Biomedical subjects
Publications and source records attributed to C Cohen.
A toxoplasma cyst and the distinctive histopathologic changes of toxoplasmic lymphadenitis in a non-immunosuppressed patient with acute acquired toxoplasmosis are described. This is the third reported case in which the cyst form of toxoplasma has been observed in nodal tissue, and the first to be confirmed by electron microscopy.
In a series of 46 cases of primary mammary ductal carcinoma, immunohistochemical markers of differentiation (casein, human placental lactogen, alphalactalbumin, pregnancy specific beta-1 glycoprotein, secretory component, CEA, and peanut lectin agglutinins [PLA]), were quantitated via point-counting. An immunoperoxidase bridge (PAP) was used to identify all except the PLA, in which an avidin-biotin complex with alkaline phosphatase development was employed. For none of the markers was there any difference in the quantity present in tumors of patients who had recurred versus the tumors of patients who had enjoyed a minimum of five years disease-free survival. Nonneoplastic epithelium was only rarely positive for these markers. Although eventually surmounted, technical problems significantly hampered application of morphometry to this histochemical material. The authors conclude that these markers have little relationship to differentiation toward mammary duct epithelium and that they do not provide significant prognostic information in patients with breast cancer.
Two patients with leukocytoclastic vasculitis of dermal vessels and evidence of infection by herpesvirus in the overlying epidermis showed, by conventional microscopy, viral inclusions in endothelial cells and in dermal fibroblasts adjacent to them and, by electron microscopy, viral inclusions in endothelial cells and pericytes of involved vessels. It is speculative whether viral involvement of the latter structures was the result of direct spread of the virus along dermal nerves, from the overlying intraepidermal viral vesicles, or from hematogenous dissemination of the virus.
Noninbred rabbits that were characterized for antigens of the major histocompatibility complex (MHC) by serological (RLA) typing were used as adult donors and newborn recipients of lymphoid cells. The majority of RLA-heterozygous (CE) animals transplanted with homozygous type C cells died before 7 weeks of age with clinical and histological signs of graft-versus-host disease, but a small proportion survived with their lymphoid and erythroid systems completely converted to phenotypes of the donors. Takeover of the host's hematopoietic system was associated with a transient hyperimmunoglobulinemia, mostly of donor origin, and with a striking and permanent abrogation of allotype suppression on the part of donor lymphocytes. In contrast, as shown in this and in earlier publications, recipients of RLA-compatible cells become stable B lymphocyte chimeras without detectable T cells or erythrocytes of donor type. In the latter case allotype suppression is neither established in the recipient nor abrogated in the donor's cells.
We studied the effect of transcendental meditation (TM) on breathing using 16 experienced meditators and 16 control subjects. In controls, there was no significant difference in minute ventilation (VE), respiratory pattern, or hypercapnic response, whether breathing with eyes open-awake (CA), or with eyes closed-relaxing (CR). In meditators, VE decreased significantly during quiet breathing from 14.0 +/- 0.7 1/min with eyes open-awake (MA) to 12.4 +/- 0.6 1/min during meditation (MM) (P less than 0.02). The change in VE during meditation was due to a decrease in tidal volume (VT) resulting from a shortened inspiratory time (TI). Meditation was associated with a decreased response to progressive hypercapnia from 3.7 +/- 0.4 to 2.5 +/- 0.21 X min-1 X Torr-1 during MA and MM trials, respectively (P less than 0.01). During meditation VT was smaller at a given alveolar PCO2 than during MA studies because of a decrease in mean inspiratory flow rate (VT/TI). These observations suggest that an alteration in wakefulness, more subtle than sleep or the unconscious state, can significantly affect the chemical and neural regulation of breathing.
Ipratropium (40 micrograms) and theophylline (oxtriphylline 400 mg) were administered to 24 asthmatics in a randomized double-blind placebo controlled trial. The combination of these agents produced additive bronchodilation for up to two hours, with a 23 percent maximal increase in FEV1. This regimen promises to be safe, effective therapy for patients with asthma.
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Nevus comedonicus (NC) is rarely associated with the histopathologic changes of epidermolytic hyperkeratosis (EH). A parent with mild focal NC had a child with severe generalized EH. The histopathologic findings of skin biopsy specimens from parent and child showed the distinctive granular and spinous layer vacuoles and coarse keratohyaline granules of EH. This parent and child may be examples of the extremes in expression of an autosomal dominant trait.
Small-angle X-ray diffraction patterns of chemically skinned pedal retractor muscles from Mytilus (PRM) in the relaxed state show a set of diffuse off-meridional reflections that arise from a helical array of myosin crossbridges with 8/3 screw symmetry. Experiments involving extraction of myosin as well as analysis of the rigor pattern have been used to confirm the origin of these reflections. The relatively high myosin/paramyosin molar ratio (1.3 to 1.6) in PRM compared to other molluscan smooth muscles may account for the observation of the relatively stronger diffraction from the myosin array. Thick filaments isolated from PRM and contrasted by negative staining for electron microscopy appear to be very long (up to 17 micron), and to have a rather small diameter (about 40 nm at the center); they taper gradually toward the ends. These filaments show a clear transverse band pattern repeating at 14.4 nm and elongated projections (crossbridges) at the surface except in the central bare zone. Optical diffraction patterns show reflections from crossbridges consistent with the X-ray patterns of the relaxed whole muscle. Filaments unidirectionally shadowed with platinum show diagonal striations running at an angle of about 17 degrees to the filament axis, revealing that the crossbridges are arrayed in a right-handed helix. The paramyosin core is clearly seen upon extraction of myosin. Observations on both negatively stained and sectioned material are consistent with the results of Elliott (1979) and Bennett & Elliott (1981) suggesting a layered structure of the core. Cores stripped of myosin, however, appear to undergo some distortion indicating that the three-dimensional structure is not yet completely solved. The assembly of these thick filaments presents intriguing structural problems since the myosin surface lattice does not appear to have the same symmetry as the underlying paramyosin core.
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Our present low resolution model for fibrinogen based on electron microscopy and x-ray diffraction data has been described by Cohen et al. A unique aspect of the structural analysis of fibrous proteins is that the molecular packing in ordered arrays reflects biologically significant intermolecular interactions. We have shown that the orthogonal sheet microcrystals, which are closely related to fibrin, are made up of a highly regular arrangement of two-stranded protofibrils, and we have visualized aspects of both the substructure of the protofibrils as well as their packing to form the fibrin clot. By correlation of structural data with biochemical studies we have begun to identify certain functional regions of the fibrinogen model related to fibrin. Many aspects of fibrinogen's physiological activity remain to be related to its structure. As our present model is improved by higher resolution studies, we will see with increasing clarity molecular features critical for clot formation and fibrinolysis.
Two cases of gas formation in the urinary tract are described. Both patients were diabetics. In the first patient the gas was situated in the collecting system while in the second the gas was confined to the perinephric space. The prognosis in the latter situation is especially poor and review of the literature suggests that surgical intervention either by incision and drainage or by nephrectomy is the treatment of choice.
Measurements of binding of certain divalent cations to yeast apoenolase were made using a pH-meter, chromatography, a divalent cation electrode, and ultrafiltration. The binding of the activating metal ions Mg2+ and Co2+ and the nonactivator Ca2+ were studied as functions of the presence or absence of substrate/product, phosphate, and fluoride or level of Tb3+. The data suggest phosphate and fluoride increase Mg2+ binding but not Ca2+ binding. Substrate/product appears to increase Ca2+ binding as well as that of Mg2+ and Co2+. In the presence of substrate, Co2+ binding was 5-6 mol/mol dimer. In the absence of substrate/product, Tb3+ reduced Co2+ binding from 4 mol/mol to 2. These data are interpreted in terms of binding to "conformational," "catalytic" (substrate/product dependent), and "inhibitory" sites. Measurements of Tb3+ fluorescence quenching by Co2+ suggested that the distance between "conformational" sites on the two subunits was large, while the distance between "conformational" and "inhibitory" sites was ca. 17 +/- 4 A. Potentiometric titrations of apoenzyme with Ca2+ and Mg2+ showed that the metal ions produced the same proton release in the presence or absence of substrate/product. If phosphate and fluoride were present, then more protons were released if Ca2+ was the titrant rather than Mg2+, suggesting a difference in ionization state in the complex with the activating metal. Electron paramagnetic resonance studies of Co2+ binding to the various sites in the enzyme are presented. The Co2+ bound to all three sites appears to be high spin, consistent with a preponderance of oxyligands in an octahedral environment. Substrate, citrate, and a strongly binding substrate analogue strongly enhance the hyperfine structure of conformational Co2+. This is interpreted as the result of a change in interaction of an axial ligand to conformational Co2+ produced by carbon-3 of substrate or analogue.
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Fifty normal kindergarten and 50 first-grade children were examined three times at six-month intervals for synkineses to stress gaits and mirror movements to finger lifting, finger spreading, and timed motor maneuvers. Motor signs in the age-sensitive range showed substantial individual differences between children of the same chronological age. The frequency of associated movements changed reliably in the expected direction over a 12-month period, and within each domain of neuromotor function the individual motor signs conformed to a stable sequence of developmental stages. It is concluded that age-appropriate motor signs for associated movements are a reliable measure of developmental age, in contrast to chronological age, among elementary-school children.
Review of the case notes of 660 patients with a diagnosis of breast cancer during a five-year period showed that in 119 cases there had been thoracic metastases. These were recorded as pleural or extrapleural metastases (79 patients), mediastinal tumour (46 patients), lymphangitic carcinoma (41 patients), pulmonary nodules (34 patients), and solitary pulmonary nodule (nine patients). Endobronchial metastases were present in seven patients and multiple pulmonary tumour emboli in two. The thorax was often the initial site of tumour recurrence. Most of these recurrences were present in several locations (intrathoracic or both intrathoracic and extrathoracic) simultaneously, facilitating the clinical diagnosis of metastatic breast cancer. Histopathological confirmation of metastasis was mandatory for the 10 patients who had a solitary intrathoracic abnormality without evidence of disease elsewhere. The median survival after diagnosis and treatment of a solitary thoracic metastasis was 42+ months and three of 10 patients are currently in remission (at 44, 87, and 121 months). The small tumour burden and early diagnosis giving lead time may explain the long survival in this group of patients.
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