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Biomedical subjects

C S Ha

Publications and source records attributed to C S Ha.

67 records · Page 4Linked to original sources
PubMed1994

Radiation-induced injury to the visual pathway.

Radiation-induced injury to the visual pathway was reviewed in a cohort of patients treated for various cancers of the nasal cavity and paranasal sinuses between 1969 and 1985. The study subjects consisted of 219 patients, 137 men and 82 women, in whom detailed records were available on the extent of orbital shielding, treatment plan for estimating doses delivered to various optic structures, and visual acuity follow-up information. There was a wide range in doses administered to various optic structures because patients with different primary lesion types were included and the radiotherapy techniques used varied during this era. The endpoint of the study was visual acuity < 20/100. The Cox proportional hazard model was used to assess the influence of various factors on the latent time to visual impairment and to fit the LQ model to the failure-time data. Actuarial curves showing the proportion of patients with visual impairment as a function of dose and time were generated. Corneal injury occurred in 24 of the 49 patients treated with the 3-field technique without any orbital shielding; variables affecting the incidence of cornea injury were total radiation dose and chemotherapy. Symptomatic retinopathy was diagnosed in 7 of 77 patients who received irradiation to a relatively large retinal surface, but no variables were found to correlate with this complication. Eight patients developed ipsilateral blindness due to optic neuropathy and 11 patients had bilateral visual impairment secondary to chiasm injury. The total radiation dose was identified as the predominant determinant. None of patients receiving a dose of < 50 Gy developed optic neuropathy or chiasm injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Blindness↗
PubMed1993

Gain in target dose from using Computer Controlled Radiation Therapy (CCRT) in the treatment of non-small cell lung cancer.

PURPOSE: A study was undertaken to evaluate the gain from Computer Controlled Radiation Therapy in the treatment of non-small cell lung cancer. The purpose of this study is two-fold: (a) to measure the gain in the minimum target dose provided by Computer Controlled Radiation Therapy and (b) to determine the change in the minimum target dose as a function of the lung tolerance limits. METHODS AND MATERIALS: Six cases of non-small cell lung cancer were studied by stimulating treatments with conventional and Computer Controlled Radiation Therapy techniques. For conventional treatments, a boost dose was delivered to the gross tumor volume via a pair of opposed oblique fields with a fixed gantry angle. For Computer Controlled Radiation Therapy, the gantry angle was allowed to change along the longitudinal axis of the patient. Prescriptions had to satisfy a bound on the maximum dose in the spinal cord and a limit on the amount of contralateral lung which could exceed 20 Gy. The boost dose was increased until either a tolerance limit was reached or minimum target dose of 80 Gy was delivered. RESULTS: A minimum target dose of 80 Gy could be given to three of four patients who could not receive 80 Gy with conventional therapy. A minimum target dose of 80 Gy could be given to the remaining two patients with either technique. CONCLUSION: The gain from computer controlled radiation therapy strongly depended on the chosen lung tolerance limit. A 10 to 20 Gy gain in minimum target dose could be found for some patients, but the gain was significantly reduced for a relatively small decrease in the amount of lung permitted a dose above 20 Gy.

Carcinoma, Non-Small-Cell Lung↗
PubMed1993

An acute toxicity study of recombinant human interferon alpha A (LBD-007) in Sprague-Dawley rats.

The acute toxicity of a recombinant human interferon alpha A (code name: LBD-007) was evaluated in both sexes of Sprague-Dawley rats, 5 weeks old, by the oral, subcutaneous and intravenous routes of administration. Based on the results, LBD-007 was not considered to induce any toxicological effect on the rats in mortalities, clinical findings, body weights and gross findings. It is suggested that LD50 values in rats would be > 48 x 10(8) IU/kg in the study of oral administration and > 24 x 10(8) IU/kg in the study of subcutaneous or intravenous administration.

Administration, Oral↗
PubMed1993

A 4-week subcutaneous toxicity study of recombinant human interferon alpha A (LBD-007) in Sprague-Dawley rats.

Recombinant human interferon alpha A (code name: LBD-007) was subcutaneously administered to both sexes of Sprague-Dawley rats at the doses of 0, 6, 12 and 24 x 10(6) IU/kg of body weight five days per week for 4 weeks to evaluate the subchronic toxicity. 20 to 50% of rats except the male control group showed minimal to mild, focal to multifocal renal mineralization. Whether renal mineralization is related to the test substance is not elucidated. Male rats dosed at 24 x 10(6) IU/kg showed the decrease of the absolute kidney weights and the increase of the brain relative weights. Female rats dosed at 24 x 10(6) IU/kg showed the increase of the absolute and relative ovary weights, and the decreases of specific gravity, bilirubin and urobilinogen in urine. However, no drug-related changes were noted in clinical findings, body weights, food consumption, water consumption, hematology, blood clinical chemistry and necropsy findings. Based on the results it is concluded that the estimated subcutaneous non-toxic dose of the recombinant human interferon alpha A (LBD-007) in rats is (6 approximately 12) x 10(6) IU/kg.

Animals↗
PubMed1993

A 6-month subcutaneous toxicity study of recombinant human interferon alpha A (LBD-007) in Sprague-Dawley rats.

Recombinant human interferon alpha A (code name: LBD-007) was subcutaneously administered to both sexes of Sprague-Dawley rats at the doses of 0, 3, 6 and 12 x 10(6) IU/kg of body weight six days per week for 6 months to evaluate the chronic toxicity. Male rats dosed at 12 x 10(6) IU/kg for 26 weeks showed a decrease of ketone body in the urine, and female rats dosed at 12 x 10(6) IU/kg for 26 weeks showed a decrease of serum alkaline phosphatase. Microscopic changes with remarkable incidence were nephropathy, renal mineralization and ultimobranchial cysts of the thyroid gland in all groups of both sexes of rats. These changes were not considered to be drug-related toxicity because they appeared to be minimal, occasionally mild in severity and did not have dose-dependency as well as clinical significance. In general, no drug-related change was noted in clinical findings, body weights, food consumption, water consumption, hematology, organ weights and necropsy findings. Based on the results, it is concluded that the estimated subcutaneous non-toxic dose of the recombinant human interferon alpha A (LBD-007) in rats would be 6 x 10(6) IU/kg.

Alkaline Phosphatase↗
PubMed1992

A new concentrated perfluorochemical emulsion and carbogen breathing as an adjuvant to treatment with antitumor alkylating agents.

Many anticancer drugs require oxygen to be cytotoxic or are selectively cytotoxic toward cells under oxygenated conditions. The effects of the dilute perfluorochemical emuolsion Fluosol with a wide variety of chemotherapeutic agents have been explored; however, it has not been possible to determine the optimal level of circulating perfluorochemical emulsion with anticancer drugs because the volume of Fluosol that may be administered is limiting. Using a new concentrated perfluorochemical emulsion, a wide range of perfluorochemical doses has been examined in combination with melphalan, cyclophosphamide and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) in the FSaIIC fibrosarcoma. When the perfluorochemical emulsion was administered by injection i.v. just prior to the injection of melphalan (10 mg/kg), cyclophosphamide (150 mg/kg) or BCNU (50 mg/kg), the greatest tumor growth delays were obtained with dosage levels between 4 g and 12 g of the perfluorochemical perfluorooctyl bromide/kg. With each drug the greatest tumor growth delays were obtained when the drug was prepared in the emulsion and the combination injected i.v. In each case, each dose of drug was followed by 6 h of breathing carbogen. The addition of the perfluorochemical emulsion/carbogen breathing to treatment with melphalan, BCNU or cyclophosphamide resulted in significant increases in the killing of tumor cells by these drugs without a concomitant increase in toxicity to bone marrow granulocyte/macrophage-colony-forming units. In each case, preparing the drug in the perfluorochemical emulsion was most effective. These results indicate that clinical trial of this perfluorochemical emulsion/carbogen breathing in combination with cancer chemotherapy may be warranted.

Administration, Inhalation↗
PubMed1992

Multiple modality treatment of carcinoma cells with Pt(Rh-123)2 plus x-ray plus light.

A complex of platinum tetrachloride with two molecules of rhodamine-123 (Rh-123), Pt(Rh-123)2, has been reported to act as hypoxic cell radiosensitizer of carcinoma cells in vitro and in vivo. In the present paper we report that Pt(Rh-123)2 photosensitizes human mammary carcinoma (MCF-7) cells and cis-platinum resistant human mammary carcinoma (MCF-7/CP) cells to 400-800 nm light in vitro. The efficiency of photosensitization by Pt(Rh-123)2 was 10 times greater than for Rh-123. Combination therapy using Pt(Rh-123)2 plus x-ray plus light was also much more effective compared to the combination therapy using Rh-123 plus x-ray plus light. After 15 microM of Rh-123 plus x-ray (0-8 Gy) plus light (5 J/cm2) treatment, cell survival curve was parallel to the x-ray cell survival curve with an initial decrease in the surviving fraction corresponding to the drug plus light mediated killing. Cell killing caused by Rh-123 (15 microM) plus x-ray (0-8 Gy) plus light (5 J/cm2) was additive as determined by the product of the surviving fraction after Rh-123 plus light and x-ray. In contrast, for 15 microM of Pt(Rh-123)2 plus x-ray (8 Gy) plus light (5 J/cm2) treatment, whereas additive killing predicts a survival fraction of approximately 0.024, in reality, the combination therapy caused the survival fraction to decrease to 0.0012, implying that the cell killing was enhanced by a factor of 20. Using Pt(Rh-123)2 plus x-ray plus light, supra-additive cell killing was also observed under hypoxic conditions, although compared to normally oxygenated conditions the degree of cytotoxicity was significantly reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1987

Dequalinium, a topical antimicrobial agent, displays anticarcinoma activity based on selective mitochondrial accumulation.

Positively charged lipophilic compounds, such as rhodamine 123, localize in mitochondria and are selectively accumulated and retained by carcinoma cells. It has been suggested that this phenotype may be exploited for selective killing of carcinoma cells by lipophilic cations. Here we report that doubly positively charged dequalinium, which has been used for 30 years as an antimicrobial agent in over-the-counter mouthwashes, lozenges, ointments, and paints, exhibits significant anticarcinoma activity. Dequalinium is more effective than seven of eight established anticancer drugs in prolonging the survival of mice with intraperitoneally implanted mouse bladder carcinoma MB49. Dequalinium also inhibits the growth of subcutaneously implanted human colon carcinoma CX-1 in nude mice and recurrent rat colon carcinoma W163 in rats. Lipophilic cationic compounds, such as dequalinium, could comprise a unique class of anticarcinoma agents.

Animals↗
PubMed1983

Purification and partial characterization of ring-shaped miniparticles.

Small ring-shaped miniparticles, found in the nucleus nucleolus and cytoplasm of a variety of normal and malignant cells, have been purified by a procedure involving differential and gradient centrifugation, hydroxylapatite chromatography and preparative electrophoresis. They are multisubunit proteins comprised of at least six polypeptide chains of Mr 20,000-30,000 Daltons (by one-D SDS-PAGE which present a series of 20-30 spots on two-D IEF/SDS gels. They can be reversibly dissociated in EDTA containing buffers. They are not membrane associated and contain no carbohydrate. They have an S20,W of 21S on sucrose gradients. They are immunologically similar in several human cell lines.

Cell Fractionation↗
PubMed1982

Mechanism of destruction of Brugia malayi microfilariae in vitro: the role of antibody and leucocytes.

Human and monkey leucocytes in serum from previously patent Brugia malayi infected monkeys adhered to and caused cytotoxicity to microfilariae of B. malayi in vitro. The phenomenon also occurred in human serum from confirmed cases of bancroftian and malayan elephantiasis. Adherence of leucocytes was not seen in serum from uninfected monkeys, monkeys with patent B. malayi infection and serum from rats infected with Breinlia booliati but now amicrofilaraemic. Immune serum failed to promote adherence of leucocytes to L3 of B. malayi. The activity was lost when the serum was either incubated with Protein A-bearing Staphylococcus aureus or heat inactivated at 56 degrees C for 30 min. Light and electron microscopic observations regarding the type of adhering cells and sequence of events following adherence are described.

Animals↗
PubMedDate not supplied

Effects of 2-bromopropane on spermatogenesis in the Sprague-Dawley rat.

In 1995, 2-bromopropane (2-BP) was associated with occupational reproductive and hematopoietic toxicity in Korea. The effect of 2-BP on spermatogenesis, or Leydig cells, has not been determined in adult rats. In the present study, 40 ten-week-old Sprague-Dawley (SD) rats were treated orally with 3.5 g/kg/d of 2-BP for 3 consecutive days. At 1, 3, 5, 7, 14, 28, 42, and 70 d after treatment, testes were perfused with Karnovsky's solution or immersed in Bouin's solution, embedded in plastic or Epon and evaluated with light and electron microscopy. DNA ploidy distributions of testicular suspensions were determined by flow cytometry, which allowed comparison of quantitative spermatogenesis with histopathologic observations. Degeneration of spermatogonia was observed during Stages I-IV in seminiferous tubules on Day 1 after treatment. Spermatocytes, spermatids, Sertoli cells, and Leydig cells appeared normal in the early stage of the study. Whereas spermatid retention in Stages IX-XI was observed on Day 7 after treatment, depletion of spermatocytes and spermatids continued over time, followed by a marked increase of germ cells on Day 42 after treatment. However, the seminiferous tubules did not completely recover by study termination. Leydig cell cellularity increased mildly without any significant morphologic modification at the end of the study. Immunohistochemistry using an antibody against proliferating cell nuclear antigen (PCNA), showed an increased number of immunoreactive Leydig cells in the interstitium. In the flow cytometry analysis, proportions of diploid and tetraploid cells gradually decreased time-dependently until Day 28 after treatment, but showed an increase on Day 42, followed by a decrease on Day 70 after treatment. These data are strengthened by qualitative descriptions of lesions observed by histopathology. These results suggest that a high dose of 2-BP can decrease spermatogenesis by adversely affecting spermatogonia followed by depletion of spermatocytes, spermatids, and spermatozoa, with subsequent testicular atrophy. The atrophied testes may not regenerate completely. The number of Leydig cells may increase mildly with 10 weeks of recovery.

Animals↗
PubMedDate not supplied

Correlation of gallium-67 SPECT and CT findings in primary gynecologic lymphoma.

Primary gynecologic malignant lymphomas are rare and gallium (Ga)-67 imaging has proven to be useful to differentiate viable lymphoma from fibrotic or necrotic tissue. Computed tomographic (CT) scan is often used in initial localization and staging of the lymphoma. In this study, we retrospectively analyzed the findings of Ga-67 single photon emission computed tomography (SPECT) correlated with those of CT scan for staging initial disease and also differentiation between active lymphoma and post-treatment changes in the follow-up studies.

Antineoplastic Agents↗