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Biomedical subjects

D Fischer

Publications and source records attributed to D Fischer.

At least 37 records · Page 2Linked to original sources

Phytoalexin synthesis in soybean: purification and characterization of NADPH:2'-hydroxydaidzein oxidoreductase from elicitor-challenged soybean cell cultures.

An NADPH:2'-hydroxydaidzein oxidoreductase (HDR) from elicitor-challenged soybean cell cultures was purified to apparent homogeneity by a five-step procedure. The purification procedure included affinity adsorption on Blue Sepharose and elution of the enzyme with NADP+. It was shown by gel filtration and by sodium dodecyl sulfate-polyacrylamide gel electrophoresis that HDR consists of only one polypeptide, which has a Mr about 34,700. The pH optimum of the reaction was 7.0. Apparent Michaelis constants determined for 2'-hydroxydaidzein, 2'-hydroxyformononetin, and NADPH were, respectively, 50, 60, and 56 microM. A low conversion of 2'-hydroxygenistein to the corresponding isoflavanone was also observed but isoflavones lacking a 2'-hydroxyl group and various other flavonoids did not serve as substrates. Enzymatically derived 2'-hydroxydihydrodaidzein gave a positive CD spectrum at 328 nm, which shows its 3R stereochemistry. Antibodies against HDR were raised in rats.

Blotting, Western

Regional nodal irradiation in the conservative treatment of breast cancer.

At this institution conservative treatment of breast cancer was begun in the 1960's. The following analysis represents our experience through 1984 with specific reference to the management of the regional lymph nodes. A total of 432 patients with clinical stage I and II breast cancer were treated between 1962 and 1984 with lumpectomy and radiation therapy. The breast was treated with tangential fields to a median dose of 4800 cGy and electron conedown to a total tumor bed dose of 6400 cGy. Axillary dissection was not routinely performed, particularly in the earlier years. More recently, axillary dissection has been used with increasing frequency if it was felt that the results of the dissection would influence systemic treatment. One hundred eighty-seven patients (43%) underwent axillary dissection (30% pathologically positive) and routinely received regional nodal irradiation (median dose 4600 cGy) to the internal mammary and supraclavicular lymph nodes. Two hundred forty-five patients (57%) did not undergo axillary dissection and routinely received regional nodal irradiation to the internal mammary, supraclavicular, and entire axillary regions to a total median dose of 4600 cGy. As of May 1989 with a median follow-up of 7.5 years, there have been a total of 12 nodal failures for an actuarial nodal control rate of 97% at 5 years and 96% at 10 years. The actuarial 5-year regional nodal control rate was the same for both the group of patients receiving regional RT alone without axillary dissection and the group of patients receiving axillary dissection and supraclavicular/internal mammary radiation. There has been minimal morbidity associated with this treatment policy. We conclude that regional nodal irradiation as described above, with or without axillary dissection, results in a high rate of regional nodal control and minimal treatment morbidity in patients undergoing conservative treatment of early stage breast cancer.

Axilla

Perioperative assessment of cardiac energy metabolism by means of arterio-coronary venous difference in lactate concentration (acDL). A parameter for optimizing ventricular function of the postcardioplegic myocardium.

Fourty-three patients undergoing open heart surgery were subjected to extended hemodynamic and metabolic monitoring (arterial and coronary sinus (CS) lactate concentration). In 95% of patients investigated, a significant increase in CS lactate concentration above the arterial lactate concentration was established at the beginning of reperfusion (RPT). In these cases, a decrease in the CS lactate below the arterial concentration occurs within the RPT creating a cross-over point (COP) from negative to positive lactate extraction values. Whereas the initial rise in CS lactate is an expression of the expected ischemia-induced acceleration of anaerobic glycolysis, the onset of a positive lactate extraction can be related to reconsolidation of mitrochondrial oxidative phosphorylation. We found two groups with an early and late COP at 7.2 +/- 0.8 min (ECOP) and 42.5 +/- 5.2 min (LCOP) (P less than 0.005). Whereas a short cross-over time was associated with a normal postoperative outcome, cardiac recovery was delayed in the LCOP group. With the aid of metabolic monitoring it is possible to identify the COP and cardiac overload situations and so to optimize the perioperative outcome, especially in selected patients (NYHA stage III/IV, re-operation, high-risk operation).

Adenosine Triphosphate

[Arterio-coronary venous difference in lactate concentration--a new objective and topical available parameter for the estimation of the energy metabolism status of the heart].

Cardiosurgical operations were tested experimentally by means of a perioperative metabolic-energetic monitoring and by the conventional method of the hemodynamic monitoring (Swan-Ganz-catheter). By that could be shown that a perioperative monitoring by means of the arterio-coronary venous difference of the lactate level is possible. Intraoperative information about the topical metabolic-energetic condition of the myocardium is to receive as the decisive advantage of this method. An improvement of the therapy results is possible in that way by an optimum of the treatment. A metabolic recovery of the heart during the operation was substantial more favourable for the postoperative myocardial restitution than an early application of catecholamins. This method for perioperative observation should be used specially in risk operations (NYHA-stadium III-IV, reoperations, etc.).

Biomarkers

Changes in intact parathyroid hormone levels during hemodialysis following exposure to either differing dialyzate calcium concentrations or calcium-free dialysis with varying calcium infusion rates.

To determine the optimal infusion rate for calcium, when using a dialyzate which was calcium free, six patients were treated sequentially, in random order, with six different dialyzates. Three were calcium free and they were infused with replacement calcium at either 10, 15 or 20 ml/hour using 10% CaCl2. The other three used standard bicarbonate dialyzate with either 1.25, 1.5 or 1.75 mmol/l calcium. Ionized calcium and intact parathyroid hormone (Nichols IRMA PTH) were measured at the start and end of each dialysis. Ionized calcium rose slightly with 15 ml/hour calcium infusion and PTH fell 137 +/- 111 pg/ml. These changes were similar to those of 1.5 mmol/l calcium in standard bicarbonate. More PTH suppression and higher end dialysis calcium resulted from 20 ml/hour infusion or 1.75 mmol/l dialyzate calcium. It was concluded that 15 ml/hour is a suitable calcium infusion rate under normal conditions when using calcium-free dialyzate.

Analysis of Variance

[Heart surgery interventions in risk patients. New possibilities for improving therapeutic results].

Perioperative therapy in conjunction with cardiac surgery had so far been guided by functional, paraclinical, and clinical parameters which only conditionally enabled objective appraisal of the present condition of the myocardium. Perioperative recording of the arterio-coronary-venous concentration difference of lactate (acDL) has now enabled the use of an objectivated parameter for accurate description of the metabolic-energetic situation of the myocardium. This will be helpful in metabolic-energetic condition monitoring (MESM) to optimise perioperative cardiotonic therapy. Stabilisation of the metabolic-energetic situation of the myocardium, objectivated by MESM, has proved to be superior to premature cardiac support, using catecholamines. It has been associated with improved restitution with high significance (p less than 0.005).

Adult

Conservative surgery with radiation therapy in clinical stage I and II breast cancer. Results of a 20-year experience.

Conservative surgery and radiation therapy have been increasingly utilized at Yale-New Haven (Conn) Hospital since the 1960s. This analysis represents our experience from 1962 to 1982, with a total of 281 patients having a minimum assessable follow-up of five years and a median follow-up of 7.4 years. Five- and ten-year actuarial survivals were 83% and 67%, respectively. The actuarial breast recurrence-free rate was 91% at five years and 80% at ten years. Of 31 patients having recurrences in the breast alone, the actuarial five-year survival following recurrence was 48%. Twenty-eight (90%) of these 31 recurrences were salvageable with mastectomy or repeated wedge resection. Patients experiencing an early breast recurrence (less than three years) following initial treatment had a poorer prognosis than patients having recurrences later.

Adult

Conservative surgery and radiation therapy in breast carcinoma: local recurrence and prognostic implications.

Conservative surgery with radiation therapy has been used with increasing frequency at Yale-New Haven Hospital since the late 1960's, resulting in a minimum evaluable follow-up time of 5 years on 278 patients treated prior to 1982. The radiation therapy technique generally encompassed treatment to the breast and regional lymph nodes of 4600 cGy with an electron beam boost to the tumor bed of 6400 cGy. Axillary dissection was performed in 19%, adjuvant chemotherapy in 7.3%, and adjuvant hormonal therapy in 5.7%; 65% were clinical Stage I and 35% were clinical Stage II. As of July 1987, with a minimum evaluable follow-up of 5 years and a median follow-up of 7.46 years, the actuarial 5- and 10-year survival for all 278 patients was 83% and 67%, respectively. The breast recurrence-free rate was 91% at 5 years and 80% at 10 years. Whereas the 5-year survival was significantly greater for clinical Stage I patients (91% vs 68%, p = .01), the breast recurrence-free rates did not significantly differ between clinical Stage I & II (93% vs 88%). There were 31 patients who failed in the breast alone as the first site of failure; 67% were at or near the primary site whereas 33% were distinctly removed from the primary site. Salvage mastectomy was performed in 25 patients, repeat wedge resection in two patients, and biopsy only in four patients. Axillary nodes were positive in five (33%) of 15 evaluable patients undergoing axillary dissection at the time of recurrence. The 5-year actuarial survival following local recurrence for the 31 patients was 48% at a mean follow-up of 5.06 years. The local recurrences were further subclassified into localized breast recurrences (LBR), defined clinically as greater than 3 cm and/or with dermal involvement. The 22 patients experiencing localized breast recurrences tended to occur later (median time to recurrence 4.3 years) than the nine patients experiencing a diffuse breast recurrence (median time to recurrence 2.9 years). At last follow-up, three (14%) of the 22 localized breast recurrences had subsequently failed distantly and none had subsequent local failure, whereas four (44%) of nine diffuse breast recurrences had subsequent distant failure and five (55%) of the nine diffuse breast recurrences experienced further local disease. The 5-year actuarial survival following salvage treatment was 90% for the localized breast recurrences and only 13% for the diffuse breast recurrences.

Breast Neoplasms

[Idiopathic portal hypertension associated with connective tissue disease similar to systemic lupus erythematosus].

A case of idiopathic portal hypertension associated with connective disease resembling systemic lupus erythematosus is described. The patient was a 50-year-old woman with splenomegaly, ascites, esophageal varices, and pancytopenia, but without extrahepatic portal obstruction or cirrhosis of the liver. Electron microscopy of the liver showed perisinusoidal fibrosis. High titers of autoantibodies against proliferating cell nuclear antigen (PCNA) were found in the sera as well as in ascites; anti-DNA antibodies appeared after anti-PCNA antibodies and remained thereafter at a moderate titer. The possibility of an immunological process in the pathogenesis of idiopathic portal hypertension is discussed.

Antibodies, Antinuclear

[Quantitative comparison of the secretion of salivary and mucous glands].

The flow rates and the Na+/K+ quotients of the saliva from the parotid and palatine glands were determined by direct comparison in 121 patients. The results showed that the flow rates and the Na+/K+ quotients of the same types of glands were not correlated with each other. Pronounced and specific interrelations as to the amount of secretion were observed only in patients complaining about dry mouth or smarting of the mucosa or patients under chronic treatment with psychoactive drugs where secretory inhibition is a side effect. The evaluation of the Na+/K+ quotients demonstrated that the secretion examined was almost exclusively resting saliva secretion. Based on these observations it is important that our understanding of the control mechanisms governing the activities of the different gland types within the masticatory system be reassessed.

Adult

The primary structure of the human ribosomal protein S6 derived from a cloned cDNA.

Polyclonal antibodies directed against a synthetic octapeptide of the cAMP-dependent phosphorylation site of the ribosomal protein S6 of rat liver were used to screen a lambda gt11 cDNA expression library of human lymphoblasts. An S6 specific clone was isolated. It consists of the complete coding sequence of 747 base pairs and the 3' noncoding region of 40 base pairs. The sequence of 249 amino acids was deduced from the nucleotide sequence. The amino- and carboxyl-terminal regions are almost identical to the reported partial peptide sequences of rat liver S6. The yeast protein S10 is homologous to the human S6 with the exception of 3 amino acid insertions and a carboxyl-terminal extension of 10 amino acids within the human S6. The only two phosphorylation sites at the carboxyl terminus of yeast S10 are homologous to the two cAMP-dependent sites in human S6. Since there are additional phosphorylation sites in mammalian S6, one can assume that they are located in the cluster of 5 serines within the carboxyl-terminal extension. The sequence comparison of these two ribosomal proteins from evolutionarily distant eucaryotes, such as man and yeast, indicates that the structure and probably the function of the phosphoprotein S6 of the small ribosomal subunit has been highly conserved. The expression of the S6 gene has been investigated in proliferating lymphocytes stimulated by concanavalin A. During all stages of lymphoblast development the level of S6 mRNA appeared to be similar. Southern blot analysis of human genomic DNA suggests that multiple genes exist for the S6 protein.

Amino Acid Sequence

Multiple myeloma involving the iris.

Intraocular invasion by neoplastic plasma cells is a rare ophthalmic manifestation of plasma cell dyscrasias. A 67-year-old man who had documented multiple myeloma presented with an infiltration of the iris that simulated a nongranulomatous uveitis. Cytologic examination of the aspirate obtained by anterior chamber paracentesis demonstrated that the infiltrate was composed of neoplastic plasma cells.

Aged

Purification and characterization of (+)dihydroflavonol (3-hydroxyflavanone) 4-reductase from flowers of Dahlia variabilis.

Individual flowers from inflorescences of Dahlia variabilis (cv Scarlet Star) in young developmental stages contained relatively high activity of (+)-dihydroflavonol (DHF) 4-reductase. The DHF reductase was purified from such flowers to apparent homogeneity by a five-step procedure. This included affinity adsorption on Blue Sepharose and elution of the enzyme with NADP+. By gel filtration and by sodium dodecyl sulfate-polyacrylamide gel electrophoresis it was shown that DHF reductase contains only one polypeptide chain with a Mr of about 41,000. The reductase required NADPH as cofactor and catalyzed transfer of the pro-S hydrogen of NADPH to the substrate. Flavanones and dihydroflavonols (3-hydroxyflavanones) were substrates for DHF reductase with pH optima of about 6.0 for flavanones and of about 6.8 for dihydroflavonols. Flavanones were reduced to the corresponding flavan-4-ols and (+)-dihydroflavonols to flavan-3,4-cis-diols. Apparent Michaelis constants determined for (2S)-naringenin, (2S)-eriodicytol, (+)-dihydrokaempferol, (+)-dihydroquercetin, and NADPH were, respectively, 2.3, 2, 10, 15, and 42 microM. V/Km values were higher for dihydroflavonols than for flavanones. Conversion of dihydromyricetin to leucodelphinidin was also catalyzed by the enzyme at a low rate, whereas flavones and flavonols were not accepted as substrates. DHF reductase was not inhibited by metal chelators.

Alcohol Oxidoreductases

Late follow-up of children after heart transplantation.

The majority of late recipients of heart transplantation have returned to age-appropriate activities and are showing normal linear growth. The only child who has significant symptoms is an 11-year-old heart-lung transplant recipient who developed airway rejection with restrictive pulmonary function 14 months after transplantation. Rejection continues to be a major threat to these children more than a year removed from their transplantation procedure. Until a satisfactory noninvasive method is developed to monitor graft rejection, endomyocardial biopsies will continue to be performed at 6-month intervals. Cyclosporine nephrotoxicity and systemic hypertension remain important and unresolved problems that could limit the initial success of transplantation. We believe that heart transplantation is an acceptable option for children with end-stage heart and heart-lung disease who have a grim outlook. Future improvements in immune suppression, and the development of improved methods of assessing rejection, will allow for improved survival.

Adolescent

[Weight of the thyroid gland in the Brandenburg district before introduction of iodized salt].

The first prospective investigation of thyroid weights of over 20 years old adults in the GDR is presented. The material is based on autopsy findings from the Brandenburg area before using salt with iodine. Judging by the results this area appears as an endemiological one. Relationships to iodine content of drinking water, comparisons with autopsy statistics of other countries, and the role of regional epidemiological differences are pointed out. The importance of the investigation for patients care and the possibility of controlling the effect of using salt with iodine is underlined. The examination of relations between thyroid weight and anthropometric data showed no additional results.

Adolescent