PubMed Health⌕ Search

Biomedical subjects

C J Schultz

Publications and source records attributed to C J Schultz.

At least 37 records · Page 2Linked to original sources
PubMed1998

Arabidopsis mutants define an in vivo role for isoenzymes of aspartate aminotransferase in plant nitrogen assimilation.

Arabidopsis contains five isoenzymes of aspartate aminotransferase (AspAT) localized to the cytosol, chloroplast, mitochondria, or peroxisomes. To define the in vivo function of individual isoenzymes, we screened for Arabidopsis mutants deficient in either of the two major isoenzymes, cytosolic AAT2 or chloroplastic AAT3, using a native gel activity assay. In a screen of 8,000 M2 seedlings, three independent mutants deficient in cytosolic AAT2 (aat2) and two independent mutants deficient in chloroplastic AAT3 (aat3) were isolated. Mapping of aat2 and aat3 mutations and the five AspAT genes (ASP1-ASP5) established associations as follows: the mutation affecting aat2 maps with and cosegregates with ASP2, one of two expressed genes for cytosolic AspAT; the mutation affecting aat3 maps to the same location as the ASP5 gene encoding chloroplastic AspAT. Phenotypic analysis of the aat2 and aat3 mutants revealed a dramatic aspartate-related phenotype in one of the mutants deficient in cytosolic AAT2. The aat2-2 mutant displays an 80% reduction in levels of aspartate transported in the phloem of light-grown plants, and a 50% reduction in levels of asparagine transported in dark-adapted plants. These results indicate that cytosolic AAT2 is the major isoenzyme controlling aspartate synthesized for nitrogen transport in the light, and that this aspartate pool is converted to asparagine when plants are dark adapted.

Arabidopsis↗
PubMed1997

The role of dental prostheses in alveolar ridge squamous carcinomas.

BACKGROUND: Alveolar ridge squamous carcinomas develop in patients outside the usual constellation of risk factors. OBJECTIVE: To determine whether the use of dentures was a risk factor specific to patients with alveolar ridge carcinoma. DESIGN: Case-control method with a unique control group-a concurrent cohort of patients with head and neck cancer with primaries in the oropharynx, hypopharynx, and larynx. SETTING: Tertiary care hospital-based clinic. PATIENTS: Forty-one patients with squamous carcinomas centered on the maxillary or mandibular alveolar ridges. The control group was 175 concurrently seen patients with squamous carcinomas of the laryngopharynx for whom dental status was known. MAIN OUTCOME MEASURES: Age at diagnosis, sex, tobacco use, alcohol use, and denture use. RESULTS: Patients with alveolar ridge were more likely to be female, older, nonsmokers, and nondrinkers. The crude odds ratio of denture use in patients with alveolar ridge cancer was 2.28 (P=.03). Eliminating other confounding factors with logistic regression, the adjusted odds ratio dropped to 1.30 (P=.59). Among patients with alveolar ridge, smoking status correlated with age and gender: current smokers were on average 64.4 years old and 9 of 16 were men. Nonsmokers' average age was 79.1 years and 1 of 11 was a man. CONCLUSIONS: In this study, denture use was not an independent risk factor for alveolar ridge carcinomas. Among patients with little to no tobacco or alcohol exposure, the alveolar ridge carcinomas tended to occur in the elderly and in women.

Aged↗
PubMed1997

Molecular characterisation of a cDNA sequence encoding the backbone of a style-specific 120 kDa glycoprotein which has features of both extensins and arabinogalactan proteins.

Nicotiana alata has a style-specific hydroxyproline-rich glycoprotein (the 120 kDa glycoprotein) which has properties of both extensins and AGPs [19, 20]. The 120 kDa glycoprotein is a soluble component in the extracellular matrix of the transmitting tract of styles where it accounts for ca. 9% of the total buffer-soluble protein. Here we describe the molecular cloning of a cDNA representing the gene NaPRP5 which encodes the backbone of the 120 kDa glycoprotein. Expression of mRNA is restricted to styles, consistent with observations on the distribution of the 120 kDa glycoprotein. Levels of accumulation of the transcript encoding the 120 kDa protein backbone are not altered significantly by pollination with either compatible or incompatible pollen. The protein backbone of the 120 kDa glycoprotein, as predicted by the cDNA sequence, is composed of three distinct domains. The sequence of these domains, together with linkage analysis of the carbohydrate component of the 120 kDa glycoprotein, allows predictions of the likely distribution of substituent glycosyl chains along the protein backbone. The similarity of the C-terminal domains of the 120 kDa glycoprotein and GaRSGP, the galactose-rich style glycoprotein of N. alata, is consistent with the two molecules sharing a common antigenic domain in their backbones [31]. The sharing of domains between distinct hydroxyproline-rich glycoproteins suggests that identification of a glycoprotein of this class solely by its protein or carbohydrate epitope is not valid.

Amino Acid Sequence↗
PubMed1996

A multiinstitutional outcome and prognostic factor analysis of radiosurgery for resectable single brain metastasis.

PURPOSE: Recent randomized trials of selected patients with single brain metastasis comparing resection followed by whole-brain radiotherapy (WBRT) to WBRT alone have shown a statistically significant survival advantage for surgery and WBRT. A multiinstitutional retrospective study was performed, which identified comparable patients who were treated with stereotactic radiosurgery (RS) and WBRT. METHODS AND MATERIALS: The RS databases of four institutions were reviewed to identify patients who met the following criteria: single-brain metastasis; no prior cranial surgery or WBRT; age > 18 years; surgically resectable lesion; Karnofsky Performance Status (KPS) > or = 70 at time of RS; nonradiosensitive histology. One hundred twenty-two patients were identified who met these criteria. Patients were categorized by: (a) status of the primary, (b) status of non-CNS metastasis, (c) age, (d) baseline KPS (from 70-100), (e) histology, (f) time from diagnosis of primary to the detection of the brain metastasis, (g) gender, and (h) tumor volume. RS was performed with a linear accelerator based technique (peripheral dose range was 10-27 Gy, median was 17 Gy). WBRT was performed in all but five patients who refused WBRT (dose range was 25-40 Gy, median was 37.5 Gy). RESULTS: The median follow-up for all patients was 123 weeks. The overall local control rate (defined as lack of progression in the RS volume) was 86%. Intracranial recurrence outside of the RS volume was seen in 27 patients (22%). The actuarial median survival from date of RS is 56 weeks, and the 1-year and 2-year actuarial survival rates are 53% and 30%. The median duration of functional independence (sustained KPS > or = 70) is 44 weeks. Nineteen of 77 deaths were attributed to CNS progression (25% of all deaths). Multivariate analysis revealed the following factors to be statistically significant predictors of survival: baseline KPS (p < .0001) and absence of other sites of metastasis (p = 0.008). CONCLUSION: The RS in conjunction with WBRT for single brain metastasis can produce substantial functional survival, especially in patients with good performance status and without extracranial metastasis. These results are comparable to recent randomized trials of resection and WBRT. The advantages of RS over surgery in terms of cost, hospitalization, morbidity, and wider applicability strongly suggest that a randomized trial to compare RS with surgery is warranted.

Adult↗
PubMed1996

A phase II trial of ilmofosine in non-small cell bronchogenic carcinoma.

We have conducted a study of ilmofosine (1-hexadecylthio; 2-methoxyethyl-rac-glycero-3-phosphocholine) in non-small cell bronchogenic carcinoma, using a schedule of continuous infusion for 5 days and a dose of 300 mg/m2/day. Toxicities were gastrointestinal (nausea, vomiting, diarrhea), fatigue and liver function abnormalities. These were severe and resulted in the removal of some patients from study. No consistent pattern of bone marrow suppression was seen. No tumor regressions occurred in 14 evaluable patients including 5 with no prior therapy. We conclude that ilmofosine is inactive in this tumor at this dose and schedule.

Adult↗
PubMed1996

Stage I and II Hodgkin's disease in the pediatric population. Long-term follow-up of patients staged predominantly clinically.

Between January 1, 1970, and December 31, 1990, 42 consecutive pediatric patients were treated at the Medical College of Wisconsin Affiliated Hospitals for early-stage Hodgkin's disease. Thirty patients were clinically staged. Twelve underwent staging laparotomy as a part of staging work-up. Thirty-one patients were treated with radiation therapy (RT) alone. Eleven were treated with combined chemotherapy and RT. For the entire group, overall survival at 5, 10, and 15 years was 98, 98, and 92%, respectively. Disease-free survival was 86, 86, and 79, respectively. There was no significant difference in overall survival or disease-free survival comparing clinically versus pathologically staged patients. There was a trend toward improved disease-free survival favoring pathologically staged patients; however, this difference did not reach statistical significance (p = 0.07). The long-term results of this series fail to show statistically significant superior disease-free or overall survival with surgical staging.

Adolescent↗
PubMed1995

Risk factors which predict persistent cancer in the abnormal larynx following definitive irradiation.

Laryngeal abnormalities following definitive irradiation for carcinoma of the larynx are common. The objective of this study was to identify risk factors for persistent cancer in such patients who were found to have abnormal larynges following definitive irradiation. A retrospective evaluation of 185 consecutive patients undergoing primary irradiation for a glottic or supraglottic laryngeal squamous carcinoma treated between 1976 and 1990 at the Affiliated Hospitals of the Medical College of Wisconsin was performed. From chart review, data concerning site, stage, intent of treatment, smoking history, treatment dose, fraction size, failure patterns, and outcome were obtained. In addition, worrisome signs and symptoms including ulceration, dysphasia, odynophagia, airway distress, aphonia, blood, pain, oedema, aspiration, and pneumonia were recorded. Univariate association with failure and a persistently abnormal laryngeal examination was assessed using the Mantel-Haenszel test. The odds ratio was used to estimate relative risk associated with dichotomous risk factors. Disease-free and overall survival were estimated using Kaplan-Meier methodology. The log rank test was used to compare survival as defined by the levels of various risk factors. Two-year disease-free survival was 83% (T1 = 93%, T2 = 72%, T3/T4 = 66%). Primary failure was associated with the presence of an abnormal examination (P = 0.001), tracheotomy (P = 0.001), symptom index (P = 0.002), aphonia (P = 0.003), advanced T stage (P = 0.03), and lower total dose (P = 0.03). Of 151 patients who survived 6 months disease-free with an intact larynx, an abnormal examination was seen in those with advanced T stage (P = 0.002), supraglottic primary (P = 0.003), symptom index (P = 0.008), eventual failure at the primary site (P = 0.008), continued smoking (P = 0.01), and higher total dose (P = 0.01). The symptom index (total signs and symptoms of airway distress, aphonia, ulceration, pain, oedema, dysphagia, blood production, aspiration, pneumonia, and odynophagia) was correlated with primary failure and continued smoking. Of 37 patients with continually normal examinations, only 1 (3%) failed at the primary site. Of 102 who survived 6 months but with an abnormal examination, 22 (22%) eventually developed a primary failure. Persistently abnormal larynges are common after radiation therapy, yet not all harbour cancer. Risk factors for persistent cancer include stage, airway, total dose, and symptom index. Patients whose larynges return to normal after radiation rarely fail at the primary site.

Carcinoma, Squamous Cell↗
PubMed1995

Perilipin: unique proteins associated with intracellular neutral lipid droplets in adipocytes and steroidogenic cells.

For several reasons it seems reasonable to suspect that perilipins participate in lipid hydrolysis. First, they are located at the lipid droplet surface, the presumed site of HSL and cholesteryl esterase action. Secondly, they are polyphosphorylated by PKA in concert with lipid hydrolysis. Finally, these proteins appear to be expressed primarily, if not solely, in adipocytes and steroidogenic cells, cells in which lipid hydrolysis is stimulated by cyclic AMP and mediated by HSL or cholesteryl esterase(s), whereas other cells that contain abundant neutral lipid depositions contain no perilipin [13]. Interestingly, these closely related hydrolases share no homology with other mammalian lipases [3]. Although such attributes provide a link between perilipin and lipid hydrolysis, we have no evidence that perilipins participate directly in, or are necessary for, lipid catabolism. The basis for the strong affinity between the perilipins and neutral lipids is unknown. Clearly, lipids and perilipins are tightly linked, as evidenced by selective targeting of epitope-tagged perilipin to lipid droplets and by the paradoxical appearance of lipid droplets in pre-adipocytes transfected with a sense perilipin A construct. Indeed, in differentiating adipocytes the earliest lipid depositions are associated with perilipins, and restriction of perilipin synthesis with anti-sense constructs may impede lipid formation and deposition. It remains to be determined if, in the normal course of events, perilipins are directed toward lipid depositions or if lipids are transported to perilipin foci. Whatever the temporal sequence, the result is that neutral lipids are encased in perilipin-bounded droplets.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1995

The aspartate aminotransferase gene family of Arabidopsis encodes isoenzymes localized to three distinct subcellular compartments.

Here, a complete study is described of all the genes and isoenzymes for aspartate aminotransferase (AspAT) present in Arabidopsis thaliana. Four classes of cDNAs representing four distinct AspAT genes (ASP1-ASP4) have been cloned from Arabidopsis. Sequence analysis of the cDNAs suggests that the encoded proteins are targeted to different subcellular compartments. ASP1 encodes a mitochondrial form of AspAT, ASP3 encodes a chloroplastic/plastidic form of AspAT, whereas ASP2 and ASP4 each encode cytosolic forms of AspAT. Three distinct AspAT holoenzymes (AAT1-AAT3) were resolved by activity gel analysis. Organelle isolation reveals that AAT1 is mitochondrial-localized, AAT3 is plastid-localized, and AAT2 is cytosolic. Gene-specific Northern analysis reveals that each Asp mRNA accumulates differentially with respect to organ-type. However, the individual Asp mRNAs show no dramatic fluctuations in response to environmental stimuli such as light. Southern analysis reveals that four distinct nuclear genes probably represent the entire AspAT gene family in Arabidopsis. These molecular studies shed light on the subcellular synthesis of aspartate in Arabidopsis and suggest that some of the AspAT isoenzymes may play overlapping roles in plant nitrogen metabolism.

Amino Acid Sequence↗
PubMed1994

Continuous split course irradiation for stage I and II Hodgkin's disease: 20 year experience at the Medical College of Wisconsin.

Between January 1970 and December 1989, 153 consecutive patients with stage I or II Hodgkin's disease were treated at the Medical College of Wisconsin Affiliated Hospitals. Eighty-eight patients were clinically staged and 65 patients underwent staging laparotomy. Ninety-nine patients were treated using continuous split course irradiation (CSCI) technique. Overall survival (OS) at 5, 10, and 15 years was 89%, 79%, and 68%, respectively. Disease-free survival (DFS) at 5, 10, and 15 years was 75%, 72%, and 68%, respectively. No significant differences were found in OS or DFS when comparing pathologically and clinically staged patients or when comparing patients treated using CSCI with those treated with the standard technique. Patients treated using CSCI tended to complete therapy in a shorter time, without increased morbidity.

Adolescent↗
PubMed1993

Central lymphatic irradiation for stage III nodular malignant lymphoma: long-term results.

PURPOSE: To report the long-term results of central lymphatic irradiation for stage III nodular malignant lymphoma. PATIENTS AND METHODS: Between 1969 and 1985, 34 patients (26 with nodular poorly differentiated lymphoma, four with nodular mixed lymphocytic/histiocytic lymphoma, and four with nodular histiocytic lymphoma) were treated with central lymphatic irradiation. Median age of the group was 51 years (range, 30 to 73). There were 15 men and 19 women. Staging work-up included a physical examination and bone marrow biopsy in all patients. Seventy-four percent had a lymphangiogram (LAG) and 44% a laparotomy (LAP). Eighty-two percent had either a LAP or a LAG. Thirty-two patients were Ann Arbor stage IIIA and two were stage IIIB. All patients received lymphatic irradiation that encompassed cervical, supraclavicular, axillary, mediastinal, paraaortic, mesenteric, pelvic, and femoral lymphatics to total doses ranging from 20 to 30 Gy in 1.0- to 1.8-Gy fractions. Waldeyer's ring was initially treated in 17 patients. Follow-up information is available on all 34 patients. Median follow-up is 9 years, 8 months (range, 15 to 244 months). RESULTS: Life-table actuarial overall, disease-free, and cause-specific survival rates at 15 years are 28%, 40%, and 46%, respectively. Only one relapse was observed after 9 years. Disease-free survival was significantly improved in patients with five or fewer sites of involvement (P = .02). Age, sex, B symptoms, histology, and technique of irradiation were not prognostically significant. Salvage therapy, including further irradiation and/or chemotherapy, was delivered to 20 patients. Ten percent of these patients remain alive without evidence of disease. Toxicity data were available for the patients treated at the Medical College of Wisconsin (MCW). Radiation Therapy Oncology Group (RTOG) acute hematologic, gastrointestinal, and salivary toxicity scores were < or = 2 in 83% of patients. Late toxicity scores were < or = 2 in 96%. Persistent xerostomia was noted in 23% of patients who received initial treatment to Waldeyer's ring. CONCLUSION: These results suggest that initial comprehensive central lymphatic irradiation may be the preferred approach to achieve a durable relapse-free interval for this group of patients.

Adult↗
PubMed1992

Retention of glucose by N-linked oligosaccharide chains impedes expression of lipoprotein lipase activity: effect of castanospermine.

The effect of castanospermine (CSTP), an inhibitor of glucosidase I, on processing, activity, and secretion of lipoprotein lipase was studied in 3T3-L1 adipocytes. Processing was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of endoglycosidase H (endo H)-digested subunits of lipoprotein lipase from cells incubated 1-2 h with [35S]methionine. Lipoprotein lipase in untreated cells consisted of two groups of subunits, M(r) = 55,000-58,000 and M(r) = 53,000-55,000. The heavier subunits were endo H-resistant, whereas the others were either totally or partially endo H-sensitive. The lipase secreted by untreated cells contained primarily endo H-resistant subunits. Immunofluorescent studies showed that lipoprotein lipase accumulated in Golgi in untreated cells. CSTP, 100 micrograms/ml for 18 h, decreased intracellular lipase activity by 80% and decreased secretion of lipase activity by 91%. Most of the lipase subunits in CSTP-treated cells were totally endo H-sensitive with M(r) = 57,000, some were partially endo H-sensitive, and a trace was endo-H resistant. Totally endo H-sensitive subunits in CSTP-treated cells had a M(r) 2,000-4,000 larger than that in untreated cells, indicating impaired trimming of sugar residues from oligosaccharide chains of the lipase in CSTP-treated cells. The small amount of lipase secreted by CSTP-treated cells consisted primarily of partially endo H-sensitive subunits, with one sensitive and one resistant chain per subunit. Immunofluorescent studies showed that lipoprotein lipase was excluded from Golgi in CSTP-treated cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1991

Glycosylation, activity and secretion of lipoprotein lipase in cultured brown adipocytes of newborn mice. Effect of tunicamycin, monensin, 1-deoxymannojirimycin and swainsonine.

The effect of inhibitors on the glycosylation, activity and secretion of lipoprotein lipase was studied in brown adipocytes cultured from newborn mice. Such cells synthesized and secreted active lipoprotein lipase. It is generally accepted that active lipoprotein lipase is a homodimer. Glycosylation of lipoprotein lipase was analysed by PAGE of endoglycosidase H (endo H)-digested subunits of lipoprotein lipase immunoprecipitated from cells incubated for 1-2 h with [35S]methionine. The most prevalent 35S-labelled lipase subunit (Mr 57,000-58,000) in these cells contained endo H-resistant oligosaccharide chains, the next most prevalent contained totally endo H-sensitive chains, and the least prevalent subunit contained partially endo H-sensitive chains. Complete blocking of the glycosylation of lipoprotein lipase with tunicamycin (1 microgram/ml) for 24 h resulted in synthesis of an inactive non-secretable form of lipase with a smaller subunit (Mr 51,000-52,000). Immunofluorescent studies showed that unglycosylated lipase in tunicamycin-treated cells was retained in the endoplasmic reticulum. Cells treated with 1 microM-monensin, an intra-Golgi transport inhibitor, synthesized an active form of lipase which was not secreted, but was retained in the Golgi. The lipase in monensin-treated cells contained only partially or totally endo H-sensitive chains. Blocking either Golgi mannosidase I with 4 mM-1-deoxymannojirimycin or Golgi mannosidase II with 10 microM-swainsonine resulted in production of a form of lipoprotein lipase which was active and secreted, and which contained only endo H-sensitive chains. Our findings demonstrate that core glycosylation of lipoprotein lipase in the endoplasmic reticulum is required for lipase activity and transport from the reticulum, whereas processing of the oligosaccharide chains to endo H-resistant (complex) type chains in the Golgi is not required for either the activity or the secretion of lipoprotein lipase.

1-Deoxynojirimycin↗
PubMed1991

Characterization of serum-stimulated lipoprotein lipase from bovine heart.

1. A triglyceride (TG) lipase is present in whole homogenate and tissue extracts of beef myocardium with characteristics of lipoprotein lipase (LPL); i.e., activity is stimulated by serum, inhibited by NaCl and protamine sulfate, the protein binds to heparin-Sepharose, and the enzyme has an alkaline pH optimum. 2. This TG lipase, eluted from heparin-Sepharose at 0.9-1.0 M NaCl, has an apparent mol. wt of 64 K daltons. Its primary mRNA is 3.7 kb. 3. Expression of LPL mRNA and enzyme activities are in the ratio of approximately 20:8:1 for hearts of mouse, rat and beef, respectively and correlate with r = +0.99.

Animals↗
PubMed1990

Radioresponse of human astrocytic tumors across grade as a function of acute and chronic irradiation.

Astrocytomas make up the largest group of primary brain tumors of glial origin. Long term survival is rare with high grade tumors (grades 3 and 4), which recur despite subtotal resection, chemotherapy, and aggressive postoperative radiation therapy. In contrast, the 5-year survival for low grade astrocytomas (grades 1 and 2) following subtotal resection and postoperative radiotherapy approaches 50%. Variable sensitivity across grade may contribute to the difference in the behavior of these tumors. To investigate this possibility, the radioresponse of human glial tumors across grade as a function of the dose rate of irradiation was studied. Cell lines derived from a low grade astrocytoma (grade 1) and two high grade astrocytomas (grades 3 and 4) were established in culture. Clonal survival was determined following irradiation of the three cell lines with Cesium 137 gamma rays at high dose rate, 78 Gy/hr, and at low dose rate, range 14 cGy to 79 cGy/hr. The low grade astrocytoma was found to be more radiosensitive than either of the high grade tumors. The alpha/beta (Gy-1/Gy-2) values (linear quadratic model) were 0.35/0.082 for the grade 1 line and 0.20/0.036 and 0.30/0.045 for the grade 3 and 4, respectively. D0 (cGy) values (single-hit multi-target model) were 99, 144, and 117 for grades 1, 3, and 4, respectively. A dose rate effect was present for all three tumor lines irradiated from 14 cGy/hr to 78 Gy/hr. An inverse dose rate effect was also noted at 37 cGy/hr for each of the astrocytic lines. These findings may be useful in the development of strategies to treat astrocytic brain tumors which use high and/or low dose rate irradiation.

Astrocytoma↗
PubMed1988

Chromosome elimination in micronuclei: a common cause of hypoploidy.

An excess of hypoploid cells has repeatedly been reported in studies of aneuploidy and has often been attributed to technical artifact. We have examined at least 200 anaphase or early-telophase cells from each of 28 normal women and found that chromosome or chromatid lagging occurs in an average of 2.43% of cells. In a separate study, we have examined the frequency of micronuclei in cytochalasin B-arrested, binucleate cells and shown that a similar frequency of cells (1.6%) contain one or more micronuclei. Using in situ hybridization of an alpha centromeric probe (alpha R1), which hybridizes to 9 of the 22 human autosomes, we were able to infer that most, if not all, of the micronuclei contain whole chromosomes or chromatids. Since the loss of a chromosome by lagging will induce hypoploid daughter nuclei (two where a chromosome is lost and one where a chromatid is lost), we conclude that lagging is a major mechanism for chromosome loss in human lymphocyte cultures. This loss occurs in the cells of normal individuals under control conditions.

Anaphase↗