The biomechanical and morphological changes in the medial collateral ligament of the rabbit after immobilization and remobilization

The effects of immobilization and remobilization on the biomechanical and morphological properties of the femur-medial collateral ligament-tibia complex and each of its components were investigated in the rabbit. Specimens that had been obtained after periods of unilateral immobilization of the knee and remobilization were evaluated for structural properties. In addition, the mechanical properties of the substance of the medial collateral ligament and the histological characteristics of both the substance of the ligament and its sites of insertion were evaluated. After immobilization, there were significant reductions in the ultimate load and energy-absorbing capabilities of the bone-ligament complex, and an increased number of failures occurred by tibial avulsion. The tissue of the medial collateral ligament also became less stiff as a result of immobilization. Histologically, the femoral and tibial insertion sites showed increased osteoclastic activity, resorption of bone, and disruption of the normal attachment of the bone to the ligament. With remobilization, the ultimate load and energy-absorbing capabilities of the bone-ligament complex improved but did not return to normal. Failure by tibial avulsion became less frequent, and the stress-strain characteristics of the medial collateral ligament returned to normal. Histologically, the sites of insertion of the ligament also showed evidence of recovery.     

A learned odor decreases the number of Fos-immunopositive granule cells in the olfactory bulb of young rats

Olfactory stimulation evokes a column of activity within the olfactory bulb extending from the glomerular layer to the granule cell layer that can be visualized with 2-deoxyglucose autoradiography, optical imaging, Fos protein immunohistochemistry and c-fos mRNA in situ hybridization. The Fos response to odors is typified by the activity of relatively few juxtaglomerular cells, which often occur in foci, and a large number of granule cells extending through much of the bulb. In this study, we characterized the granule cell response to an odor for which young rats had acquired a preference. Fos-like immunoreactive granule cells were quantified by image analysis, and densely stained cells were counted in a region previously shown to be responsive to peppermint odor. We found that odor-trained pups have about half the number of Fos-immunopositive superficial granule cells which respond to a learned odor than do control pups. We then determined whether there was a correlation between the juxtaglomerular cell response and the response of the superficial granule cells deep to those glomerular layer cells. We found a positive correlation between the number of juxtaglomerular cells and the number of granule cells demonstrating Fos immunoreactivity in both control and trained pups, a relationship that changed with early olfactory training.     

VESICO-URETERIC REFLUX AND SURGICALLY TREATED PELVI-URETERIC JUNCTION OBSTRUCTION IN INFANTS UNDER THE AGE OF 12 MONTHS

Background : Pelvi-ureteric junction obstruction has been increasingly diagnosed in infants, mostly as a consequence of antenatal ultrasound examinations. Methods : Of 55 infants below the age of 12 months who underwent dismembered pyeloplasty over a 7-year period, we aimed to determine the patterns and outcome of associated vesico-ureteric reflux that was present in 15 (28%) of the 53 infants in whom follow-up was available. Results : A total of eight infants had resolution of their reflux with conservative management and the median time to resolution was 15 months. Five infants proceeded to ureteroneocystotomy. Conclusions : Given the association of vesico-ureteric reflux and pelvi-ureteric junction obstruction, routine cystography is recommended when the diagnosis of pelvi-ureteric junction obstruction is made.     

Extensive Aberrant Mongolian Spot

A 9-month-old male infant had generalized diffuse blue-gray pigmentation over most of his body, sparing the scalp, face, neck, palms, soles, periumbilical area, genital area, and nipples. Within the lesion, there were several conspicuous macules of considerably darker hue. Histologic examination revealed numerous dermal melanocytes. By 16 months of age, the child's blue-gray pigmentation had decreased substantially.     

Pharmacology of glutamate neurotoxicity in cortical cell culture: attenuation by NMDA antagonists

The antagonist pharmacology of glutamate neurotoxicity was quantitatively examined in murine cortical cell cultures. Addition of 1-3 mM DL-2-amino-5-phosphonovalerate (APV), or its active isomer D-APV, acutely to the exposure solution selectively blocked the neuroexcitation and neuronal cell selectively blocked the neuroexcitation and neuronal cell loss produced by N-methyl-D-aspartate (NMDA), with relatively little effect on that produced by either kainate or quisqualate. As expected, this selective NMDA receptor blockade only partially reduced the neuroexcitation or acute neuronal swelling produced by the broad-spectrum agonist glutamate; surprisingly, however, this blockade was sufficient to reduce glutamate-induced neuronal cell loss markedly. Lower concentrations of APV or D-APV had much less protective effect, suggesting that the blockade of a large number of NMDA receptors was required to acutely antagonize glutamate neurotoxicity. This requirement may be caused by the amplification of small amounts of acute glutamate-induced injury by subsequent release of endogenous NMDA agonists from injured neurons, as the "late" addition of 10-1000 microM APV or D-APV (after termination of glutamate exposure) also reduced resultant neuronal damage. If APV or D-APV were present both during and after glutamate exposure, a summation dose-protection relationship was obtained, showing substantial protective efficacy at low micromolar antagonist concentrations. Screening of several other excitatory amino acid antagonists confirmed that the ability to antagonize glutamate neurotoxicity might correlate with ability to block NMDA-induced neuroexcitation: The reported NMDA antagonists ketamine and DL-2-amino-7-phosphono-heptanoate, as well as the broad-spectrum antagonist kynurenate, were all found to attenuate glutamate neurotoxicity substantially; whereas gamma-D-glutamylaminomethyl sulfonate and L-glutamate diethyl ester, compounds reported to block predominantly quisqualate or kainate receptors, did not affect glutamate neurotoxicity. The present study suggests that glutamate neurotoxicity may be predominantly mediated by the activation of the NMDA subclass of glutamate receptors--occurring both directly, during exposure to exogenous compound, and indirectly, due to the subsequent release of endogenous NMDA agonists. Given other studies linking NMDA receptors to channels with unusually high calcium permeability, this suggestion is consistent with previous data showing that glutamate neurotoxicity depends heavily on extracellular calcium.     

GABAergic neocortical neurons are resistant to NMDA receptor-mediated injury

N-methyl-D-aspartate (NMDA) receptors are thought to mediate much of the central neuronal loss produced by certain neurologic insults, including hypoxia-ischemia, hypoglycemia, and trauma. Therefore, the specific vulnerability of GABAergic inhibitory neurons to NMDA receptor-mediated toxicity might be an important determinant of the potential for epileptogenesis following these insults. We have examined the fate of GABAergic cortical neurons in mouse cell cultured neuronal population) were identified either by immunoreactivity with antisera to GABA or by autoradiography following high-affinity uptake of 3H-GABA. Cultures exposed for 5 min to 20 to 750 microM NMDA showed NMDA concentration-dependent, widespread neuronal loss. However, GABAergic neurons were relatively spared, and thus represented an enhanced fraction of neuronal survivors. These observations suggest that GABAergic cortical neurons may possess some intrinsic resistance to NMDA receptor-mediated neurotoxicity, a property which might convey an anticonvulsant "inhibitory safety factor" to neocortex against certain forms of injury.     

Comparative analysis of NK/T-cell lymphoma and peripheral T-cell lymphoma in Korea: Clinicopathological correlations and analysis of EBV strain type and 30-bp deletion variant LMP1

Natural killer/T-cell lymphoma (NKTL) and peripheral T-cell lymphomas (PTCL) are prevalent in the Asian population and exhibit a high association with the Epstein-Barr virus (EBV). Moreover, differentiation of these two groups is often difficult and problematic. We investigated 35 cases of NKTL (22 nasal cases and 13 extranasal cases) and 30 cases of PTCL in terms of their clinical features, immunohistology, EBV positivity, EBV strain-type polymorphism and latent membrane protein 1 (LMP1) deletion variant distribution. Eighteen cases (82%) of nasal NKTL and seven (54%) of extranasal NKTL showed EBV positivity by EBV in situ hybridization. Fifteen cases (50%) of PTCL revealed EBV positivity. EBV strain type A was predominant in NKTL (18:5), and EBV strain types A and B were distributed evenly in PTCL (6:6). EBV-positive patients had significantly shorter survival than EBV-negative patients (P < 0.05), and EBV positivity correlated with advanced clinical stage (P < 0.05). Patients harboring type A EBV showed slightly poorer prognoses than those having type B, though it was not obviously statistically different (P = 0.07). The LMP1 deletion variant was prevalent in both NKTL (three wild-type LMP1, 15 deletion variants) and PTCL (three wild-type LMP1, eight deletion variants, two coexistent forms) patients, but did not have prognostic impact. Our results indicate that EBV acts as a negative prognostic factor in NKTL and PTCL, and that the intrinsic properties of a specific viral strain might influence the clinical behavior of these diseases.     

Haplotypes and mutations of the PAH locus in Egyptian families with PKU

A high degree of molecular heterogeneneity at the phenylalanine hydroxylase (PAH) locus was established by examining RFLP haplotypes and PAH mutations in the families of 13 Egyptians with phenylketenouria (PKU). Thirteen different haplotypes were unequivocally determined in these kindreds. Haplotypes 1.8, 3.9, 4.3, 7.8, 22.11, 27.6, and 52.8 were found segregating with normal chromosomes, whilst haplotypes 1.8, 5.9, 23.8, 32.8, the newly assigned 73.9, and two as yet incomplete but novel haplotypes were found segregating with the mutant chromosomes. There was no particular preference for a single haplotype among normal or mutant chromosomes. Nine different mutations were also identified among the 26 alleles. IVS 10nt11g (8/26), IVS 2nt5g-c (4/26), R261Q (3/26), R176X (2/26), Y206D (2/26), S231P (2/26), Y198fs [593-614del22bp]; (2/26), G46fs [136/137delG]; (1/26), and E178G (1/26). Six of these mutations (IVS 2nt5g-c, R176X, Y198fs, R261Q, S231P, and IVS 10nt11g) are common to other Mediterranean populations. Two mutations not previously reported in the Mediterranean basin were also observed (Y206D and G46fs). These intriguing preliminary findings confirm IVS 10nt11g as a major mutation among Mediterranean mutations and demonstrate the need for a more comprehensive study of Arab populations to confirm the uniqueness of the two novel mutations to the Egyptian population.     

Hot spot mutations in morphological transforming region II (ORF 79) of cytomegalovirus strains causing disease from bone marrow transplant recipients

Summary.  Nested polymerase chain reaction (PCR) amplifying the morphological transforming region II (mtrII) of cytomegalovirus (CMV) has been shown to be useful in the detection of CMV DNA in bone marrow transplant (BMT) recipients. However, there has never been any report on mutation hot spots and subtypes of this open reading frame. Using primers derived from sequences upstream and downstream of mtrII (ORF 79), CMV DNA from peripheral blood leukocytes (PBL) and conventional CMV culture of 16 BMT recipients were amplified by PCR, cloned into pUC118, and sequenced. The amino acid sequences were predicted using the standard triplet code. The DNA sequences obtained from direct amplification of CMV in PBL obtained from the 16 patients were 100% identical to the corresponding ones obtained by amplification of CMV DNA extracted from conventional CMV culture. Within mtrII (ORF 79), hot spot single base mutations were observed at positions +40 (G→A), +123 (A→G), +213 (T→C), and +219 (T→C). However, because of third base degeneracy, only amino acid 14 was changed from valine to isoleucine in the predicted protein of 13 patients. This corresponded to the hot spot mutation at position +40 (GTC→ATC), while the rest were silent mutations. An insertion of 3 bases (ACG) was observed in the CMV DNA of 10 patients at positions +91 to +93, leading to a threonine insertion at amino acid 31 in these patients. For patient no. 147 there was a 65 bp deletion in the CMV DNA amplified later in the course of BMT as compared with that early in the course. This gave rise to a frame shift mutation and a change of more than 70% in the predicted amino acid sequence of the protein. Accepted October 14, 1998 Received May 20, 1998