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AN UNIDENTIFIED HEREDITARY DISEASE
1359
kg. body-weight
was
given
to
reveal any signs of H.P.I., in
hepatomegaly has been consistently found. This precipitated hypoglycaemic shock with decrease in bloodglucose to 12 mg. per 100 ml. A detailed history did not reveal any ill health in the other members of the family. However, a 3-year-old brother, always in excellent health and well nourished, was reported to dislike sugar and sweets profoundly. He also avoided fruit, only tasting them occasionally. His liver was enlarged which
down to the umbilicus. An oral test dose of fructose, now 0-5 g. per kg. body-weight, brought about hypoglyceenlic shock, as in the sister, the blood-glucose level falling to 18 mg. per 100 ml.
The
finding of
a
boy with
no
history of disease, yet
affected by H.F.I., with concomitant gross enlargement of the liver, may imply that this specific metabolic defect is than is apparent from the very few cases reported. The urine of this boy might never have been positive in routine tests for mellituria, which reveal cases of benign fructosuria. Questioning of the family did not commoner
explicitly point
conditioning by early experience as a containing fructose; and inherent self-selection mechanisms seem another possible explanation. Adding H.F.I. to the diseases which can cause hepatomegaly may decrease the number of those remaining unexplained; moreover, the whole family of any patient with H.F.I should be closely studied for any dormant forms of the disease, even in the absence of to
cause for his avoidance of foods
PHAGOCYTOSIS OF LEUCOCYTES IN THE CEREBROSPINAL FLUID SIR,-Metchnikoff showed that degenerating cells are ingested by leucocytes and large macrophages of the reticuloendothelial system. Phagocytosis of the leucocytes may be caused by exposure to"heteroimmune sera, " by the action of autocytotropins formed in certain diseases, and, finally, by a non-specific effect. Destruction and phagocytosis of cells may be considerable in some infections, and we report here a case of extensive phagocytosis of leucocytes in the cerebrospinal fluid. A man of 40 who had otorrhoea for twenty years developed a mastoid infection with signs of meningitis and died three days after operation. His cerebrospinal-fluid pressure had been raised before death and the fluid was opalescent. Necropsy revealed a cerebral abscess, purulent meningitis, and internal pyocephalus. The cerebrospinal fluid obtained before death showed extensive phagocytosis of masses of dead and
dying leucocytes. Phagocytosis of leucocytes can be seen occasionally in other cases of meningitis, but in this case it was as high as 5-4% instead of about 1%. The intense phagocytosis of leucocytes was caused by a non-specific destruction of masses of leucocytes. We were unable to detect antibodies to leucocytes in the cerebrospinal fluid by the method of Finch et all The phagocytosis could be differentiated easily from the so-called L.E.-cell phenomenon,2 in the cerebrospinal fluid of patients with disseminated lupus erythematosus. MAV Hospital and Policlinic Central Laboratory, Budapest.
subjective complaints.
J. PERHEENTUPA E. PITKÄNEN.
Children’s Hospital, University of Helsinki, Helsinki, Finland.
AN UNIDENTIFIED HEREDITARY DISEASE SIR,-We should like to draw attention to a hereditary disease which we had the good fortune to observe in a family of 127 members, in 6 generations, with 29 affected
individuals.
description
We have been unable to find a previous of the disease, which has the following
features:
(1) Autosomal dominant heredity. (2) Onset at birth with generalised hypertonia in flexion, disappearing during sleep, and reappearing upon awaking. This life.
hypertonia diminishes in
the
course
of the first year of
(3) Abnormally exaggerated startle reactions after sudden sensory stimulus. Often these startle reactions are accompanied by the acute diffuse hypertonia which makes the patients fall like a log, mostly on their face. As soon as they touch the ground, they can get up again. There is no concomitant clouding of consciousness, or any epileptic phenomenon. (4) The disease varies in severity: some patients show only exaggerated startle reactions, others, the majority, fall as well. (5) In some affected members (but not in those free of the disease) epilepsy occurs. (6) All patients show extremely strong brainstem reflexes-
notably the head-retraction reflex. (7) Alcohol or phenobarbitone often prevent
the abnormal
startle reactions.
Extensive E.E.G. examinations are now being carried out. The disease is not identical with the so-called " epilepsiesursaut "
or
the
"
syncindsie-sursant ". 12
We would be very grateful if those of your readers who are familiar with the syndrome would report their
experiences
to us.
Pædiatric Department,
University Hospital, Leiden, The Netherlands.
1. 2.
O. KOK G. W. BRUYN.
Alajouanine, T., Gastaut, H. Rev. neurol., 1955, 93/1, 29. Alajouanine, T. Bases Physiologiques et l’Aspect Clinique p. 199. Paris, 1958.
de
l’Epilepsie;
GY. VAJDA O. SZÜCS.
PREPARATION OF A CRUDE HUMAN LEUCOCYTE GROWTH FACTOR FROM PHASEOLIS VULGARIS SIR,-Variations in the efficacy of commercial phytohsemagglutinin preparations in stimulating mitosis and growth of human leucocytes in short-term tissue cultures have prompted us to re-examine the methods of preparation of this material, with the working hypothesis that the observed haemagglutinating and growth-stimulating properties are in fact due to separate factors in the bean extract.
Fractions obtained from Phaseolus vulgaris bean meal by the methods of Rigas and Osgood3 were tested with and without further treatments for their ability to stimulate growth of leucocytes in short-term tissue cultures, and to agglutinate human red cells. Cultures were grown and harvested by a modification of the method of Moorhead et al.4 Growth was determined as the number of viable large cells with enlarged nuclei. The fraction of these cells having mitotic figures was also determined. Hmmagglutination was determined by standard techniques. The results demonstrate that there is a substance in the cotyledons of Ph. vulgaris, separable from phytohaemagglutinin, which stimulates leucocyte growth. Details of procedures employed and the biochemical and biological properties of the fractions will be presented more fully elsewhere, but because of the widespread use of phytohaemagglutinin in leucocyte culture and human chromosome studies, a scheme based on Rigas and Osgood’s method is herewith given for the isolation of a crude highly active preparation of a growth-promoting substance which we have called leucocyte growth factor (L.G.F.).
(1) Suspend 10 g. of ground red kidney beans in 50 ml. of cold 1% NaCl. Keep at 0-4°C and stir for 24 hours. (2) Remove undissolved materials by centrifugation for 10 minutes at 10,000 g, and discard the pellet. 1. 2. 3. 4.
Finch, S. J. Lab. clin. Med. 1953, 42, 555. Hargraves, M., Richmond, H., Morton, R. Amer. J. med. Sci. 1950, 219, 660. Rigas, D. A., Osgood, E. E. J. biol. Chem. 1955, 212, 607. Moorhead, P. S., Nowell, P. C., Mellman, W. J., Battips, D. M., Hungerford, D. A. Exp. Cell. Res. 1960, 20, 613.
kg. body-weight
was
given
to
reveal any signs of H.P.I., in
hepatomegaly has been consistently found. This precipitated hypoglycaemic shock with decrease in bloodglucose to 12 mg. per 100 ml. A detailed history did not reveal any ill health in the other members of the family. However, a 3-year-old brother, always in excellent health and well nourished, was reported to dislike sugar and sweets profoundly. He also avoided fruit, only tasting them occasionally. His liver was enlarged which
down to the umbilicus. An oral test dose of fructose, now 0-5 g. per kg. body-weight, brought about hypoglyceenlic shock, as in the sister, the blood-glucose level falling to 18 mg. per 100 ml.
The
finding of
a
boy with
no
history of disease, yet
affected by H.F.I., with concomitant gross enlargement of the liver, may imply that this specific metabolic defect is than is apparent from the very few cases reported. The urine of this boy might never have been positive in routine tests for mellituria, which reveal cases of benign fructosuria. Questioning of the family did not commoner
explicitly point
conditioning by early experience as a containing fructose; and inherent self-selection mechanisms seem another possible explanation. Adding H.F.I. to the diseases which can cause hepatomegaly may decrease the number of those remaining unexplained; moreover, the whole family of any patient with H.F.I should be closely studied for any dormant forms of the disease, even in the absence of to
cause for his avoidance of foods
PHAGOCYTOSIS OF LEUCOCYTES IN THE CEREBROSPINAL FLUID SIR,-Metchnikoff showed that degenerating cells are ingested by leucocytes and large macrophages of the reticuloendothelial system. Phagocytosis of the leucocytes may be caused by exposure to"heteroimmune sera, " by the action of autocytotropins formed in certain diseases, and, finally, by a non-specific effect. Destruction and phagocytosis of cells may be considerable in some infections, and we report here a case of extensive phagocytosis of leucocytes in the cerebrospinal fluid. A man of 40 who had otorrhoea for twenty years developed a mastoid infection with signs of meningitis and died three days after operation. His cerebrospinal-fluid pressure had been raised before death and the fluid was opalescent. Necropsy revealed a cerebral abscess, purulent meningitis, and internal pyocephalus. The cerebrospinal fluid obtained before death showed extensive phagocytosis of masses of dead and
dying leucocytes. Phagocytosis of leucocytes can be seen occasionally in other cases of meningitis, but in this case it was as high as 5-4% instead of about 1%. The intense phagocytosis of leucocytes was caused by a non-specific destruction of masses of leucocytes. We were unable to detect antibodies to leucocytes in the cerebrospinal fluid by the method of Finch et all The phagocytosis could be differentiated easily from the so-called L.E.-cell phenomenon,2 in the cerebrospinal fluid of patients with disseminated lupus erythematosus. MAV Hospital and Policlinic Central Laboratory, Budapest.
subjective complaints.
J. PERHEENTUPA E. PITKÄNEN.
Children’s Hospital, University of Helsinki, Helsinki, Finland.
AN UNIDENTIFIED HEREDITARY DISEASE SIR,-We should like to draw attention to a hereditary disease which we had the good fortune to observe in a family of 127 members, in 6 generations, with 29 affected
individuals.
description
We have been unable to find a previous of the disease, which has the following
features:
(1) Autosomal dominant heredity. (2) Onset at birth with generalised hypertonia in flexion, disappearing during sleep, and reappearing upon awaking. This life.
hypertonia diminishes in
the
course
of the first year of
(3) Abnormally exaggerated startle reactions after sudden sensory stimulus. Often these startle reactions are accompanied by the acute diffuse hypertonia which makes the patients fall like a log, mostly on their face. As soon as they touch the ground, they can get up again. There is no concomitant clouding of consciousness, or any epileptic phenomenon. (4) The disease varies in severity: some patients show only exaggerated startle reactions, others, the majority, fall as well. (5) In some affected members (but not in those free of the disease) epilepsy occurs. (6) All patients show extremely strong brainstem reflexes-
notably the head-retraction reflex. (7) Alcohol or phenobarbitone often prevent
the abnormal
startle reactions.
Extensive E.E.G. examinations are now being carried out. The disease is not identical with the so-called " epilepsiesursaut "
or
the
"
syncindsie-sursant ". 12
We would be very grateful if those of your readers who are familiar with the syndrome would report their
experiences
to us.
Pædiatric Department,
University Hospital, Leiden, The Netherlands.
1. 2.
O. KOK G. W. BRUYN.
Alajouanine, T., Gastaut, H. Rev. neurol., 1955, 93/1, 29. Alajouanine, T. Bases Physiologiques et l’Aspect Clinique p. 199. Paris, 1958.
de
l’Epilepsie;
GY. VAJDA O. SZÜCS.
PREPARATION OF A CRUDE HUMAN LEUCOCYTE GROWTH FACTOR FROM PHASEOLIS VULGARIS SIR,-Variations in the efficacy of commercial phytohsemagglutinin preparations in stimulating mitosis and growth of human leucocytes in short-term tissue cultures have prompted us to re-examine the methods of preparation of this material, with the working hypothesis that the observed haemagglutinating and growth-stimulating properties are in fact due to separate factors in the bean extract.
Fractions obtained from Phaseolus vulgaris bean meal by the methods of Rigas and Osgood3 were tested with and without further treatments for their ability to stimulate growth of leucocytes in short-term tissue cultures, and to agglutinate human red cells. Cultures were grown and harvested by a modification of the method of Moorhead et al.4 Growth was determined as the number of viable large cells with enlarged nuclei. The fraction of these cells having mitotic figures was also determined. Hmmagglutination was determined by standard techniques. The results demonstrate that there is a substance in the cotyledons of Ph. vulgaris, separable from phytohaemagglutinin, which stimulates leucocyte growth. Details of procedures employed and the biochemical and biological properties of the fractions will be presented more fully elsewhere, but because of the widespread use of phytohaemagglutinin in leucocyte culture and human chromosome studies, a scheme based on Rigas and Osgood’s method is herewith given for the isolation of a crude highly active preparation of a growth-promoting substance which we have called leucocyte growth factor (L.G.F.).
(1) Suspend 10 g. of ground red kidney beans in 50 ml. of cold 1% NaCl. Keep at 0-4°C and stir for 24 hours. (2) Remove undissolved materials by centrifugation for 10 minutes at 10,000 g, and discard the pellet. 1. 2. 3. 4.
Finch, S. J. Lab. clin. Med. 1953, 42, 555. Hargraves, M., Richmond, H., Morton, R. Amer. J. med. Sci. 1950, 219, 660. Rigas, D. A., Osgood, E. E. J. biol. Chem. 1955, 212, 607. Moorhead, P. S., Nowell, P. C., Mellman, W. J., Battips, D. M., Hungerford, D. A. Exp. Cell. Res. 1960, 20, 613.