A case of HTLV-I associated myelopathy (HAM) complicated by mononeuritis multiplex

A 42-year-old woman with progressive myelopathy and mononeuritis multiplex is reported. The neurological examination on admission revealed hyperreflexia of the four extremities with pathological reflexes and moderate muscle weakness of the lower extremities with spasticity. Sensory disturbance was distributed on the areas of the bilateral lateral cutaneous femoral, the superficial peroneal and sural nerves. The antibody to HTLV-I in the serum and cerebrospinal fluid was more than 8192X and 512X, respectively. No sensory potential was recorded in the sensory conduction study of bilateral lateral femoral cutaneous nerves. Corticosteroid therapy caused a marked improvement of the sensory and urinary disturbances and had a slight effect on the spastic gait. Our nerve conduction study found small sensory potentials with normal conduction velocities in the bilateral lateral femoral cutaneous nerves. These results suggested the presence of an axonal degeneration in the peripheral nerves in this case. There have been no reports in the literature regarding a case of HAM with mononeuritis multiplex.     

Post operative upper gastrointestinal bleeding in the aged]

A 10-year experience with 2,441 patients over 65 years of age undergoing operations for non-upper gastrointestinal tracts was reviewed to evaluate both the incidence of postoperative upper gastrointestinal bleeding and the clinical risk factors associated with the complication. A total of 18 (0.7%, 7 males and 11 females) patients had overt postoperative upper gastrointestinal bleeding of non-variceal origin documented by endoscopic findings or blood transfusions. Of these, the complication developed in 10 (1.5%) of 646 patients after an operation for biliary or pancreatic disease, 1 (1.5%) of 64 for aneurysmal or obstructive arterial disease, 5 (1.1%) of 43 for colorectal cancer and 2 (0.3%) of 916 for hernia. The incidences of bleeding after an operation for obstructive jaundice (3.8%), for biliary or pancreatic malignancy (4.5%), and of unavoidable diversion colostomy for colorectal anastomosis (3.1%) were significantly higher than for non-jaundice (0.6%), for non-malignancy (1.1%) and of postoperative upper gastrointestinal bleeding in the present study. The origins of bleeding were gastric ulcer in 11, acute gastric mucosal lesion in 4, duodenal ulcer in 1 and other in 2. All cases of bleeding were treated and met success in hemostasis using H2-blockers. Of these, however, 5 patients died of multiple organ failure despite discontinued hemorrhage, prophylactic use of H2-blockers showed a decrease in occurrence of postoperative upper gastrointestinal bleeding in the present study.     

Equivalent current dipole estimated from SSR potential distribution over the human hand. Sympathetic skin response.

OBJECTIVE: We aimed to determine whether or not the potential distribution of the sympathetic skin response (SSR) on the palm and dorsum of the hand can be described by an equivalent current dipole (ECD) as an SSR source model. METHODS: The SSR of 22 normal subjects were simultaneously obtained from two electrodes placed on the palm and the dorsum of hand, with an indifferent electrode on the thumbnail. We then measured the SSR potential distribution in 10 of the 20 subjects who had responded to stimulation with a clear dorsal SSR. To do this, 18 electrodes were attached to the palm and dorsum of the hand. SSR-evoking stimulation (sound, voice and rapid inspiration) were randomly delivered to the subject at time intervals of more than 1min to minimize the habituation effect. We estimated the ECD from the measured potential distribution. RESULTS AND CONCLUSIONS: The SSR-evoked by stimulation was negative in potential at the palmar sites of all 22 subjects, and was positive in potential at the dorsal sites of the hand in 20 of the 22 subjects. The SSR potential distribution, which was measured in 10 subjects, reached its maximum negative and positive potential near the base of the middle finger on the palm, and near the corresponding site on the dorsum of the hand, respectively. The SSR potential measured on the dorsum of the hand, however, was about 1/3 in amplitude of those on the palmar sites. These results suggest that the SSR source is located on the palm (probably the sweat glands) as confirmed by the estimated ECD (a negative pole on the palm and a positive pole on the dorsum of the hand). We speculate that the SSR may result from the potential difference caused by the Na(+) concentration gradient in the sweat, which results from intracanal reabsorption of Na(+). SIGNIFICANCE: The ECD resulting from the Na(+) concentration gradient within the canal of sweat glands is thought to be the source of the SSR from the negative pole on the palm to the positive pole on the dorsum.     

Nerve conduction and microanatomy in the rabbit sciatic nerve after gradual limb lengthening-distraction neurogenesis.

To clarify how the peripheral nerve adapts to elongation during gradual limb lengthening, electrophysiological and histomorphometric examinations were performed on the sciatic nerves in 18 rabbits. External fixators were used to lengthen the right femora by 30 mm (30%), at a daily rate of 0.5 mm (Group 1) or 2.0 mm (Group 2). Examinations were performed immediately after the limb lengthening procedure. Electrophysiologically, mild conduction slowing was observed in Group 1; a conduction block was evident in Group 2. Histologically, the mean diameter of myelinated fibers was unchanged in Group 1, but a significantly decreased diameter was observed in Group 2. Electron microscopy revealed that mild degenerative change of unmyelinated axons occurred sporadically in two cases in Group 2, but neither group showed evidence of thinning of myelin sheath of myelinated fibers. The mean internodal length (between nodes of Ranvier) of teased fibers was 1216+/-295 microm in the control contralateral side, 1484+/-347 microm in Group 1, and 1467+/-322 microm in Group 2. Thus the internodes were lengthened by 22.1% (Group 1) and 20.7% (Group 2) in comparison with those of the controls. Straightening of the geometry of paranodal myelin sheath was significantly correlated with the rate of distraction. These results indicate that myelinated nerve fibers adapt to gradual elongation by lengthening each Schwann cell body, not by proliferation of Schwann cells.     

EFFECTS OF SARAFOTOXIN S6c ON RENAL HAEMODYNAMICS AND URINE FORMATION IN ANAESTHETIZED DOGS

1. The effects of sarafotoxin S6c (S6c), a selective endothelin ETB receptor agonist, on renal haemodynamics and urine formation were examined in anaesthetized dogs. 2. Intrarenal arterial infusion of S6c at a rate of 1 or 5 ng/kg per min produced a transient increase in renal blood flow (RBF), with no change in systemic blood pressure and heart rate; RBF then decreased gradually to below the basal value. There were significant and dose-dependent increases in urine flow and free water clearance and decreases in urine osmolality during S6c infusion, whereas urinary excretion of sodium and glomerular filtration rate (GFR) remained unchanged. Simultaneously, S6c administration elicited a marked increase in urinary excretion of nitric oxide (NO) metabolites, N0₂^? and N0₃^? (UNO*V). 3. In dogs simultaneously administered S6c (5 ng/kg per min) and iV^G-nitro-L-arginine (NOARG; 40 (jig/kg per min), a NO synthase inhibitor, the renal vasodilator effect of S6c was abolished and marked reductions in RBF and GFR were observed. The S6c-induced diuretic action was not affected by NOARG. In the presence of NOARG, there was a small amount of UNO_xV at the basal level and the administration of S6c did not increase UNOxV. 4. These results suggest that an intrarenal arterial infusion of S6c enhances the production of NO in the kidney and that this enhancement contributes to the peptide-induced renal vasodilation. In contrast, it is unlikely that S6c-induced water diuresis is related to NO production stimulated by this peptide.     

Cloning and analysis of a gene (sms13) encoding sannamycin B-glycyltransferase from Streptomyces sannanensis and its distribution among actinomycetes.

A gene encoding sannamycin B-glycyltransferase (sms13) of Streptomyces sannanensis IFO 14239 was identified by cloning and complementation of S. sannanensis mutant SN13 which is blocked at the interconversion of sannamycins B and A. The cloned DNA fragment also permitted the conversion of fortimicin B to A both in S. sannanensis SN13 and Streptomyces lividans TK23. DNA sequences similar to sms13 were detected in all five producers of the fortimicin-group antibiotics, Micromonospora olivasterospora ATCC 21819 (fortimicin-producer), Micromonospora sp. strain SF-2098 ATCC 31580 (SF-2052), Dactylosporangium matsuzakiense ATCC 31570 (dactimicin), Streptomyces tenjimariensis ATCC 31603 (istamycin), and Saccharopolyspora hirsuta ATCC 20501 (sporaricin). This suggests that these genes of similar function from different genera were derived from a common ancestral gene.     

Evidence for a glycosaminoglycan on the nudel protein important for dorsoventral patterning of the drosophila embryo.

Dorsoventral patterning of the Drosophila embryo requires Nudel, a large mosaic protein with a protease domain. Previous studies have implicated Nudel's protease domain as the trigger of a proteolytic cascade that activates the Toll signaling pathway to establish dorsoventral polarity in the embryo. However, the function of other regions of Nudel has been unclear. By using two-dimensional gel electrophoresis and site-directed mutagenesis, we have obtained evidence that the N-terminal region of Nudel contains a site for glycosaminoglycan (GAG) attachment that is required for dorsoventral patterning. Disruption of this site blocks a disulfide-based association between N- and C-terminal Nudel polypeptides and proteolytic activation of Nudel's protease domain. We discuss how a GAG chain on Nudel might be required for Nudel protease activation.     

Simulation for population analysis of Michaelis-Menten elimination kinetics

A simulation study was conducted to compare the cost and performance of various models for population analysis of the steady state pharmacokinetic data arising from a one-compartment model with Michaelis-Menten elimination. The usual Michaelis-Menten model (MM) and its variants provide no estimate of the volume of distribution, and generally give poor estimates of the maximal elimination rate and the Michaelis-Menten constant. The exact solution to the Michaelis-Menten differential equation (TRUE) requires a precise analysis method designed for estimation of population pharmacokinetic parameters (the first-order conditional estimation method) and also considerable computational time to estimate population mean parameters accurately. The one-compartment model with dose-dependent clearance (DDCL), in conjunction with the first-order conditional estimation or Laplacian method, ran approximately 20-fold faster than TRUE and gave accurate population mean parameters for a drug having a long biological half-life relative to the dosing interval. These findings suggest that the well-known MM and its variants should be used carefully for the analysis of blood concentrations of a drug with Michaelis-Menten elimination kinetics, and that TRUE, in conjunction with a precise analysis method, should be considered for estimating population pharmacokinetic parameters. In addition, DDCL is a promising alternative to TRUE with respect to computation time, when the dosing interval is short relative to the biological half-life of a drug. This work was supported in part by the Epilepsy Research Foundation, the Nakatomi Foundation, and a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture of Japan.     

Collagen abnormalities in the spinal cord from patients with amyotrophic lateral sclerosis

During the last 10 years, we have demonstrated morphological and biochemical abnormalities of skin extracellular matrices in amyotrophic lateral sclerosis (ALS). However, currently little is known concerning collagen of the spinal cord in ALS. We measured the amount of collagen and characterized collagen at light and electron microscopic levels in posterior funiculus, posterior half of lateral funiculus and anterior horn of cervical enlargement of the spinal cord obtained from ten patients with ALS, 11 patients with other neurologic diseases (control group A), and ten patients without neurologic ones (control group B). In posterior half of lateral funiculus and anterior horn, (1) by light microscopy, there was no significant difference in vessel wall area between ALS patients and control groups A and B; (2) ultrastructurally, collagen bundles were more fragmented and widely separated, and the fibrils were randomly oriented in the perivascular space of capillaries in ALS patients, which were not observed in any areas of control groups or in posterior funiculus of ALS patients; and (3) the collagen contents in ALS were significantly lower (P<0.001 and P<0.001, respectively) than those in control groups A and B. Fragmented and widely separated collagen bundles in the interstitial tissue surrounding capillaries and markedly decreased amount of collagen in posterior half of lateral funiculus and in anterior horn of ALS could be related to the degeneration of the upper and lower motor neurons in the spinal cord in ALS, that is, selective neuronal vulnerability in ALS.