Biomedical subjects
Publications and source records attributed to H Wiegand.
A 17-year-old man was resuscitated after being struck by lightning. The ECG showed a development similar to anterior infarction. The patient died on the 12th day due to irreversible brain damage. Autopsy showed normal myocardium.
Three brothers from one family died of Hodgkin disease and a fourth brother from a diffuse malignant non-Hodgkin lymphoma. This patient exhibited a constant deficiency of serum immunoglobulins and elevated antibody titers to Epstein-Barr viral antigens. Epstein-Barr virus DNA sequences were detected in DNA isolated from lymph node biopsies from two of the patients. Initially, no abnormalities in the numbers of B and T cells could be detected. Peripheral blood lymphocytes of the patients did not react in the mixed lymphocyte culture assay. We suggest that an immune deficiency to Epstein-Barr virus may favor the proliferation of malignant lymphocytes after Epstein-Barr viral infection. Monoclonal lymphoid B cell lines established spontaneously in vitro from a lymph node biopsy specimen and from peripheral blood specimens from two of the patients. The cells harbor Epstein-Barr viral DNA sequences in multiple genome equivalents and express Epstein-Barr nuclear antigen. The cells contain a tenfold increased level of c-fgr-related RNA transcripts compared with peripheral blood lymphocytes of healthy adults. No obvious amplifications or translocations of the c-myc, c-abl, or c-fgr gene could be detected.
The effects of acute lead exposure on extracellularly recorded evoked responses in the CA1 region of hippocampal slices were investigated. Field potentials in response to paired-pulse stimulation were assessed while perfusing the slices with normal media and media containing lead in concentrations of 0.2 microM to 53 microM. The evoked population excitatory postsynaptic potentials decreased during lead exposure to a lesser extent than the orthodromically evoked population spike, whereas the presynaptic fiber volley remained unchanged. The maximal inhibition of the orthodromically evoked responses depended strongly on the lead concentration. The input-output relations of the orthodromic responses obtained during perfusion with lead significantly differed from those during control conditions. The somatic short-term potentiation obtained by paired-pulse stimulation increased during the lead exposure. Lead seemed to inhibit the evoked activities only transiently: within 20 min after lead onset, the recorded responses had reached the control level again in spite of further lead perfusion. In contrast to the orthodromically evoked responses, the antidromically evoked population spikes remained constant at all concentrations used. It is concluded from these results that lead acts presynaptically in the hippocampal slice preparation. Additionally, lead interferes with non-synaptic processes at the pyramidal neurons in the CA1. Possible influences of lead over different neurotransmitter systems are discussed.
In 3 patients seropositive for HIV 1 (2 homosexual men and 1 female drug addict), we found "oral hairy leukoplakia" on the lateral margin of their tongues. DNA of Epstein-Barr virus (EBV) and Human Papillomavirus (HPV) were identified in cellular DNA by molecular-virological means using Southern blot hybridization and/or DNA/DNA filter hybridization on epithelial cells taken by swabs from the epithelium of the tongue. The results were compared with those obtained from the identical anatomical sites of 2 HIV-1-seropositive patients without "oral hairy leukoplakia", 3 clinically healthy HIV-1-seronegative patients, and 2 HIV-1-negative patients suffering from oral leukoplakia on their lateral tongues. In all 3 cases investigated, EBV DNA was detected in cells taken from "oral hairy leukoplakia" by filter in situ hybridization. In addition, EBV DNA was found in cells taken from clinically normal epithelia of the tongue as well as in those taken from the 2 leukoplakias mentioned. EBV DNA was regularly detected on the lateral margin of the tongue, but only in one case on the pharyngeal mucosa. Electronmicroscopy on ultrathin sections revealed particles of herpes virus (EBV), particles of HPV, in one case particles of retrovirus, and in another coronavirus and diplococci.
The toxic effect of thallium added to the bath solution was studied with intra- and extracellular recordings from mammalian nerve-muscle preparations. To elucidate the target region, 3 different functional parameters were studied: (1) Post-synaptic endplate potentials (EPPs) resulting from evoked transmitter release; (2) Post-synaptic miniature endplate potentials (MEPPSs) resulting from spontaneous transmitter release; and (3) Presynaptic ion currents at the nerve terminal. At a concentration of 0.5 mM/l thallium acetate, EPP amplitudes were irreversibly decreased while MEPP amplitudes remained unaffected. MEPP frequencies were reversibly increased, indicating a presynaptic rather than a post-synaptic target site of thallium toxicity. The subpopulation of small MEPPs (sub-MEPPs) behaved like the MEPP population, except that upon addition of 4-AP, the sub-MEPP population was augmented at the cost of the MEPP population. In view of the slow time course of the toxic effects (30 min for a 10-fold increase of MEPP frequency, 100-180 min for a 50% reduction of EPP amplitudes), it is concluded that thallium needs to be transported across the cell membrane before it finally interferes with release mechanisms. It is hypothesised that thallium reduces the number of active sites recruited by one action potential (reduced EPP amplitude), while at the same time the probability of transmitter liberation is enhanced (increased MEPP frequency). The rather indirect mode of action of thallium was also found when presynaptic ion currents were recorded using extracellular electrodes. In proportion to the decrease of the EPP amplitudes, a reduction of all inward and outward currents was observed. This effect was also irreversible. It is concluded that in spite of some similarities, thallium behaves quite differently from bivalent heavy metals like cobalt and cadmium, which act as competitive calcium antagonists at the presynaptic nerve terminal. In these toxic substances, the time course of intoxication is much faster, the required concentration is much lower, and the inhibition of the slow calcium current is reversible.
The two most important methods used for objective determination of visual acuity are those of Ohm-von Romberg and Günther. A newly developed instrument based on Günther's principle is described which combines the advantages of both methods. Using a Leitz projector and a specially designed accessory unit, a constantly moving screen of dots measuring 64 X 64 cm is projected. The setting was standardized on the basis of 358 eyes with visual acuities ranging from finger counting to 1.0. The correlation between the measured distance (from screen to patient) at which an optokinetic nystagmus was just induced and visual acuity was r = 0.98 over the entire visual acuity range. The visual acuity to be expected can be read off from the diagrams or a table, with a scatter range of +/- 1 sigma, +/- 2 sigma, or +/- 3 sigma. The relevant literature is discussed. Replication of the accessory unit described can be recommended.
Between 1975 und 1985 we performed 281 percutaneous cervical cordotomies in 212 patients among whom there were 35 patients with urological malignancies. We report about the method, localisation of tumour and pain, results and complications. Altogether we can say, that percutaneous cervical cordotomy is an efficacious procedure with an acceptable complication rate in patients with chronic pain from malignant diseases especially in the urological field.
A diagnostic hybridization assay for detecting varicella zoster virus (VZV), herpes simplex virus (HSV), and Epstein-Barr virus (EBV) in different clinical specimens was developed using cloned viral DNAs as probes. All probes detected at least 5 pg of homologous DNA and did not cross-react with other viral or cellular DNA. Results of cell culture, serology, and DNA assay were highly concordant. Using a simple standardized protocol for preparation of specimens, hybridization, and washing procedures, this sensitive and specific assay appears to be useful for screening clinical specimens and may be helpful in confirming the serological diagnosis of HSV encephalitis and persistent EBV infections or EBV-associated diseases.
Endplate potentials (EPP's) and miniature endplate potentials (MEPP's) were recorded from neuromuscular junctions of the mouse phrenic nerve-diaphragm preparation, blocked by high Mg++ (12 X 10(-3) mol/l)-Ringer. Superfusion of the preparations with Mg++-Ringer solutions containing thallium acetate (5 X 10(-4) mol/l Tlac) decreased phasic transmitter release as judged by EPP amplitudes as well as average quantal content, until total synaptic blockade (within about 300 min) occurred. Simultaneously MEPP amplitudes remained unchanged, whereas the frequency of MEPP's increased. When EPP amplitudes and/or quantal content were reduced by 50% (usually within about 180 min), superfusion with Mg++-Ringer solution without Tlac did not restore phasic transmitter release. However, the increase in spontaneous transmitter release was reversible, as MEPP frequencies returned to normal values. 4-Aminopyridine (5 X 10(-4) mol/l 4-AP) as added to the bath solution in the state of 50%-reduced phasic release temporarily restored EPP amplitudes and average quantal content, whereas MEPP amplitudes remained unchanged. It is concluded that thallium irreversibly blocks phasic transmitter release, whereas spontaneous transmitter release is reversibly enhanced.
A new diagnostic assay was developed to detect herpes simplex virus (HSV) and adenovirus DNA in clinical specimens using in vitro synthesized radioactively labelled RNA transcripts from virus-specific DNA fragments cloned in transcription vector pSP 64/65. RNA probes derived from HSV-I-Eco-RI-G-DNA fragment show a sensitivity of less than 3 pg of whole plasmid DNA and hybridize only with DNA of HSV I and II, but not with other viral or cellular DNA. The analysis of 15 clinical specimens showed concordance with virus isolation, except for two culture-negative samples of cerebrospinal fluid of patients with suspected HSV encephalitis, which was confirmed by serology as well as by hybridization. Using RNA transcripts from adenovirus-2-Hind-III-D-DNA fragment, we attained a sensitivity of less than 3 pg of whole plasmid DNA. This probe detected different types of adenovirus, but failed to hybridize to other viral, bacterial or cellular DNA. Compared with the cell culture method this assay did not show any false-positive or false-negative results in 16 different clinical specimens. The technique is sensitive, specific and useful for screening clinical specimens and may be helpful in confirming the diagnosis of HSV encephalitis.
A diagnostic hybridization assay for detecting human cytomegalovirus (HCMV) DNA in urine specimens was developed by using cloned viral DNA and in vitro-synthesized RNA probes. Both probes detected 3 pg of homologous DNA and hybridized with DNA of HCMV but not with other viral or human cellular DNA tested. In 95 urine specimens simultaneously tested by cell culture, the sensitivity of hybridization was at least 83%, and the specificity was at least 92%. This assay will be useful for rapid viral diagnosis with wide clinical applications such as screening of immunocompromised patients and quantitation of viral shedding in patients with primary or reactivated HCMV infection who may be receiving antiviral therapy.
Health effects of substances in the environment are considered from the viewpoint of cellular and molecular biology. There are nephrotoxic effects of cadmium to be discussed as well as mechanisms of carcinogenesis and neurotoxicity. Finally, the influences of noxious substances on lung clearance and immune reactions are demonstrated.
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From August 1980 to May 1981, high-frequency lesions of the dorsal root entry zone of the spinal cord were performed on 35 patients with chronic deafferentiation pains. Among them were 15 patients with traumatic transverse cord lesions, 5 with non-traumatic transverse lesions and 7 with cervical root tears or traumatic brachial plexus lesions, 6 with stump or phantom pain after amputation, and 1 each with sciatic paralysis or spinal arachnopathy. Treatment results were best in complete transverse lesions, cervical root avulsion and brachial plexus lesion, less so for stump or phantom pain of the lower extremities. It failed in patients with sciatic-nerve lesion and arachnopathy. Thus best results are to be expected if the method is limited to genuine deafferentiation pain.
Tissue samples taken from the A. cerebri media and A. temporalis superficialis were examined via electron microscope in 52 patients surgically treated by applying an externa-interna anastomosis. The findings are described.
We report about hypertensive crises, cardial arrhythmia and respiratory complications in 47 patients undergoing thermocoagulation of the gasserian ganglion. Therapeutic proposals are discussed.
In the isolated phrenic nerve-hemidiaphragm preparation from the rat, thallium acetate induced a dose-dependent irreversible paralysis. There was a major time lag between the onset of the exposure and the decline in the indirectly elicited muscle twitches. The slope of the decline was in proportion to the applied concentration, which ranged from 1 X 10(-3) to 5 X 10(-6) mol/l. The paralysis was definitively manifest after approximately 40 min of incubation. In the phase of paralysis, both electrical stimulation of the muscle and chemical stimulation by addition of K+ were fully effective. However, addition of 4-aminopyridine and/or guanidine restored the indirect muscle twitches, indicating a previous reduction of synaptic activity by thallium. Lowering the Ca2+-concentration resulted in a reduced paralysis time. From these results it is suggested that thallium interferes with synaptic transmission by presynaptically antagonizing Ca2+-dependent processes.
Frequencies and amplitudes of miniature endplate potentials (MEPP's) were recorded from neuromuscular junctions of the rat phrenic nerve-diaphragm preparation in vitro. Superfusion of the preparations with Ringer solution containing thallium acetate (Tlac) gradually increased the frequency of MEPP's by a factor of 10 within 30 min (1 X 10(-3) mol/l Tlac) and 180 min (5 X 10(-4) mol/l Tlac), whereas the amplitude of MEPP's remained unchanged. Frequency of MEPP's fitted a Poisson-distribution which persisted during superfusion with Tl+-Ringer. Sub-MEPP amplitudes remained unaffected by the action of thallium. It is concluded that thallium interferes presynaptically with spontaneous transmitter release.