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Biomedical subjects

M Rodriguez

Publications and source records attributed to M Rodriguez.

At least 73 records · Page 4Linked to original sources

Cytotoxic T cells isolated from the central nervous systems of mice infected with Theiler's virus.

Intracerebral inoculation of resistant mice (C57BL/10SNJ) with Theiler's murine encephalomyelitis virus (TMEV) results in acute encephalitis followed by subsequent clearance of virus from the central nervous system (CNS). In contrast, infection of susceptible mice (SJL/J) results in virus persistence and chronic immune-mediated demyelination. Both resistance and susceptibility to TMEV-induced disease appear to be immune mediated, since immunosuppression results in enhanced encephalitis in resistant mice but diminished demyelination in susceptible mice. The purpose of these experiments was to determine whether anti-TMEV cytotoxic T lymphocytes (CTLs) are generated during acute and chronic TMEV infection. Nonspecific lectin-dependent cellular cytotoxicity was used initially to detect the cytolytic potential of lymphocytes infiltrating the CNS irrespective of antigen specificity. Using TMEV-infected targets, H-2-restricted TMEV-specific CTLs of the CD8+ phenotype were demonstrated in lymphocytes from the CNS of susceptible and resistant mice, arguing against the hypothesis that the ability to generate CD8+ CTLs mediates resistance. In chronically infected SJL/J mice, TMEV-specific CTL activity was detected in the CNS as late as 226 days postinfection. These experiments demonstrate that virus-specific CTLs are present in the CNS during both acute and chronic TMEV infection. Anti-TMEV CTLs in the CNS of chronically infected SJL/J mice may play a role in demyelination through their ability to lyse TMEV-infected glial cells.

Animals

Identification of an enhancer required for the expression of a mouse major urinary protein gene in the submaxillary gland.

The MUP1.5b gene was previously found to be expressed specifically in the submaxillary gland and at high levels when introduced into mice as a transgene including 4.7 kb of 5'-flanking DNA and 0.3 kb of 3'-flanking DNA. To localize regulatory elements responsible for this tissue-specific pattern of expression, we tested the expression of three additional MUP1.5b transgenes including various amounts of 5'-flanking DNA. These experiments indicated that sequences between -1.85 and -3.46 kb from the transcription initiation site were required for high-level expression in the submaxillary gland. The presence of regulatory elements in this region was also suggested by the detection of a DNase I-hypersensitive site, seen only in submaxillary gland nuclei, at position -2.5 kb upstream from the MUP1.5a gene, a member of the same MUP gene subfamily and virtually identical to the MUP1.5b gene. Further evidence for enhancer activity was provided by the ability of the 1.6-kb DNA fragment including sequences between -1.85 and -3.46 kb to stimulate the expression of an otherwise inactive MUP1.5b-chloramphenicol acetyltransferase fusion gene specifically in the submaxillary gland. The nucleotide sequence of this 1.6-kb DNA fragment was found to be identical for the MUP1.5a and MUP1.5b genes. Together, these results provide the first localization of a cis-acting regulatory sequence involved in the differential tissue-specific expression of the MUP gene family.

Animals

Multiple sclerosis: histopathologic and MR and/or CT correlation in 37 cases at biopsy and three cases at autopsy.

The authors retrospectively reviewed the cases of 40 patients with biopsy- or autopsy-proved inflammatory demyelination consistent with multiple sclerosis (MS); each patient underwent magnetic resonance (MR) and/or computed tomographic (CT) imaging. In review of the 32 MR and 30 CT examinations, three predominant radiologic patterns were apparent: (a) relatively small homogeneous lesions with no or minimal diffuse enhancement; (b) hypoattenuating lesions on CT scans and hypointense lesions on short-TR MR images, with a contrast material-enhanced, isoattenuating or isointense ring; and (c) lesions that were more infiltrative and ill defined, with mixed attenuation and signal intensity and scattered enhancement. A common radiologic feature was lack of mass effect or edema in white matter surrounding even large lesions. In all but four patients the lesions were classified as active by using both histologic and clinical criteria. Histologically active lesions had various radiologic appearances; however, in all contrast-enhanced studies they demonstrated some form of enhancement. Inactive lesions were homogeneously hypoattenuating on CT scans, hypointense on short-TR MR images, and hyperintense on unenhanced, long-TR MR images.

Adolescent

The effect of high parathyroid hormone levels on the development of aluminum-induced osteomalacia in the rat.

A relative deficiency of parathyroid hormone (PTH) is generally observed in dialysis patients with aluminum-associated osteomalacia or aplastic bone disease. It has been suggested that high PTH levels may protect against the development of aluminum-associated bone disease. Through the use of a previously established model of aluminum-induced osteomalacia in the rat, the protective effect of PTH was evaluated. Aluminum was administered intraperitoneally at doses of 0, 5, 10, and 20 mg during a 2-day period, and rats were sacrificed 5 and 12 days after aluminum administration. PTH (bovine 1-34) was administered via a subcutaneously implanted Alzet pump at 2 U/h starting 4 days before aluminum administration and continuing until sacrifice. As the aluminum dose was increased to 20 mg, the osteoblast surface and the bone formation rate decreased. PTH supplementation increased the osteoblast surface at all doses of aluminum and increased the bone formation rate at 0 and 5 mg of aluminum. However, even with PTH supplementation, osteoblast surface decreased as the aluminum dose increased. In the absence of PTH supplementation, osteoblast surface was markedly reduced when the serum aluminum concentration was greater than 400 micrograms/liter or stainable trabecular aluminum surface exceeded 15%. When the stainable trabecular aluminum surface was greater than 12%, the bone formation rate was zero even during supplemental PTH administration. A significant correlation was observed between serum aluminum and stainable trabecular aluminum surface (r = 0.80 at 5 days and r = 0.86 at 12 days; P less than 0.001). However, after PTH administration, less stainable trabecular aluminum was present for the same serum aluminum concentration. Both with and without PTH, the slope of the correlation between serum aluminum and stainable trabecular aluminum surface was steeper at 5 days after aluminum administration than at 12 days. In conclusion, for an equivalent aluminum exposure, high PTH levels protected against the development of low turnover aluminum bone disease in the rat.

Aluminum

The effect of long-term intravenous calcitriol administration on parathyroid function in hemodialysis patients.

Secondary hyperparathyroidism is common in dialysis patients. Intravenous calcitriol has proven to be an effective therapy for the reduction of parathyroid hormone (PTH) levels. However, the effect of i.v. calcitriol on parathyroid function, defined as the sigmoidal PTH-calcium curve developed during hypocalcemia and hypercalcemia, has not been evaluated during the prolonged administration of i.v. calcitriol. Six hemodialysis patients with marked secondary hyperparathyroidism, PTH levels greater than 500 pg/mL (normal, 10 to 65 pg/mL), were treated for 42 wk with 2 micrograms of i.v. calcitriol after each hemodialysis. Parathyroid function was evaluated before and after 10 and 42 wk of calcitriol therapy. Between baseline and 42 wk, the basal PTH level decreased from 890 +/- 107 to 346 +/- 119 pg/mL (P less than 0.02) and the maximally stimulated PTH level decreased from 1293 +/- 188 to 600 +/- 140 pg/mL (P less than 0.01). In addition, calcitriol administration significantly decreased PTH levels throughout the hypocalcemic range of the PTH-calcium curve. Although the slope of the PTH-calcium curve (with maximal PTH as 100%) decreased between baseline and 42 wk (P less than 0.05), the set point of calcium did not change. Two patients with a decrease in both basal and maximally stimulated PTH levels after 10 wk of calcitriol, developed marked hyperphosphatemia between 10 and 42 wk; this resulted in an exacerbation of hyperparathyroidism despite continued calcitriol therapy. In conclusion, prolonged i.v. calcitriol administration is an effective treatment for secondary hyperparathyroidism in hemodialysis patients provided that reasonable control of the serum phosphate is achieved. In addition, the slope of the PTH-calcium curve may be a better indicator of parathyroid cell sensitivity than the set point of calcium.

Adult

Hysteresis of the parathyroid hormone response to hypocalcemia in hemodialysis patients with low turnover aluminum bone disease.

During the study of parathyroid function in 19 hemodialysis patients with low turnover aluminum bone disease, it was observed that serum parathyroid hormone (PTH) levels were higher during the induction of hypocalcemia than during the recovery from hypocalcemia. This type of PTH response has been termed hysteresis. Hypocalcemia was induced during hemodialysis with a calcium-free dialysate. When the total serum calcium level decreased to 7 mg/dL, the dialysate calcium concentration was changed to 3.5 mEq/L and the dialysis session was completed. One week later, hypercalcemia was induced during hemodialysis with a high-calcium dialysate. The mean basal PTH level was 132 +/- 37 pg/mL (normal, 10 to 65 pg/mL; immunoradiometric (IRMA), Nichols Institute, San Juan Capistrano, CA) and increased to a maximal PTH level of 387 +/- 91 pg/mL during hypocalcemia. For the same ionized calcium concentration, the PTH level was higher during the induction of hypocalcemia than during the recovery from hypocalcemia. Conversely, for the same ionized calcium concentration, the PTH level was greater when hypercalcemia was induced from the nadir of hypocalcemia than when hypercalcemia was induced from basal serum calcium. The set point of calcium (defined as the serum calcium concentration required to reduce maximal PTH by 50%) was greater during the induction of hypocalcemia than during the recovery from hypocalcemia (4.44 +/- 0.10 versus 4.25 +/- 0.09 mg/dL; P = 0.03). The mean basal ionized calcium concentration and the mean ionized calcium concentration at the intersection of the two PTH-calcium curves were the same (4.61 +/- 0.13 versus 4.61 +/- 0.12 mg/dL).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

EEG and skeletal development in children with different psychosocial characteristics.

Two groups of children with different socioeconomic level were studied. One minute EEG at rest was recorded in monopolar leads F3, F4, C3, C4, P3, P4, O1, O2, F7, F8, T3, T4, T5 and T6. Absolute and relative power in four EEg bands (delta, theta, alpha and beta) were computed. Radiographies of the left hand and the wrist were also obtained in all children. Age regression equations of the variables derived from EEG spectra were calculated in each group. In the group with low socioeconomic level many children had antecedents of risk factors. In this group absolute and relative power in the four bands presented a great dispersion and no correlation with age. In the group with good socioeconomic level the age regression equations of the EEG variables were significant, absolute values in the four bands decreased with age, as well as delta and theta relative power, while alpha and beta relative power increased with age. The area of the ossification center of each bone of the hand of the lower end of the ulna and radius were obtained from the X-ray film. Linear regression equations for the area of each ossification center were significant in both groups. No intercept or slope differences existed between both groups in any area. It is concluded that psychosocial disadvantage and antecedents of risk factors, although not producing any effect on skeletal development, do affect EEG maturation.

Adolescent

Variation in somatic cell count, California mastitis test, and electrical conductivity among various fractions of ewe's milk.

Variation of three estimates of udder inflammation (SCC, California mastitis test, and electrical conductivity) among the foremilk, machine milk, and hand stripping samples were studied. Foremilk and hand stripping milks were taken from each individual teat; machine milk was taken from the entire udder. For this experiment a total of 30 Manchega ewes were subjected to machine milking during the 9th wk of lactation. Samples were taken in duplicate during two milkings on consecutive mornings. Significant differences were observed in the SCC and electrical conductivity, but not in California mastitis test, between foremilk and stripping milk. The stripping fraction had higher SCC (70 +/- 12%) and lower electrical conductivity (difference = .52 +/- .03 mS/cm) than did the foremilk fraction in both healthy and mastitic udders. Machine milk, foremilk, and stripping milk fractions in udders where both halves were healthy were compared. The electrical conductivity values for the machine milk were intermediate and significantly different from conductivity of foremilk and stripping fractions. The log SCC of the machine milk did not differ from that of the foremilk fraction but was significantly less than the stripping milk.

Animals

DNA-RFLP analysis and genotyping of HLA-DR alleles in the south of Spain.

42 healthy individuals previously HLA-DR typed by serology, were HLA class II typed using RFLPs. The pattern of hybridization revealed allele specific DNA fragments for some DR specificities. Three fragments highly associated with HLA-DR antigens: a 7 kb RFLP with DR1; a 10 kb RFLP with DR-3/DR-5 and a 13 kb band with DR4/DR7.

Alleles

On the occurrence of BBB syndrome and hereditary sensory motor neuropathy in the same family.

We report the occurrence of the BBB syndrome and type 1 hereditary sensorimotor neuropathy (HSMN) in the same family: both disorders concurred in two brothers and a third presented only type 1 HSMN. The clinical findings in this family support the idea that the BBB and the G syndromes are variable manifestations of the same entity. The hypothesis that the BBB syndrome and type 1 HSMN might represent a contiguous gene syndrome is, however, not fully supported.

Child

Reproduction in the older gravida. A literature review.

Infertility, spontaneous abortions and trisomic anomalies increase with maternal age, as do ectopic pregnancy, low birth weight, macrosomia, abruptio placentae and labor dysfunction. However, those phenomena are multifactorial in origin and cannot be ascribed solely to advancing age. Older pregnant women are also at increased risk for diabetes and hypertension. Whereas the older gravida is at increased risk for maternal mortality and morbidity and for fetal and infant mortality, those problems are explainable in large part by coexisting medical complications. The healthy older pregnant woman who receives appropriate prepregnancy counseling and up-to-date perinatal care can achieve results comparable to those achieved by younger ones.

Abortion, Spontaneous

Paraneoplastic anti-Purkinje and type I anti-neuronal nuclear autoantibodies bind selectively to central, peripheral, and autonomic nervous system cells.

Autoantibodies provide serologic markers for subacute cerebellar degeneration in the setting of gynecologic or breast cancer (anti-Purkinje cell cytoplasmic antibodies, PCAb), and for encephalomyeloradiculoneuropathies in the setting of small cell lung carcinoma (type I anti-neuronal nuclear antibodies, ANNA-I). PCAb and ANNA-I are not species-restricted in their specificities. The subject of this report is a systematic immunocytochemical investigation of the distribution and types of cells in the mouse central and peripheral nervous system that bind these IgG autoantibodies. Sera used for the study were from two patients with prototypic PCAb reactivity and two with prototypic ANNA-I reactivity, none of whom had evidence of other autoantibodies, and from four age- and sex-matched healthy control subjects. The patients' clinical features were consistent with the classic syndromes that have been reported with PCAb and ANNA-I, respectively. PCAb bound prominently to the cytoplasm of cerebellar Purkinje cells, and also to other large cytoplasm-rich neurons throughout the central nervous system, to neurons in sensory and sympathetic ganglia and myenteric plexus, and to cells of the adrenal medulla. ANNA-I, on the other hand, bound to virtually all neurons in the central and peripheral nervous system, including sensory and autonomic ganglia, myenteric plexus and cells of the adrenal medulla. An unanticipated finding was that immunoreactivity with ANNA-I was enhanced by fixing tissues briefly with formalin. Astrocyte processes were stained by PCAb and by ANNA-I (but not by the control sera). The cytoplasm of sciatic nerve Schwann cells was stained strikingly by PCAb, but ANNA-I did not bind to Schwann cells. Although it has not yet been determined whether or not PCAb or ANNA-I per se are pathogenic, it is apparent that they represent at least a component of an immune response that is initiated by tumor antigens. The distribution of these tumor-related antigens in the nervous system is consistent with the diversity of neurologic manifestations that can occur in individual patients with the associated paraneoplastic syndromes.

Aged

Immunoglobulins stimulate central nervous system remyelination: electron microscopic and morphometric analysis of proliferating cells.

Infection with the Daniel strain of Theiler's murine encephalomyelitis virus results in immunemediated primary demyelination in the spinal cords of susceptible SJL/J mice. Treatment of chronically infected mice (3 to 7 months) with purified immunoglobulins directed against spinal cord homogenate resulted in an increase in the number and average size of lesions that were undergoing remyelination by oligodendrocytes. In vivo autoradiography with [3H]thymidine demonstrated labeling of many lymphocytes in areas of demyelination and remyelination. A direct correlation was found between number of labeled lymphocytes infiltrating the lesion and size of demyelinating lesions. Remyelinated areas contained proliferating cells that resembled immature oligodendrocytes or progenitor glial cells morphologically. The number of labeled presumptive glial cells correlated with the area of remyelination. However, central nervous system remyelination occurred even in the presence of proliferating lymphocytes and astrocytic hypertrophy. In addition, treatment of normal uninfected SJL/J mice with antiserum to spinal cord homogenate resulted in increased numbers of proliferating cells in the spinal cord. These experiments suggest that immunoglobulins to a spinal cord antigen may induce proliferation of cells in the central nervous system to promote remyelination.

Animals