Antennal deformities of chironomid larvae and their use in biomonitoring of heavy metal pollutants in the river Damodar of West Bengal, India.

Analyses of sediment and water indicate the presence of heavy metal pollutants like lead, zinc, copper, mercury and cadmium of the river Damodar of India. These metals are responsible for causing morphological deformities of antennae and other parts of chironomid larvae. Percentage of deformity correlated positively with the concentrations of Pb in water and sediment (r > 0.6) at the confluence point. A new severity index, SISS((antenna)) has been proposed here to assess deformity at the family or subfamily level.

Phytotoxic and antimicrobial constituents of Bacopa monnieri and Holmskioldia sanguinea.

The phytochemicals betulinic acid (1), wogonin (2) and oroxindin (3) isolated from the aerial parts of Bacopa monnieri and Holmskioldia sanguinea showed significant antifungal activity against the two fungi Alternaria alternata and Fusarium fusiformis. Inhibition of root growth germination of wheat seeds was observed for all three compounds which showed 100% inhibition at 10 micro g/mL. Compounds (1) and (2) showed potent inhibition of Alternaria alternata compared with oroxindin at a concentration of 4 micro g/mL, whereas compound (2) was an effective inhibitor of both fungi. The structures of the compounds were established by spectral and chemical studies.

Pharmacokinetics of mitomycin C in pelvic stopflow infusion and hypoxic pelvic perfusion with and without hemofiltration: a pilot study of patients with recurrent unresectable rectal cancer.

This pilot study was conducted to evaluate the advantage in drug delivery for regional chemotherapy in patients with unresectable recurrent rectal carcinoma by different methods. For this research, the pharmacokinetic advantages of mitomycin C delivery by four different methods were compared: intraaortic infusion with aortic stopflow; intraaortic infusion with inferior vena cava stopflow; intraaortic infusion with aortic and inferior caval vein stopflow (hypoxic pelvic perfusion); and hypoxic pelvic perfusion with hemofiltration. The results of this study indicate that pelvic stopflow infusion followed by hypoxic pelvic perfusion significantly increases mitomycin C concentrations in the blood coming from the tumor site. Also, use of hemofiltration reduces mitomycin C levels in peripheral blood after high-dose regional chemotherapy. Further investigations involving more patients should be carried out in the future to validate these results.

Long-term (1980-94) population trends of pestiferous Chironomidae (Diptera) along a lakefront in central Florida.

Populations of adult chironomids occurring along 5-6 km of waterfront in the city of Sanford facing Lake Monroe, central Florida, were monitored from January 1980 to December 1994 using New Jersey light traps. The annual mean number of total midges per trap per day ranged from 269 (1994) to 8,009 (1980). Among the more than 20 species of midges occurring in the traps, Glyptotendipes paripes was the most abundant, followed by Chironomus crassicaudatus. These 2 species comprised 95.6% of total midges collected. Annual cycles of midge abundance were positively correlated with air temperature. Maxima of most species occurred in late spring/early summer; G. paripes peaked in late summer. Year-to-year midge population levels showed significant inverse correlations with Lake Monroe water depth and annual rainfall in the Sanford area.

Differential regulation of folate receptor isoforms in normal and malignant tissues in vivo and in established cell lines. Physiologic and clinical implications.

BACKGROUND: Despite significant differences in ligand binding between the two known isoforms of the human membrane folate receptor (FR), designated herein as FR-beta (placenta) and FR-alpha (placenta, KB cells), little is known about their tissue specificities, and there is no report on the relative expression of FR-beta in any tissue other than in placenta. METHODS: The mRNA for each FR isoform in a wide variety of normal fetal and adult tissue explants, primary normal cell cultures, malignant tumor explants, and established tumor cell lines was estimated by a polymerase chain reaction assay. Total receptor levels were estimated by a [3H] folic acid binding assay. RESULTS: Both the FR isoforms were expressed in fetal as well as adult tissues. Normal tissues generally expressed low to moderate amounts of FR-beta. FR-alpha alone was expressed in normal epithelial cells and was frequently strikingly elevated in a variety of carcinomas, with the exception of squamous cell carcinomas of the head and neck. In contrast, a variety of malignant tissues of nonepithelial origin generally expressed elevated levels of FR-beta alone. Established tumor cell lines expressed FR-alpha virtually alone and did not reflect FR expression patterns in vivo. KB cells and JEG-3 cells grown at low folate concentrations further up-regulated FR-alpha but not FR-beta. CONCLUSIONS: Although FR-beta is the more common isoform, FR-alpha and FR-beta are differentially regulated in normal tissues, carcinomas, nonepithelial malignancies, and immortalized cells or in response to changes in extracellular folate concentrations. The tissue specificity of FR isoforms and their elevation in malignant tissues may be a significant factor in FR-mediated folate uptake, in tissue responsiveness to promising novel antifolates, and in FR-related immunodiagnosis/immunotherapy.

Distribution of estrogen receptor in ductal carcinoma in situ of the breast.

BACKGROUND: Long-term antiestrogen therapy has been suggested as a possible treatment alternative for ductal carcinoma in situ (DCIS) of the breast. However, very little information is available on the distribution of estrogen receptor (ER) and treatment success with antiestrogen for such lesions. METHODS: Thirty-two formalin-fixed tissue specimens of DCIS from 32 female patients aged 38 to 71 years were evaluated for the presence of ER by an immunoperoxidase technique. Antigenic sites for ER were exposed by treating the tissue sections with deoxyribonuclease followed by peroxidase-antiperoxidase staining with monoclonal antibody against ER. Parallel negative controls were run with negative control monoclonal antibody and normal rat serum. The quality control for positive staining was performed with tissue sections from specimens with known ER detected by the radioreceptor method. RESULTS: Eighteen (60%) of the 32 lesions were positive for ER. In 7 of the 18 lesions less than 25% of cells stained positive for ER and in 4 of the 18 more than 50% of cells stained positive for ER. CONCLUSIONS: The incidence of ER in DCIS is similar to the incidence of ER in invasive carcinoma, leading to the speculation that ER-positive invasive carcinoma originates from an ER-positive precursor lesion. Because only 60% of the cases have detectable ER and approximately 70% of positively stained ERs are expected to be functional (as in invasive carcinoma), it appears that approximately 42% of the patient population with DCIS will benefit from antiestrogen therapy.

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.

Placement of an endotracheal tube in the short tracheal stump.

Placement of an endotracheal tube in the short tracheal stump, such as after a mediastinal tracheostomy, can be a difficult task. The tube may easily slide into the right main bronchus or slip out of the trachea completely. We have described a method for securing such an airway for ventilation during general anesthesia.

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.

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.

The pattern of injury to rear seat passengers involved in automobile collisions.

This retrospective study analyzed the pattern of injury among rear seat occupants in automobile collisions and compared the incidence and type of injury with that of front seat occupants. During a 2-year study period, 253 persons involved in automobile collisions were admitted to our hospital. Among these patients 168 were drivers, 54 were front seat passengers, and 24 were rear seat occupants. Injuries were classified into the following categories: neurologic, orthopedic, soft tissue, thoracic, and abdominal. No significant differences were observed in the type or extent of injury, in the incidence of permanent disability, or in the mortality rate based on the location of the passengers within automobiles involved in these crashes.

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.

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.

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.

Estrogen receptor in normal and neoplastic human thyroid tissue.

Clinical evidence suggests the possible influence of estrogen on the biologic behavior of thyroid neoplasm. In this study we evaluated the distribution and characteristics of intracellular receptors for estrogen in normal and neoplastic thyroid tissue obtained from 54 patients. Forty-two percent of all specimens assayed by the protamine sulfate precipitation technique had a detectable intracellular binding site for estrogen. Differentiated carcinomas (eight of eight) and adenomas (seven of nine) had high incidences of receptors compared with goiter (five of 23) and normal thyroid (three of eight). However, there were no detectable receptors for estrogen in medullary carcinomas of the thyroid (0 of six). Also, carcinomas and adenomas had higher receptor contents than did goiter and normal differentiated thyroid tissue. There was no significant difference in the affinity of estrogen for receptors among the different histologic groups. There were both 4S and 8S receptor types, which were specific for estrogen. The binding of estrogen to thyroid tissue and differentiated neoplasm originating from thyroid tissue were comparable to the binding of estrogen to other hormone-dependent normal and neoplastic tissues.

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).

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.