The inheritance of Alzheimer's disease: a new interpretation

Ninety-one families of Alzheimer patients were studied to determine the proportion of familial cases, to obtain pedigrees for the analysis of the mode of inheritance, and to look for clinical differences between the familial and the nonfamilial cases. The diagnosis was confirmed by autopsy in 26 cases. Thirty-nine cases (43%) were familial, which is defined as more than one case in the family. Our interpretation of the pedigree data is that Alzheimer's disease is etiologically heterogeneous: it may be genetic or sporadic. In the familial type we think that the disease is inherited as an autosomal dominant, with a wide range of age of onset within a family. In one-third of these families the gene is not expressed until over age 70. No clinical differences were found between the familial and the sporadic groups.     

Epidemiology and diagnosis of acute conjunctivitis at an inner-city hospital

Chlamydia has been found to be the cause of a high percentage of cases of neonatal and chronic conjunctivitis in an inner-city population. To assess the etiology and epidemiology of acute conjunctivitis in this population, conjunctival scrapings were sampled from 45 patients presenting to an ocular emergency room; and replicate chlamydial, viral, and bacterial cultures and cytology tests were done. No cases of chlamydial conjunctivitis were diagnosed, although a viral etiology was established in 36% of the cases and a bacterial etiology in 40%. Twenty-four percent of the cases were not diagnosed. The authors recommend limiting the initial laboratory workup of patients with acute conjunctivitis to obtaining conjunctival smears for Gram and Giemsa staining. Chlamydial direct immunofluorescent monoclonal antibody (DFA) should be done if the patient is sexually active. Hyperacute conjunctivitis or acute conjunctivitis refractory to treatment mandates a more complete set of laboratory tests.     

Long-range movement and fibril association of type X collagen within embryonic cartilage matrix.

A recent immunoelectron microscopic study of type X collagen in developing cartilage gave results that could be explained by movement of the molecule from one region of the cartilage matrix to another, there becoming associated with preexisting collagen fibrils. In the present study, to test the feasibility of this model we incubated pieces of nonhypertrophic, embryonic chicken sternal cartilage (which has no endogenous type X collagen) in medium with type X collagen and then used immunofluorescence and immunoelectron microscopy to evaluate movement of the molecule through the matrix. The results show that type X collagen molecules can indeed pass through embryonic sternal cartilage matrix and subsequently become fibril-associated.     

Induced Microgyria and Auditory Temporal Processing in Rats: A Model for Language Impairment?

Studies have shown the existence of minor developmental corticalmalformations, including microgyria, in the brains of dyslexics.Concomitant studies have shown that language-impaired individualsexhibit severe deficits in the discrimination of rapidly presentedauditory stimuli, including phonological and nonverbal stimuli(i.e., sequential tones). In an effort to relate these results,male rats with neonatally induced microgyria were tested inan operant paradigm for auditory discrimination of stimuli consistingof two sequential tones. Subjects were shaped to perform a go/no-gotarget identification, using water reinforcement. Stimuli werereduced in duration from 540 to 249 msec across 24 d of testing.Results showed that all subjects were able to discriminate atlonger stimulus durations. However, bilaterally lesioned subjectsshowed specific impairment at stimulus durations of 332 msecor less, and were significantly depressed in comparison to shams.Right- and left-lesioned subjects were significantly depressedin comparison to shams at the shortest duration (249 msec).These results suggest a possible link between the neuropathologicanomalies and the auditory temporal processing deficits reportedfor language-impaired individuals.     

The interaction of 14C-morphine with sera from immunized rabbits and from patients addicted to heroin

An intravenous injection of morphine reduced the binding of ¹⁴C-morphine by sera from rabbits immunized with morphine-6-hemisuccinated bovine serum albumin. Treatment of the sera with dialysis against glycine buffer (pH 3) followed by dialysis against phosphate buffered saline (PBS), conditions known to dissociate antigen–antibody complexes, restored approximately 76% of the original binding capacity. The heterogeneity of the antibody affinities was shown in both early `nonavid' and hyperimmune `avid' antisera by the demonstration of at least two distinct populations of antibodies. One population of antibodies formed loosely bonded antigen–antibody complexes and these complexes completely dissociated within 30 min. The second population had different dissociation times in the `nonavid' and `avid' antisera (15 and >72 hr respectively). The presence of the low affinity antibody resulted in different degrees of reduction of detectable binding by the standard washing procedures usually employed in the radioimmunoassay used in these studies. Washing caused less reduction in the amount of antigen bound by the more `avid' antisera.

Seventy-three per cent of sixty-three serum samples from heroin addicts studied, contained opioid capable of inhibiting the binding of morphine in the radioimmunoassay employed. Methadone at concentrations likely to be present in sera did not interfere with the binding of ¹⁴C-morphine. Sera from thirty-one of the patients were treated by dialysis against glycine buffer and PBS and then studied for the capacity to bind morphine. Only one of these thirty-one sera and none of the thirty-two sera that were not pretreated bound ¹⁴C-morphine suggesting that an immune response to heroin is not a significant contributing factor to opioid tolerance or the development of complications, such as pulmonary oedema, following opioid administration.

     

Hair Whorl as an Indicator of a Mediastinal Plexiform Neurofibroma

Abstract: We report a boy with neurofibromatosis type 1 (NF-1) who had nonspecific respiratoi symptoms and a mediastinal mass. In addition to multiple cafe au lait macules and subcutaneous neurofibromas, he had a hair whorl over the spine at the level of a deep mediastinal mass demonstrated by CT scan and MR examination. Thoracoscopy and biopsy of the mass revealed a plexiform neurofibroma. The clinical sign of a hair whorl may assist the clinician in early recognition of a paraspinal plexiform neurofibroma.     

Biochemical and ultrastructural changes in skeletal muscle induced by a creatine antagonist

To evaluate the essentiality of creatine and phosphocreatine for the maintenance of the ultrastructure of skeletal muscle, chicks were fed a creatine antagonist, β-guanidinobutyric acid (β-GBA), as 2% of a Chow diet. Chicks fed β-GBA exhibited growth retardation and weakness, and they accumulated large amounts of a monosubstituted guanidino compound, presumably β-GBA, in their skeletal muscles. After 2 wk, there was a 74% decrease in the uptake of [¹⁴C]-1-creatine into pectoralis muscles of chicks fed β-GBA. After 3 wk there was a significant decrease in phosphocreatine concentrations in pectoralis muscles from 20.1 ± 2.8 μmoles per g wet weight (mean ± S.D.) for 8 control chicks to 16.5 ± 2.5 for 7 chicks fed β-GBA. Selected fibers of the pectoralis and gastrocnemius muscles of chicks fed β-GBA exhibited ultrastructural abnormalities including loss of thick and thin filaments, disruption of the Z band, dilated mitochondria, and dilated and displaced sarcoplasmic reticulum. The pectoralis muscles of chicks given 6% creatine in addition to 2% β-GBA in the diet accumulated little β-GBA, maintained normal phosphocreatine concentrations, and exhibited no significant ultrastructural abnormalities. These findings are the first experimental evidence that high concentrations of phosphocreatine are essential for the maintenance of the ultrastructural integrity of skeletal muscle.     

Sequestration of the chloroquine receptor in cell-free preparations of erythrocytes infected with Plasmodium berghei.

When mouse erythrocytes infected with Plasmodium berghei were preincubated with [14C]chloroquine and then lysed by hypotonic shock, chloroquine remained bound to the resulting cell-free preparation. In an isotonic medium at pH 7.4 and 25 degrees C, chloroquine was bound to the cell-free preparation with an apparent dissociation constant of 1.8 x 10(-7) M. The bound [14C]chloroquine could be displaced by nonradioactive chloroquine, amodiaquine, quinacrine, and mefloquine, as would be predicted from knowledge of the specificity of ferriprotoporphyrin IX for antimalarial drugs. Also, as predicted, primaquine did not displace the [14C]chloroquine. The ability of these cell-free preparations to bind chloroquine with high affinity decreased rapidly with incubation at 37 degrees C and became undetectable within 1 h; at 4 degrees C the decrease occurred more slowly. This behavior of the endogenous receptor-chloroquine complex was duplicated by an exogenous ferriprotoporphyrin IX-chloroquine complex loaded into cell-free preparations of erythrocytes infected with P. berghei. These findings support the hypothesis that ferriprotoporphyrin IX is the endogenous chloroquine receptor of P. berghei and indicate that it can be sequestered rapidly in a form that is inaccessible to chloroquine.