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A genetically determined deficiency of the third component of complement (C3) has been identified in a colony of Brittany spaniels. Immunochemical methods show no detectable C3 in the serum of the affected dogs, and there is no evidence of an inhibitor of C3 in the serum. The C3 deficiency appears to be transmitted as an autosomal recessive trait.

Summary Among 240 children reporting to the Out-Patient Service of Mulago Hospital, Kampala, Uganda, 179 (74.6%) were found to have malaria parasites in the blood. Plasmodium falciparum, which was the predominant parasite, was found either alone or mixed with P. malariae in 98 (76%), P. malariae was found alone or mixed with P. falciparum in 76 (59%), and the species present could not be identified in 50 of the infected children. It can be concluded from these results that P. malariae is a common parasite of children in the Kampala area of Uganda, and its importance in clinical malaria should be further investigated.

Del Río-Hortega believed that phagocytic cells in the CNS arise from microglia; however, recent autoradiographic studies have suggested a hematogenous origin for brain macrophages. To clarify this issue, we studied a young man with acute lymphoblastic leukemia and a peripheral white blood cell count of 22/mm3 who had an embolic brain infarct 2 weeks before he died. Macrophages were scarce within the lesion, suggesting that the principal phagocytic cell is hematogenous.

In Alzheimer's disease (AD) and Parkinson's disease (PD), dysfunction in the basal forebrain cholinergic system is accompanied by a consistent loss of presynaptic cholinergic markers in cortex, but changes in cholinergic receptor binding sites are poorly understood. In the present study, we used receptor autoradiography to map the distribution of nicotinic (/sup 3/H)acetylcholine binding sites in cortices of individuals with AD and PD and matched control subjects. In both diseases, a profound loss of nicotinic receptors occurs in all cortical layers, particularly the deepest layers.

The nucleus basalis of Meynert (nbM) provides most of the cholinergic input to the cerebral cortex. The loss of cortical choline acetyltransferase (CAT) activity in Alzheimer's disease (AD) and senile dementia of the Alzheimer's type (SDAT) appears to be related to a severe depopulation of the nbM in this dementia. In Huntington's disease (HD), by contrast, there is no loss of cortical CAT activity. The present quantitative study indicates that (1) there is no significant loss of neurons from the nbM in HD, and (2) that the previously described cytologic changes in the neurons of this nucleus in HD patients do not differ significantly from controls. These findings are consistent with the working hypothesis that the types of dementia associated with reductions of neocortical CAT activity are characterized by dysfunction or death of neurons in the nbM, but dementing disorders with normal neocortical CAT activity manifest no major abnormalities in this cholinergic nucleus of the basal forebrain.

Neuronal loss and the presence of neurofibrillary tangles (NFTs) within aminergic nuclei were examined in a series of patients with Alzheimer's disease (AD). Neuromelanin-containing neurons within the locus ceruleus and large nucleolus-containing neurons within the dorsal raphe nucleus and the central superior (raphe) nucleus were counted in 25 patients with AD and in 12 age-matched control subjects. Numbers of NFTs were quantified in the same regions. Counts were compared with clinical data, including psychiatric evaluations, available for 21 of the patients with AD. Within the locus ceruleus in the patients with AD, abnormalities were more severe at mid level than at caudal or rostral levels (p less than 0.01). Within the dorsal raphe nucleus, neuronal loss was most severe caudally (p less than 0.05). NFTs, but not neuronal loss, were demonstrated within the central superior nucleus. Neuronal and NFT counts did not correlate at individual levels; the relative severity of both pathological processes was consistent from level to level within nuclei but was less consistent between nuclei. Neuronal loss correlated inversely with age, particularly within the locus ceruleus. Duration of disease correlated inversely with counts of NFTs, particularly within the dorsal raphe nucleus, implying a correlation between NFT counts and rate of progression of disease as all but 3 patients had severe dementia. Significantly, patients with AD complicated by major depression had fewer neurons at the mid level of the locus ceruleus and at the rostral level of the central superior nucleus in comparison with nondepressed patients. There was a trend suggesting greater loss of neurons at all levels of the locus ceruleus and dorsal raphe nucleus in depressed individuals.

At autopsy, four homosexual men with acquired immunodeficiency syndrome (AIDS) were found to have selective degeneration of the gracile tract, a finding previously unreported in AIDS. Clinically, these patients had progressive lower extremity paresthesias and dysesthesias with reduced or absent ankle jerks, and eventually they developed dementia. Postmortem examination of spinal cords showed a striking loss of both axons and myelin sheaths confined to the fasciculus gracilis, with the most severe involvement in upper thoracic or cervical segments. Lumbar dorsal columns showed only a mild fiber loss, and no fiber loss was observed in lumbar dorsal roots. Lumbar dorsal root ganglia were available from one patient and showed a mild sensory ganglionitis. In all cases examined, microglial nodules were present in the brain. In 23 other individuals with AIDS who had autopsies consecutively with these four subjects, none had sensory neuropathy and the gracile tracts were normal. The combination of distal sensory neuropathy and gracile tract degeneration suggests a "dying-back" process of dorsal root ganglia neurons.

Decreased numbers of pigmented neurons of the dopaminergic nigrostriatal system are the most striking pathology in the brains of individuals with Parkinson's disease (PD), but it is clear that neurons in the locus ceruleus, vagal nuclei, and nucleus basalis of Meynert are also affected in this disease. Because neurochemical evidence suggested that the mesolimbic dopaminergic system originating in the ventral tegmental area (VTA) may also be involved, the present study was designed to evaluate the mesolimbic dopamine system in PD by counting pigmented neurons in the VTA contralateral to therapeutic lesions placed in the basal ganglia or thalamus. In PD, VTA neurons were depleted to 36 to 55% of control values. Moreover, the VTA showed excessive free pigment, a marker for death of pigmented neurons. These changes may be important in disorders of movement or mentation occurring in PD.

Neurologic diseases are frequently characterized by morphologic changes in neuronal tissue. Neuropathologists evaluate such changes by microscopic examination of brain and other tissues. This paper provides an overview of a microcomputer-based image acquisition and analysis system interfaced to an automated microscope directed at aiding neuropathologists in evaluating neuropathologic alterations. Information is provided on general system architecture and function. Details are provided on measurement techniques, key morphologic parameter calculations, data display, and analysis.

Two patients developed dementia, erethism, colitis, and renal failure following the chronic ingestion of a laxative containing calomel (mercurous chloride). Brains of both patients were small and showed loss of cerebellar granular cells. Histochemical stains demonstrated mercury granules within the cytoplasm of neurons, particularly those of the inferior olive and dentate nucleus, and in the choroid plexus. Electron microscopy showed ultradense particles in the basement membrane of the choroid plexus; these were similar to but smaller than those in the kidney that electron diffraction analysis showed to be β-mercuric sulfide. Tissue mercury levels were elevated in both cases. In patient 1, the kidney level was 421μg/gm, and levels from 21 areas within the brain ranged from 105μg to 0.13μg/gm. Highest levels were in the inferior olive, red nucleus, and choroid plexus.

Examination of brains from four individuals with the clinical diagnosis of primary dystonia revealed histopathologic abnormalities in two cases. A 29-year-old man with a 15-year history of dystonia musculorum deformans (DMD) had numerous neurofibrillary tangles (NFT) and mild neuronal loss within the locus ceruleus; occasional NFT were also recognized in the substantia nigra pars compacta, pedunculopontine nucleus, and dorsal raphe nucleus. A 68-year-old man with a 35-year history of Meige syndrome had moderate-to-severe neuronal loss in several brainstem nuclei, including the substantia nigra pars compacta, locus ceruleus, raphe nuclei, and pedunculopontine nucleus. Infrequent NFT were also noted in substantia nigra. An examination of these and other brain regions in a 10-year-old boy with a 6-year history of DMD and a 50-year-old woman with a 3-year history of spasmodic torticollis did not disclose similar abnormalities.

Focal neurologic signs developed in a 71 year old man after insertion of an aortic valve prosthesis. The patient died, and autopsy showed a mycotic thrombus on the prosthesis and fungal thromboemboli in branches of the coronary and left middle cerebral arteries, with infarcts in the heart and brain. Aspergillus niger was cultured from the thrombus. Only three previous cases have been reported in which focal neurologic deficits were associated with Aspergillus infection of a valve prosthesis. The present case is the first in which the pathogenesis of the neurologic abnormalities has been clearly shown to be related to fungal emboli.

A microfilaria was described by Poynton and Hodgkin (1939) from a macaque (Macaca irus) which was collected in the lower reaches of the Perak river in the state of Perak, Malay. Edeson (1954)* observed microfilariae in the peripheral blood of several M. irus collected in the state of Pahang, Malaya, which closely approximated the description given by Poynton and Hodgkin. Adult filarial worms collected later by Dr. Edeson and the author from one of these macaques were determined to belong to the genus Dirofilaria. After returning to the United States, the author had an opportunity to examine at Walter Reed Army Medical Center, Washington, D. C., National Institutes of Health, Bethesda, Maryland, and Eli Lilly Research Laboratories, Indianapolis, Indiana, a total of 510 M. irus believed to have originated in Malaya.** In 12 of these monkeys microfilariae were found similar to those previously observed in Malaya. Adult worms were collected also from several of these macaques, and the microfilariae were associated with them in most cases.

Filarioid worms (Dirofilaria immitis, D. tenuis, Dipetalonema procyonis, and D. Ilewellyni) were discovered in raccoons (Procyon lotor) in Maryland. Raccoons were trapped in lowland, upland, and agricultural-residential areas, which were further classified as stream borders, poorly drained, and well drained. Data on incidence of D. Ilewellyni were analyzed on basis of host distribution within these areas to indicate type of habitat in which one might seek the vector. It was concluded that exposure takes place in the spring of the year. The arthropod found associated most often with the raccoon in spring was Ixodes texanus. Larvae of this tick which were fed on infected raccoons presented no evi- dence of development of the microfilariae. Feeding experiments were also conducted with mosquitoes: Aedes aegypti, A. canadensis, A. sollicitans, A. triseriatus, A. vexans, Culex pipiens, Anopheles punctipen- nis, and A. quadrimaculatus. Although microfilariae remained alive and active in the gut contents of all these mosquitoes for 2 days, only in Aedes aegypti did they enter the hemocele, but no developmental changes were noted and all microfilariae were dead by the eighth day. Although the intermediate host of D. llewellyni was not determined, evaluation of the accumulated data provides criteria for seeking the vector. It appeared unlikely that exposure of the raccoons took place in the den or that the filarioids were transmitted by an ectoparasite commonly found in raccoon dens. The data suggest that the vector is available only early in spring, although there are infected raccoons throughout the year. Prevalence in juveniles was 21 percent; in subadults, 64 percent; in adults, 87 percent.