Cerebello-thalamo-cortical projections to the posterior parietal cortex in the macaque monkey.

The cerebello-thalamo-posterior parietal cortical projections were investigated electrophysiologically and morphologically in macaque monkeys. In anesthetized monkeys, electrical stimulation of every cerebellar nucleus evoked marked surface-positive, depth-negative (s-P, d-N) cortical field potentials in the superior parietal lobule and the cortical bank of the intraparietal sulcus, but no responses in the inferior parietal lobule. Tract-tracing experiments combining the anterograde method with the retrograde one indicated that the interposed and lateral cerebellar nuclei projected to the posterior parietal cortex mainly through the nucleus ventral lateralis caudalis of the thalamus. The significance of the projections is discussed in connection with cognitive functions.

Cortical field potentials associated with audio-initiated vocalization in monkeys.

Five monkeys vocalizing at self-pace (self-paced vocalization) were well trained to vocalize in response to a monkey call (audio-initiated vocalization). Field potentials associated with audio-initiated vocalizations were recorded by using electrodes which were implanted chronically on the surface and at a 2.0-3.0 mm depth in various cortical areas. A surface-negative (s-N), depth-positive (d-P) potential (at about 70 ms latency after stimulus onset) was recorded in the rostral bank of the inferior limb of the arcuate sulcus in the left hemisphere, in which an insignificant potential was associated with self-paced vocalizations. An s-N, d-P slow potential which occurred in the motor and somatosensory cortices with a latency of about 300 ms after stimulus, started about 700 ms before vocalizations. The duration and amplitude of this potential was substantially the same with those of the potential which occurred with self-paced vocalizations. Reaction times from stimulus onset to vocalization start were variable, but were about 0.9s on the average. The findings were discussed in connection with reaction-time hand movements.

Conformational analysis of potent sweet taste ligands by nuclear magnetic resonance, computer simulations and X-ray diffraction studies.

Four potent sweet-tasting molecules, N-(3,3-dimethylbutyl)-L-aspartyl-L-phenylalanine methylester 1 (7000 times more potent than sucrose), N-(3,3-dimethylbutyl)-L-aspartyl-D-valine (S)-alpha-ethylbenzylamide 2 (3000 time more potent than sucrose), L-aspartyl-D-valine (R)-alpha-methoxymethylbenzylamide 3 (1350 times more potent than sucrose and L-aspartyl-(1R,2S,4S)-1-methyl-2-hydroxy-4-phenylhexylamide 4 (2500 times more potent than sucrose) were studied by 1H NMR and computer simulations. These flexible molecules adopt multiple conformations in solution. The "L-shaped" structure, which we believe to be responsible for sweet taste is accessible to all four compounds in solution. Extended conformations with the AH and B-containing moieties in the +y-axis and the hydrophobic group X pointing in the y-axis have also been observed for all four sweeteners. For compounds 1 and 3, the solid-state conformations were determined by X-ray diffraction studies. These results demonstrate that compounds 1 and 3 adopt an "L-shaped" structure even in the crystalline state. The extraordinary potency of the N-alkylated compound 1 compared with the unsubstituted Asp-Phe-OMe may be explained by the effect of a second hydrophobic binding domain in addition to interactions arising from the "L-shaped" structure.

Conformational analysis of the dipeptide taste ligand L-aspartyl-D-2-aminobutyric acid-(S)-alpha-ethylbenzylamide and its analogues by NMR spectroscopy, computer simulations and X-ray diffraction studies.

A dipeptide taste ligand L-aspartyl-D-2-aminobutyric acid-(S)-alpha-ethylbenzylamide was found to be about 2000 times more potent than sucrose. To investigate the molecular basis of its potent sweet taste, we carried out conformational analysis of this molecular and several related analogues by NMR spectroscopy, computer simulations and X-ray crystallographic studies. The results of the studies support our earlier model that an L-shape molecular array is essential for eliciting sweet taste. In addition, we have identified an aromatic group located between the stem and the base of the L-shape, which is responsible for enhancement of sweetness potency. In this study, we also assessed the optimal size of the essential hydrophobic group (X) and the effects of the chirality of the second residue toward taste.

[An elderly case of small cell lung cancer showing complete response by oral administration of etoposide].

An 87-year-old female was admitted with left chest pain and dyspnea in January 1989. The chest X-ray film revealed complete atelectasis of the left lung. Bronchoscopic observation revealed a tumor which was bleeding easily at left main bronchus. Cytological findings of the bronchial aspirates showed small cell lung cancer. Because she was old and had some complications, she was difficult to treat by standard combination chemotherapy. Only etoposide at 150 mg/day was administered orally for 3 days (first course). After the first course the whole lung atelectasis improved; and after the second course (etoposide at 150 mg/day for 4 days) the tumor of the left main bronchus disappeared under endoscopic examination. Malignant cells were not detected in the bronchial aspirates and biopsy specimens. No severe side effect except for alopecia and mild gastrointestinal symptoms such as nausea and vomiting was noted. Myelosuppression was not evident. This case suggested that etoposide administered orally is useful in the treatment of small cell lung cancer especially in elderly patients with complications.