Aqueous picloram degradation by hydroxyl radicals: Unveiling mechanism, kinetics, and ecotoxicity through experimental and theoretical approaches.

Pesticides are chemical compounds widely used to combat pests in crops, and they thus play a key role in agricultural production. However, due to their persistence in aquatic environments, even at low concentrations, their use has been considered an environmental problem and caused concern regarding the adverse effects on human health. This paper reports, for the first time, the mechanisms, kinetics, and an evaluation of the toxicity of picloram degradation initiated by OH radicals in the aqueous environment using quantum chemistry and computational toxicology calculations. The rate constants are calculated using a combination of formulations derived from the Transition State Theory in a realistic temperature range (250-310 K). The results indicate that the two favorable pathways (R1 and R5) of OH -based reactions occur by addition to the pyridine ring. The calculated rate constant at 298 K is compared with the overall second-order reaction rate constant, quantified herein experimentally via the competition kinetics method and data available in the literature showing an excellent agreement. The toxicity assessment and a photolysis study provide important information: i) picloram and the majority of degradation products are estimated as harmful; however, ii) these compounds can suffer photolysis in sunlight. The results of the present study can help understand the mechanism of picloram, also providing important clues regarding risk assessment in aquatic environments as well as novel experimental information.

Heated distributed temperature sensing for field scale soil moisture monitoring.

Characterizing both spatial and temporal soil moisture (θ) dynamics at site scales is difficult with existing technologies. To address this shortcoming, we developed a distributed soil moisture sensing system that employs a distributed temperature sensing system to monitor thermal response at 2 m intervals along the length of a buried cable which is subjected to heat pulses. The cable temperature response to heating, which is strongly dependent on soil moisture, was empirically related to colocated, dielectric-based θ measurements at three locations. Spatially distributed, and temporally continuous estimates of θ were obtained in dry conditions (θ≤ 0.31) using this technology (root mean square error [RMSE] = 0.016), but insensitivity of the instrument response curve adversely affected accuracy under wet conditions (RMSE = 0.050).

The identification and development of specific monoclonal antibodies to squamous cell carcinoma.

We have developed specific monoclonal antibodies to immunogenic glycoproteins expressed selectively on the cell membrane of squamous cell malignancies. These proteins serve to act as tumor markers that characterize this malignancy; there has be no evidence of cross reactivity to normal epithelial cells. Analysis of patterns of expression reveals that those membrane proteins identified by monoclonals AD7 and 5C6 appear early in cellular transformation to malignancy. At such a time, immunohistochemical recognition is seen in the presence of genotypic alterations, yet phenotypic changes may not be apparent. Of additional interest is that these monoclonal antibodies exhibit strong ADCC allowing the tumor proteins to not only serve as a marker of malignancy but as a target for therapeutic destruction.

Immunotherapy of colon cancer using chimeric mAb 31.1.

We have produced two monoclonal antibodies specific for membranes of colon carcinoma cells that demonstrate minimal if any cross reactivity with normal colon tissue. The antigen of one of the two antibodies (mAb 33.28) is extremely immunogenic eliciting both cell mediated and humoral immunity. The monoclonal antibodies developed in in vitro studies suggested strong antibody dependent cell cytotoxicity (ADCC) for both antibodies, but somewhat stronger for the mAb 31.1. The murine version of mAb 31.1 produced approximately 90% tumor cell destruction in the same period of time. Nude mice with LS174T xenografts (human colon carcinoma) were challenged with 1 x 10(6) cells given subcutaneously in the thigh. By day 10, well animals were incapacitated by tumor growth. Among those animals receiving 400 micrograms of intraperitoneal chimeric 31.1 at day one, all were protected and remained free of disease. Those challenged with chimeric antibody and human effector cells at day 7 demonstrated regression of established tumor nodules among 80% of the animals so treated. Therapy of patients with extensive primary as well as metastatic colon cancer may be found to respond to the above form of therapy post surgery, when employed alone or in combination with an effective cytotoxic (chemotherapeutic) agent.

Case report 872. "Ancient" schwannoma (degenerated neurilemoma).

A case of an ancient schwannoma was presented. The rare occurrence of this tumor has resulted in only a few reported cases with descriptions of its features on imaging. Our patient's tumor, like one previously reported case, demonstrated calcification on the plain film - a finding not associated with other histologic types of schwannomas. Angiography revealed the tumor to be hypervascular. Evaluation by MRI demonstrated a lobulated, encapsulated soft tissue mass containing several cystic areas that corresponded histologically to areas of necrosis. Hypertrophied blood vessels were seen in the periphery of the tumoral mass. Too few ancient schwannomas have been reported to conclude whether or not radiographic evidence of soft tissue calcification is characteristic of this histologically distinctive subtype of schwannoma. However, since calcification is seen histologically as part of the degenerating process, its presence on plain films could be a feature of this tumor. Furthermore, the presence of cystic areas on MRI is not surprising given the pathological changes that occur in this tumor. We suggest that a diagnosis of ancient schwannoma be considered when a patient presents with a hypervascular soft tissue mass containing amorphous calcification on plain films and cystic areas on MRI. Despite the nonspecificity of these imaging findings, this point is relevant because each of these features suggests the presence of a malignant mass. Awareness of the possibility of a benign ancient schwannoma could obviate unnecessary radical surgery.

Monoclonal antibodies and their role in modulation of the immune response.

Clinical studies in patients having been vaccinated with immunogenic glycoproteins suggest that a monoclonal antibody response is important in helping to induce cell mediated tumor destruction. Such a monoclonal response was noted to characterize the reaction to several different immunogenic antigens administered in an adjuvant setting. The resulting cell mediated reaction appeared to be associated with concomitant antibody dependent cell mediated cytotoxicity (ADCC) and an anti-idiotype monoclonal response. Both 31.1 and 33.28 protein derived colon carcinoma monoclonal antibodies have been found to be capable of turning on natural killer (NK) cell activity as part of ADCC. In vivo studies with specific antigens to induce an anti-tumor response have suggested that the mechanism of tumor cell destruction is complex and associated with T-cell activation, anti-idiotype production, and complement binding on the tumor membrane.

Sarcoma management based on a standardized TNM classification.

The proper management of soft tissue sarcomas, that offering the highest cure rate while attempting limb sparing should the extremities be involved, requires a standard approach best achieved with the TNM classification. Such staging of the sarcomatous lesion is based primarily on the histologic grade, followed by size and finally histologic classification. The definitive approach is surgical, with muscle group dissection employed at all sites, including the extremities, trunk, and head and neck region. Radiation therapy alone or in combination with chemotherapy improves survival in all high-grade lesions at risk for recurrence. Evaluation of the primary and recurrent lesion by computed tomography, magnetic resonance when necessary, and angiography offers the best approach for evaluation of the lesion in treatment planning.

Specific active immunotherapy in patients with adenocarcinoma of the colon utilizing tumor-associated antigens (TAA). A phase I clinical trial.

Twenty-two patients received specific active immunotherapy (TAA vaccine once per month for 3 months), with the duration of follow-up, as of July 1984, ranging from 3 months to 36 months (median, 21 months). Of these, seven had Dukes B2, seven had Dukes C, and eight had Dukes D lesions. All received surgical resection, and those with Dukes D disease underwent resection of all metastases where possible, with six clinically disease-free at the time of initiation of therapy. The age range of the 22 patients was 40 to 73 years (median, 60 years); sex distribution was 12 males and 10 females. All patients were monitored by physical examination and by laboratory parameters including complete blood count, liver and renal function tests, blood chemistries, urinalysis, chest x-ray, carcinoembryonic antigen levels, migration inhibition assays, complete immune complexes, serum chemistries, helper and suppressor and total T-cell and B-cell assays, and TAA antibody levels. As measured by delayed cutaneous hypersensitivity skin test and by migration inhibition assays (MIA), a strong postimmunization response is developed approximately 5 months after vaccination is completed. There were no clinical or biochemical manifestations of any type of systemic toxicity including hepatic, renal, gastrointestinal, respiratory, or neurologic during the period of follow-up. All patients developed skin ulcers at the vaccination and required 4 to 5 months to heal. With this small number of patients in a Phase I trial, survival is indicative of the safety of the vaccine only: 82% of the patients are alive (mean survival, 21 months) thus far, and 59% of the patients are without evidence of disease (NED) (mean NED, 22 months). These studies, therefore, justify a Phase II-III trial in a larger number of patients and have provided selection of appropriate monitoring tests for the larger trial.

Immunoglobulin allotypes in patients with squamous cell carcinoma of the head and neck.

Gm, A2m, and Km allotypic markers were examined in 40 Caucasian patients with squamous cell carcinomas of the head and neck. Serum IgA levels, the A2m(1) allotypic marker, and antibodies against IgA1, A2m(1), and A2m(2) were measured quantitatively. The frequency of Km(1) was found to be significantly increased in patients with head and neck cancer as compared to the control population.

Pilot studies using melanoma tumor-associated antigens (TAA) in specific-active immunochemotherapy of malignant melanoma.

Highly purified melanoma TAA which induce melanoma-related cellmediated immune responses have been further characterized using hyperimmune TAA antisera after affinity chromatography for double immunodiffusion-immunoelectrophoresis and indirect immunofluorescence studies. An additional study of antigenic modulation was performed in 23 nonanergic and seven anergic melanoma patients, tested simultaneously with melanoma TAA prepared from primary and metastatic tumors, which had been obtained from one patient at different time periods. The results of pilot clinical trials are reported, including toxicity, timing and dosage studies in 20 patients and subsequent studies of patients with metastatic melanoma treated at three separate centers, using a single lot of purified, allogeneic melanoma TAA. The results of these latter studies in 51 patients with Stage III (distantly metastatic) melanoma and in five patients with earlier stages of disease indicate that: (1) when the interval from primary therapy to recurrence is greater than one year and when liver, bone and brain are not involved, partial or total clinical regression may be noted in up to 25% of patients with metastatic disease receiving immunochemotherapy; (2) when total regression does occur, the effect usually lasts from one to three years; (3) cytoreductive (debulking) surgery, when possible, in cutaneous, nodal retroperitoneal, and visceral regions may enhance the response to specific active immunochemotherapy, although some debulked patients had less tumor burden and this factor alone may lead to an improved prognosis in patients undergoing any subsequent treatment; (4) when circulating inhibitory factors are modified through preimmunization chemotherapy, an enhanced host response may be seen; and (5) Cancer Serum Indices (CSI) may be useful in predicting recurrence and in following tumor load and response to therapy. Information obtained from these studies suggest the need for further trials to determine the effect of immunization on patients with earlier stages of disease where recurrence rates remain high, and to evaluate the mechanisms of tumor rejection or tumor progression in the face of immune stimulation.

Combined radiation-methotrexate therapy in preoperative management of carcinoma of the head and neck.

Fifty patients with primary carcinoma of the head and neck were treated preoperatively with 2,000 r and 500 mg/m2 of methotrexate. This combination reduces the tumor size in more than 90 per cent of patients, converts many of the tumors to a more manageable state, and appears to indicate that improved survival will occur.

Nodal response in medullary carcinoma of the breast.

From 1954 to 1970, ninety-five patients with medullary carcinoma of the breast were evaluated in terms of immunologic activity based on the histologic changes seen within the tumor and regional nodes. Each patient was studied for the degree of lymphocytic infiltration in the tumor as well as the extent of sinus histiocytosis present within the regional nodes. Contrary to what would normally be expected, those nodes with increased sinus histiocytosis were associated with the larger tumors. In addition, lymph node metastasis increased from 26 to 75 per cent as the degree of sinus histiocytosis became more pronounced. There was no evidence that increased lymphocytic infiltration in the tumor resulted in a statistically significant improvement in the five and ten year survival rates. Similarly, sinus histiocytosis activity did not seem to enhance the survival rate among this particular group of patients. There is a suggestion that a correlation exists between sinus histiocytosis and lymphocytic infiltration in the tumor and that, whatever the stimulus present, its effect is on both the lymph node and the degree of lymphocyte response within the tumor. The antigenic substance in the tumor, which initiates the immune response, possibly produces an abortive reaction, which may result in the induction of blocking factors rather then those factors necessary for destruction. It appears that histologic evidence of immunologic enhancement does not necessarily signify improved survival, at least with those patients having carcinoma of the breast.