Klaus Hummeler

Beta cell nesidioblastosis in idiopathic hypoglycemia of infancy

A histochemical technique (pinacyanole metachromasia), specific for insulin in vitro and in beta cells of pancreatic tissue sections, was used to study surgically resected pancreases of 12 patients with documented idiopathic hypoglycemia of infancy. Hematoxylin and eosin—stained sections from 3 patients revealed overt hypertrophy and hyperplasia of all insular units. In the pancreases of the other 9 patients, hematoxylin and eosin sections showed histologically unremarkable islets, whereas the histochemically stained sections revealed the presence of many additional beta cells scattered either singly or in small packets of 2 to 6 cells. These were separate from the islets and most often seen about the walls of small ducts or in the glandular acini proper. The term beta cell nesidioblastosis most appropriately describes this cellular variant. These results, including electron microscopic findings of membrane-bound insulin inclusions in many cells, provide histomorphologic correlation with other evidence in support of the concept that excess production of insulin is an important feature of idiopathic hypoglycemia of infancy.

B virus infection in man.

B virus, herpes B, or Herpesvirus simiae may cause in man a viral encephalitis or encephalomyelitis, usually with fatal consequences. In monkeys, the disease may give a clinical picture similar to that produced by H . hominus in man. The disease is rare, the first known case occurring in 1932 and reported by Sabin and Wright in 1934.l There is no record of another case until Sabin2 in 1949 reported a second one. Thus the disease was almost completely unknown to the medical profession until recently. Standard clinical texts did not mention it, and only brief mention of the disease was made in more specialized texts. It was only with the tremendous increase in the importation and use of the Macaca mulatta (rhesus) monkey and the M . philippinensis (cynomolgus) monkey for research and for biological production, in which monkey renal cclls were used for tissue culture, that the importance of the disease in man and of its prevention became apparent. The total number of known cases is somewhat in doubt, but probably does not exceed fifteen. Twelve of them are reviewed in this paper. Nine occurred in 1957 and 1958 in England, Canada, and the United States.

Biochemical and biophysical studies on the nucleocapsid and on the RNA of rabies virus.

Abstract Nucleocapsids containing the viral ribonucleic acid (RNA) were isolated from deoxycholate (DOC)-disrupted rabies virions by rate zonal centrifugation in sucrose gradient followed by equilibrium centrifugation in CsCl gradient. The sedimentation coefficient of the nucleocapsid is approximately 200 S and its buoyant density in CsCl is 1.32. The nucleocapsid is composed of 96% protein and 4% RNA. It is a single-stranded, right-handed helix. The helix is about 1.0 μ long, 100 A in diameter, and has a periodicity of 75 A. The helical structure of the nucleocapsid is extremely labile. The uncoiled strand of the helix is about 4.2 μ long, and its width varies from 20 to 65 A depending on the angle of viewing. The nucleocapsid exhibits complement fixing, but not hemagglutinating (HA), activity. It is noninfectious. The viral RNA isolated from virions or nucleocapsids is single-stranded and has a sedimentation coefficient of 45 S. The envelope of the virion exhibiting HA activity is disintegrated by DOC into slowly sedimenting subunits. They possess hemagglutination-inhibition activity, but not HA activity.

[15N] leucine as a source of [15N] glutamate in organotypic cerebellar explants

Approximately 26.0% of the [15N] glutamate and [alpha 15N] glutamine formed in organotypic cerebellar explants was derived from [15N] leucine. Approximately 14.0% of the 15NH3 and [amide 15N] glutamine synthesized came from leucine nitrogen. Another 4.0% of the alpha nitrogen of both glutamate and glutamine was derived from [15N] valine. These results suggest that branched-chain amino acids, particularly leucine, may be important for the synthesis of glutamic acid by the brain.

Relationship between viral RNA and viral protein synthesis

Abstract Low concentrations of p-fluorophenylalanine (5–10 μg/ml) inhibit the maturation of Western equine encephalomyelitis and poliomyelitis viruses. Much higher concentrations are required (125 μg/ml) to inhibit the synthesis of the respective infectious RNA. By means of fluorescent antibodies against poliovirus, it was found that the formation of the viral antigens and the viral RNA are inhibited in a parallel manner by FPA. The implications of these findings suggesting a mutual dependency of viral protein and viral RNA synthesis are discussed.

Beta cell adenoma in a child with hypoglycemia controlled with diazoxide

The clinical course and laboratory investigations of a child with a beta cell adenoma of the pancreas are presented. The onset of both fasting and reactive hypoglycemia at age 39/12 years suggested the diagnosis. Inappropriately elevated serum insulin levels at the times of hypoglycemia were documented in the fasting state and after administration of glucose, tolbutamide, and leucine. The blood glucose concentration was well controlled for 11 months preoperatively with diazoxide therapy, an observation not previously reported in childhood. Although selective celiac arteriography did not demonstrate the lesion, a small nodule was palpable at surgery and was removed by partial pancreatectomy. The beta cell origin was confirmed histologically, and electron microscopy revealed excessive insulin granulations within the neoplastic cells. Postoperatively, the previous abnormalities of fasting and reactive hypoglycemia have disappeared.

Investigating the Rabies Virus

Modern virological techniques are providing valuable information about the rabies virus and its behaviour in infected nerve tissue.

Sudden and unexpected death in infants: II. Viral infections as causative factors**

This study was undertaken in an attempt to isolate viral agents responsible for sudden, unexpected death in apparently well infants. Eight different samples of tissue were taken from each of 109 necropsies on infants who had died suddenly and unexpectedly. Isolation techniques included the use of adult mice, suckling mice, chick embryos, and tissue cultures in HeLa cells and monkey kidney cells. A viral agent was isolated from but one autopsy, a Coxsackie B 5 from the lungs of a 3-month-old Negro female in whom histologic sections revealed no evidence of any inflammatory process. Thus, at least so far as present techniques can demonstrate them, viral infections do not play a role in the cause of these sudden deaths.

Thymic dysplasia ("Swiss agammaglobulinemia"). II. Morphologic and functional observations.

An infant with thymic dysplasia (“Swiss agammaglobulinemia”) has been studied with regard to several aspects of reticuloendothelial function. Significant abnormalities were suggested in (a) the morphology of the eosinophils, (b) phagocytosis by the polymorphonuclear leukocytes, and (c) cellular response to inflammatory stimulation. Capacity to produce interferon was within the expected range. Serum complement values were within normal limits and the concentration of plasminogen was elevated. These data suggest an involvement of elements of the reticuloendothelial system aside from the thymus and lymphoid tissues in thymic dysplasia. Production of interferon in response to viral challenge was found to be within normal expectations.

Diagnosis of cystinosis by rectal biopsy.

CHILDHOOD cystinosis is an inherited disease presenting in the first year of life with polyuria, polydipsia, vomiting and dehydration with underlying renal tubule dysfunction resulting in glycosuri...