Lactase synthesis is pretranslationally regulated in protein-deficient pigs fed a protein-sufficient diet.

The in vivo effects of protein malnutrition and protein rehabilitation on lactase phlorizin hydrolase (LPH) synthesis were examined. Five-day-old pigs were fed isocaloric diets containing 10% (deficient, n = 12) or 24% (sufficient, n = 12) protein. After 4 wk, one-half of the animals in each dietary group were infused intravenously with [(13)C(1)]leucine for 6 h, and the jejunum was analyzed for enzyme activity, mRNA abundance, and LPH polypeptide isotopic enrichment. The remaining animals were fed the protein-sufficient diet for 1 wk, and the jejunum was analyzed. Jejunal mass and lactase enzyme activity per jejunum were significantly lower in protein-deficient vs. control animals but returned to normal with rehabilitation. Protein malnutrition did not affect LPH mRNA abundance relative to elongation factor-1alpha, but rehabilitation resulted in a significant increase in LPH mRNA relative abundance. Protein malnutrition significantly lowered the LPH fractional synthesis rate (FSR; %/day), whereas the FSR of LPH in rehabilitated and control animals was similar. These results suggest that protein malnutrition decreases LPH synthesis by altering posttranslational events, whereas the jejunum responds to rehabilitation by increasing LPH mRNA relative abundance, suggesting pretranslational regulation.

Are we ordering too many PSA tests? Prostate cancer diagnosis and PSA screening patterns for a single Veterans Affairs Medical Center.

BACKGROUND: Limits on the frequency of PSA testing and an endpoint for the age of the screened population have not been established. The numbers of performed serum PSA tests, cost evolution, and utilization patterns by various subspecialties in one medical center were analyzed to gain insight into trends in screening for early detection of prostate cancer and gather information about the appropriate use of PSA testing. METHOD: Computerized records were reviewed for numbers of PSA tests obtained, prostate biopsies performed, and prostate cancer cases diagnosed in the VA NJ-Health Care System from 1996 to 1998. In addition, PSA tests performed during two representative weeks in 1996 and 1997 were analyzed to evaluate a smaller cohort of patients with regard to age, consequences of the test results in their management, and subspecialties ordering the tests. RESULTS: PSA testing increased steadily between 1992 and 1998, with the most significant change (152% increase) between 1997 (9,410 tests) and 1998 (23,684). Prostate cancer diagnoses by biopsy were 164/434 (37.8%) in 1997 and 195/507 (38.5%) in 1998. For the 14,274 additional PSA tests obtained in 1998, 31 more prostate cancers were diagnosed. Prostate cancer diagnoses per PSA tests were 164/9,410 (1.8%) in 1997 and 195/23,684 (0.8%) in 1998. Primary care providers ordered 61% of the PSA tests. CONCLUSIONS: Most PSA tests at this institution were ordered by general practitioners, and the number of PSA tests ordered for men over 75 was high. The dramatic increase between 1997 and 1998 was not accompanied by a similar rise in the diagnosis of prostate cancer, raising the possibility of indiscriminate PSA testing or unnecessary repetition of testing. Guidelines for prostate cancer screening and continued PSA testing in the geriatric population may need further clarification.

Parenteral nutrition selectively decreases protein synthesis in the small intestine.

We investigated the effects of an elemental diet fed parenterally or enterally on total mucosal protein and lactase phlorizin hydrolase (LPH) synthesis. Catheters were placed in the stomach, jugular vein, and carotid artery of 12 3-day-old pigs. Half of the animals were given an elemental regimen enterally and the other half parenterally. Six days later, animals were infused intravenously with [2H3]leucine for 6 h and killed, and the midjejunum of each animal was collected for analysis. The weight of the midjejunum was 8 +/- 1.5 and 17 +/- 1.6 g in parenterally fed and enterally fed piglets, respectively. LPH activities (mumol.min-1.g protein-1) were significantly higher in parenterally vs. enterally fed piglets. Total small intestinal LPH activities were lower in parenterally vs. enterally fed animals. The abundance of LPH mRNA relative to elongation factor-1 alpha mRNA was not different between groups. The fractional synthesis rate of total mucosal protein and LPH was significantly lower in parenterally fed animals (67 +/- 7 and 66 +/- 7%/day, respectively) than in enterally fed animals (96 +/- 7 and 90 +/- 6%/day, respectively). The absolute synthesis rate (the amount of protein synthesized per gram of mucosa) of total mucosal protein was significantly lower in parenterally fed than in enterally fed piglets. However, the absolute synthesis rate of LPH was unaffected by the route of nutrient administration. These results suggest that the small intestine partially compensates for the effects of parenteral feeding by maintaining the absolute synthesis rate of LPH at the same levels as in enterally fed animals.

Lactase phlorizin hydrolase synthesis is decreased in protein-malnourished pigs.

We have examined the effect of protein malnutrition on brush border (BB) lactase phlorizin hydrolase (LPH) synthesis in young pigs. Two groups of four 3-wk-old pigs were fed diets containing either 19 g soy protein, 63 g carbohydrate and 5 g fat per 100 g diet (a protein-sufficient diet) or 3 g soy protein, 85 g carbohydrate and 5 g fat per 100 g diet (a protein-deficient diet). After 8 wk of consuming the diets, pigs were infused intravenously with 2H3-leucine for 8 h, then killed. The jejunum was collected for measurement of lactase activity, LPH mRNA abundance and the rate of LPH post-translational synthesis. Lactase activities did not differ between groups (mean 8.1 +/- 1.2 micromol x min(-1) x g mucosa(-1)). LPH mRNA abundance relative to elongation factor-1alpha mRNA (the constitutive/reference mRNA) was significantly (P < 0.05) higher in well-nourished pigs (0.36 +/- 0.03%) than in protein-malnourished pigs (0.21 +/- 0.02%). The rate constants of BB LPH post-translational synthesis were also significantly higher in the well-nourished (103 +/- 9% x d(-1)) than in the protein-malnourished pigs (66 +/- 8% x d(-1)). Further, the absolute synthesis rate of BB LPH, a measure of the amount of enzyme synthesized per gram of tissue, was significantly higher in well-nourished than in protein-malnourished pigs (in arbitrary units, 892 +/- 90 vs. 450 +/- 34, respectively). Thus, protein malnutrition affects both LPH mRNA abundance and post-translational processing in young pigs.

Time-dependent variability of infarct size and hemispheric volume in experimental focal cerebral ischemia in the rabbit.

Studies measuring the volume of infarcted tissue and survival after pharmacologic intervention in stroke are complicated by the potential effect of survival time on infarct volume. In this study, the volume of infarcted tissue as defined by 2,3,5-triphenyltetrazolium chloride staining was determined in rabbits at 28 h, 7 days, and 3 weeks after permanent middle cerebral artery occlusion. Compared to values at 28 h, infarcted tissue volume did not change at 7 days after occlusion, but decreased significantly by three weeks after occlusion (p < 0.01). Infarcted tissue volume expressed as a percent of hemispheric volume did not significantly change at either timepoint (p < 0.08). Immunocytochemical staining for glial fibrillary acidic protein (GFAP) indicated that infarct volume changes were not due to glial infiltration. Total hemispheric volume decreased by 7 days (p < 0.01) and 3 weeks (p < 0.01) after occlusion. These results suggest that changes in hemispheric volume may confound comparison of injury volumes in animals at differing times after occlusion. In experiments where drug treatments increase survival after focal cerebral ischemia, comparisons of the absolute infarct volume may not be valid if drug-treated animals survive greater than 1 week and untreated animals do not.

The duration of medium-chain triglyceride feeding determines brush border membrane lipid composition and hydrolase activity in newly weaned rats.

To better understand the effect of dietary fat on intestinal brush border (BB) membranes in the young animal, we compared the effect of dietary medium-chain triglycerides (MCT) with that of monounsaturated and saturated long-chain triglycerides (LCT) on jejunal brush border membrane lipid composition and hydrolase activity in newly weaned rats. Twenty-day-old rat pups were divided into three groups and were weaned to diets containing 14% MCT + 6% soybean oil, 18% olive oil + 2% soybean oil, or 14% tallow + 6% soybean oil, and fed for 40 h or for 33 d. The diets were isonitrogenous and contained similar amounts of cholesterol and polyunsaturated fatty acids. Within 40 h, the fatty acid compositions of the brush border membranes were significantly different among treatment groups. These differences were maintained in rats fed for 33 d. No medium-chain fatty acids, but significantly greater amounts of polyunsaturated fatty acids, especially 18:2(n-6) and 20:4(n-6), were found in the brush border membranes of rats fed the medium-chain triglyceride diet. The cholesterol and phospholipid concentrations in the membranes were highest in rats fed the medium-chain triglyceride diet for 33 d. Rats fed that diet for 40 h had generally higher leucine aminopeptidase, sucrase and maltase activities compared with rats fed the olive oil or tallow diets. However, after 33 d of feeding, the differences between dietary treatment groups disappeared. This study demonstrates that, in the newly weaned rat pup, dietary medium-chain triglycerides and long-chain triglycerides rapidly affect the fatty acid composition of the brush border membrane. However, the changes in the hydrolase activities associated with the changes in the lipid composition of the membranes are transient.

The effect of long-term high-dose naloxone infusion in experimental blunt spinal cord injury.

The effect of long-term continuous subcutaneous infusion of naloxone on blunt spinal cord injury in the rat was assessed using four tests of neurological function, seven histological categories, and two electrophysiological measures. All four neurological function tests showed a trend toward improvement in naloxone-treated animals: the degree of improvement was statistically significant in two of the four categories. A significant reduction in myelin sheath edema was found in the naloxone-treated animals. Although there was a decrease in corticomotor-evoked potentials complexity following injury, there was no significant difference in naloxone-treated animals. Somatosensory-evoked potentials were significantly increased in amplitude and latency in naloxone-treated animals. This increase was most apparent at 60 min: no difference was found by 3 weeks postinjury. These results confirm earlier reports that naloxone can ameliorate the functional neurological deficits of spinal cord injury. Naloxone also produces alterations in the somatosensory-evoked responses in the early phase of treatment and significantly reduces myelin sheath edema.

The influence of long-term nifedipine or indomethacin therapy on neurologic recovery from experimental spinal cord injury.

Inhibition of prostaglandin pathways and calcium channel conduction has been shown to improve neurological outcome after spinal cord injury. Functional recovery from such intervention has been routinely evaluated by a simple motor examination or somatosensory evoked potentials (SSEPs) after short-term drug administration. We comprehensively evaluated the influence of continuously administered indomethacin and nifedipine on functional outcome after impact spinal cord injury. SSEP and cortico-motor evoked potential records and neurologic examinations were obtained over 6 weeks after injury. Terminal histopathologic changes within the spinal cord were also examined. Only indomethacin significantly improved neurological function and reduced the severity of histopathologic change. Evoked potential analysis was not found to be of prognostic value. Modulation of prostaglandin pathways may enhance neurological recovery after spinal cord injury.

Crisis in sickle cell trait.

A 34-year-old black male with hemoglobin AS was admitted for renal failure, polydipsia, hypertension, schizophrenia, mental confusion, and visual hallucinations. Abnormal electrolytes were corrected by dialysis, but blood specimens were reported as hemolyzed with hyperkalemia. Peaked T waves on electrocardiographic analysis were followed by cardiac arrest. An autopsy revealed sickled cells in the visual cortex and other symptomatic organs, but normal erythrocytes in most of the vascular tree. These findings suggest true progressive sickle cell crisis in a hemoglobin AS patient.

Increased incidence of monoclonal gammopathy of undetermined significance in blacks and its age-related differences with whites on the basis of a study of 397 men and one woman in a hospital setting.

Serum samples from 398 individuals (270 whites and 128 blacks) exhibiting quantitatively normal amounts of five typically seen fractions (albumin, alpha 1-globulin, alpha 2-globulin, beta-globulin, and gamma-globulin) in serum protein electrophoresis and showing no evidence of multiple myeloma, other immunoproliferative diseases, or any of the other diseases known to produce monoclonal proteins were tested for monoclonal gammopathy of undetermined significance (MGUS) by immunofixation electrophoresis. No individual in the study had a serum protein electrophoresis pattern suggestive of monoclonal protein gammopathy. Except for one 37-year-old woman, all subjects were men. Subjects were divided into seven age groups: 20 to 29 years (I), 30 to 39 years (II), 40 to 49 years (III), 50 to 59 years (IV), 60 to 69 years (V), 70 to 79 years (VI), and all over 79 years (VII) of age. Considering all subjects in a given race, blacks had two times (14.8%) higher incidence of MGUS than whites (7.8%); this difference was statistically significant. An increased incidence of MGUS in blacks when compared with whites prevailed in each age group, and the difference was statistically significant in all age groups except group II. No MGUS was found in groups I and III in either race. Both races showed a threefold increase in incidence of MGUS from group II to group VII. No routine laboratory test such as erythrocyte sedimentation rate in subjects with MGUS was significantly different than that in age- and race-matched individuals without MGUS. These results show that the incidence of MGUS is higher in the group (blacks) also known to have a higher prevalence of multiple myeloma.

Immunohistochemical characterization of pulmonary blastoma.

The immunohistochemical staining patterns of three pulmonary blastomas (PBs) were studied for markers of mesenchymal (vimentin, muscle-specific actin) and epithelial (cytokeratin, epithelial membrane antigen) differentiation to clarify their phenotypic nature and, possibly, their histogenesis. Epithelial markers were confined to the tubular component of the tumors, and the mesenchymal markers were confined to the stromal component, demonstrating that PBs are true mixed tumors. These findings are consistent with origin from a primitive pluripotential stem cell but do not rule out derivation from a single germ layer with subsequent metaplastic transformation.

Quadriceps Insufficiency following Repair of the Anterior Cruciate Ligament*.

This study was originally presented at the American College of Sports Medicine annual meeting in San Diego, CA, 1984. Following repair of the anterior cruciate ligament, it is fairly typical for a patient to return to activity at approximately 12 months postsurgery. The purpose of the study was to quantify quadriceps size and function at 1 year postsurgery. Bilateral isokinetic torque measurements, tomographic scans, muscle biopsies, and anthropometrics were performed on 13 patients (3 females, 10 males) at 13 months post-surgery. The operative leg was 3% smaller in circumference, 10% smaller in total muscle area, 12% smaller in quadriceps area (all p < 0.05) and had a 9% larger subcutaneous fat area (p = 0.06). No difference in hamstrings area was seen. Isokinetic torques for the quadriceps were reduced by 11-15% in the operative leg (p < .05) with no difference seen between the hamstrings torques. Types I and II fibers were clinically smaller in both legs with the type II fibers being significantly (p < 0.05) reduced in the operative leg. It was concluded that 1) leg circumference was a poor indicator of muscle size due to the selective fat deposition in the operative leg, 2) the cross-sectional area of muscle was proportional to isokinetic torque at 240/sec, and 3) there were clinically and statistically significant isokinetic torque differences between quadriceps 13 months post-surgery.J Orthop Sports Phys Ther 1988;9(7):245-249.

Cerebral vasculitis in relapsing polychondritis.

Recurrent inflammation of cartilage in multiple sites is a hallmark of relapsing polychondritis (RP). Neurologic complications of this disease have begun to attract increasing attention, but the neuropathologic basis of these complications has not been described. We report a patient with RP whose autopsy showed extensive cerebral and systemic vasculitis.

Colloid (hyaline) inclusion bodies in the central nervous system: their presence in the substantia nigra is diagnostic of Parkinson's disease.

Intracytoplasmic "colloid" inclusions have been described within neurons of several discrete central nervous system nuclei in a variety of entities. Although they lack specificity for any particular disease, they are believed to represent one of the morphologic changes of neuronal aging. Because premature aging of the substantia nigra has been one of the claimed mechanisms occurring in Parkinson's disease, the prevalence of colloid inclusions was studied within the substantia nigra in 15 patients with Parkinson's disease, 15 age-matched controls, 50 "normal" individuals, 10 patients with dementia of Alzheimer's type, and two patients with amyotrophic lateral sclerosis. Colloid bodies were found in the substantia nigra of all patients with Parkinson's disease and were virtually absent in the other populations. Histochemical and ultrastructural analyses showed that colloid bodies differ from early and mature Lewy bodies. They may represent the "pale" inclusions rarely mentioned in the literature and often mistaken for early Lewy bodies. "Colloid" bodies in the substantia nigra are diagnostic of Parkinson's disease. These findings support the theory of "premature" aging of the substantia nigra in this disease.

The intranuclear cleft of the intervertebral disk: magnetic resonance imaging.

Three cadaver spines, 40 patients who were symptomatic for lumbar disk disease, and ten healthy subjects were examined by MR. T2 weighted spin echo images were used to evaluate the character of an intranuclear cleft. This cleft appears identical to annular tissue both on T2 weighted images and histologically. A 120 msec TE, 3 sec TR image was used to delimit the normal nucleus pulposus from the annulus. The incidence and age distribution of the cleft were calculated. An intranuclear cleft was present in all normal disks in both control and symptomatic subjects who were 30 years of age and older. If present in one disk, it was also present in 94% of the other disks in the same subject. This cleft represents a normal anatomic structure and appears to be a constant feature in subjects 30 years of age or older. Its absence, in the presence of an increased signal intensity within the disk, suggests a pathological process with a long T2 value, such as inflammation.

Magnetic resonance of brain tumors: considerations of imaging contrast on the basis of relaxation measurements.

Proton spin-lattice and spin-spin relaxation times have been measured in surgically-removed normal CNS tissues and a variety of tumors of the brain. All measurements were made at 20 MHz and 37 degrees C. Between grey and white matter from autopsy human or canine specimens significant differences in T1 or T2 were observed, with greater differences seen in T1. Such discrimination was reduced in samples obtained from live brain-tumor patients due to lengthening in T1 and T2 of white matter near tumorous lesions. Edematous white matter showed T1 and T2 values higher than those of autopsy disease-free white matter. Compared to normal CNS tissues, most brain tumors examined in this study demonstrated elevated T1 and T2 values. Exceptions, however, did exist. No definitive correlation was indicated on a T1 or T2 basis which allowed a distinction to be made between benign and malignant states. Furthermore, considerable variation in relaxation times occurred from tumor to tumor of the same type, suggesting that within a tumor type there are important differences in physiology, biology, and/or pathologic state. Such variation caused partial overlap in relaxation times among certain tumor types and hence may limit the capability of magnetic resonance imaging (MR) alone for the diagnosis of specific disease. Nonetheless, this study predicts that on the basis of T1 or T2 differences most brain tumors are readily detectable by MR via saturation recovery or inversion recovery with appropriate selections of pulse-spacing parameters. In general, tumors can be discriminated against white matter better than grey matter and contrast between glioma and grey matter is usually superior to that between meningioma and grey matter. This work did not consider tissue-associated proton density which should be addressed together with T1 and T2 for a complete treatment of MR contrast.

Neuropathologic changes following direct-current stimulation of the rat sciatic nerve.

Peripheral nerve stimulators can be of value in surgical dissections. Recent investigations have questioned the safety of direct-current nerve stimulators, while verifying the safety of pulsed-current nerve stimulators. However, the studies failed to adequately simulate the routine clinical setting in which a nerve stimulator was used. Therefore, an experiment was designed to approximate as closely as possible--given the limitations of the animal model--the use of a direct-current peripheral nerve stimulator in a surgical dissection. The results of this study did not show a difference between experimental and control groups. We conclude that direct-current nerve stimulation is safe when used judiciously and appropriately.