Involvement of 4-hydroxymandelic acid in the degradation of mandelic acid by Pseudomonas convexa

A microorganism capable of degrading DL-mandelic acid was isolated from sewage sediment of enrichment culture and was identified as Pseudomonas convexa. It was found to metabolize mandelic acid by a new pathway involving 4-hydroxymandelic acid, 4-hydroxybenzaldehyde, 4-hydroxybenzoic acid, and 3,4-dihydroxybenzoic acid as aromatic intermediates. All the enzymes of the pathway were demonstrated in cell-free extracts. L-Mandelate-4-hydroxylase, a soluble enzyme, requires tetrahydropteridine, nicotinamide adenine dinucleotide phosphate, reduced form, and Fe2+ for its activity. The next enzyme, L-4-hydroxymandelate oxidase (decarboxylating), a particulate enzyme, requires flavine adenine dinucleotide and Mn2+ for its activity. A nicotinamide adenine dinucleotide-dependent, as well as a nicotinamide adenine dinucleotide phosphate-dependent, benzaldehyde dehydrogenase has been resolved and partially purified.     

Dependence of centriole formation on protein synthesis

Electron microscope observations were made of rat peroneal nerve after crushing using intravenously injected horseradish peroxidase (HRP) as a tracer protein to indicate changes in vascular permeability. At 1/2 h and 2 d after the crush there was gross leakage of HRP from damaged capillaries at the site of injury but none from vessels above or below this. Ultrastructurally vessels at the site of crush showed broken and separated endothelial cells. Proximally and distally there was little abnormal in the vessel walls; vesicles containing HRP were absent and tight-junctions between cells remained intact. Twenty-one days after the crush, leakage of HRP was found both at the site of crush and along the distal segment. The only change in vessel walls was an obvious increase in vesicles filled with HRP. Tracer was also found both in perivascular locations and throughout the endoneurial space.     

Acute renal failure in patients with acute pancreatitis

We describe five patients with acute pancreatitis in whom acute renal failure developed in the absence of hypotension. Pancreatitis was diagnosed clinically, with mean serum and urinary amylase levels of 766 +/- 197 (SE) and 2,378 +/- 572 units/100 ml, respectively. Acute renal failure developed within 24 hours after admission in all patients. It was manifested by oliguria, elevated levels of serum creatinine (mean, 6.9 +/- 1.1 mg/100 ml) and BUN (105 +/-28 mg/100 ml); a urinary sodium level of 72.0 +/- 6.6 mEq/liter; and isosmotic urine (355 +/- 31 mOsm/liter). The mean uric acid level was 18.6 +/- 1.6 mg/100 ml. Blood pressure was recorded frequently, and the lowest mean diastolic pressure was 96 +/- 6 mm Hg. The duration of the oliguric phase of acute renal failure was 8.2 +/- 1.7 days, and all patients recovered from both the acute pancreatitis and acute renal failure. In summary, acute pancreatitis, per se, can precipitate acute renal failure. It occurs early in the course of the pancreatitis, and extreme hyperuricemia is frequent finding that does not adversely affect the recovery of renal function.     

Emergent textural contours: a new technique for visual monitoring in nystagmus, oculomotor dysfunction, and accommodative disorders

Emergent textural contours, the perceptual effect seen during continuous rotation of symmetrical arrays of uniform pattern elements, provide a unique source of visual feedback for eye movements and resolutional states and have potential for use as a new clinical tool. The phenomenon is produced by a combination of factors including the effects of visual persistence and differential resolution. A total of 28 subjects including 17 normals, 4 nystagmus, 4 oculomotor dysfunction, and 3 accommodative facility cases were shown an emergent textural contour with an instrument (the Goldrich Contour Rotator) for its display. Subjects were enabled to monitor their own eye movements and accommodative training. Nystagmus subjects were provided with a continuous source of visual input reflecting their ocular oscillations and a determination of the null point of nystagmus was made with the instrument.     

Primary aortic mural thrombus: presentation and treatment

Schizophrenic patients are extremely heavy tobacco smokers. However, a lower incidence of lung cancer in schizophrenic patients has been observed in comparison to other heavy smokers. Nicotine increases the proliferation of pulmonary neuroendocrine tissue, causing the release of a bombesin-like peptide. Thus, bombesin-like peptide levels in urine may be an indicator of precancerous, cigarette-induced lung damage. Bombesin-like peptide levels of 10 schizophrenic smokers and 11 schizophrenic nonsmokers were compared to those of nonschizophrenic subjects matched for age and pack-years of smoking. The nonschizophrenic smokers showed the expected increase in urinary bombesin-like peptide levels, as compared to nonschizophrenic nonsmokers. Schizophrenic patients had lower bombesin-like peptide levels independent of smoking effects. The mechanism of the difference in bombesin-like peptide levels between schizophrenic patients and nonschizophrenic subjects is unknown, but one possibility involves alteration in the alpha 7-nicotinic acetylcholine receptor, which mediates the growth of some neuroendocrine cell lines in vitro.     

The role of voltage-gated Ca2+ channels in anoxic injury of spinal cord white matter

Dorsal column axons of the rat spinal cord are partially protected from anoxic injury following blockade of voltage-sensitive Na+ channels and the Na+/--Ca2+ exchanger. To examine the potential contribution of voltage-gated Ca2+ channels to anoxic injury of spinal cord axons, we studied axonal conduction in rat dorsal columns in vitro following a 60-min period of anoxia. Glass microelectrodes were used to record field potentials from the dorsal columns following distal local surface stimulation. Perfusion solutions containing blockers of voltage-gated Ca2+ channels were introduced 60 min prior to onset of anoxia and continued until 10 min after reoxygenation. Pharmacological blocking agents which are relatively selective for L- (verapamil, diltiazem, nifedipine) and N- (omega-conotoxin GVIA) type calcium channels were significantly protective against anoxia-induced loss of conduction, as was non-specific block using divalent cations. Other Ca2+ channel blockers (neomycin and omega-conotoxin MVIIC) that affect multiple Ca2+ channel types were also neuroprotective. Ni2+, which preferentially blocks R-type Ca2+ channels more than T-type channels, was also protective in a dose-dependent manner. These data suggest that the influx of Ca2+, through L-, N- and possibly R-type voltage-gated Ca2+ channels, participates in the pathophysiology of the Ca2+-mediated injury of spinal cord axons that is triggered by anoxia.     

Outcome of moderate carotid artery stenosis in patients who are asymptomatic

PURPOSE: The incidence rate of disease progression and stroke after the diagnosis of a moderate (50% to 79%) carotid stenosis was determined by means of color-flow duplex scanning. METHODS: During a 4-year period, 344 male veterans with moderate internal carotid artery stenoses, on one or both sides, were examined at regular intervals for a mean period of 25 months. Carotid color-flow scans were obtained semiannually. Clinical follow-up was performed to determine the incidence rate of amaurosis fugax, transient ischemic attacks, nonhemispheric symptoms, and strokes. RESULTS: New neurologic symptoms developed in 75 patients (21.8%). Fifty-one (14.8%) had ipsilateral symptoms during follow-up: 18 amaurosis fugax (5.2%), 14 transient ischemic attacks (4%), 5 nonhemispheric symptoms (1.4%), and 14 strokes (4%). Twenty-four patients (6.9%) had contralateral symptoms: 20 strokes (5.8%) and 4 transient ischemic attacks (1.2%). Life-table analysis showed that the annual rate of ipsilateral neurologic events was 8.1%, and the annual rate of stroke was 2.1%. Seventy-five patients (22%) died in the follow-up period. Disease progression to 80% to 99% stenosis or occlusion occurred in 71 of 458 vessels (15.5%). The internal carotid arteries that showed evidence of disease progression had a significantly higher initial peak systolic velocity (251 vs 190 cm/s; P <.0001) and end diastolic velocity (74 vs 52 cm/s; P < 0.0001). Black patients and patients with ischemic heart disease were at a higher risk for disease progression. We could not identify any atherosclerotic risk factors that reliably predicted patients in whom future ipsilateral neurologic symptoms were more likely to develop. However, there was an increased risk of stroke associated with progression of disease. CONCLUSION: Patients who are asymptomatic and who have moderate carotid stenoses are at significant risk for neurologic symptoms and death, but have a relatively low incidence rate of ipsilateral events. The initial flow characteristics in the stenotic vessel are predictive of future disease progression, but they are not helpful in identifying patients in whom symptoms will develop.     

A histomorphometric evaluation of heparin-induced bone loss after discontinuation of heparin treatment in rats

Although it is well established that long-term heparin therapy causes osteoporosis, it is unknown whether heparin-induced bone loss is reversible when heparin treatment is stopped. To address this question, we randomized rats to once daily subcutaneous injections of either unfractionated heparin (1.0 U/g or 0.5 U/g) or saline for 28 days and then followed the rats for an additional 28 days off treatment. Based on histomorphometric analysis of the distal third of the right femur proximal to the epiphyseal growth plate, 1.0 U/g heparin caused a 30% loss in cancellous bone volume over the first 28 days. This was accompanied by a 137% increase in osteoclast surface and a 60% decrease in both osteoblast and osteoid surface. One month after cessation of heparin treatment, no recovery in these parameters was observed. Similarly, serum levels of alkaline phosphatase, a biochemical marker of bone formation, which continued to decrease over the course of heparin treatment, showed no signs of recovery in the subsequent 28 days off treatment. To explore the mechanism responsible for the prolonged effect of heparin on bone, we repeated the experiment giving 125I-labeled heparin in place of unlabeled heparin. 125I-labeled heparin was found to accumulate in bone during the course of its administration, and be retained in bone for at least 56 days after stopping heparin treatment. These findings suggest that heparin-induced osteoporosis is not rapidly reversible because heparin is sequestered in bone for an extended period.     

Ability of lymphokine-activated killer cells to lyse mycobacteria-infected cells

In cats and monkeys, we examined the parasympathetic component of the oculomotor complex, which directly innervates the ciliary muscle, using horseradish peroxidase (HRP). Labeled neurons of varying form and size were found in the Edinger-Westphal(EW) and the Perlia nuclei of the cat and in the anteromedian, EW, and Perlia nuclei of the monkey. Our study confirmed that a direct parasympathetic pathway exists from the midbrain to the ciliary muscles, and that accommodation is controlled in part by this direct link from the midsagittal region via a parasympathetic neuron of the oculomotor nuclear complex.