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Biomedical subjects

J Kahn

Publications and source records attributed to J Kahn.

At least 127 records · Page 7Linked to original sources
PubMed1986

Alzheimer's paired helical filaments share epitopes with neurofilament side arms.

A panel of monoclonal antibodies to neurofilaments have been investigated with regard to the location of their respective epitopes on neurofilament polypeptides and their ability to label the neurofibrillary tangles and paired helical filaments (PHF) which are characteristic of Alzheimer's disease. All of the neurofilament monoclonal antibodies that label tangles and PHF are directed against epitopes in the side arm domains of the two larger neurofilament polypeptides, NF-H and NF-M, and do not recognise the alpha-helical rod domains of these proteins. Immuno-electron microscopy demonstrates that the neurofilament antibodies label the constituent PHF per se and do not simply stain neurofilaments that might be admixed with PHF. These neurofilament epitopes are differentially retained by PHF, following isolation. Thus, antibody labelling of PHF is not simply due to the presence of normal neurofilament polypeptides. We propose that in tangle-bearing neurons, neurofilaments are degraded by proteases and that it is fragments of the side arms which contribute to the composition of PHF.

Alzheimer Disease↗
PubMed1986

Thermochemotherapy (combined cyclophosphamide and hyperthermia) with or without hyperglycemia as an adjuvant to radiotherapy.

Our previous study demonstrated the presence of a thermochemotherapy-resistant cell fraction in a tumor. The present study investigated whether thermochemotherapy-resistant cells are radioresistant and whether thermochemotherapy changes the size of hypoxic cell fraction in the tumor. Early generation isotransplants of a spontaneous fibrosarcoma, FSa-II tumors, were used. A radiation dose that yields 50% tumor control rate in 150 days after local irradiation, TCD50, was determined. Cyclophosphamide (CY) was the test agent. TCD50 values of the 4 mm tumor following gamma-ray alone given under hypoxic conditions or in air were 80.9 or 65.8 Gy, respectively. Thermochemotherapy reduced TCD50 values congruent to 20 Gy, suggesting that thermochemotherapy resistant cells are not identical to the radioresistant cells. Glucose administered 60 min before thermochemotherapy further reduced TCD50 values. Foot-reaction scored in the tumor-controlled animals was significantly less severe following combined thermochemo- and radiotherapy compared to that following radiotherapy alone. Acute foot reaction studies also supported this observation. These results indicated that thermochemotherapy could be an excellent adjuvant to radiotherapy. Further studies using a 6 mm tumor indicated that thermochemotherapy was less effective on the large tumor than on the small tumor. Indirect analysis showed no significant changes in the size of hypoxic cell fraction following thermochemotherapy.

Animals↗
PubMed1986

Differential kinetics of thermal resistance (thermotolerance) between murine normal and tumor tissues.

The kinetics of thermotolerance were studied in mouse normal and tumor tissues. Early generation isotransplants of a spontaneous fibrosarcoma, FSa-II, were used. Tumor cell suspension was transplanted into the C3Hf/Sed mouse foot. Hyperthermia was given by immersing animal feet into a water bath. The TG (tumor growth) time, the time required for half the treated tumors to reach 1000 mm3 from the first treatment day, was the end point. Foot reaction was studied as a normal tissue response. The RD50, the treatment time that induces a loss of one toe or greater reaction in half the treated animals, was analyzed. Thermotolerance developed rapidly and extensively in normal and tumor tissues. A significant difference was observed in the decay of thermotolerance between these tissues. The decay of thermal resistance was incomplete in the murine foot tissue, even at 14 days after the initial heat treatment. Although some experimental difficulties were involved in the tumor study, present results suggest a complete decay of thermotolerance in the FSa-II tumor in 8 days after a 7.5 min treatment of 45.5 degrees C. Thermal resistance again developed in both tissues following the second heat treatment, which was given 7 or 8 days after the first heat treatment. The development, maximum magnitude and decay of the second thermal resistance was comparable to those of the first thermal resistance in each tissue.

Adaptation, Physiological↗
PubMed1986

Alzheimer neurofibrillary tangles contain phosphorylated and hidden neurofilament epitopes.

Three monoclonal antibodies to neurofilaments (RT97, BF10 and 147), two of which also recognised neurofibrillary tangles (RT97 and BF10), have all been shown to be specific for phosphorylated epitopes. Treatment of histological sections with alkaline phosphatase prior to immunostaining resulted in reduction of axonal neurofilament staining with all three whilst the neurofibrillary tangles staining with BF10 was unaffected. Antibody 147 was found to recognise weakly some neurofibrillary tangles following alkaline phosphatase treatment. The results presented confirm the presence of structurally abnormal but phosphorylated neurofilaments in neurofibrillary tangles.

Alkaline Phosphatase↗
PubMed1985

Immunohistological study of granulovacuolar degeneration using monoclonal antibodies to neurofilaments.

Neurons undergoing granulovacuolar degeneration have been examined in paraffin sections with three monoclonal antibodies to neurofilaments. Two of these antibodies (BF10, RT97) had been shown previously to react with neurofibrillary tangles. One of these antibodies (RT97) reacted with granular component of granulovacuolar degeneration. BF10 sometimes reacted with the surrounding neuronal cytoplasm. Granulovacuolar degeneration was also detected in a few cells of the anterior olfactory nucleus.

Alzheimer Disease↗
PubMed1985

Effect of 42 degrees C hyperthermia on murine normal and tumor tissues.

The effect of one or two heat treatments at 42.0 degrees C was studied in murine normal and tumor tissues. Early-generation isotransplants of a spontaneous fibrosarcoma, FSa-II tumors, were used. Single-cell suspension was transplanted into the mouse foot. Tumor growth time, the time required for half the treated tumors to reach 1000 cu mm from treatment day was the end point. For normal tissue studies, the foot reaction was scored according to our numerical score system. Hyperthermia was given in a constant temperature water bath. Tumors were treated when they reached an average diameter of 4 (35 cu mm) or 8 mm (270 cu mm). The 4-mm tumor responded poorly to a single heat treatment at 42.0 degrees C, while the 8-mm tumor showed a substantial initial response, followed by the development of thermal resistance. The dose-response curve for the foot reaction was characterized by a large shoulder followed by a linear relationship. Thermal resistance developed in the 8-mm tumor following a continuous treatment of 150 min while in the foot tissue, 800 min were required before the development of thermal resistance. The kinetics of thermal resistance were studied following the first dose of 150 min. Substantial resistance developed in both 4- and 8-mm tumors, as well as in the foot tissue, and reached maximum within 1 day. The decay of thermal resistance in the 8-mm tumor and in the foot was incomplete even at 5 days after the first heat dose, while the analysis was difficult for the 4-mm tumor because of continuous tumor growth. Comparison with treatments at 43.5 degrees C and 45.5 degrees C gave a conclusion that (a) a short single heat treatment of the 8-mm tumor at 42.0 degrees C (below 43.0 degrees C) resulted in a differential response between tumor and foot tissues, but a longer treatment did not; (b) the treatment temperature above 43.0 degrees C was highly recommended; and (c) fractionated heat treatment at 42.0 degrees C was not the choice of treatment for both 4- and 8-mm tumors.

Animals↗
PubMed1985

Effect of thermochemotherapy (combined cyclophosphamide and hyperthermia) given at various temperatures with or without glucose administration on a murine fibrosarcoma.

The effect of combined cyclophosphamide (CY) and heat treatments on a murine tumor was studied at various temperatures. FSa-II tumors, the early generation isotransplants of a spontaneous fibrosarcoma in a C3Hf/Sed mouse, were used. A single cell suspension was transplanted into the animal foot. Hyperthermia was given by immersing animal feet into a water bath maintained at a desired temperature +/- 0.1 degrees C. An average diameter of the tumor at the time of treatment was 4 mm. The tumor growth time, the time required for one-half of the treated tumors to reach 1000 mm3, was the end point. Hyperthermia enhanced the effect of CY at test temperatures ranging from 40.5 degrees - 44.5 degrees C. The enhancement was independent of the temperature when CY was administered 30 min before the beginning of hyperthermia. However, the enhancement was most substantial at temperatures of 40.5 degrees -42.5 degrees C when CY was administered immediately before hyperthermia. The most effective timing of the CY administration was immediately before hyperthermia. The glucose administered 60 min before hyperthermia enhanced the effect of combined CY and hyperthermia when CY was given 30 min before heating. This enhancement was lost when CY was given immediately before hyperthermia. The CY dose response curves at elevated temperatures were downward concave, which may indicate the presence of a CY- and heat-resistant cell population in the tumor. Implications of these observations in clinical hyperthermia were discussed.

Animals↗
PubMed1984

Alzheimer's disease: immunoreactivity of neurofibrillary tangles with anti-neurofilament and anti-paired helical filament antibodies.

The origin of the paired helical filaments (PHF) that accumulate in human neurons during aging and in Alzheimer's disease and their relationship to normal neurofilaments remain unclear. The observation that a rabbit antiserum to highly enriched PHF fractions specifically labeled PHF in Alzheimer neurofibrillary tangles but showed no reaction with neurofilaments or other normal cytoskeletal proteins led us to compare this antiserum to two monoclonal antibodies, RT97 and BF10, previously found to cross-react with tangles and with the 210,000 and 155,000 mol. wt. neurofilament proteins, respectively. Both alpha-PHF serum and the neurofilament monoclonals strongly immunolabel almost all neurofibrillary tangles in Alzheimer cortical sections. Double-immunolabeling studies show that both reagents recognize the same tangles and usually show identical patterns of staining of intraneuronal fibrous material. Following prolonged extraction of cortex in sodium dodecyl sulfate, a step which removes normal neurofilaments but leaves PHF intact, almost all isolated tangles retain strong immunoreactivity with alpha-PHF serum at an intensity which is slightly reduced from that in cortical sections. In contrast, only a small number of isolated tangles are stained strongly by RT97 and BF10; most show much decreased or no reactivity with these monoclonal neurofilament antibodies. This differential immunoreactivity was confirmed by double-labeling studies. Tangles prepared under gentle extraction conditions show strong reactivity with alpha-PHF antibodies but again only a small number are strongly labeled by RT97 and BF10. We conclude that neurofibrillary tangles in Alzheimer's disease are heterogeneous as regards their filamentous content and contain both antigens cross-reacting with neurofilaments and antigens which are apparently unique to PHF and not shared with normal neurofilaments.

Alzheimer Disease↗
PubMed1984

Two brains, one child: interhemispheric information transfer deficits and confabulatory responding in children aged 4, 7, 10.

In an investigation of developmental trends in the ability to transfer information between the cerebral hemispheres, 138 children, ages 4, 7, and 10, viewed pictures presented to either the right or left hemisphere and were asked to describe what was viewed. Responses were socored for the number of accurate pictorial features reported (inclusion score), confabulation (erroneous embellishment), perceptual, semantic, and syntactic errors. Misses (failure to provide a response) were also noted. A preponderance of errors were found, such that 4-year olds engaged in a significant degree of confabulatory responding following right vs. left presentation. A significant inverse relationship was found between inclusion and confabulation such that the larger the gap in information reported the greater was the tendency to insert (confabulate) erroneous material. In addition, all children were given a tactile-shape recognition task employing both transfer and non-transfer conditions and requiring tactile exploration and visual recognition. Significantly more errors were found on the transfer vs. non transfer task among the 4-year olds only. In that deficits in information transfer were not complete but only partial, and given that significant intra-hemispheric (non-transfer) errors were also discovered, it was concluded that the hemispheres of children age 4 are not completely but only partially disconnected, and that intra-hemispheric (cortical) immaturity plays a significant role in the production of processing deficits.

Cerebral Cortex↗
PubMed1984

Iontophoresis.

Explore the source record for details and available documents.

Electricity↗
PubMed1984

The pericardial effusion pattern on phase images.

UNLABELLED: The effect of pericardial effusion on phase images of gated studies was investigated. Twenty-six patients with suspected or known pericardial effusion were correlated with echocardiography and/or clinical and other laboratory data to ascertain the presence and size of effusion. The phase image pattern and parameters were compared to the results previously obtained in seven normal patients, and in 26 patients with documented regional wall motion abnormalities but no evidence of pericardial effusion. The phase pattern was graded into five categories: typical (IV) (wide histogram, well defined concentric convex pattern, progressive delay toward the inferolateral area, identifiable also over the right ventricle); less pronounced (III); atypical (II); ill defined changes (I); and normal (0). RESULTS: Group L (large pericardial effusion): four of six had pattern (IV) and the left ventricular histogram showed abnormal parameters. These patients had large free effusions in the pericardial sac and none had regional wall motion abnormalities. Two of six had pattern (III) and (II) but also had ancillary pericardial pathology and/or decreased ejection fraction. Group M (moderate pericardial effusion), S (small pericardial effusion), and A (absent pericardial effusion, but not normal) had variable phase images and numeric parameters. After therapeutic drainage of pericardial fluid two patients changed pattern from IV and III to 0 and a third from III to I. Category IV pattern is 100% specific for pericardial effusion; the combination of category IV or III is 87.5% specific and 61% sensitive for large and moderate pericardial effusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1983

A study of glial fibrillary acidic protein (GFAP) in childhood brain tumours.

A retrospective study of 366 primary brain tumours in childhood has been carried out, GFAP was detected in juvenile astrocytoma (76/121), adult astrocytoma (34/78), malignant glioma (0/8), other astrocytic tumours (2/4) and medulloblastoma (0/101). In eight medulloblastomas scanty positive cells were seen but were regarded as reactive rather than neoplastic. The presence of GFAP was only found to be of prognostic value in adult astrocytoma, where its occurrence was associated with a more favourable outcome.

Adolescent↗
PubMed1983

Pick's disease: an immunocytochemical study of neuronal changes. Monoclonal antibodies show that Pick bodies share antigenic determinants with neurofibrillary tangles and neurofilaments.

We used rabbit antisera to the 210,000; 155,000; and 70,000 mol. wt. neurofilament - polypeptides and monoclonal antibodies (BF 10; RT97) known to react with human neurofilaments in an immunohistochemical study of neuronal changes in Pick's disease and in senile dementia of the Alzheimer type. Pick bodies as well as neurofibrillary tangles and neurites showed strong reactivity with the monoclonal antibodies but remained unlabeled when treated with the rabbit polyclonal antisera. Our results indicate that the stained material in Pick bodies share antigenic determinants with neurofibrillary tangles and neurofilaments.

Aged↗
PubMed1983

Studies on fractionated hyperthermia in experimental animals systems III. Uneven daily doses.

The effect of daily hyperthermia on the murine normal and tumor tissues was investigated. Tumors were early generation isotransplants of a fibrosarcoma (FSa-II) and a mammary carcinoma (MCa) in C3Hf/Sed mice. Hyperthermia was given by immersing animal feet into a water bath at 45.5 degrees C. Tumor response was studied by TG time assay (determination of the time required for half of the treated animals' tumors to reach 1000 mm3 from the treatment day). Average peak foot reaction was also investigated to compare the therapeutic effectiveness of various fractionation regimens. In the first experiment the first dose (D1) of 10 min was followed by 10, 20, or 30 min daily doses. The treatment regimen "D1 of 10 min + daily 30 min" resulted in a significant therapeutic gain. The smaller doses were unable to overcome the repopulation of surviving tumor cells and the increasing magnitude of thermal resistance. To overcome tumor cell repopulation and thermal resistance, a regimen of increasing daily doses was attempted without success. These results indicated that doses following a D1 of 10 min must be as large as 30 min to obtain a therapeutic gain. Any fractionation regimens for MCa tumors, which developed the greatest thermal resistance among our animal tumors tested, failed to result in a therapeutic gain.

Animals↗