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Biomedical subjects

S Carpenter

Publications and source records attributed to S Carpenter.

At least 145 records · Page 8Linked to original sources
PubMed1990

Down's syndrome and thyroid disorder.

The thyroid status of 106 adults with Down's syndrome was assessed. Six were previously diagnosed as hypothyroid and were already receiving thyroxine. A further 37 patients showed abnormal thyroid function. Biochemical evidence of hypothyroidism (T4 less than 50 nmol/l and T.S.H. greater than 4 mu/less than) was found in one person. Six patients were found to have an unequivocally elevated T.S.H. but normal T4 (T4 greater than 50 nmol/l and T.S.H. greater than 20 mu/l) and 29 were found to have a modest elevation of T.S.H. but normal T4 concentration (T4 greater than 50 nmol/l and T.S.H. between 4 and 20 mu/l). There was one patient with mild thyrotoxicosis (T4 = 180 nmol/l and T.S.H. less than 0.1 mu/l). Clinical findings were of little use in making a diagnosis of hypothyroidism in this group of patients. A raised level of thyroid microsomal auto-antibodies was found in about a third of the patients, this occurred more commonly in females and slightly more often in those with a raised thyroid stimulating hormone. The importance of this is discussed. Recommendations for regular biochemical screening are made.

Adult↗
PubMed1990

Congenital inflammatory myopathy.

We present 3 patients with congenital inflammatory myopathy and summarize the literature. CNS involvement (microcephaly/intellectual delay) may or may not be present. Serum creatine kinase activity is elevated, the EMG is myopathic, and the muscle biopsy reveals inflammatory infiltrates, muscle fiber damage, and class I major histocompatibility complex products in muscle sarcolemma. Possible etiologies include intrauterine viral infection or an autoimmune process. Treatment with steroids may result in some motor improvement but has no effect on the CNS involvement. Despite a common time of presentation, these patients have a heterogeneous clinical profile, often suggesting a congenital muscular dystrophy syndrome.

Female↗
PubMed1989

Muscle pain associated with tubular aggregates and structures resembling cylindrical spirals.

A 42-year-old man complained of muscle pain in the legs and episodes of left-sided limb weakness. Light microscopy of his quadriceps muscle showed abundant subsarcolemmal accumulations with typical histochemical features for tubular aggregates. Electron microscopy showed areas filled with tubular aggregates and vesicular profiles. Scattered within some of the tubular aggregates circular profiles reminiscent of cylindrical spirals were seen. The presence of structures resembling cylindrical spirals within tubular aggregates suggest that they may arise from a component of the sarcoplasmic reticulum. There appears to be an intimate relationship between myalgia and these various types of abnormal membranous profiles; however, the pathophysiology remains to be elucidated.

Adult↗
PubMed1989

Myoclonus epilepsy and ragged-red fibres (MERRF). 1. A clinical, pathological, biochemical, magnetic resonance spectrographic and positron emission tomographic study.

Thirteen patients, including 6 from one family, with the syndrome of myoclonus epilepsy and ragged-red fibres (MERRF) were studied. There was considerable heterogeneity in the age of onset, severity and associated clinical features. Postmortem studies in 3 patients from the one family showed a particular system degeneration. In addition, the youngest and most severely affected family member showed the pathological changes of Leigh's syndrome. Cortical dysfunction is a prominent clinical feature in MERRF, but postmortem examination failed to reveal cortical abnormalities. Positron emission tomographic studies, however, showed decreased cortical metabolic rates for glucose and oxygen utilization, with normal cortical blood flow and cerebral pH. Analyses of kinetic rate constants for uptake and phosphorylation of the glucose analogue, fluorodeoxyglucose showed decreased hexokinase-mediated phosphorylation: normal K1 and k2 values but reduced k3. Phosphorus magnetic resonance spectroscopy studies suggested a normal cerebral intracellular pH. Biochemical studies on muscle homogenates in 6 patients showed partial deficiencies of the activities of certain mitochondrial enzymes in 4 cases, whereas in 2 patients no abnormality was found. Our data, combined with previous reports, show that MERRF is biochemically and genetically heterogeneous. Our experience, and analysis of the literature, suggests that many cases previously described as the Ramsay Hunt syndrome, as well as other hitherto unclassified system degenerations associated with myoclonus epilepsy, are examples of MERRF. These data permit the formulation of a hypothesis to explain the clinical, biochemical and genetic heterogeneity of MERRF, and its overlap with Leigh's syndrome. We suggest that different biochemical defects of the mitochondrial respiratory chain may cause similar cerebral metabolic effects, as measured by positron emission tomography, resulting in similar phenotypes. Reduced activity of one enzyme, however, may result in different phenotypes, depending on the severity of the defect and its tissue distribution. Moreover, the phenotypic expression of certain biochemical defects may be influenced by randomly occurring factors such as fever, which may increase metabolic demand and result in more deleterious cellular metabolic effects.

Adolescent↗
PubMed1989

Segmental necrosis and its demarcation in experimental micropuncture injury of skeletal muscle fibers.

Muscle fibers of rat gastrocnemii were punctured in vivo with a tungsten wire whose tip was 10 microns wide. After two hours, most punctured fibers had clearly necrotic segments. The length of necrotic segments appeared to increase between three and four hours. Demarcation of surviving stumps from necrotic segments by a membrane was complete in most muscles by seven hours. At the boundary between necrotic segments and nondemarcated stumps there was a cap of densely aggregated or hypercontracted myofilaments which stained strongly for precipitated calcium. The membrane which demarcated the stumps was found partially formed in the necrotic pulp close to this cap, attached to the plasma membrane. While forming it had a free edge and probably resulted from spontaneous aggregation of phospholipids in the pulp. Other portions of newly formed membrane were found encircling organelles inside necrotic segments. Prompt formation of a demarcating membrane probably limits the extent of necrosis in injured fibers.

Animals↗
PubMed1989

Change in host cell tropism associated with in vitro replication of equine infectious anemia virus.

Similar to other human and animal lentiviruses, equine infectious anemia virus (EIAV) is detectable in vivo in cells of the monocyte-macrophage lineage. Owing to their short-lived nature, horse peripheral blood macrophage cultures (HMC) are rarely used for in vitro propagation of EIAV, and equine dermal (ED) or kidney cell cultures, which can be repeatedly passed in vitro, are used in most studies. However, wild-type isolates of EIAV will not grow in these cell types without extensive adaptation, a process which may attenuate viral virulence. To better define the effect of host cell tropism on the virulence and pathogenesis of EIAV, we studied a field isolate of EIAV during in vitro adaptation to growth in an ED cell line. Interestingly, as the virus adapted to growth in ED cells, there was a corresponding decrease in infectivity for HMC, and the final ED-adapted isolate was more than 100-fold more infectious for ED cells than for HMC. In vivo studies indicated that the ED-adapted isolate was able to replicate in experimentally infected horses, although no clinical signs of EIA were observed. Thus, selection for in vitro replication on ED cells correlated with a loss of EIAV tropism for HMC in vitro and was associated with avirulence in vivo.

Animals↗
PubMed1989

Creutzfeldt-Jakob disease presenting as isolated aphasia.

Progressive aphasia without dementia (primary progressive aphasia) is increasingly recognized as an important neurobehavioral syndrome. Clinical diagnosis of progressive aphasia is difficult early in its course, and the differential diagnosis is usually said to include Alzheimer's and Pick's diseases. We report a 61-year-old man with autopsy-proven Creutzfeldt-Jakob disease (CJD) whose major initial manifestation was a progressive, fluent aphasia. Myoclonus was absent, and characteristic EEG abnormalities appeared relatively late. We believe that this case of CJD is unique in its presentation of profound and isolated aphasia. CJD should be considered in the differential diagnosis of the progressive aphasia syndrome.

Aphasia↗
PubMed1989

Dystrophin is expressed in mdx skeletal muscle fibers after normal myoblast implantation.

In mdx mice, the dystrophin gene of the X chromosome is defective and, as a result, immunoreactive dystrophin is undetectable in all muscle fibers of all animals of this highly inbred strain. This study showed that implantation of suspensions of clonal cultures of normal human myoblasts into different regions of quadriceps muscles of 6-to-10-day-old mdx mice or 60-day-old mdx mice (whose muscles have been crushed 4 days before implantation) results in the appearance of scattered fiber segments containing microscopically demonstrable immunoreactive dystrophin. In the animals that received the normal myoblast implantation in the prenecrotic stage of the disease (6 to 10 days of age), the dystrophin-positive fiber segments (demonstrated at ages 35, 45, and 60 days) escaped necrosis. This was determined by the absence of the characteristic chains of central nuclei, a reliable marker of prior necrosis in mdx muscle fibers. By heavy labeling of the nuclear DNA of the transplantable human myoblasts with H3-thymidine during culturing, and by sequential performance of an immunocytochemical staining for dystrophin and autoradiography on the same sections, some dystrophin-positive fiber segments were shown to contain radiolabeled myonuclei. It was concluded that nondystrophic myoblasts fused with host muscle fibers to form mosaic muscle fibers in which the normal dystrophin gene of the implanted myoblasts was expressed. This approach may be employed for the mitigation of the deleterious consequences of a gene defect in recessively inherited human muscle diseases such as Duchenne dystrophy.

Animals↗
PubMed1989

Radiobiology of ultrasoft X rays. II. Cultured C3H mouse cells (10T1/2).

In the first paper of this series (Radiat. Res. 110, 396-412 (1987], using V79 cells, we reported that the relative biological effectiveness (RBE) of ultrasoft X rays was found to increase with decreasing energy, and the oxygen enhancement ratio (OER) was found to decrease with decreasing energy. In this report, we present RBE and OER results for 10T1/2 cells that are known to grow uniformly flat and are considerably thinner than V79 cells. Thus the variation in dose across the cell nucleus is considerably reduced. The OER results agree well with our earlier V79 results. However, the RBE values for 10T1/2 cells compared to V79 cells are systematically less for all soft X rays and especially for 0.28 keV carbon-K (1.3 compared to 3.4 for V79 cells). Some plausible explanations are presented to reconcile the apparent discrepancy between V79 and 10T1/2 results.

Animals↗
PubMed1989

Radiobiology of ultrasoft X rays. IV. Flat and round-shaped hamster cells (CHO-10B, HS-23).

The results reported earlier in this series indicated that the relative biological effectiveness (RBE) of ultrasoft X rays decreases with decreasing cell thickness, approaching unity for the thinnest cells used, plateau-phase human skin fibroblasts (HSF). The possible dependence of RBE on the configuration of the cell nucleus is investigated further in this paper using two CHO cell lines that attach well and have similar intrinsic radiosensitivities to 60Co gamma rays. One of the lines forms monolayers similar to V79 cells, while the other remains more spherical during growth. We find an increasing RBE with decreasing X-ray energy for both of these cell lines, consistent with our results using V79 cells. Also consistent with our results obtained with 10T1/2 and HSF cells, we find an increasing RBE with increasing cell thickness. The possible dependence of RBE on radiosensitivity and the use of the concept of mean dose for ultrasoft X rays is discussed.

Animals↗
PubMed1988

Morphological diagnosis and misdiagnosis in Batten-Kufs disease.

Skin biopsy is a reliable method for diagnosis of Batten disease; it is probably not reliable in Kufs disease. Eccrine secretory cells are the most consistently involved cell type. The abundance of lysosomal storage facilitates diagnosis in infantile and late-infantile cases. The curvilinear bodies of the late-infantile cases have high specificity and should be easily recognizable, though their lamination must be demonstrable. In the usual juvenile cases the cell types involved are more limited, and a superficial biopsy, which does not include eccrine secretory cells, may be nondiagnostic. These cells may contain fingerprint profiles in occasional juvenile, adolescent, or adult patients with other diseases. Thus, verification of involvement of a second cell type, such as duct cells, Schwann cells, and smooth or skeletal muscle, is essential. In all varieties of the disease strict criteria for the ultrastructural patterns must be followed. Otherwise, confusion may arise with normal organelles, with banal lipofuscin, or with nonspecific lysosomes.

Diagnostic Errors↗
PubMed1988

Kufs disease: clinical features and forms.

In patients with an acceptable pathological diagnosis of Kufs disease, two major forms have been identified: Type A presenting as progressive myoclonus epilepsy around the age of 30, and Type B presenting in the same age range with dementia as well as cerebellar and/or extra-pyramidal signs. In adolescence, two subgroups of neuronal ceroid-lipofuscinosis (NCL) emerge. The first group consists of patients resembling either type A or B Kufs disease, but with earlier onset (20% of all cases). These must be distinguished from the second group of rare patients with protracted juvenile NCL presenting with early and prominent visual failure. Although Kufs disease is rare, diagnosis during life should now be possible. The advantages, techniques, and pitfalls of biopsy diagnosis are presented by Carpenter et al. [1988]. We believe that delineation of these two clinical syndromes should aid in the identification of other possible cases of Kufs disease, leading to appropriate pathological examinations to confirm the diagnosis. Knowledge of whether this clinical distinction is biologically meaningful must await the discovery of the more fundamental biochemical defects.

Adolescent↗
PubMed1988

The Newfoundland aggregate of neuronal ceroid-lipofuscinosis.

We have found a group of individuals with the late infantile, the early juvenile variant, and juvenile neuronal ceroid-lipofuscinosis (NCL) in Newfoundland, an island with a population of 500,000. In the past 25 yr, we have ascertained 44 cases of NCL in 32 sibships: 32 cases of late infantile NCL (LINCL) in 24 sibships, 11 cases of the early juvenile variant in 7 sibships, and one patient with the juvenile form (JNCL). The clinical presentation of the LINCL patients is very characteristic, with onset of seizures at age 2 1/2 to 3 1/2 yr, frequently with drop attacks and myoclonic jerks, followed by mental deterioration, ataxia, visual loss, and death by the end of the first decade. Typical curvilinear profiles are seen on electron microscopy (EM). The second group of patients mainly have the early juvenile variant with onset of seizures at age 5 to 6 yr and fingerprint profiles with occasional curvilinear profiles on EM. However, a child with the juvenile form presenting with blindness was also encountered. In both of these types, death occurs in the second decade of life. There is no overlap of these three clinical forms within sibships, although both late infantile and early juvenile variant types may occur in the same small fishing village. All three forms appear to be inherited as autosomal recessive traits. Although the early juvenile variant has been postulated to represent a double heterozygote between LINCL and JNCL, this cannot be confirmed on the basis of the present study.(ABSTRACT TRUNCATED AT 250 WORDS)

Child, Preschool↗
PubMed1988

Expression of immunoreactive major histocompatibility complex products in human skeletal muscles.

Immunoreactive class 1 and class 2 major histocompatibility complex gene products (MHCP) and beta 2 microglobulin (beta 2 MG) were demonstrated by microscopic immunocytochemistry in cryostat sections of skeletal muscle biopsies of 67 patients with various neuromuscular diseases. Diagnoses included normal muscle, chronic partial denervation, Duchenne dystrophy, polymyositis, dermatomyositis, inclusion body myositis, and miscellaneous neuromuscular diseases. Normal mature muscle fibers did not express MHCP, but blood vessels showed both class 1 and 2 MHCP and beta 2 MG. Regenerating muscle fibers showed consistent sarcolemmal class 1 MHCP expression irrespective of the disease. In polymyositis, the majority of extrafusal muscle fibers of most patients showed strong sarcolemmal class 1 MHCP expression. In dermatomyositis, muscle fibers situated either in perifascicular or in randomly clustered distribution revealed strong class 1 MHCP reactivity. In inclusion body myositis, scattered small clusters of muscle fibers were positive for class 1 MHCP. In polymyositis and inclusion body myositis, particularly strong class 1 MHCP expression was invariably seen in nonnecrotic muscle fibers partially invaded by lymphocytes whose cytotoxic effects are believed to be class 1 MHCP restricted. Factors or agents that trigger class 1 MHCP expression are presumed also to sensitize lymphocytes to muscle fibers in these diseases, but their identity remains obscure at this time. In dermatomyositis, the expression of MHCP in perifascicular muscle fibers and in areas of capillary loss may represent the triggering of MHCP expression by a nonspecific cellular stress reaction, in this case probably low-grade ischemia.

Adult↗