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Biomedical subjects

M Hay

Publications and source records attributed to M Hay.

At least 91 records · Page 5Linked to original sources

[Cancer of the prostate. Results and causes of failure after exclusive radiotherapy in 131 cases treated at in locoregional stage between 1972 and 1981].

A retrospective study was carried out to evaluate results of exclusively physical treatment by external radiotherapy of 131 cases of cancer of prostate treated between 1972 and 1981. Median follow up has been for 8 years in 19 cases (stage A), 61 cases (stage B) and 51 cases (stage C). Patients were treated exclusively by external irradiation after histopathologic diagnosis and assessment of possible extension of tumor. High energy photons were developed by a linear accelerator and irradiation carried out through four portals, two anteroposterior, two lateral, with precise guidance by rectal and bladder opacification. Irradiation delivered to a pelvic volume over 5 weeks was subsequently reduced to the prostate bed until a total dose of about 65 to 70 Gy has been given. Primary glandular chains received 60 to 65 Gy, and critical organs, bladder, rectum, small intestine a smaller dose of less than the tolerance levels for these organs. Clinical, biologic and scintiscan examinations were repeated every three months. Results are presented as actuarial survival, as survival without local recurrence and a detailed analysis of failure of treatment. The 8-year survival rate was 60% for stage A, 47% for stage B and 33% for stage C. Unsuccessful cases were evaluated in terms of isolated metastases, metastases associated with local recurrence and isolated local recurrence. The highest incidence of ineffectiveness of therapy was noted in patients with distant metastases (26%), the rate being higher (41%) in stage C cases than in stage B cases (19%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

[Radiotherapy of seminomas of the testis. Apropos of 41 cases].

Our study reports on 41 patients with testicular seminoma (21 stage I and 20 stage II). Stage I patients received 20 Gy and stage II 35 to 36 Gy on infradiaphragmatic nodes and 20 Gy preventive mediastino-supraclavicular irradiation. The survival rate at 5 years for stage I patients was 100%. The stage II 5-year survival rate was 70%: 83.3% for stage IIA and 50% for stage IIB. For stage I patients only one death occurred and this was the result of a second cancer (bronchial cancer) which was diagnosed during the 8th year postirradiation. Of the stage II patients who did not respond to treatment, 3 were misdiagnosed histologically, one was due to the evolution of a secondary site (bladder), the 5th was due to insufficient irradiation and the 6th (anaplastic seminoma) presented extension of the disease in both irradiated and non-irradiated zone. Excluding these latter cases our study substantiates the curability of testicular seminomas by radiotherapy when dealing with stage I and stage II tumors. This early forms represent three fourths of all seminoma patients.

Adult↗

Calmodulin-dependent protein phosphorylation in synaptic junctions.

Synaptic junctions (SJs) from rat forebrain were examined for Ca2+/calmodulin (CaM)-dependent kinase activity and compared to synaptic plasma membrane (SPM) and postsynaptic density (PSD) fractions. The kinase activity in synaptic fractions was examined for its capacity to phosphorylate endogenous proteins or exogenous synapsin I, in the presence or absence of Ca2+ plus CaM. When assayed for endogenous protein phosphorylation, SJs contained approximately 25-fold greater amounts of Ca2+/CAM-dependent kinase activity than SPMs, and fivefold more activity than PSDs. When kinase activities were measured by phosphorylation of exogenous synapsin I, SJs contained fourfold more activity than SPMs, and 10-fold more than PSDs. The phosphorylation of SJ proteins of 60- and 50-kilodalton (major PSD protein) polypeptides were greatly stimulated by Ca2+/CaM; levels of phosphorylation for these proteins were 23- and 17-fold greater than basal levels, respectively. Six additional proteins whose phosphorylation was stimulated 6-15-fold by Ca2+/CAM were identified in SJs. These proteins include synapsin I, and proteins of 240, 207, 170, 140, and 54 kilodaltons. The 54-kilodalton protein is a highly phosphorylated form of the major PSD protein and the 170-kilodalton component is a cell-surface glycoprotein of the postsynaptic membrane that binds concanavalin A. The CaM-dependent kinase in SJ fractions phosphorylated endogenous phosphoproteins at serine and/or threonine residues. Ca2+-dependent phosphorylation in SJ fractions was strictly dependent on exogenous CaM, even though SJs contained substantial amounts of endogenous CaM (15 micrograms CaM/mg SJ protein). Exogenous CaM, after being functionally incorporated into SJs, was rapidly removed by sequential washings. These observations suggest that the SJ-associated CaM involved in regulating Ca2+-dependent protein phosphorylation may be in dynamic equilibrium with the cytoplasm. These findings indicate that a brain CaM-dependent kinase(s) and substrate proteins are concentrated at SJs and that CaM-dependent protein phosphorylation may play an important role in mechanisms that underlie synaptic communication.

Amino Acids↗

[Cancer of the prostate: intolerability and morbidity of external radiotherapy].

The pertherapeutic intolerance and morbidity are analyzed in a group of 597 patients with localized prostatic carcinoma treated by definitive radiotherapy between 1975 and 1982. Minimum follow-up is 2 years, median is 46 months. The results are compared to following parameters: associated diseases, associated surgical treatments, doses and irradiated target volumes. Pertherapeutic intolerance manifestations were found in 73% of patients and lead to complications. Urinary incontinence and chronic cystitis were more frequent after transurethral resection or prostatic surgery. Proctitis was the most disabling and can be reduced by a better estimation of prostatic target volume and by split course irradiation. Chronic diarrhea was more frequent when using large target volume. Leg edema was closely associated with pelvic lymphadenectomy. The control of pertherapeutic manifestations and the prevention of complications should improve survival in patients treated by external radiotherapy.

Follow-Up Studies↗

Piperacillin plus vancomycin in the therapy of febrile episodes in cancer patients.

Piperacillin and vancomycin were used as initial empirical therapy for 211 febrile episodes in cancer patients. The response rate in 95 episodes of documented infection was 72%. The response of bacteremias, soft tissue infections, and pneumonias was 78, 71, and 38%, respectively. The response in infections caused by gram-negative organisms was 73%. Only 6 of 10 Pseudomonas aeruginosa infections responded to therapy, although the organisms were sensitive in vitro to piperacillin. Of 14 infections caused by gram-positive organisms, 12 responded to this combination. No major side effects were observed with this regimen. Although the overall response rate with this antibiotic combination was comparable with other regimens used for neutropenic patients, superior results might be obtained by combining piperacillin with an extended-spectrum cephalosporin or an aminoglycoside.

Bacterial Infections↗

Postnatal dendritic development in motoneurons: evaluation by a Monte Carlo technique.

A Monte Carlo method was used to quantitate the dendritic characteristics of horseradish peroxidase-injected lumbar motoneurons (MNs) from kittens 44 to 73 days old (during the postnatal interval when motor cortical input/output linkages mature) and compared with those from adults. All of the 6 MNs analyzed were within the same range of somal sizes (40-61 micron) and dendritic domain volumes. However, two-dimensional distributions of dendritic diameter versus distance from the soma revealed that in the youngest MNs' (44 and 51 days) most dendritic processes (82 and 84%) were less than 2 micron in diameter, and had no dendrites greater than 5 micron. The adult MNs had large dendrites (20 and 24% were greater than 5 mu), while the kittens of intermediate age (66 and 73 days) exhibited both adult-like (6 and 13% greater than 5 micron) and immature (48 and 73% less than 2 micron) characteristics. "Hit probabilities" calculated from the Monte Carlo data suggest that immature MNs' dendrites may present denser targets per unit volume for ingrowing growth cones than adult MNs, and may facilitate the probability of contact with appropriate afferent axons.

Animals↗

Postnatal histogenetic death of rat forelimb motoneurons.

Previous workers have reported a five fold decrease in motoneuron numbers occurring from birth to adulthood in the rat. It has also been reported that forelimb muscles receive connections from motoneurons in both ventral horns prior to day 14 of life in the rat and that the contralateral cells subsequently degenerate completely by day 21. In the present study, postnatal changes in motoneuron number and distribution within the ventral horn were studied in the rat using the technique of retrograde horseradish peroxidase (HRP) transport following intramuscular infusion of HRP into biceps brachii (BB). Peripheral nerves other than those to BB were sectioned and ligated to control for HRP diffusion. The spatial organization of BB motoneurons was compared in animals 9-14 days old and adult animals using computer 3-D reconstruction. This allowed observations of the BB motoneurons from a variety of perspectives in relationship to a number of spinal cord landmarks and avoided the necessity for transverse and horizontal sectioning of the cords in alternate animals. A decrease of 50-75% in the number of HRP filled motoneurons number was found from birth to adulthood (adults 98-150, neonates 172-243). The spatial arrangement of the BB motoneurons with regard to the root entry zones and other landmarks such as the dorsolateral convexity of the ventral horn, remains constant from birth to adulthood. No evidence was found to support the existence of inappropriate connections from motoneurons in either the ipsi or contralateral ventral horns of neonate rats. It is suggested that the comparatively small decreases in motoneurons postnatally could be a continuation of the histogenetic processes of cell death begun in utero and is related to the postnatal development of the central and peripheral connections of motoneurons.

Aging↗

Laboratory-scale procedure for preparation of horse anti-dog lymphocyte globulin (HADLG).

Procedure of preparation of horse anti-dog lymphocyte globulin on laboratory scale is described. Adsorption of antibodies against dog plasma proteins was performed with the use of immunosorbent prepared by coupling dog plasma proteins to aluminium hydroxide gel. Anti-lymphocyte immunoglobulins G and T were purified using two-step fractionation. Addition of glycine to the purified immunoglobulins prevented the aggregate formation. Purified immunoglobulins were tested in dogs receiving kidney allografts. The short term administration of HADLG significantly prolonged the time of survival of allografted kidney in comparison to the untreated controls.

Animals↗

Active enhancement of dog kidney allografts using ALG and donor platelets.

The results of the studies indicate that platelets can be used as donor specific antigen in protocols of "biological suppression". Administration of donor specific platelets 10 days after transplantation to unmatched mongrel dogs treated for a brief period with ALG resulted in a marked prolongation of kidney allograft survival. Acute rejection of a second kidney from an indifferent donor suggests that a state of specific unresponsiveness was achieved by recipients pretreatment with ALG and donor antigen challenge.

Animals↗

Purification of Clostridium toxoids.

A two-step fractionation procedure was applied for purification and concentration of the individual Clostridium toxoids. The toxoids were precipitated with hydrochloric acid in the presence of sodium sextametaphosphate, then antigenic fractions were separated from inactive contaminants by Sephadex G-75 filtration. Specific activity of the preparations thus obtained, as determined by Mancini radial immunodiffusion, was 150--565 binding units per mg of protein nitrogen for Clostridium perfringens toxoid, 204--352 binding units for Clostridium oedematiens toxoid and 26.6 -- 51.2 binding units for Clostridium septicum toxoid.

Clostridium↗

UDPGlucose 4-epimerase from Saccharomyces fragilis. Allosteric kinetics with UDP-glucose as substrate.

UDPglucose 4-epimerase from Saccharomyces fragilis catalyzes a freely reversible reaction between UDP-galactose and UDP-glucose. With UDP-galactose as the substrate the enzyme shows a classical hyperbolic kinetics but when UDP-glucose is used as the substrate a distinct allostericity is observed. As a consequence, at low concentrations of UDP-glucose, the enzyme fails to establish the equilibrium at a significant rate. Glucose 6-phosphate acts as a strong activator for the enzyme with low concentrations of UDP-glucose as the substrate. In view of these rather unusual kinetic data for an enzyme catalyzing a freely reversible reaction, UDPglucose 4-epimerase may play a regulatory role in controlling the flux of galactose metabolism.

Allosteric Regulation↗