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Notes: Summary With the use of monoclonal antibodies, raised against the human polyglucosan, positive staining of polyglucosan bodies (PGB) was detected in the brain, spinal cord and cecum of aged dogs. PGB in feline brain were also positively stained with these antibodies. These findings indicate that animal PGB share common antigenicity with human PGB.

Notes: Summary Lafora-like bodies in an 8-year-old cat were studied light and electron microscopically and histochemically. In addition to Lafora-like bodies composed of branching filaments, glycogen granules and electron-dense materials, abnormal accumulations of glycogen granules attracted attention. The most remarkable features were the developmental processes of the branching filaments originating directly from glycogen granules. Lafora-like bodies in the present study showed ultrastructural, histochemical, and enzymatic similarities to those described in the previous reports in Lafora's disease, glycogenosis and other cases. From these results, a certain disturbance of the glycogen metabolism is considered to be probably related to the productive mechanism of Lafora-like bodies.

Notes: Summary In a previous report on a 16-year-old Japanese girl with type A insulin resistance, we found that one allele of the insulin receptor gene was inherited from her mother and contained a 1.2 kilobase pair deletion which removed the 14th exon in the β subunit. We extended investigation of the proband and found the deletion between two Alu sequences. To determine the effect of the deletion on the level of transcription and the splicing pattern of messenger ribonucleic acid (mRNA), we synthesized the complimentary DNA and used the polymerase chain reaction to amplify the region which included the deleted area. The deletion shifted the reading frame, resulting in a termination codon after amino acid 867 (Glu), thereby producing a truncated insulin receptor without a transmembrane region and cytoplasmic domain. We also sequenced each of 22 exons of the insulin receptor gene but found no mutation in exons of the insulin receptor gene, except for deletion of exon 14 of the maternal allele. Thus, the proband is a heterozygote for a single mutant allele. Abnormal mRNA transcribed from the mutant allele resulted in a decrease in insulin binding.

Notes: Summary Defects in insulin receptor function lead to impairment of the insulin response. We treated a patient with the typical phenotype of type A syndrome of insulin resistance whose insulin receptor seemed to lack the transmembrane region and cytoplasmic domain. Hyperinsulinaemia and resistance to exogenous insulin were evident, and insulin binding to cells and uptake of 2-deoxyglucose into fibroblasts were greatly decreased. Molecular weight of the α-subunit of the insulin receptor was normal, but autophosphorylation and kinase activity were impaired. In the pedigree analysis, defects in insulin binding were also observed in the mother, maternal grandfather and two maternal aunts, corresponding with the abnormality of the insulin receptor gene and mild insulin resistance. In the mother, much the same kinase defects as were seen in the patient became evident. However, no relatives had clinical symptoms similar to those seen in the patient. In the father there was a mild insulin resistance in the glucose clamp study and a borderline impaired glucose tolerance. Although insulin binding to cells was normal in the father, both autophosphorylation and kinase activity were reduced. Our findings suggest that insulin resistance in the patient may be caused by the defects in insulin receptor kinase activity as well as by a reduction in insulin binding activity.

Notes: Summary Recent studies have shown that the interstitial nucleus of Cajal (INC) in the midbrain reticular formation is involved in the conversion of vertical semicircular canal signals into eye position during vertical vestibuloocular reflexes. Secondary vestibulo-ocular relay neurons related to the vertical canals, which constitute the majority of output neurons sending signals from the vestibular nuclei directly to the oculomotor nuclei, have been shown to project axon collaterals to the region within and near the INC. To understand how the INC is involved in the signal conversion, latencies of response of neurons in the INC region to electrical stimulaton of the vestibular nerve were examined in alert cats. The responses of 96 cells whose activity was clearly modulated by sinusoidal pitch rotation (at 0.31 Hz) were analyzed. These included 41 cells whose activity was closely correlated with vertical eye movement (38 burst-tonic and 3 tonic neurons), and 55 other cells (called pitch cells as previously). Twenty nine of the 96 cells (30%) were activated at disynaptic latencies following single shock stimulation of the contralateral vestibular nerve. Disynaptically activated cells were significantly more frequent for pitch cells than for eye movement-related cells (25/55 = 45% vs 4/41 = 10%; p 〈 0.001, Chi-square test). Conversely, cells that did not receive short-latency activation (〈 6 ms) were more frequent among eye movement-related cells than pitch cells (26/41 = 63% vs 13/55 = 24%; p 〈 0.001, Chi-square test). Pitch cells showed significantly less phase lag (re head acceleration) than eye movement-related cells during sinusoidal pitch rotation (mean ± SD 124° ± 17° vs 138° ± 14°. p 〈 0.01, t-test). These results suggest that 1) cells in the INC region other than burst-tonic and tonic neurons mainly receive direct inputs from secondary vestibulo-ocular relay neurons, and that 2) vertical canal signals reach eye movement-related neurons mainly polysynaptically.

Notes: Summary 1. Maximal activation directions of vertical burst-tonic and tonic neurons in the region of the interstitial nucleus of Cajal (INC) were examined in alert cats during vertical vestibulo-ocular reflex induced by sinusoidal rotation (at 0.11 Hz±10 deg, or 0.31 Hz±5 deg) in a variety of vertical planes using a null point analysis. The results were compared with the angles of anatomical and functional planes of vertical canals reported by Blanks et al. (1972) and Robinson (1982), and with the angles of vertical eye muscles measured in this study and by Ezure and Graf (1984). 2. Maximal activation directions of 23 cells (21 burst-tonic and 2 tonic neurons) were determined from their responses during rotation in 4 or more different vertical planes. All cells showed sinusoidal gain curves and virtually constant phase values except near the null regions, suggesting that their responses were evoked primarily by canal inputs. Phase values of 5 cells near the null regions depended on the rotation plane, suggesting additional otolith inputs. We used a measurement error range of ±10 deg for calculating the maximal activation directions from the null regions of individual cells and the values of error ranges of null calculation. Of the 23, the maximal activation directions of 7 cells were outside the measurement error ranges of vertical eye muscle angles and within the ranges of vertical canal angles (class A), those of 5 cells were within the ranges of eye muscle angles and outside the ranges of vertical canal angles (class B), and those of the remaining 11 cells were in the overlapping ranges for both angles (class C). Even if only the cells in which 5 or more measurement points were taken to determine maximal activation directions (n = 15), the results were similar. During vertical rotation with the head orientation +60 deg off the pitch plane, dissociation of cell activity and vertical compensatory eye movement was observed in 5 cells in class A or C that had null angles near +45 deg. These results suggest that the cells in class A and B carried individual vertical canal and oculomotor signals, respectively, although it is difficult to tell for the majority of cells (class C) which signals they reflected. Some cells in class A and C were antidromically activated from the medial longitudinal fasciculus at the level of abducens nucleus, suggesting that the signals carried by these cells may be sent to the lower brainstem. 3. Most burst-tonic neurons did not respond to horizontal rotation; significant responses were obtained in only 3 of 10 cells tested for which the gain was only 14–17% of their maximal vertical gain. There was no clear difference in gain or phase values of the responses to vertical rotation, or in eye position sensitivity (during spontaneous saccades) between cells whose responses coincided with individual vertical canal angles and those matching the angles of vertical recti muscles. The values of phase lag (re head acceleration during pitch rotation) and eye position sensitivity of these cells are still smaller compared to those of extraocular motoneurons reported by Delgado-Garcia et al. (1986), although they were larger than those of secondary vestibulo-ocular neurons (Perlmutter et al. 1988). All these results suggest that the signals carried by burst-tonic and tonic neurons in the INC region are different from oculomotor signals. 4. Similar analysis was done for comparison for 19 other cells that did not show close correlation with spontaneous eye movement but whose activity was clearly modulated by pitch rotation (pitch cells). More than a half (10/19) had maximal activation directions outside the measurement error ranges of individual vertical canal angles, and many shifted towards roll. Horizontal rotation produced responses with higher gain than burst-tonic neurons, suggesting a difference in the spatial response properties of burst-tonic and tonic neurons on one hand and pitch cells on the other.