Functional reorganization of primary somatosensory cortex in adult owl monkeys after behaviorally controlled tactile stimulation

1. Multiple microelectrode maps of the hand representation within and across the borders of cortical area 3b were obtained before, immediately after, or several weeks after a period of behaviorally controlled hand use. Owl monkeys were conditioned in a task that produced cutaneous stimulation of a limited sector of skin on the distal phalanges of one or more fingers. 2. Analysis of microelectrode mapping experiment data revealed that 1) stimulated skin surfaces were represented over expanded cortical areas. 2) Most of the cutaneous receptive fields recorded within these expanded cortical representational zones were unusually small. 3) The internal topography of representation of the stimulated and immediately surrounding skin surfaces differed greatly from that recorded in control experiments. Representational discontinuities emerged in this map region, and "hypercolumn" distances in this map sector were grossly abnormal. 4) Borders between the representations of individual digits and digit segments commonly shifted. 5) The functionally defined rostral border of area 3b shifted farther rostralward, manifesting either an expansion of the cutaneous area 3b fingertip representation into cortical field 3a or an emergence of a cutaneous input zone in the caudal aspect of this normally predominantly deep-receptor representational field. 6) Significant lateralward translocations of the borders between the representations of the hand and face were recorded in all cases. 7) The absolute locations--and in some cases the areas or magnifications--of representations of many skin surfaces not directly involved in the trained behavior also changed significantly. However, the most striking areal, positional, and topographic changes were related to the representations of the behaviorally stimulated skin in every studied monkey. 3. These experiments demonstrate that functional cortical remodeling of the S1 koniocortical field, area 3b, results from behavioral manipulations in normal adult owl monkeys. We hypothesize that these studies manifest operation of the basic adaptive cortical process(es) underlying cortical contributions to perception and learning.     

An investigation of Japanese subjects maps susceptibility to type 1 (insulin-dependent) diabetes mellitus close to the DQA1 gene.

Insulin-dependent diabetic and control subjects of Japanese origin were HLA-DRB1, -DQB1, and -DQA1 typed using restriction fragment length polymorphism analysis and sequence-specific oligonucleotide gene probing. The DQA1 allele DQA1*0301 was positively associated with the disease [48/52 (92%) diabetic patients versus 44/64 (69%) control subjects, Pc less than 0.03, RR = 4.97]. Alleles of the DRB1 and DQB1 genes showed no significant association with the disease. The frequency of DQB1 genotypes encoding the amino acid aspartic acid at position 57 of the DQ beta chain did not differ significantly between subjects with insulin-dependent diabetes mellitus (IDDM) and controls. These findings suggest that a susceptibility allele for IDDM in the Japanese is more closely associated with the DQA1 gene than the DQB1 gene.     

A cytogenetic study of 53 human gliomas

Cytogenetic studies were performed on human glioma samples obtained by stereotactic biopsy, stereotactic craniotomy, or routine craniotomy. Using in situ culture and robotic harvesting techniques, we obtained suitable metaphases in 50 (94%) of 53 tumors, including 28 diffuse astrocytomas, four juvenile pilocytic astrocytomas, two gliosarcomas, three other miscellaneous astrocytomas, eight oligodendrogliomas, four mixed oligodendroglioma-astrocytomas, and four ependymomas. Cytogenetic studies were performed only on primary cultures; the mean culture time was 9.6 days (range 1-31 days). One or more chromosomally abnormal clones were observed in 35 (66%) tumors. Eleven (21%) other specimens had random nonclonal chromosome abnormalities. In four (8%) specimens, no chromosome abnormalities were noted. The results of this study suggest that grade 3 and 4 tumors are more likely to contain an abnormal clone than tumors of grade 1 or 2 (p less than 0.01). The most common numeric chromosome abnormalities were -6, +7, -10, -13, -14, -15, -18, and -Y. The most common structural abnormalities involved 1p, 6q, 7q, 8p, 9p, 11p, 11q, 13q, and 19q. Four tumors had two or more independent clones and ten contained subclones demonstrating karyotype evolution. With in situ culture and robotic harvesting techniques, cytogenetic studies can be successful on nearly all human gliomas, including those derived from small stereotactic biopsies.     

Experience with prenatal fragile X detection

We have attempted the prenatal detection of the fra(X) 9 times. Three fra(X) positive fetuses have been diagnosed: 2 males and one female. The diagnosis on the 2 males has been confirmed. The testes of the 2 fra(X) positive fetuses appeared large for gestational age. However, results of anthropometric, bone age, anatomical and neurohistological studies were normal. Normal outcome was confirmed after birth in 2 males and one female on the basis of whole blood fra(X) studies. A presumptively positive female and a presumptively negative female await confirmation. Two presumptively negative males remain unborn. Further experience is needed to establish the reliability of the prenatal detection of fra(X) (q27).     

Methylation alterations of the MyoD1 upstream region are predictive of subclassification of human rhabdomyosarcomas.

MyoD1 expression is a distinguishing characteristic of rhabdomyosarcoma. In this study, distinct methylation alterations were identified in the 5'' flanking region of the MyoD1 gene from the two major subtypes, ie, alveolar and embryonal rhabdomyosarcoma. The MyoD1 methylation patterns of 26 rhabdomyosarcomas were compared with that of normal skeletal muscle and nonmuscle specimens by Southern blot analysis using methylation-sensitive restriction enzymes HhaI and HpaII. A 5-kb region immediately upstream of the MyoD1 coding sequence was found to be methylated in adult muscle and all nonmuscle tissues tested. The MyoD1 upstream region was unmethylated in the majority of the alveolar rhabdomyosarcomas (13 of 15, 87%) examined in this study. In contrast, 10 of 11 (91%) embryonal rhabdomyosarcomas showed a methylation pattern that was also observed in fetal muscle cells, in which the CpG sites in the MyoD1 upstream region were partially methylated. Our data suggest that the methylation status of the MyoD1 upstream CpG sites may be related to rhabdomyosarcoma tumorigenesis and may have valuable implications for its differential diagnosis.     

Reflex responses induced by tooth unloading

The reflex response of the masseter muscle to the rapid unloading of a single maxillary incisor tooth was studied. Unloading of a static force of 2 N in the horizontal direction resulted in a short-latency excitation, inhibition, and long-latency excitation of masseter muscle activity occurring at latencies of approximately 13, 20, and 40 ms, respectively, with a corresponding change in bite force occurring slightly later in each case. Following the blocking of periodontal input by the injection of local anesthetic around the stimulated tooth, inhibitory responses were abolished. Therefore, it is concluded that the observed masseteric inhibition was caused by the unloading of periodontal mechanoreceptors and thus that these receptors may contribute to the jaw unloading reflex.     

How could pathologists improve the initial diagnosis of colitis? Evidence from an international workshop

BACKGROUND: The taking of multiple colorectal biopsies is in widespread use although there is little research into their benefit for the pathological diagnosis of inflammatory bowel disease. There is also still debate about appropriate morphological criteria for interpreting these biopsies. AIMS: To determine the effect of single versus multiple biopsies on the accuracy of diagnosis and to study the accuracy and reproducibility of the different criteria used in the diagnosis of multiple biopsies by expert and non-expert pathologists. METHOD: Thirteen expert and 12 non-expert international diagnostic histopathologists attended a workshop. Sixty cases with full follow up were viewed, blinded, in two rounds. Diagnoses were made on rectal biopsies and then full colonoscopic series. RESULTS: Experts correctly identified 24% of Crohn's disease cases (non-experts, 12%) from the rectal biopsies. This improved to 64% (non-experts, 60%) with the full series. The accuracy of the diagnosis of ulcerative colitis also improved slightly with the full series from 64% to 74% overall. Experts had a similar (moderate) level of agreement and accuracy to non-experts. For Crohn's disease, the likelihood ratios (LR) for the most important individual features were 12.4 for granulomas and 3.3 for focal or patchy inflammation. Features favouring ulcerative colitis were diffuse crypt architectural irregularity (LR, 3.4), general crypt epithelial polymorphs (LR, 3.7), and reduced crypt numbers (LR, 2.9). CONCLUSIONS: A full colonoscopic series gave more accurate diagnosis than a rectal biopsy. Accurate pathologists used the same evidence based criteria for multiple biopsies as for single biopsies.     

Defining duodenitis: quantitative histological study of mucosal responses and their correlations

Biopsies from 56 patients with endoscopically normal duodenal bulbs, duodenitis, or duodenal ulceration were studied for counts of plasma cells, polymorphs, and eosinophils and extent of gastric metaplasia, villous atrophy, and mucosal oedema. A correlation matrix showed that the counts of different types of plasma cells were closely correlated with each other and that there was also a close correlation between the presence of intraepithelial polymorphs, villous atrophy, and gastric metaplasia. Cluster and discriminant analysis indicated that the histological changes could be grouped by their statistical association into three simple categories: normal, which includes many cases incorrectly labelled in some classification systems as mild or chronic duodenitis; histologically defined mild duodenitis, characterised by an appreciable plasma cell response and oedema usually with intraepithelial polymorph infiltration and gastric metaplasia; and severe duodenitis, with an appreciable polymorph response and villous atrophy but decreased plasma cells. Decreased plasma cells may be an important indication of peptic ulceration.