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Biomedical subjects

R S Freedman

Publications and source records attributed to R S Freedman.

At least 37 records · Page 2Linked to original sources

Differential expression of cytokine transcripts in human epithelial ovarian carcinoma by solid tumour specimens, peritoneal exudate cells containing tumour, tumour-infiltrating lymphocyte (TIL)-derived T cell lines and established tumour cell lines.

T cell lines derived in low concentrations of recombinant IL-2 (rIL-2) from TIL of patients with epithelial ovarian carcinoma (EOC) often exhibit specific cytotoxicity against autologous tumour cells. However, the ability of T cells at the tumour site to respond to ovarian carcinoma cells may be affected by the production of cytokines by the various cell types present. Using reverse transcriptase-polymerase chain reaction (RT-PCR) we investigated cytokine transcripts in: (i) established EOC tumour cell lines; (ii) solid tumour specimens or peritoneal exudate cells (PEC) from ascites or peritoneal washings of patients with EOC; and (iii) CD4+ TCRalphabeta+ and CD8+ TCRalphabeta+ TIL-derived T cell lines developed in rIL-2. We have found that (i) established EOC tumour cell lines expressed transcripts for transforming growth factor-beta 2 (TGF-beta2) (7/7), but not IL-10 (0/7) or interferon-gamma (IFN-gamma) (0/7) and rarely IL-2 (1/7); (ii) PEC expressed transcripts for IL-2 (12/13), IL-10 (9/13), and TGF-beta2 (12/13), and less often, IFN-gamma (3/13), whereas solid tumour specimens from eight patients with EOC expressed transcripts for IL-2 (4/8), TGF-beta2 (4/8), and IL-10 (5/8), but not for IFN-gamma (0/8); (iii) CD4+ TCRalphabeta+ T cell lines expressed transcripts for IFN-gamma (4/4), IL-2 (4/4) and IL-10 (3/4), whereas CD8+ TCRalphabeta+ T cell lines expressed transcripts for IFN-gamma (5/5), IL-2 (1/5) and IL-10 (2/5). None of these T cell lines expressed TGF-beta2 transcripts. The frequency of IL-2 and TGF-beta2 transcripts in solid tumours was significantly lower than in the PEC (P = 0.0475). CD4+ or CD8+ T cell lines expressing IFN-gamma, IL-2 and IL-10 transcripts were derived in culture with rIL-2 from the TIL of specimens that did not necessarily express these cytokines in the absence of rIL-2. The frequency of cytokine transcripts in T cell lines compared with these same transcripts in the PEC was significantly higher for IFN-gamma (P = 0.0005) and lower for TGF-beta2 (P = 0.0001). An association was observed between the expression of cytokine transcripts in vivo or by TIL-derived cell lines and functions exhibited by either production of cytokines or in vitro cytotoxicity.

Adenocarcinoma↗

A phase I clinical and pharmacological study of oral 9-nitrocamptothecin, a novel water-insoluble topoisomerase I inhibitor.

9-Nitrocamptothecin (9NC) is a water-insoluble topoisomerase I inhibitor with a broad antitumor activity in animal models. To determine the maximum tolerated oral dose (MTD), a phase I study was performed in patients with advanced cancer refractory to conventional chemotherapy. 9NC was administered orally with escalating doses to cohorts of five patients beginning at 1 mg/m2/day for five consecutive days every week for 4 weeks. Increments were 0.5 mg/m2/day for each cohort. Toxicity was evaluated in 28 patients diagnosed with various malignancies. Seven patients received 1 mg/m2/day for 28 weeks; 10 patients, 1.5 mg/m2/day for 68 weeks; and 26 patients, 2 mg/m2/day for 159 weeks. At 1.5 mg/m2/day or higher, the dose-limiting toxicity was hematologic, with grade 4 anemia in eight (29%); neutropenia in seven (25%) and thrombocytopenia in five (18%). Grade 2 or higher toxic effects occurred at each dose level: nausea and vomiting in 15 (54%), diarrhea in nine (32%), chemical cystitis in seven (25%), neutropenic sepsis in six (21%) and weight loss in five (18%) (N=28). Responses were observed after 2-8 weeks of therapy in five patients with pancreatic, breast, ovarian and hematologic tumors. Fourteen patients had a disease stabilization and one patient received treatment up to 18 months. The MTD of 9NC given orally has been estimated at 1.5 mg/m2/day for five consecutive days weekly. 9NC may be tolerated for sustained periods of time, but has the potential for significant hematologic, gastrointestinal and urinary bladder toxicity. Significant antitumor activity was observed, warranting further clinical investigations.

Adult↗

Phase II study of i.v. CI-980 in patients with advanced platinum refractory epithelial ovarian carcinoma.

CI-980 is a synthetic mitotic inhibitor that binds to tubulin at the colchicine site, inhibiting the polymerization of microtubules and arresting cellular division in metaphase. Myelosuppression and neurotoxicity were dose-limiting in phase I studies. Sixteen patients with stage III and IV platinum-refractory ovarian cancer received 4.5 mg/m2/day of CI-980 as a continuous i.v. infusion for 72 h, repeated every 3 weeks. Eleven patients had progression and four patients had stable disease. One patient (6%; 95% CI 0-25%) achieved a partial response after 9 months of treatment which lasted for 27 months. The overall median survival was 7 months. Grade 4 granulocytopenia occurred in five patients, with two episodes of neutropenic fever. Neurological toxicity was mild with 12 episodes of transient subclinical recent memory loss documented in four patients by specialized neuropsychological evaluations. One patient each had hallucinations and mild truncal ataxia, and four patients had mild, reversible neurosensory toxicity. One episode of severe hypoxemia and dyspnea occurred in a patient with chronic obstructive pulmonary disease. CI-980 has minimal activity and is tolerable in a population of heavily pretreated patients with platinum refractory ovarian cancer.

Adult↗

Indium-111- and yttrium-90-labeled human monoclonal immunoglobulin M targeting of human ovarian cancer in mice.

UNLABELLED: Most patients with ovarian cancer have disease in the peritoneal cavity. Treatment of this region is inadequate because recurrences are frequent. Increased radiation doses to tumor and, hence, greater tumor control may be possible with intraperitoneal (i.p.) administration of radiolabeled human monoclonal immunoglobulin M (IgM), which is reactive with tumor-associated antigens. METHODS: Biodistribution studies were performed in nude mice bearing i.p. nodules of human ovarian cancer after administration of human monoclonal IgMlambda (AC6C3-2B12), labeled with 111In or 90Y. Irrelevant 111In-labeled human IgMlambda (CH-1B9) and 90Y-aggregate served as specificity controls. RESULTS: Intravenous administration of 111In-labeled AC6C3-2B12 produced low tumor and high liver and spleen uptake. Intraperitoneal administration of AC6C3-2B12 labeled with 111In or 90Y resulted in rapid, high tumor uptake (>45% of injected dose per gram of tumor at 3 hr) that was at least three-fold higher than any normal organ. Biodistribution results were similar for 111In- and 90Y-labeled IgM. Tumor uptake of 111In-labeled AC6C3-2B12 was two-fold greater than that of 111In-labeled CH-1B9. Normal organ uptakes were similar for tumor-reactive and irrelevant IgM. Radioimmunoconjugates were retained in the peritoneal cavity for a prolonged period of time. Yttrium-90 aggregate demonstrated high tumor and bone uptake. CONCLUSION: Higher tumor uptake was observed after i.p. administration of tumor-reactive IgM than after irrelevant IgM. The in vivo behavior of tumor-reactive IgM was similar when it was radiolabeled with either 111In or 90Y. Therefore, 111In-based imaging studies can be used to predict the biodistribution of subsequently administered 90Y-labeled IgM. Further development of radiolabeled AC6C3-2B12 as a diagnostic and therapeutic agent for patients with advanced ovarian carcinoma is warranted.

Animals↗

Lineage-negative human leukocyte antigen-DR+ cells with the phenotype of undifferentiated dendritic cells in patients with carcinoma of the abdomen and pelvis.

The characteristics of antigen-presenting cells in carcinomas that involve the abdominopelvic cavity are unknown. Dendritic cells, a population of antigen-presenting cells, have been identified as lineage-negative human leukocyte antigen (HLA)-DR+ cells by two-color flow cytometry. We used this criterion to study the putative dendritic cells in ascites from 25 patients with peritoneal carcinomatosis. The mean proportion +/- SD of lineage-negative HLA-DR+ cells in ascites was 3.1 +/- 4.6% (range, 0.05-17.3%). Most lineage-negative HLA-DR+ cells expressed CD45RA or CD4 antigens. Dendritic cells had low proportions of CD80, CD11c, CD45RO, and CD58, suggesting that they were of low maturity. The proportion of lineage-negative HLA-DR+ cells in ascites of seven patients was significantly higher than the proportion in peripheral blood from the identical patients (4.5 +/- 5.7 versus 0.5 +/- 0.4; P < 0.05). In paired specimens of ascites and peripheral blood, the proportion of lineage-negative HLA-DR+ cells that coexpressed CD86 or CD58 was significantly lower in ascites than in peripheral blood, whereas a higher proportion of lineage-negative HLA-DR+ cells in ascites expressed CD4. Relative fluorescence intensity of HLA-DR+ was also lower in dendritic cells from ascites and blood from patients with carcinomatosis than it was in blood from normal donors. As an indicator of macrophage activation, the concentration of neopterin in ascitic fluid correlated negatively with the numbers of lineage-negative HLA-DR+ cells in ascites (Spearman correlation coefficient, -0.44; P = 0.05) correlated positively with the concentration of interleukin 10 in ascitic fluid (Spearman correlation coefficient, -0.40; P = 0.05). IFN-gamma and tumor necrosis factor alpha were also not detected. These findings suggest that certain factors associated with the tumor microenvironment might influence the number of these dendritic cells and their expression of function-associated markers.

Abdominal Neoplasms↗

Intraperitoneal immunotherapy of peritoneal carcinomatosis.

Carcinomas that originate in the ovary or from different sites in the gastrointestinal tract frequently develop metastases that involve the peritoneal and serosal surfaces. Carcinomatous involvement of the peritoneum is a significant cause of morbidity and mortality. Advances in our understanding of the immunobiology of the peritoneal cavity and the availability of technically advanced immunotherapeutic agents are providing an important opportunity for the intraperitoneal delivery of these agents. This review describes newer concepts in tumor immunology that have a bearing on the further development of intraperitoneal immunotherapy; delivery systems for and issues to be resolved in intraperitoneal immunotherapy, and results of studies with recombinant interferons alpha and gamma and interleukin (IL)-2, cellular therapies including lymphokine-activated killer cells, tumor-infiltrating lymphocytes, monoclonal antibodies, and intraperitoneal radioimmunotherapy. New trials of intraperitoneal immunotherapy employing novel agents, including IL-12 and genetically modified tumor vaccines, are discussed, as are issues related to the integration of immunotherapy with standard chemotherapy agents. A number of immunotherapy agents have been tested intraperitoneally and have shown promising clinical activity with acceptable toxicity. Complete responses have been documented at surgical restaging, and intraperitoneal treatments with these agents may soon be included in the therapeutic armamentarium for patients with peritoneal carcinomatosis.

Carcinoma↗

Growth inhibitory effects of aromatic fatty acids on ovarian tumor cell lines.

Epithelial ovarian cancer is a major cause of cancer-related mortality in women, making the search for new treatment modalities essential. Sodium phenylacetate (NaPa), a phenylalanine derivative, has been shown to induce cytostasis and differentiation by inhibiting protein isoprenylation. Similar effects have been observed with phenylbutyrate, a phenylacetate congener. We examined in parallel the growth inhibitory activity against human ovarian carcinoma cell lines of phenylacetate, phenylbutyric acid (PB), and certain related compounds, and comparisons were made with lovastatin. On a molar basis, hydroxykynurenine and kynurenine showed the highest activity followed by PB and NaPa. Ovarian carcinoma cell lines were also sensitive to lovastatin in micromolar concentrations. Additive effects were observed when PB was combined with cisplatin or when NaPa or PB were combined with lovastatin. NaPa and PB, but not kynurenine, inhibited incorporation of [3H]mevalonate into ovarian carcinoma cells. An immune modulatory role might also be suggested for PB because it resulted in increased ovarian tumor cell expression of human leukocyte antigen class I and the cluster of differentiation molecule CD58, whereas transforming growth factor-beta2 expression was decreased. Phenylbutyrate, which is the ester form of PB, has shown acceptable pharmacological properties and clinical responses in patients with other malignancies, and might be considered for evaluation in ovarian cancer.

Aminobutyrates↗

Growth inhibitory effects of sodium phenylacetate (NSC 3039) on ovarian carcinoma cells in vitro.

The aim of this study was to determine the antiproliferative activity of sodium phenylacetate (NaPa) against ovarian carcinoma cell lines. NaPa induced a dose-dependent inhibition (IC50 from 12 mM to >20 mM) of all ovarian carcinoma cell lines, although the sensitivity of individual lines to NaPa varied. Both cisplatin-sensitive and -resistant cell lines responded to NaPa, and growth-inhibitory activity was also detected against cells freshly isolated from malignant ascites of previously treated patients. The growth inhibitory effects that were produced by NaPa were time dependent, showing a maximum effect at 72 h, and were not associated with cytotoxic action. Growth inhibitory effects of NaPa were also reversible. After 48- and 72-h exposures to NaPa, a reduction in the percentage of cells in the S-phase was detected, with a concomitant recruitment of cells in the G0-G1 phase. Treatment with NaPa after different exposure times did not significantly increase the proportion of cells undergoing apoptosis. NaPa also produced a significant reduction in the percentage of cyclin-D1- and p21/ras-positive cells and in the percentage of cells positive for bcl-2, whereas the percentages of bax/p21-positive cells increased. NaPa produced minimal, if any, alterations of expression of HLA class I and transforming growth factor beta1 antigens. In contrast, the percentage of transforming growth factor beta2-positive cells decreased after exposure to NaPa. The combination of NaPa with cisplatin resulted in an additive inhibitory effect. Our results show, for the first time, that NaPa inhibits the growth of ovarian carcinoma cell lines and the cells from malignant ascites of chemotherapy-treated patients with ovarian carcinoma. The growth-inhibitory properties of NaPa suggest that this molecule could represent a prototype of a new class of compounds with possible therapeutic potential in patients with ovarian carcinoma.

Antimetabolites, Antineoplastic↗

Intralesional radiolabeled human monoclonal IgM in human tumor xenografts.

BACKGROUND AND PURPOSE: Intralesional (i.l.) administration of radiolabeled human monoclonal IgM could provide a new method for increasing the radiation dose delivered to a tumor without exceeding normal tissue tolerance. MATERIALS AND METHODS: Nude mice with subcutaneous human head and neck squamous cell carcinoma nodules were injected either intralesionally or intravenously with a tumor-reactive human monoclonal IgM (CR4E8) labeled with indium-111 (111In) or yttrium-90 (90Y). Groups of mice were sacrificed at different time points and their tumors and major organs were excised and counted for radioactivity. Additional mice that were treated with i.l. 90Y-labeled CR4E8 were sacrificed at the same time points for tumor autoradiography. Serial whole-body gamma camera images were obtained from additional mice treated with i.l. 111In-labeled CR4E8. Intralesionally administered 111In-labeled irrelevant IgM (CH-1B9) and 90Y-aggregate served as specificity controls. RESULTS: Intralesional administration of radiolabeled IgM resulted in prolonged high tumor radioactivity with little normal tissue uptake, with kidney and liver having the highest values. The biodistribution of i.l. CR4E8 was similar whether labeled with 111In or 90Y. Tumor uptake of i.l. irrelevant IgM appeared to be lower and tumor retention appeared to be shorter. Intravenous administration of tumor-reactive IgM resulted in very low tumor radioactivity with high liver and moderate spleen uptake. The i.l. administration of 90Y-aggregate produced prolonged high tumor radioactivity with little normal tissue uptake, with bone having the highest value. Tumor autoradiographs demonstrated that the radiolabeled IgM diffused through the tumor over time while the 90Y-aggregate remained localized at the injection site. Gamma camera scintigraphy corroborated the results of the biodistribution studies. CONCLUSIONS: Intralesional but not intravenous administration of 111In- or 90Y-labeled human IgM results in high tumor radioactivity with low normal tissue exposure. Myelotoxicity is not anticipated to be the dose-limiting normal tissue toxicity of this treatment. Further development of human IgM for the i.l. treatment of human malignancies appears to be warranted.

Animals↗

A phase II and pharmacokinetic study of enloplatin in patients with platinum refractory advanced ovarian carcinoma.

This was a study of enloplatin in 18 evaluable patients with platinum refractory ovarian cancer. They received an i.v. infusion of enloplatin over 1.5 h without prehydration every 21 days. One patient had a partial response (6%; 95% CI 0-26%) lasting 2.8 months. The median survival was 9.4 months (95%; CI 5.1-19.7%). Neutropenia was the dose-limiting toxicity. Nephrotoxicity was manageable. Enloplatin is the major form of the free drug in plasma. However, 13.5 h after initiation of treatment, 85% of the drug in plasma is protein bound. Elimination of the drug is mainly renal. Enloplatin pharmacokinetics is similar to that of carboplatin. Thus, the plasma pharmacokinetics of enloplatin is dictated by the cyclobutanedicarboxylato (CBDCA) ligand and not the novel amino ligand.

Adult↗

An update of a phase II study of paclitaxel in advanced or recurrent squamous cell cancer of the cervix.

UNLABELLED: Thirty-two evaluable patients with squamous cell cancer of the cervix were treated with i.v. paclitaxel 250 mg/m2 over 3 h every 21 days. They received standard premedications and granulocyte colony stimulating factor (G-CSF) support (5 micrograms/kg/day). Median (range) age was 49 (29-81) years and performance status Zubrod was 1 (0-2). One patient had a complete response and seven patients had a partial response (25%, 95% CI 8-38%). The median survival was 7.3 months. Granulocytopenia was brief and non-cumulative. G-CSF was used for a median (range) of 8 (1-15) days per cycle. IN CONCLUSION: paclitaxel is active in patients with squamous cell cancer of the cervix and is well tolerated in this dose schedule with G-CSF support.

Adult↗

Phase II study of irinotecan in prior chemotherapy-treated squamous cell carcinoma of the cervix.

PURPOSE: A phase II study was performed to evaluate the antitumor activity and toxicity of irinotecan (CPT-11), a water-soluble derivative of camptothecin, in patients with prior chemotherapy-treated squamous cell cancer of the cervix. PATIENTS AND METHODS: Forty-two patients were included in the study. The median age was 44 years (range, 24 to 59 years). The median Zubrod performance status was 1. All patients were refractory to first-line chemotherapy and 88% had received prior radiotherapy. The initial dose of CPT-11 was 125 mg/m2 given as a weekly 90-minute intravenous infusion for 4 weeks, every 6 weeks. Subsequent doses were unchanged, reduced, or omitted according to toxicity grade. RESULTS: Forty-two patients were assessable for response. The overall response rate was 21%. The median time to response was 6 weeks and the median duration of response was 12 weeks. The overall median duration of survival was 6.4 months. A statistically significant survival advantage (median of 12.6 v 5.1 months) was found in patients whose disease responded to the treatment (P < .015). The major dose-limiting toxic effects (grade > or = 3) were nausea and vomiting (45%), diarrhea (24%), and granulocytopenia (36%). Grade > or = 3 anemia was encountered in 62% of patients and the incidence of thrombocytopenia was negligible. Less severe side effects were alopecia (48%), drug fever (43%), anorexia (33%), fatigue (33%), skin rash (21%), stomatitis (14%), and allergic reaction (9%). The gastrointestinal intolerance was dose-related. The incidence of bone marrow depression did not decrease with dose reduction, possibly because of a cumulative effect or hematologic intolerance by a subset of patients. CONCLUSIONS: CPT-11 has significant activity in refractory cervical carcinoma. Gastrointestinal intolerance and hematologic toxicity must be monitored carefully. Further studies of alternative schedules may improve the tolerance and response rate.

Adult↗

A phase I study of TNP-470 administered to patients with advanced squamous cell cancer of the cervix.

A Phase I study of the novel angiogenesis inhibitor TNP-470 was performed. Patients with inoperable recurring or metastatic squamous cell cancer of the cervix with evaluable disease, no coagulopathy, and adequate renal, hepatic, and hematological function were eligible. One course of treatment consisted of an i.v. infusion of TNP-470 over 60 min every other day for 28 days, followed by a 14-day rest period. The starting dose was 9.3 mg/m2. Eighteen evaluable patients were treated, with a median age of 48 years (range 27-55) and performance status Zubrod 1 (range 0-2). Grade 3 neurotoxicities consisting of weakness, nystagmus, diplopia, and ataxia were encountered in two patients receiving the 71.2 mg/m2 dose. An intermediate dose level of 60 mg/m2 was evaluated and found to be well tolerated by three patients. Only one patient experienced grade 3 nausea on the 60 mg/m2 dose level. No myelosuppression, retinal hemorrhage, weight loss, or significant alopecia were observed. One patient had a complete response, which continues for 26 months, and three patients with initially progressive disease stage had stable disease for 5, 7.7, and 19+ months. Other Phase I studies, including over 200 patients, were performed concurrently with this study. Based on this experience, the dose of TNP-470 recommended for further studies is 60 mg/m2 as a 60-min i.v. infusion every Monday, Wednesday, and Friday. Neurotoxicity was dose limiting, but appears to be reversible. Otherwise, the treatment was well tolerated. The drug may be active in squamous cell cancer of the cervix. Further studies of TNP-470 in squamous cell cancer of the cervix are warranted.

Adult↗

HLA class I expression on human ovarian carcinoma cells correlates with T-cell infiltration in vivo and T-cell expansion in vitro in low concentrations of recombinant interleukin-2.

This study was carried out to determine whether HLA class I or class II expression on ovarian tumor cells and lymphocytic infiltration of the epithelial ovarian carcinoma (EOC) tissues were responsible for the ability to expand tumor-infiltrating lymphocytes (TIL) in vitro in low concentrations of recombinant interleukin-2 (rIL-2). Immunohistochemical analysis was performed using monoclonal antibodies that recognize framework determinants of either HLA class I or HLA class II or leukocyte differentiation antigens (LCA, CD3, CD4, and CD8). Cryostat sections of EOC had HLA class I and HLA class II expression on at least 5% of tumor cells in 18 of 20 specimens (90%). From another portion of the same tumor specimens T-cell lines were developed from TIL in low concentrations of rIL-2 (200-600 IU/ml) in 7 of 17 patients. Tumors from which TIL were expanded in vitro with rIL-2 had significantly higher proportions of HLA class I-positive tumor cells (73 +/- 10%) compared to tumors from which TIL failed to grow (40 +/- 10%) (P = 0.036). However, there was no difference in the proportions of HLA class II-positive tumor cells between the two groups. Tumor specimens of patients whose TIL were expanded in rIL-2 had significantly higher numbers per field (423 +/- 114 vs 154 +/- 20; P = 0.005) and proportions (90 +/- 3% vs 77 +/- 4%; P = 0.023) of infiltrating CD3+ cells, significantly higher numbers per field (115 +/- 44 vs 19 +/- 5; P = 0.003) and proportions (25 +/- 5% vs 11 +/- 2%; P = 0.017) of CD8+ cells and significantly higher numbers per field of CD4+ cells (318 +/- 101 vs 113 +/- 18; P = 0.025), in comparison to tumor specimens from patients whose TIL did not grow in vitro. Significant correlations were observed between the proportions of HLA class I-positive EOC tumor cells and the numbers of infiltrating LCA-positive cells (r = 0.67; P = 0.005) CD3+ cells (r = 0.70; P = 0.002), CD4+ cells (r = 0.69; P = 0.003), and CD8+ cells (r = 0.82; P = 0.001). The proportions of HLA class II-positive tumor cells correlated positively (r = 0.45; P = 0.049) only with the numbers of CD8+-infiltrating cells. In conclusion, we report here that HLA class I expression on EOC cells correlates with T-cell infiltration in vivo and T-cell expansion in vitro, in low concentrations of rIL-2.

Adult↗

Atmospheric, evolutionary, and spectral models of the brown dwarf Gliese 229 B.

Theoretical spectra and evolutionary models that span the giant planet-brown dwarf continuum have been computed based on the recent discovery of the brown dwarf Gliese 229 B. A flux enhancement in the 4- to 5-micrometer wavelength window is a universal feature from jovian planets to brown dwarfs. Model results confirm the existence of methane and water in the spectrum of Gliese 229 B and indicate that its mass is 30 to 55 jovian masses. Although these calculations focus on Gliese 229 B, they are also meant to guide future searches for extrasolar giant planets and brown dwarfs.

Astronomical Phenomena↗

Solar and thermal radiation in Jupiter's atmosphere: initial results of the Galileo probe net flux radiometer.

The Galileo probe net flux radiometer measured radiation within Jupiter's atmosphere over the 125-kilometer altitude range between pressures of 0.44 bar and 14 bars. Evidence for the expected ammonia cloud was seen in solar and thermal channels down to 0.5 to 0.6 bar. Between 0.6 and 10 bars large thermal fluxes imply very low gaseous opacities and provide no evidence for a deep water cloud. Near 8 bars the water vapor abundance appears to be about 10 percent of what would be expected for a solar abundance of oxygen. Below 8 bars, measurements suggest an increasing water abundance with depth or a deep cloud layer. Ammonia appears to follow a significantly subsaturated profile above 3 bars. Unexpectedly high absorption of sunlight was found at wavelengths greater than 600 nanometers.

Ammonia↗