https://www.cell.com/cell/pdf/0092-8674(88)90383-2.pdf

The Complete Sequence of Dystrophin Predicts a Rod-Shaped Cytoskeletal Protein

The amyloid state of proteins in human diseases

The tissue photosensitizer protoporphyrin IX (PpIX) is an immediate precursor of heme in the biosynthetic pathway for heme. In certain types of cells and tissues, the rate of synthesis of PpIX is determined by the rate of synthesis of 5-aminolevulinic acid (ALA), which in turn is regulated via a feedback control mechanism governed by the concentration of free heme. The presence of exogenous ALA bypasses the feedback control, and thus may induce the intracellular accumulation of photosensitizing concentrations of PpIX. However, this occurs only in certain types of cells and tissues. The resulting tissue-specific photosensitization provides a basis for using ALA-induced PpIX for photodynamic therapy. The topical application of ALA to certain malignant and non-malignant lesions of the skin can induce a clinically useful degree of lesion-specific photosensitization. Superficial basal cell carcinomas showed a complete response rate of approximately 79% following a single exposure to light. Recent preclinical studies in experimental animals and human volunteers indicate that ALA can induce a localized tissue-specific photosensitization if administered by intradermal injection. A generalized but still quite tissue-specific photosensitization may be induced if ALA is administered by either subcutaneous or intraperitoneal injection or by mouth. This opens the possibility of using ALA-induced PpIX to treat tumors that are too thick or that lie too deep to be accessible to either topical or locally injected ALA.

Endogenous protoporphyrin IX, a clinically useful photosensitizer for photodynamic therapy.

Pseudoneglect: a review and meta-analysis of performance factors in line bisection tasks.

A large International Restless Legs Syndrome (RLS) Study Group has been formed. As its first task, the group has taken upon itself the role of definig the clinical features of the RLS. As minimal criteria for diagnosis, the group proposes the following four features: (a) desire to move the extremities, often associated with paresthesias/dysesthesias; (b) motor restlessness; (c) worsening of symptoms at rest with at least temporary relief by activity, and (d) worsening of symptoms in the evening or night. Other features commonly seen in RLS include sleep disturbance, periodic limb movements in sleep and similar involuntary movements while awake, a normal neurological examination in the idiopathic from, a tendency for the symptoms to be worse in middle to older age, and, in some cases, a family history suggestive of an autosomal dominant mode of inheritance.

Toward a better definition of the restless legs syndrome

An autopsy case of a 52-year-old man suffering from chronic manganese poisoning (CMP) is reported with determination of the manganese distribution in the brain. The patient had been working in a manganese ore crushing plant since 1965. In 1967 he began to complain of difficulties in walking and diminished libido. Later, he developed various neuropsychiatric symptoms including euphoria, emotional incontinence, masked face, monotonous speech, "cock-walk", increased muscle tone, weakness of upper and lower extremities, tremor of the eye lids, and exaggeration of knee jerks. The major neuropathological change was degeneration of the basal ganglia, in which the pallidum was severely affected. The pallidum disclosed a loss and degeneration of nerve cells, which was especially marked in the medial segment, a prominent decrease of myelinated fibers, and moderate astrocytic proliferation. The substantia nigra was intact. Distribution of manganese in the brain of the present case of CMP was determined using flameless atomic absorption spectrometry and compared with control cases and also a case of Parkinson's disease (PD). There was no significant difference between the control cases and the case of PD in average concentration of manganese and its distribution in the brain. The present case of CMP showed no elevation in average concentration of manganese in the brain. However, there were some changes in its distribution. Thus, the continuance of neurological disorders in CMP is not linked to an elevated manganese concentration itself in the brain. CMP appears to be different from PD in neuropathology and manganese behavior in brain.

Chronic manganese poisoning: A neuropathological study with determination of manganese distribution in the brain

Cerebral amyloid angiopathy (CAA) was found in 57% of 123 autopsy brains removed from patients aged 59–101 years. The incidence of CAA increased with age. CAA was seen most frequently in the occipital cortex. Immunohistochemically, amyloid of CAA was positive for amyloid P component and negative for human AA protein and human prealbumin. The presence and severity of CAA were significantly correlated with the number of senile plaques and neurofibrillary tangles. The incidence of CAA in 17 patients with dementia of Alzheimer type (DAT) was estimated to be 88% and was significantly higher than that in 26 patients with dementia of non-Alzheimer type. CAA had a pathogenetic relationship with both brain ageing and DAT. Lobar cerebral haemorrhage was found in 3 patients with CAA of marked or moderate degree. Lobar cerebral haemorrhage in the aged and in patients with DAT suggest the presence of CAA.

Cerebral amyloid angiopathy in the aged.

Sleep-related periodic leg movements (nocturnal myoclonus) due to spinal cord lesion.

Eye-fixation patterns in homonymous hemianopia and unilateral spatial neglect.

Patients with unilateral spatial neglect fail to report or respond to stimuli contralateral to the lesion which usually involves the right parietal lobe. When asked to mark the centre of a horizontal line, these patients place the mark to the right of the true midpoint. It has been considered that they neglect the left part of the line and bisect the perceived line segment. We investigated the eye-fixation patterns of hemianopic patients with or without unilateral spatial neglect during the bisection of lines, using an eye camera. Hemianopic patients without unilateral spatial neglect saw the whole lines, searching to the endpoint on the hemianopic side, and bisected it correctly. In contrast, left hemianopics with unilateral spatial neglect never searched to the left hemianopic side. Once they fixated a certain point on the right part of the line, they persisted with this point and marked the subjective midpoint there. Taking left homonymous hemianopia into account, the subjective midpoint appeared to be marked, not at the centre of the line segment perceived in the seeing right visual field, but at the leftmost point of it. However, they could appreciate the deviation of the subjective midpoint in the right visual field when forced to fixate the left endpoint of the line. These findings suggest that the left hemisphere has the ability to estimate the midpoint of the line through the right visual field and that visuospatial disorder in the line bisection test is attributable to the pathological change in the right hemisphere. The results are interpreted to mean that left hemianopic patients with unilateral spatial neglect see a totalized image of a line extending equally to either side of the point where they are going to mark the subjective midpoint. We considered that the right hemisphere completes the line, using the visual input relating to the right part of the line perceived by the left hemisphere.

Hiroshi Tsukagoshi

Papers

Chronic manganese poisoning: A neuropathological study with determination of manganese distribution in the brain

Cerebral amyloid angiopathy in the aged.

Sleep-related periodic leg movements (nocturnal myoclonus) due to spinal cord lesion.

Eye-fixation patterns in homonymous hemianopia and unilateral spatial neglect.

Visuospatial processes of line bisection and the mechanisms underlying unilateral spatial neglect