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Biomedical subjects

S Kroll

Publications and source records attributed to S Kroll.

13 recordsLinked to original sources

Salvage treatment for loco-regional recurrence following breast conservation therapy for early breast cancer.

We reviewed the management of 55 cases of loco-regional recurrence after limited surgery and irradiation for breast cancer. Forty-three patients had disease localized to the breast, with axillary involvement in seven. Four had axillary relapse without tumor recurrence in the breast. Eight had breast recurrence extending to involve the chest wall. Mastectomy was used successfully for 41 first recurrences, and seven were controlled by wide excision; 21 of 48 patients also received chemotherapy and/or hormonal manipulation. Diffuse soft-tissue tumor required systemic therapy first, followed by wide excision when possible. Eighty-nine percent of first recurrences were controlled but disease recurred again in eight patients. Overall, 80% of cases were free of loco-regional disease at a median follow-up of 27 months. Reconstructive surgery was valuable for wound closure after wide resections, and for cosmetic procedures. Despite the previous irradiation, surgery complications were acceptable.

Actuarial Analysis

Long-term effects of radiotherapy in childhood and adolescence.

The records of 50 selected pediatric patients who were treated and followed at M. D. Anderson Cancer Center were reviewed to study the late effects of nonsurgical treatment of cancer in children. There were 26 girls and 24 boys ranging in age between 2 months and 16 years. Patients with head and neck cancer received chemotherapy and radiotherapy for rhabdomyosarcoma (n = 27), retinoblastoma (n = 8), or nasopharynx cancer (n = 2). Median follow-up was 13 years. The most severe side effects were noted in the fields of radiation and included hypoplasia of the jaw, orbit, or hemi-face with varying degrees of atrophy of the overlying soft tissues. A wide range of endocrine, dental, and psychologic abnormalities was also documented. Since 1 in every 1,000 adults older than 20 years today is likely to be a survivor of childhood cancer, recommendations are made for this "new" class of patients whom the head and neck surgeon will be seeing in the future.

Adolescent

Ultrasonographic measurement of uveal melanoma thickness: interobserver variability.

We retrospectively reviewed ultrasonographic data on 32 uveal melanomas that had been studied both at a referral institution and at our centre within a six-week period. Generally there were good correlations between ultrasonographic measurements of tumour thickness. The mean absolute difference in ultrasound measurements of tumour thickness was 0.64 mm (range 0-2.2 mm); the mean tumour thickness was 5.2 mm (range 3.5-10.2 mm). Tumour diameter, location, the relative ultrasonographic experience with uveal melanoma, type of equipment, and tumour thickness all affected the interobserver variation of measurement.

Humans

The regulation of the cyclic GMP phosphodiesterase by the GDP-bound form of the alpha subunit of transducin.

The functional interactions of the retinal G protein, transducin, with the cyclic GMP phosphodiesterase (PDE) have been examined using the different purified subunit components of transducin and the native and trypsin-treated forms of the effector enzyme. The limited trypsin treatment of the PDE removes the low molecular weight gamma subunit (Mr approximately 14,000) of the enzyme, yielding a catalytic moiety comprised of the two larger molecular subunits (alpha, Mr approximately 85,000-90,000; beta, Mr approximately 85,000-90,000), which is insensitive to the addition of either the pure alpha T.GTP gamma S species or the pure beta gamma T subunit complex. However, the addition of the pure alpha T.GDP species to the trypsin-treated PDE (tPDE) results in a significant (90-100%) inhibition of the enzyme activity. This inhibition can be reversed by excess beta gamma T, suggesting that the holotransducin molecule does not (functionally) interact with the tPDE. However, the inhibition by alpha T.GDP is not reversed by the alpha T.GTP gamma S complex, over a range of [alpha T.GTP gamma S] which elicits a marked stimulation of the native enzyme activity, suggesting that the activated alpha T species does not effectively bind to the tPDE. The alpha T.GDP complex also is capable of inhibiting the alpha T.GTP gamma S-stimulated cyclic GMP hydrolysis by the native PDE. This inhibition can be reversed by excess alpha T.GTP gamma S, as well as by beta gamma T, indicating that the binding site for the activated alpha T species is in close proximity and/or overlaps the binding site for the alpha T.GDP complex on the enzyme. Overall, these results are consistent with a scheme where (a) both the small and larger molecular weight subunits of PDE participate in alpha T-PDE interactions, (b) the activation of PDE by the alpha T.GTP gamma S (or alpha T.GTP) species does not result in the complete dissociation of the gamma subunit from the enzyme, and (c) the deactivation of this signal transduction system results from a direct interaction between the alpha T.GDP species and the catalytic moiety of the effector enzyme.

3',5'-Cyclic-GMP Phosphodiesterases

Effect of various doses of radiation for uveal melanoma on regression, visual acuity, complications, and survival.

We reviewed 284 choroidal and ciliary body melanomas treated with 50, 60, 70, or 80 gray equivalents (GyE) of helium ion radiation. Multivariate methods of data analysis were used to adjust for differences between dose groups with respect to the characteristics of patients (and their tumors). Radiation dose level did not affect survival, complications, visual outcome, or tumor regression in this model. The minimum radiation dose necessary to achieve tumor control with charged particles may be less than 50 GyE.

Dose-Response Relationship, Radiation

Opsonic requirements and interaction of Haemophilus influenzae with human polymorphonuclear neutrophil leucocytes studied by luminol-enhanced chemiluminescence.

We have used human polymorphonuclear leucocyte (PMNL)-dependent chemiluminescence (CL) to study bacteria opsonised with those factors in serum which are reported to be important in opsonisation of H. influenzae, and to determine whether alteration of various surface characteristics of H. influenzae influence those CL responses by PMNL. Although complement plays a role, immunoglobulin and a heat-labile factor(s) were found to be the principle stimulants of PMNL-dependent CL when H. influenzae was opsonised in pooled normal human serum. Acquisition of capsule (serotype a,b,c,e, or f) by an uncapsulated strain significantly (P less than 0.001) reduced its ability to stimulate PMNL-dependent CL, but the type of capsule did not discriminate between the strains in this regard. Surface-adherent capsule inhibited PMNL-dependent CL stimulation more than capsular material released into the supernatant. Altering the lipooligosaccharide composition of the bacterial cell wall also affected PMNL-dependent CL stimulation independent of capsule. We conclude that, although surface characteristics of H. influenzae influenced its ability to stimulate PMNL-dependent CL, these experiments provide no evidence to support the hypothesis that the increased virulence of serotype b capsulated strains compared with other capsulated types could be explained by any specific ability to avoid opsonisation.

Haemophilus influenzae

Uveal melanoma radiation. 125I brachytherapy versus helium ion irradiation.

The optimum radiation therapy for uveal melanoma is uncertain. Both helium ion irradiation and 125I brachytherapy have been used to treat this neoplasm. This investigation analyzed the control and complication rates of uveal melanomas treated with helium ions of 125I plaques. In both a retrospective and a prospective dynamically balanced study, the control rates appeared to be similar. There were more posterior segment complications after 125I plaques and more anterior segment complications, including neovascular glaucoma, after helium ion irradiation. The follow-up period is too short to draw definitive conclusions on the radiation complications. Overall, approximately 89% of eyes were retained and less than 4% of treated eyes were removed because of failure to control the tumor.

Adult

Failure of preenucleation radiation to decrease uveal melanoma mortality.

We analyzed uveal melanoma metastases in a group of 41 patients who received 20 Gy of preenucleation radiation in a Northern California Oncology Group preliminary phase I/II study, and compared their survival rates with a retrospective control group of 31 patients with characteristics matching the entrance criteria but treated with enucleation alone. Using the Cox proportional hazards model, we found that increased tumor diameter, mixed or epithelioid cell type, and radiation adversely affected survival. In vivo studies of cell cycling indicated that 20 Gy of preenucleation radiation appeared to diminish the reproductive integrity of the tumor cells. It is most likely that the failure of preenucleation irradiation to prolong patient survival was because of micrometastases that occurred before treatment.

Adult

An antibody directed against the carboxyl-terminal decapeptide of the alpha subunit of the retinal GTP-binding protein, transducin. Effects on transducin function.

An antibody (AS/7) prepared against the carboxyl-terminal decapeptide of the alpha subunit of transducin (alpha T) has been used in various reconstitution studies aimed at characterizing the role of the carboxyl-terminal domain in the different functional activities of transducin. The peptide-specific antibody is a potent inhibitor of the rhodopsin-stimulated GTPase activity in phospholipid vesicle systems containing pure rhodopsin and pure holo-transducin, or rhodopsin and the purified alpha T and beta/gamma (beta gamma T) subunit components, with the highest levels of inhibition (80-95%) occurring under conditions where the molar ratio of holo-transducin (or alpha T) to AS/7 approximately equal to 1. The inhibition of the receptor-stimulated GTPase does not represent an interference in the interactions between the alpha T subunit and the beta gamma T complex, since essentially identical levels of inhibition are observed when AS/7 is preincubated with either free alpha T, holo-transducin, or alpha T in the presence of excess beta gamma T, prior to assay. The AS/7-induced inhibition also does not appear to reflect an alteration in the ability of alpha T to bind or hydrolyze GTP and, in fact, the incubation of alpha T with AS/7 results in a stimulation of the intrinsic GTPase activity for alpha T alone (i.e. in the absence of rhodopsin). Thus, we conclude that the inhibition of the rhodopsin-stimulated GTPase activity by AS/7 is due to the direct blocking (by the antibody) of rhodopsin-alpha T interactions. While AS/7 is capable of uncoupling rhodopsin-transducin interactions, it appears to promote the stimulation of the cyclic GMP phosphodiesterase (PDE) by an activated alpha T subunit. Specifically, when the pure alpha T-guanosine 5-O-(3-thiotriphosphate) (alpha TGTP gamma S) species is preincubated with AS/7 prior to its addition to an assay solution containing PDE, there is at least a 4-fold increase in the resultant cyclic GMP hydrolysis relative to the activities measured with alpha TGTP gamma S, alone, or with alpha TGTP gamma S preincubated with nonimmune (control) rabbit IgG. The AS/7-induced promotion is specific for the active form of alpha T; the inactive alpha TGDP species does not stimulate PDE activity either in the presence or absence of the antibody. The different effects by AS/7 on the various activities of the alpha T subunit highlight the existence of distinct functional domains on alpha T.(ABSTRACT TRUNCATED AT 400 WORDS)

3',5'-Cyclic-GMP Phosphodiesterases

Mediastinal tracheostomy.

Upper airway obstruction in primary or recurrent carcinomas of the head and neck extending into the mediastinum may demand surgical intervention despite severe technical difficulties in patients with tumors previously considered inoperable. In fact, many of these tumors may be operable and some perhaps curable. A technique has been developed based in part on our experience with previously described procedures. A preliminary sternal split is used to demonstrate the extent of the mediastinal involvement as well as to provide enhanced exposure and proximal control of the great vessels. The pectoralis major muscle is used with a generous flap of overlying skin comprising nearly half of the anterior portion of the chest. A tracheostomy is then created in a fashion similar to the placement of a cardiac valvular prosthesis by creating a circular defect in the pectoralis major flap and suturing it to the tracheal remnant. This technique offers a reasonably safe and reliable means of creating a low anterior mediastinal tracheostomy for tumors previously considered inoperable. The preliminary sternal split makes the procedure safer and easier to perform, and the use of a very large pectoralis major island flap allows for reliable closure of the resulting mediastinal and sternal defects.

Aged

Mechanisms of heat inactivation of a proteinase from Pseudomonas fluorescens biotype I.

Heat inactivation of a metalloproteinase, isolated from Pseudomonas fluorescens biotype I strain 112, was investigated in the temperature ranges 50-60 degrees C and 90-140 degrees C. At 90 degrees C the denaturation of the enzyme followed first-order kinetics with a decimal reduction time of 110 min and a velocity constant K of 3.5 X 10(-4) S-1. Activation energy Ea was 100 kJ/mol for this temperature range. In the 50-60 degrees C region the proteinase was inactivated by autolysis, as shown by electrophoresis and gel filtration. At 55 degrees C the decimal reduction time was approximately 22 s, at 57 degrees C it was 8 s. Rapid inactivation at 55 degrees C was only possible if the enzyme was heated from lower temperatures, but not if cooled down from 90 degrees C. This is due to a conformational change of the protein at this temperature. A model for the description of heat inactivation in the two temperature ranges is proposed.

Endopeptidases

Influence of EDTA and metal ions on a metalloproteinase from Pseudomonas fluorescens biotype I.

The inactivation of a metalloproteinase from Pseudomonas fluorescens Biotype I with EDTA was investigated at 22 degrees C and 37 degrees C. At 22 degrees C proteolytic activity decreases linearly with time and an inactive apoenzyme is obtained by dialysis. Proteolytic activity can be restored with several metal-ions, Ca2+, Zn2+, Mg2+, Sr2+ and co2+ give the best results. Activity and substrate specificity are influenced by the metal-ions. Reactivation depends on the concentration of the metal-ions, optimum concentration is 1 mM for Ca2+ and 50 microM for Zn2+. The isoelectric point of the apoenzyme is around 8.0, this is about 0.3 pH-units lower than the isoelectric point of the native proteinase. At 37 degrees C inactivation follows first order kinetics and is irreversible because of autolysis as shown by a gel filtration-experiment.

Apoenzymes