to the enzyme glycerokinase. We have looked for histologically identifiable BAT in 32 human subjects and found it in 12 subjects. Most of the BAT samples were obtained from perirenal adipose depots in children undergoing surgery. Some of the samples were almost totally comprised of BAT cells, whereas others were a mixture of BAT cells and WAT cells. The glycerokinase activity per gram of tissue was higher in BAT than in WAT in all the subjects where the above comparison was made. The activity per mg protein or per microgram DNA was higher in most BAT samples. In one pure BAT specimen, the basal lipolytic rate and the lipoprotein lipase activity were measured and they were both higher in BAT than in the WAT obtained from the same patient. These results show that human brown adipose tissue possesses an enzymatic profile very similar to that of rodent brown adipose tissue.

Adipose Tissue↗
PubMed1981

A transplantable human malignant Schwannoma.

A human malignant Schwannoma was serially transplanted through three generations in nude mice. The tumours grew readily and the take-up rate was 100 per cent. No metastasis was observed in nude mice. Morphological features of the original tumour were strictly maintained through all the transplant generations. The tumour cells of the original and of the transplants showed features of primitive Schwann cells of embryonic nerve trunks.

Adult↗
PubMed1981

Conjunctival inflammation and amyloidosis in allergic granulomatosis and angiitis (Churg-Strauss syndrome).

A 37-year-old woman developed nodular, waxy conjunctival lesions associated with the exacerbation of Churg-Strauss syndrome. Conjunctival and skin biopsy specimens demonstrated a diffuse inflammatory process composed of eosinophils, plasma cells, lymphocytes, and focal collections of histiocytes. There were amyloid deposits in the conjunctiva and skin. To our knowledge, this is the first report of conjunctival changes and amyloidosis associated with the Churg-Strauss syndrome.

Adult↗
PubMed1980

Angiosarcoma arising in a plexiform neurofibroma: a case report.

A left cervical mass developed in a 14-year-old white boy with stigmata of von Recklinghausen's disease. Excision biopsy examination showed a plexiform neurofibroma with angiosarcoma. Ultrastructural studies confirmed the endothelial nature of the malignant cells.

Adolescent↗