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Biomedical subjects

J P Lin

Publications and source records attributed to J P Lin.

At least 37 records · Page 2Linked to original sources
PubMed1999

Continuum of reflex excitability in hemiplegia: influence of muscle length and muscular transformation after heel-cord lengthening and immobilization on the pathophysiology of spasticity and clonus.

The electromyographic (EMG) responses to tendon taps at the ankle and ensuing muscular twitch forces and temporal parameters were studied at varying angles across the joint range in 18 children, aged 3 to 14.9 years, with congenital hemiparetic cerebral palsy and 22 healthy (control) children, aged 3 to 13.6 years. Those subjects with hemiparesis were community ambulators without assistance. In all subjects, passive muscle stretch caused a waxing of the reflex EMG and twitch force near neutral (with the sole of the foot at right angles to the tibia) and a diminution of these with further dorsiflexion. Twitch times increased with each dorsiflexing increment, being slowest at maximum dorsiflexion and fastest at the resting plantarflexion angle. Heterogeneity of the hemiparetic-limb data is evident when compared with data of non-paretic and unaffected limbs, with clear differences in the clonic (fast twitch) as opposed to non-clonic (slow twitch) muscles. In four cases with clinical clonus, clonus frequency was reduced by passive dorsiflexion. Plaster immobilization for 1 month produced clonus which was previously absent in one subject, and caused a fast-twitch phenotype to emerge in two subjects. Follow-up after heel-cord lengthening in one subject showed that clonus frequency diminished from 9 to 3 Hz with slowing and strengthening of muscle-twitch phenotype. Short- and long-term peripheral manipulations appear to regulate neuromuscular excitability according to whether muscles are loaded or unloaded. Although damage to the nervous system provides the setting for reflex excitability, the data suggest that the muscle length (which specifies the joint angle) and the muscle-twitch phenotype of any given limb for any given case appear to dictate the actual speed and strength of reflex muscle-twitch and clonus profiles. This study illustrates how peripheral manipulations of muscles and tendons may alter the expression of what have hitherto been considered as exclusively central phenomena.

Adolescent↗
PubMed1999

A unique point mutation in the PMP22 gene is associated with Charcot-Marie-Tooth disease and deafness.

Charcot-Marie-Tooth disease (CMT) with deafness is clinically distinct among the genetically heterogeneous group of CMT disorders. Molecular studies in a large family with autosomal dominant CMT and deafness have not been reported. The present molecular study involves a family with progressive features of CMT and deafness, originally reported by Kousseff et al. Genetic analysis of 70 individuals (31 affected, 28 unaffected, and 11 spouses) revealed linkage to markers on chromosome 17p11.2-p12, with a maximum LOD score of 9.01 for marker D17S1357 at a recombination fraction of .03. Haplotype analysis placed the CMT-deafness locus between markers D17S839 and D17S122, a approximately 0.6-Mb interval. This critical region lies within the CMT type 1A duplication region and excludes MYO15, a gene coding an unconventional myosin that causes a form of autosomal recessive deafness called DFNB3. Affected individuals from this family do not have the common 1.5-Mb duplication of CMT type 1A. Direct sequencing of the candidate peripheral myelin protein 22 (PMP22) gene detected a unique G-->C transversion in the heterozygous state in all affected individuals, at position 248 in coding exon 3, predicted to result in an Ala67Pro substitution in the second transmembrane domain of PMP22.

Amino Acid Sequence↗
PubMed1998

Description of a large kindred with autosomal dominant inheritance of branchial arch anomalies, hearing loss, and ear pits, and exclusion of the branchio-oto-renal (BOR) syndrome gene locus (chromosome 8q13.3).

It has been suggested that branchio-oculo-facial (BOF) syndrome, deafness with ear pits, and associated conditions [MIM nos. 125100, 120502], and branchio-oto-renal (BOR) [MIM no. 113650] or Melnick-Fraser syndrome represent phenotypic variants of the BOR syndrome, which is inherited in an autosomal dominant (AD) manner and has variable clinical expression. Recently, the BOR gene was mapped to chromosome region 8q13.3 and its sequence was identified as the human homolog of the Drosophila eyes absent (EYA1) gene. We studied an extended family with AD inheritance of branchial arch anomalies (BAA), hearing loss, and ear pits, whose phenotype differed from that of patients with BOR in that none of the affected members had renal abnormalities or lacrimal duct stenosis. Fifteen affected members were studied; ear pits were present in all of them, whereas hearing loss and other BAA were present in 40 and 20%, respectively. Blood was collected from 31 patients; DNA was extracted by standard methods and amplified using primers from microsatellite sequences flanking the BOR locus on chromosome 8q13.3 (D8S1807, D8S530, and D8S543). Linkage analysis was performed under two models of AD inheritance with different penetrance: 100% and 80%. In both cases, the logarithm of odds (LOD) scores produced were significantly less than -2; exclusion of the 8q13.3 locus was also confirmed by multipoint LOD score analysis. We conclude that, in one large family with AD inheritance of BAA, hearing loss and ear pits, the BOR locus was excluded. This represents the first documentation of heterogeneity in branchio-oto anomalies, syndromes with phenotypes similar to BOR syndrome.

Branchial Region↗
PubMed1998

Familial autoimmunity in pedigrees of idiopathic inflammatory myopathy patients suggests common genetic risk factors for many autoimmune diseases.

OBJECTIVE: To test the hypothesis that many autoimmune diseases share common genetic risk factors and to define the frequency and distribution of autoimmune diseases in relatives of patients with very rare disorders, the idiopathic inflammatory myopathies (IIM). METHODS: We evaluated, in a prospective case-control study, consecutive patients with IIM who were referred to our center and ascertained without regard to family history or known risk factors for autoimmunity, and all available family members. We used a standardized assessment to determine the presence and type of autoimmune disease in each subject. A matched comparison group of control subjects without autoimmune disease who were referred to our center and their families were similarly assessed. RESULTS: Autoimmune diseases were significantly increased in prevalence (21.9%) in the 151 first-degree relatives of the 21 IIM probands compared with the prevalence (4.9%) in the 143 relatives of the 21 control probands (odds ratio [OR] by regression analysis 7.9, 95% confidence interval [95% CI] 2.9-21.9, P < 0.001). Women had more autoimmune disease than men (OR by regression analysis 4.6, 95% CI 2.3-9.0) and the odds ratio for autoimmune disease increased 0.02 per year of age. These disorders tended to follow the frequency distribution of autoimmune diseases in the general population. Genetic modeling studies showed that a non-Mendelian polygenic inheritance pattern for autoimmune disease was most consistent with these data. CONCLUSION: Autoimmune diseases are significantly increased in frequency in first-degree relatives of IIM patients, affect more women than men, increase with age, and are distributed in a pattern similar to that in the general population. Many autoimmune disorders share genes that together act as polygenic risk factors for autoimmunity.

Adolescent↗
PubMed1998

Rheumatoid arthritis in the Pima Indians: the intersection of epidemiologic, demographic, and genealogic data.

OBJECTIVE: To describe the clinical features and familial distribution of rheumatoid arthritis (RA) in the Pima Indians. METHODS: From 1965 through 1990, all cases of RA as defined by the American College of Rheumatology (formerly, the American Rheumatism Association) 1987 criteria or all cases of seropositive, erosive disease as defined by the Rome criteria were identified in individuals who were age 20 years and older and were of 50% or more Pima/Tohono-O'odham heritage. Radiographs were reviewed by 2 musculoskeletal radiologists who were blinded to case status. Kinship coefficients were used to evaluate familial aggregation. RESULTS: Eighty-eight RA cases were identified from this population-based sample. Over 66% of the cases had seropositive disease, over 60% had erosive disease, and over 40% had subcutaneous nodules. Of the 88 RA cases, 40 were members of families with more than 1 RA case. The remainder were simplex cases. CONCLUSION: In this population, clinical markers of severe RA were present in a majority of cases. The presence of familial aggregation for RA in the Pima Indians suggests underlying genetic factors in disease pathogenesis.

Adult↗
PubMed1998

Familial clustering of rheumatoid arthritis with other autoimmune diseases.

Previous studies have shown that rheumatoid arthritis aggregates within families. However, no formal genetic analysis of rheumatoid arthritis in pedigrees together with other autoimmune diseases has been reported. We hypothesized that there are genetic factors in common in rheumatoid arthritis and other autoimmune diseases. Results of odds-ratio regression and complex segregation analysis in a sample of 43 Caucasian pedigrees ascertained through a rheumatoid arthritis proband or matched control proband, revealed a very strong genetic influence on the occurrence of both rheumatoid arthritis and other autoimmune diseases. In an analysis of rheumatoid arthritis alone, only one inter-class measure, parent-sibling, resulted in positive evidence of aggregation. However, three inter-class measures (parent-sibling, sibling-offspring, and parent-offspring pairs) showed significant evidence of familial aggregation with odds-ratio regression analysis of rheumatoid arthritis together with all other autoimmune diseases. Segregation analysis of rheumatoid arthritis alone revealed that the mixed model, including both polygenic and major gene components, was the most parsimonious. Similarly, segregation analysis of rheumatoid arthritis together with other autoimmune diseases revealed that a mixed model fitted the data significantly better than either major gene or polygenic models. These results were consistent with a previous study which concluded that several genes, including one with a major effect, is responsible for rheumatoid arthritis in families. Our data showed that this conclusion also held when the phenotype was defined as rheumatoid arthritis and/or other autoimmune diseases, suggesting that several major autoimmune diseases result from pleiotropic effects of a single major gene on a polygenic background.

Adult↗
PubMed1998

Familial hyperaldosteronism type II: description of a large kindred and exclusion of the aldosterone synthase (CYP11B2) gene.

Familial hyperaldosteronism type II (FH-II) is characterized by autosomal dominant inheritance and hypersecretion of aldosterone due to adrenocortical hyperplasia or an aldosterone-producing adenoma; unlike FH type I (FH-I), hyperaldosteronism in FH-II is not suppressible by dexamethasone. Of a total of 17 FH-II families with 44 affected members, we studied a large kindred with 7 affected members that was informative for linkage analysis. Family members were screened with the aldosterone/PRA ratio test; patients with aldosterone/PRA ratio greater than 25 underwent fludrocortisone/salt suppression testing for confirmation of autonomous aldosterone secretion. Postural testing, adrenal gland imaging, and adrenal venous sampling were also performed. Individuals affected by FH-II demonstrated lack of suppression of plasma A levels after 4 days of dexamethasone treatment (0.5 mg every 6 h). All patients had negative genetic testing for the defect associated with FH-I, the CYP11B1/CYP11B2 hybrid gene. Genetic linkage was then examined between FH-II and aldosterone synthase (the CYP11B2 gene) on chromosome 8q. A polyadenylase repeat within the 5'-region of the CYP11B2 gene and 9 other markers covering an approximately 80-centimorgan area on chromosome 8q21-8qtel were genotyped and analyzed for linkage. Two-point logarithm of odds scores were negative and ranged from -12.6 for the CYP11B2 polymorphic marker to -0.98 for the D8S527 marker at a recombination distance (theta) of 0. Multipoint logarithm of odds score analysis confirmed the exclusion of the chromosome 8q21-8qtel area as a region harboring the candidate gene for FH-II in this family. We conclude that FH-II shares autosomal dominant inheritance and hyperaldosteronism with FH-I, but, as demonstrated by the large kindred investigated in this report, it is clinically and genetically distinct. Linkage analysis demonstrated that the CYP11B2 gene is not responsible for FH-II in this family; furthermore, chromosome 8q21-8qtel most likely does not harbor the genetic defect in this kindred.

Aldosterone↗
PubMed1998

Impacts of low-skilled immigration on the internal migration of the U.S.-born low-skilled Americans in the United States: an assessment in a multivariate context.

"This paper assesses the impacts of low-skilled immigration on the interstate migration of...U.S.-born low-skilled Americans, based on the disaggregated data of the 1990 Census. Our results reveal that the push effects of...immigration on the departure process [were] much stronger than its discouraging and complementary effects on the destination choice process; and that the push effects of low-skilled immigration are (1) stronger on whites than on non-whites, (2) much stronger on the poor than on the non-poor, (3) weaker on the 15-24 age group than on older age groups, and (4) the strongest on poor whites."

Age Factors↗
PubMed1997

Parental transmission and D18S37 allele sharing in bipolar affective disorder.

We combined the five chromosome 18 bipolar affective disorder data sets provided by GAW10, totaling 185 families with 3,394 individuals, and performed analysis of differential parental transmission and chromosome 18 marker allele sharing in families with transmission through fathers vs those through mothers. Results indicated a significant excess of maternal transmission of bipolar disorder. All pedigrees were then broken into nuclear families and affected sib-pair linkage analyses performed on the marker, D18S37. There was significant linkage in the data overall, as well as in each subgroup of paternal, maternal and unknown parental transmission nuclear families. There were no significant differences in identical-by-descent (IBD) scores among the three transmission subgroups. These findings support an excess of maternal transmission, and linkage between bipolar disorder and marker D18S37. However, our results do not support the previous suggestion that there are differences in chromosome 18 marker allele sharing depending on the transmitting parent.

Alleles↗
PubMed1997

Linkage studies in erythrokeratodermias: fine mapping, genetic heterogeneity and analysis of candidate genes.

Erythrokeratodermias are a clinically heterogeneous group of rare autosomal dominant disorders of cornification with overlapping features including hyperkeratosis and erythema. We ascertained five extended pedigrees with different phenotypes for a linkage study. Three families presented with localized erythrokeratodermia variabilis, and one with erythrokeratodermia and ataxia. Another family had Greither disease associated with variable hyperkeratotic plaques. Despite their phenotypic differences, both erythrokeratodermia variabilis and erythrokeratodermia with ataxia map to a common region in 1p34-p35. Multipoint linkage and haplotype analyses place erythrokeratodermia variabilis between the marker D1S496 and D1S186 with a maximum LOD score of 12.88. Our linkage results provide compelling evidence for genetic homogeneity among families of mixed European and French-Canadian origin. In contrast, results excluded Greither's disease from the established erythrokeratodermia variabilis gene region indicating genetic heterogeneity of erythrokeratodermias. Based on recombinations, two genes assigned to 1p34-p35 were excluded: cartilage matrix protein and avian myelocytosis viral oncogene. Connexin-37 (GJA4), a member of the connexin gene family, maps within the erythrokeratodermia variabilis region and is an attractive candidate gene. Direct sequencing of the coding region of GJA4 in four patients revealed several variations, including a novel polymorphism within the 5' cytoplasmic domain, but no pathogenic mutations were found, thus excluding Connexin-37 as a candidate. There is evidence, however, that other epidermally expressed connexins cluster in this region, and one may yet be determined to play a role in the pathogenesis of erythrokeratodermia variabilis.

Chromosome Mapping↗
PubMed1997

Soleus muscle length, stretch reflex excitability, and the contractile properties of muscle in children and adults: a study of the functional joint angle.

The influence of the joint angle on stretch reflex excitability of the soleus muscle at the ankle has been studied in 22 children aged 3.9 to 13.6 years and 9 adults aged 19 to 70 years. For all subjects, reflex EMG and mechanical twitch torque gain were trivial at resting plantar flexion. The reflex EMG gain reached a maximum between -15 degrees and -10 degrees of plantar flexion beyond the neutral angle, 0 degrees, defined as the foot at right angle to the tibia, diminishing steeply with further dorsiflexion. The reflex mechanical gain rose to a peak between 0 degrees and +10 degrees of dorsiflexion beyond neutral, declining steeply thereafter. By contrast, axonally stimulated muscle twitch torque increased serially up to +30 degrees dorsiflexion beyond neutral. For the soleus muscle, the optimal reflex neuromechanical angle lies approximately midway between the angle for optimal reflex EMG gain (in mild plantar flexion, at which the largest and strongest motor units can be activated) and the optimal muscle mechanical angle (at the extreme of soleus muscle dorsiflexion). These studies confirm that the excitability of the spinal alpha motor neuron pool in vivo is strongly influenced by muscle length and explain the variability in reflex excitability within and between subjects, if the joint angle is not controlled. They also indicate how posture influences movement, agreeing with the known function of the soleus muscle in the stance phase of gait and the modulation of motor unit recruitment during voluntary alternating movements at the ankle. Soleus muscle twitch characteristics show a fivefold to eightfold increase in peak force associated with a tenfold reduction in compliance in the first two decades of life and an apparent speeding up of twitch time in the first decade.

Adolescent↗
PubMed1997

Segregation of Allgrove (triple-A) syndrome in Puerto Rican kindreds with chromosome 12 (12q13) polymorphic markers.

Allgrove syndrome (AS), also known as triple-A syndrome, is a rare cause of congenital adrenal insufficiency due to adrenocorticotropic hormone resistance. It is inherited in an autosomal recessive manner and is associated with achalasia, alacrima, and other neurological abnormalities, including autonomic, sensory, and upper- and lower-motor neuropathy, deafness, and mental retardation. Although the etiology of AS remains unknown, recently the disease was linked to a chromosome 12 locus (corresponding cytogenetic band 12q13) in consanguineous families of European ancestry. In the present study, we investigated four nonconsanguineous families with documented inheritance of AS for linkage with the reported 12q13 locus. Eighteen subjects were studied, of whom five were affected by AS. DNA was extracted from peripheral blood lymphocytes and amplified by standard methods with primers from polymorphic sequence tagged sites (STSs) located in the chromosome 12q13 region. Two-point logarithm-of-odds (LOD) score analysis revealed a maximum LOD score of 1.7 for STSs D12S361 and D12S368 without any recombinants [recombination distance (theta) = 0]. Multipoint linkage analysis defined an area of estimated genetic distance less than 0.5 cM (approximately 500,000 bp) between STSs D12S361 and D12S359 that is most likely to contain the AS gene(s). We conclude that, in Puerto Rican families, AS segregates with polymorphic markers that have been mapped to the chromosome 12q13 locus, revealing the absence of heterogeneity for this syndrome in a genetically distinct population. Candidate genes in the region include those that code for several of the keratin proteins, transcription factors, and others.

Abnormalities, Multiple↗
PubMed1996

Carney complex, a familial multiple neoplasia and lentiginosis syndrome. Analysis of 11 kindreds and linkage to the short arm of chromosome 2.

Carney complex is an autosomal dominant syndrome characterized by multiple neoplasias, including myxomas at various sites and endocrine tumors, and lentiginosis. The genetic defect(s) responsible for the complex remain(s) unknown. We studied 101 subjects, including 51 affected members, from 11 North American kindreds with Carney complex. Blood samples were collected from patients and their family members. Hospital records, photographs, and tissue specimens of deceased individuals were reviewed. DNA was extracted from blood samples, patient-derived cell lines, and/or paraffin-embedded tissues. Linkage analysis was performed with highly polymorphic microsatellite markers, distributed over areas of the human genome harboring the most likely candidate genes. The most prevalent clinical manifestation in patients with Carney complex was spotty skin pigmentation, similar to that observed in Peutz-Jeghers and other lentiginosis syndromes. Skin and cardiac myxomas, Cushing syndrome, and acromegaly were present in 62, 30, 31 and 8 percent of the patients, respectively. Linkage was obtained for three markers on the short arm of chromosome 2 (2p16), with a maximum two-point lod score of 5.97 at theta = 0.03 for the marker CA-2 (odds in favor of linkage 10(6):1. The flanking markers CA7 and D2S378 defined a region of approximately 6.4 cM that is likely to contain the gene(s) associated with Carney complex. Candidate genes in the proximity, including the propiomelanocortin and the DNA-mismatch repair hMSH2 genes, were excluded. We conclude that the genetic defect(s) responsible for Carney complex map(s) to the short arm of chromosome 2 (2p16). This region has exhibited cytogenetic aberrations in atrial myxomas associated with the complex, and has been characterized by microsatellite instability in human neoplasias.

Canada↗
PubMed1996

Evidence for genetic heterogeneity in monilethrix.

Monilethrix is a rare inherited defect of the hair shaft resulting in hair fragility and dystrophic alopecia. In contrast to recent reports mapping monilethrix to the type II epithelial and trichocyte keratin gene cluster on 12q13, we strongly excluded these candidate genes in another family with autosomal dominant monilethrix. Moreover, there was no evidence for linkage of the disease to the keratin gene cluster on chromosome 17q12-q21, thus excluding defects in all known trichocyte and epithelial keratins as the cause of monilethrix in this family. Likewise, several other genes known to play an important role in hair shaft formation (trichohyalin and involucrin, ultra-high sulfur matrix proteins, and transglutaminases 1, 2, and 3) did not provide any evidence for linkage. Our results indicate genetic heterogeneity in monilethrix and suggest that aberrations in at least one other gene result in a similar phenotype.

Age Factors↗
PubMed1996

The maturation of motor dexterity: or why Johnny can't go any faster.

The speed of alternating movements at the ankle, metacarpophalangeal and wrist joints in 11 healthy children and 13 adults doubled between age 3 and 11 years, despite a 32-fold increase in limb-segment inertia produced by the doubling in limb length over the same period. The data for the children showed little or no practice effect. The speeds for the adults, though faster than those for the children, were more widely dispersed, indicating the possibility that training might increase the speed of the slowest adult. The findings are consistent with a previous report demonstrating a parallel increase in the speed of calf muscles over the first 10 years of life and it is inferred that the increase in dexterity at the wrist and metacarpophalangeal joints also depends on an increase in muscle speed with age. Muscle maturation may impose a rate-limiting envelope for all motor tasks which is particularly evident in rapidly alternating movements. These findings have implications for training in sport and music and for the understanding of motor delay, clumsiness and speech difficulties.

Adult↗
PubMed1996

Painful and painless ophthalmoplegia with cavernous sinus pseudotumour.

Acquired isolated ophthalmoplegia in childhood has many potential causes. Although other ophthalmological or clinical features may aid lesion localisation, the absence of these does not preclude structural pathology. Two cases of cavernous sinus pseudotumour presented as ophthalmoplegia with and without pain. Magnetic resonance imaging of the cavernous sinus revealed the presence of enhancing tissue consistent in appearance with pseudotumour in both cases, and they responded well to steroid treatment. These cases emphasise the importance of detailed imaging of the cavernous sinus in the investigation of these symptoms in order to exclude this treatable condition.

Adolescent↗
PubMed1995

Development of prospective control of catching moving objects in preterm at-risk infants.

Healthy term infants and infants classified as neurologically at-risk because of low birthweight and preterm birth were tested longitudinally between 20 and 48 weeks on the ability to use visual information predictively. Reaching for an object moving at different speeds was assessed; the object was occluded from view by a screen during the last part of its approach. At each infant's first reaching session, gaze anticipated the reappearance of the moving toy; however, onset of reaching and prospective control of gaze and hand varied considerably between the normal and at-risk groups. In addition, some at-risk infants geared their actions not to the time but to the distance that the toy was from the catching place, causing problems with faster-moving toys. The two children who anticipated least well were the only two of the at-risk group who were later diagnosed as having cerebral palsy.

Case-Control Studies↗