Biomedical subjects
B Miller
Publications and source records attributed to B Miller.
Hereditary microphthalmia with colobomatous cyst.
We examined five members of a highly inbred kinship who had isolated microphthalmia associated with colobomatous cysts and various other ocular lesions. They were all offspring of consanguineous (first cousins) and unaffected parents. Microphthalmia in this kindred was transmitted as an autosomal recessive trait. Ultrasonography was effective for prenatal diagnosis in two pregnancies at risk.
Factors affecting the stability of methanol dehydrogenase from Paracoccus denitrificans.
Methanol dehydrogenase from Paracoccus denitrificans was purified to homogeneity in two steps from the periplasmic fraction of methanol-grown cells. The enzyme was composed of subunits of M(r) 67,000 and 12,000, and non-covalently bound pyrroloquinoline quinone. It exhibited a pH optimum at pH values of 9.0 and above. It was not stable at pH greater than 9.0, but exhibited little loss of activity after prolonged incubation at pH values as low as 4.5. Methyl dehydrogenase was relatively stable to thermal denaturation. The thermal stability was enhanced by the presence of Ca2+ and diminished by the presence of EDTA. These data suggest a structural role for Ca2+ in this enzyme, similar to what has been observed with quinoprotein glucose and ethanol dehydrogenases.
Potentiation of NMDA receptor currents by arachidonic acid.
Arachidonic acid is released by phospholipase A2 when activation of N-methyl-D-aspartate (NMDA) receptors by neurotransmitter glutamate raises the calcium concentration in neurons, for example during the initiation of long-term potentiation and during brain anoxia. Here we investigate the effect of arachidonic acid on glutamate-gated ion channels by whole-cell clamping isolated cerebellar granule cells. Arachidonic acid potentiates, and makes more transient, the current through NMDA receptor channels, and slightly reduces the current through non-NMDA receptor channels. Potentiation of the NMDA receptor current results from an increase in channel open probability, with no change in open channel current. We observe potentiation even with saturating levels of agonist at the glutamate- and glycine-binding sites on these channels; it does not result from conversion of arachidonic acid to lipoxygenase or cyclooxygenase derivatives, or from activation of protein kinase C. Arachidonic acid may act by binding to a site on the NMDA receptor, or by modifying the receptor's lipid environment. Our results suggest that arachidonic acid released by activation of NMDA (or other) receptors will potentiate NMDA receptor currents, and thus amplify increases in intracellular calcium concentration caused by glutamate. This may explain why inhibition of phospholipase A2 blocks the induction of long-term potentiation.
Low antibody avidity in elderly chickenpox patients.
A small outbreak of chickenpox confirmed serologically in 3 elderly patients from a geriatric home is described. Disease was probably due to exogenous reinfection, yet nevertheless the avidity of specific antibodies measured by the urea denaturation test was even lower than in primary chickenpox controls, which themselves were, as expected, significantly lower than zoster controls. In elderly individuals susceptibility to reinfection with varicella-zoster virus (VZV) with clinical manifestation such as chickenpox may well be associated with the decay of specific humoral immunity detectable by antibodies of particularly low avidity, in contrast to reactivation of latent VZV presenting clinically as zoster, which is related to deficiencies in specific cellular immunity.
Comparison of the fracture strengths of ceramometal crowns versus several all-ceramic crowns.
Fracture resistance to forces applied to the incisal edges of four types of anterior crowns was tested. Ceramometal crowns fractured at significantly higher values (720 psi) than the all-ceramic crowns (approximately 360 psi). No significant difference was found among the fracture values of the Dicor crowns, the aluminous porcelain jackets, and the crowns fabricated from Dicor veneered with aluminous body and incisal porcelain.
Antibody response to Bordetella pertussis antigens after immunization with American and Canadian whole-cell vaccines.
Because of apparent differences in the incidence and epidemiology of pertussis in the United States and Canada, we measured the antibody response to four Bordetella pertussis antigens and to a whole-bacteria preparation in children immunized with American and Canadian whole-cell pertussis vaccines. All infants received combined pertussis, tetanus, and diphtheria vaccines from one of two American manufacturers or a single Canadian manufacturer. The Canadian children received either oral poliomyelitis vaccine, inactivated poliomyelitis vaccine as a separate injection, or a product that combined inactivated poliomyelitis vaccine with diphtheria, tetanus, and pertussis components. The Canadian trivalent diphtheria, tetanus, and pertussis vaccine given with oral poliovirus vaccine induced lower anti-pertussis toxin antibody titers than did the American vaccines (p < or = to 0.05) but higher antifimbriae and anti-69-kilodalton outer-membrane protein (pertactin) antibody titers (p < or = to 0.02). Canadian children immunized with inactivated poliomyelitis vaccine either as a separate injection or as a combined diphtheria, tetanus, and pertussis vaccine had consistently lower pertussis antibody titers than did those who received oral poliomyelitis vaccine (p < or = 0.001). We conclude that there is a wide range of antibody responses to B. pertussis antigens after immunization with various whole-cell pertussis vaccines, and that these responses may be influenced by concurrent administration of other vaccines.
Gender differences in caregiving: fact or artifact?
This study applies meta-analysis techniques to the results of 14 descriptive studies of gender differences in caregiving to determine the size and significance of gender differences in caregiving stressors (level of elder impairment and level and type of task involvement) and in caregiver burden. There were essentially no significant gender differences in functional impairment of the frail care recipient, total caregiver involvement in care, or in money management tasks. Female caregivers were more likely to carry out personal care and household tasks and more likely to report greater burden. Given the relatively small size of the effects found, we conclude that future research should focus on the part that gender-role explanations play in assigning meaning to caregiving behaviors.
A survey of interhospital transfer of head-injured patients with inadequately treated life-threatening extracranial injuries.
A 12 month prospective study was undertaken to determine the frequency of untreated life-threatening extracranial injuries in patients transferred to a major trauma centre because of head injury. Of the 43 patients transferred (15 with isolated head injury and 28 with multiple injuries), four (9%) had an untreated life-threatening extracranial injury, which caused death in two. All four patients with untreated extracranial injuries were transferred from hospitals with general surgical staff and facilities. In three of the patients (none with a major head injury), the extracranial injuries were recognized at the referring hospital, but were left untreated in the rush to transfer the patient to a neurosurgical facility. In the fourth patient, who had a severe head injury, recurrent hypotension from a ruptured spleen was mistakenly ascribed to a scalp wound. The series shows that the dangerous practice of hurriedly transferring patients to trauma centres because of actual or perceived head injuries, while leaving major extracranial injuries untreated, continues despite warnings in the literature and the efforts of the Royal Australasian College of Surgeons through the Early Management of Severe Trauma programme.
Connective tissue of the orbital cavity in retinal detachment: an ultrastructural study.
The connective tissue from Tenon's capsule of 7 patients who underwent surgery for retinal detachment was studied ultrastructurally. Five patients were 58-70 years old, and 2 were young adults. The Tenon capsules of 6 children and of 2 aged patients without retinal problems were used as controls. In young controls the Tenon capsule was composed mainly of round, smooth collagen fibrils and a few elastic fibers. The collagen fibrils varied in size from 70 to 110 nm. In the aged patients with retinal detachment, the collagen fibrils showed marked variation of size and also abnormalities of shape in 4 out of 5 cases. The diameter of collagen fibrils varied from 32 to 160 nm, and the elastic fibers were fewer as compared with controls. The possibility arises that age-related structural changes of the orbital connective tissue could predispose to retinal detachment.
Tenon's capsule: ultrastructure of collagen fibrils in normals and infantile esotropia.
No detailed information about the ultrastructure of Tenon's capsule has been published. The purpose of the present study was to compare the ultrastructural features of collagen fibrils from Tenon's capsule in a nonstrabismic control group (seven children) to those in an infantile esotropic group (10 children). Small biopsy specimens from Tenon's capsule were taken during various operations to be examined by electron microscopy. On electron microscopy, the capsule was found to be composed of groups of collagen fibrils arranged irregularly in different orientations, forming a three-dimensional network that provides tissue resistance to stress. The cross-sectioned collagen fibrils were studied by an image analyzer. In both study groups, all fibrils had a round, regular contour. In the esotropic group, the Tenon's collagen fibrils were thicker, as reflected by their significantly greater mean diameter: 101 +/- 5 nm (mean +/- standard deviation) compared to 86 +/- 5 nm in the control group. Also, significantly greater heterogeneity was found in the collagen fibril thickness of each individual in the esotropic group compared to the control group. Moreover, the mean number of collagen fibrils per unit area was significantly higher in the esotropic group: 98 +/- 13 fibrils per 10(6) nm2 compared to 73 +/- 5 fibrils per 10(6) nm2 in the control group. These ultrastructural changes may be stress-induced secondary alterations of the Tenon's collagen fibrils resulting from prolonged deviation of the eye in infantile esotropia. The significantly denser collagen fibrils may cause a decrease in the elasticity of Tenon's capsule in infantile esotropia.
Loss of transforming growth factor beta 1 (TGF-beta 1)-induced growth arrest and p34cdc2 regulation in ras-transfected epithelial cells.
Transforming growth factor beta 1 (TGF-beta 1) is a potent inhibitor of mink lung epithelial (CCL64) cell growth in culture. The fact that many transformed epithelial cells have escaped from negative growth control by TGF-beta 1 suggests that transfected epithelial cells may be an appropriate model for investigating the growth-inhibitory mechanism of TGF-beta 1. We transfected CCL64 cells with a mouse c-myc oncogene (pSVc-myc1), a mutated Harvey-ras (Ha-ras) oncogene, or a combination of both. The results indicate that cells transfected with c-myc alone exhibit normal morphology and maintain sensitivity to TGF-beta 1 growth arrest, but are unable to form colonies in soft agar in the presence or absence of TGF-beta 1. Cells transfected with Ha-ras, or co-transfected with c-myc, display a transformed morphology, grow spontaneously under anchorage-independent conditions and acquire a complete resistance to growth inhibition by TGF-beta 1. Affinity cross-linking of [125I]TGF-beta 1 to cell-surface receptors from these transfectants revealed that all three TGF-beta receptor types were present and no significant differences in [125I]TGF-beta 1 labeling of these receptors was observed. Since we have previously demonstrated that modulation of p34cdc2 kinase is a marker for TGF-beta 1 growth inhibition, we investigated p34cdc2 activity in the CCL64 transfected clones. The results show that in the control CCL64 cells and in the myc-transfected clones TGF-beta 1 regulation of p34cdc2 activity is maintained. In the ras- and ras + myc-transfected cells p34cdc2 phosphorylation and histone H1 kinase activity is significantly increased and regulation by TGF-beta 1 is lost.
Structure of 6 beta,6'beta-bi(7 alpha-allyl-3-oxo-4-estren-17 beta-yl acetate).
C46H62O6, Mr = 711.0, orthorhombic, P2(1)2(1)2(1), a = 20.187 (3), b = 22.004 (3), c = 9.180 (1) A, V = 4078 (2) A3, Z = 4, Dx = 1.16 g cm-3, lambda (Mo K alpha) = 0.71069 A, mu = 0.7 cm-1, F(000) = 1544, T = 295 K, R = 0.096 for 3894 unique observed reflections with Fo greater than 2 sigma(Fo). The title compound is a dimer connected by a single bound between C6 and C6' [bond length 1.560 (7) A]. The two steroid moieties are oriented beta-face to beta-face, head to head and lie in almost parallel planes (7.6 degrees), rotated by 45 degrees to one another. The two conformations of the identical portions of the dimer differ chiefly in the orientation of the allyl and acetate groups. C23' (acetate) and O3' form the shortest intermolecular contact less than 3.5 A; C...O = 3.35 (1) A.
Neurobehavioral effects of phenytoin prophylaxis of posttraumatic seizures.
In order to determine potential negative neurobehavioral effects of phenytoin given to prevent the development of posttraumatic seizures, 244 subjects were randomized to phenytoin or placebo. They received neurobehavioral assessments at 1 and 12 months postinjury while receiving their assigned drug and at 24 months while receiving no drugs. In the severely injured, phenytoin significantly impaired performance at 1 month. No significant differences were found as a function of phenytoin in the moderately injured patients at 1 month or in either severity group at 1 year. Patients who stopped receiving phenytoin according to protocol between 1 and 2 years improved more than corresponding placebo cases on several measures. We conclude that phenytoin has negative cognitive effects. This, combined with lack of evidence for its effectiveness in preventing posttraumatic seizures beyond the first week, raises questions regarding its use for long-term prophylaxis. Our findings do not negate phenytoin's proven efficacy in controlling established seizures nor do they indicate that its cognitive effects are worse than other anticonvulsant drugs.
Alterations in Alzheimer's disease-associated protein in Alzheimer's disease frontal and temporal cortex.
Alzheimer's disease (AD)-associated protein is present in brain and cerebrospinal fluid of patients with AD but not in adult, nondemented, normal controls. This protein may represent an abnormal epitope of the "tau" microtubule-associated protein and has been detected before the appearance of senile plaques and neurofibrillary tangles. The amount of AD-associated protein in the frontal and temporal cortices in 93 cases of neuropathologically confirmed AD was compared with the amount that was present in 20 cases without AD. The amount of AD-associated protein was significantly increased in the cases of AD for both brain regions compared with that in the cases without AD. The presence of high levels of this protein is a useful adjunct, postmortem marker of the presence of AD and may eventually lead to tests that allow early detection of individuals at risk for this disease.
Lymphoepithelioma-like carcinoma of the lung.
Historically lymphoepithelioma was a term used to describe an undifferentiated mucosal carcinoma with a lymphocytic component arising only from the nasopharynx, although recently, lymphoepithelioma-like carcinoma has been found to occur as a primary tumor of the lung. Thus far, five patients have been documented as having this rare anatomical presentation. The patient that is being presented is the latest case of lymphoepithelioma-like carcinoma of the lung and will be compared clinically and histologically with the other four cases. The case is presented in order to discuss optimal methods of diagnoses and treatment for this condition.
Small cell carcinoma of the cervix: a clinical and flow-cytometric study.
The clinical course of 14 patients diagnosed with small cell carcinoma of the cervix (SCC) was reviewed and compared to that of 37 cases of undifferentiated large cell nonkeratonizing carcinoma (LCNK). We observed the following differences between the two: SCC patients had a higher incidence of pelvic wall involvement and distant metastasis; the development of progressive disease was more frequent in SCC than in LCNK patients; median survival time was 9 months in SCC and 40 months in LCNK patients; flow cytometry revealed aneuploidy in all SCC and in 30% of the LCNK patients; the mean DNA index was 2.24 in SCC, significantly higher than in LCNK (1.15). DNA index in cases of SCC was related to survival time. SCC of the cervix is an extremely aggressive tumor, even when compared to other undifferentiated cervical cancers. Aneuploidy is a consistent feature and thus helpful for diagnosis. Due to the wide range of values, the DNA index cannot be used for diagnostic purposes, but it is of prognostic importance in SCC cases.
The impact of elder health, caregiver involvement, and global stress on two dimensions of caregiver burden.
This study examined the simultaneous effects of an elder's health, caregiver involvement, and stress on caregiver burden, addressing the questions: (a) What are the direct and indirect effects of level of elder's impairment, caregiver involvement, and stress on personal and interpersonal burden? (b) How do these relationships differ between spouse and adult-child caregivers? Data were from the 1982 National Long Term Care Survey. Results using linear structural relations analysis showed the effect of a frail elder's health and functioning on personal and interpersonal burden is mediated by task involvement and perceived global stress. Contrary to expectation, there were few differences in the direct effect of each dimension of health, functional limitations, cognitive status, and global health rating on each dimension of burden. Although the results suggested mean differences between spouse and adult child caregivers on key variables, there were no differences by family relationship in the system of relationships that comprise the process linking health and burden.