B-RAF mutation and accumulated gene methylation in aberrant crypt foci (ACF), sessile serrated adenoma/polyp (SSA/P) and cancer in SSA/P.

BACKGROUND: Sessile serrated adenomas/polyps (SSA/Ps) are a putative precursor of colon cancer with microsatellite instability (MSI). However, the developmental mechanism of SSA/P remains unknown. We performed genetic analysis and genome-wide DNA methylation analysis in aberrant crypt foci (ACF), SSA/P, and cancer in SSA/P specimens to show a close association between ACF and the SSA/P-cancer sequence. We also evaluated the prevalence and number of ACF in SSA/P patients. METHODS: ACF in the right-side colon were observed in 36 patients with SSA/Ps alone, 2 with cancers in SSA/P, and 20 normal subjects and biopsied under magnifying endoscopy. B-RAF mutation and MSI were analysed by PCR-restriction fragment length polymorphism (RFLP) and PCR-SSCP, respectively, in 15 ACF, 20 SSA/P, and 2 cancer specimens. DNA methylation array analysis of seven ACF, seven SSA/P, and two cancer in SSA/P specimens was performed using the microarray-based integrated analysis of methylation by isochizomers (MIAMI) method. RESULTS: B-RAF mutations were frequently detected in ACF, SSA/P, and cancer in SSA/P tissues. The number of methylated genes increased significantly in the order of ACF

Neurological abnormalities in cognitively impaired but not demented elderly.

OBJECTIVE: We determined the prevalence and clinical characteristics of elderly people with cognitively impaired but not demented (CIND) in the community. MATERIAL AND METHODS: We examined 945 elderly residents (aged 65 years or more) in a cross-sectional study of a standardized clinical examination in 27 randomly selected communities in the town of Mifune, a standard farming town in Japan. RESULTS: The prevalence of CIND and dementia were 10.8% and 4.8%, respectively, with both rates increasing with age. The frequency of most neurological signs in CIND elderly was greater than that found in subjects with no cognitive impairment (NCI) and less than that in subjects with dementia. The mean ADL disability score in CIND subjects also lay between the mean values for those with NCI and those with dementia. There were no differences in lifestyles between the CIND group and the other groups. CONCLUSION: The results suggest that a majority of CIND elderly suffer from brain dysfunction due to chronic neurological disorders or aging itself.

[A case of acute quadriplegic myopathy].

A 22-year-old man developed unconsciousness, severe quadriplegia and muscle atrophy, and had markedly elevated serum creatine kinase levels after using the high-dose steroid and nondepolarizing neuromuscular blocking agents during the course of sepsis and DIC. On neurological examination, he was lethargic. The patient had generalized muscle weakness and wasting, and diminished deep tendon reflexes. He weakly responsed to painful stimuli on the legs. The motor nerve conduction study demonstrated decreased CMAP (compound muscle action potential) amplitudes. Motor and sensory nerve conduction velocities and their distal latencies were normal. Muscle biopsy revealed marked muscle fiber atrophy predominantly in type 2 fibers and numerous basophilic and a few necrotic fibers. Some atrophic fibers had decreased to absent myosin adenosine triphosphatase activity in their center. Accordingly, he was diagnosed as having acute quadriplegic myopathy (AQM), which has been reported mainly in Western countries. The mechanism of muscle fiber degradation in this myopathy is still unknown. On immunohistochemical analysis to our patient, enzyme activities of various proteases such as calpain, cathepsin B, and proteasomes were increased in the sarcoplasm, especially in the atrophic fibers. We suggest that lysosomal cathepsin, nonlysosomal calpain, and ATP-ubiquitin-proteasome proteolytic pathways participate in muscle fiber degradation in AQM.

An incident involving blood sucking by a tick in a suburb in Japan.

We encountered a patient whose blood was sucked by Haemaphysalis longicornis in the suburb of a business city in Tokushima prefecture in Japan. The tick, which had been attached to the lower limb of the patient for one week, measured 10 mm in length. There were no notable objective or subjective findings after the complete extirpation of the tick. The area had not been known in recent history to be a habitat of ticks, and, thus, this case is of importance in terms of predicting future trends of tick-borne diseases in Japan.

Isolated third nerve palsy due to sarcoidosis.

We present a 28-year-old man with isolated third nerve palsy as the initial manifestation of sarcoidosis. MRI demonstrated abnormal enhancement of the cisternal portion of the right third nerve. One month after steroid therapy, he showed almost complete recovery with resolution of the contrast enhancement on MRI. This patient illustrates the usefulness of enhanced MRI for detection of cranial nerve lesions of sarcoidosis.

[A case of radiation myelopathy with characteristic findings of thermoregulatory sweat distribution and magnetic resonance images].

A 73-year-old man had undergone resection of a lung carcinoma of the right upper lobe in 1987. Post-operative irradiation (40 Gy) was given to the right hilus. In November 1988, recurrence was detected in the trachea. Laser therapy was done in December 1988. From January 9 to February 13 in 1989, irradiation (50 Gy) was given to the mediastinum. From the beginning of 1991, the patient developed muscle weakness in the right lower extremity and pain temperature sensations were impaired below the Th12 level on the left side. On October 3, 1991, he was admitted to our hospital. Neurological examination revealed mild muscle weakness in the right lower extremity. Superficial sensations were impaired below the Th6 level bilaterally. Deep tendon reflexes were hyperactive in the lower extremities. A bilateral Babinski sign was positive. The T1 weighted MRI showed a low signal intensity in the spinal cord at the level of thoracic vertebra (TV)2-TV6. T2 weighted images revealed a high signal intensity area of the spinal cord from TV4-TV6. A gadolinium-DTPA injection revealed an enhancement on the left side of the spinal cord at the TV2-3 level, and right side of the spinal cord at the TV4-5 level on the sagittal and axial images. A thermal sweating test revealed hypohidrosis below the Th8 level on the right side, and the Th11 level on the left side. Sweating was delayed at the Th7-8 levels on the right side and Th10-11 levels on the left side. An irradiated field on the chest revealed hypohidrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Pure progressive autonomic failure presenting severe orthostatic hypotension.

A 59-year-old woman showed chronic progressive autonomic failure consisting of orthostatic hypotension and dyshidrosis. No signs of Parkinsonism, cerebellar or peripheral neuropathy were observed. Autonomic nervous function tests and findings of biopsied sural nerve suggested that this case had both sympathetic and parasympathetic dysfunctions, mainly postganglionic. A decrease in the total peripheral resistance and no increase in the heart rate on standing seemed to be the mechanism of orthostatic hypotension in this case. We conclude that pure PAF can be recognized as a distinct clinical syndrome of systematic degeneration of the autonomic nervous system.

[A case of acute idiopathic pandysautonomia].

A 19-year-old male student who complained of orthostatic syncope and low grade fever was admitted to our hospital and diagnosed acute idiopathic pandysautonomia (AIPD). He had dysesthesia and hypalgesia of his face and the upper part of the level of Th4, slight hypalgesia of the limbs and slightly exaggerated jaw jerk and diminished deep tendon reflexes of the limbs, but his main clinical manifestations were orthostatic hypotension (OH), sweating disturbance and alternative diarrhea and constipation. Paroxysmal cough and vomiting attack, severe weight loss and slight emotional change were also observed. There were no abnormal findings in the routine laboratory examinations, but the protein in the cerebrospinal fluid was slightly elevated in the initial state. The results of autonomic function tests, such as OH on tilting, no blood pressure effects on cold pressor test and hand grip test, no overshoot in Valsalva maneuver, low norepinephrine (NE) level at resting and poor NE response on tilting, exaggerated response to a small dose of NE infusion (denervation supersensitivity), suggested that the sympathetic post-ganglionic sites were chiefly affected. The parasympathetic nervous functions were seemed to be almost intact by the results of Aschner test, Czermak test and coefficient variation of R-R intervals. Sural nerve biopsy revealed a marked loss of small myelinated and unmyelinated fibers, suggesting axonal degeneration. These findings were different from those of the Guillain-Barré syndrome (GBS), although the allergic or immunological mechanisms are suggested as the cause of both AIPD and GBS. In this case, amezinium metilsulfate, an indirect sympathomimetic agent, was most effective to OH and cough attack.