PubMed HealthSearch

Biomedical subjects

J A Kim

Publications and source records attributed to J A Kim.

16 recordsLinked to original sources

Effects of site-directed mutations on processing and activities of penicillin G acylase from Escherichia coli ATCC 11105.

Penicillin G acylase from Escherichia coli ATCC 11105 is synthesized from its precursor polypeptide into a catalytically active heterodimer via a complex posttranslational processing pathway. Substitutions in the pair of aminoacyl residues at the cleavage site for processing the small and large subunits were made. Their processing phenotypes and penicillin G acylase activities were analyzed. By the introduction of a prolyl residue at either position, the processing of the small subunit was blocked without a change in enzymatic activity. Four other substitutions had no effect. At the site for processing the large subunit, four substitutions out of the seven examined blocked processing. In general, penicillin G acylase activity seemed to be proportional to the efficiency of the large-subunit-processing step. Ser-290 is an amino acid critical for processing and also for the enzymatic activity of penicillin G acylase. In the mutant pAATC, in which Ser-290 is mutated to Cys, the precursor is processed, but there is no detectable enzymatic activity. This suggests that there is a difference in the structural requirements for the processing pathway and for enzymatic activity. Recombination analysis of several mutants demonstrated that the small subunit can be processed only when the large subunit is processed first. Some site-directed mutants from which signal peptides were removed showed partial processing phenotypes and reduced enzymatic activities. Their expression showed that the prerequisite for penicillin G acylase activity is the efficient processing of the large subunit and that the maturation of the small subunit does not affect the enzymatic activity.

DNA Mutational Analysis

Vitiligo in autoimmune thyroid disease.

The authors studied the association between vitiligo and autoimmune thyroid disease. Vitiligo was found in 20 of 293 patients with autoimmune thyroid disease (6.83%), 2 out of 227 patients with nonautoimmune thyroid disease (0.88%), and 3 out of 386 control group (0.78%). These results showed that vitiligo is closely associated with autoimmune thyroid disease (chi 2 = 24.33, p < 0.0001), but not with nonautoimmune thyroid disease. Prevalence of vitiligo in nonautoimmune thyroid disease was not different from that in control. Vitiligo in autoimmune thyroid disease was most frequently found on dorsum hands and forearms, and usually preceded the onset of thyroid disease. Four out of twenty patients with vitiligo associated autoimmune thyroid disease had another presumed autoimmune disease, that is, alopecia areata, alopecia totalis, and rheumatoid arthritis. These findings suggested that autoimmunity plays an important role in the pathogenesis of vitiligo.

Adult

Beta-VLDL increases endothelial cell plasma membrane cholesterol.

In this study, the distribution of free cholesterol in cholesterol-loaded endothelial cells was examined. For these studies, cell fractionation methods were used to assess marker enzyme activity and cholesterol distribution. Treatment of rabbit aortic endothelial cells for 3 days with 50 micrograms/ml of beta-very low density lipoprotein (beta-VLDL) or malondialdehyde-low density lipoprotein (MDA-LDL) but not LDL caused a 50-100% increase in total cell unesterified cholesterol. The accumulation of free rather than esterified cholesterol in endothelial cells may be due to the ratio of hydrolysis to esterification, which we have shown in this study to be 10-fold higher in endothelial cells than in smooth muscle cells. This free cholesterol is found in the fractions enriched in plasma membrane markers and, to a lesser extent, in the Golgi-enriched fractions. The amount of cholesterol per mg of protein was increased approximately 50% in these fractions from cells treated for 3 days with 50 micrograms/ml of beta-VLDL. These increases in cholesterol content were reversible upon incubation of cells for 3 days in medium containing 15% fetal bovine serum. Alterations in several membrane functions were also observed in cholesterol-loaded cells. The activity of alkaline phosphatase, an enzyme marker for plasma membranes, was decreased by 25% and an alteration in membrane-associated microfilaments was seen with phalloidin staining. This morphological change in microfilaments was reflected in a decrease in filament ends as shown by cytochalasin binding and occurred without a change in total actin or vinculin. These microfilament changes were reversible.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins

Minimally modified low density lipoprotein stimulates monocyte endothelial interactions.

The effect of minimally modified LDL (MM-LDL) on the ability of large vessel endothelial cells (EC) to interact with monocytes and neutrophils was examined. These LDL preparations, obtained by storage or by mild iron oxidation, were indistinguishable from native LDL to the LDL receptor and were not recognized by the scavenger receptor. Treatment of EC with as little as 0.12 micrograms/ml MM-LDL caused a significant increase in the production of chemotactic factor for monocytes (sevenfold) and increased monocyte binding (three- to fivefold). Monocyte binding was maximal after 4 h of EC exposure to MM-LDL, persisted for 48 h, and was inhibited by cycloheximide. In contrast, neutrophil binding was not increased after 1-24 h of exposure. Activity in the MM-LDL preparations was found primarily in the polar lipid fraction. MM-LDL was toxic for EC from one rabbit but not toxic for the cells from another rabbit or any human umbilical vein EC. The resistant cells became sensitive when incubated with lipoprotein in the presence of cycloheximide, whereas the sensitive strain became resistant when preincubated with sublethal concentrations of MM-LDL. We conclude that exposure of EC to sublethal levels of MM-LDL enhances monocyte endothelial interactions and induces resistance to the toxic effects of MM-LDL.

Animals

[The effect of supportive nursing care on depression, mood and satisfaction in military patients with low back pain].

Support has always been considered an important nursing concept. However, there is no agreement among nurse researchers as to a conceptual definition of supportive nursing or meaningful supportive behaviors. Clarification of the concept, support in nursing, is necessary to promote communication among nurses on nursing behaviors that are effective in providing support and on understanding the relevant properties and characteristics of the concept, supportive nursing care. The objectives of the study were: 1. to analyze the concept, support in nursing, in order to provide a definition of supportive nursing care, and 2. to operationalize the definition of supportive nursing care and use it as an experimental nursing intervention for patients with low back pain. The first part of the study used the concept analysis approach developed by Walker and Avant (1983) to define the concept of supportive nursing care. The properties of supportive nursing care, defined by this analysis, included perception of supportive need, reciprocal interaction (Transaction), listening, providing empathy and information related to health, and confirmation of the patient's verbal and non-verbal response. The second part, the experimental part of the study, was done using King's(1970) Interpersonal Theory for Nursing. The concept, supportive nursing care, as defined in the concept analysis was operationalized and used as the experimental intervention. The experiment tested the effectiveness of the independent variable, supportive nursing care on the dependent variables, depression, mood and patient satisfaction, in the patients with low back pain in army hospitals. The instruments used to measure the dependent variables were Zung's(1965) Self-Rating Depression Scale, Ryman and Colleagues' (1974) Mood Questionnaire and LaMonica and Colleagues' (1986) Patient Satisfaction Scale. The experimental design used for this study was a Solomon 4 group experimental design. This design has the strength of allowing for observation of the main effects of supportive nursing care and pretesting, and for observation of the interaction effects of pretesting and supportive nursing care. The design includes one experimental group and three control groups. The Subjects of this study were 150 young male patients with low back pain on Neuro-Surgical Wards in three general army hospitals. There were 35 in the experimental group, 39 in the pre-posttest control group, 36 in the treatment-posttest control group and 40 in the posttest only control group. Supportive nursing care, as operationalized by the researcher according to the concept analysis, was given to the patients in the experimental group and the treatment-posttest control group, individually for 30 minute sessions, every other day for 5 days.(ABSTRACT TRUNCATED AT 400 WORDS)

Affect

Flow cytometric DNA analysis of primary and concurrent metastatic squamous cell carcinoma of the head and neck.

Adequate flow cytometric DNA analysis comparing primary and concurrent metastatic squamous cell carcinoma of the head and neck has not been done in the past. The purpose of this study was to define any differences between the primary and concurrent metastasis of each patient with respect to flow cytometric parameters and histologic grade. Paraffin-embedded archival specimens from 28 patients with primary and metastatic tumors were prepared into nuclei and analyzed by flow cytometry using human lymphocyte standards. The mean DNA index was 0.82 for primary tumors and 0.83 for the metastases. Aneuploidy was found in 68 percent of primary tumors and in 82 percent of metastases. The percentage of cells in the proliferative fraction was 40.4 in the primary tumors and 24.5 in the metastases. A direct correlation was found between the differentiation of the primary and metastatic tumors. No survival difference was discovered among the flow cytometric parameters and histologic grade. We conclude that there is no difference between the primary and concurrent metastasis in squamous cell carcinoma of the head and neck with regard to DNA index, aneuploidy, or histologic grade.

Aneuploidy

Results of the radiotherapeutic management of carcinoma of the cervix with emphasis on the influence of histologic classification.

The histology of 365 of 396 patients (92%) treated with radiation therapy at the University of Virginia from 1968 to 1978 has been reviewed. Staging and treatment policies were consistent throughout this period, and have enabled the influence of histologic classification on treatment results to be evaluated. Large cell nonkeratinizing carcinoma (LCNK) was the most common type, 69%; followed by keratinizing (KSCC), 13%; and adenocarcinoma, 6.6%. Other varieties included adenosquamous, 3.6%; small cell undifferentiated carcinoma, 2.7%; papillary squamous, 1.6%; and glassy cell, 1.4%. Overall survivals by stage were similar to those reported from other centers. When examined by histologic type, the 5-year survival rates ranged from 64% for adenosquamous to 13% for small cell. The most common varieties, LCNK and KSCC, had survival rates of 61% and 40% (P = 0.008). Considering both stage and histologic type, the differences between LCNK and KSCC persisted and were significant for Stage IIB (P = 0.023). Of particular interest are the poor results in small cell carcinoma and adenocarcinoma, except in the earliest stages, and the good results for adenosquamous carcinoma. The patterns of failure by histologic type showed that local failures were higher in cases of KSCC than in LCNK, indicating a probable difference in radiosensitivity. Distant spread was similar for both types. Both small cell carcinoma and adenocarcinoma showed high rates of distant spread and local failure except in the early stages. Considering survival and failure rates, three prognostic groups could be identified. In descending order of curability these were: 1) LCNK and adenosquamous carcinoma; 2) KSCC, papillary squamous carcinoma, and adenocarcinoma; and 3) small cell carcinoma and glassy cell carcinoma.

Brachytherapy

The prognostic significance of lymph node involvement in pyriform sinus and supraglottic cancers.

Three hundred and thirty-three patients with carcinoma of the pyriform sinus or supraglottis were reviewed with regard to lymph node involvement and prognosis. All patients were treated with curative intent and had a minimum follow-up of 3 years. Every patient was restaged according to the AJCC, 1983 recommendations. In addition, nodal fixation to cervical fascia or muscle was evaluated with regard to prognosis. Seventy-five percent (89/119) of the pyriform sinus cancer and 47% (101/214) of the supraglottic cancer patients presented with clinically palpable cervical nodes. The distribution of patients according to N stage was 143 (43%), 84 (25%), 58 (17%), 48 (14%) for N0, N1, N2, N3 respectively. In patients where information on nodal fixation was available, 29% had fixed nodes. No difference in prognosis was noted between N0 and N1 or N2 and N3 stages, and these groups were therefore combined. The 3-year survival was 85% for T1 (N0/N1), 77% for T2 (N0/N1), 63% for T3 (N0/N1), and 65% for T4 (N0/N1) cases compared to 19% for T1 (N2/N3), 34% for T2 (N2/N3), 33% for T3 (N2/N3), and 32% for T4 (N2/N3) cases demonstrating that N stage predominates over T stage with respect to survival. Both the local recurrences and distant metastases increased as N stage advanced. A noteworthy difference between patients with fixed nodes and mobile nodes was found with regard to neck recurrence (35% versus 17%), distant metastases (33% versus 19%) and survival (27% versus 58%). In conclusion, nodal stage is a highly significant determinant of survival independent of T stage in cancers of the pyriform sinus and supraglottis. N0, N1 status and mobility were predictive of a favorable prognosis as opposed to N2, N3 status and fixation. These findings were consistent when the pyriform sinus cancers and supraglottic cancers were analyzed separately.

Humans

Uncommon variants of cervical carcinoma treated with radical irradiation. A clinicopathologic study of 66 cases.

Although certain histologic types are uncommon in cervical carcinoma, these tumors as a group comprise almost one in five patients. The present study throws some light on the therapeutic approaches that are appropriate. From 1968 through 1978, 396 patients with carcinoma of the cervix were treated primarily with radiation therapy, at the University of Virginia Medical Center. The treatment policy remained consistent throughout the study interval. Diagnostic pathologic material was reviewed and uniformly classified in 365 cases (92.2%). Over 80% were invasive keratinizing or nonkeratinizing squamous cell carcinoma. There were 66 patients with uncommon histologic types including 24 adenocarcinomas (6.6%), 13 adenosquamous carcinomas (3.6%), 10 small cell carcinomas (2.7%), 6 papillary squamous carcinomas (1.6%), 5 glassy cell carcinomas (1.4%), and 8 miscellaneous types (2.2%). These 66 patients form the basis for this report. Five-year survival rates and causes of failure are presented along with management recommendations.

Adenocarcinoma

Dose response to preoperative irradiation in rectal cancer: implications for local control and complications associated with sphincter sparing surgery and abdominoperineal resection.

Sixty patients with locally advanced adenocarcinoma of the rectum have been treated with preoperative high dose pelvic irradiation at the University of Virginia and Rockingham Memorial Hospital. Fifty-six patients showed no evidence of distant metastases at surgery. A dose response was observed with a 67% incidence of local control with 4000 cGy vs. 91% incidence with 5000 cGy. For the 52 patients who received curative surgery, there has been no local failure alone; 6 of these patients have had local plus distant failure and 16 have had distant failure only. Forty-three percent had anterior resection (AR) and 57% had abdominoperineal resections (APR). The major complication rate was 5% and the minor 14%. No increase in complications or decrease in local control was found between APR and AR. Five-year actuarial survival was 64% for lesions limited to the bowel wall, 59% for node negative lesions with disease extending through the wall, and 23% for node positive patients.

Adenocarcinoma

Papillary squamous cell carcinoma of the uterine cervix: a clinicopathologic study of nine cases.

Papillary squamous cell carcinoma (PSCC) of the uterine cervix is an infrequently described subtype of cervical malignancy. Nine cases of PSCC encountered at the University of Virginia Medical Center are reviewed. The clinical course of these patients, including a propensity for late metastases and recurrences, appears distinctive. The papillae of PSCC are lined by dysplastic cells, unlike verrucous carcinoma. PSCC may exist in an in situ state, and demonstration of invasion, when present, requires deep biopsies or cervical conization. Therapy for PSCC appears to be the same as for ordinary squamous cell carcinoma of equivalent clinical stage.

Adult

Carcinoma of the middle ear and external auditory canal.

Thirty-one patients with malignant tumors of the middle ear and external auditory canal (EAC) were observed at the University of Virginia Hospital from 1956 through 1980. Of 27 patients with carcinoma, 21 had squamous cell carcinoma, 4 had basal cell carcinoma and 2 had adenoid cystic carcinoma. One Ewing's sarcoma and 3 rhabdomyosarcomas occurred in an age group of one to 10 years. The 27 patients with carcinoma are reviewed with regard to clinical presentation, treatment modality, results and complications. The majority (67%) of patients had a history of chronic ear drainage, 22% had a previous mastoidectomy or polypectomy and 7% had an associated cholesteatoma. The treatment modalities employed depended on the extent of disease and the patient's general condition. Eighty percent of patients with carcinoma limited to EAC were alive and well at 5 years, compared to 43% of patients with involvement of the middle ear. Fifty-six percent of patients without invasion of the petrous bone were alive at 5 years compared to only 20% of patients with petrous bone involvement. The data strongly suggest that survival depends on the extent of disease. The corrected disease free 5 year survival rates were 14% for patients who had surgery alone and 50% for those who had surgery and radiotherapy. Of the three patients with advanced disease who received radiotherapy alone, none survived five years. Surgery or radiotherapy alone is not sufficient for most of the cases of carcinoma of the middle ear, since these patients often present with advanced disease. We recommend combined therapy, especially postoperative radiotherapy, except for early lesions that do not involve the mastoid or petrous bone. Other series suggest radiotherapy would be adequate and more effective than surgery for early lesions. Surgery will provide the diagnosis, determine the extent of disease, offer adequate drainage of infected material and relieve most pain before radiation therapy.

Adult